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Zhao-Li Zhang,1,&ast; Zhen Xu,2,&ast; Shi-Kun Yang,3 Jin-Gui Huang,2 Feng-Mei Huang,2 Yu-Mei Shi2 1Department of Nursing, Chongqing University Cancer Hospital, Chongqing, 400030, People’s Republic of China; 2Department of Medical Oncology, Chongqing University Cancer Hospital, Chongqing, 400030, People’s Republic of China; 3Department of Pathology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400072, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu-Mei Shi, Email 515342831@qq.comPurpose: The purpose of this study is to understand the level of quality of life (QOL) of lung cancer patients receiving immunotherapy and to clarify the potential mediating role of self-perceived burden (SPB) in the relationship between financial toxicity (FT) and QOL.Patients and Methods: A convenience sample of 342 lung cancer patients receiving immunotherapy was recruited from a cancer hospital from October 2022 to April 2023 for this cross-sectional study. The participants were requested to complete the following structured questionnaires: a sociodemographic and clinical questionnaire, the Functional Assessment of Cancer Therapy–Lung (FACT-L), the Self-Perceived Burden Scale (SPBS) and the COmprehensive Score for Financial Toxicity (COST). The data were subjected to Pearson correlation analysis and bootstrapping analysis in structural equation modelling.Results: The total FACT-L score was 79.90± 15.84 points in 322 lung cancer patients receiving immunotherapy. FT (β = 0.37, P < 0.01) and SPB (β = − 0.27, P < 0.01) had a direct effect on QOL. In addition, SPB partly mediated the association between FT and QOL, and the standardized indirect effect was 0.19, accounting for 33.9% of the total effect.Conclusion: The present study revealed that there is still much room for improvement in the QOL of lung cancer patients during immunotherapy. A greater financial burden resulted in a greater self-perceived burden and was thus associated with inferior QOL. It is imperative for oncology nurses to routinely assess QOL, FT or risk and SPB for lung cancer patients undergoing immunotherapy as well as to assist those patients in understanding the potential financial risk of each choice and help them take more active roles in their routine clinical care.Keywords: lung cancer, immunotherapy, quality of life, financial toxicity, self-perceived burden

Bai Xiang,1,* Xue-Li Jia,1,* Jin-Long Qi,2 Li-Ping Yang,1 Wei-Hong Sun,1 Xiao Yan,1 Shao-Kun Yang,1 De-Ying Cao,1 Qing Du,1 Xian-Rong Qi3 1Department of Pharmaceutics, School of Pharmaceutical Sciences, 2Department of Pharmacology, Hebei Medical University, Shijiazhuang, Hebei, 3School of Pharmaceutical Sciences, Peking University, Beijing, China *These authors contributed equally to this work Abstract: As a potent therapeutic agent, small interfering RNA (siRNA) has been exploited to silence critical genes involved in tumor initiation and progression. However, development of a desirable delivery system is required to overcome the unfavorable properties of siRNA such as its high degradability, molecular size, and negative charge to help increase its accumulation in tumor tissues and promote efficient cellular uptake and endosomal/lysosomal escape of the nucleic acids. In this study, we developed a new activatable cell-penetrating peptide (ACPP) that is responsive to an acidic tumor microenvironment, which was then used to modify the surfaces of siRNA-loaded liposomes. The ACPP is composed of a cell-penetrating peptide (CPP), an acid-labile linker (hydrazone), and a polyanionic domain, including glutamic acid and histidine. In the systemic circulation (pH 7.4), the surface polycationic moieties of the CPP (polyarginine) are “shielded” by the intramolecular electrostatic interaction of the inhibitory domain. When exposed to a lower pH, a common property of solid tumors, the ACPP undergoes acid-catalyzed breakage at the hydrazone site, and the consequent protonation of histidine residues promotes detachment of the inhibitory peptide. Subsequently, the unshielded CPP would facilitate the cellular membrane penetration and efficient endosomal/lysosomal evasion of liposomal siRNA. A series of investigations demonstrated that once exposed to an acidic pH, the ACPP-modified liposomes showed elevated cellular uptake, downregulated expression of polo-like kinase 1, and augmented cell apoptosis. In addition, favorable siRNA avoidance of the endosome/lysosome was observed in both MCF-7 and A549 cells, followed by effective cytoplasmic release. In view of its acid sensitivity and therapeutic potency, this newly developed pH-responsive and ACPP-mediated liposome system represents a potential platform for siRNA-based cancer treatment. Keywords: siRNA, ACPP, hydrazone, liposome, endosomal/lysosomal escape

Li Tao Zhang,1 Sung Won Lee,2 Kwangsung Park,3 Woo Sik Chung,4 Sae Woong Kim,5 Jae Seog Hyun,6 Doo Geon Moon,7 Sang-Kuk Yang,8 Ji Kan Ryu,9 Dae Yul Yang,10 Ki Hak Moon,11 Kweon Sik Min,12 Jong Kwan Park1 1Department of Urology, Chonbuk National University, Medical School and Biomedical Research Institute and Clinical Trial Center for Medical Devices of Chonbuk National University Hospital, Jeonju; 2Department of Urology, College of Medicine, Sungkyunkwan University, Seoul; 3Department of Urology, College of Medicine, Chonnam National University, Gwangju; 4Department of Urology, College of Medicine, Ewha Woman’s University, Seoul; 5Department of Urology, College of Medicine, Catholic University, Seoul; 6Department of Urology, College of Medicine, Kyungsang National University, Jinju; 7Department of Urology, College of Medicine, Korea University, Seoul; 8Department of Urology, Chungju Hospital, College of Medicine, Konkuk University, Chungju; 9Department of Urology, College of Medicine, Inha University, Incheon; 10Department of Urology, College of Medicine, Hallym University, Seoul; 11Department of Urology, College of Medicine, Youngnam University, Daegu; 12Department of Urology, College of Medicine, Inje University, Busan, Republic of Korea Background: The objective of this study was to assess the efficacy and safety of alfuzosin 10 mg monotherapy or combined antihypertensive medication on blood pressure (BP) in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH/LUTS) with or without antihypertensive medication.Methods: This was a 3-month, multicenter, randomized, open-label study in 335 patients aged ≥45 years with a clinical diagnosis of BPH/LUTS by medical history and clinical examination, a total International Prostatic Symptom Score (IPSS) ≥8 points, a maximum flow rate >5 mL/sec and ≤15 mL/sec, and a voided volume ≥120 mL. Eligible subjects were randomized to receive alfuzosin 10 mg as monotherapy (group 1) or alfuzosin 10 mg + antihypertensive combination therapy (group 2). Based on baseline BP and hypertensive history with or without antihypertensive medications at first medical examination, group 1 was divided into two subgroups of normotensive and untreated hypertensive patients, and group 2 into two subgroups of controlled hypertensive and uncontrolled hypertensive patients. The primary study outcomes were change in IPSS, BP, and heart rate from baseline. Secondary outcomes were change in IPSS-quality of life score, maximum flow rate, average flow rate, voided volume, and post-voided volume.Results: The overall BP change was not significantly different between groups 1 and 2 (systolic BP, P=0.825; diastolic BP, P>0.999). In patients with uncontrolled or untreated hypertension, alfuzosin 10 mg alone or combined with antihypertensive therapy significantly decreased systolic and diastolic BP. The mean difference in total IPSS and IPSS-quality of life scores from baseline between groups 1 and 2 was 0.45 (95% CI: −1.26, 2.16) and 0.12 (95% CI: −0.21, 0.45), respectively (both P>0.05). Maximum flow rate, average flow rate, voided volume, and post-voided volume at endpoint were numerically, but not significantly, changed from baseline (all P>0.05).Conclusion: This study shows that alfuzosin 10 mg is effective and well tolerated in patients with BPH/LUTS with or without antihypertensive medications. However, in patients with uncontrolled or untreated hypertension, alfuzosin 10 mg alone or in combination with antihypertensive medication appears to decrease systolic and diastolic BP, and these patients should be warned about a decrease in BP on initiation of therapy. Keywords: alfuzosin, lower urinary tract symptoms, benign prostatic hyperplasia, antihypertensive medication, blood pressureA Letter to the Editor has been received and published for this article.

The current study aimed to investigate the physicochemical properties of the natural eggshell membrane (NEM) and its protective effects against H 2 O 2 -induced oxidative stress in human chondrocytes (SW-1353). Bioactive components from NEM related to cartilage were profiled, consisting of 1.1 ± 0.07% hyaluronic acid, 1.2 ± 0.25% total sulfated glycosaminoglycans as chondroitin sulfate, 3.1 ± 0.33% collagen, and 54.4 ± 2.40% total protein. Protein was hydrolyzed up to 43.72 ± 0.76% using in vitro gastro-intestinal digestive enzymes. Peptides eluted at 9.58, 12.46, and 14.58 min using nano-LC-ESI-MS were identified as TEW, SWVE, and VYL peptides with an M/Z value of 435.1874, 520.2402, and 394.2336, respectively. Radical scavenging activity of NEM at 10 mg/mL using the ABTS assay was revealed to be 2.1 times higher than that of the positive control. NEM treatment significantly enhanced cellular SOD expression ( p < 0.05). Pre-treatment with NEM (0.1, 1, and 10 mg/mL) dose-dependently reduced H 2 O 2 -induced ROS levels in SW-1353. Cell live imaging confirmed that NEM pre-treatment led to a significant reduction in apoptosis expression compared to control. Results from the present study suggest that NEM rich in cartilage protective components including hyaluronic acid, collagen, and chondroitin antioxidative peptides could be a potential therapeutic agent for osteoarthritis (OA) by scavenging oxidative stress.

Nanoplastics are prevalent in the environment and emerging evidence suggests they can induce organ injury by activating oxidative stress. Given that both nanoplastics and Zn 2+ levels are intertwined with oxidative stress, it is crucial to investigate the influence of nanoplastics on the level of labile Zn 2+ and get a better understanding of their cytotoxicity mechanisms. At the organelle level, the Golgi apparatus plays an active role in stress responses. In this study, we synthesized Golgi-Zn, the first ratiometric fluorescence nanosensor with Golgi apparatus targeting ability for monitoring of Zn 2+ . This nanosensor demonstrated high sensitivity and selectivity as well as robust pH stability for Zn 2+ sensing. The ratio of the two fluorescence signals of Golgi-Zn showed a good linearity with Zn 2+ concentration in the range of 0.5-10 μM, achieving a limit of detection of ∼72.4 nM. Furthermore, the nanosensor exhibited low cytotoxicity and effectively targeted the Golgi apparatus. Leveraging these fascinating features, we successfully applied Golgi-Zn for visualizing exogenous and endogenous Zn 2+ levels in the Golgi apparatus. Moreover, with the help of Golgi-Zn, we found that nanoplastics stimulation could increase the level of Zn 2+ in the Golgi apparatus., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Recognising inflammatory endotypes in chronic rhinosinusitis (CRS) has become more important, especially with the advent of biological treatments. In this study, we investigated the correlations of pre- and post-operative symptoms with cytokine positivity in different endotypes and phenotypes of CRS., Methodology: In total, 102 patients undergoing routine functional endoscopic sinus surgery were enrolled. The endotype classification (type 1, 2, or 3 CRS) was defined based on positivity for interferon-γ, interleukin (IL)-5, or IL-17 respectively, in sinonasal tissue samples. Clinical symptom scores were evaluated pre- and post-operatively using the 22-item Sinonasal Outcome Test and its four symptom subdomains: sleep, nasal, otologic/facial symptoms, and emotional function. Symptoms were compared between endotypes and phenotypes, and exploratory factor analysis (EFA) based on principal component analysis (PCA) was performed. The correlations of cytokine levels with baseline symptoms and changes in symptoms after 1 year were analysed., Results: Symptoms in the otologic/facial pain category were associated with non-type 2 endotypes in PCA and confirmatory analysis. Non-type 2 CRS patients exhibited significantly more improvement in facial symptoms 1 year after surgery. Neutrophil-associated cytokines, such as IL-17, matrix metalloproteinase 9, and myeloperoxidase, were significantly correlated with baseline otologic/facial pain symptoms and changes in those symptoms after surgery., Conclusions: Otologic/facial pain symptoms may be indicative of non-type 2 endotypes. Neutrophil-associated cytokines, such as IL-17, MMP-9, and MPO, were significantly correlated with these symptoms. The establishment of links between specific symptoms and certain cytokines may help use and develop biological therapies for CRS.

Background: Crohn's disease (CD) exhibits variability in colorectal cancer (CRC) incidence and prognostic factors due to diverse clinical and behavioral characteristics, presenting inconsistencies between Western and Eastern patients., Objectives: This study compared clinical characteristics between CD patients with CRC from the US and Korean tertiary referral centers and defined the prognostic factors related to mortality., Design: Retrospective study., Methods: We reviewed the electronic medical records of 236 adult CD patients with colorectal adenocarcinoma evaluated at Mayo Clinic Rochester, Florida, or Arizona ( N  = 200) and Asan Medical Center in Korea ( N  = 36) between January 1989 and August 2022., Results: Asan patients had a younger age, shorter CD duration, more colonic involvement (L2 plus L3), penetrating behavior, perianal fistula, and shorter biological treatment duration before CRC diagnosis than Mayo patients. Furthermore, despite significant differences in body mass index, smoking status, primary sclerosing cholangitis, immunomodulators, CRC diagnosis period, clinical presentation, CRC location, surgery, and some histopathological details between the two groups, overall survival was not statistically different ( p value, 0.29, log-rank test). Advanced age (adjusted hazard ratio (aHR), 1.03 per year; 95% confidence interval (CI), 1.01-1.04; p value, <0.01), unresectable CRC (aHR, 5.02; 95% CI, 2.49-10.12; p value, <0.01), and advanced CRC stage (aHR, 1.45 per stage; 95% CI, 1.07-1.97; p value, 0.02) were significantly associated with increased risk of death. CD remission at CRC diagnosis (aHR, 0.26; 95% CI, 0.08-0.91; p value, 0.04), CRC diagnosis period of 2011-2022 (aHR relative to 1989-2000, 0.46; 95% CI, 0.25-0.87; p value, 0.02), and CRC diagnosis by surveillance (aHR, 0.56; 95% CI, 0.32-0.98; p value, 0.04) were significantly associated with decreased risk of death., Conclusion: Notably, some clinical features of CD with CRC differed between Asan and Mayo patients; however, overall survival was not different. CD remission, CRC surveillance, and more recent diagnosis of CRC were associated with a reduced risk of death., Competing Interests: N.C.-P. has served as a consultant for Alexion Pharma and Boston Scientific. J.B.K. is an inventor of Mayo Clinic intellectual property, licensed to Exact Sciences (Madison, WI, USA), in the early detection of colorectal cancer, for which he may receive royalties paid to Mayo Clinic. B.D.Y. has received consulting fees from AbbVie Korea, BMS Pharmaceutical Korea Ltd, Celltrion, Chong Kun Dang Pharm, CJ Red BIO, Daewoong Pharma, Ferring Korea, IQVIA, Janssen Korea, Kangstem Biotech, Korea Otsuka Pharm., Korea United Pharm. Inc., Medtronic Korea, NanoEntek, ORGANOIDSCIENCES LTD, Pfizer Korea, Samsung Bioepis, Takeda, and Takeda Korea; speaker fees from AbbVie Korea, Celltrion, Cornerstones Health, Curacle, Daewoong Pharma, Ferring Korea, IQVIA, Janssen Korea, Pfizer Korea, and Takeda Korea; and research support from Celltrion and Pfizer Korea. None of these disclosures are directly associated with this study. E.V.L. has served as a consultant for AbbVie, Alvotech, Amgen, Arena, Astellas, Avalo Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion Healthcare, Eli Lilly, Fresenius Kabi, Genentech, Gilead, Gossamer Bio, GlaxoSmithKline, Iota Biosciences, Iterative Scopes, Janssen, KSL Diagnostics, Morphic, Ono Pharma, Protagonist, Sun Pharma, Surrozen, Takeda, TR1X, and UCB; received research support from AbbVie, AstraZeneca, Bristol-Myers Squibb, Celgene/Receptos, Genentech, Gilead, Gossamer Bio, Janssen, Pfizer, Takeda, Theravance, and UCB; and shareholder of Exact Sciences. T.S., S.W.H., S.-K.Y., and S.H.P. disclose no conflicts., (© The Author(s), 2024.)

Objectives: Chronic rhinosinusitis (CRS) endotypes have demonstrated clinical value in guiding treatment decisions. Bacterial lysates are immunomodulators that have shown beneficial effects in various respiratory inflammatory diseases. This study aimed to evaluate the effect of postoperative bacterial lysate therapy on different CRS endotypes., Methods: Patients diagnosed with CRS who underwent endoscopic sinus surgery were recruited. Bacterial lysates were administered postoperatively for 10 days per month for 3 months to the experimental group comprising patients with a history of frequent upper respiratory infections without adverse reactions. The remaining participants were allocated to the control group. The results of the postoperative 3-, 6-, and 12-month assessments, including the modified Lund-Kennedy (mLK) endoscopic and Sinonasal Outcome Test (SNOT) 22 scores, for the groups were compared. The tissue samples obtained from the participants were evaluated to detect the presence of relevant inflammatory mediators., Results: Among the 92 participants, 47 started bacterial lysate therapy 2 weeks after the surgery. The tissue cytokine profiles and clinical parameters, such as the disease severity and blood eosinophil percentage, of the bacterial lysate and control groups were comparable before treatment. The mLK endoscopic and SNOT-22 scores did not differ after 3, 6, and 12 months of follow-up. The subgroup analysis revealed that the bacterial lysate group had significantly lower mLK endoscopic scores than the control group for CRS without nasal polyps, while there was a tendency toward significance for the interleukin (IL)-5 negative group after 6 months., Conclusion: Postoperative bacterial lysate therapy has some beneficial effects on the endoscopic findings of patients with CRS without nasal polyps or those who are negative for IL-5., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background/aims: Video capsule endoscopy is rarely used to diagnose Crohn's disease in patients with negative ileocolonoscopy or cross-sectional image findings. We evaluated clinical characteristics and long-term outcomes of these rare cases., Methods: This multicenter study included patients with Crohn's disease from 3 tertiary hospitals from January 2007 to October 2022. Patients with normal findings on ileocolonoscopy and computed tomography (CT)/magnetic resonance (MR) enterography but had ulcerations at the small bowel detected by video capsule endoscopy were included. The controls were patients with abnormal findings on endoscopy or CT/MR enterography. Controls were case-matched in a ratio of 3:1 for sex, calendar year of diagnosis, and age at diagnosis., Results: Among 3,752 patients, 24 (0.6%) were diagnosed with Crohn's disease using video capsule endoscopy findings. The disease location (P< 0.001) and behavior at diagnosis (P= 0.013) of the cases significantly differed from that of controls. The perianal fistula modifier (25.0% vs. 33.3%, P= 0.446) did not differ significantly between the 2 groups. Initial disease activity and C-reactive protein and fecal calprotectin levels were significantly lower in cases versus controls. The median Lewis score was 838 (interquartile range, 393-1,803). Over 10 years of follow-up, the cases showed significantly lower cumulative risk of complicated behavior, biologics use, Crohn's disease-related hospitalization, and surgeries (log-rank test P< 0.05)., Conclusions: Patients with Crohn's disease whose lesions were observed only by video capsule endoscopy were rare, and exhibit different clinical characteristics and a more favorable long-term disease course compared to those who were conventionally diagnosed.

Purpose: The purpose of this study was to conduct a pre-conception care program for women of childbearing age with inflammatory bowel disease (IBD) in Korea and verify its effects on self-efficacy for IBD management, IBD-related pregnancy knowledge, and IBD-related pregnancy anxiety. It also aimed to explore the changes in participants through the program., Methods: A convergent mixed-methods study design was adopted. In the quantitative phase, 35 women (17 and 18 in the intervention and control group, respectively) participated. The intervention group attended a program that included small-group sessions and individual tele-coaching. To confirm the effects, data were collected before and one and four weeks after the intervention. In the qualitative stage, focus group interviews and tele-coaching were conducted with the intervention group., Results: After the program ended, significant differences were observed over time between the intervention and control groups for self-efficacy for IBD management (Wald χ² = 4.41, p = .036), IBD-related pregnancy knowledge (Wald χ² = 13.80, p < .001) and IBD-related pregnancy anxiety (Wald χ² = 8.61, p = .003). Qualitative data analysis revealed the following themes: (1) improving confidence in IBD management and awareness for planned pregnancy; (2) improving IBD awareness related to pregnancy and childbirth; and (3) relieving anxiety about and actively facing pregnancy., Conclusion: This study is meaningful in that, to the best of our knowledge, it is the first to develop a pre-conception care program for women diagnosed with IBD and confirm its effectiveness. Furthermore, this program is expected to be suitable for patient counseling and education in clinical practice., Competing Interests: The authors declared no conflict of interest., (© 2024 Korean Society of Nursing Science.)

Background: The impact of continuing or stopping 5-aminosalicylates (5-ASA) after commencing anti-tumour necrosis factor (anti-TNF) therapy in patients with inflammatory bowel disease (IBD) remains unclear., Aims: To compare the outcomes of patients with IBD who stopped or continued 5-ASA after starting anti-TNF therapy., Methods: We analysed data from the Korean National Health Insurance claims database between 2007 and 2020. We compared the clinical outcomes of patients who stopped or continued 5-ASA within 90 days of anti-TNF initiation. The primary outcome was any adverse clinical event defined as a composite of new corticosteroid use, IBD-related hospitalisation, or intestinal surgery., Results: Among 7442 patients included for analysis (4479 [60.2%] with Crohn's disease [CD] and 2963 [39.8%] with ulcerative colitis [UC]), 1037 (13.9%) discontinued 5-ASA within 90 days of starting anti-TNF therapy. During a median 4.3-year follow-up, discontinuation of 5-ASA was not associated with an increased risk of adverse clinical events (adjusted hazard ratio 1.01, 95% confidence interval 0.93-1.10). The cumulative incidence of each adverse clinical event and the composite outcome were not significantly different between groups (all, p > 0.05). Additionally, separate analyses in CD and UC cohorts revealed no differences in adverse clinical outcomes between the 5-ASA continuation and discontinuation groups. Subgroup analyses by presumed risk factors for disease relapse showed no significant differences in the risk of adverse events between groups., Conclusions: In this nationwide population-based study, discontinuing 5-ASA after starting anti-TNF therapy was not associated with an increased risk of adverse events in patients with IBD., (© 2024 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Background/aims: Studies on elective switching to the subcutaneous (SC) formulation of infliximab revealed comparable efficacy and safety and higher infliximab level than those exhibited by intravenous (IV) infliximab. However, no studies have reported on the effectiveness of SC switching in ulcerative colitis (UC) patients who experienced IV infliximab failure during maintenance treatment., Methods: This retrospective study included UC patients who had been switched to SC infliximab because of IV infliximab failure, between January 2021 and January 2023. Group A was defined as having clinically and biochemically active UC (secondary loss of response), and group B consisted of patients with stable symptoms but biochemically active UC., Results: Twenty-three patients met the inclusion criteria: 15 in group A and eight in group B. The serum infliximab levels significantly increased after SC switching in both groups. The electively switched group also exhibited increased infliximab levels after SC switching. Patients in group A showed improved partial Mayo score with a significant decrease in fecal calprotectin and C-reactive protein after switching. In group B, the fecal calprotectin level significantly decreased without clinical relapse after switching. A high proportion of patients (≥80%) in both groups achieved clinical and/or biochemical responses at the last follow-up. During the follow-up period, only two patients in group A discontinued SC infliximab, and only one complained of severe injection site reaction., Conclusions: In UC patients who experience IV infliximab failure during maintenance treatment, switching to SC infliximab may be a promising option because of better efficacy and safety.

Background/aim: We aimed to validate clinical decision support tools (CDSTs) to predict real-life effectiveness of vedolizumab (VDZ) in patients with inflammatory bowel disease., Methods: We retrospectively enrolled patients with Crohn's disease (CD) or ulcerative colitis (UC) treated with VDZ at 10 tertiary referral centres in Korea between January 2017 and November 2021. We assessed clinical remission (CREM) and response (CRES), corticosteroid-free clinical remission (CSF-CREM) and response (CSF-CRES), biochemical response based on C-reactive protein (BioRES[CRP]) and faecal calprotectin (BioRES[FC]), endoscopic healing (EH), and the need to optimise or switch drugs based on CDST-defined response groups. Additionally, the area under the receiver operating characteristics curve (AUC) for the CDSTs was calculated., Results: We included 143 patients with CD and 219 with UC. We observed incremental trends on CSF-CRES at week 14 (W14) (p trend  = 0.004) and decreasing trends for the need to optimise or switch drugs (p trend  = 0.016) in CD from the low to high probability groups. Except for CSF-CREM at W54, we noticed incremental trends for all clinical responses at W14, W26 and W54 (p trend  <0.001) in UC. W26 and W54 BioRES[CRP] and W14 EH also showed increasing trends (p trend  <0.05) in UC. With increasing probabilities of response, drug optimisation or switching was less frequently required in UC (p trend  = 0.013). With 26 points cut-off, CDSTs effectively identified W14 CSF-CRES, W26 BioRES[CRP], BioRES[FC] and W54 BioRES[CRP] in UC, all with AUCs >0.600, whereas CDSTs showed poor accuracy in CD., Conclusions: CDSTs for VDZ had acceptable accuracy in predicting effectiveness outcomes including clinical and biochemical outcomes in UC. However, their utility in CD was limited., (© 2024 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Nowadays, a wide variety of labels of items are widely available, and human consumption is increasingly tailored to meet their individual needs. So, many businesses are starting to focus on improving the functionality of modern packaging. Sensorial paradigms and emotional reactions could change during the user-product interaction lifecycle. The designer's emotional imagination and past experiences are the backbone of conventional product package design, which has limitations due to unmanageable content and an absence of professional advice-the majority of previous research on emotional image analysis aimed to forecast the most common viewer emotions. Since the feelings a picture evokes are quite individual and vary from viewer to viewer, this overarching feeling isn't always enough for practical uses. The research presented an approach to packaging design evaluation based on image emotion perception computing (PDE-IEPC), which combines emotion perception technology with a deep LSTM (Long short-term model), resulting in an immersive and dynamic experience for the human senses. Emotion Perception Computing's Dynamic Multi-task Hypergraph Learning (DMHL) approach considers graphical data, social context, spatial evolution, and location, among other criteria, to evaluate packaging designs efficiently based on their emotional impact. Image-Emotion-Social-Net is a large dataset used to evaluate multidimensional and categorical attitude representation. The dataset is sourced from Flickr and contains over 1 million images presented by over 9000 users. Personalized emotion categorization is an area where research on this dataset shows that the suggested strategy outperforms many modern techniques. The experimental results show that the proposed method achieves a high packaging design quality rate of 94.1 %, a performance success rate of 97.5 %, and a mean square error rate of 2 % compared to other existing methods., 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., (© 2024 The Authors.)

Purpose: Studies on intestinal Behçet's disease (BD) complicated by myelodysplastic syndrome (MDS) are rare, and no established therapeutic guidelines exist. This study aimed to evaluate the clinical presentation and outcomes of patients with intestinal BD complicated by MDS (intestinal BD-MDS) and suggest a treatment strategy., Materials and Methods: Data from patients with intestinal BD-MDS from four referral centers in Korea who were diagnosed between December 2000 and December 2022 were retrospectively analyzed. Clinical features and prognosis of intestinal BD-MDS compared with age-, sex-matched intestinal BD without MDS were investigated., Results: Thirty-five patients with intestinal BD-MDS were included, and 24 (70.6%) had trisomy 8. Among the 35 patients, 23 (65.7%) were female, and the median age at diagnosis for intestinal BD was 46.0 years (range, 37.0-56.0 years). Medical treatments only benefited eight of the 32 patients, and half of the patients underwent surgery due to complications. Compared to 70 matched patients with intestinal BD alone, patients with intestinal BD-MDS underwent surgery more frequently (51.4% vs. 24.3%; p =0.010), showed a poorer response to medical and/or surgical treatment (75.0% vs. 11.4%; p <0.001), and had a higher mortality (28.6% vs. 0%; p <0.001). Seven out of 35 patients with intestinal BD-MDS underwent hematopoietic stem cell transplantation (HSCT), and four out of the seven patients had a poor response to medical treatment prior to HSCT, resulting in complete remission of both diseases., Conclusion: Patients with intestinal BD-MDS frequently have refractory diseases with high mortalities. HSCT can be an effective treatment modality for medically refractory patients with intestinal BD-MDS., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2024.)

Crohn's disease (CD) is a chronic inflammatory disorder affecting the bowel wall. Tissue-resident memory T (Trm) cells are implicated in CD, yet their characteristics remain unclear. We aimed to investigate the transcriptional profiles and functional characteristics of Trm cells in the small bowel of CD and their interactions with immune cells. Seven patients with CD and four with ulcerative colitis as controls were included. Single-cell RNA sequencing and paired T cell receptor sequencing assessed T cell subsets and transcriptional signatures in lamina propria (LP) and submucosa/muscularis propria-enriched fractions (SM/MP) from small bowel tissue samples. We detected 58,123 T cells grouped into 16 populations, including the CD4 + Trm cells with a Th17 signature and CD8 + Trm clusters. In CD, CD4 + Trm cells with a Th17 signature, termed Th17 Trm, showed significantly increased proportions within both the LP and SM/MP areas. The Th17 Trm cluster demonstrated heightened expression of tissue-residency marker genes (ITGAE, ITGA1, and CXCR6) along with elevated levels of IL17A, IL22, CCR6, and CCL20. The clonal expansion of Th17 Trm cells in CD was accompanied by enhanced transmural dynamic potential, as indicated by significantly higher migration scores. CD-prominent Th17 Trm cells displayed an increased interferon gamma (IFNγ)-related signature possibly linked with STAT1 activation, inducing chemokines (i.e., CXCL10, CXCL8, and CXCL9) in myeloid cells. Our findings underscored the elevated Th17 Trm cells throughout the small bowel in CD, contributing to disease pathogenesis through IFNγ induction and subsequent chemokine production in myeloid cells., Competing Interests: Declaration of competing interest Suk-Kyun Yang has received a research grant from Janssen Korea. Byong Duk Ye has received research grants from Celltrion and Pfizer Korea; consulting fees from AbbVie Korea, BMS Pharmaceutical Korea Ltd., Celltrion, Chong Kun Dang Pharm, CJ Red BIO, Curacle, Daewoong Pharm, Ferring Korea, IQVIA, Janssen Korea, Kangstem Biotech, Korea Otsuka Pharm, Korea United Pharm, Medtronic Korea, NanoEntek, ORGANOIDSCIENCES LTD., Pfizer Korea, Samsung Bioepis, Takeda, and Takeda Korea; and speaking fees from AbbVie Korea, Celltrion, Cornerstones Health, Curacle, Ferring Korea, IQVIA, Janssen Korea, Pfizer Korea, and Takeda Korea. None of these disclosures are directly associated with this study., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: This study aimed to evaluate the safety of biologics and small molecules for the treatment of inflammatory bowel diseases (IBD) in patients receiving antirejection therapies after organ transplants., Materials and Methods: We reviewed the medical records of patients with IBD who received organ transplants at the Asan Medical Center between January 1989 and December 2021. We compared the parameters of patients receiving biologics or small molecules to those of patients without those therapies., Results: This study included a total of 53 patients (ulcerative colitis, 41; Crohn's disease, 6; and gastrointestinal Behçet's disease, 6). Among them, 15 patients were receiving biologics or small molecules and 38 were not. During a mean follow-up of 119 months, the proportion of patients experiencing severe infections was significantly higher in those treated with biologics or small molecules than in those not treated. However, other safety outcomes (e.g., malignancies, adverse events, including organizing pneumonia or hepatic failure, and death) were not different between the two groups. Kaplan-Meier curve analysis revealed no significant difference in the safety outcome rate related to the use of biologics or small molecules. During follow-up, eight patients underwent bowel resections for IBD. The rate of bowel resection was not different between the two groups., Conclusion: The use of biologics or small molecules for patients with IBD who received organ transplants did not show a significant difference in safety outcomes. However, the possibility of severe infections must be considered., Competing Interests: The authors have no potential conflicts of interest to disclose, (© Copyright: Yonsei University College of Medicine 2024.)

Fecal calprotectin (FC) is commonly used to assess Crohn's disease (CD) activity. However, standardized cut-off values accounting for bowel resection history and disease location are lacking. In this study, we analyzed data from patients with CD who underwent magnetic resonance enterography, ileocolonoscopy, and FC measurements from January 2017 to December 2018. In 267 cases from 254 patients, the FC levels in the 'operated' patients were higher when the disease was active compared with those who were in the remission group (178 vs. 54.7 μg/g; p < 0.001), and similar findings were obtained for the 'non-operated' patients (449.5 vs. 40.95 μg/g; p < 0.001). The FC levels differed significantly according to the location of inflammation, with lower levels in the small bowel compared to those in the colon. The FC cut-off levels of 70.8 μg/g and 142.0 μg/g were considered optimal for predicting active disease for operated and non-operated patients, respectively. The corresponding FC cut-off levels of 70.8 μg/g and 65.0 μg/g were observed for patients with disease only in the small bowel. In conclusion, different FC cut-off values would be applicable to patients with CD based on their bowel resection history and disease location. Tight control with a lower FC target may benefit those with a history of bowel resection or small-bowel-only disease.

Acetylation of α-tubulin at the lysine 40 residue (αK40) by αTAT1/MEC-17 acetyltransferase modulates microtubule properties and occurs in most eukaryotic cells. Previous literatures suggest that acetylated microtubules are more stable and damage resistant. αK40 acetylation is the only known microtubule luminal post-translational modification site. The luminal location suggests that the modification tunes the lateral interaction of protofilaments inside the microtubule. In this study, we examined the effect of tubulin acetylation on the doublet microtubule (DMT) in the cilia of Tetrahymena thermophila using a combination of cryo-electron microscopy, molecular dynamics, and mass spectrometry. We found that αK40 acetylation exerts a small-scale effect on the DMT structure and stability by influencing the lateral rotational angle. In addition, comparative mass spectrometry revealed a link between αK40 acetylation and phosphorylation in cilia., Competing Interests: SY, SK, CB, KP, DD, TL, MV, JG, KB No competing interests declared, (© 2023, Yang, Kubo et al.)

Objective: To analyze changes in olfactory function after endoscopic endonasal skull base surgery and compare performance of the olfactory questionnaire with those of conventional psychophysical tests. Methods: Patients were classified into 5 categories for olfactory function evaluation (normal, mild hyposmia, moderate hyposmia, severe hyposmia, and anosmia) based on a self-assessment. Patients also underwent the butanol threshold test (BTT), Cross-Cultural Smell Identification Test (CCSIT), and 11-item olfactory questionnaire. Subjects with normosmia preoperatively and who were followed up at least 6 months after surgery were analyzed. Receiver operating characteristic curves and confusion matrix analysis were performed for BTT, CCSIT, and olfactory questionnaire to compare their diagnostic abilities. The effects of age, preoperative olfaction, septal flap, tumor pathology, and tumor size on postoperative olfaction were evaluated using multivariate linear regression analysis. Results: Data from 108 patients were analyzed. Postoperative changes in the olfactory questionnaire were significantly associated with changes in the BTT and CCSIT. The area under the curve for postoperative self-olfactory function classification was highest for olfactory questionnaire (0.894), followed by BTT (0.767) and CCSIT (0.688). Patient age at the time of surgery and preoperative BTT score were significantly related to postoperative olfactory outcomes. Conclusion: The olfactory questionnaire correlated well with conventional psychosomatic olfactory function tests. In combination with clinical parameters and preoperative psychosomatic olfactory function tests, the olfactory questionnaire is suitable for assessing subjective olfactory function after endoscopic endonasal skull base surgery., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Aims: Creeping fat [CF] is a poorly understood feature of Crohn's disease [CD], characterized by the wrapping of mesenteric adipose tissue [MAT] around the inflamed intestine. The aim of this study was to investigate the transcriptional profile and compositional features of CF., Methods: We collected 59 MAT samples: 23 paired samples from patients with CD (CF [CD-CF] and MAT around the uninflamed intestine [CD-MAT]) and 13 MAT samples from non-CD patients [Con-MAT]. Differentially expressed gene [DEG], functional pathway, cell deconvolution, and gene co-expression network analyses were performed., Results: By comparing three different MAT samples, we identified a total of 529 DEGs [|log2FoldChange| > 1.5; false discovery rate < 0.05]. Of these, 323 genes showed an incremental pattern from Con-MAT to CD-MAT, and to CD-CF, while 105 genes displayed a decremental pattern. Genes with an incremental pattern were related to immune cell responses, including B- and T-cell activation, while genes with a decremental pattern were involved in cell trafficking and migration. Cell deconvolution analysis revealed significant changes in cellular composition between the CD-CF and Con-MAT groups, with increased proportions of B-cells/plasma cells [p = 1.16 × 10-4], T-cells [p = 3.66 × 10-3], and mononuclear phagocytes [p = 3.53 × 10-2] in the CD-CF group. In contrast, only the B-cell/plasma cell component showed a significant increase [p = 1.62 × 10-2] in the CD-MAT group compared to Con-MAT., Conclusion: The distinct transcriptional profiles and altered cellular components of each MAT found in our study provide insight into the mechanisms behind CF and highlight its possible role in the pathogenesis of CD., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

This study evaluates the accuracy of a newly developed intraocular lens (IOL) power calculation method that applies four different IOL power calculation formulas according to 768 biometric subgroups based on keratometry, anterior chamber depth, and axial length. This retrospective cross-sectional study was conducted in at Korea University Ansan Hospital. A total of 1600 eyes from 1600 patients who underwent phacoemulsification and a ZCB00 IOL in-the-bag implantation were divided into two datasets: a reference dataset (1200 eyes) and a validation dataset (400 eyes). Using the reference dataset and the results of previous studies, the Eom IOL power calculator was developed using 768 biometric subgroups. The median absolute errors (MedAEs) and IOL Formula Performance Indexes (FPIs) of the Barrett Universal II, Haigis, Hoffer Q, Holladay 1, Ladas Super, SRK/T, and Eom formulas using the 400-eye validation dataset were compared. The MedAE of the Eom formula (0.22 D) was significantly smaller than that of the other four formulas, except for the Barrett Universal II and Ladas Super formulas (0.24 D and 0.23 D, respectively). The IOL FPI of the Eom formula was 0.553, which ranked first, followed by the Ladas Super (0.474), Barrett Universal II (0.470), Holladay 1 (0.444), Hoffer Q (0.396), Haigis (0.392), and SRK/T (0.361) formulas. In conclusion, the Eom IOL power calculator developed in this study demonstrated similar or slightly better accuracy than the Barrett Universal II and Ladas Super formulas and was superior to the four traditional IOL power calculation formulas., (© 2024. The Author(s).)

Background: The aim of this study was to compare the diagnostic performance of native antigen ELISAs and ADAMU-AE/CE commercial ICT test kits in subjects either exposed to Echinococcus infection or with clinically diagnosed alveolar (AE) or cystic (CE) echinococcosis., Methods: A total of 370 subjects with a previous clinical confirmation of CE or AE from northwestern China were recruited. Serum samples were also obtained from 3923 children/teenagers during a community survey. All sera were tested using native antigen ELISAs. The ADAMU-AE/CE test kits were subsequently used for the serology of the 370 clinically confirmed individuals and of 251 children/teenagers that were ELISA antibody-positive for both Echinococcus species but ultrasound-negative during baseline survey. An analysis of the association between the serological tests and ultrasound classification was carried out amongst 89 AE and 164 CE cases. A Kappa consistency analysis was undertaken to compare the diagnostic performance of the native antigen ELISAs and the ADAMU kits and the ultrasound imaging results. The χ² test was also used for a comparison of the different seropositivity rates between the groups., Findings: There was poor consistency (Kappa = 0.26 and 0.28 for AE and CE respectively) between the native antigen ELISAs and the ADAMU kits for the diagnosis of AE and CE among the cases and the surveyed children/teenagers, but a relatively good consistency (Kappa = 0.63) between the ADAMU-AE kit and ultrasound observations for the AE cases. Additionally, of the 251 teenagers co-positive for both AE and CE antibodies by the native antigen ELISAs, only one was found positive by the ADAMU-AE kit, verified as a new AE case on subsequent ultrasound follow-up. The remainder (N = 250) were negative by serology using the ADAMU-AE/CE kits and by ultrasound examination. The two native antigen ELISAs did not discriminate well between cases of clinically diagnosed AE and CE. In contrast, ADAMU-AE and ADAMU-CE commercial ICT test kits readily differentiated cases of AE from CE with specificities of 99% for AE and 100% for CE., Conclusions: The ADAMU-AE/CE kits proved reliable, accurate, and amenable diagnostic tools in the clinical setting for confirmation of suspected AE/CE cases. The native antigen ELISAs tests can provide useful information on the level of human exposure to Echinococcus infection.

Fungus ball is the most common form of non-invasive fungal sinusitis, and maxillary sinus is the most commonly involved site. Maxillary sinus fungus ball (MFB) accounts for a considerable proportion of unilateral maxillary sinusitis. The prevalence of MFB has recently increased; however, its contributing factors are unclear. This study analyzed the association between MFB and dental implants. One hundred one patients who underwent unilateral maxillary sinus surgery were divided into two groups based on surgical biopsy results: unilateral bacterial sinusitis (UBS, n = 45) and MFB (n = 56). Stratified random sampling of 30 patients from each group was performed to adjust for age. The number of dental implants on maxillary teeth and degree of penetration into the maxillary sinus was radiologically evaluated. The number of patients with dental implants was greater (P = 0.085) and the number of implants was significantly higher (P = 0.031) in the MFB group. Dental implant can be a potential risk factor for MFB development. Therefore, dental implant surgeons should take caution in penetrating the maxillary sinus floor during implant insertion and otolaryngologists should consider the possibility of fungus ball when assessing patients with sinusitis who have dental implants., (© 2024. The Author(s).)

Background and Aim: This study aimed to investigate the effect of stenting-related factors, including endoscopists' expertise, on clinical outcomes after bridge-to-surgery (BTS) stenting for obstructive colorectal cancer (CRC)., Methods: We analyzed BTS stenting-related factors, including stenting expertise and the interval between stenting and surgery, in 233 patients (63 [13] years, 137 male) who underwent BTS stenting for obstructive CRC. We evaluated the influence of these factors on post-BTS stenting clinical outcomes such as stent-related complications and cancer recurrence., Results: The interval between stenting and surgery was ≤ 7 days in 79 patients (33.9%) and > 7 days in 154 patients (66.1%). BTS stenting was performed by endoscopists with ≤ 50, 51-100, and > 100 prior stenting experiences in 94, 43, and, 96 patients, respectively. The clinical success rate of BTS stenting was 93.1%. Stent-related and postoperative complications developed in 19 (8.2%) and 20 (8.6%) patients, respectively. Cancer recurrence occurred in 76 patients (32.6%). Short BTS interval of ≤ 7 days increased the risk of postoperative complications (odds ratio [OR], 2.61 [1.03-6.75]; P = 0.043). Endoscopists' stenting experience > 100 showed greater clinical success of stenting (OR, 5.50 [1.45-28.39]; P = 0.021) and fewer stent-related complications (OR, 0.26 [0.07-0.80]; P = 0.028) compared with stenting experience ≤ 50. BTS stenting-related factors did not affect long-term oncological outcomes., Conclusion: Greater expertise of endoscopists was associated with better short-term outcomes, including high stenting success rate and low rate of stent-related complications after BTS stenting for obstructive CRC. An interval of > 7 days between BTS stenting and surgery was required to decrease postoperative complications., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: Low-volume bowel preparation solutions, including 1-L polyethylene glycol plus ascorbate (PEG-A), have been developed to improve tolerability. The oral sodium sulfate tablet (OST) is a new agent with simethicone as a preloaded component. We investigated the efficacy, safety, and tolerability of OST compared to 1-L PEG-A., Methods: A single-center, prospective, controlled study was performed with randomization into the OST (group A) and 1-L PEG-A (group B) groups. Bowel preparation efficacy was assessed on the Boston Bowel Preparation Scale (BBPS) and Bubble Scale. Safety and tolerability were evaluated using a questionnaire and laboratory examination., Results: Final analysis was performed on 171 patients (group A: 87, group B: 84). The proportion of bowel preparation success (BBPS ≥ 2 for each colonic segment) in group A was not inferior compared to group B (95.4% vs 96.4%, P = 0.736, 1-sided 97.5% lower confidence limit -7.0%). The adenoma detection rate was not different (59.6% vs 41.9%; P = 0.087). The bubble scale was better in group A (0.2 ± 0.9 vs 1.9 ± 1.7, P < 0.001). All adverse events were mild in both groups. Nausea was less frequent in group A (14.9% vs 38.1%, P = 0.001). Overall satisfaction was better in group A (8.1 ± 2.1 vs 6.4 ± 2.8, P < 0.001). No clinically significant laboratory abnormality developed in both groups. These findings were similarly shown in old patients ≥65 years., Conclusions: Both OST and 1-L PEG-A were efficacious, safe, and tolerable for bowel preparation of colonoscopy. The OST showed fewer bubbles and slightly better tolerability., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: The lateral pharyngeal wall (LPW) is a critical anatomic structure in patients with obstructive sleep apnea (OSA). Resolving the retropalatal circumferential (RC) narrowing caused by combination of both LPW collapse and antero-posterior (AP) narrowing holds promise for surgical treatment of OSA. We sought to determine the clinical characteristics and distinctive alterations in sleep parameters of patients with OSA who have RC narrowing and LPW collapse., Methods: Drug-induced sleep endoscopy (DISE), polysomnography findings, and sleep questionnaires were reviewed retrospectively in patients with OSA., Results: Of the 106 OSA patients examined, 48% showed RC narrowing and 44% showed AP narrowing at the oropharynx level during sleep while 8% of the patients showed only LPW collapse. Patients with RC narrowing with LPW collapse exhibited a higher BMI than those with AP narrowing only. In addition, patients with RC narrowing showed more aggravated sleep parameters including apneic events than patients with AP narrowing alone. The degree of RC narrowing correlated significantly with the severity of OSA as shown by a higher apnea index and lower oxygen desaturations., Conclusions: Our clinical findings suggest that the presence of RC narrowing with LPW collapse in OSA is closely related to increased apneic and oxygen desaturation events. RC narrowing with LPW collapse may be targets for surgical correction in patients with OSA to improve therapeutic outcomes., (© 2023. The Author(s).)