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Chin-Yi Yang,1,2,&ast; Ya-Ching Chang,2,&ast; Hao-Chih Tai,3 Yi-Hua Liao,4 Yu-Huei Huang,2 Rosaline Chung-Yee Hui,2 Yuan-Sung Kuo,3 Shyue-Yih Horng,3 Yi-Shuan Sheen,4 Tim-Mo Chen,5 Yuan-Sheng Tzeng,5 Chih-Hsin Wang,5 Shou-Cheng Teng,5 Chun-Kai Oscar Chang,5 Chang-Yi Chou5 1Department of Dermatology, New Taipei Municipal TuCheng Hospital, New Taipei City, 236, Taiwan; 2Department of Dermatology, Linkou Chang-Gung Memorial Hospital, Taoyuan, 333, Taiwan; 3Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, 100, Taiwan; 4Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, 100, Taiwan; 5Division of Plastic Surgery, Tri-Service General Hospital, Taipei, 100, Taiwan&ast;These authors contributed equally to this workCorrespondence: Hao-Chih Tai, Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, No. 7, Zhongshan S. Road, Zhongzheng Dist, Taipei, 100225, Taiwan, Tel +886 2 2312-3456&num;65062 65520, Email taihc1@gmail.com; taihc@ntu.edu.tw Yi-Hua Liao, Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, No. 7, Zhongshan S. Road, Zhongzheng Dist, Taipei, 100225, Taiwan, Tel +886 2 2312-3456&num; 265317, Email yihualiao@ntu.edu.twPurpose: Porcine-based dermal injectable collagen is effective for nasolabial fold correction. In the present study, a new dermal injectable collagen, incorporating a novel cross-linking technology and premixed with lidocaine, was introduced. The study aimed to determine the efficacy of the new dermal injectable collagen in improving bilateral nasolabial fold wrinkles, and reducing pain during injection.Patients and Methods: This prospective, double-blind, multicenter, parallel-group, randomized trial enrolled participants with moderate-to-severe bilateral nasolabial fold wrinkles from February 2019 to March 2021. Participants were randomly assigned to the test group (new dermal injectable collagen with lidocaine featuring a novel cross-linking technology) or control group (traditionally cross-linked dermal injectable collagen with lidocaine). Participants were monitored for adverse events (AEs), and for pain using the Thermometer Pain Scale (TPS) and a visual analog scale (VAS). Efficacy was measured using the Wrinkle Severity Rating Scale (WSRS) and the Global Aesthetic Improvement Scale (GAIS).Results: On the poor or better sides, the 2 groups exhibited a significant decrease in WSRS scores at 4, 12, 24, and 36 weeks after treatment, compared to baseline WSRS scores (all, p < 0.05). Compared to the control group, the test group had a greater decrease in WSRS score (poor or better sides) at 12, 24, 36, and 52 weeks after treatment (all, p < 0.05). A similar observation was also found in the WSRS response rate and GAIS score of the 2 groups. VAS and TPS scores were not significantly different between the 2 groups (p > 0.05), indicating that pain reduction was similar in the 2 groups. All AEs were anticipated AEs associated with facial aesthetic injections, and most recovered within 0 to 30 days without sequelae. There were no differences in AEs between the 2 groups (all, p > 0.05).Conclusion: The new dermal injectable collagen with lidocaine exhibited better efficacy for correcting nasolabial fold wrinkles compared to the control group. Both relieved pain and produced only transient and tolerable AEs.Keywords: adverse event, bilateral nasolabial folds, dermal filler, pain, porcine collagen, wrinkles

Lei Qin,1,* Yi-Wei Kao,2,* Yueh-Lung Lin,3 Bou-Yue Peng,4 Win-Ping Deng,5 Tsung-Ming Chen,6 Kuan-Chou Lin,7 Kevin Sheng-Po Yuan,8 Alexander TH Wu,9 Ben-Chang Shia,10 Szu-Yuan Wu11–14 1School of Statistics, University of International Business and Economics, Beijing, China; 2Graduate Institute of Business Administration, Fu Jen Catholic University, Taipei, Taiwan; 3School of Mathematical Sciences, University of Nottingham, Ningbo, China; 4Department of Dentistry, Taipei Medical University Hospital, Taipei, Taiwan; 5Graduate Institute of Biomedical Materials and Engineering, Taipei Medical University, Taipei, Taiwan; 6Department of Otorhinolaryngology, Shuang-Ho Hospital, Taipei Medical University, Taipei, Taiwan; 7Department of Oral and Maxillofacial Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 8Department of Otorhinolaryngology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 9PhD Program for Translational Medicine, Taipei Medical University, Taipei, Taiwan; 10College of Management, Taipei Medical University, Taipei, Taiwan; 11Institute of Clinical Science, Zhongshan Hospital, Fudan University, Shanghai, China; 12Department of Radiation Oncology, Wanfang Hospital, Taipei Medical University, Taipei, Taiwan; 13Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 14Epidemiology and Bioinformatics Center, Wanfang Hospital, Taipei Medical University, Taipei, Taiwan *These authors contributed equally to this work Background: Few studies have evaluated the risk of oral cavity cancer (OC) in patients with recurrent oral aphthae (ROA) and dry eye syndrome (DES). This study assessed the risk of OC in patients who had received diagnoses of ROA and DES in Taiwan.Methods: A population-based frequency-matched case–control study was conducted in which data were analyzed from the National Health Insurance Research Database of Taiwan. Patients with ROA and DES were identified as the case cohort. Patients and controls without ROA and DES were frequency matched (1:4) on the basis of age, sex, monthly income, geographical location, and urbanization level. Chi-squared tests were conducted to compare demographic factor distributions between the patients and controls. Cox proportional hazards models were used to calculate the adjusted hazard ratios (aHRs) and 95% CI of OC diagnoses among the patients and controls. Risk consistency between the two cohorts was determined using subgroup analysis.Results: A total of 7,110 patients with ROA and DES and 28,388 controls were identified. The OC risk was significantly higher for female patients than controls (aHR=3.41, 95% CI=1.69–6.86). Furthermore, women aged 50–69 years exhibited a higher risk of OC than those in the other age groups. Female patients aged 50–59 years exhibited the highest aHR for OC (aHR=5.56, 95% CI=1.70–18.25), followed by those aged 60–69 years (aHR=4.34, 95% CI=1.26–15.99).Conclusion: ROA and DES may be associated with a high risk of OC in elderly women. Keywords: risk factor, oral cavity cancer, recurrent oral aphthae, dry eye syndrome, women

OBJECTIVE: Because Chinese Americans are known to underutilize mental health services, routine screening for depression in primary care clinics has been advocated as a means of identifying Chinese-American patients with depression and initiating appropriate treatment. This analysis evaluated the utility of the nine-item depression module of the Patient Health Questionnaire (PHQ-9) for depression screening and monitoring treatment outcomes among Chinese Americans at a primary health care setting. METHODS: A total of 3,417 patients who presented for an initial or annual physical examination with their primary care providers were screened for depression between January and October 2003 at the Charles B. Wang Community Health Center, a primary health care center in New York City serving primarily low-income Chinese Americans. The depression screen was a two-tier process: if patients endorsed one or more of three initial questions on an abridged version of the PHQ-9, they were then administered the PHQ-9. RESULTS: A total of 141 individuals (4.1 percent) had clinically significant depressive symptoms (PHQ-9 score of 10 or higher). Women were more likely to have significant levels of depressive symptoms than men (17.3 percent compared with 11.6 percent). A total of 114 of the 141 patients with clinically significant depressive symptoms received treatment plans initiated by their primary care provider. Forty (35.1 percent) responded to treatment (50 percent decrease in PHQ-9 score) by eight weeks of treatment. CONCLUSIONS: The PHQ-9 can be used to screen for depression as well as guide depression treatment planning among Chinese Americans in primary care. Screening for major depression with the PHQ-9 in primary care settings should be considered for appropriate identification and treatment of depression for Chinese-American patients. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is a deadly type of brain tumor with low patient survival rates. Previous studies have shown that inhibiting the intracellular bile acid transport protein can suppress brain tumor growth, migration, and angiogenesis. This study aims to investigate the effects of the bile acid nuclear receptor (farnesoid X receptor, FXR) agonist GW4064 on the migration, and invasion in GBM cells. GW4064 treatment inhibited the migration and invasion of GBM cells. The protein expression of phosphorylated focal adhesion kinase and protein kinase C alpha (PKCα) and activity of matrix metalloproteinase-2 (MMP2) were decreased by GW4064. The PKC activator phorbol 12-myristate 13-acetate (PMA) reversed the GW4064-reduced invasion ability in LN229 cells. Moreover, GW4064 combined with temozolomide (TMZ) treatment inhibited tumor progression in null mice. According to the hematoxylin and eosin stain (HE) and immunostaining, the tumor area and p-PKCα were reduced in the GW4064 combined with TMZ group. These results suggested that GW4064 declined the progression of GBM cells, with the inhibition of invasion mediated through PKC signaling. Targeting FXR may contribute to future therapeutic strategies for GBM., 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 © 2025 Elsevier B.V. All rights reserved.)

Objective: To analyze the clinical characteristics and outcomes of Haemophilus influenzae (Hi) meningitis in children. Methods: This is a retrospective case series study. This study included 34 Hi meningitis patients who admitted to Beijing Children's Hospital, Capital Medical University, from January 1, 2010, to December 31, 2023. Data on clinical presentations, laboratory tests, hearing assessment and outcomes at discharge were collected. Patients were divided into 2 groups according to the outcome at discharge: favorable outcome group and unfavorable outcome group. Mann-Whitney U test and Fisher exact test was used to estimate the risk factors for an unfavorable outcome at discharge. Results: Thirty-four patients were enrolled. There were 16 males and 18 females. The age at onset ranged from 3 months to 12 years. Fever (34 patients (100%)), convulsions (17 patients (50%)), and coma (21 patients (62%)) were the common clinical presentations. Twenty-four patients (71%) developed complications. There were 15 patients (44%) needed treatment in the intensive care unit, 5 patients (15%) received intubation, and 4 patients (12%) had developed shock. The favorable outcome group included 23 patients, and the unfavorable outcome group included 11 patients. Female, patients with limb movement disability, dystonia, ventriculomegaly or hydrocephalus, and a concentration of glucose in the initial cerebrospinal fluid lower than 1 mmol/L were risk factors of unfavorable outcome at discharge (all P <0.05). Among the 23 patients (68%) in favorable outcomes group, 13 patients (57%) had data available on their long-term follow-up results, including 12 patients with favorable long-term outcomes and 1 patient with unfavorable long-term outcome. Among the 11 patients (32%) in unfavorable outcomegroup, 1 patient died, the other 10 patients (91%) had data available on their long-term outcomes. Eight patients had unfavorable long-term outcomes and 2 patients with favorable long-term outcomes. Patients who had unfavorable outcomes at discharge were at a greater risk of experiencing unfavorable long-term outcomes ( P =0.001). Conclusions: It is common for patients with Hi meningitis to have intracranial complications or develop into critical conditions. Patients who have limb movement disability, dystonia, ventriculomegaly or hydrocephalus, and who exhibit a concentration of glucose in the initial cerebrospinal fluid lower than 1 mmol/L tend to have unfavorable outcomes; they need to be assessed for sequelae.

Competing Interests: Conflicts of interest and sources of funding: none declared.

Ferroelectricity realized in van der Waals (vdW) materials with non-centrosymmetric stacking configurations holds promise for future 2D devices with nonvolatile and reconfigurable functionalities. However, the epitaxial growth of ferroelectric vdW materials often struggles to achieve an energetically unfavorable stacking configuration that enables electric polarization. This challenge is particularly evident when performing heteroepitaxy on another vdW substrate to create versatile and scalable ferroelectric building blocks designed for large-area, atomic-scale thicknesses. Here, epitaxial hexagonal boron nitride (h-BN) multilayer films are successfully grew on single-crystal graphene synthesized on a miscut SiC (0001) substrate. Theoretical calculations illustrate that the moiré-patterned h-BN/graphene hetero-interface intrinsically exhibits polarization, leading to a polarized AB stacking in multilayer h-BN films to minimize the total formation energy, which is validated experimentally by the layer-dependent band dispersions. The as-grown multilayer h-BN layers demonstrated robust, homogeneous ferroelectricity with switchable out-of-plane polarization via interlayer sliding. This study establishes an effective route for stacking-controlled heteroepitaxy, enabling the large-scale integration of vdW materials with ferroelectricity and versatile functionalities, offering a promising platform for next-generation 2D ferroelectric devices., (© 2025 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Bladder cancer, more prevalent in men, has high recurrence rates in non-muscle-invasive forms and is highly lethal upon metastasis in muscle-invasive cases. Transient receptor potential canonical channels (TRPCs), specifically TRPC3, play a role in calcium signaling, influencing cancer cell behavior. This study examines the effects of Pyr3, a TRPC3 inhibitor, and TRPC3 knockdown on both muscle-invasive (T24) and non-muscle-invasive (RT4) bladder cancer cells. Pyr3 treatment reduced cell viability, migration, adhesion, and calcium influx in these cells. Additionally, Pyr3 treatment and siTRPC3 downregulated protein kinase C alpha (PKCα), phospho-PKCα, and protein phosphatase 2A (PP2A) levels. While PKC activator phorbol 12-myristate 13-acetate (PMA) could not restore Pyr3-induced viability loss, it reversed the migration inhibition. In a xenograft model, Pyr3 suppressed T24 cell viability, Ki67, phospho-PKCα, PP2A and TRPC3 expression. These findings suggest that Pyr3 inhibits bladder cancer cell migration through PKC signaling and holds potential as a therapeutic agent for bladder cancer., 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: The question as to whether prolonged diagnosis-to-surgery intervals (DSIs) may compromise survival outcomes in patients with oral cavity squamous cell carcinoma (OCSCC) remains unanswered. This nationwide study was designed to address this issue., Methods: We analyzed data from 26,214 patients with first primary OCSCC identified in the Taiwanese Cancer Registry Database between 2011 and 2021. The optimal DSI cutoff was determined based on 5-year disease-specific survival (DSS) and overall survival (OS) rates using Cox regression analysis. Patients were categorized into three distinct DSI groups: ≤20 days (47 %), 21-31 days (31 %), and > 31 days (22 %)., Results: The 5-year DSS and OS rates for the ≤20/21-31/>31 days groups were 81 %/78 %/77 % and 73 %/70 %/68 %, respectively (both p < 0.0001). Patients in the ≤20 days group had a higher prevalence of pathological stages I-II. After adjustment for potential confounders in multivariable analysis, a DSI > 31 days (versus ≤ 20 days) retained independent associations with adverse outcomes at 5 years, with hazard ratios of 1.07 for both DSS and OS. Propensity score matching and multivariable analysis comparing DSI ≤ 20 days to DSI > 31 days stratified by pathological stage III-IV showed that higher DSS and OS rates were observed in patients with DSI ≤ 20 days than DSI > 31 days (68 %/66 %, p = 0.0586; 60 %/57 %, p = 0.0228, respectively), with hazard ratios of 1.09 for both DSS and OS., Conclusions: Our findings indicate that DSI is an independent predictor of 5-year DSS and OS in patients with OCSCC. A DSI exceeding 31 days, or even 21 days, may potentially decrease survival outcomes., 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 © 2025. Published by Elsevier Ltd.)

Purpose: To share our 20-year experience in major burn management and the impact of a newly implemented burn protocol since 2015 at Tri-Service General Hospital (TSGH)., Materials and Methods: We performed a retrospective cohort study of severely burned patients who were admitted to the intensive care unit (ICU) at TSGH from January 2003 to September 2023. Data regarding demographics, complications, and mortality were collected and analyzed. We compared the patient data before (pre-implementation) and after 2015 (post-implementation), when the new major burn management protocol was introduced., Results: No statistically significant differences were observed in the mean total body surface area of the burns between the groups. The post-implementation group had younger age (34.62 vs 45.06, P < 0.001) and lower rate of inhalation injury (60.8 % vs 82.5 %, P = 0.005). No statistically significant difference was observed in the ICU stays between the groups. The post-implementation group had a statistically significant lower all-cause mortality (8.1 % vs 47.6 %, P < 0.0001) and lower rate of renal replacement therapy (RRT) (20.3 % vs 42.9 %, P = 0.004) but earlier initiation of RRT., Conclusion: The new TSGH Burns Protocol revolutionized the care of major burns by introducing tailored, multidisciplinary burn management and improved patient outcomes., Competing Interests: Declaration of Competing Interest Authors declare no conflict of interests for this article., (Copyright © 2024 Elsevier Ltd and International Society of Burns Injuries. All rights reserved.)

Introduction: OBI-858 is a brand-new botulinum Type A complex toxin with a specific molecular weight of 760 kDa intended for development for both aesthetic and therapeutic applications. This is a phase I, dose-escalation study to evaluate the safety and preliminary efficacy of OBI-858 in subjects with moderate to severe glabellar lines., Methods: Each subject received OBI-858 by intramuscular injections with an assigned dose (10 U, 20 U, and 30 U). The safety and preliminary efficacy were evaluated at each of the in-person visits., Results: A total of 36 subjects (12 subjects per cohort) were enrolled. The response rates (≥ 1 point) for all groups at maximum frown were assessed at week 4 were 100%. The initial improvement for 30 U occurred at day 3. Response rates revealed benefits lasting 4-6 months or longer. Subject satisfaction at week 4 was high in all groups. Adverse effects were mild and infrequent. Among them, one subject had drug-related AE, and one subject had grade ≥ 3 unrelated AE., Conclusions: This study demonstrated that OBI-858 is well tolerated and showed preliminary efficacy. Overall, the OBI-858 has a clinically favorable profile of safety and efficacy that warrants proceeding to the next studies., Competing Interests: Declarations. Conflict of Interest: Chien-Chih Ou is the stockholder of OBIGEN PHARMA. Drs. Chih-Hung Lee and Tim-Mo Chen are the principal investigators for this phase I clinical trial and have no disclosures related to this product or the company. Ethical Approval: There were institutional approvals of experiments by the Tri-Service General Hospital and Kaohsiung Chang Gung Memorial Hospital Institutional Review Board. Written informed consent was obtained from all participants., (© 2024. The Author(s).)

Background: The prognostic significance of margin-to-depth ratio (MDR) in oral cavity squamous cell carcinoma (OCSCC) remains unclear, particularly in comparison to traditional margin status. We aimed to examine the association between MDR and clinical outcomes in a large Taiwanese cohort., Methods: A total of 18,324 patients with first primary OCSCC were categorized by margin status: positive (1013), <5 mm (8371), and ≥ 5 mm (8940). Disease-specific survival (DSS) and overall survival (OS) served as the main outcome measures., Results: After excluding patients with positive margins (MDR = 0), the optimal MDR cutoff value for DSS and OS was 0.6. Patients with MDR > 0.6 showed significantly better 5-year DSS and OS rates (87 %, 81 %) compared to those with MDR ≤ 0.6 (71 %, 63 %) and MDR = 0 (53 %, 43 %). Multivariable analysis identified MDR ≤ 0.6 as independently associated with both DSS and OS in the entire cohort (hazard ratio [HR] = 1.34/1.32). This finding was consistent in the subgroups with surgical margins < 5 mm (HR = 1.39 for DSS and 1.38 for OS) and margins ≥ 5 mm (HR = 1.21 for both DSS and OS). In subgroups with surgical margins < 5 mm and ≥ 5 mm, an MDR > 0.6 was associated with better survival outcomes., Conclusions: An MDR (cutoff: 0.6) is independently associated with prognosis in OCSCC, offering improved risk stratification compared to margin status alone. While MDR may guide surgical margin modification, further research is needed to determine whether MDR could serve as a postoperative indicator for adjuvant therapy in patients with close or clear margins., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: This study investigated whether artificial intelligence (AI) models combining voice signals, demographics, and structured medical records can detect glottic neoplasm from benign voice disorders., Methods: We used a primary dataset containing 2-3 s of vowel "ah", demographics, and 26 items of structured medical records (e.g., symptoms, comorbidity, smoking and alcohol consumption, vocal demand) from 60 patients with pathology-proved glottic neoplasm (i.e., squamous cell carcinoma, carcinoma in situ, and dysplasia) and 1940 patients with benign voice disorders. The validation dataset comprised data from 23 patients with glottic neoplasm and 1331 patients with benign disorders. The AI model combined convolutional neural networks, gated recurrent units, and attention layers. We used 10-fold cross-validation (training-validation-testing: 8-1-1) and preserved the percentage between neoplasm and benign disorders in each fold., Results: Results from the AI model using voice signals reached an area under the ROC curve (AUC) value of 0.631, and additional demographics increased this to 0.807. The highest AUC of 0.878 was achieved when combining voice, demographics, and medical records (sensitivity: 0.783, specificity: 0.816, accuracy: 0.815). External validation yielded an AUC value of 0.785 (voice plus demographics; sensitivity: 0.739, specificity: 0.745, accuracy: 0.745). Subanalysis showed that AI had higher sensitivity but lower specificity than human assessment (p < 0.01). The accuracy of AI detection with additional medical records was comparable with human assessment (82% vs. 83%, p = 0.78)., Conclusions: Voice signal alone was insufficient for AI differentiation between glottic neoplasm and benign voice disorders, but additional demographics and medical records notably improved AI performance and approximated the prediction accuracy of humans., Level of Evidence: NA Laryngoscope, 134:4585-4592, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: The evidence for adjuvant chemoradiotherapy (CRT) of oral cavity squamous cell carcinoma (OCSCC) with extra-nodal extension (ENE) in National Comprehensive Cancer Network (NCCN) guidelines is derived from patients with head and neck cancer. The guidelines further suggest a radiation dose ranging from 6000 to 6600 cGy. In this nationwide study, we sought to evaluate the prognostic significance of adjuvant therapy and the specific radiation dosage in Taiwanese patients with pure OCSCC and ENE., Methods: A retrospective analysis of 1577 OCSCC patients with ENE who underwent resection and received adjuvant CRT or radiotherapy (RT) between January 2011 and December 2020 was conducted., Results: Multivariable analysis revealed that adjuvant RT, more than four pathologically positive nodes, and radiation dosage below 6000 cGy were independent risk factors for unfavorable 5-year disease-specific survival (DSS) and overall survival (OS). Comparing patients who received CRT (n = 1453) to those treated with RT (n = 124) before and after propensity score (PS) matching, the 5-year outcomes were as follows: before PS matching, DSS (54% versus 30%, p < 0.0001), OS (42% versus 18%, p < 0.0001); after PS matching (n = 111 in each group), DSS (52% versus 30%, p = 0.0016), OS (38% versus 21%, p = 0.0019). For patients who underwent CRT, the 5-year outcomes for different radiation dose groups (6600 - 7000 cGy, n = 1155 versus 6000 - 6500 cGy, n = 199) were as follows: before PS matching, DSS (52% versus 54%, p = 0.1904), OS (43% versus 46%, p = 0.1610); after PS matching (n = 199 in each group), DSS (55% versus 54%, p = 0.8374), OS (46.5% versus 46.3%, p = 0.7578)., Conclusions: For OCSCC patients with ENE, our study shows CRT improved survivals than RT alone, underscoring the clinical significance of chemotherapy. Patients undergoing CRT with irradiation doses ranging from 6000 to 6500 cGy exhibited comparable survival outcomes to those receiving doses of 6600-7000 cGy. This observation suggests that irradiation doses exceeding the 6600 cGy may not confer the survival advantage in these patients. Further research is needed to confirm our results and explore the optimal irradiation dose for managing these patients., (© 2024. The Author(s).)

Background: Pancreatic cancer remains one of the most lethal malignancies, and has limited effective treatment. Gemcitabine (GEM), a chemotherapeutic agent, is commonly used for clinical treatment of pancreatic cancer, but it has characteristics of low drug delivery efficiency and significant side effects. The study tested the hypothesis that human bone marrow mesenchymal stem cell (MSC)-derived exosomes loaded with GEM (Exo-GEM) would have a higher cytotoxicity against human pancreatic cancer cells by enhancing their apoptosis., Aim: To investigate the cytotoxicity of MSC-derived Exo-GEM against pancreatic cancer cells in vitro ., Methods: Exosomes were isolated from MSCs and characterized by transmission electron microscopy and nanoparticle tracking analysis. Exo-GEM through electroporation, sonication, or incubation, and the loading efficiency was evaluated. The cytotoxicity of Exo-GEM or GEM alone against human pancreatic cancer Panc-1 and MiaPaca-2 cells was assessed by MTT and flow cytometry assays., Results: The isolated exosomes had an average size of 76.7 nm. The encapsulation efficacy and loading efficiency of GEM by electroporation and sonication were similar and significantly better than incubation. The cytotoxicity of Exo-GEM against pancreatic cancer cells was stronger than free GEM and treatment with 0.02 μM Exo-GEM significantly reduced the viability of both Panc-1 and MiaPaca-2 cells. Moreover, Exo-GEM enhanced the frequency of GEM-induced apoptosis in both cell lines., Conclusion: Human bone marrow MSC-derived Exo-GEM have a potent cytotoxicity against human pancreatic cancer cells by enhancing their apoptosis, offering a promising drug delivery system for improving therapeutic outcomes., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Hypersensitivity to the new dermal injectable porcine-based collagen with lidocaine featuring a novel cross-linking technology (test filler) for nasolabial fold correction was compared to the commercially available traditional cross-linked dermal injectable porcine-based collagen with lidocaine (control filler). Methods: Recruited participants (n = 279) received a single 0.1 mL intradermal injection of either test filler or control filler in the left forearm as a screening skin allergy test. Injection sites were assessed clinically at 24 h post-implant. Treatment was given to 252 successfully screened participants, and injection sites were monitored for 21 days. Immunological examinations were performed at screening and then at 4 and 24 weeks post-treatment. Observations for adverse events continued until the 52nd week. Results: Intradermal allergy testing results were negative for all the test recipients (0/124) and positive for two control recipients (2/132, 1.5%). Most of the participants exhibited no changes in serum immunoglobulin (IgG, IgM) and complement (C3, C4) levels. No serious adverse events related to the device were recorded. Most adverse events were common complications of dermal filler treatment and were related to the injection site. Most adverse effects were resolved or under control by 52 weeks. Conclusions: Hypersensitivity reactions with the test filler were lower than those with the control filler, validating the safe use of test filler for nasolabial fold correction without the need for pretreatment skin testing.

Background: Group A streptococcal(GAS) meningitis is a severe disease with a high case fatality rate. In the era of increasing GAS meningitis, our understanding about this disease is limited., Purpose: To gain a better understanding about GAS meningitis., Methods: Five new cases with GAS meningitis were reported. GAS meningitis related literatures were searched for systematic review in PUBMED and EMBASE. Case reports and case series on paediatric cases were included. Information on demographics, risk factors, symptoms, treatments, outcomes, and emm types of GAS was summarized., Results: Totally 263 cases were included. Among 100 individuals, 9.9% (8/81) had prior varicella, 11.1% (9/81) had anatomical factors, and 53.2% (42/79) had extracranial infections. Soft tissue infections were common among infants (10/29, 34.5%), while ear/sinus infections were more prevalent in children ≥ 3 years (21/42, 50.0%). The overall case fatality rate (CFR) was 16.2% (12/74). High risk of death was found in patients with shock or systemic complications, young children(< 3 years) and cases related to hematogenic spread. The predominate cause of death was shock(6/8). Among the 163 patients included in case series studies, ear/sinus infections ranged from 21.4 to 62.5%, while STSS/shock ranged from 12.5 to 35.7%, and the CFR ranged from 5.9 to 42.9%., Conclusions: A history of varicella, soft tissue infections, parameningeal infections and CSF leaks are important clinical clues to GAS in children with meningitis. Young children and hematogenic spread related cases need to be closely monitored for shock due to the high risk of death., (© 2024. The Author(s).)

Background: While surgery remains the primary treatment for oral squamous cell carcinoma (OCSCC), induction chemotherapy (IC) can be used as a bridging or neoadjuvant therapy. This nationwide study in Taiwan examines the survival outcomes of OCSCC patients who received IC before surgery., Methods: We analyzed data from 29,891 patients with OCSCC. Of these, 29,058 initially underwent surgery (OP group), whereas 833 received IC before surgery (IC + OP group). A propensity score (PS)-matched analysis (4, 1 ratio, 3260 vs. 815 patients) was performed considering tumor subsite, sex, age, Charlson comorbidity index, clinical T1-T4b tumors, clinical N0-3 disease, and clinical stage I-IV., Results: In the PS-matched cohort, the 5-year disease-specific survival (DSS) and overall survival (OS) rates were 65% and 57%, respectively. When comparing the OP and IC + OP groups, the 5-year DSS rates were 66% and 62%, respectively (p = 0.1162). Additionally, the 5-year OS rates were 57% and 56%, respectively (p = 0.9917). No significant intergroup differences in survival were observed for specific subgroups with cT4a tumors, cT4b tumors, cN3 disease, pT4b tumors, and pN3 disease. However, for patients with pT4a tumors, the OP group demonstrated superior 5-year outcomes compared to the IC + OP group, with a DSS of 62% versus 52% (p = 0.0006) and an OS of 53% versus 44% (p = 0.0060). Notably, patients with cT2-3, cN1, and c-Stage II disease in the IC + OP group were significantly more likely to achieve pT0-1 status (p < 0.05)., Conclusions: Following PS matching, the IC + OP group generally exhibited similar prognosis to the OP group. However, for pT4a tumors, the OP group showed superior 5-year outcomes. While IC may not universally improve survival, it could be advantageous for patients who respond positively to the treatment., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Data on pyogenic liver abscess (PLA) of children in China have been limited. We aimed to summarize the clinical feather, microbiological characteristics, management, and outcome of PLA in children., Method: We retrospectively reviewed PLA cases from January 2008 to June 2023 at Beijing Children's Hospital. Clinical characteristics, pathogens and management were analyzed., Results: We diagnosed 57 PLA patients in our center. The median onset age was 4.5 years and the male-to-female ratio was 1.6:1. The median diagnostic time was nine days and the median length of stay was 22 days. Twenty-eight patients (49.1%) had predisposing factors, around 71.4% of the patients had malignant hematology and primary immunodeficiency disease. Patients with underlying factors were more likely to have extrahepatic organ involvement (p = 0.024), anemia (p < 0.001), single abscess (p = 0.042), unilateral involvement (p = 0.039), and small size of the abscess (p = 0.008). Twenty-four patients (42.1%) had extrahepatic organ involvement. Pathogens were identified in 17 patients (29.8%), the most common pathogens were Klebsiella pneumoniae and Staphylococcus aureus. The positive rate of metagenomic next-generation sequencing (mNGS) was 87.5% (7/8). On multivariable analysis, the extrahepatic organ involved (p = 0.029) and hepatomegaly (p = 0.025) were two independent factors associated with poor outcomes., Conclusions: PLA is usually seen in children with predisposing factors. Malignant hematology and primary immunodeficiency disease were the most common underlying diseases. Extrahepatic organ involvement and hepatomegaly are associated with poor prognosis. Increased use of mNGS could be beneficial for identifying pathogens., (© 2024. The Author(s).)

Background: Elective tracheotomy is commonly performed in resected oral squamous cell carcinoma (OCSCC) to maintain airway patency. However, the indications for this procedure vary among surgeons. This nationwide study evaluated the impact of tracheotomy on both the duration of in-hospital stay and long-term survival outcomes in patients with OCSCC., Methods: A total of 18,416 patients with OCSCC were included in the analysis, comprising 7981 patients who underwent elective tracheotomy and 10,435 who did not. The primary outcomes assessed were 5-year disease-specific survival (DSS) and overall survival (OS). To minimize potential confounding factors, a propensity score (PS)-matched analysis was performed on 4301 patients from each group. The duration of hospital stay was not included as a variable in the PS-matched analysis., Results: Prior to PS matching, patients with tracheotomy had significantly lower 5-year DSS and OS rates compared to those without (71% vs. 82%, p < 0.0001; 62% vs. 75%, p < 0.0001, respectively). Multivariable analysis identified tracheotomy as an independent adverse prognostic factor for 5-year DSS (hazard ratio = 1.10 [1.03-1.18], p = 0.0063) and OS (hazard ratio = 1.10 [1.04-1.17], p = 0.0015). In the PS-matched cohort, the 5-year DSS was 75% for patients with tracheotomy and 76% for those without (p = 0.1488). Five-year OS rates were 66% and 67%, respectively (p = 0.0808). Prior to PS matching, patients with tracheotomy had a significantly longer mean hospital stay compared to those without (23.37 ± 10.56 days vs. 14.19 ± 8.34 days; p < 0.0001). Following PS matching, the difference in hospital stay duration between the two groups remained significant (22.34 ± 10.25 days vs. 17.59 ± 9.54 days; p < 0.0001)., Conclusions: While elective tracheotomy in resected OCSCC patients may not significantly affect survival, it could be associated with prolonged hospital stays., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Measuring elasticity without physical contact is challenging, as current methods often require deconstruction of the test sample. This study addresses this challenge by proposing and testing a photoacoustic effect-based method for measuring the elasticity of polydimethylsiloxane (PDMS) at various mixing ratios, which may be applied on the wide range of applications such as biomedical and optical fields. A dual-light laser source of the photoacoustic (PA) system is designed, employing cross-correlation signal processing techniques. The platform systems and a mathematical model for performing PDMS elasticity measurements are constructed. During elasticity detection, photoacoustic signal features, influenced by hardness and shapes, are analyzed using cross-correlation calculations and phase difference detection. Results from phantom tests demonstrate the potential of predicting Young's modulus using the cross-correlation method, aligning with the American Society for Testing and Materials (ASTM) standard samples. However, accuracy may be affected by mixed materials and short tubes. Normalization or calibration of signals is suggested for aligning with Young's coefficient., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. Published by Elsevier Ltd.)

Bladder cancer (BC) is a malignant tumor of the urinary system with high mortality and recurrence rates. Proteasome subunit type 4 (PSMB4) is highly expressed and has been identified as having oncogenic properties in a variety of cancer types. This study aimed to explore the effect of PSMB4 knockdown on the survival, migration, and angiogenesis of human bladder cancer cells with different degrees of malignancy. We analyzed the effects of PSMB4 knockdown in bladder cancer cells and endothelial cells in the tumor microenvironment. PSMB4 was highly expressed in patients with low- and high-grade urothelial carcinoma. Inhibition of PSMB4 reduced protein expression of focal adhesion kinase (FAK) and myosin light chain (MLC), leading to reduced migration. Furthermore, the suppression of PSMB4 decreased the levels of vascular endothelial factor B (VEGF-B), resulting in lower angiogenic abilities in human bladder cancer cells. PSMB4 inhibition affected the migratory ability of HUVECs and reduced VEGFR2 expression, consequently downregulating angiogenesis. In the metastatic animal model, PSMB4 knockdown reduced the relative volumes of lung tumors. Our findings suggest the role of PSMB4 as a potential target for therapeutic strategies against human bladder cancer.

Background: To compare the clinical outcomes of two treatment modalities, initial surgery and primary definitive radiotherapy (RT), in Taiwanese patients diagnosed with cT1-2N0M0 oral cavity squamous cell carcinoma (OCSCC)., Methods: Between 2011 and 2019, we analyzed data for 13,542 cT1-2N0M0 patients who underwent initial surgery (n = 13,542) or definitive RT with a dosage of at least 6600 cGy (n = 145) for the treatment of OCSCC. To account for baseline differences, we employed propensity score (PS) matching, resulting in two well-balanced study groups (initial surgery, n = 580; definitive RT, n = 145)., Results: Before PS matching, the 5-year disease-specific survival (DSS) rates were 88% for the surgery group and 58% for the RT group. After PS matching, the 5-year DSS rates of the two groups were 86% and 58%, respectively. Similarly, the 5-year overall survival (OS) rates before PS matching were 80% for the surgery group and 36% for the RT group, whereas after PS matching, they were 73% and 36%, respectively. All these differences were statistically significant (p < 0.0001). A multivariable analysis identified treatment with RT, older age, stage II tumors, and a higher burden of comorbidities as independent risk factors for both DSS and OS. We also examined the 5-year outcomes for various subgroups (margin ≥5 mm, margin <5 mm, positive margins, RT combined with chemotherapy, and RT alone) as follows: DSS, 89%/88%/79%/63%/51%, respectively, p < 0.0001; OS, 82%/79%/68%/39%/32%, respectively, p < 0.0001., Conclusions: In Taiwanese patients with cT1-2N0M0 OCSCC, a remarkably low proportion (1.1%) completed definitive RT. A significant survival disparity of 30% was observed between patients who underwent initial surgery and those who received definitive RT. Interestingly, even patients from the surgical group with positive surgical margins exhibited a significantly superior survival compared to those in the definitive RT group., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: While several studies have indicated that a margin status of < 1 mm should be classified as a positive margin in oral cavity squamous cell carcinoma (OCSCC), there is a lack of extensive cohort studies comparing the clinical outcomes between patients with positive margins and margins < 1 mm., Methods: Between 2011 and 2020, we identified 18,416 Taiwanese OCSCC patients who underwent tumor resection and neck dissection. Of these, 311 had margins < 1 mm and 1013 had positive margins. To compare patients with margins < 1 mm and those with positive margins, a propensity score (PS)-matched analysis (n = 253 in each group) was conducted., Results: The group with margins < 1 mm displayed a notably higher prevalence of several variables: 1) tongue subsite, 2) younger age, 3) smaller depth of invasion), 4) early tumor stage, and 5) treatment with surgery alone. Patients with margins < 1 mm demonstrated significantly better disease-specific survival (DSS) and overall survival (OS) rates compared to those with positive margins (74 % versus 53 %, 65 % versus 43 %, both p < 0.0001). Multivariable analysis further confirmed that positive margins were an independent predictor of worse 5-year DSS (hazard ratio [HR] = 1.38, p = 0.0103) and OS (HR = 1.28, p = 0.0222). In the PS-matched cohort, the 5-year outcomes for patients with margins < 1 mm compared to positive margins were as follows: DSS, 71 % versus 59 %, respectively (p = 0.0127) and OS, 60 % versus 48 %, respectively (p = 0.0398)., Conclusions: OCSCC patients with a margin status < 1 mm exhibited distinct clinicopathological characteristics and a more favorable prognosis compared to those with positive resection margins., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

The ability of bladder cancer to invade and metastasize often leads to poor prognosis in bladder cancer patients. The aim of this study was to evaluate the effect of the farnesoid X receptor (FXR) agonist GW4064 on the migration and invasion of human bladder cancer cells. Long-term exposure to GW4064 decreased the colony formation of RT4 and T24 cells. The wound healing migration assay revealed an inhibitory effect of GW4064 on both of these bladder cancer cell lines. In addition, integrin β3 expression and myosin light chain phosphorylation were decreased after GW4064 treatment. Immunocytochemistry showed an increase in E-cadherin and a decrease in β-catenin in the cell membrane of bladder cancer cells. Total protein expression and membrane fractionation assays also indicated upregulation of E-cadherin and downregulation of β-catenin. Moreover, GW4064 reduced the invasion of muscle-invasive T24 cells. The GW4064-decreased migration and invasion were reversed by the proteasome inhibitor MG132 and the lysosome inhibitor NH 4 Cl. Furthermore, the GW4064-induced inhibition of matrix metalloproteinase-2 (MMP2) and cathepsin B expression was reversed by NH 4 Cl. Xenograft animal studies revealed that GW4064 declined MMP2, cathepsin B and lung metastasis of bladder cancer. In conclusion, GW4064 decreases the migration and invasion of human bladder cancer cells, which may provide a new therapeutic strategy for the treatment of human bladder cancer., 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.)

Rationale: Follow-up of patients with emphysema treated with endobronchial valves is limited to 3-12 months after treatment in prior reports. To date, no comparative data exist between treatment and control subjects with a longer follow-up. Objectives: To assess the durability of the Spiration Valve System (SVS) in patients with severe heterogeneous emphysema over a 24-month period. Methods: EMPROVE, a multicenter randomized controlled trial, presents a rigorous comparison between treatment and control groups for up to 24 months. Lung function, respiratory symptoms, and quality-of-life (QOL) measures were assessed. Results: A significant improvement in forced expiratory volume in 1 second was maintained at 24 months in the SVS treatment group versus the control group. Similarly, significant improvements were maintained in several QOL measures, including the St. George's Respiratory Questionnaire and the COPD Assessment Test. Patients in the SVS treatment group experienced significantly less dyspnea than those in the control group, as indicated by the modified Medical Research Council dyspnea scale score. Adverse events at 24 months did not significantly differ between the SVS treatment and control groups. Acute chronic obstructive pulmonary disease exacerbation rates in the SVS treatment and control groups were 13.7% (14 of 102) and 15.6% (7 of 45), respectively. Pneumothorax rates in the SVS treatment and control groups were 1.0% (1 of 102) and 0.0% (0 of 45), respectively. Conclusions: SVS treatment resulted in statistically significant and clinically meaningful durable improvements in lung function, respiratory symptoms, and QOL, as well as a statistically significant reduction in dyspnea, for at least 24 months while maintaining an acceptable safety profile. Clinical trial registered with www.clinicaltrials.gov (NCT01812447).

This study compared the proliferation and differentiation potential of bone marrow-derived mesenchymal stem cells (BMSCs) derived from infants with polydactyly and adults with basal joint arthritis. The proliferation rate of adult and infant BMSCs was determined by the cell number changes and doubling times. The γH2AX immunofluorescence staining, age-related gene expression, senescence-associated β-galactosidase (SA-β-gal) staining were analyzed to determine the senescence state of adult and infant BMSCs. The expression levels of superoxide dismutases (SODs) and genes associated with various types of differentiation were measured using Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR). Differentiation levels were evaluated through histochemical and immunohistochemical staining. The results showed that infant BMSCs had a significantly higher increase in cell numbers and faster doubling times compared with adult BMSCs. Infant BMSCs at late stages exhibited reduced γH2AX expression and SA-β-gal staining, indicating lower levels of senescence. The expression levels of senescence-related genes ( p16 , p21 , and p53 ) in infant BMSCs were also lower than in adult BMSCs. In addition, infant BMSCs demonstrated higher antioxidative ability with elevated expression of SOD1 , SOD2 , and SOD3 compared with adult BMSCs. In terms of differentiation potential, infant BMSCs outperformed adult BMSCs in chondrogenesis, as indicated by higher expression levels of chondrogenic genes ( SOX9 , COL2 , and COL10 ) and positive immunohistochemical staining. Moreover, differentiated cells derived from infant BMSCs exhibited significantly higher expression levels of osteogenic, tenogenic, hepatogenic, and neurogenic genes compared with those derived from adult BMSCs. Histochemical and immunofluorescence staining confirmed these findings. However, adult BMSCs showed lower adipogenic differentiation potential compared with infant BMSCs. Overall, infant BMSCs demonstrated superior characteristics, including higher proliferation rates, enhanced antioxidative activity, and greater differentiation potential into various lineages. They also exhibited reduced cellular senescence. These findings, within the context of cellular differentiation, suggest potential implications for the use of allogeneic BMSC transplantation, emphasizing the need for further in vivo investigation., 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: The current NCCN guidelines recommend considering elective neck dissection (END) for early-stage oral cavity squamous cell carcinoma (OCSCC) with a depth of invasion (DOI) exceeding 3 mm. However, this DOI threshold, determined by evaluating the occult lymph node metastatic rate, lacks robust supporting evidence regarding its impact on patient outcomes. In this nationwide study, we sought to explore the specific indications for END in patients diagnosed with OCSCC at stage cT2N0M0, as defined by the AJCC Eighth Edition staging criteria., Methods: We examined 4723 patients with cT2N0M0 OCSCC, of which 3744 underwent END and 979 were monitored through neck observation (NO)., Results: Patients who underwent END had better 5-year outcomes compared to those in the NO group. The END group had higher rates of neck control (95% vs. 84%, p < 0.0001), disease-specific survival (DSS; 87% vs. 84%, p = 0.0259), and overall survival (OS; 79% vs. 73%, p = 0.0002). Multivariable analysis identified NO, DOI ≥5.0 mm, and moderate-to-poor tumor differentiation as independent risk factors for 5-year neck control, DSS, and OS. Based on these prognostic variables, three distinct outcome subgroups were identified within the NO group. These included a low-risk subgroup (DOI <5 mm plus well-differentiated tumor), an intermediate-risk subgroup (DOI ≥5.0 mm or moderately differentiated tumor), and a high-risk subgroup (poorly differentiated tumor or DOI ≥5.0 mm plus moderately differentiated tumor). Notably, the 5-year survival outcomes (neck control/DSS/OS) for the low-risk subgroup within the NO group (97%/95%/85%, n = 251) were not inferior to those of the END group (95%/87%/79%)., Conclusions: By implementing risk stratification within the NO group, we found that 26% (251/979) of low-risk patients achieved outcomes similar to those in the END group. Therefore, when making decisions regarding the implementation of END in patients with cT2N0M0 OCSCC, factors such as DOI and tumor differentiation should be taken into account., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Competing Interests: Conflicts of interest and sources of funding: none declared.

Polymer blending has been a facile method to resolve the brittle issue of poly(lactic acid) (PLA). Yet, miscibility becomes the primary concern that would affect the synergy effect of polymer blending. This study aimed to improve the miscibility of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P34HB) and PLA by lowering their molecular weights via a melt-blending-induced thermal degradation during mechanical mixing to form m-P34HB/PLA blends. The molecular weight of the P34HB was significantly reduced after blending, thereby improving the miscibility of the blends, as evidenced by the shift of glass transition temperatures. Also, simulation based on Flory-Huggins theory demonstrated increased miscibility with decreasing molecular weight of the polymers. Moreover, the thermal gravimetric analysis revealed that the PLA provided a higher shielding effect to the P34HB in the blends prepared by melt-blending than those by solution-blending, that the addition of PLA could retard the chain scission of P34HB and delay its degradation. The addition of m-P34HB at 20 wt% in the blend contributed to a 60-fold enhancement in the elongation at break and an increment of 4.6 folds in the Izod impact strength. The enzymatic degradation using proteinase K revealed the preferential to degrade the PLA in the blends and followed the surface erosion mechanism., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Cisplatin (CP) induces acute kidney injury (AKI) whereby proximal tubules undergo regulated necrosis. Repair is almost complete after a single dose. We now demonstrate a role for Apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (Apobec-1) that is prominently expressed at the interface between acute and chronic kidney injury (CKD), in the recovery from AKI. Apobec-1 knockout (KO) mice exhibited greater mortality than in wild type (WT) and more severe AKI in both CP- and unilateral ischemia reperfusion (IR) with nephrectomy. Specifically, plasma creatinine (pCr) 2.6 ± 0.70 mg/dL for KO, n = 10 and 0.16 ± 0.02 for WT, n = 6, p < 0.0001 in CP model and 1.34 ± 0.22 mg/dL vs 0.75 ± 0.06, n = 5, p < 0.05 in IR model. The kidneys of Apobec-1 KO mice showed increased necrosis, increased expression of KIM-1, NGAL, RIPK1, ASCL4 and increased lipid accumulation compared to WT kidneys (p < 0.01). Neutrophils and activated T cells were both increased, while macrophages were reduced in kidneys of Apobec-1 KO animals. Overexpression of Apobec-1 in mouse proximal tubule cells protected against CP-induced cytotoxicity. These findings suggest that Apobec-1 mediates critical pro-survival responses to renal injury and increasing Apobec-1 expression could be an effective strategy to mitigate AKI., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Introduction: The injectable skin fillers available for soft tissue augmentation are constantly growing, providing esthetic surgeons with more options in the treatment of scars, lines, and wrinkles. Hyaluronic acid (HA)-derived injectable fillers are ideal to reduce the appearance of nasolabial folding. This study investigated the efficacy and safety of the commercially available HA filler from Maxigen Biotech Inc. (MBI-FD) in the treatment of nasolabial folds (NLFs)., Methods: We analyzed 1,4-butanediol diglycidyl ether (BDDE) residues and injection force test and observed the protein content in MBI-FD, and then was cultured in fibroblast L929 cells and examined for cytotoxicity. Finally, 95 healthy participants underwent dermal filler injection therapy to evaluate the efficacy and safety for 24 and 52 weeks, respectively., Results: BDDE residues in MBI-FD was <0.125 µg/mL. MBI-FD was fitted using 27- and 30-G injection needles with an average pushing force of 14.30 ± 2.07 and 36.43 ± 3.11 N, respectively. Sodium hyaluronate protein in MBI-FD was 7.19 µg/g. The cell viabilities of 1× and 0.5× MBI-FD were 83.25% ± 3.58% and 82.23% ± 1.85%, respectively, indicating MBI-FD had no cytotoxicity, and decreased NLF wrinkles with no serious adverse events., Conclusion: MBI-FD is an effective filler for tissue augmentation of the NLFs and may be a suitable candidate as an injectable dermal filler for tissue augmentation in humans in the future.

Dacarbazine (DTIC) is the primary first-line treatment for advanced-stage metastatic melanoma; thus, DTIC resistance is poses a major challenge. Therefore, investigating the mechanism underlying DTIC resistance must be investigated. Dicer, a type III cytoplasmic endoribonuclease, plays a pivotal role in the maturation of miRNAs. Aberrant Dicer expression may contribute to tumor progression, clinical aggressiveness, and poor prognosis in various tumors. Dicer inhibition led to a reduction in DTIC sensitivity and an augmentation in stemness in melanoma cells. Clinical analyses indicated a low Dicer expression level as a predictor of poor prognosis factor. Metabolic alterations in tumor cells may interfere with drug response. Adenylosuccinate lyase (ADSL) is a crucial enzyme in the purine metabolism pathway. An imbalance in ADSL may interfere with the therapeutic efficacy of drugs. We discovered that DTIC treatment enhanced ADSL expression and that Dicer silencing significantly reduced ADSL expression in melanoma cells. Furthermore, ADSL overexpression reversed Dicer silencing induced DTIC resistance and cancer stemness. These findings indicate that Dicer-mediated ADSL regulation influences DTIC sensitivity and stemness in melanoma cells.

Objective: To report the success rate and complications of combined phacoemulsification and pars plana vitrectomy (PPV) for treatment of cataracts and retinal detachment in the Siberian Husky breed., Animals Studied: Client-owned Siberian Husky dogs that underwent combined phacoemulsification and PPV at two veterinary referral centers., Procedure: Retrospective study of 16 Siberian Husky dogs that underwent combined phacoemulsification and PPV with a minimum 3-month postoperative follow-up. Signalment and preoperative ophthalmic examination findings, intraoperative findings, and postoperative visual status and complications were recorded. Functional success was defined as the maintenance or restoration of vision., Results: Seventeen eyes of 16 dogs were evaluated. Immediate postoperative anatomic success was achieved in all 17 eyes (100%), with functional success through the last known follow-up examination achieved in 88.2% of operated eyes (15/17). The most common postoperative complication was silicone oil migration into the anterior chamber (AC-SiO migration), occurring in 47.1% of eyes (8/17), followed by corneal endothelial decompensation and glaucoma each occurring in 17.6% of eyes (3/17)., Conclusions: Combined phacoemulsification and PPV is a viable option in Siberian Husky dogs with cataracts and preoperative retinal detachment. Visual success was achieved in 88.2% of eyes, with the most common postoperative complication being AC-SiO migration., (© 2023 American College of Veterinary Ophthalmologists.)

Objective:  The main aim of this study is to compare the impact of six proximal tibial osteotomies on the geometry and alignment of tibias with and without excessive tibial plateau angle (TPA)., Study Design:  Mediolateral radiographs of 30 canine tibias were divided into three groups ( n  = 10/group): moderate TPA (≤34 degrees), severe TPA (34.1-44 degrees) and extreme TPA (>44 degrees). Six proximal tibial osteotomies were simulated on each tibia using orthopaedic planning software: cranial closing wedge ostectomy (CCWO), modified CCWO (mCCWO), isosceles CCWO (iCCWO), neutral isosceles CCWO (niCCWO), tibial plateau levelling osteotomy with CCWO (TPLO/CCWO) and coplanar centre of rotation of angulation-based levelling osteotomy (coCBLO). All tibias were reduced to a standard target TPA. Pre- and postoperative measurements were obtained for each virtual correction. Compared outcome measures included tibial long axis shift (TLAS), cranial tibial tuberosity shift (cTTS), distal tibial tuberosity shift (dTTS), tibial shortening and osteotomy overlap., Results:  Across all TPA groups, TPLO/CCWO had the lowest mean TLAS (1.4 mm) and dTTS (6.8 mm); coCBLO had the largest TLAS (6.5 mm) and cTTS (13.1 mm); CCWO had the largest dTTS (29.5 mm). CCWO had the largest degree of tibial shortening of 6.5 mm, while mCCWO, niCCWO and coCBLO resulted in minimal tibial lengthening (1.8-3.0 mm). These trends were generally conserved across different TPA groups. All findings had a p -value less than 0.05., Conclusion:  mCCWO balances moderate alterations to tibial geometry while preserving osteotomy overlap. The TPLO/CCWO has the least effect on tibial morphology alteration, whereas the coCBLO results in the largest alteration., Competing Interests: None., (Thieme. All rights reserved.)

Strain engineering has quickly emerged as a viable option to modify the electronic, optical, and magnetic properties of 2D materials. However, it remains challenging to arbitrarily control the strain. Here we show that, by creating atomically flat surface nanostructures in hexagonal boron nitride, we achieve an arbitrary on-chip control of both the strain distribution and magnitude on high-quality molybdenum disulfide. The phonon and exciton emissions are shown to vary in accordance with our strain field designs, enabling us to write and draw any photoluminescence color image in a single chip. Moreover, our strain engineering offers a powerful means to significantly and controllably alter the strengths and energies of interlayer excitons at room temperature. This method can be easily extended to other material systems and offers promise for functional excitonic devices.

The reconstruction of defects of the lateral malleolus involving the exposed fibular bone or tendon is challenging. This study aimed to evaluate the clinical application of the peroneal artery perforator flap with or without split-thickness skin grafting for soft tissue reconstruction of the bony defect of the lateral malleolus of the ankle joints. Reconstruction using a peroneal artery perforator flap with or without split-thickness skin grafting was performed for 15 patients (10 men, 5 women) between January 2007 and December 2018. The mean age was 53.7 years, and the mean size of the flaps was 40 cm 2 . The flaps were elevated in the form of a perforator flap, and split-thickness skin grafting was performed over the flaps and adjoining raw areas. The flaps survived in all cases; however, partial necrosis was observed in 3 cases. In cases of small-sized defects of the lateral malleolus of the ankle joints where a flap is required for the exposed bone or tendon, reconstruction using the peroneal artery perforator flap is advantageous, since the morbidity rate of the donor site is low and soft tissue is reconstructed.

Objective: To characterize the incidence, contributing risk factors, and healing characteristics of immediate postoperative corneal erosions (IPCE) in dogs undergoing routine phacoemulsification., Animals Studied: Medical records of 313 canine eyes (159 dogs) undergoing routine phacoemulsification surgery., Procedures: Medical records of dogs undergoing planned cataract surgery at UW Veterinary Care were retrospectively reviewed. Patient-related variables including age, skull conformation, diabetes status, and cataract stage at the time of surgery were recorded. Intraoperative variables per eye were also recorded including surgical technique, surgeon expertise level, average phacoemulsification power, and phacoemulsification time. Diagnosis of IPCE ≤ 24 h after completion of surgery and time to IPCE healing were recorded where follow-up data were available., Results: Immediate postoperative corneal erosions were observed in 48/313 (15.3%) operated eyes. The presence of diabetes mellitus or brachycephalic skull conformation, preoperative Schirmer tear test (STT) value, surgical technique and surgeon experience level, phacoemulsification time, and absolute phacoemulsification time were not statistically significant risk factors for IPCE. Average phacoemulsification power was associated with IPCE (RR 1.52, p = .001). Time to IPCE healing was similar in diabetic and non-diabetic dogs (median [IQR] 8 [6-11] days and 8 [6-15] days, respectively). Diabetes mellitus, brachycephaly, and phacoemulsification parameters were not associated with IPCE healing at 7 or 14 days postoperatively., Conclusions: Higher average phacoemulsification power may be associated with the development of IPCE in canine eyes. The presence of diabetes mellitus or brachycephaly are not risk factors for the development of IPCE, nor are they factors that influence IPCE healing., (© 2022 The Authors. Veterinary Ophthalmology published by Wiley Periodicals LLC on behalf of American College of Veterinary Ophthalmologists.)