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Ming-Shao Tsai,1– 4,&ast; Hung-Chin Chen,1,&ast; Hsueh-Yu Li,2,5 Yao-Te Tsai,1,2 Yao-Hsu Yang,4,6,7 Chia-Yen Liu,4 Yi‑Chan Lee,2,8 Cheng-Ming Hsu,1,2 Li-Ang Lee2,5,9 1Department of Otolaryngology – Head and Neck Surgery, Chiayi Chang Gung Memorial Hospital, Chiayi, 613, Taiwan; 2Faculty of Medicine, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan; 3Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan; 4Health Information and Epidemiology Laboratory of Chang Gung Memorial Hospital, Chiayi, 613, Taiwan; 5Department of Otolaryngology – Head and Neck Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan, 333, Taiwan; 6Department of Traditional Chinese Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, 613, Taiwan; 7School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan; 8Department of Otolaryngology – Head and Neck Surgery, Keelung Chang Gung Memorial Hospital, Keelung, 204, Taiwan; 9School of Medicine, National Tsing Hua University, Hsinchu, 300, Taiwan&ast;These authors contributed equally to this workCorrespondence: Li-Ang Lee, Department of Otolaryngology – Head and Neck Surgery, Linkou Chang Gung Memorial Hospital, No. 5, Fu-Hsing Street, Gueishan District, Taoyuan City, 33305, Taiwan, Tel +886 3 3281200 ext. 3968, Fax +886 3 3979361, Email 5738@cgmh.org.twPurpose: We executed the presented retrospective cohort study with the purpose of probing the risk of severe acute respiratory infection (SARI) following influenza in patients with sleep apnea.Materials and Methods: We executed this real-world study by gathering Taiwan National Health Insurance Research Database (NHIRD) data. From a database containing 1 million individuals sampled at random from the NHIRD, we identified all patients aged 20 years or older with a sleep apnea diagnosis between 1997 and 2013 as the study group. We established a comparison cohort of individuals without sleep apnea by randomly matching patients with respect to monthly income, gender, urbanization level, and age at a 1:4 ratio. Follow-up was performed until death or the end of 2015 for both groups. We determined the study outcome to be the occurrence of influenza-associated SARI.Results: We enrolled 6508 and 26,032 patients into the study and comparison groups, respectively. A significantly higher cumulative incidence of influenza-associated SARI was discovered in the study group (p < 0.001). In our multivariate analysis, sleep apnea, chronic obstructive pulmonary disease, and coronary artery disease were independent risk factors for influenza-associated SARI. The hazard ratio of sleep apnea for influenza-associated SARI was 1.98 (95% CI: 1.26– 3.10) after adjustment for all comorbidities, gender, age, monthly income, and urbanization level.Conclusion: Sleep apnea increased the risk of influenza-associated SARI. We suggest that physicians be cautious about the development of severe influenza illness in patients with sleep apnea. Vaccination and early oseltamivir administration should be actively considered in this group of patients.Keywords: sleep apnea, sleep disturbance, influenza, severe acute respiratory infection

Shiue-Chin Liou,1 Chen-Ming Hsu,2 Chit Chen,1 Ming-Yao Su,2 Cheng-Tang Chiu2 1Department of Anesthesiology, Chang Gung Memorial Hospital at Taoyuan, Taoyuan, Taiwan; 2Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan Background: Subjects with obstructive sleep apnea (OSA) are vulnerable to sedation-related complications during endoscopic procedures. A significant portion of subjects undergoing routine endoscopy is at high risk of OSA, but most are undiagnosed. The purpose of this study was to estimate the prevalence of high risk for OSA among Chinese subjects undergoing deep sedation for screening gastrointestinal endoscopy and to evaluate the hypoxemia risk of these examinees stratified by Berlin Questionnaire (BQ). Patients and methods: We performed a prospective cohort study in subjects undergoing deep sedation with monitored anesthesia care for combined esophagogastroduodenoscopy plus colonoscopy. Subjects who were Chinese were stratified into high- and low-risk groups for OSA by administration of BQ. Deep sedation was achieved via a propofol target-controlled infusion system. Hypoxemia was defined as pulse oximetry reading of less than 90%. The frequency of hypoxemia was compared between high- and low-risk groups for OSA. Results: A total of 615 Chinese subjects were recruited during the study period, and 614 subjects were included for analysis. Two hundred eighteen (35.5%) subjected were classified to be at high risk of OSA, and 396 (64.5%) were stratified to be at low risk of OSA by BQ. Hypoxemia occurred in 83 (13.5%) subjects during endoscopy procedures. The risk of developing hypoxemia in the high-risk group was significantly higher when compared to that of the low-risk group subjects (24.8% vs 7.3%; relative risk, 3.37; 95% CI, 2.22–5.13). Conclusion: About one-third Chinese subjects undergoing deep sedation for screening endoscopy were at high risk of OSA. Subjects at high risk of OSA are associated with an increased risk of hypoxemia in comparison to the low-risk group when undergoing deep sedation for screening gastrointestinal endoscopy. Keywords: endoscopy, deep sedation, hypoxemia, obstructive sleep apnea, monitored anesthesia care, Berlin Questionnaire

Chi-Huan Wu,1,2 Tsung-Hsing Chen,1–3 Chen-Ming Hsu,1,2 Ming-Yao Su,1,2 Cheng-Tang Chiu,1,2 Ren-Chin Wu,4 Cheng-Chou Lai5 1Department of Gastroenterology and Hepatology, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan, 2Chang Gung University, College of Medicine, Taoyuan, 3Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, 4Department of Pathology, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan, 5Department of Colon and Rectal Surgery, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan Introduction: Linked-color imaging (LCI) is a recently developed system used in endoscopy. It creates clear and bright endoscopic images using short-wavelength, narrow-band laser light combined with white laser light. The illuminating light and signal processing emphasize slight color differences in abnormal regions that approximate the normal color of the mucosa. As a result, regions initially appearing red become a deeper shade of red, while regions originally appearing white become brighter, yet with natural tones. This process facilitates recognition of slight differences in the color of the mucosa and clarifies the boundaries of the mucosal pit. Aim: To determine whether LCI of the colon can improve the correlation between endoscopic findings and pathological diagnosis. Methods: Consecutive patients who underwent colonoscopy requiring polypectomy or removal by biopsy forceps if possible were recruited. Probable polyp histology was assessed by two endoscopists using the Narrow-band imaging International Colorectal Endoscopic (NICE) classification and LCI data. All detected polyps were sent to the pathology department for pathological diagnosis by two pathologists. Results: In total, 94 polyps were found in 43 patients. The sensitivity, specificity, positive predictive value, and negative predictive value for neoplastic lesion prediction (NICE type2/3) were 96.5%, 83.8%, 90.2%, and 93.9%, respectively. Conclusion: LCI combined with the NICE classification system is a powerful tool for predicting probable histology of colon polyps. Keywords: linked-color imaging, NICE classification, colon polyps, histology, sensitivity, specificity

Circulating tumor cells (CTCs), originating from primary neoplastic tissues, infiltrate blood vessels, migrate through the bloodstream, and establish secondary tumor foci. The detection of CTCs holds significant promise for early-stage identification, diagnostic precision, therapeutic monitoring, and prognostic evaluation. It offers a non-invasive approach and has broad clinical relevance in cancer management. This comprehensive review primarily focused on CTCs as biomarkers in the diagnostic, therapeutic, and prognostic surveillance of hepatocellular carcinoma, compared their correlation with key clinical parameters and the identification of gene characteristics. It also highlighted current methodologies in CTC detection. Despite approval by the U.S. Food and Drug Administration for select malignancies, the comprehensive integration of CTCs into routine clinical practice requires procedural standardization and a deeper understanding of the underlying molecular intricacies. The challenges in CTC detection, including limited quantity, technical impediments, and cellular heterogeneity, call for concerted and further investigational efforts to advance precision in cancer diagnostics and prognostication, thus realizing the objectives of precise and personalized medicine., Competing Interests: JFH has been an Editorial Board Member of Journal of Clinical and Translational Hepatology since 2022. The other authors have no conflict of interests related to this publication., (© 2024 Authors.)

Diffuse large B-cell lymphoma (DLBCL) is an aggressive B-cell lymphoma characterized by distinct subtypes and heterogeneous treatment outcomes. Oxidative stress and the dysregulation of related regulatory genes are prevalent in DLBCL, prompting an investigation into the nuclear factor erythroid 2-related factor 2 (Nrf2)-kelch-like ECH-associated protein 1 (Keap1) signaling pathway and associated genes. The present study assessed pathological specimens and clinical data from 43 newly diagnosed patients with DLBCL, comparing the associations and correlations between the expression of Nrf2, Keap1, microtubule-associated protein 1 light chain 3β (LC3B) and nitrotyrosine and the activated B-cell (ABC) and germinal center B-cell (GCB) subtypes of DLBCL using immunohistochemistry and digital image analysis software. Nuclear Nrf2 activation was observed in 33.3% of patients with DLBCL ABC, demonstrating a higher prevalence of hepatitis B surface antigen positivity, calcium ions and significant body weight loss (P<0.05). Total Nrf2 expression was associated with the DLBCL GCB subtype and inversely correlated with Keap1 expression in the DLBCL ABC subtype. Furthermore, a positive correlation was demonstrated between Nrf2 and LC3, indicating that total Nrf2 is inhibited by Keap1 and regulates LC3 expression. The ABC subtype was also associated with lower white blood cell counts and more frequent chemotherapy courses than the GCB subtype. These findings suggest that nuclear Nrf2 could be a biomarker for DLBCL clinical diagnosis., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Hsu et al.)

Objective: The association between gastroesophageal reflux disease (GERD) and laryngeal disorders remains debatable, although it has been the focus of extensive clinical and laboratory research. We conducted this study to obtain evidence on the association., Study Design: Population-based cohort study., Setting: Taiwan National Health Insurance Research Database (NHIRD)., Methods: Using data from Taiwan's NHIRD (January 2000 to December 2018), we performed a population-based analysis to estimate the risk of laryngeal disorders in patients with GERD and those without GERD., Results: The GERD and non-GERD cohorts comprised 176,319 and 705,276 patients, respectively. The cohorts were matched at a ratio of 1:4 based on sex, age, urbanization level, and income level. The risk of laryngeal disorders was higher in the GERD cohort than in the non-GERD cohort (adjusted hazard ratio: 1.64; 95% confidence interval: 1.61-1.67)., Conclusion: This study is the first to use population data for identifying the association between GERD and laryngeal disorders for real-world findings. Our population-based analysis indicates that patients with GERD have an elevated risk of laryngeal disorders., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

In the post-pandemic era, medical education faces significant shifts in learning modes. This study, employing cross-sectional research from 2021 to 2022, surveyed 214 participants, including 104 medical interns and 110 Post-Graduate Year trainees in Taiwan. Findings revealed notable differences between the groups in age and current internship hospital. Medical interns spent significantly more time in daily self-directed learning, with a higher proportion exceeding 3 hours post-work. Although weekly self-directed learning hours did not show statistical significance, more medical students studied over 7 hours weekly. In terms of learning attitudes and motivations, medical interns outscored Post-Graduate Year trainees, indicating a substantial contrast. The study suggests strategic integration of online and traditional education, tailored to course characteristics. Future research should further explore the effectiveness of online learning, aiming to optimize digital learning while preserving traditional education values., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: There are scanty population-based studies investigating the incidence and prevalence rates of inflammatory bowel disease (IBD) in Taiwan., Aims: This study aimed to estimate the nationwide prevalence and incidence of IBD and identify its noticeable trends in Taiwan between 2016 and 2020., Methods: A retrospective study by analyzing the data from the National Health Insurance Research Database of Taiwan., Results: A total of 2595 patients with catastrophic IBD illness were registered from 2016 to 2020 in Taiwan (CD, 880; UC, 1715). The male-to-female ratio in the study sample was 1.83:1 for CD and 1.69:1 for UC. The median age of those registered with CD and UC was 37 and 47 years, respectively. The incidence rate of CD was 0.65 per 100,000 persons in 2016 and it was increased to 0.81 per 100,000 persons in 2020. The incidence rate of UC was 1.16 per 100,000 persons in 2016 and it was increased to 1.53 in 2020. Overall, the incidence of IBD was increase from 1.81 per 100,000 persons to 2.34 per 100,000 persons between 2016 and 2020. Overall, the prevalence rates of IBD was increase from 14.95 per 100,000 persons to 20.02 per 100,000 persons between 2016 and 2020., Conclusion: The epidemiological stages of IBD in Taiwan was considered in the acceleration in incidence stage, during which incidence rises and prevalence is relatively low. Understanding these geographical differences is important for the rising global burden of IBD., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Rationale & Objective: Reasons for transfer from peritoneal dialysis (PD) to hemodialysis (HD) remain incompletely understood. Among incident and prevalent patients receiving PD, we evaluated the association of clinical factors, including prior treatment with HD, with PD technique survival., Study Design: Retrospective cohort study., Setting & Participants: Adults who initiated PD at a Dialysis Clinic, Inc (DCI) outpatient facility between January 1, 2010, and September 30, 2019., Exposure: The primary exposure of interest was timing of PD start, categorized as PD-first, PD-early, or PD-late. Other covariates included demographics, clinical characteristics, and routine laboratory results., Outcome: Modality switch from PD to HD sustained for more than 90 days., Analytical Approach: Multivariable Fine-Gray models with competing risks and time-varying covariates, stratified at 9 months to account for lack of proportionality., Results: Among 5,224 patients who initiated PD at a DCI facility, 3,174 initiated dialysis with PD ("PD-first"), 942 transitioned from HD to PD within 90 days ("PD-early"), and 1,108 transitioned beyond 90 days ("PD-late"); 1,472 (28%) subsequently transferred from PD to HD. The PD-early and PD-late patients had a higher risk of transfer to HD as compared with PD-first patients (in the first 9 months: adjusted hazard ratio [AHR], 1.51 [95% CI, 1.17-1.96] and 2.41 [95% CI, 1.94-3.00], respectively; and after 9 months: AHR, 1.16 [95% CI, 0.99-1.35] and AHR, 1.43 [95% CI, 1.24-1.65], respectively). More peritonitis episodes, fewer home visits, lower serum albumin levels, lower residual kidney function, and lower peritoneal clearance calculated with weekly Kt/V were additional risk factors for PD-to-HD transfer., Limitations: Missing data on dialysis adequacy and residual kidney function, confounded by short PD technique survival., Conclusions: Initiating dialysis with PD is associated with greater PD technique survival, though many of those who initiate PD-late in their dialysis course still experience substantial time on PD. Peritonitis, lower serum albumin, and lower Kt/V are risk factors for PD-to-HD transfer that may be amenable to intervention., Plain-Language Summary: Peritoneal dialysis (PD) is an important kidney replacement modality with several potential advantages compared with in-center hemodialysis (HD). However, a substantial number of patients transfer to in-center HD early on, without having experienced the quality-of-life and other benefits that come with sustained maintenance of PD. Using retrospective data from a midsize national dialysis provider, we found that initiating dialysis with PD is associated with longer maintenance of PD, compared with initiating dialysis with HD and a later switch to PD. However, many of those who initiate PD-late in their dialysis course still experience substantial time on PD. Peritonitis, lower serum albumin, and lower small protein removal are other risk factors for PD-to-HD transfer that may be amenable to intervention., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: This study aimed to elucidate the bacterial profile of chronic rhinosinusitis (CRS) in patients with end-stage renal disease (ESRD) and chronic kidney disease (CKD) compared with nonrenal patients, guiding antibiotic selection for clinicians., Methods: We retrospectively analyzed 13,906 inpatients from the Chang Gung Research Database who underwent sinus surgery (2004-2018). Patients were categorized into ESRD-CRS, CKD-CRS, and non-CKD-CRS based on the estimated glomerular filtration rate. Bacterial cultures from surgical samples were classified as facultative anaerobes or aerobes (e.g., Klebsiella pneumoniae [KP], Pseudomonas aeruginosa [Ps.a]), anaerobes, and fungi and ranked by prevalence., Results: Data from 47 ESRD-CRS, 230 CKD-CRS, and 13,123 non-CKD-CRS patients were analyzed. In ESRD-CRS, the predominant species were KP (31.6%), Ps.a (21.1%), and Coagulase-negative Staphylococcus (CoNS, 15.8%). CKD-CRS showed Staphylococcus epidermidis (27.7%), CoNS (20.5%), and Ps.a (20.5%). Non-CKD-CRS had Staphylococcus epidermidis (29.8%), CoNS (25.0%), and Staphylococcus aureus (15.5%). For anaerobes, ESRD-CRS was dominated by Fusobacterium nucleatum (10.5%) and Peptostreptococcus micros (10.5%), whereas CKD-CRS and non-CKD-CRS showed Propionibacterium acnes as a primary strain (14.5% and 28.7%, respectively)., Conclusion: For CRS in ESRD, antibiotics targeting KP and Fusobacterium nucleatum are recommended. In CKD-CRS, a focus on Staphylococcus epidermidis and Propionibacterium acnes is suggested., Level of Evidence: 4 Laryngoscope, 134:3499-3507, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

We conducted a systematic review of the literature to assess the potential prognostic utility of geriatric nutritional risk index (GNRI) for head and neck cancer (HNC). We selected studies and extracted data after searching the Cochrane Library, EMBASE, and PubMed databases. The associations between GNRI and survival outcomes were explored by calculating hazard ratios (HRs) and 95% confidence intervals (CIs) through a random-effects meta-analysis. We included 11 studies that involved 2887 patients with HNC. The combined HR demonstrated significant associations of low GNRI with unfavorable progression-free survival (HR = 1.87, 95% CI = 1.32-2.65, p < 0.001) and overall survival (HR = 3.04, 95% CI = 2.30-4.03, p < 0.001). The association between the GNRI and overall survival persisted across various subgroups. The GNRI could serve as a valuable prognostic biomarker for patients with HNC. Low GNRI scores are significantly associated with unfavorable survival outcomes., (© 2024 Wiley Periodicals LLC.)

Astragalus polysaccharides (APSs), the compounds extracted from the common herb Astragalus membranaceus, have been extensively studied for their antitumor properties. In this study, we investigated the effect of APS on lung adenocarcinoma A549 cells. The effects of APS and the anti-diabetic drug metformin on apoptosis and ferroptosis were compared. Furthermore, the combination treatment of APS and metformin was also investigated. We found that APS not only reduced the growth of lung cancer cells but also had a synergistic effect with metformin on A549 cells. The study results showed that it may be promising to use APS and metformin as a combination therapy for the treatment of lung adenocarcinoma.

We probed the associations of preoperative modified geriatric nutritional risk index (mGNRI) values with prognosis in patients receiving surgery for oral cavity squamous cell carcinoma (OCSCC). This retrospective study analyzed the clinical data of 333 patients with OCSCC and undergoing surgery between 2008 and 2017. The preoperative mGNRI was calculated using the following formula: (14.89/C-reactive protein level) + 41.7 × (actual body weight/ideal body weight). We executed receiver operating characteristic curve analyses to derive the optimal mGNRI cutoff and employed Kaplan-Meier survival curves and Cox proportional hazard model to probe the associations of the mGNRI with overall survival (OS) and disease-free survival (DFS). The optimal mGNRI cutoff was derived to be 73.3. We noted the 5-year OS and DFS rates to be significantly higher in the high-mGNRI group than in the low-mGNRI group (both p < 0.001). A preoperative mGNRI below 73.3 was independently associated with unfavorable DFS and OS. A mGNRI-based nomogram was constructed to provide accurate OS predictions (concordance index, 0.781). Hence, preoperative mGNRI is a valuable and cost-effective prognostic biomarker in patients with OCSCC. Our nomogram facilitates the practical use of mGNRI and offers individualized predictions of OS., (© 2024. The Author(s).)

Dysregulation of RNA splicing processes is intricately linked to tumorigenesis in various cancers, especially breast cancer. Cdc2-like kinase 2 (CLK2), an oncogenic RNA-splicing kinase pivotal in breast cancer, plays a significant role, particularly in the context of triple-negative breast cancer (TNBC), a subtype marked by substantial medical challenges due to its low survival rates. In this study, we employed a structure-based virtual screening (SBVS) method to identify potential CLK2 inhibitors with novel chemical structures for treating TNBC. Compound 670551 emerged as a novel CLK2 inhibitor with a 50% inhibitory concentration (IC 50 ) value of 619.7 nM. Importantly, Compound 670551 exhibited high selectivity for CLK2 over other protein kinases. Functionally, this compound significantly reduced the survival and proliferation of TNBC cells. Results from a cell-based assay demonstrated that this inhibitor led to a decrease in RNA splicing proteins, such as SRSF4 and SRSF6, resulting in cell apoptosis. In summary, we identified a novel CLK2 inhibitor as a promising potential treatment for TNBC therapy., (© 2024 The Authors. Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.)

Objective: To investigate and statistically synthesise data on the effects of interprofessional education on healthcare professionals' collaborative practice among healthcare professionals., Design: A systematic review and meta-analysis., Data Sources: Seven databases and the grey literature were searched to collect relevant studies from database inception to 15 May 2023., Review Methods: A random-effects model was used to assess the pooled effect size. Each pooled analysis was tested for publication bias using Egger's regression test., Results: Eleven studies were included in the final analysis. The evaluation of pooled results showed that interprofessional education significantly enhanced attitudes towards or mutual respect among healthcare professionals (pooled standardized mean difference: 0.14; 95 % Confidence Interval: 0.01-0.28; p = 0.04) and interprofessional knowledge (pooled standardized mean difference: 0.43; 95 % Confidence Interval: 0.22-0.65; p < 0.001)., Conclusions: Interprofessional education is a feasible approach to enhance attitudes towards or mutual respect among healthcare professionals as well as their interprofessional knowledge. Future research is needed to consider the inclusion of a module designed to develop mutual interests and communication to enhance students' perspectives on the importance of the interprofessional education approach., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background and Aim: Colonoscopy is a useful method for the diagnosis and management of colorectal diseases. Many computer-aided systems have been developed to assist clinicians in detecting colorectal lesions by analyzing colonoscopy images. However, fisheye-lens distortion and light reflection in colonoscopy images can substantially affect the clarity of these images and their utility in detecting polyps. This study proposed a two-stage deep-learning model to correct distortion and reflections in colonoscopy images and thus facilitate polyp detection., Methods: Images were collected from the PolypSet dataset, the Kvasir-SEG dataset, and one medical center's patient archiving and communication system. The training, validation, and testing datasets comprised 808, 202, and 1100 images, respectively. The first stage involved the correction of fisheye-related distortion in colonoscopy images and polyp detection, which was performed using a convolutional neural network. The second stage involved the use of generative and adversarial networks for correcting reflective colonoscopy images before the convolutional neural network was used for polyp detection., Results: The model had higher accuracy when it was validated using corrected images than when it was validated using uncorrected images (96.8% vs 90.8%, P < 0.001). The model's accuracy in detecting polyps in the Kvasir-SEG dataset reached 96%, and the area under the receiver operating characteristic curve was 0.94., Conclusion: The proposed model can facilitate the clinical diagnosis of colorectal polyps and improve the quality of colonoscopy., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

The factors related to conflicts in emergency departments (EDs) have been studied for decades. The post-pandemic digital era may transform the medical landscape in EDs, potentially changing the patterns of conflict between healthcare professionals. This study used focus group interviews to explore conflicts in EDs. Four groups, each with 4-6 participants, took part in this study. Semi-structured interviews were conducted using six research questions. Summative content analysis was used to analyze the data. The participant's average age was 37.82 years, and the average number of working years was 12.12. The following five themes emerged: multiple patterns of internal conflict; external conflicts arising from cross-departmental coordination; conflicts due to unclear job boundaries; adapting to conflicts in diverse ways; and seeking hospital arbitration. The results of this study suggest extending interdisciplinary collaborative practice from emergency departments to all coordinating departments. An inclusive environment for equality between professions and open communication should be promoted by hospitals.

A Go endgame database consists of optimal game values and moves for every legal arrangement of no more than S pieces on an N by N board. This paper describes methods for constructing such databases when 1 < N ≤ 5 and S = N 2 . When cycles of plies with lengths greater than 4 are encountered, two rules, one allowing cycles and the other disallowing them, are implemented. Observations and knowledge are obtained for these endgames, which may elucidate the fundamental properties of the popular game Go. First, the optimal game values are different when N is even and odd, regardless of whether the repetition of positions is allowed. When N is odd, the first player can occupy the whole board, while this is not the case when N is even. Second, allowing cycles makes the first and second players equal in strength when N is even, whereas the first player always dominates when N is odd. Using the state-of-the-art open-source deep learning Go engine KataGo to correctly solve a given position as an indicator, factors affecting level of difficulty are found, including the distributions of the optimal game values among all legal plies and the cardinality and values of the true optimal plies. A simple formula is designed that works on more than 10% of the positions so that positions with a given level of difficulty can be found with a high probability., (© 2024. The Author(s).)

Objectives: This study assessed functional outcomes and quality of life (QoL) in the long term in individuals treated for laryngohypopharyngeal cancer (LHC) by estimating their life expectancy (LE), survival-weighted psychometric scores (SWPSs), and quality-adjusted LE (QALE). Materials and methods: To estimate survival outcomes, we retrospectively reviewed the data of 1576 patients treated for primary LHC between January 2010 and December 2018 and followed them until death or December 2020. We also prospectively collected QoL and functional data between October 2013 and November 2022 from 232 patients by administering the Taiwanese Chinese versions of the QoL Questionnaire Core 30, Head and Neck 35, and EQ-5D-3L. To estimate LE, we employed linear extrapolation of a logit-transformed curve. We calculated QALE and SWPSs by combining the QoL data with the LE results. Results: We estimated the LE of the patients with LHC to be 7.8 years and their loss of LE to be 15.7 years. The estimated QALE was 7.0 QALYs, with a loss of QALE of 16.5 QALYs. Lifetime impairment durations were estimated for cognitive (4.9 years), physical (4.2 years), emotional (3.4 years), social (3.4 years), and role functions (2.7 years). We estimated the durations of problems related to swallowing, speech, and teeth to be 6.2, 5.6, and 4.8 years, respectively. The patients were expected to be dependent on feeding tubes for 1.2 years. Conclusions: Patients with LHC experience significant reductions in both LE and QALE. SWPSs may constitute a valuable tool for obtaining subjective information regarding how LHC affects multifaceted QoL outcomes., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: This study aimed to explore the prognostic utility of the preoperative platelet-to-albumin ratio (PAR) among patients with oral cavity squamous cell carcinoma (OSCC)., Methods: We retrospectively reviewed of 355 patients with surgically-treated OSCC between 2008 and 2017. The optimal PAR cutoff for patient stratification was determined through X-tile analysis. Prognostic variables for disease-free survival (DFS) and overall survival (OS) were identified using Cox proportional hazards models. We developed a PAR-based nomogram to predict personalized OS., Results: We determined the optimal PAR cutoff to be 7.45. A PAR of ≥7.45 was an independent negative prognostic factor for DFS and OS (hazard ratio = 1.748 and 2.386; p = 0.005 and p < 0.001, respectively). The developed nomogram demonstrates the practical utility of PAR and accurately predicts personalized OS., Conclusions: The preoperative PAR is a promising and cost-effective prognostic biomarker for patients with surgically-treated OSCC; the PAR-based nanogram accurately predicts OS for such patients., (© 2023 Wiley Periodicals LLC.)

Pollen germination is a crucial process in the life cycle of flowering plants, signifying the transition of quiescent pollen grains into active growth. This study delves into the dynamic changes within organelles and the pivotal role of autophagy during lily pollen germination. Initially, mature pollen grains harbor undifferentiated organelles, including amyloplasts, mitochondria, and the Golgi apparatus. However, germination unveils remarkable transformations, such as the redifferentiation of amyloplasts accompanied by starch granule accumulation. We investigate the self-sustained nature of amylogenesis during germination, shedding light on its association with osmotic pressure. Employing BODIPY 493/503 staining, we tracked lipid body distribution throughout pollen germination, both with or without autophagy inhibitors (3-MA, NEM). Typically, lipid bodies undergo polarized movement from pollen grains into elongating pollen tubes, a process crucial for directional growth. Inhibiting autophagy disrupted this essential lipid body redistribution, underscoring the interaction between autophagy and lipid body dynamics. Notably, the presence of tubular endoplasmic reticulum (ER)-like structures associated with developing amyloplasts and lipid bodies implies their participation in autophagy. Starch granules, lipid bodies, and membrane remnants observed within vacuoles further reinforce the involvement of autophagic processes. Among the autophagy inhibitors, particularly BFA, significantly impede germination and growth, thereby affecting Golgi morphology. Immunogold labeling substantiates the pivotal role of the ER in forming autophagosome-like compartments and protein localization. Our proposed speculative model of pollen germination encompasses proplastid differentiation and autophagosome formation. This study advances our understanding of organelle dynamics and autophagy during pollen germination, providing valuable insights into the realm of plant reproductive physiology., (© 2024. The Author(s).)

Background: Indigofera suffruticosa Mill. is used as a folk medicine for treating patients with leukemia, however very little is known regarding the molecular mechanism of its anti-leukemic activity and the chemical profile of the active extract. The present study aimed to reveal the molecular effect of I. suffruticosa aerial parts extract (ISAE) on leukemia cells and its chemical constituents., Methods: Cytotoxicity of ISAE were determined by resazurin viability assay, multitox - Glo multiplex cytotoxicity assay, and Annexin V staining assay. Cell cycle profiles were revealed by propidium iodide staining assay. The effects of ISAE on G2/M arrest signaling and DNA damage were evaluated by Western blot assay and phospho-H2A.X staining assay. The chemical profile of ISAE were determined by tandem mass spectroscopy and molecular networking approach., Results: We showed that the acute lymphoblastic leukemia cell line Jurkat cell was more responsive to ISAE treatment than other leukemia cell lines. In contrast, ISAE did not induce cytotoxic effects in normal fibroblast cells. Cell cycle analysis revealed that ISAE triggered G2/M arrest in Jurkat cells in dose- and time-dependent manners. Elevation of annexin V-stained cells and caspase 3/7 activity suggested ISAE-induced apoptosis. Furthermore, ISAE alone could increase the phosphorylation of CDK1 at Y15 and activate the ATR/CHK1/Wee1/CDC25C signaling pathway. However, the addition of caffeine, a widely used ATR inhibitor to ISAE, reduced the phosphorylation of ATR, CHK1, and CDK1, as well as G2/M arrest in Jurkat cells. Moreover, increased phospho-H2A.X stained cells indicated the involvement of DNA damage in the anti-leukemic effect of ISAE. Finally, qualitative analysis using UPLC-tandem mass spectroscopy and molecular networking revealed that tryptanthrin was the most abundant organoheterocyclic metabolite in ISAE. At equivalent concentrations to ISAE, tryptanthrin induced G2/M arrest of Jurkat cells, which can be prevented by caffeine., Conclusions: ISAE causes G2/M arrest via activating ATR/CHK1/CDK1 pathway and tryptanthrin is one of the active components of ISAE. Our findings provide subtle support to the traditional use of I. suffruitcosa in leukemia management in folk medicine., (© 2024. The Author(s).)

Objectives: The role of autoimmune diseases on the risk for acute epiglottitis remains uncertain. This study aimed to delineate the association between epiglottitis and autoimmune diseases using population database., Methods: A population-based retrospective study was conducted to analyze claims data from Taiwan National Health Insurance Research Database collected over January, 2000, to December, 2013., Results: In total, 2339 patients with epiglottitis were matched with 9356 controls without epiglottitis by sex, age, socioeconomic status, and urbanization level. The correlation between autoimmune diseases and epiglottitis was analyzed by multivariate logistic regression. Compared with controls, patients with epiglottitis were much more likely to have preexisting Sjögren syndrome (adjusted odds ratio [aOR]: 2.37; 95% CI: 1.14-4.91; P = .021). In addition, polyautoimmunity was associated with increased risk of epiglottitis (aOR: 2.08; 95% CI: 1.14-3.80; P = .018), particularly in those aged >50 years (aOR: 2.61; 95% CI: 1.21-5.66; P = .015)., Conclusions: Among autoimmune diseases, we verify the association between epiglottitis and Sjögren syndrome in Taiwan. Furthermore, we present the novel discovery that patients with epiglottitis have an increased risk of polyautoimmunity, particularly those aged >50 years., 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.

Soil microorganisms play key roles in soil nutrient transformations and have a notable effect on plant growth and health. Different plant genotypes can shape soil microbial patterns via the secretion of root exudates and volatiles, but it is uncertain how a difference in soil microorganisms induced by crop cultivars will respond to short-term seasonal variations. A field experiment was conducted to assess the changes in soil bacterial communities of seven rhizoma peanut (Arachis glabrata Benth, RP) cultivars across two growing seasons, April (Spring season) and October (Fall season). Soils' bacterial communities were targeted using 16S rRNA gene amplicon sequencing. Bacterial community diversity and taxonomic composition among rhizoma peanut cultivars were significantly affected by seasons, cultivars, and their interactions (p < 0.05). Alpha diversity, as estimated by the OTU richness and Simpson index, was around onefold decrease in October than in April across most of the RP cultivars, while the soils from Arblick and Latitude had around one time higher alpha diversity in both seasons compared with other cultivars. Beta diversity differed significantly in April (R = 0.073, p < 0.01) and October (R = 0.084, p < 0.01) across seven cultivars. Bacterial dominant taxa (at phylum and genus level) were strongly affected by seasons and varied towards more dominant groups that have functional potentials involved in nutrient cycling from April to October. A large shift in water availability induced by season variations in addition to host cultivar's effects can explain the observed patterns in diversity, composition, and co-occurrence of bacterial taxa. Overall, our results demonstrate an overriding effect of short-term seasonal variations on soil bacterial communities associated with different crop cultivars. The findings suggest that season-induced shifts in environmental conditions could exert stronger impacts on soil microorganisms than the finer-scale rhizosphere effect from crop cultivars, and consequently influence largely microbe-mediated soil processes and crop health in agricultural ecosystems., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The K 2 S 2 O 8 -mediated generation of p -iminoquinone contributed to the regioselective substitution of isoquinolin-5,8-dione. This hydroxyl group-guided substitution was also applied to selected heterocycles and addressed the regioselectivity issue of quinones. This study has provided an expeditious pathway from isoquinolin-5-ol (5) to ellipticine (1) and isoellipticine (2), which benefits the comprehensive comparison of their activity. Compounds 1 and 2 displayed marked MYLK4 inhibitory activity with IC 50 values of 7.1 and 6.1 nM, respectively. In the cellular activity of AML cells (MV-4-11 and MOLM-13), compound 1 showed better AML activity than compound 2., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Genomic imprinting, an epigenetic mechanism that regulates gene expression from parental chromosomes, holds substantial relevance in multiple cancers, including hematopoietic malignancies. In the present study, the expression of a panel of 16 human imprinted genes in bone marrow samples from 64 patients newly diagnosed with cytogenetically normal-acute myeloid leukemia (CN-AML) were examined alongside peripheral blood samples from 85 healthy subjects. The validated findings of the present study revealed significant upregulation of seven genes [COPI coat complex subunit gamma 2 ( COPG2 ), H19 imprinted maternally expressed transcript ( H19 ), insulin like growth factor 2 ( IGF2 ), PEG3 antisense RNA 1 ( PEG3-AS1 ), DNA primase subunit 2 ( PRIM2 ), solute carrier family 22 member 3 SLC22A3 and Zinc finger protein 215 ( ZNF215 )] in patients with CN-AML (P<0.001). Notably, the expression level of H19 exhibited an inverse association with the survival duration of the patients (P=0.018), establishing it as a predictive marker for two- and five-year survival in patients with CN-AML. Kaplan-Meier analysis demonstrated that patients with lower H19 expression had superior two- and five-year survival rates compared with those with higher H19 expression. The results of the present study highlighted the association between loss of imprinting and leukemogenesis in CN-AML, underscoring the significance of H19 imprinting loss as a prognostic indicator for unfavorable two- and five-year survival in CN-AML patients., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Yang et al.)

Background: Soft tissue release (STR) is an established treatment for spastic hip displacement, but recurrence of hip displacement is not uncommon. This study aims to (1) evaluate the recurrence of hip displacement after STR, (2) define associated factors of recurrence, and (3) elucidate the effects of guided growth on hip displacement recurrence., Methods: The study subjects included 66 individuals with spastic cerebral palsy treated by STR with or without guided growth for hip displacement. The treatment goal was the maintenance of migration percentage (MP) to <40%. Recurrence was defined by a rebound of the MP by 5% or more after the first postoperative year. Children with recurrence were compared with those without recurrence using the Mann-Whitney U test and the χ 2 test. The risk factors for recurrence were evaluated using multiple logistic regression analysis., Results: Nineteen individuals (29%) had a recurrence of hip displacement after the first postoperative year. They sustained a 2-fold increase in the rate of treatment failure ( P < 0.001) and reoperation ( P = 0.04). Age, sex, motor function, and preoperative radiographic parameters were comparable between individuals with and without recurrence. The use of guided growth was associated with less risk of recurrence than without (5% and 39%, respectively, odds ratio = 0.01 to 0.45, respectively) despite the similar risk of failure (35% and 48%, respectively, odds ratio = 0.15 to 4.82)., Conclusions: Recurrence of the MP >5% after the first postoperative year is an important early indicator for failure to control MP to <40% and reoperation. Guided growth not only decreases coxa valga but also reduces the risk of recurrent hip displacement after STR., Level of Evidence: Level III; case-control study., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Spinal fusion surgery leads to the restriction of mobility in the vertebral segments postoperatively, thereby causing stress to rise at the adjacent levels, resulting in early degeneration and a high risk of adjacent vertebral fractures. Thus, to address this issue, non-fusion surgery applies some pedicle screw-based dynamic stabilisation systems to provide stability and micromotion, thereby reducing stress in the fusion segments. Among these systems, the hybrid performance stabilisation system (HPSS) combines a rigid rod, transfer screw, and coupler design to offer a semi-rigid fixation method that preserves some mobility near the fusion site and reduces the adjacent segment compensatory effects. However, further research and confirmation are needed regarding the biomechanical effects of the dynamic coupler stiffness of the HPSS on the intrinsic degenerated adjacent segment. Therefore, this study utilised the finite element method to investigate the impact of the coupler stiffness of the HPSS on the mobility of the lumbar vertebral segments and the stress distribution in the intervertebral discs under flexion, extension, and lateral bending, as well as the clinical applicability of the HPSS on the discs with intrinsic moderate and severe degeneration at the adjacent level. The analytical results indicated that, regardless of the degree of disc degeneration, the use of a dynamic coupler stiffness of 57 N/mm in the HPSS may reduce the stress concentrations at the adjacent levels. However, for severely degenerated discs, the postoperative stress on the adjacent segments with the HPSS was still higher compared with that of the discs with moderate degeneration. We conclude that, when the discs had moderate degeneration, increasing the coupler stiffness led to a decrease in disc mobility. In the case of severe disc degeneration, the effect on disc mobility by coupler stiffness was less pronounced. Increasing the coupler stiffness ked to higher stress on intervertebral discs with moderate degeneration, while its effect on stress was less pronounced for discs with severe degeneration. It is recommended that patients with severe degeneration who undergo spinal dynamic stabilisation should remain mindful of the risk of accelerated adjacent segment degeneration.

The importance of coach leadership to athlete development and performance has been identified in the literature. We respond to the call to investigate antecedents of coach transformational leadership and their indirect effects on athlete outcomes. We propose that coach extraversion as an antecedent of coach transformational leadership can indirectly impact follower cohesion and satisfaction. Building on this mediation model, we assert that educational environment (i.e., high school and university) may serve as a first-stage moderator between coach extraversion and transformational leadership. We used 48 coaches and their 570 athletes from competitive high school and university basketball teams to test this moderated mediation model. Our results indicate that coach extraversion indirectly impacts athlete cohesion and satisfaction via transformational leadership. Moreover, the indirect effects of coach extraversion on athlete outcomes via coach transformational leadership is conditionally significant only when coaches and athletes are in universities but not in high schools. Our findings highlight the importance of educational environment in determining the association between coach personality and leadership perception. Implications for research and practice are discussed.

Purpose: This study is to compare risks of developing renal cell carcinoma or urothelial cancer between hemodialysis (HD) and peritoneal dialysis (PD) patients., Methods: The age-, sex-, and index year-matched patients with newly diagnosed end-stage kidney disease (ESKD) undergoing dialysis [HD (N = 22,587) or PD (N = 11,547)] from 2000 to 2015 in Taiwan were identified. Patients were followed until the development of renal cell carcinoma or urothelial cancer, renal transplantation, death, or the end of follow-up (December 31, 2017). The hazard ratio (HR), and sub-hazards ratio (SHR), in which death was considered as a competing risk, of developing renal cell carcinoma or urothelial cancer were compared between the HD and PD patients., Results: The incidence rate of renal cell carcinoma was higher in the PD group than in age-, sex-, and index year-matched HD group (11.5 versus 5.52 per 10,000 person-years), with an adjusted HR of 2.15 (95% confidence interval (CI) = 1.59, 2.92), and an adjusted SHR of 1.97 (95% CI = 1.46, 2.67). The incidence rate of urothelial cancer was also higher in the PD group than in corresponding HD group (40.3 and 34.0 per 10,000 person-years), with an adjusted HR of 1.15 (95% CI = 1.00, 1.33) and an adjusted SHR of 1.08 (95% CI = 0.94, 1.25). These findings were further validated in propensity score-matched dialysis cohorts., Conclusions: ESKD patients undergoing PD are at a higher risk of developing renal cell carcinoma than those on HD, but risks of developing urothelial cancer are similar among the two groups., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Given the importance and beneficial characteristics of decorated azetidines in medicinal chemistry, efficient strategies for their synthesis are highly sought after. Herein, we report a facile synthesis of the elusive all-carbon quaternary-center-bearing azetidines. By adopting a well-orchestrated polar-radical relay strategy, ring strain release of bench-stable benzoylated 1-azabicyclo[1.1.0]butane (ABB) can be harnessed for nickel-catalyzed Suzuki Csp 2 -Csp 3 cross-coupling with commercially available boronic acids in broad scope (>50 examples), excellent functional group tolerance, and gram-scale utility. Preliminary mechanistic studies provided insights into the underlying mechanism, wherein the ring opening of ABB with a catalytic quantity of bromide accounts for the conversion of ABB into a redox-active azetidine, which subsequently engages in the cross-coupling reaction through a radical pathway. The synergistic bromide and nickel catalysis could intriguingly be derived from a single nickel source (NiBr 2 ). Application of the method to modify natural products, biologically relevant molecules, and pharmaceuticals has been successfully achieved as well as the synthesis of melanocortin-1 receptor (MC-1R) agonist and vesicular acetylcholine transporter (VAChT) inhibitor analogues through bioisosteric replacements of piperidine with azetidine moieties, highlighting the potential of the method in drug optimization studies. Aside from the synthesis of azetidines, we demonstrate the ancillary utility of our nickel catalytic system toward the restricted Suzuki cross-coupling of tertiary alkyl bromides with aryl boronic acids to construct all-carbon quaternary centers.

Rationale & Objective: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are likely underdiagnosed, but the degree of underdiagnosis among patients receiving maintenance dialysis is unknown. The durability of the immune response after the third vaccine dose in this population also remains uncertain. This descriptive study tracked antibody levels to (1) assess the rate of undiagnosed infections and (2) characterize seroresponse durability after the third dose., Study Design: Retrospective observational study., Setting & Participants: SARS-CoV-2-vaccinated patients receiving maintenance dialysis through a national dialysis provider. Immunoglobulin G spike antibodies [anti-spike immunoglobulin (Ig) G] titers were assessed monthly after vaccination., Exposures: Two and 3 doses of SARS-CoV-2 vaccine., Outcomes: Undiagnosed and diagnosed SARS-CoV-2 infections; anti-spike IgG titers over time., Analytical Approach: Undiagnosed SARS-CoV-2 infections were identified as an increase in anti-spike IgG titer of ≥100 BAU/mL, not associated with receipt of vaccine or diagnosed SARS-CoV-2 infection (by polymerase chain reaction test or antigen test). In descriptive analyses, anti-spike IgG titers were followed over time., Results: Among 2,703 patients without previous coronavirus disease 2019 (COVID-19) who received an initial 2-dose vaccine series, 271 had diagnosed SARS-CoV-2 infections (3.4 per 10,000 patient-days) and 129 had undiagnosed SARS-CoV-2 infections (1.6 per 10,000 patient-days). Among 1,894 patients without previous COVID-19 who received a third vaccine dose, 316 had diagnosed SARS-CoV-2 infections (7.0 per 10,000 patient-days) and 173 had undiagnosed SARS-CoV-2 infections (3.8 per 10,000 patient-days). In both cohorts, anti-spike IgG levels declined over time. Of the initial 2-dose cohort, 66% had a titer of ≥500 BAU/mL in the first month, with 24% maintaining a titer of ≥500 BAU/mL at 6 months. Of the third dose cohort, 95% had a titer of ≥500 BAU/mL in the first month after the third dose, with 77% maintaining a titer of ≥500 BAU/mL at 6 months., Limitations: The assays used had upper limits., Conclusions: Among patients receiving maintenance dialysis, about 1 in every 3 SARS-CoV-2 infections was undiagnosed. Given this population's vulnerability to COVID-19, ongoing infection control measures are needed. A 3-dose primary mRNA vaccine series optimizes seroresponse rate and durability., Plain-Language Summary: Patients receiving maintenance dialysis have been particularly vulnerable to COVID-19. Using serially measured antibodies, we found that a substantial proportion (about one-third) of SARS-CoV-2 infections among this population had been missed, both among those who had completed a 2-dose vaccine series and among those who had received a third vaccine dose. Such missed infections likely had only mild or minimal symptoms, but this failure to recognize all infections is concerning. Furthermore, vaccines have been effective among patients receiving dialysis, but our study additionally shows that the immune response wanes over time, even after a third dose. There is therefore a role for ongoing vigilance against this highly transmissible infection., (© 2023 The Authors.)

Background: Diffuse large B-cell lymphoma (DLBCL) is a malignant lymphoid tumor disease that is characterized by heterogeneity, but current treatment does not benefit all patients, which highlights the need to identify oncogenic genes and appropriate drugs. G9a is a histone methyltransferase that catalyzes histone H3 lysine 9 (H3K9) methylation to regulate gene function and expression in various cancers., Methods: TCGA and GTEx data were analyzed using the GEPIA2 platform. Cell viability under drug treatment was assessed using Alamar Blue reagent; the interaction between G9a and niclosamide was assessed using molecular docking analysis; mRNA and protein expression were quantified in DLBCL cell lines. Finally, G9a expression was quantified in 39 DLBCL patient samples., Results: The TCGA database analysis revealed higher G9a mRNA expression in DLBCL compared to normal tissues. Niclosamide inhibited DLBCL cell line proliferation in a time- and dose-dependent manner, reducing G9a expression and increasing p62, BECN1, and LC3 gene expression by autophagy pathway regulation. There was a correlation between G9a expression in DLBCL samples and clinical data, showing that advanced cancer stages exhibited a higher proportion of G9a-expressing cells., Conclusion: G9a overexpression is associated with tumor progression in DLBCL. Niclosamide effectively inhibits DLBCL growth by reducing G9a expression via the cellular autophagy pathway; therefore, G9a is a potential molecular target for the development of therapeutic strategies for DLBCL.

Parkinson's disease (PD) is associated with a range of non-motor symptoms that lack effective treatments. Acupuncture is a popular alternative therapy for PD patients that has been shown to improve motor symptoms. However, the efficacy of acupuncture in treating non-motor symptoms has remained controversial. The goal of our study was to systematically assess the existing evidence for acupuncture's efficacy in treating PD non-motor symptoms of sleep disorders, depression, anxiety, and fatigue. We conducted a meta-analysis of clinical trials by searching Pubmed, Embase, CINAHL, and Web of Science as electronic databases to evaluate acupuncture treatment for PD non-motor symptoms. Thirteen clinical trials met our inclusion criteria, and their methodological quality was assessed using the modified Jadad scale, indicating a moderate overall quality. Our results showed that acupuncture improved PD-related sleep disorders and depression but had no effect on anxiety and fatigue. Our meta-analysis suggests that acupuncture can be used as a complementary treatment for sleep disturbances and depression in PD patients and may exhibit a dual therapeutic effect on motor and non-motor symptoms. However, further well-designed clinical trials with larger sample sizes are needed to confirm these findings. Overall, our study highlights the potential of acupuncture as a viable complementary therapy for the treatment of PD non-motor symptoms of sleep disorders and depression, which can improve the quality of life of PD patients.

We investigated the prognostic utility of preoperative neck lymph node-to-primary tumor maximum standardized uptake value ratios (NTRs) in oral cavity squamous cell carcinoma (OSCC). We retrospectively reviewed the medical records of 141 consecutive patients who were diagnosed as having OSCC and had received fluorodeoxyglucose-positron emission tomography within 2 weeks prior to radical surgery between 2009 and 2018. To determine the optimal NTR cutoff, receiver operating characteristic analysis for overall survival (OS) was executed. The NTR's prognostic value for disease-free survival (DFS) and OS were determined through Cox proportional hazards analysis and the Kaplan-Meier method. We determined the median (range) follow-up duration to be 35.2 (2.1-122.4) months. The optimal NTR cutoff was 0.273, and patients with a higher NTR (≥0.273) exhibited significantly worse DFS and OS ( p = 0.010 and 0.003, respectively). A higher NTR (≥0.273) predicted poorer DFS (hazard ratio: 2.696, p = 0.008) and OS (hazard ratio: 4.865, p = 0.003) in multivariable analysis. We created a nomogram on the basis of the NTR, and it could accurately predict OS (concordance index: 0.774). Preoperative NTRs may be a useful prognostic biomarker for DFS and OS in patients with OSCC who have undergone surgery. NTR-based nomograms may also be helpful prognostic tools in clinical trials.

Danshen has been widely used for the treatment of central nervous system diseases. We investigated the effect of dihydroisotanshinone I (DT), a compound extracted from Danshen, as well as the corresponding mechanisms in an in vitro-based 6-OHDA-induced Parkinson's disease (PD) model. SH-SY5Y human neuroblastoma cell lines were pretreated with 6-hydroxydopamine (6-OHDA) and challenged with DT. Subsequently, the cell viability and levels of reactive oxygen species (ROS) and caspase-3 were analyzed. The effect of DT on the 6-OHDA-treated SH-SY5Y cells and the expression of the core circadian clock genes were measured using a real-time quantitative polymerase chain reaction. Our results indicated that DT attenuated the 6-OHDA-induced cell death in the SH-SY5Y cells and suppressed ROS and caspase-3. Moreover, DT reversed both the RNA and protein levels of BMAL1 and SIRT1 in the 6-OHDA-treated SH-SY5Y cells. Additionally, the SIRT1 inhibitor attenuated the effect of DT on BMAL1 and reduced the cell viability. The DT and SIRT1 activators activated SIRT1 and BMAL1 , and then reduced the death of the SH-SY5Y cells damaged by 6-OHDA. SIRT1 silencing was enhanced by DT and resulted in a BMAL1 downregulation and a reduction in cell viability. In conclusion, our investigation suggested that DT reduces cell apoptosis, including an antioxidative effect due to a reduction in ROS, and regulates the circadian genes by enhancing SIRT1 and suppressing BMAL1. DT may possess novel therapeutic potential for PD in the future, but further in vivo studies are still needed.

The Chiehyuan herbal oral protection solution (GB-2) is a herbal mixture commonly utilized in Taiwan for combating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as per traditional Chinese medicine practices. This study assessed the clinical impact of GB-2 through prospective clinical trials. With twice-daily use for a week, GB-2 was shown to diminish the expression of angiotensin-converting enzyme 2 (ACE2) in oral mucosal cells. Moreover, after two weeks of use, it could reduce transmembrane protease, serine 2 (TMRPSS2) expression in these cells. Additionally, in vitro experiments demonstrated that GB-2 lessened the entry efficiency of the Omicron, L452R-D614G, T478K-D614G, and L452R-T478K-D614G variants of the SARS-CoV-2 pseudotyped lentivirus. It also impeded the interaction between ACE2 and the receptor-binding domain (RBD) presenting N501Y-K417N-E484A-G339D-Q493R-G496S-Q498R and L452R-T478K mutations. Glycyrrhizic acid, a major compound in GB-2, also hindered the entry of the Omicron variant (BA.1) of the SARS-CoV-2 pseudotyped lentivirus by obstructing the binding between ACE2 and the RBD presenting the N501Y-K417N-E484A-G339D-Q493R-G496S-Q498R mutation. To sum up, these findings suggest that GB-2 can decrease ACE2 and TMPRSS2 expression in oral mucosal cells. Both glycyrrhizic acid and GB-2 were found to reduce the entry efficiency of the Omicron variant (BA.1) of the SARS-CoV-2 pseudotyped lentivirus and block the binding between ACE2 and the RBD with the N501Y-K417N-E484A-G339D-Q493R-G496S-Q498R mutation. This evidence implies that GB-2 might be a potential candidate for further study as a preventative measure against SARS-CoV-2 infection., 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, (© 2023 The Authors. Published by Elsevier Ltd.)

Whether the modified Glasgow prognostic score (mGPS) is useful for patients with head and neck squamous cell carcinoma (HNSCC) remains controversial. An electronic database search on EMBASE, PubMed, and the Cochrane Library from inception to 30 June 2022 was performed for study selection and data extraction. The associations between the mGPS and survival outcomes were evaluated using a random-effects meta-analysis and expressed as pooled hazard ratios (HRs) and 95% CIs. We included 11 studies involving a total of 2017 patients with HNSCC. A higher mGPS was associated with poorer progression-free survival (HR = 2.39, 95% CI 1.69-3.38), overall survival (HR = 2.40, 95% CI 1.94-2.98), disease-specific survival (HR = 2.57, 95% CI 1.71-3.88), and disease-free survival (HR = 2.67, 95% CI 1.51-4.73, all p ≤ 0.001) in HNSCC. The mGPS can function as a valid prognostic biomarker for patients diagnosed as having HNSCC., (© 2023 Wiley Periodicals LLC.)