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Soyeon Jang,1 Soyoung Jang,1 Si-Yong Kim,1 Jiwon Ko,1 Eungyung Kim,2 Ji Yeong Park,1 Hyejin Hyung,1 Jin Hong Lee,1 Su-Geun Lim,3 Sijun Park,3 Junkoo Yi,4 Heon-Jin Lee,5 Myoung Ok Kim,2 Hyun-Shik Lee,1 Zae Young Ryoo1 1School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, Korea; 2Department of Animal Science and Biotechnology, Kyungpook National University, Daegu, Korea; 3School of Life Science, Kyungpook National University, Daegu, Korea; 4Gyeongsangbukdo Livestock Research Institute, Yeongju, Korea; 5Department of Microbiology and Immunology, School of Dentistry, Kyungpook National University, Daegu, 41940, KoreaCorrespondence: Zae Young Ryoo; Hyun-Shik LeeSchool of Life Science, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, KoreaTel +82-53-950-7361; +82-53-950-7367Fax +82-53-943-6925; +82-53-943-2762Email jaewoong64@knu.ac.kr; leeh@knu.ac.krPurpose: Psoriasis is a common and well-studied autoimmune skin disease, which is characterized by plaques. The formation of psoriasis plaques occurs through the hyperproliferation and abnormal differentiation of keratinocytes, infiltration of numerous immune cells into the dermis, increased subepidermal angiogenesis, and various autoimmune-associated cytokines and chemokines. According to previous research, Lin28 regulates the let-7 family, and let-7b is associated with psoriasis. However, the link between Lin28 and psoriasis is unclear. In this study, an association was identified between Lin28a and psoriasis progression, which promoted the pathological characteristic of psoriasis in epidermal keratinocytes.Patients and Methods: This study aims to investigate the role of Lin28a and its underlying mechanism in psoriasis through in vivo and in vitro models, which include the Lin28a-overexpressing transgenic (TG) mice and Lin28a-overexpressing human keratinocyte (HaCaT) cell lines, respectively.Results: In vivo and in vitro results revealed that overexpression of Lin28a downregulated microRNA let-7 expression levels and caused hyperproliferation and abnormal differentiation in keratinocytes. In imiquimod (IMQ)-induced psoriasis-like inflammation, Lin28a overexpressing transgenic (TG) mice exhibited more severe symptoms of psoriasis.Conclusion: Mechanistically, Lin28a exacerbated psoriasis-like inflammation through the activation of the extracellular-signal-regulated kinase (ERK) and signal transducer and activator of transcription 3 signaling (STAT 3) by targeting proinflammatory cytokine interleukin-6 (IL-6).Keywords: psoriasis, keratinocyte, Lin28a, let-7

Directional differentiation is a key factor determining the result of stem cell therapy. Herein, we developed a polyethylenimine (PEI)-coated poly(lactic- co -glycolic) acid (PLGA) nanoparticle (mPDN) carrying both nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA and dexamethasone (Dex) to human mesenchymal stem cells (hMSCs). The combination of Dex and Nrf2-mRNA delivered by mPDN promoted the osteogenic differentiation of hMSCs. In particular, Nrf2-mRNA rapidly reduced the DNA damage caused by ROS due to early and efficient gene expression at 3 h after treatment, which was not achieved in traditional pDNA systems. High and rapid transfection, effective ROS-scavenging effect, and protection of mitochondrial dynamics were observed in hMSCs after treatment with the resulting Nrf2-mPDN. Osteogenic differentiation was also observed in 3D pellets for up to 5 weeks. Finally, the effects of rapid DNA repair in hMSCs by Nrf2-mPDN and on in vivo bone regeneration were evaluated in a rat femoral bone defect model using CT. This study demonstrated the potential of an NP-based codelivery system and efficient transfection of mRNA at early stages in hMSCs for bone regeneration and stem cell therapy.

In solid tumors, the exhaustion of natural killer (NK) cells and cytotoxic T cells in the immunosuppressive tumor microenvironment poses challenges for effective tumor control. Conventional humanized mouse models of hepatocellular carcinoma patient-derived xenografts (HCC-PDX) encounter limitations in NK cell infiltration, hindering studies on NK cell immunobiology. Here, we introduce an improved humanized mouse model with restored NK cell reconstitution and infiltration in HCC-PDX, coupled with single-cell RNA sequencing (scRNA-seq) to identify potential anti-HCC treatments. A single administration of adeno-associated virus carrying human interleukin-15 reinstated persistent NK cell reconstitution and infiltration in HCC-PDX in humanized mice. scRNA-seq revealed NK cell and T cell subpopulations with heightened PDCD1 and TIGIT levels. Notably, combination therapy with anti-PD-1 and anti-TIGIT antibodies alleviated HCC burden in humanized mice, demonstrating NK cell-dependent efficacy. Bulk-RNA sequencing analysis also revealed significant alterations in the tumor transcriptome that may contribute to further resistance after combination therapy, warranting further investigations. As an emerging strategy, ongoing clinical trials with anti-PD-1 and anti-TIGIT antibodies provide limited data. The improved humanized mouse HCC-PDX model not only sheds light on the pivotal role of NK cells but also serves as a robust platform for evaluating safety and anti-tumor efficacy of combination therapies and other potential regimens, complementing clinical insights., Competing Interests: Declaration of interests Q.C. is the scientific cofounder of two biotech companies., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Aims: The rapid urease test (RUT) is widely used to detect Helicobacter pylori infection; however, it is not preferred as a monitoring strategy after eradication owing to its low sensitivity. In this study, we evaluated the diagnostic performance of RUT using the sweeping method, which overcomes the limitations of conventional tissue sampling methods after eradication., Methods: Patients who received H pylori eradication treatment were enrolled. Each of the sweeping and conventional methods was performed on the same patients to compare diagnostic performance. Urea breath test (UBT), histology, and polymerase chain reaction were performed to determine true infection. Logistic regression analysis was conducted to investigate reasons for discrepancies between the results of the 2 methods., Results: In 216 patients, the eradication success rate was 68.1%, and the sensitivity and specificity of the sweeping method were 0.812 and 0.912, respectively, whereas those of the conventional method were 0.391 and 0.993, respectively (P < .05 for all). The area under the receiver operating characteristic curve for the sweeping method was higher than that for the conventional method (0.862 vs 0.692, P < .001). The mean time to H pylori detection for the sweeping method was 4.7 ± 4.4 minutes and 12.3 ± 16.1 minutes for the conventional method (P < .001). The risk for inconsistent results between the 2 methods was the highest for UBT values of 1.4‰ to 2.4‰ (odds ratio, 3.8; P = .016)., Conclusions: The RUT with the sweeping method could potentially replace the tissue sampling method as a test to confirm H pylori eradication and be an alternative option to UBT for patients requiring endoscopy., Competing Interests: Disclosure All authors disclosed no financial relationships. This work was partly supported by the Korean College of Helicobacter and Upper Gastrointestinal Research Foundation Grant (no. KCHUGR-202101002)., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background/aims: Early diagnosis of esophageal cancer (EC) remains challenging despite the increasing frequency of endoscopic screenings globally. The rapidly increasing number of endoscopic screenings performed over a certain period might influence diagnostic performance. This study evaluated the association between the number of endoscopic screenings and EC detection rates in a nationwide cohort., Methods: This retrospective population-based study used the Korean National Cancer Screening Program database, comprising 32,774,742 males and females aged ≥40 years between 2015 and 2019. Negative binomial regression model and least-squares mean evaluation were used to assess the association between month of the year and EC detection rates., Results: This study enrolled 28,032,590 participants who underwent upper endoscopy. The number of participants in the fourth quarter (October to December: 10,923,142 [39.0%]) was 2.1 times higher than that in the first quarter (January to March: 5,085,087 [18.1%]); this trend continued for all 5 years. Contrarily, detection rates for EC in the fourth quarter (0.08/1,000 person) were half that in the first quarter (0.15/1,000 person). The odds of detecting EC were lowest in November; in 2015 the odds were 0.57 (95% confidence interval, 0.41 to 0.79; p=0.001) times lower and in 2016, they were 0.51 (95% confidence interval, 0.37 to 0.68; p<0.001) times lower compared to January. The predicted detection rates showed a decreasing trend toward the end of the year (p>0.05 for all)., Conclusions: The workload of endoscopists increased excessively with the rising number of endoscopies toward the end of the year, which was reflected by the decreased EC detection rates during this period.

This study compared the thickness of each intraretinal layer in patients with neurofibromatosis 1 (NF1) and controls to analyze the association between intraretinal layer thickness and visual function. The macular spectral-domain optical coherence tomography volumetric dataset obtained from 68 eyes (25 adult eyes, 43 pediatric eyes) with NF1 without optic glioma and 143 control eyes (100 adult eyes, 43 pediatric eyes) was used for image auto-segmentation. The intraretinal layers segmented from the volumetric data included the macular retinal nerve fiber layer (RNFL), ganglion cell-inner plexiform layer (GCIPL), inner nuclear layer, outer plexiform layer, outer nuclear layer, and photoreceptor layer. Cases and controls were compared after adjusting for age, sex, refractive error, and binocular use. The association between retinal layer thickness and visual acuity was also analyzed. The GCIPL was significantly thinner in both adult and pediatric patients with NF1 compared with healthy controls. Average RNFL and GCIPL thicknesses were associated with visual acuity in adult patients with NF1. In pediatric patients, average GCIPL thickness was associated with visual acuity. These results suggest that changes in the inner retinal layer could be a biomarker of the structural and functional status of patients with NF1., (© 2024. The Author(s).)

Glucose-dependent insulinotropic polypeptide (GIP), a 42-aminoacid hormone, exerts multifaceted effects in physiology, most notably in metabolism, obesity, and inflammation. Its significance extends to neuroprotection, promoting neuronal proliferation, maintaining physiological homeostasis, and inhibiting cell death, all of which play a crucial role in the context of neurodegenerative diseases. Through intricate signaling pathways involving its cognate receptor (GIPR), a member of the G protein-coupled receptors, GIP maintains cellular homeostasis and regulates a defense system against ferroptosis, an essential process in aging. Our study, utilizing GIP-overexpressing mice and in vitro cell model, elucidates the pivotal role of GIP in preserving neuronal integrity and combating age-related damage, primarily through the Epac/Rap1 pathway. These findings shed light on the potential of GIP as a therapeutic target for the pathogenesis of ferroptosis in neurodegenerative diseases and aging. [BMB Reports 2024; 57(9): 417-423].

Background/aim: Skin wound healing is a physiological process restoring the structural and functional integrity of injured skin. During this process, wound management preventing bacterial infection and complications is important for the regeneration of skin layers and adnexa, as well as the protective function of the skin. Therefore, the development of an effective ointment to promote wound healing without complications is beneficial., Materials and Methods: This study developed Raepenol™ cream, comprising a base cream and natural compounds including paeonol, D-panthenol and extract of Centella asiatica, and assessed its therapeutic effect in wound healing. A rat model of skin wound healing and a mouse model of imiquimod-induced pruritus were employed. The effect of Raepenol™ cream was evaluated by wound size and histological analysis, including the integrity of skin structures and inflammatory response., Results: Raepenol™ cream treatment effectively restored the structural integrity of the skin in rats, including wound closure, regeneration of skin adnexa, and reconstitution of collagen, comparable to commercial ointment. Additionally, Raepenol™ cream significantly suppressed pruritus by inhibiting mast cell infiltration or retention in the inflammatory site of mouse ears., Conclusion: Raepenol™ cream effectively promoted wound healing and relieved pruritus in animal models. These results suggest that it could be a promising option for wound care and pruritus relief, offering potential advantages over current ointments., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Inflammatory bowel disease (IBD) is characterized by dysregulated immune responses and a multifactorial etiology. While imatinib has demonstrated efficacy in the treatment of immune-related diseases, its potential effects in IBD treatment remain underexplored., Materials and Methods: This study aimed to investigate the therapeutic effects of imatinib in colitis treatment. A dextran sulfate sodium (DSS)-induced colitis model was used to mimic IBD in mice. Imatinib was administered orally to mice simultaneously with DSS treatment. The effects of imatinib on DSS-induced colitis were evaluated by analyzing colitis-related pathology, including the disease activity index (DAI), histological lesions, inflammatory markers, and tight junction integrity. Additionally, western blot analysis and quantitative real-time polymerase chain reaction were used to assess inflammatory markers, tight-junction proteins, and cell death., Results: In the DSS-induced colitis model, imatinib treatment exerted protective effects by attenuating weight loss, restoring colon length, reducing spleen weight, and improving the DAI score and histological lesions. Additionally, imatinib reduced the level of proinflammatory cytokines, including TNF-α, IL-6, and IL-1β. Furthermore, imatinib treatment restored tight-junction integrity and decreased the expression of apoptosis marker proteins., Conclusion: Overall, imatinib treatment significantly alleviated the symptoms of DSS-induced colitis by influencing the expression of proinflammatory cytokines, tight junction proteins, and apoptotic markers in mice. These findings highlight imatinib as a potential therapeutic candidate for IBD., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: To investigate the efficacy of early surgical intervention in ameliorating aniseikonia among patients with epiretinal membrane., Methods: This prospective cohort study enrolled patients who underwent surgery for epiretinal membrane. Patients were divided into early (symptom onset within 1 year) and late (symptom onset ≥1 year) treatment groups. Changes in aniseikonia, best-corrected visual acuity, and tangential retinal displacement were assessed and compared at 6 and 12 months postoperatively., Results: Of the 56 patients, 30 (53.6%) belonged to the early treatment group and 26 (46.4%) to the late treatment group. The early treatment group demonstrated a significant reduction in aniseikonia score at 6- and 12-month follow-up visits (-1.10 ± 1.50 [P = 0.002] and -1.18 ± 1.79 [P = 0.003], respectively); however, no improvement was observed in the late treatment group (0.98 ± 4.62 [P = 0.310] and 1.52 ± 4.35 [P = 0.124], respectively). The early treatment group showed larger tangential retinal displacement at the 12-month postoperative follow-up visit. In addition, the amount of tangential retinal displacement was associated with postoperative changes in aniseikonia., Conclusion: Early surgical intervention is helpful in improving aniseikonia in patients with epiretinal membrane. The degree of recovery in inner retinal displacement was associated with the improvement of aniseikonia.

Malignant gastric outlet obstruction (GOO) is a condition characterized by blockage or narrowing where the stomach empties its contents into the small intestine due to primary malignant tumors or metastatic diseases. This condition leads to various symptoms such as nausea, vomiting, abdominal pain, and weight loss. To manage malignant GOO, different treatment options have been employed, including surgical gastrojejunostomy (SGJ), gastroduodenal stenting (GDS) using self-expandable metallic stent (SEMS), and endoscopic ultrasound-guided gastrojejunostomy (EUS-GJ). This review focuses on comparing the clinical outcomes of endoscopic stenting (GDS and EUS-GJ) with SGJ for malignant GOO. Studies have shown that GDS with SEMS provides comparable clinical outcomes and safety for the palliation of obstructive symptoms. The choice between covered and uncovered SEMS remains controversial, as different studies have reported varying results. EUS-GJ, performed via endoscopic ultrasound guidance, has shown promising efficacy and safety in managing malignant GOO, but further studies are needed to establish it as the primary treatment option. Comparative analyses suggest that GDS has higher recurrence and reintervention rates compared to EUS-GJ and SGJ, with similar overall procedural complications. However, bleeding rates were lower with GDS than with SGJ. Randomized controlled trials are required to determine the optimal treatment approach for malignant GOO.

Background and Aims: Recommendations for stopping nucleoside analogue (NA) therapy in hepatitis B e antigen-negative chronic hepatitis B (CHB) are unclear. End-of-treatment quantitative hepatitis B serum antigen (EOTqHBsAg) thresholds <100 IU/mL or <1000 IU/mL have been proposed as stopping criteria, which we assessed by meta-analysis and meta-regression., Methods: We searched PubMed, EMBASE, and conference abstracts for studies of hepatitis B e antigen-negative CHB NA discontinuation. Extracted studies were analyzed for risk of bias, pooled risk of hepatitis B serum antigen (HBsAg) loss, virological relapse (VR), and biochemical relapse (BR). Significant heterogeneity (I 2 ) was addressed by subgroup analysis and random-effects meta-regression with known important covariates, including EOTqHBsAg thresholds, ethnicity, duration of therapy, and follow-up., Results: We found 24 articles (3732 subjects); 16 had low and 8 had moderate risk of bias. The pooled risks of HBsAg loss, VR, and BR for stopping therapy at EOTqHBsAg <100 IU/mL were 41.8%, 33.4%, and 17.3%, respectively, vs 4.6%, 72.1%, and 34.6%, respectively, for EOTqHBsAg ≥100 IU/mL. The pooled risks of HBsAg loss, VR, and BR for stopping therapy at EOTqHBsAg <1000 IU/mL were 22.0%, 52.7%, and 15.9%, respectively, vs 3.4%, 63.8%, and 26.4%, respectively, for EOTqHBsAg ≥1000 IU/mL. Multivariable analysis for HBsAg loss showed that ethnicity, follow-up duration, and EOTqHBsAg <100 IU/mL and ≥100 IU/mL explained 85% of the variance in heterogeneity; Asians with EOTqHBsAg <100 IU/mL had 28.2%, while non-Asians with EOTqHBsAg <1000 IU/mL had 38.4% HBsAg loss. Multivariable analysis showed EOTqHBsAg <100 IU/mL and ≥100 IU/mL and other covariates only explained 43% and 63% of the variance in heterogeneity for VR and BR, respectively, suggesting that other factors are also important for relapse., Conclusions: While EOTqHBsAg thresholds, ethnicity, and follow-up duration strongly predict HBsAg loss, this is not true for VR and BR, hence stopping NA therapy should be considered cautiously., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Genomic alterations in tumors play a pivotal role in determining their clinical trajectory and responsiveness to treatment. Targeted panel sequencing (TPS) has served as a key clinical tool over the past decade, but advancements in sequencing costs and bioinformatics have now made whole-genome sequencing (WGS) a feasible single-assay approach for almost all cancer genomes in clinical settings. This paper reports on the findings of a prospective, single-center study exploring the real-world clinical utility of WGS (tumor and matched normal tissues) and has two primary objectives: (1) assessing actionability for therapeutic options and (2) providing clarity for clinical questions. Of the 120 patients with various solid cancers who were enrolled, 95 (79%) successfully received genomic reports within a median of 11 working days from sampling to reporting. Analysis of these 95 WGS reports revealed that 72% (68/95) yielded clinically relevant insights, with 69% (55/79) pertaining to therapeutic actionability and 81% (13/16) pertaining to clinical clarity. These benefits include the selection of informed therapeutics and/or active clinical trials based on the identification of driver mutations, tumor mutational burden (TMB) and mutational signatures, pathogenic germline variants that warrant genetic counseling, and information helpful for inferring cancer origin. Our findings highlight the potential of WGS as a comprehensive tool in precision oncology and suggests that it should be integrated into routine clinical practice to provide a complete image of the genomic landscape to enable tailored cancer management., (© 2024. The Author(s).)

Background and Aims: As practice patterns and hepatitis C virus (HCV) genotypes (GT) vary geographically, a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HCV elimination goal. This study aimed to assess the effectiveness and tolerability of DAA treatment in routine clinical practice in a multinational cohort for patients infected with all HCV GTs, focusing on GT3 and GT6., Methods: We analyzed the sustained virological response (SVR12) of 15,849 chronic hepatitis C patients from 39 Real-World Evidence from the Asia Liver Consortium for HCV clinical sites in Asia Pacific, North America, and Europe between 07/01/2014-07/01/2021., Results: The mean age was 62±13 years, with 49.6% male. The demographic breakdown was 91.1% Asian (52.9% Japanese, 25.7% Chinese/Taiwanese, 5.4% Korean, 3.3% Malaysian, and 2.9% Vietnamese), 6.4% White, 1.3% Hispanic/Latino, and 1% Black/African-American. Additionally, 34.8% had cirrhosis, 8.6% had hepatocellular carcinoma (HCC), and 24.9% were treatment-experienced (20.7% with interferon, 4.3% with direct-acting antivirals). The largest group was GT1 (10,246 [64.6%]), followed by GT2 (3,686 [23.2%]), GT3 (1,151 [7.2%]), GT6 (457 [2.8%]), GT4 (47 [0.3%]), GT5 (1 [0.006%]), and untyped GTs (261 [1.6%]). The overall SVR12 was 96.9%, with rates over 95% for GT1/2/3/6 but 91.5% for GT4. SVR12 for GT3 was 95.1% overall, 98.2% for GT3a, and 94.0% for GT3b. SVR12 was 98.3% overall for GT6, lower for patients with cirrhosis and treatment-experienced (TE) (93.8%) but ≥97.5% for treatment-naive patients regardless of cirrhosis status. On multivariable analysis, advanced age, prior treatment failure, cirrhosis, active HCC, and GT3/4 were independent predictors of lower SVR12, while being Asian was a significant predictor of achieving SVR12., Conclusions: In this diverse multinational real-world cohort of patients with various GTs, the overall cure rate was 96.9%, despite large numbers of patients with cirrhosis, HCC, TE, and GT3/6. SVR12 for GT3/6 with cirrhosis and TE was lower but still excellent (>91%)., Competing Interests: FJ: Speaker fees: Gilead Sciences, MSD, and Ascletis. Consultancy: Gilead Sciences, MSD. FJ has been an Editorial Board Member of Journal of Clinical and Translational Hepatology since 2023. YJW: Speaker fees: Gilead Science, AbbVie. Research Grant: Medicine Academic Clinical Program, SingHealth, Singapore. YJW has been an Editorial Board Member of Journal of Clinical and Translational Hepatology since 2020. HT: Speaker fees: Gilead Science, AbbVie, Eisai, Fujifilm WAKO, Takeda, Kowa, Terumo, Astra Zeneca. VWSW: Consultancy: AbbVie, Boehringer Ingelheim, Echosens, Gilead Sciences, Intercept, Inventiva, Novo Nordisk, Pfizer, Sagimet Biosciences, TARGET PharmaSolutions, Visirna. Speaker fees: Abbott, AbbVie, Gilead Sciences, Novo Nordisk, Unilab. Research grants: Gilead Sciences. Stock: Co-founder of Illuminatio Medical Technology Limited. MA: Speakers’ fees: AbbVie, Gilead Sciences. SD: Speakers fees: Gilead Sciences. MFY: Speakers’ fees: Fujirebio Incorporation, Gilead Sciences, Roche, Sysmex Corporation. Consulting or advisory board: AbbVie, Abbott Diagnostics, Aligos Therapeutics, AiCuris, Antios Therapeutics, Arbutus Biopharma, Arrowhead Pharmaceuticals, Assembly Biosciences, Clear B Therapeutics, Dicerna Pharmaceuticals, Finch Therapeutics, Fujirebio Incorporation, GlaxoSmithKline, Gilead Sciences, Immunocore, Janssen, Precision BioSciences, Roche, Sysmex Corporation, Tune Therapeutics, Vir Biotechnology and Visirna Therapeutics. Research grant: AbbVie, Assembly Biosciences, Arrowhead Pharmaceuticals, Fujirebio Incorporation, Gilead Sciences, Immunocore, Sysmex Corporation and Roche. MFY has been an Associate Editor of Journal of Clinical and Translational Hepatology since 2021. CW: Research grant: Gilead Sciences. MLYu: Research support (grant) from Abbvie, BMS, Gilead, Merck, and Roche diagnostics. Consultant of Abbvie, BMS, Gilead, Roche, and Roche diagnostics. Speaker of Abbvie, BMS, Eisai, Gilead, Roche, and Roche diagnostics. MLYu has been an Associate Editor of Journal of Clinical and Translational Hepatology since 2023. MHN: Research grants via institution: Pfizer, Enanta, Astra Zeneca, GSK, Delfi, Innogen, Exact Science, CurveBio, Gilead, Vir Biotech, Helio Health, National Cancer Institute, Glycotest. Consulting/Advisory board: Intercept, Exact Science, Gilead, GSK. JL, MLYe, WLC and JFH have been Editorial Board Members of Journal of Clinical and Translational Hepatology since 2022. HR has been an Editor-in-Chief of Journal of Clinical and Translational Hepatology since 2013. The other authors have no conflict of interests related to this publication., (© 2024 Authors.)

Background & Aims: Oral antiviral therapy with nucleos(t)ide analogues (NAs) for chronic hepatitis B (CHB) is well-tolerated and lifesaving, but real-world data on utilization are limited. We examined rates of evaluation and treatment in patients from the REAL-B consortium., Methods: This was a cross-sectional study nested within our retrospective multinational clinical consortium (2000-2021). We determined the proportions of patients receiving adequate evaluation, meeting AASLD treatment criteria, and initiating treatment at any time during the study period. We also identified factors associated with receiving adequate evaluation and treatment using multivariable logistic regression analyses., Results: We analyzed 12,566 adult treatment-naïve patients with CHB from 25 centers in 9 countries (mean age 47.1 years, 41.7% female, 96.1% Asian, 49.6% Western region, 8.7% cirrhosis). Overall, 73.3% (9,206 patients) received adequate evaluation. Among the adequately evaluated, 32.6% (3,001 patients) were treatment eligible by AASLD criteria, 83.3% (2,500 patients) of whom were initiated on NAs, with consistent findings in analyses using EASL criteria. On multivariable logistic regression adjusting for age, sex, cirrhosis, and ethnicity plus region, female sex was associated with adequate evaluation (adjusted odds ratio [aOR] 1.13, p = 0.004), but female treatment-eligible patients were about 50% less likely to initiate NAs (aOR 0.54, p <0.001). Additionally, the lowest evaluation and treatment rates were among Asian patients from the West, but no difference was observed between non-Asian patients and Asian patients from the East. Asian patients from the West (vs. East) were about 40-50% less likely to undergo adequate evaluation (aOR 0.60) and initiate NAs (aOR 0.54) (both p <0.001)., Conclusions: Evaluation and treatment rates were suboptimal for patients with CHB in both the East and West, with significant sex and ethnic disparities. Improved linkage to care with linguistically competent and culturally sensitive approaches is needed., Impact and Implications: Significant sex and ethnic disparities exist in hepatitis B evaluation and treatment, with female treatment-eligible patients about 50% less likely to receive antiviral treatment and Asian patients from Western regions also about 50% less likely to receive adequate evaluation or treatment compared to Asians from the East (there was no significant difference between Asian patients from the East and non-Asian patients). Improved linkage to care with linguistically competent and culturally sensitive approaches is needed., (Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: HBeAg loss is an important endpoint for antiviral therapy in chronic hepatitis B (CHB), however there are no reliable biomarkers to identify patients who will respond to the addition of pegylated interferon to nucleos(t)ide analogue (NA) therapy., Aim: To evaluate the use of serum biomarkers to predict HBeAg loss., Methods: HBeAg positive CHB participants on NAs who switched-to or added-on 48 weeks pegylated interferon alpha2b (clinicaltrial.gov NCT01928511) were evaluated at week 72 for HBeAg loss. The predictive ability of qHBeAg, qHBsAg, HBV RNA and clinical variables for HBeAg loss were investigated., Results: HBeAg loss occurred in 15/55 (27.3%) participants who completed 48 weeks of pegylated interferon. There was a lower baseline qHBeAg (1.18 IU/mL [2.27] versus 10.04 IU/mL [24.87], P = 0.007) among participants who lost HBeAg. Baseline qHBeAg (OR = 0.15, 95% CI 0.03-0.66, P = 0.01) and detectable HBV DNA at baseline (OR = 25.00, 95% CI 1.67-374.70, P = 0.02) were independent predictors of HBeAg loss. In addition, on-treatment qHBeAg was also a strong predictor of HBeAg loss (OR = 0.39, 95% CI 0.18-0.81, P = 0.012). The models combining detectable baseline HBV DNA with baseline (C-statistic 0.82) and on-treatment (C-statistic 0.83) had good accuracy for predicting HBeAg loss. A rise in qHBeAg ≥ 10 IU/ml was a predictor of flare (ALT ≥ 120 U/ml) on univariable analysis but not after adjustment for treatment arm., Conclusions: Baseline and on-treatment qHBeAg is a useful biomarker that can identify participants on NA therapy who may benefit from adding or switching to pegylated interferon., 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.Daniel Q. Huang Advisory board: Eisai, Gilead. Liang Shen nil; Wah Phyo nil; Gavin Cloherty Employee of Abbott Diagnostics; Emily K. Butler Employee of Abbott Diagnostics; Mary C. Kuhns Employee of Abbott Diagnostics; Anne L. McNamara Employee of Abbott Diagnostics; Vera Holzmayer Employee of Abbott Diagnostics; Jeffrey Gersch Employee of Abbott Diagnostics; Mark Anderson Employee of Abbott Diagnostics; Wei Lyn Yang: Advisory board: Gilead, Abbie, Bristol Myers Squibb, MSD; Jing Hieng Ngu Advisory Board: Gilead Sciences; Speakers Bureau: Abbvie; Jason Chang nil; Jessica Tan nil; Taufique Ahmed nil; Yock Young Dan Advisory Board: BMS, Gilead, Novartis, Abbvie, MSD; Speaker's Bureau: Sanofi Aventis, Siemens; Research grants: BMS, Novartis and Johnson & Johnson; Yin Mei Lee nil; Guan Huei Lee nil; Poh Seng Tan nil; Htet Toe Wai Khine nil; Amy Tay nil; Seng Gee Lim: Advisory Board: Gilead Sciences, Roche, GSK, Janssen, Grifols, Assembly, Arbutus, Abbott, Sysmex. Speakers Bureau: Gilead Sciences, Abbott, Sysmex, Roche, GSK. Educational/research funding: Abbott, Gilead Sciences., (Copyright © 2024. Published by Elsevier B.V.)

Background & Aims: Hepatitis B surface antigen (HBsAg) loss or functional cure (FC) is considered the optimal therapeutic outcome for patients with chronic hepatitis B (CHB). However, the immune-pathological biomarkers and underlying mechanisms of FC remain unclear. In this study we comprehensively interrogate disease-associated cell states identified within intrahepatic tissue and matched PBMCs (peripheral blood mononuclear cells) from patients with CHB or after FC, at the resolution of single cells, to provide novel insights into putative mechanisms underlying FC., Methods: We combined single-cell transcriptomics (single-cell RNA sequencing) with multiparametric flow cytometry-based immune phenotyping, and multiplexed immunofluorescence to elucidate the immunopathological cell states associated with CHB vs. FC., Results: We found that the intrahepatic environment in CHB and FC displays specific cell identities and molecular signatures that are distinct from those found in matched PBMCs. FC is associated with the emergence of an altered adaptive immune response marked by CD4 cytotoxic T lymphocytes, and an activated innate response represented by liver-resident natural killer cells, specific Kupffer cell subtypes and marginated neutrophils. Surprisingly, we found MHC class II-expressing hepatocytes in patients achieving FC, as well as low but persistent levels of covalently closed circular DNA and pregenomic RNA, which may play an important role in FC., Conclusions: Our study provides conceptually novel insights into the immuno-pathological control of HBV cure, and opens exciting new avenues for clinical management, biomarker discovery and therapeutic development. We believe that the discoveries from this study, as it relates to the activation of an innate and altered immune response that may facilitate sustained, low-grade inflammation, may have broader implications in the resolution of chronic viral hepatitis., Impact and Implications: This study dissects the immuno-pathological cell states associated with functionally cured chronic hepatitis B (defined by the loss of HBV surface antigen or HBsAg). We identified the sustained presence of very low viral load, accessory antigen-presenting hepatocytes, adaptive-memory-like natural killer cells, and the emergence of helper CD4 T cells with cytotoxic or effector-like signatures associated with functional cure, suggesting previously unsuspected alterations in the adaptive immune response, as well as a key role for the innate immune response in achieving or maintaining functional cure. Overall, the insights generated from this study may provide new avenues for the development of alternative therapies as well as patient surveillance for better clinical management of chronic hepatitis B., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background/aims: This study aimed to investigate the clinical characteristics and treatment outcomes of patients with active central serous chorioretinopathy (CSC) and foveal atrophy., Methods: Patients diagnosed with active idiopathic CSC using multimodal imaging and followed up for at least 6 months were included. They were divided into two groups (foveal atrophy group vs foveal non-atrophy group) according to a cut-off central foveal thickness of 120 µm on baseline optical coherence tomography (OCT). Baseline characteristics, angiographic and tomographic features and treatment outcomes were compared between the two groups., Results: Of the 463 patients, 92 eyes of 92 patients (19.9%) were in the foveal atrophy group and 371 eyes of 371 patients (80.1%) were in the foveal non-atrophy group. The baseline subretinal fluid (SRF) height was 111.3±76.8 µm in the foveal atrophy group and 205.0±104.4 µm in the foveal non-atrophy group on OCT images (p<0.001). Complete resolution of SRF after treatment was noted in 60.4% and 93.5% of patients in the foveal atrophy and foveal non-atrophy groups at the final visit, respectively (p<0.001). The foveal atrophy group showed worse visual acuity at baseline (logarithm of the minimum angle of resolution, 0.43±0.33 vs 0.13±0.18, p<0.001) and final visit (0.41±0.32 vs 0.05±0.15, p=0.035)., Conclusions: CSC with foveal atrophy was associated with a shallow SRF height, low treatment efficacy and poor vision before and after treatment. We suggest that early active treatment should be considered for eyes with CSC accompanied by a persistent shallow SRF and foveal atrophy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Long intergenic non-coding RNA 346 (LINC00346) has been reported to be involved in the development of atherosclerosis and specific cancers by affecting signaling pathways. However, its function in inflammation has not been thoroughly studied. Therefore, its expression pattern and function were determined in the human macrophage-like cell line THP-1. Lipopolysaccharide (LPS) treatment induced the expression of LINC00346. LPS-induced NF-κB activation and proinflammatory cytokine expression were suppressed or enhanced by the overexpression or knockdown of LINC00346, respectively. Analyses using dual luciferase assay and decoy RNAs that could block RNA-RNA interactions indicated that LINC00346 improves phosphatase and tensin homolog (PTEN) expression by sponging miR-25-3p. Subsequently, PTEN suppresses phosphoinositide-3 kinase (PI3K)-mediated conversion of phosphatidylinositol-4,5-bisphosphate (PIP 2 ) into phosphatidylinositol-3,4,5-trisphosphate (PIP 3 ) as well as consequent activation of protein kinase B (AKT) and NF-κB. Interestingly, database analysis revealed that the expression levels of LINC00346 and PTEN were simultaneously decreased in breast cancer tissues. Further analyses conducted using a breast cancer cell line, MDA-MB-231, confirmed the functional relationship among LINC00346, miR-25-3p, and PTEN in LPS-induced activation of NF-κB. These results indicate that miR-25-3p-sponging activity of LINC00346 affects the balance between PTEN and PI3K as well as the downstream activation of AKT/NF-κB pathway in inflammatory conditions., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest. The funders had no role in the design of the study; collection, analyses, or interpretation of data; writing of the manuscript, or decision to publish the results., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Maintaining epidermal homeostasis relies on a tightly organized process of proliferation and differentiation of keratinocytes. While past studies have primarily focused on calcium regulation in keratinocyte differentiation, recent research has shed light on the crucial role of lysosome dysfunction in this process. TLR adaptor interacting with SLC15A4 on the lysosome (TASL) plays a role in regulating pH within the endo-lysosome. However, the specific role of TASL in keratinocyte differentiation and its potential impact on proliferation remains elusive. In our study, we discovered that TASL deficiency hinders the proliferation and migration of keratinocytes by inducing G1/S cell cycle arrest. Also, TASL deficiency disrupts proper differentiation process in TASL knockout human keratinocyte cell line (HaCaT) by affecting lysosomal function. Additionally, our research into calcium-induced differentiation showed that TASL deficiency affects calcium modulation, which is essential for keratinocyte regulation. These findings unveil a novel role of TASL in the proliferation and differentiation of keratinocytes, providing new insights into the intricate regulatory mechanisms of keratinocyte biology., (© 2024. The Author(s).)

As human society has advanced, nuclear energy has provided energy security while also offering low carbon emissions and reduced dependence on fossil fuels, whereas nuclear power plants have produced large amounts of radioactive wastewater, which threatens human health and the sustainability of water resources. Here, we demonstrate a hydrate-based desalination (HBD) technology that uses methane as a hydrate former for freshwater recovery and for the removal of radioactive chemicals from wastewater, specifically from Cs- and Sr-containing wastewater. The complete exclusion of radioactive ions from solid methane hydrates was confirmed by a close examination using phase equilibria, spectroscopic investigations, thermal analyses, and theoretical calculations, enabling simultaneous freshwater recovery and the removal of radioactive chemicals from wastewater by the methane hydrate formation process described in this study. More importantly, the proposed HBD technology is applicable to radioactive wastewater containing Cs + and Sr 2+ across a broad concentration range of low percentages to hundreds of parts per million (ppm) and even subppm levels, with high removal efficiency of radioactive chemicals. This study highlights the potential of environmentally sustainable technologies to address the challenges posed by radioactive wastewater generated by nuclear technology, providing new insights for future research and development efforts.

Background/aims: Four-week treatment of linvencorvir (RO7049389) was generally safe and well tolerated, and showed anti-viral activity in chronic hepatitis B (CHB) patients. This study evaluated the efficacy, safety, and pharmacokinetics of 48-week treatment with linvencorvir plus standard of care (SoC) in CHB patients., Methods: This was a multicentre, non-randomized, non-controlled, open-label phase 2 study enrolling three cohorts: nucleos(t)ide analogue (NUC)-suppressed patients received linvencorvir plus NUC (Cohort A, n=32); treatment-naïve patients received linvencorvir plus NUC without (Cohort B, n=10) or with (Cohort C, n=30) pegylated interferon-α (Peg-IFN-α). Treatment duration was 48 weeks, followed by NUC alone for 24 weeks., Results: 68 patients completed the study. No patient achieved functional cure (sustained HBsAg loss and unquantifiable HBV DNA). By Week 48, 89% of treatment-naïve patients (10/10 Cohort B; 24/28 Cohort C) reached unquantifiable HBV DNA. Unquantifiable HBV RNA was achieved in 92% of patients with quantifiable baseline HBV RNA (14/15 Cohort A, 8/8 Cohort B, 22/25 Cohort C) at Week 48 along with partially sustained HBV RNA responses in treatment-naïve patients during follow-up period. Pronounced reductions in HBeAg and HBcrAg were observed in treatment-naïve patients, while HBsAg decline was only observed in Cohort C. Most adverse events were grade 1-2, and no linvencorvir-related serious adverse events were reported., Conclusion: 48-week linvencorvir plus SoC was generally safe and well tolerated, and resulted in potent HBV DNA and RNA suppression. However, 48-week linvencorvir plus NUC with or without Peg-IFN did not result in the achievement of functional cure in any patient.

An ideal hydrogel for stem cell therapy would be injectable and efficiently promote stem cell proliferation and differentiation in body. Herein, an injectable, single-component hydrogel with hyaluronic acid (HA) modified with phenylboronic acid (PBA) and spermidine (SM) is introduced. The resulting HAps (HA-PBA-SM) hydrogel is based on the reversible crosslinking between the diol and the ionized PBA, which is stabilized by the SM. It has a shear-thinning property, enabling its injection through a syringe to form a stable hydrogel inside the body. In addition, HAps hydrogel undergoes a post-injection "self-curing," which stiffens the hydrogel over time. This property allows the HAps hydrogel to meet the physical requirements for stem cell therapy in rigid tissues, such as bone, while maintaining injectability. The hydrogel enabled favorable proliferation of human mesenchymal stem cells (hMSCs) and promoted their differentiation and mineralization. After the injection of hMSCs-containing HAps into a rat femoral defect model, efficient osteogenic differentiation of hMSCs and bone regeneration is observed. The study demonstrates that simple cationic modification of PBA-based hydrogel enabled efficient gelation with shear-thinning and self-curing properties, and it would be highly useful for stem cell therapy and in vivo bone regeneration., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Inflammatory bowel disease (IBD) is a chronic inflammatory condition that is influenced by various factors, including environmental factors, immune responses, and genetic elements. Among the factors that influence IBD progression, macrophages play a significant role in generating inflammatory mediators, and an increase in the number of activated macrophages contributes to cellular damage, thereby exacerbating the overall inflammatory conditions. HSPA9, a member of the heat shock protein 70 family, plays a crucial role in regulating mitochondrial processes and responding to oxidative stress. HSPA9 deficiency disrupts mitochondrial dynamics, increasing mitochondrial fission and the production of reactive oxygen species. Based on the known functions of HSPA9, we considered the possibility that HSPA9 reduction may contribute to the exacerbation of colitis and investigated its relevance. In a dextran sodium sulfate-induced colitis mouse model, the downregulated HSPA9 exacerbates colitis symptoms, including increased immune cell infiltration, elevated proinflammatory cytokines, decreased tight junctions, and altered macrophage polarization. Moreover, along with the increased mitochondrial fission, we found that the reduction in HSPA9 significantly affected the superoxide dismutase 1 levels and contributed to cellular death. These findings enhance our understanding of the intricate mechanisms underlying colitis and contribute to the development of novel therapeutic approaches for this challenging condition., (© 2024. The Author(s).)

Background & Aims: It is unclear if there may be sex differences in response to nucleos(t)ide analogs including virologic response (VR), biochemical response (BR), complete response (CR), and hepatocellular carcinoma (HCC) incidence among hepatitis B patients. We compared nucleos(t)ide analog treatment outcomes by sex., Methods: We performed a retrospective cohort study of 3388 treatment-naïve adult hepatitis B patients (1250 female, 2138 male) from the Real-World Evidence from the Global Alliance for the Study of Hepatitis B Virus consortium who initiated therapy with either entecavir or tenofovir from 22 sites (Argentina, Korea, Japan, Taiwan, and the United States). We used propensity-score matching to balance background characteristics of the male and female groups and competing-risks analysis to estimate the incidence and subdistribution hazard ratios (SHRs) of VR, BR, CR, and HCC., Results: Females (vs males) were older (52.0 vs 48.6 y); less likely to be overweight/obese (49.3% vs 65.7%), diabetic (9.9% vs 13.1%), or cirrhotic (27.9% vs 33.0%); and had a lower HBV DNA level (5.9 vs 6.0 log10 IU/mL) and alanine aminotransferase level (91 vs 102 IU/L) (all P < .01). However, after propensity-score matching, relevant background characteristics were balanced between the 2 groups. Females (vs males) had similar 5-year cumulative VR (91.3% vs 90.3%; P = .40) and HCC incidence rates (5.1% vs 4.4%; P = .64), but lower BR (84.0% vs 90.9%; P < .001) and CR (78.8% vs 83.4%; P = .016). Males were more likely to achieve BR (SHR, 1.31; 95% CI, 1.17-1.46; P < .001) and CR (SHR, 1.16; 95% CI, 1.03-1.31; P = .016), but VR and HCC risks were similar., Conclusions: Sex differences exist for treatment outcomes among hepatitis B patients. Male sex was associated with a 16% higher likelihood of clinical remission and a 31% higher likelihood of biochemical response than females, while virologic response and HCC incidence were similar between the 2 groups., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background and Aims: HCC risk in chronic hepatitis B (CHB) is higher in the indeterminate phase compared with the inactive phase. However, it is unclear if antiviral therapy reduces HCC risk in this population. We aimed to evaluate the association between antiviral therapy and HCC risk in the indeterminate phase., Approach and Results: We analyzed 855 adult (59% male), treatment-naïve patients with CHB infection without advanced fibrosis in the indeterminate phase at 14 centers (USA, Europe, and Asia). Inverse probability of treatment weighting (IPTW) was used to balance the treated (n = 405) and untreated (n = 450) groups. The primary outcome was HCC development. The mean age was 46±13 years, the median alanine transaminase was 38 (interquartile range, 24-52) U/L, the mean HBV DNA was 4.5±2.1 log 10 IU/mL, and 20% were HBeAg positive. The 2 groups were similar after IPTW. After IPTW (n = 819), the 5-, 10-, and 15-year cumulative HCC incidence was 3%, 4%, and 9% among treated patients (n = 394) versus 3%, 15%, and 19%, among untreated patients (n = 425), respectively ( p = 0.02), with consistent findings in subgroup analyses for age >35 years, males, HBeAg positive, HBV DNA>1000 IU/mL, and alanine transaminase

HDV is a defective virus that uses the HBV surface antigen to enter hepatocytes. It is associated with an accelerated course of liver fibrosis progression and an increased risk of hepatocellular carcinoma. Negative HDV RNA 24 weeks after the end of therapy has been proposed as an endpoint but late relapses make this endpoint suboptimal, hence HBsAg loss appears to be more appropriate. Current HBV antiviral agents have poor activity against HDV hence the search for improved therapy. Drugs only active against HDV, such as lonafarnib, have shown efficacy in combination with nucleoside analogues and peginterferon, but do not lead to HBsAg loss. HBsAg loss sustained 24 weeks after the end of therapy with negative HBV DNA is termed functional cure. Agents that are being investigated for functional cure include those that inhibit replication such as entry inhibitors, polymerase inhibitors and capsid assembly modulators but seldom lead to functional cure. Agents that reduce HBV antigen load such as RNA interference and inhibitors of HBsAg secretion are promising. Immunomodulators on their own seldom achieve functional cure, hence these agents in combination to assess the optimal combination are being investigated. Consequently, agents leading to functional cure of HBV are ideal for both HBV and HDV., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Objectives : Peripherally inserted central catheter (PICC) placement plays an important role in clinical practice. This study aimed to provide an equation for the proper estimation of catheter length in cases of PICC placement without imaging guidance in relation to patient height, weight, sex, and age. Materials and Methods : For 1137 PICC placement cases in both arm veins of 954 patients at a single center, the elbow crease to the cavoatrial junction length (ECL) was calculated as follows: ECL = (PICC length) + (distance from the elbow crease to the puncture site). We analyzed the relationship between ECL and patient characteristics and suggested a new equation for ECL based on height, weight, sex, and age. Results : The average ECL was 48.0 ± 2.4 cm in the right side and 51.0 ± 3.0 cm in the left side. ECL in the right arm was significantly correlated with patient height, sex, and age, whereas the ECL in the left arm was additionally significantly correlated with patient weight. The ECL (cm) prediction model was as follows: right ECL = 26.32 + 1.33 × (female = 1, male = 2) - 0.02 × age (years) + 0.13 × height (cm); left ECL = 22.09 + 1.28 × (female = 1, male = 2) + 0.02 × age (years) + 0.14 × height (cm) + 0.042 × weight (kg). Conclusions : The appropriate PICC length was predicted based on the patient's height, weight, sex, and age. The equations in our study can help predict the optimal catheter length and can be automatically calculated using computerized patient information for bedside procedures in PICC.

Background/aims: : This study aimed to review the indications, methods, cooperation, complications, and outcomes of percutaneous endoscopic gastrostomy (PEG)., Methods: : Questionnaires were sent to 200 hospitals, of which 62 returned their questionnaires, with a response rate of approximately 30%. Descriptive statistics were calculated to analyze the responses to the questionnaires., Results: : In 2019, a total of 1,052 PEGs were performed in 1,017 patients at 62 hospitals. The main group who underwent PEG was older adult patients with brain disease, particularly stroke. Nutritional supply was an important purpose of the PEG procedure. "The pull method" was the most commonly used for initial PEG insertion. The complications related to PEG were mostly mild, with leakage being the most common. Patients who underwent PEG procedures were primarily educated regarding the post-procedure management and complications related to PEG. Preoperative meetings were skipped at >50% of the institutions. Regarding the cooperation between the nutrition support team (NST) and the physician performing PEG, few endoscopists answered that they cooperated with NST before and after PEG. Moreover, the rate of NST certification obtained by physicians performing PEG and the frequency of attendance at NST-related conferences were relatively low., Conclusions: : This study shows a similar trend to that found in the previous PEG guidelines. However, it covers new aspects, including team-based work for PEG procedure, nutrition support, and education for patients and guardians. Therefore, each medical institution needs to select an appropriate method considering the medical environment and doctor's abilities.

Here, we introduce CO 2 hydrate-based desalination (CHBD) technology for freshwater recovery from radioactive wastewater, for water particularly containing Cs and Sr. The hydrate equilibrium curves of CO 2 hydrates shift towards lower temperature and higher pressure regions as the concentrations of CsCl and SrCl 2 increase. X-ray diffraction and Raman spectroscopy measurements found that neither CsCl nor SrCl 2 can affect the structure of CO 2 hydrates. The high-pressure micro-differential scanning calorimetric results demonstrate that CO 2 hydrates in the presence of CsCl and SrCl 2 started to dissociate at lower temperatures due to the enrichment of CsCl and SrCl 2 in the remaining solutions. The formation kinetics results indicate that increases in the concentrations of the radioactive chemicals lead to a decrease in the initial reaction rate and sub-cooling temperature. Solid-state nuclear magnetic resonance spectroscopy was utilized to confirm the exclusion of radioactive isotopes from solid gas hydrates. Importantly, the CHBD technology proposed in this study is applicable to radioactive wastewater containing Cs + and Sr 2+ across broad concentration ranges, spanning from a percent to hundreds of parts per million (ppm), and even sub-ppm levels, with comparable recovery efficiency. This study presents new insights into the potential of environmentally sustainable technologies to overcome the challenges posed by radioactive wastewater., 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 © 2023 Elsevier B.V. All rights reserved.)

We aimed to evaluate the survival benefits of coadministering statins and multityrosine kinase inhibitors (TKIs) in patients with advanced hepatocellular carcinoma (HCC). Data from the Health Insurance Review and Assessment Service in Korea (2010-2020) were utilized. Statin use (≥28 cumulative defined daily doses) was analyzed, with 1534 statin users matched to 6136 non-users (1:4 ratio) using propensity scores. Primary and secondary outcomes were overall survival (OS) and progression-free survival (PFS). Statin use significantly improved OS (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.72-0.82, p < 0.001) and PFS (HR 0.78, 95% CI 0.74-0.84, p < 0.001). Continuous or post-TKI statin users had better OS, while discontinuation after TKI use led to poorer OS. Both lipophilic and hydrophilic statins improved OS and PFS, particularly with ≥730 cumulative defined daily doses. In conclusion, combining statins and TKIs in patients with advanced HCC yielded significant survival benefits, influenced by statin dosage and duration. Continuous statin administration post-TKI treatment is crucial for improving outcomes in patients with HCC.

Background: Patients with Barcelona clinic liver cancer (BCLC) stage B hepatocellular carcinoma (HCC) are considerably heterogeneous in terms of tumor burden, liver function, and performance status. To improve the poor survival outcomes of these patients, treatment approaches other than transarterial chemoembolization (TACE), which is recommended by HCC guidelines, have been adopted in real-world clinical practice. We hypothesize that this non-adherence to treatment guidelines, particularly with respect to the use of liver resection, improves survival in patients with stage B HCC., Aim: To assess guideline adherence in South Korean patients with stage B HCC and study its impact on survival., Methods: A retrospective analysis was conducted using data from 2008 to 2016 obtained from the Korea Central Cancer Registry. Patients with stage B HCC were categorized into three treatment groups, guideline-adherent, upward, and downward, based on HCC guidelines recommended by the Asian Pacific Association for the Study of the Liver (APASL), the European Association for the Study of the Liver (EASL), and the American Association for the Study of Liver Diseases (AASLD). The primary outcome was HCC-related deaths; tumor recurrence served as the secondary outcome. Survival among the groups was compared using the Kaplan-Meier method and the log-rank test. Predictors of survival outcomes were identified using multivariable Cox regression analysis., Results: In South Korea, over the study period from 2008 to 2016, a notable trend was observed in adherence to HCC guidelines. Adherence to the EASL guidelines started relatively high, ranging from 77% to 80% between 2008 and 2012, but it gradually declined to 58.8% to 71.6% from 2013 to 2016. Adherence to the AASLD guidelines began at 71.7% to 75.9% from 2008 to 2010, and then it fluctuated between 49.2% and 73.8% from 2011 to 2016. In contrast, adherence to the APASL guidelines remained consistently high, staying within the range of 90.14% to 94.5% throughout the entire study period. Upward treatment, for example with liver resection, liver transplantation, or radiofrequency ablation, significantly improved the survival of patients with BCLC stage B HCC compared to that of patients treated in adherence to the guidelines (for patients analyzed according to the 2000 EASL guidelines, the 5-year survival rates were 63.4% vs 27.2%, P < 0.001), although results varied depending on the guidelines. Progression-free survival rates were also significantly improved upon the use of upward treatments in certain groups. Patients receiving upward treatments were typically < 70 years old, had platelet counts > 10 5 /μL, and serum albumin levels ≥ 3.5 g/dL., Conclusion: Adherence to guidelines significantly influences survival in South Korean stage B HCC patients. Curative treatments outperform TACE, but liver resection should be selected with caution due to disease heterogeneity., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Directional differentiation of stem cells is a key step in stem cell therapy. In this study, we developed saponin-based nanoparticles (Ad-SNPs) containing dexamethasone (Dex) and alpha-lipoic acid (ALA) to promote osteogenic differentiation of human mesenchymal stem cells (hMSCs) and bone regeneration. The Ad-SNPs can achieve rapid cellular uptake through a pore-forming effect without cytotoxic cationic charges. They also provide extended retention in cell cytosol due to their uptake route. These properties are advantageous in efficiently supplying drugs to the hMSCs. The combination of Dex and ALA facilitated mitochondrial fusion and prevented reactive oxygen species-induced DNA damage. It also helped to preserve mitochondrial dynamics, and the efficient supply of it provided by the Ad-SNPs induced differentiation of hMSCs into osteoblasts. The Ad-SNPs showed outstanding performance in osteoblast differentiation, maturation, and mineralization in 3D culture compared with NPs without saponin and with free drugs. When Ad-SNP-treated hMSCs were tested in a rat femoral bone defect model, they showed the fastest regeneration of bones and complete repair in the shortest period among all groups. To the best of our knowledge, this study is the first application of pore-forming saponin-based NPs with rapid cellular uptake and extended retention to stem cell therapy, and we demonstrated their promising potential in bone regeneration and efficient delivery of Dex and ALA., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Heebeom Koo reports financial support was provided by Korea Ministry of Science and ICT. Heebeom Koo reports financial support was provided by Korean Ministry of Health & Welfare. Ji Sun Park reports financial support was provided by Korea Ministry of Science and ICT. Heebeom Koo reports financial support was provided by Catholic Medical Center of the Catholic University of Korea. Heebeom Koo has patent pending to The Catholic University of Korea., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Competing Interests: SGL has received grants from Gilead Sciences, Abbott Diagnostics, and Sysmex; consulting fees for participation on advisory boards from Janssen, Roche, Fibronostics, Gilead, GSK, Sysmex, Assembly, Arbutus, and Grifols; and payments for participation in speakers' bureau from Gilead Sciences, Janssen, Roche, Sysmex, and GSK. SGL is an Asia Pacific regional advisor to AASLD; an ICE-HBV governing board member; an HBV Forum board member; a scientific advisory board member of ANRS; and chairman of Singapore Hepatology Conference and Science of HBV Cure Conference, all of which are unpaid.

Introduction: Current guidelines discourage the use of direct-acting antiviral (DAA) containing protease-inhibitor (PI) in advanced HCV cirrhosis. We aimed to compare the real-world tolerability of PI vs. non-PI DAA regimens in this population., Methods: We identified advanced cirrhosis patients treated with DAA from the REAL-C registry. The primary outcome was significant worsening or improvement in CPT or MELD scores following DAA treatment., Results: From the REAL-C registry of 15,837 patients, we included 1077 advanced HCV cirrhosis patients from 27 sites. 42% received PI-based DAA. Compared to non-PI group, the PI group was older, had higher MELD and higher percentage with kidney disease. Inverse probability of treatment weighting (IPTW; matching on age, sex, history of clinical decompensation, MELD, platelet, albumin, Asia site, Asian ethnicity, hypertension, hemoglobin, genotype, liver cancer, ribavirin) was used to balance the two groups. In the IPTW-matched cohorts, the PI and non-PI groups had similar SVR12 (92.9% vs. 90.7%, p = 0.30), similar percentages of significant worsening in CTP or MELD scores at posttreatment week 12 and 24 (23.9% vs. 13.1%, p = 0.07 and 16.5% vs. 14.6%, p = 0.77), and similar frequency of new HCC, decompensating event, and death by posttreatment week 24. In multivariable analysis, PI-based DAA was not associated with significant worsening (adjusted odds ratio = 0.82, 95% CI 0.38-1.77)., Conclusion: Tolerability and treatment outcomes were not significantly different in advanced HCV cirrhosis treated with PI-based (vs. non-PI) DAA up to CTP-B or MELD score of 15. Safety of PI-based DAA in those with CTP-C or MELD beyond 15 awaits further data., (© 2023. Asian Pacific Association for the Study of the Liver.)

Experiments were conducted to identify different ratios of Bacillus sp. SJ-10 and Lactobacillus plantarum KCCM 11322 mixtures at a concentration of 1 × 10 8  CFU/g diet; the effects on growth and cellular and humoral immune responses and the characteristics of disease protection in olive flounder (Paralichthys olivaceus). Flounder were divided into six groups and fed control diet D-1 (without Bacillus sp. SJ-10 and L. plantarum KCCM 11322), positive control diets D-2 (Bacillus sp. SJ-10 at 1 × 10 8  CFU/g feed) and D-3 (L. plantarum KCCM 11322 at 1 × 10 8  CFU/g feed); or treatment diets D-4 (3:1 Bacillus sp. SJ-10 and L. plantarum KCCM 11322 at 0.75 + 0.25 × 10 8  CFU/g feed), D-5 (1:1 Bacillus sp. SJ-10 and L. plantarum KCCM 11322 at 0.50 + 0.50 × 10 8  CFU/g feed), or D-6 (1:3 Bacillus sp. SJ-10 and L. plantarum KCCM 11322 at 0.25 + 0.75 × 10 8  CFU/g feed) for 8 weeks. Group D-4 demonstrated better growth and feed utilization (P < 0.05) compared with the controls and positive controls. Similar modulation was also observed in respiratory burst for all treatments and in the expression levels of TNF-α, IL-1β, IL-6, and IL-10 in different organs in D-4. D-4 and D-5 increased respiratory burst, superoxide dismutase, lysozyme, and myeloperoxidase activities compared with the controls, and only D-4 increased microvilli length. When challenged with 1 × 10 8  CFU/mL Streptococcus iniae, the fish in the D-4 and D-5 groups survived up to 14 days, whereas the fish in the other groups reached 100% mortality at 11.50 days. Collectively, a ratio-specific Bacillus sp. SJ-10 and L. plantarum KCCM 11322 mixture (3:1) was associated with elevated growth, innate immunity, and streptococcosis resistance (3:1 and 1:1) compared with the control and single probiotic diets., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background & Aims: Antiviral therapy may attenuate the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). We aimed to explore how tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) affect HCC risk in patients with CHB., Methods: The REACH-B, aMAP, and mPAGE-B models were utilized to assess HCC risk in patients with CHB from two global randomized-controlled trials evaluating the impact of TAF vs. TDF treatment. Standard incidence ratios (SIRs) were calculated using data from the REACH-B model as a ratio of observed HCC cases in the TAF- or TDF-treated patients vs. predicted HCC cases for untreated historical controls. Proportions of treated patients shifting aMAP and mPAGE-B risk categories between baseline and Week 240 were calculated., Results: Of the 1,632 patients (TAF, n = 1,093; TDF, n = 539) followed for up to 300 weeks, 22 HCC cases developed. Those receiving TAF had an SIR that was lower compared to the SIR of individuals receiving TDF: 0.32 ( p <0.001) vs. 0.56 ( p  = 0.06). In the general study population, individuals without cirrhosis at baseline had an SIR that was lower compared to the SIR of individuals with cirrhosis at baseline: 0.37 ( p <0.001) vs. 0.58 ( p  = 0.15). Of the patients at low risk of HCC at baseline, the majority (97%) remained low risk by mPAGE-B and aMAP scoring at Week 240. Among those at medium or high risk at baseline, substantial portions shifted to a lower risk category by Week 240 (mPAGE-B: 22% and 42%; aMAP: 39% and 63%, respectively)., Conclusions: This evaluation provides evidence that treatment with TAF or TDF can reduce HCC risk in patients with CHB, particularly in patients without cirrhosis., Impact and Implications: Despite the substantial impact of HCC on long-term outcomes of patients with CHB, the differential risk of HCC development among those receiving treatment with TAF vs. TDF has not been well elucidated. Using three validated risk prediction models, we found that TAF is at least as effective as TDF in reducing HCC risk in patients with CHB. While TDF is well-studied in the context of HCC risk reduction, our novel findings underscore the effectiveness of TAF as a treatment option for patients with CHB., Clinical Trial Numbers: NCT01940341; NCT02836249; NCT01940471; NCT02836236., Competing Interests: AJH: There are no financial disclosures for this author. CP: Has served as a speaker for Gilead and received research grants from Gilead. DRS: There are no financial disclosures for this author. EG: Member of scientific advisory boards for AbbVie, Abbott Diagnostics, Aligos, Arbutus, Arrowhead, Assembly, Avalia, Clear B Therapeutics, Dicerna, Enanta, Gilead Sciences, GSK, Intellia, Janssen, Merck, Novartis, Genentech-Roche, Vaccitech, Ventorx, Vir Bio and Virion Therapeutics. FA: Gilead Sciences employee and stock ownership. HJ: Received grants from: AbbVie, Gilead Sciences, GSK, Janssen, Roche, Vir Biotechnology Inc. Is a consultant for: Aligos, Antios, Arbutus, Eiger, Gilead Sciences, GSK, Janssen, Merck, Roche, VBI Vaccines, Vir Biotechnology Inc., Viroclinics. HC: Has served as an advisor for Aligos, Arbutus, Hepion, Janssen, Gilead, GSK, Roche, Vaccitech, Vir Biotechnology, Virion Therapeutic, and as a speaker for Gilead, Roche, and Mylan. HW: Employee and stockholder for Gilead. JF: Employee and stockholder for Gilead. JK: Consultant for Abbvie, Abbott, Gilead Sciences, Roche and Sysmex. On speaker’s bureaus for Abbvie, Bristol-Myers Squibb, Gilead Sciences, and Fujirebio. JH: Has received consulting fee from AbbVie, Arbutus, Bristol Myers Squibb, Gilead Sciences, Johnson & Johnson, Roche and received grants from Bristol Myers Squibb and Johnson & Johnson. KA: Aligos, Assembly, Bluejay, BMS, BI, DrugFarm, Gilead, GSK, Janssen, Merck, Roche, Sobi. LJY: Employee of Gilead Sciences and own stock in Gilead Sciences. MB: Has served as an advisor for Abbvie, Arbutus, Assembly, Janssen, Gilead, GSK, Roche, and as a speaker for Gilead and Abbvie. MBr: Speakers Bureau for AbbVie and Gilead. Advisory for AbbVie, Gilead, Janssen, Roche, EISAI-MSD. NI: There are no financial disclosures for this author. QN: Has served as a consultant for BMS, GSK, MSD, and Novartis. SHA: Has acted as advisors and investigator for Gilead, Janssen, AbbVie, Roche, Assembly Biosciences, Arbutus, Brii, Vaccitech, GSK, Inovio, Aligos, Vir Biotechnology, SL Vaxigen, GeneOne Life Science, GreenCross, Yuhan, Samil and Ildong. SF: Has received research support from Gilead. Consultant for Abbvie, Assembly Bio, Janssen, and Gilead. Teacher and speaking for Abbvie and Gilead. SGL: Speakers bureau for Gilead, Janssen, Roche, Sysmex. Advisory board for Gilead, Abbott, Roche, GSK, Janssen, Sysmex, Springbank, Arbutus, Assembly, Grifols, Eisai. Research support from Gilead, Abbott, Roche, Sysmex, Fibronostics, Merck. TTC: There are no financial disclosures for this author. WLC: Member of Advisory Board for Gilead, AbbVie, BMS, Roche, and PharmaEssentia. Speaker for Gilead, AbbVie, BMS, Roche, PharmaEssentia. WKS: Received speaker’s fees from Mylan and AstraZeneca, is an advisory board member of Abbott, is an advisory board member and received speaker’s fees from AbbVie, and is an advisory board member, received speaker’s fees and research funding from Gilead Sciences. YSL: Advisor/consultant/speaker for AbbVie, Assembly Biosciences, Bayer Healthcare, GlaxoSmithKline, Gilead Sciences, Janssen, Olix Pharmaceuticals, Roche, Vaccitech, and Vir Biotechnology; and received grant/research support from Gilead Sciences. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2023 The Author(s).)

The sense of spiciness is related to the stimulation of vanilloid compounds contained in the foods. Although, the spiciness is commonly considered as the part of taste, it is more classified to the sense of pain stimulated on a tongue, namely, pungency, which is described as a tingling or burning on the tongue. Herein, first, a reusable electronic tongue based on a transient receptor potential vanilloid 1 (TRPV1) nanodisc conjugated graphene field-effect transistor is fabricated and spiciness-related pain evaluation with reusable electrode is demonstrated. The pungent compound reactive receptor TRPV1 is synthesized in the form of nanodiscs to maintain stability and reusability. The newly developed platform shows highly selective and sensitive performance toward each spiciness related vanilloid compound repeatably: 1 aM capsaicin, 10 aM dihydrocapsaicin, 1 fM piperine, 10 nM allicin, and 1 pM AITC. The binding mechanism is also examined by simulation. Furthermore, the elimination of the burning sensation on the tongue after eating spicy foods is not investigated. Based on the synthesis of micelles composed of casein protein (which is contained in skim milk) that remove pungent compounds bound to TRPV1 nanodisc, the deactivation of TRPV1 is investigated, and the electrode is reusable that mimics electronic tongue., (© 2023 Wiley-VCH GmbH.)

Background: Comparative outcomes of HBV-infected compensated cirrhosis with low-level viremia (LLV) versus maintained virological response (MVR) are unclear. We conducted a large, multiethnic, multicenter study to examine the natural history of LLV versus MVR in compensated cirrhosis., Patients and Methods: We enrolled patients with HBV-infected compensated cirrhosis (n=2316) from 19 hospitals in South Korea, Singapore, and Japan. We defined the LLV group as untreated patients with ≥1 detectable serum HBV-DNA (20-2000 IU/mL), Spontaneous-MVR group as untreated patients with spontaneously achieved MVR, and antiviral therapy (AVT)-MVR group as patients achieving AVT-induced MVR. Study end points were HCC or hepatic decompensation., Results: The annual HCC incidence was 2.7/100 person-years (PYs), 2.6/100 PYs, and 3.3/100 PYs for LLV (n=742), Spontaneous-MVR (n=333), and AVT-MVR (n=1241) groups, respectively ( p = 0.81 between LLV vs. Spontaneous-MVR groups and p = 0.37 between LLV vs. AVT-MVR groups). Similarly, the annual decompensation incidence was 1.6/100 PYs, 1.9/100 PYs, and 1.6/100 PYs for LLV, Spontaneous-MVR, and AVT-MVR groups, respectively ( p = 0.40 between LLV vs. Spontaneous-MVR groups and p = 0.83 between LLV vs. AVT-MVR groups). Multivariable analyses determined that HCC and decompensation risks in the LLV group were comparable to those with Spontaneous-MVR and AVT-MVR groups (all p >0.05). Propensity score matching also reproduced similar results for HCC and decompensation risks (all p >0.05 between LLV vs. Spontaneous-MVR groups and between LLV vs. AVT-MVR groups)., Conclusions: Untreated LLV in HBV-infected compensated cirrhosis is not associated with increased risk of disease progression compared with Spontaneous-MVR and AVT-MVR. These data have important implications for practice and further research., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Background & Aims: Hepatitis B core-related antigen (HBcrAg) is a new biomarker for chronic hepatitis B (CHB) whose performance has not been critically or systematically appraised. Herein, we performed a systematic review to determine its clinical utility., Methods: We evaluated the biological pathway of HBcrAg and performed a systematic review of PubMed for clinical trials, cohort studies, and case-control studies that evaluated the clinical utility of HBcrAg. The effectiveness of HBcrAg in predicting HBV-specific clinical events (e.g. HBeAg seroconversion, phases of CHB, HBsAg loss, treatment response, and relapse after stopping therapy) was examined using receiver-operating characteristic curves. The correlation coefficients of HBcrAg with HBV DNA, quantitative HBsAg (qHBsAg), HBV RNA, and cccDNA were summarised from published studies. Median values were used as estimates., Results: HBcrAg consists of three precore/core protein products: HBcAg, HBeAg, and a 22 kDa precore protein. HBcrAg assays have been associated with false-positive rates of 9.3% and false-negative rates of between 12-35% for CHB. The new iTACT-HBcrAg is more sensitive but does not reduce the false-positive rate. A PubMed search found 248 papers on HBcrAg, of which 59 were suitable for analysis. The clinical performance of HBcrAg was evaluated using AUROC analyses, with median AUROCs of 0.860 for HBeAg seroconversion, 0.867 for predicting HBeAg(-) hepatitis, 0.645 for HBsAg loss, 0.757 for treatment response, and 0.688 for relapse after stopping therapy. The median correlation coefficient (r) was 0.630 with HBV DNA, 0.414 with qHBsAg, 0.619 with HBV RNA and 0.550 with cccDNA. Correlation decreased during antiviral therapy, but combined biomarkers improved performance., Conclusions: HBcrAg has a mixed performance and has a poor correlation with HBsAg loss and antiviral therapy, hence HBcrAg results should be interpreted with caution., Impact and Implications: Hepatitis B core-related antigen (HBcrAg) has been used to assess management of patients with chronic hepatitis B (CHB) without a systematic and critical Sreview of its performance. Our finding that HBcrAg had a false-positive rate of 9% and a false-negative rate of 12-35% raises concerns, although larger studies are needed for validation. A systematic review showed that the performance of HBcrAg was variable depending on the CHB endpoint; it was excellent at predicting HBeAg seroconversion and HBeAg-negative chronic hepatitis (vs. chronic infection), which should be its main use, but it was poor for relapse after stopping antiviral therapy and for HBsAg loss. HBcrAg results should be interpreted with considerable caution, particularly by physicians, researchers, guideline committees and agencies that approve diagnostic tests., (Copyright © 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Functional cure of chronic hepatitis B (CHB) - or hepatitis B surface antigen (HBsAg) loss after 24 weeks off therapy - is now the goal of treatment, but is rarely achieved with current therapy. Understanding the hepatitis B virus (HBV) life cycle and immunological defects that lead to persistence can identify targets for novel therapy. Broadly, treatments fall into three categories: those that reduce viral replication, those that reduce antigen load and immunotherapies. Profound viral suppression alone does not achieve quantitative (q)HBsAg reduction or HBsAg loss. Combining nucleos(t)ide analogues and immunotherapy reduces qHBsAg levels and induces HBsAg loss in some patients, particularly those with low baseline qHBsAg levels. Even agents that are specifically designed to reduce viral antigen load might not be able to achieve sustained HBsAg loss when used alone. Thus, rationale exists for the use of combinations of all three therapy types. Monitoring during therapy is important not just to predict HBsAg loss but also to understand mechanisms of HBsAg loss using viral and immunological biomarkers, and in selected cases intrahepatic sampling. We consider various paths to functional cure of CHB and the need to individualize treatment of this heterogeneous infection until a therapeutic avenue for all patients with CHB is available., (© 2023. Springer Nature Limited.)

The relationship between androgen excess and bone health in patients with congenital adrenal hyperplasia (CAH) with 21-hydroxylase (21-OH) deficiency is not fully understood. This study demonstrated positive correlations between androgen hormones and bone mineral density (BMD) in CAH women with 21-OH deficiency., Purpose: This study aims to assess BMD and its association with androgen excess in women with CAH., Methods: We enrolled 92 women with CAH with 21-OH deficiency and retrospectively reviewed their clinical features, hormone concentrations, body composition, glucocorticoid (GC) dose, and BMD., Results: BMD was not different according to the subtypes of CAH. BMD at the lumbar spine was lower in women with CAH with regular menstruation than those with irregular menstruation (1.081 vs. 1.165 g/cm 2 , P < 0.05). BMD was lower in women with CAH with 17-hydroxyprogesterone (17-OHP) < 10 ng/mL than in those with ≥ 10 ng/mL (lumbar spine, 1.019 vs. 1.150 g/cm 2 ; femur neck, 0.806 vs. 0.899 g/cm 2 ; total hip, 0.795 vs. 0.943 g/cm 2 ; all P < 0.05). After adjusting for age and BMI in correlation analyses, testosterone concentrations were positively correlated with lumbar spine, femur neck, and total hip BMD (r = 0.46, r = 0.38, and r = 0.35, respectively; all P < 0.05), while 17-OHP was positively correlated with lumbar spine BMD (r = 0.38, P < 0.01). In subgroup analysis, 17-OHP was positively correlated with BMD (lumbar spine, r = 0.22; femur neck, r = 0.22; total hip, r = 0.24; all P < 0.05) only in the group with a total cumulative dose of GC ≥ 156.0 g/m 2 ., Conclusion: Androgen excess may have a protective effect on BMD in women with classic CAH and high cumulative doses of GC., (© 2022. International Osteoporosis Foundation and National Osteoporosis Foundation.)

The long-term effect of Helicobacter pylori eradication on metachronous gastric neoplasm prevention after endoscopic submucosal dissection (ESD) of gastric adenoma is unclear. This study included patients with confirmed H. pylori infection after ESD with curative resection for gastric adenoma. Patients were divided based on the success of H. pylori eradication treatment into two groups: eradication and non-eradication. Patients with any newly detected lesion within 1 year after ESD and recurrence at the ESD site were excluded from the analysis. Further, 1:1 propensity score matching was also performed to eliminate baseline differences between the two groups. H. pylori eradication treatment was administered to 673 patients after ESD (163 in the successful eradication group and 510 in the non-eradication group). During the median follow-up periods of 25 and 39 months in the eradication and non-eradication groups, metachronous gastric neoplasm was identified in 6 (3.7%) and 22 patients (4.3%), respectively. Adjusted Cox analysis revealed that H. pylori eradication was not associated with increased risk of metachronous gastric neoplasm after ESD. Kaplan-Meier analysis in the matched population yielded similar findings ( p = 0.546). H. pylori eradication treatment was not associated with metachronous gastric neoplasm after ESD with curative resection for gastric adenoma.

Semiconducting lead halide perovskite nanocrystals (PNCs) are regarded as promising candidates for next-generation optoelectronic devices due to their solution processability and outstanding optoelectronic properties. While the field of light-emitting diodes (LEDs) and photovoltaics (PVs), two prime examples of optoelectronic devices, has recently seen a multitude of efforts toward high-performance PNC-based devices, realizing both devices with high efficiencies and stabilities through a single PNC processing strategy has remained a challenge.  In this work, diphenylpropylammonium (DPAI) surface ligands, found through a judicious ab-initio-based ligand search, are shown to provide a solution to this problem. The universal PNC ink with DPAI ligands presented here, prepared through a solution-phase ligand-exchange process, simultaneously allows single-step processed LED and PV devices with peak electroluminescence external quantum efficiency of 17.00% and power conversion efficiency of 14.92% (stabilized output 14.00%), respectively. It is revealed that a careful design of the aromatic rings such as in DPAI is the decisive factor in bestowing such high performances, ease of solution processing, and improved phase stability up to 120 days. This work illustrates the power of ligand design in producing PNC ink formulations for high-throughput production of optoelectronic devices; it also paves a path for "dual-mode" devices with both PV and LED functionalities., (© 2022 Wiley-VCH GmbH.)