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Lin Mi,1,2 Ke Wang,3 Jianfeng Yao,1 Jianxia Ma,1 Yuan-Wen Chen,1 Qinglian Zeng,1 Kangwei Liu1 1Department of Gastroenterology, Huadong Hospital, Fudan University, Shanghai, 200040, People’s Republic of China; 2Department of General Medicine, Huadong Hospital, Fudan University, Shanghai, 200040, People’s Republic of China; 3Department of Gastroenterology, Jinan Third People’s Hospital, Jinan, Shandong Province, 250132, People’s Republic of ChinaCorrespondence: Jianfeng Yao; Jianxia Ma, Department of Gastroenterology, Huadong Hospital, Fudan University, NO. 221 West Yan’an Road, Shanghai, 200040, People’s Republic of China, Tel +8602162483180, Email yjf1966@126.com; yz_mjx@163.comAim: In order to better understand the incidence of IBD in China, we conducted a retrospective study to analyze the clinical information of IBD patients in Shanghai, China.Methods: From January 2014 to December 2021, patients diagnosed with IBD and hospitalized were enrolled. The demographic, clinical features, symptoms, laboratory tests and treatment data of the patients were retrospectively analyzed.Results: This study included 454 patients with UC and 333 patients with CD. The rate of hospitalization for IBD showed an escalating trend throughout the period, the number of hospitalizations was significantly higher in CD patients than in UC patients. The male patients had more complications than the female patients (p < 0.05). Definitive diagnosis of IBD in older patients was difficult (p < 0.05), and misdiagnosis was common. The incidence of complications and extraintestinal manifestations in elderly IBD patients was lower, but the incidence of intestinal obstruction was higher (p < 0.05). There was a significant correlation between the disease activity grades of IBD and fibrinogen, hemoglobin, albumin. Elderly IBD patients presented with lower rates of immunosuppressant, biologics, surgery or enteral nutrition.Conclusion: This study analyzed the incidence, characteristics and treatment of IBD patients in Shanghai, and provided evidence-based evidence for doctors to more effectively diagnose and treat IBD in the future.Keywords: inflammatory bowel disease, ulcerative colitis, Crohn’s disease, clinical features, treatment

Yi-Wen Chen,1,2 Ai-Chia He,3 Tzu-Yun Huang,1,3 De-Hao Lai,3 Yi-Ping Wang,1 Wei-Wen Liu,1,3 Wei-Ting Kuo,1,3 Hsin-Han Hou,1,3 Shih-Jung Cheng,1,3 Chen-Yi Lee,1 Wei-Chun Chuang,1 Che-Chen Chang,4 Bor-Shiunn Lee1,3 1Department of Dentistry, National Taiwan University Hospital, Taipei, 100229, Taiwan; 2Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, 100229, Taiwan; 3Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, 100229, Taiwan; 4Department of Chemistry, National Taiwan University, Taipei, 10617, TaiwanCorrespondence: Bor-Shiunn Lee, Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, No. 1, Changde Street, Taipei, 100229, Taiwan, Tel +886-2-23123456 ext 66846, Fax +886-2-2383-1346, Email leebs@ntu.edu.twIntroduction: Cisplatin is one of the most effective chemotherapeutic drugs used in oral cancer treatment, but systemic administration has side effects. The purpose of this study was to evaluate the effect of iontophoresis on the enhancement of cisplatin release from cisplatin-encapsulated chitosan nanoparticles.Methods: The effect of different mass ratios of chitosan to tripolyphosphate (TPP) (5:1, 10:1, 15:1, 20:1) on the encapsulation efficiency of cisplatin was investigated. Uptake of cisplatin-encapsulated chitosan by cells was observed using a confocal laser scanning microscope. The cell viability at different cisplatin concentrations was examined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Three iontophoresis methods, namely constant-current chronopotentiometry (CCCP), cyclic chronopotentiometry (CCP), and differential pulse voltammetry (DPV), were used to enhance cisplatin release from cisplatin-encapsulated chitosan nanoparticles. In addition, mouse oral squamous cell carcinoma cell lines were implanted into the mouse oral mucosa to induce oral cancer. The effects of enhanced cisplatin release by CCCP, CCP, and DPV on tumor suppression in mice were evaluated. Tumors and lymph nodes were isolated for hematoxylin-eosin staining and immunohistochemistry staining including Ki-67 and pan CK after sacrifice. Inductively coupled plasma mass spectrometry was conducted to quantify the platinum content within the tumors.Results: The results showed that nanoparticles with a mass ratio of 15:1 exhibited the highest cisplatin encapsulation efficiency (approximately 15.6%) and longest continued release (up to 35 days) in phosphate buffered saline with a release rate of 100%. Cellular uptake results suggested that chitosan nanoparticles were delivered to the cytoplasm via endocytosis. The results of the MTT assay revealed that the survival rate of cells decreased as the cisplatin concentration increased. The CCP (1 mA, on:off = 1 s: 1 s) and DPV (0– 0.06 V) groups were the most effective in inhibiting tumor growth, and both groups exhibited the lowest percentage of Ki-67 positive and pan CK positive.Conclusion: This study is the first to investigate and determine the efficacy of DPV in enhancing in vivo drug release from nanoparticles for the treatment of cancer in animals. The results suggest that the CCP and DPV methods have the potential to be combined with surgery for oral cancer treatment. Keywords: oral cancer, cisplatin, chitosan, nanoparticle, iontophoresis

Shih Ping Lin,1– 3 Ching-Wein Chang,4 Chun-Yi Wu,1,5 Chun-Shih Chin,1,6 Cheng-Hsien Lin,1,7 Sz-Iuan Shiu,1,8 Yun-Wen Chen,1,9 Tsai-Hung Yen,1,9 Hui-Chi Chen,4 Yi-Hung Lai,4 Shu-Chin Hou,4 Ming-Ju Wu,3,5 Hsin-Hua Chen1,3,9– 11 1Division of General Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 2Division of Infection, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 3Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; 4Department of Nursing, Taichung Veterans General Hospital, Taichung, Taiwan; 5Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 6Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 7Division of Hematology and Oncology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 8Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 9Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 10Institute of Biomedical Science and Rong Hsing Research Centre for Translational Medicine, Big Data Center, Chung Hsing University, Taichung, Taiwan; 11School of Medicine, National Yang Ming Chiao Tung University, Taipei, TaiwanCorrespondence: Hsin-Hua Chen, Division of General Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, 1650 Taiwan Boulevard Sect. 4, Taichung, 40705, Taiwan, Email shc5555@hotmail.comObjective: Huddles are short, regular debriefings that are designed to provide frontline staff and bedside caregivers environments to share problems and identify solutions. Daily huddle implementation could improve medical safety work, problem identification and improvement, situation awareness and teamwork enhancement, the collaboration and communication between professionals and departments, and patient safety. This study aimed evaluated the effectiveness of a hospital-based huddle at a general medical ward in Taiwan.Methods: A Continuous Integration team was conducted by combining multidisciplinary frontline staff to huddle at a 74-bed general medical ward. Team Huddles started twice a week. A physical huddle run board was created, which contained four parts, including idea submitted, idea approved, working on an idea and standardizing. Problems were submitted to the board to be identified, and the solutions were evaluated through huddle discussion. We divided the problems into two groups: quick hits (resolved within 24– 48hrs) and complex issues (resolved > 48hrs). An anonymous questionnaire was designed to evaluate the huddle response.Results: A total of 44 huddles occurred from September 9th, 2020, to September 30th, 2021, and 81 issues were identified and resolved. The majority issues were policy documentation (n=23; 28.4%). Sixty-seven (82.7%) issues were defined as quick hits, and the other fourteen (17.3%) issues were complex. The mean hours to the resolution of quick hits was 5.17 hours, median 3.5 hours, and range from 0.01– 15.4 hours. The mean days to resolve completion issues were 19.73 days, median 7.5 days, and range 3.57– 26.14 days. An overwhelming 92.9% of staff responded that huddles help to expedite the process to reach treatment goals, reduce clinical mistakes, near misses, reduce patient incidences, and help teamwork enhancement, with rating of 4.52 (on a 5-point Likert scale).Conclusion: Implementing of multidisciplinary team huddle improved the accountability of issue identification, problem-solving and teamwork enhancement.Keywords: huddle run, safety culture, teamwork, patient safety

Yi-Ju Liao,1 Tzu-Hung Hsiao,2– 4 Ching-Heng Lin,2,3,5,6 Chun-Sheng Hsu,7– 10 Yen-Lin Chang,1,8 Yu-Wei Chen,11 Chiann-Yi Hsu,2,12 Yi-Ming Chen,2,10,13– 15,&ast; Ming-Fen Wu1,&ast; 1Department of Pharmacy, Taichung Veterans General Hospital, Taichung, Taiwan; 2Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan; 3Department of Public Health, Fu Jen Catholic University, New Taipei City, Taiwan; 4Institute of Genomics and Bioinformatics, National Chung Hsing University, Taichung, Taiwan; 5Institute of Public Health and Community Medicine Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan; 6Department of Industrial Engineering and Enterprise Information, Tunghai University, Taichung, Taiwan; 7Department of Physical Medicine and Rehabilitation, Taichung Veterans General Hospital, Taichung, Taiwan; 8Department of Public Health and Institute of Public Health, Chung Shan Medical University, Taichung, Taiwan; 9School of Medicine, National Defense Medical Center, Taipei, Taiwan; 10Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; 11Cardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan; 12Biostatistics Task Force of Taichung Veterans General Hospital, Taichung, Taiwan; 13Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 14Rong Hsing Research Center for Translational Medicine & Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan; 15School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan&ast;These authors contributed equally to this workCorrespondence: Yi-Ming ChenDivision of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, 1650, Section 4, Taiwan Boulevard, Xitun Dist., Taichung, 407, Taiwan, Tel +886-4-2359-2525 ext. 4400, Fax +886-4-2359-2705, Email ymchen1@vghtc.gov.twPurpose: Clopidogrel is widely used in coronary artery, peripheral arterial, and cerebrovascular disease. We aimed to study the association of the CYP2C19 phenotype with cardiovascular outcomes and interventional procedures in a hospital-based population.Patients and Methods: This cross-sectional, retrospective study enrolled patients with prior exposure to clopidogrel at the Taichung Veterans General Hospital (TCVGH) using data extracted from the Taiwan Precision Medicine Initiative (TPMI). Data on the CYP2C19 phenotype, drug-prescription profile, comorbidities, vascular intervention procedures, and hospitalization due to acute myocardial infarction (AMI) or stroke of clopidogrel users were analyzed.Results: From the 32,728 patients in the TCVGH-TPMI cohort, we selected 2687 clopidogrel users. A total of 400 (14.9%) clopidogrel poor metabolizers (PMs), 1235 (46.0%) intermediate metabolizers (IMs), and 1052 (39.2%) extensive metabolizers (EMs) were identified. The predominant loss-of-function allele is &ast;2. In 2687 patients with clopidogrel exposure, the CYP2C19 PM phenotype was unassociated with hospitalization due to AMI or stroke after adjusting for comorbidities and carotid angiographies. Among the 1554 clopidogrel users who underwent cardiovascular intervention, 193 (12.4%) received two or more types of interventional procedures. Compared with non-PMs, patients with the PM phenotype had a higher risk of multiple carotid interventions (OR: 3.13, 95% CI: 1.19– 8.22).Conclusion: In this hospital-wide cohort, 8.2% were clopidogrel users, of which 14.9% were CYP2C19 PMs. The result of this study does not support universal genotyping of CYP2C19 in all clopidogrel users to identify risks for stroke and AMI. CYP2C19 PMs are more likely to undergo multiple carotid interventions than non-PMs. Prospective studies to investigate the association of the CYP2C19 genotype and carotid interventions and outcomes are needed to validate our results.Keywords: pharmacogenomics, clopidogrel, CYP2C19, Taiwan precision medicine initiative, TPMI, carotid intervention

Peri-implant inflammation and periodontitis share a common etiology rooted in periodontopathic bacterial invasion, with periodontitis notably linked to systemic inflammatory comorbidities involving T cells. However, the intricate processes within the peri-implant microenvironment and systemic repercussions of implants, particularly related to implant materials, remain inadequately understood. We aim to elucidate the impact of contact with titanium materials, widely employed in dental implants for their high biocompatibility and excellent corrosion resistance, on diverse T cell subpopulations. This study adopts a comprehensive approach, encompassing (1) transcriptomic profiling of peri-implant epithelium in a rat model, (2) examination of phenotypic and functional changes in T cell immunity in human blood cells cultured on titanium discs, and (3) in vivo validation of T cells in implanted mice. Transcriptomic evidence and functional in vitro results revealed that exposure to titanium materials promoted T cell activation and differentiation towards inflammatory subsets, and escalated the secretion of corresponding cytokines. In vivo results showed that most of the gingiva-extracted T cells were activated in both healthy and implanted mice, the latter exhibiting significant lymphadenitis. High-dimensional flow cytometric findings in the in vivo lymphadenitis model indicated titanium-induced T cell immunity, involving preferential activation of Th1, Th17, and Tc1 cells over Tregs in adjacent lymph nodes within three days after implant placement. These findings highlight the pivotal role of T cells in the initiation of peri-implant inflammation, emphasizing the need to understand extra-periodontal inflammatory complications associated with implant surgeries. Our study provides a foundation for future therapeutic strategies targeting T cell responses to enhance the success and longevity of dental implant treatments.

Background: Partially replacing NaCl with KCl under ultrasound can improve muscle quality and reduce oxidative degeneration of myofibrillar proteins in semi-dried large yellow croaker (Larimichthys crocea). Myosin, the most important protein in myofibrillar protein, plays an important role in muscle quality. Hence, the present study aimed to investigate the effect of replacing NaCl with KCl on the physicochemical properties of myosin derived from large yellow croaker under ultrasound. Furthermore, the application potential of ultrasound to low sodium salt products was evaluated., Results: The results showed that ultrasound treatment reduced the aggregation and particle size of myosin. By contrast, at high salt concentrations, myosin oxidation was inhibited and protein aggregation increased. This led to an increase in particle size and a decrease in stability and surface hydrophobicity of myosin. Interestingly, KCl increased myosin solubility and promoted protein unfolding, the excess of which exposed some active sites, leading to oxidative destruction of the proteins. In the present study, the chromophore and surface hydrophobic groups of myosin were exposed as a result of the KCl-mediated unfolding of the α-helices of myosin after the partial replacement of NaCl with KCl. This improved the structural stability of myosin and reduced its oxidative damage., Conclusion: The findings of the present study show that the presence of NaCl and KCl in the system was more conducive to protecting the key role of myosin in the muscle tissue compared with NaCl alone. Additionally, the study provides insights into the mechanism of K + and Na + action on myosin under ultrasound, along with a theoretical basis for the application of ultrasound in low sodium salt products. © 2025 Society of Chemical Industry., (© 2025 Society of Chemical Industry.)

The noninvasive brain and nerve stimulation (NIBNS) treatments had been widely applied in numerous psychiatric diseases. They exerted preferable efficacy and had been considered as an alternative or add-on treatment to the traditional pharmacotherapy. However, the risk of complication of seizure had seized the clinicians so that they feared about this potential complication. Actually, the NIBNS techniques have emerged as an alternative adjunctive treatment method for patients with epilepsy. However, the results of randomized controlled trials (RCTs) investigating the ability of NIBNS to reduce the frequency of seizures have been inconclusive. The aim of the current network meta-analysis (NMA) was to compare the efficacy and acceptability of various NIBNS techniques for reducing the frequency of seizures in patients with epilepsy. This frequentist model-based NMA included RCTs of NIBNS techniques for patients with epilepsy. The primary outcomes were seizure frequency change and acceptability (i.e., dropout rate). This NMA of 20 RCTs indicated that only 2-mA cathodal short-duration transcranial direct current stimulation (hc-sd-c-tDCS) was associated with significantly greater reduction in seizure frequency and significantly greater improvement in quality of life than the sham/control. Further, none of the investigated NIBNS techniques had significantly increased seizure frequency compared with the sham/control. In addition, all the investigated NIBNS techniques were associated with similar acceptability with the sham/control. Our results indicated that none of the investigated NIBNS techniques was associated with an increased risk of epileptic seizure., 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 Inc. All rights reserved.)

2,4-Dichlorophenoxyacetic acid (2,4-D) is one of commonly and widely used organic herbicides in agriculture. It has been reported that 2,4-D can induce adverse effects in mammalian cells. Epidemiological and animal studies have indicated that exposure to 2,4-D is associated with poorer glycemic control and impaired pancreatic β-cell function. However, limited information is available on 2,4-D-induced toxicological effects in β-cells, with the underlying toxicological mechanisms remains unclear. Herein, our results showed that 2,4-D exposure (30-500 μg/mL) significantly reduced cell viability, induced mitochondria dysfunction (including the mitochondrial membrane potential (MMP) loss, the increase in cytosolic cytochrome c release, and the change in Bcl-2 and Bax protein expression), and triggered apoptotic events (including the increased population of apoptotic cells, caspase-3 activity, and caspase-3/-7 and PAPR activation) in RIN-m5F β-cells, accompanied with insulin secretion inhibition. Exposure of cells to 2,4-D could also evoke JNK, ERK1/2, p38, and AMP-activated protein kinase (AMPK)α activation as well as reactive oxygen species (ROS) generation. Pretreatment of cells with compound C (an AMPK inhibitor) and the antioxidantN-acetylcysteine (NAC), but not that SP600125/PD98059/SB203580 (the inhibitors of JNK/ERK/p38, respectively), obviously attenuated the 2,4-D-triggered AMPKα phosphorylation, MMP loss, apoptotic events, and insulin secretion dysfunction,as similar effects with the transfection with AMPKα1-specific siRNA. Of note, buffering the ROS production with NAC obviously prevented the 2,4-D-induced ROS generation as well as AMPKα activation, but the either compound C and AMPKα1-specific siRNA transfection could not effectively reduce 2,4-D-induced ROS generation. Collectively, these findings indicate that the induction of oxidative stress-activated AMPKα signaling is a crucial mechanism underlying 2,4-D-triggered mitochondria-dependent apoptosis, ultimately leading to β-cell death., 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.)

Human induced pluripotent stem cell (iPSC)-derived lung organoids, engineered to carry targeted genes, offer a robust platform for investigating mechanistic insights in lung research. Although lentiviral vectors (LVVs) are highly effective for stable expression due to their integrative properties, achieving efficient transduction in human iPSC-derived lung organoids poses a significant technical challenge, likely due to the complex structure of these organoids. In this study, we optimized a method to enhance LVV transduction efficiency by physically disrupting the organoids to increase surface area, followed by spinoculation to apply shear force during cell dissociation. This approach, combined with the use of an optimized culture medium, significantly improved transduction efficiency. The success of this method was validated at both the gene and protein levels using single-cell RNA sequencing (scRNA-seq) and various cellular and molecular assays. Our optimized transduction protocol may provide a valuable tool for investigating specific cellular and molecular mechanisms in development and disease models using human iPSCs-derived lung organoids., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Web-based prenatal education is increasingly employed, but its association with increased breastfeeding and predictors of breastfeeding success is uncertain., Research Aims: Our primary aim was to evaluate our live, online intervention's association with exclusive breastfeeding at hospital discharge. Secondarily, we aimed to describe participants' reports of the intervention on predictors of breastfeeding success., Method: We used a retrospective quasi-experimental cohort design to assess the association between our intervention and exclusive breastfeeding at discharge. The intervention consisted of an evidence-based live, online, 2-hour class open to all prenatal patients and supporters at our urban community medical center from June 2020 through April 2022. Patient characteristics and breastfeeding rates were extracted from the electronic medical record. Samples were drawn using stratified random sampling. Three logistic regression models were conducted to assess the associations between the intervention and exclusive breastfeeding. Two surveys assessed the participant reports of the intervention., Results: Samples of the first model, comprised of 160 participants and 160 non-participants, were similar in important characteristics. Participants were 2.12 times (95% CI [1.12, 3.69]) more likely to exclusively breastfeed. Participants reported positively on the impacts of the intervention on breastfeeding predictors., Conclusions: Our live, online intervention was significantly associated with an increased likelihood of exclusive breastfeeding at hospital discharge. A randomized, prospective examination of the intervention's association with breastfeeding duration would further define its impact., Competing Interests: Disclosures and Conflicts of InterestThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Acetaminophen (APAP) overdose can cause severe liver injury and life-threatening conditions that may lead to multiple organ failure without proper treatment. N-acetylcysteine (NAC) is the accepted and prescribed treatment for detoxification in cases of APAP overdose. Nonetheless, in acute liver failure (ALF), particularly when the ingestion is substantial, NAC may not fully restore liver function. NAC administration in ALF has limitations and potential adverse effects, including nausea, vomiting, diarrhoea, flatus, gastroesophageal reflux, and anaphylactoid reactions. Mesenchymal stromal cell (MSC)-based therapies using paracrine activity show promise for treating ALF, with preclinical studies demonstrating improvement. Recently, MSC-derived extracellular vesicles (EVs) have emerged as a new therapeutic option for liver injury. MSC-derived EVs can contain various therapeutic cargos depending on the cell of origin, participate in physiological processes, and respond to abnormalities. However, most therapeutic EVs lack a distinct orientation upon entering the body, resulting in a lack of targeting specificity. Therefore, enhancing the precision of natural EV delivery systems is urgently needed. Thus, we developed an advanced targeting technique to deliver modified EVs within the body. Our strategy aims to employ bioorthogonal click chemistry to attach a targeting molecule to the surface of small extracellular vesicles (sEVs), creating exogenous chimeric antigen receptor-modified sEVs (CAR-sEVs) for the treatment. First, we engineered azido-modified sEVs (N 3 -sEVs) through metabolic glycoengineering by treating MSCs with the azide-containing monosaccharide N-azidoacetyl-mannosamine (Ac4ManNAz). Next, we conjugated N 3 -sEVs with a dibenzocyclooctyne (DBCO)-tagged single-chain variable fragment (DBCO-scFv) that targets the asialoglycoprotein receptor (ASGR1), thus producing CAR-sEVs for precise liver targeting. The efficacy of CAR-sEV therapy in ALF models by targeting ASGR1 was validated. MSC-derived CAR-sEVs reduced serum liver enzymes, mitigated liver damage, and promoted hepatocyte proliferation in APAP-induced injury. Overall, CAR-sEVs exhibited enhanced hepatocyte specificity and efficacy in ameliorating liver injury, highlighting the significant advancements achievable with cell-free targeted therapy., (© 2025 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.)

Heart failure is a progressive condition associated with a high mortality rate. Despite advancements in treatment, many patients continue to experience less-than-ideal outcomes. ω-3 (n-3) polyunsaturated fatty acids (PUFAs) have been studied as a potential supplementary therapy for heart failure, but the optimal dosage and duration of supplementation remain unclear. This network meta-analysis (NMA) aimed to assess the efficacy of various n-3 PUFA supplementation regimens in patients with heart failure, focusing on dose-dependent and time-dependent effects. We conducted a systematic search for randomized controlled trials (RCTs) on n-3 PUFA supplementation in heart failure till 13 September, 2024. The primary outcome was the change in heart function, specifically left ventricular ejection fraction. Secondary outcomes included changes in peak oxygen consumption (VO 2 ), blood B-type natriuretic peptide concentrations, and quality of life. The safety analysis focused on dropout rates (i.e., patients leaving the study for any reason before completion) and all-cause mortality. A frequentist-based NMA was performed. This NMA, which included 14 RCTs with 9075 participants (mean age, 66.0 y; 23.3% female), found that high-dose n-3 PUFA supplementation (2000-4000 mg/d) over a duration of ≥1 y significantly improved left ventricular ejection fraction and peak VO 2 compared with those of control groups. Lower doses and shorter treatment periods did not produce the same benefits. No significant differences were found in dropout rates or all-cause mortality between the n-3 PUFAs and control groups. Long-term, high-dose n-3 PUFA supplementation, particularly with a predominance of docosahexaenoic acid or eicosapentaenoic acid, enhances cardiac function in patients with heart failure without increasing risk of adverse events. Further well-designed RCTs with long treatment durations (i.e., >1 y) and stringent heart failure inclusion criteria are necessary to confirm these findings and reduce potential biases. This trial was registered at PROSPERO as CRD42024590476., Competing Interests: Conflict of interest BS is supported by the NIHR Brendon Stubbs is part funded by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust. BS is also supported by the Maudsley Charity, King’s College London. All other authors report no conflicts of interest., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: We investigated the likelihood of timely surgery for breast cancer patients among diverse Asian subgroups., Methods: We analyzed the National Cancer Database from 2010 to 2019 and included White and Asian women diagnosed with stage I-III breast cancer. Patients with multiple cancers, patients who received chemotherapy, and those diagnosed and treated at different hospitals were excluded. The primary outcome was timely surgery within 8 weeks of diagnosis. Race was the primary independent variable. Asian Americans were stratified by geography., Results: A total of 716,701 women were analyzed, with 3.5% Asians. Delayed surgery was experienced by 13.2% of women. Adjusted analysis indicated no difference in receiving timely surgery between all Asians and Whites. However, Southeast Asians were less likely to undergo timely surgery compared to Whites (OR 0.75, 95% CI 0.67-0.84)., Conclusions: Variations among Asian ethnicities emphasize the need to explore treatment patterns to address disparities in breast cancer care., Competing Interests: Declaration of competing interest All authors have no conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Olfactory ensheathing cells (OECs) are unique glial cells found in both central and peripheral nervous systems where they support continuous axonal outgrowth of olfactory sensory neurons to their targets. Previously we reported that following severe spinal cord injury, OECs transplanted near the injury site modify the inhibitory glial scar and facilitate axon regeneration past the scar border and into the lesion. To better understand the mechanisms underlying the reparative properties of OECs, we used single-cell RNA-sequencing of OECs from adult rats to study their gene expression programs. Our analyses revealed five diverse OEC subtypes, each expressing novel marker genes and pathways indicative of progenitor, axonal regeneration, secreted molecules, or microglia-like functions. We found substantial overlap of OEC genes with those of Schwann cells, but also with microglia, astrocytes, and oligodendrocytes. We confirmed established markers on cultured OECs, and localized select top genes of OEC subtypes in olfactory bulb tissue. We also show that OECs secrete Reelin and Connective tissue growth factor, extracellular matrix molecules which are important for neural repair and axonal outgrowth. Our results support that OECs are a unique hybrid glia, some with progenitor characteristics, and that their gene expression patterns indicate functions related to wound healing, injury repair and axonal regeneration.

Background: Lumbar fusion is the most common surgical intervention for chronic or severe low back pain. However, lumbar disk replacement (LDR) may be appropriate for certain patients. The objective of this study was to describe the postoperative management costs associated with both lumbar fusion and LDR in the 2-year period after surgery., Materials and Methods: An observational cohort study was conducted using the Merative MarketScan databases. Patients who underwent lumbar fusion or LDR between January 1, 2017, and December 31, 2017, were identified and included in the study. The primary outcome was the cost of payments for physical therapy, pain medication, injections, and bladder management in the 2-year period after surgery., Results: A total of 1660 patients (mean age, 50.1±10.6 years; lumbar fusion, 99%; LDR, 1%) were included in the study. The mean total cost of postoperative interventions identified was $2832±$5461 per patient, with no differences found between patients for identified interventions. The mean 30-day episode-of-care cost was $65,777±$40,869 and was similar ( P =.894) between the two groups of patients. The main driver of cost was physical therapy for both groups of patients (lumbar fusion, 53.7%; LDR, 64.9%)., Conclusion: Patients who underwent lumbar fusion and LDR had similar postoperative management costs. The shorter recovery periods associated with LDR may not necessarily translate into reduced long-term health care expenditure. [ Orthopedics . 202x;4x(x):xx-xx.].

Background: Anaplastic thyroid cancer (ATC) is a highly lethal disease, often diagnosed with advanced locoregional and distant metastases, resulting in a median survival of just 3-5 months. This study determines the stratified effectiveness of baseline treatments in all combinations, enabling precise prognoses prediction and establishing benchmarks for advanced therapeutic options., Methods: The study extracted a cohort of pathologically confirmed ATC patients from the Surveillance, Epidemiology, and End Results program. Overall, 1879 patients from 2000 to 2018 were identified from the database. Kaplan-Meier survival curve estimation and Cox proportional hazard regression were applied., Results: Overall, compared with no treatment, surgery raised 1-year overall survival (OS) from 0.6% to 30% and median survival from <1 month to 3 months in ATC patients. For stage IVa, surgery increased 1-year OS from 21.5% to 71.8% and median survival from 2 to 23.5 months, and in stage IVb, surgery increased 1-year OS from 9.4% to 41.3% and median survival from 2 to 7 months; however, in stage IVc, the benefits of surgery were not markedly different from non-surgical approaches. When combined with surgery, other effective non-surgical ATC treatments demonstrated a surgery-dominant synergistic effect, particularly for stages IVa and IVb ATC, but not for stage IVc ATC., Conclusions: Our study provides insights into stratified baseline treatments for patients with ATC in all stages, emphasizing surgery's vital role in a multimodal approach., Competing Interests: Disclosures: Kun Zhang, Xinyi Wang, Jianyong Lei, Anping Su, Tao Wei, Zhihui Li, and Ya-Wen Chen have no conflicts of interest to declare that may be relevant to the contents of this study., (© 2025. The Author(s).)

Boronic acids have been widely applied in various biological fields, particularly achieving significant practical progress in boronic acid-based glucose sensing. However, boronic acids exhibit nonspecific binding to other nucleophiles, and the inherent lability of boronic esters in biological systems limits their further applications. Herein, we developed a stimuli-responsive controllable caging strategy to achieve photoresponsive spatiotemporally and nitroreductase-responsive cancer cell-selective glucose sensing. We introduced o -/ p -nitroaryl-containing self-immolative linkers onto δ-pinanediol derivatives, effectively caging boronic acids and blocking glucose recognition. Upon triggering by specific stimuli, the caged boronic esters decompose, releasing boronic acids and thereby restoring glucose recognition of the diboronic acid-based sensor. The proof of concept was confirmed through intracellular glucose bioimaging in living cells. Upon regional UV irradiation, we could monitor intracellular glucose with excellent spatiotemporal selectivity. Furthermore, we used the cancer biomarker nitroreductases as the internal stimuli and utilized the caged glucose sensor to selectively label hypoxic cancer cells in a cocultured living cell sample. We believe that our stimuli-responsive caging strategies will hold promising potential for the controlled release of other boronic acids in various biological contexts.

Introduction: The growing popularity of active surveillance for papillary thyroid cancer and the COVID-19 pandemic have increased surgery delay, further necessitating a reassessment of the link between surgery delay and survival outcomes for papillary thyroid cancer. In this study, we aim to investigate the interplay among various oncological factors, socioeconomic status, and surgical timing with respect to survival outcomes of papillary thyroid cancer., Methods: A total of 58,378 non-metastatic papillary thyroid cancer patients from 2000 to 2018 were screened from the Surveillance, Epidemiology, and End Results database. Kaplan-Meier survival curve, Cox proportional hazard regression, competing risk hazard regression, and multinomial logistic regression were applied., Results: Receiving neck dissection or radioactive iodine therapy, being married at diagnosis, living in an urban area, being richer, and being of other minority ethnicity were estimated to be independent predictors for better overall survival. Single, older Black patients living in rural areas that experienced long surgery delays were more associated with a higher non- papillary thyroid cancer mortality rate. High income level was the only independent socioeconomic status predictor for lower papillary thyroid cancer -specific mortality. Unmarried, older patients of minority ethnicity tended to undergo longer surgery delays., Conclusion: Surgery for non-metastatic papillary thyroid cancer patients can be safely delayed. The elevated non-papillary thyroid cancer mortality has reflected low socioeconomic status population's survival status., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Zhang, Wang, Lei, Su, Wei, Li and Chen.)

Dendritic cells (DCs) play a crucial role in initiating antitumor immune responses. However, in the tumor environment, dendritic cells often exhibit impaired antigen presentation and adopt an immunosuppressive phenotype, which hinders their function and reduces their ability to efficiently present antigens. Here, a dual catalytic oxide nanosponge (DON) doubling as a remotely boosted catalyst and an inducer of programming DCs to program immune therapy is reported. Intravenous delivery of DON enhances tumor accumulation via the marginated target. At the tumor site, DON incorporates cerium oxide nanozyme (CeO 2 )-coated iron oxide nanocubes as a peroxide mimicry in cancer cells, promoting sustained ROS generation and depleting intracellular glutathione, i.e., chemodynamic therapy (CDT). Upon high-frequency magnetic field (HFMF) irradiation, CDT accelerates the decomposition of H 2 O 2 and the subsequent production of more reactive oxygen species, known as Kelvin's force laws, which promote the cycle between Fe 3+ /Fe 2+ and Ce 3+ /Ce 4+ in a sustainable active surface. HFMF-boosted catalytic DON promotes tumors to release tumor-associated antigens, including neoantigens and damage-associated molecular patterns. Then, the porous DON acts as an antigen transporter to deliver autologous tumor-associated antigens to program DCs, resulting in sustained immune stimulation. Catalytic DON combined with the immune checkpoint inhibitor (anti-PD1) in lung metastases suppresses tumors and improves survival over 40 days.

Pyruvate kinase (PK), a key ATP-generating enzyme in glycolysis, is a target for novel sickle cell disease (SCD) therapies. Enhancing PK activity lowers 2,3-diphosphyglycerate (2,3-DPG), increases adenosine triphosphate (ATP), and may prevent red blood cell (RBC) sickling. Townes and Berkeley SCD mouse models are commonly used for the development of novel drugs for SCD, but differ from humans in 2,3-DPG and ATP levels, which could be related to underlying differences in PK properties. This study revealed important distinctions with humans (SCD vs healthy controls), such as similar PK/hexokinase (HK) ratios between sickling and non-sickling mouse models and significantly lower PK thermostability in mice. We additionally investigated the effect of a novel RBC PK activator, compound A, on PK properties and sickling tendency in these mice in order to assess SCD mouse model suitability. Results showed that a single dose of compound A led to an increased affinity of PK for phosphoenolpyruvate, a significant increase in PK/HK ratio and a decrease of 2,3-DPG levels. Together, these results offer detailed characterization in the PK properties of two commonly used SCD mouse models, and provide insight into the mode of action of PK activator therapy in SCD mice models., Competing Interests: Declaration of competing interest R.v.W. received research funding from Pfizer, USA. M.R. and R.v.W. received research funding and are consultants for Agios Pharmaceuticals Inc, USA. C.L., C.A. and Y.C. are former employees of Pfizer, USA. The other authors declare no competing interests., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Unlike conventional photon radiotherapy, particle therapy has the advantage of dose distribution. Carbon-ion radiotherapy is also advantageous in terms of biological effectiveness and other radiobiological aspects. These benefits lead to a higher response probability for previously known radioresistant tumor types. Therefore, Taipei Veterans General Hospital, which is located in the northern district of Taipei, built the first carbon-ion irradiation facility in Taiwan., Methods: Taipei Veterans General Hospital completed a phase 1 trial to evaluate the safety of carbon-ion radiotherapy. Six patients (4 males and 2 females with prostate adenocarcinoma, sacral chordoma, hepatocellular carcinoma, lung adenocarcinoma, or parotid high-grade carcinoma) were enrolled in this study. The mean age of the patients was 62.7 years. The mean dose was 57.3 Gy(RBE) (fraction range, 4-16 Gy(RBE))., Results: During this phase 1 trial, all patients were monitored for 3 months to evaluate acute toxicity and short-term outcomes after treatment with carbon irradiation. Only 2 patients experienced grade 2 toxicity, which resolved without medication 1 month after completing treatment. The tumor response demonstrated 1 complete response, 1 partial response, and 4 cases of stable disease., Conclusion: Carbon-ion radiotherapy was determined to be an effective and safe treatment., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2025, the Chinese Medical Association.)

Large yellow croaker (Larimichthys crocea) is susceptible to oxidative denaturation during storage. This work is to investigate the quality alterations by analyzing its physicochemical changes and proteomics throughout preservation under refrigeration, frozen, and slurry ice (SI) conditions. Results revealed that the freshness of large yellow croaker, as evaluated by indicators such as total volatile basic nitrogen, total viable count, and thiobarbituric acid reactive substances, was well maintained while stored in the SI group. Meanwhile, the water distribution in the muscle tissue of group SI exhibited slower fluctuations, thereby preserving the integrity of fish muscle cells. Based on label-free proteomic analysis, a considerable downregulation was observed in the mitogen-activated protein kinase (MAPK) signaling pathway, indicating that SI decelerated this metabolic pathway and effectively delayed the deterioration of muscle. Therefore, the application of SI provides potential for maintaining the quality stability of large yellow croaker., Competing Interests: Declaration of competing interest The authors declare that they do not possess any recognized competing financial interests or personal relationships that could have potentially influenced the findings presented in this research., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Debridement with antibiotics and implant retention (DAIR) is commonly utilized for treatment of prosthetic joint infection (PJI) in total knee arthroplasty (TKA), particularly in cases of acute PJI. Reported success rates of DAIR have been highly variable, but the overall success rate of DAIR cohort studies is approximately 70 to 80%. However, no large database studies have investigated the success rate of DAIR. Therefore, we seek to provide a framework for large-database analysis of PJI interventions and their outcomes and to assess the success rate of DAIR. We queried the MarketScan Database for patients who underwent a DAIR (CPT 27310 and/or CPT 27486) procedure for indication of PJI (ICD-10 T84.53 OR T84.54) between January 1, 2017 and December 31, 2021. We identified reoperations (i.e., stage 1 revision, amputation, or arthrodesis) indicating failure of DAIR. Failure of DAIR treatment was defined by subsequent reoperation. We also identified prescriptions of suppression antibiotics more than 6 months after DAIR. We identified 1,018 patients who underwent a DAIR procedure for PJI. Of these patients, 195 (19.2%) underwent reoperation within 1 year and an additional 178 (17.5%) were prescribed suppressive antibiotics. For 780 patients with a minimum of 2 years of follow-up, 164 (21%) underwent reoperation and an additional 179 (22.9%) were prescribed suppressive antibiotics. Patients with obesity and patients younger than 60 years had significantly higher rates of having reoperation or suppressive antibiotics at 1 year following DAIR. DAIR is a viable option in the treatment of PJI, with an approximately 19% rate of reoperation at 2 years. Our findings are consistent with that of previously published literature., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: To analyze the clinical features of COVID-19 infection in hospitalized immunocompromised patients in comparison with immunocompetent patients. Methods: A single-center retrospective observational study was conducted on 213 inpatients diagnosed with COVID-19 in the Peking University People's Hospital between December 2022 and October 2023. They were divided into an immunocompromised group (102 patients, 47.9%) and an immunocompetent group(111 patients, 52.1%), and clinical data were compared between the two groups. The immunocompromised group was further divided into death group (18 cases, 17.6%) and non-death group (84 cases, 82.4%). The differences in laboratory examination findings were compared. Further analysis was performed on the lymphocyte subset differences between the death group(10 patients, 9.8%) and the non-death group (36 patients, 35.3%) with complete data. Results: The proportion of severe and critical cases and the mortality rate, were significantly higher in the immunocompromised group than the immunocompetent group (47.1% vs . 40.5%, 18.6% vs . 9.0%, 17.6% vs . 9.0%, P< 0.05). The immunocompromised group had lower vaccination rate (26.5% vs . 44.1%, P <0.05). Hypertension, kidney disease and infections were more common in the immunocompromised group (63.7% vs . 48.6%, 30.4% vs . 9.0%, 49.0% vs . 19.8%, all P <0.05). CT findings of consolidation (40.2% vs . 18.9%), rate of antiviral treatment (48.0% vs . 30.6%) and the positive duration of viral nucleic acid [median 14(7.0, 19.3) days vs . 9(7.0, 18.0) days] were higher in the immunocomprised group (all P <0.05). Lactate dehydrogenase (LDH), procalcitonin (PCT), interleukin-6 (IL-6) and ferritin were higher in the immunocompromised group than those in the immunocompetent group (all P <0.05). In the death group, neutrophils (NEU), C-reactive protein (CRP), PCT, IL-6, ferritin and D-dimer were higher, while lymphocytes (LY), CD4 + T-cells, CD8 + T-cells, B-cell counts and hemoglobin (HGB) were significantly lower than those in the non-death group (all P <0.05). Conclusions: More than 60% of patients in the immunocompromised group were classified as severe or critical type, with a higher mortality rate and decreased ability to clear severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Decreases in total lymphocytes, CD4 + T lymphocytes, CD8 + T lymphocytes, and B lymphocytes, along with elevated levels of procalcitonin, ferritin, and D-dimer, indicated poor prognosis.

Purpose: The innate immune response, particularly the reaction of polymorphonuclear neutrophils (PMNs), is crucial in shaping the outcomes of chronic inflammation, fibrosis, or osseointegration following biomaterial implantation. Peri-implantitis or peri-implant mucositis, inflammatory conditions linked to dental implants, pose a significant threat to implant success. We developed a single-cell analysis approach using a murine model to assess the immune response to implant materials, offering a practical screening tool for potential dental implants., Methods: We performed bioinformatics analysis and established a peri-implant inflammation model by inserting two titanium implants into the maxillary region, to examine the immune response., Results: Bioinformatics analysis revealed that titanium implants triggered a host immune response, primarily mediated by PMNs. In the in vivo experiments, we observed a rapid PMN-mediated response, with increased infiltration around the implants and on the implant surface by day 3. Remarkably, PMN attachment to the implants persisted for 7 days, resembling the immune profiles seen in human implant-mediated inflammation., Conclusions: Our findings indicate that persistent attachment of the short-living PMNs to titanium implants can serve as an indicator or traits of peri-implant inflammation. Therefore, analyzing gingival tissue at the single-cell level could be a useful tool for evaluating the biocompatibility of candidate dental implants.

How novel structures emerge during evolution has long fascinated biologists. A dramatic example is how the diminutive bones of the mammalian middle ear arose from ancestral fish jawbones 1 . In contrast, the evolutionary origin of the outer ear, another mammalian innovation, remains a mystery, in part because it is supported by non-mineralized elastic cartilage rarely recovered in fossils. Whether the outer ear arose de novo or through reuse of ancestral developmental programs is unknown. Here we show that the outer ear shares gene regulatory programs with the gills of fishes and amphibians for both its initial outgrowth and later development of elastic cartilage. Comparative single-nuclei multiomics of the human outer ear and zebrafish gills reveals conserved gene expression and putative enhancers enriched for common transcription factor binding motifs. This is reflected by transgenic activity of human outer ear enhancers in gills, and fish gill enhancers in the outer ear. Further, single-cell multiomics of the cartilaginous book gills of horseshoe crabs reveal a shared DLX-mediated gill program with vertebrates, with a book gill distalless enhancer driving expression in zebrafish gills. We propose that elements of an invertebrate gill program were reutilized in vertebrates to generate first gills and then the outer ear., (© 2025. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Oral microbiome has been associated with various cancers, including nasopharyngeal carcinoma (NPC), but its role in cancer treatment and prognosis remains largely unknown. This study aims to address the dynamic changes in oral microbiome following cancer treatment and their prognostic implications in NPC patients., Patients and Methods: Unstimulated whole saliva samples were collected from 23 NPC patients before and after treatment, with an average of 2.8 samples per patient, and post-treatment saliva samples were collected from additional 13 NPC patients that enrolled after treatment. Following DNA extraction and purification, the salivary microbiome was assessed by 16S rRNA gene amplicon sequencing targeting the V4 hypervariable region., Results: Alpha-diversity of oral microbiome decreased progressively after treatment and during follow-up, and the beta-diversity of post-treatment samples differed significantly from the pre-treatment ones ( R 2  = 0.032, p  < 0.001). Among patients free of disease progression, 31 oral taxa were identified that changed significantly in abundances after treatment, with 8 increasing and 23 decreasing. The declining taxa included two previously reported NPC-enriched bacteria, Lautropia mirabilis and Capnocytophaga sputigena . In contrast, in the only recurrent case, the abundances of the two bacteria did not decrease, but remained at high levels or even increased until recurrence occurred., Conclusion: NPC treatment can cause persistent decline in microbial diversity of salivary microbiome and abundances of NPC-associated bacteria, and candidate bacteria could be an explanatory factor for NPC prognosis and deserve intensive research., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2025 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Tetrabromobisphenol A (TBBPA), a brominated flame retardant (BFR), has been implicated as the neurotoxic effects in mammalian. However, the exact mechanisms underlying TBBPA-induced neurotoxicity remain unclear. In the present study, Neuro-2a cells, a mouse neural crest-derived cell line, were used to examine the mechanism of TBBPA-induced neuronal cytotoxicity. TBBPA exposure caused alterations in cell viability and mitochondrial membrane potential (MMP) and induction of apoptotic events, such as increased apoptotic cell population and cleaved caspase-3, -7, -9, and poly (ADP-ribose) polymerase (PARP) protein expression). TBBPA exposure triggered CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) activation. Transfection with CHOP-specific small interfering RNA (siRNA) obviously prevented the expression of CHOP protein and markedly attenuated MMP loss, and caspase-3 and -7 activation in TBBPA-exposed Neuro-2a cells. In addition, TBBPA exposure significantly evoked the phosphorylation of c-Jun N-terminal kinase (JNK), extracellular-signal regulated kinase1/2 (ERK1/2), p38-mitogen-activated protein kinase (p38-MAPK), and AMP-activated protein kinase (AMPK)α proteins. Pretreatment of cells with pharmacological inhibitors of p38-MAPK (SB203580) and AMPK (compound C), but not inhibitors of JNK (SP600125) or ERK1/2 (PD98059), effectively prevented the increase in caspase-3 activity, MMP loss, and activated CHOP and cleaved caspase-3 and -7 protein expression in TBBPA-treated cells. Notably, transfection with either p38α-MAPK- or AMPKα1/2-specific siRNAs markedly attenuated the expression of CHOP, and cleaved caspase-3 and -7. Interestingly, transfection with each siRNA significantly reduced the TBBPA-induced phosphorylation of p38-MAPK and AMPKα proteins. Collectively, these findings suggest that CHOP activation-mediated mitochondria-dependent apoptosis contributes to TBBPA-induced neurotoxicity. An interdependent p38-MAPK and AMPKα signaling-regulated apoptotic pathway may provide new insights into the mechanism understanding TBBPA-elicited neurotoxicity., 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 PedsQL is widely used to retrospectively evaluate quality of life (QoL) in autistic adolescents. However, concerns have arisen regarding its ability to reflect real-time QoL, considering their challenges in recollecting past experiences., Objective: We examined the overall and social QoLs of autistic adolescents compared to neurotypical peers using the PedsQL and the experience sampling method (ESM), an ecological momentary assessment of QoL in real-time. Additionally, we explored the relationship between these measures in each group., Methods: A total of 175 participants, including 117 autistic and 58 neurotypical adolescents aged 10-16, completed the PedsQL and an ESM protocol with a mobile device to record their real-time experiences seven times a day for seven days. We performed multiple linear regression and multilevel analyses to compare QoLs between groups and the association between the two measures., Results: Autistic adolescents scored significantly lower than neurotypical peers on PedsQL overall and social QoL but not on the real-time experiences collected with ESM. Among neurotypical adolescents, we found significant associations between the Social Functioning score of the PedsQL and various aspects of real-time social experiences recorded with ESM. For autistic adolescents, only the real-time experience of 'loneliness' during social engagement was associated with Social Functioning on the PedsQL., Conclusions: The retrospective PedsQL does not entirely capture the real-time QoL via ESM. However, relying solely on ESM may overlook situations where participants opt out or could not complete surveys. Thus, using both retrospective and real-time assessments to examine QoL among autistic adolescents is recommended., Competing Interests: Declaration of competing interest The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: The alpine pit viper, Trimeresurus gracilis , is an endemic species in Taiwan. The incidence of human envenoming is rare., Case Summaries: We present three events in two patients bitten by Trimeresurus gracilis . In the first patient, envenoming inflicted pain, local bleeding, hemorrhagic bulla, and progressive swelling, leading to necrosis of the bite wound. In the second patient, the two snakebites caused pain and progressive swelling. There were no systemic effects such as organ damage or neurological deficits observed. A paraspecific antivenom against Trimeresurus stejnegeri and Protobothrops mucrosquamatus was used to treat both patients, with a favorable outcome in each., Discussion: Combined with the clinical manifestations of two previously reported cases of Trimeresurus gracilis envenoming, the known effects of Trimeresurus gracilis venom in humans include local toxicities, severe soft-tissue damage, compartment syndrome, and coagulopathy without spontaneous systemic bleeding. The paraspecific antivenom, which has demonstrable cross-neutralization effects in animal studies, appeared to be effective against the local toxicities as the patients showed prompt cessation of the progression of their swelling., Conclusions: The knowledge of clinical manifestations and management approaches to Trimeresurus gracilis envenoming is helpful for patient care. The use of the paraspecific antivenom should be considered in managing such envenoming.

Background and Purpose: Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking., Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance., Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64-2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal., Conclusion: s The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Background: The literature has mainly focused on the association between tooth loss and dementia, and evidence regarding the separate and joint effects of tooth loss and denture use on the risk of dementia is limited. This study investigated the links among tooth loss, denture use, and dementia risk in Taiwanese adults aged 65 years or older., Methods: This retrospective cohort study utilized data from the 2009 National Health Interview Survey and 2008-2017 National Health Insurance claim records, including the records of 2247 individuals free from dementia treatment in 2008-2009. Dementia diagnoses were tracked until 2017. The Cox proportional hazards model was used to calculate hazard ratios (HRs) for exploring the correlations among tooth loss, denture use, and dementia risk., Results: Older adults with 20 or more natural teeth and dentures had the lowest dementia incidence (1.43 per 100 person-years). Those with <20 natural teeth, with or without dentures, experienced high dementia incidence rates of 2.31 and 3.33 per 100 person-years, respectively. After adjusting for various factors (i.e., sociodemographic characteristics, health conditions/comorbidities, and lifestyles), having <20 natural teeth or not using dentures was associated with non-significantly increased HRs of 1.30 (95% CI, 0.99-1.71) and 1.20 (95% CI, 0.95-1.52). Subgroup analysis revealed that compared to older adults with 20 or more natural teeth and dentures, those with <20 natural teeth and not wearing dentures had a significantly increased risk of dementia (adjusted HR, 1.57; 95% CI, 1.04-2.37)., Conclusion: This study found that having <20 natural teeth and not using dentures was significantly associated with an increased risk of dementia in Taiwanese individuals aged 65 years or above., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024, the Chinese Medical Association.)

Background/purpose: With the gradual aging of the population, oral health has emerged as a critical concern alongside mental well-being. This study endeavored to investigate the relationship between oral health-related quality of life (OHRQoL) and mental depression in middle-aged and older population., Materials and Methods: Based on the Taiwan Longitudinal Study on Aging in 2015, 7631 participants were enrolled. OHRQoL was assessed utilizing the Taiwan version of the Oral Health Impact Profile questionnaire, stratifying individuals into five categories (excellent, good, fair, poor, and very poor). The excellent OHRQoL group was regarded as the reference group. Depression status was evaluated using the 10-item Center for the Epidemiological Studies of Depression Short Form questionnaire. Descriptive statistics and Pearson's chi square test were applied to elucidate the demographic characteristics and the differences among the five OHRQoL groups, respectively. Multivariable logistic regression was applied to elucidate the association of OHRQoL with depression after controlling for confounding factors., Results: After controlling for covariates such as age, sex, marital status, living status, residency status, religion, level of physical activity, and pressures arising from personal or familial concerns, the adjusted ORs of experiencing mental depression were 1.45 (95% CI: 1.198-1.760, P  < 0.001), 2.25 (95% CI: 1.791-2.829, P  < 0.001), 3.88 (95% CI: 2.730-5.525, P  < 0.001), and 6.87 (95% CI: 3.116-15.129, P  < 0.001) for the good, fair, poor, and very poor OHRQoL groups, respectively, which demonstrated a gradually increased relationship., Conclusion: Oral health-related quality of life was negatively associated with mental depression in middle-aged and older adults., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2024 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.Vé.)

Treating metastatic brain tumors remains a significant challenge. This study introduces and applies the Patient-Derived Tumor Spheroid (PDTS) system, an ex vivo model for precision drug testing on metastatic brain tumor. The PDTS system utilizes a decellularized extracellular matrix (dECM) derived from adipose tissue, combined with the tumor cells, to form tumor spheroids. These spheroids were subsequently used to test anticancer drugs, with results compared to the clinical outcomes observed after administering these treatments to patients. To assess the validity of the data, the correlation between the drug responses observed in the PDTS model and actual patient outcomes was analyzed. Chi-square tests evaluated the significance of associations between lab predictions and clinical outcomes, using a significance threshold of p < 0.05. In preliminary data, 17 patients met the criteria for final analysis, which showed an overall 57% accuracy (p-value = 0.463), with improvements to 73% accuracy (p-value = 0.072) when patients receiving certain treatments were excluded. This PDTS offers real-time results within three weeks, simultaneous testing of multiple drugs, and the ability to culture and store tumor cells for reproducibility. Despite some limitations, further development of this model could enhance its clinical application and improve patient outcomes., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Formerly a common childhood pathogen, mumps virus (MuV) remains active worldwide, despite relatively high vaccine coverage. MuV is thought to infect the upper respiratory tract before disseminating to other organs; however, the early cellular targets of MuV in vivo are unknown. To address this, we generated a green fluorescent protein (GFP)-tagged vaccine strain (JL5) of MuV to infect leukocytic cell lines and found that replication was greatest in monocytes. Infection of peripheral blood mononuclear cells (PBMCs) also showed that both JL5 and a circulating strain of MuV (Iowa 2006; genotype G), preferentially infected monocytes. Further, monocyte-derived macrophages showed high susceptibility to MuV, with genotype G infecting macrophages to a much greater extent. While mice are generally resistant to MuV infection, we inoculated immunocompetent Rosa26-tdTomato mice intranasally with a GFP and Cre recombinase tagged MuV to determine whether monocytes/macrophages are important targets in vivo. We observed a small population of tdTomato + cells within the lungs, which included epithelial cells; however, the vast majority were alveolar macrophages (AMs). To validate these findings, we infected murine AMs isolated from Rosa26-tdTomato mice with the GFP and Cre recombinase tagged MuV and found that while MuV could enter AMs, as determined by tdTomato positivity, only a small percentage of these expressed GFP, suggesting that inhibition in murine cells occurs postentry. To translate these findings, we infected cells from human bronchoalveolar lavage fluid with MuV and found that most infected cells were AMs. These findings highlight the high susceptibility of AMs and provide a basis for early MuV pathogenesis and subsequent dissemination., Competing Interests: Competing interests statement:The authors declare no competing interest.

Cutaneous wound healing is a slow process that often terminates with permanent scarring while oral wounds, in contrast, regenerate after damage faster. Unique molecular networks in epidermal and oral epithelial keratinocytes contribute to the tissue-specific response to wounding, but key factors that establish those networks and how the keratinocytes interact with their cellular environment remain to be elucidated. The transcription factor PITX1 is highly expressed in the oral epithelium but is undetectable in cutaneous keratinocytes. To delineate if PITX1 contributes to oral keratinocyte identity, cell-cell interactions, and the improved wound healing capabilities, we ectopically expressed PITX1 in the epidermis of murine skin. Using comparative analysis of murine skin and oral (buccal) mucosa with single-cell RNA-Seq and spatial transcriptomics, we found that PITX1 expression enhances epidermal keratinocyte migration and proliferation and alters differentiation to a quasi-oral keratinocyte state. PITX1+ keratinocytes reprogrammed intercellular communication between skin-resident cells to mirror buccal tissue while stimulating the influx of neutrophils that establish a pro-inflammatory environment. Furthermore, PITX1+ skin healed significantly faster than control skin via increased keratinocyte activation and migration and a tunable inflammatory environment. These results illustrate that PITX1 programs oral keratinocyte identity and cellular interactions while revealing critical downstream networks that promote wound closure.

Aims: Few personalized monitoring models for valproic acid (VPA) in pediatric epilepsy patients (PEPs) incorporate machine learning (ML) algorithms. This study aimed to develop an ensemble ML model for VPA monitoring to enhance clinical precision of VPA usage., Methods: A dataset comprising 366 VPA trough concentrations from 252 PEPs, along with 19 covariates and the target variable (VPA trough concentration), was refined by Spearman correlation and multicollinearity testing (366 × 11). The dataset was split into a training set (292) and testing set (74) at a ratio of 8:2. An ensemble model was formulated by Gradient Boosting Regression Trees (GBRT), Random Forest Regression (RFR), and Support Vector Regression (SVR), and assessed by SHapley Additive exPlanations (SHAP) analysis for covariate importance. The model was optimized for R 2 , relative accuracy, and absolute accuracy, and validated against two independent external datasets (32 in-hospital and 28 out-of-hospital dataset)., Results: Using the R 2 weight ratio of GBRT, RFR and SVR optimized at 5:2:3, the ensemble model demonstrated superior performance in terms of relative accuracy (87.8%), absolute accuracy (78.4%), and R 2 (0.50), while also exhibiting a lower Mean Absolute Error (9.87) and Root Mean Squared Error (12.24), as validated by the external datasets. Platelet count (PLT) and VPA daily dose were identified as pivotal covariates., Conclusion: The proposed ensemble model effectively monitors VPA trough concentrations in PEPs. By integrating covariates across various ML algorithms, it delivers results closely aligned with clinical practice, offering substantial clinical value for the guided use of VPA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Lin, Chen, Zhang, Wu, Huang, Rao, Lu and Liu.)

Background: This study investigated whether point-of-care platelet function measurements could predict favorable outcomes in patients with acute ischemic stroke (AIS). Antiplatelet agents, such as aspirin, are known to reduce the risk of recurrent stroke by 20-30%. However, identifying nonresponders to therapy remains a clinical challenge. The study aimed to assess the prognostic value of serial Platelet Function Analyzer (PFA)-100 measurements and hematological ratios in AIS patients., Methods: A prospective cohort study was conducted on 212 AIS patients in Taiwan. Platelet function was assessed at baseline, week 2, and week 4 using PFA-100. The primary outcome was functional recovery, defined by a modified Rankin Scale (mRS) score of 0-3, at 1-month and 1-year. Subgroup analyses compared outcomes between pre- and post-aspirin administrations. Statistical analyses examined the association between changes in platelet function and clinical outcomes., Results: Difference in collagen and epinephrine (CEPI) measurements between baseline and week 2 was associated with favorable mRS scores ( p < 0.001). A difference in CEPI closure time greater than 99 seconds was most predictive of a favorable outcome with an adjusted odds ratio of 11.859 (95% CI 2.318-60.669) at 1-month follow-up. Subgroup analyses revealed predictive value in pre-aspirin measurements at 1-month follow-up ( p = 0.007)., Conclusions: Serial PFA-100 measurements and hematological biomarkers, specifically changes in on-treatment CEPI closure times, may help predict favorable clinical outcome in AIS patients. These findings suggest that dynamic platelet function assessment could play a role in optimizing antiplatelet therapy in AIS management.

This study was performed to develop an optimal process for manufacturing activated carbon (AC) from pineapples' off-cuts (leaves and peels; PL and PP) by pyrolysis and for forming a bio-complex with sodium alginate (CA). In addition, the physicochemical properties were also explored under different preparation conditions, and the effects of adsorbed uremic toxins in three simulated gastrointestinal conditions (in vitro) were evaluated. This study showed that pyrolysis at 800 °C and activation by CO 2 (30 min) resulted in satisfactory porous profiles with high specific surface areas of 388.79 and 536.84 m 2 /g for PLAC and PPAC, respectively. Regarding appearance and microstructures, there are still discernible disparities compared to the AST in regular service, while it exhibits a similar peak shape to that of the AC under the Raman spectrometer. Remarkably, the adsorption capacity of PLAC and PPAC for uremic toxins was best for indole adsorption while providing a consistent effect with AST. Indole-3-acetic acid (3-IAA) and p-cresol (p-C) adsorption capacities were the second highest. Nevertheless, AST also exhibited varying degrees of reduced adsorption capacity under different gastrointestinal simulation conditions. Therefore, this study conditions the development of cost-effective adsorbent products targeting uremic toxins, which could generate novel synergistic systems based on pineapple by-products within the circular economy framework., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Non-small cell lung cancer (NSCLC) is commonly treated with tyrosine kinase inhibitors (TKIs). However, adverse events from such treatment can lead to treatment discontinuation and additional medical expenditures. Ambulatory care from oncology pharmacists in patient education and symptom management can benefit patients with NSCLC. In this study, we evaluated the effectiveness of an oncology pharmacy service at a medical center in Taiwan. We retrospectively enrolled 137 patients with NSCLC who initiated treatment with afatinib, gefitinib, or erlotinib between January 2017 and December 2021; 40 of them utilized the oncology pharmacy service (intervention group), and the remaining 97 did not (nonintervention group). To determine the effectiveness of the oncology pharmacy service, we analyzed the following outcomes: adverse event rates, number of hospital visits (unexpected outpatient department visits, emergency department visits, and hospitalization), and medical expenditure. The intervention group had significantly more skin-related adverse events (acneiform rash: 75% vs. 49%; mucositis: 40% vs. 21%; dermatitis: 30% vs. 9%; and paronychia: 85% vs. 28%) but significantly fewer monthly emergency department visits (0.04 vs. 0.17) and unexpected outpatient department visits (0.15 vs. 0.34). The intervention group also had significantly lower expenditure for emergency department visits (NT$166.4 vs. NT$734.8) and nonsignificantly lower expenditure for outpatient department visits. Our findings indicate the value of pharmacist-managed ambulatory oncology care. Although this service did not reduce the incidence rates of adverse events, it reduced the number of unplanned outpatient and emergency department visits and reduced the emergency department expenditure of patients with NSCLC receiving TKIs.

Muscle atrophy, an age-related condition, presents a growing healthcare concern within the context of global population aging. While studies have investigated Hirsutella sinensis for its potential antifatigue properties, reports on its active components remain limited. This study evaluated the efficacy of H. sinensis mycelium extract on muscle health, utilizing a 1:1 water-ethanol preparation administered to C57BL/6 mice exhibiting acute hind leg atrophy. The results indicated no adverse effects, with significant improvements in muscle endurance and soleus muscle mass observed over a 14-day period. To further elucidate the mechanisms and effects of H. sinensis mycelium on dexamethasone-induced muscle atrophy, the water extract was fractionated into components of <3.5 kDa, 3.5-10 kDa, and >10 kDa using dialysis membranes. The investigation utilized a C2C12 cell atrophy model, induced by dexamethasone, to analyze the expression of relevant genes via qPCR. The results demonstrated that the <3.5 kDa and >10 kDa fractions significantly upregulated the expression of Myh2 and Myh7 genes while simultaneously downregulating the expression of MuRF-1 and Atrogin-1 . It is noteworthy that the <3.5 kDa fraction exclusively enhanced MYHC protein expression and suppressed AMPK expression, as confirmed by Western blot analysis. This comprehensive pilot study suggests that the low-molecular-weight fraction of H. sinensis mycelium exhibits considerable potential for muscle mass preservation and atrophy mitigation. As a result, it offers a promising direction for the development of supplements aimed at addressing fatigue and preventing muscle atrophy.

Hearing impairment in patients with rheumatoid arthritis has been underestimated for decades. Rheumatoid arthritis can affect both the middle ear (specifically, the incudomalleolar and incudostapedial joints) and inner ear (including the cochlea and acoustic nerve) simultaneously. Despite ongoing research, consensus on effective treatments for hearing impairment in these patients remains elusive. This systematic review aims to consolidate clinically relevant information for healthcare providers by summarizing current evidence on hearing impairment in rheumatoid arthritis patients. We conducted the current systematic review by searching platforms of PubMed, Embase, ClinicalKey, Web of Science, and ScienceDirect to retrieve eligible articles regarding hearing impairment related to rheumatoid arthritis. We extract any data on characteristics, pathophysiology, examination, and treatment related to rheumatoid arthritis. Based on the currently available evidence, we advocate for the use of specific audiometric tests to facilitate early detection of hearing impairment in these patients. Regular audiological assessments are recommended to monitor hearing ability and potentially prevent further deterioration. Finally, we propose a modified treatment protocol that integrates steroids, hydroxychloroquine, and non-invasive brain stimulation as a novel therapeutic approach for managing these symptoms. This protocol aims to offer clinicians new strategies to address hearing impairment in patients with rheumatoid arthritis effectively.

Congenital diaphragmatic hernia (CDH) is characterized by incomplete closure of the diaphragm. While the ensuing compression to the fetal lung causes lung hypoplasia, specific cellular phenotypes and developmental signaling defects in the alveolar epithelium in CDH are not fully understood. Employing lung samples from human CDH, a surgical lamb model and a nitrogen rat model, we investigate whether lung compression impairs alveolar epithelial differentiation and Yes-associated protein (YAP)-mediated mechanosensing. We showed that CDH in humans and lambs caused defective alveolar epithelial differentiation manifested by more abundant ATII cells, fewer ATI cells, and the emergence of cells expressing both ATI and ATII markers. Associated with the alveolar epithelial defects, we found a decrease in the level and nuclear localization of YAP. Reduced nuclear YAP and abnormal distal lung development were evident as early as 21 weeks in gestation in human CDH. In addition, rat fetuses with CDH also showed diminished nuclear YAP and mor abundant ATII cells. In contrast, the littermates without the hernia had no such alveolar phenotypes. Furthermore, fetal tracheal occlusion (TO) in the surgical lamb model of CDH fully normalized nuclear YAP and rescued alveolar epithelial defects in a gestational age-dependent manner. Taken together, our findings across species indicate that lung compression in CDH is sufficient to disrupt alveolar epithelial differentiation and impair YAP signaling. TO can restore nuclear YAP and rescue the alveolar defects in CDH, depending on the timing and the duration of this prenatal surgical intervention. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

The effects of Lactiplantibacillus plantarum 1008 (LP1008) on age-related cognitive impairment and skeletal muscle atrophy have been reported previously. However, its role in obesity- and age-related hypogonadism has yet to be explored. This study investigates the therapeutic efficacy of low- and high-dose LP1008 in a high-fat-diet-fed male mouse model. Mice at 37 weeks of age were fed a standard diet ( n = 8) or a 45% high-fat diet for 28 weeks, and the high-fat-diet-fed mice were divided into vehicle, low-dose and high-dose LP1008 groups ( n = 8 per group) on the basis of the treatment administered for an additional 8 weeks. We found that LP1008 suppressed the increases in total cholesterol levels and liver function parameters and alleviated histological changes in the brain, ileum, gastrocnemius muscle and testes. In terms of reproductive function, LP1008 attenuated the decreases in sperm quality, sperm maturity, testosterone levels and levels of enzymes involved in testosterone biosynthesis. Furthermore, LP1008 altered impairments in spatial learning and memory and induced slight alterations in the gut microbiota. Moreover, LP1008 exerted antioxidant, anti-inflammatory and anti-apoptotic effects in aged, obese male mice. LP1008 reversed diet-induced obesity, age-related reproductive dysfunction and pathological damage by increasing testosterone levels and altering the gut microbiome through the regulation of mediators involved in oxidative stress, apoptosis and inflammation.

Purpose: To assess the clinimetric properties of the Stroke Self-Efficacy Questionnaire (SSEQ) and estimate the minimal detectable change (MDC) and minimal clinically important difference (MCID) from the database of our randomized controlled trials (RCT) of individuals receiving stroke rehabilitation., Methods: We retrieved the pre- and post-intervention scores of the SSEQ and Stroke Impact Scale (SIS) from 80 stroke survivors. The analysis of clinimetric properties was performed using: (1) confirmatory factor analysis and item response theory modeling (IRT) for construct validity; (2) standardized response mean and Glass's delta for responsiveness; (3) MDC based on the standard deviation (SD) or standard error of measurement (SEM) of the SSEQ change scores; (4) MCID determined by the external anchor-SIS; (5) conditional MDC (cMDC) derived from the IRT analysis., Results: There was a bi-factorial construct with excellent model-data fit and marked responsiveness. The MDC determined by the SD and SEM were 1.5 and 3.0, respectively, and the MCIDs were 3.3 and 3.7., Conclusions: This study confirmed that SSEQ is a valid and reliable assessment tool for patients receiving stroke rehabilitation. We also provided practical threshold values, especially demonstrating the benefit of using individualized cMDC, to help clinicians better interpret the change in the SSEQ scores.

Background: Chinese giant salamander protein hydrolysates (CGSPH) are beneficial to human health as a result of their high content of amino acids and peptides. However, the formation of bitter peptides in protein hydrolysates (PHs) would hinder their application in food industry. The ultrasound assisted wet-heating Maillard reaction (MR) is an effective way to improve the flavor of PHs. Thus, the effect of ultrasonic assisted wet-heating MR on the structure and flavor of CGSPH was investigated in the present study., Results: The results indicated that the ultrasound assisted wet-heating MR products (MRPs) exhibited a higher degree of graft and more significant changes in the secondary and tertiary structures of CGSPH compared to traditional wet-heating MRPs. Moreover, ultrasound assisted wet-heating MR could significantly increase the content of small molecule peptides and reduce the content of free amino acids of CGSPH, which resulted in more significant changes in flavor characteristics. The changed in flavor properties after MR (especially ultrasound assisted wet-heating MRPs) were mainly manifested by a significant reduction in bitterness, as well as a significant increase in the content of aromatic aldehyde ester compounds such as furan-2-carbaldehyde, butanal, benzaldehyde, furfural, etc. CONCLUSIONS: Ultrasound assisted wet-heating MR between CGSPH and xylose could be a promising way to improve the sensory characteristics of CGSPH. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Peritoneal dialysis (PD) is a widely used sustainable kidney replacement therapy. Prolonged use of PD fluids is associated with mesothelial-mesenchymal transition, peritoneal fibrosis, and eventual ultrafiltration (UF) failure. However, the impact of pressure on the peritoneum remains unclear. In the present study, we hypothesized increased pressure is a potential contributing factor to peritoneal fibrosis and investigated the possible mechanisms. In vitro experiments found that pressurization led to a mesenchymal phenotype, the expression of fibrotic markers and inflammatory factors in human mesothelial MeT-5A cells. Pressure also increased cell proliferation and augmented cell migration potential in MeT-5A cells. The mouse PD model and human peritoneum equilibrium test (PET) data both showed a positive association between higher pressure and increased small solute transport, along with decreased net UF. Mechanistically, we found that significant upregulation of CD44 in mesothelial cells upon pressurization. Notably, the treatment of CD44 neutralizing antibodies prevented pressure-induced phenotypic changes in mesothelial cells, while a CD44 inhibitor oligo-fucoidan ameliorated pressure-induced peritoneal thickening, fibrosis, and inflammation in PD mice. To conclude, intraperitoneal pressure results in peritoneal fibrosis in PD via CD44-mediated mesothelial changes and inflammation. CD44 blockage can be utilized as a novel preventive approach for PD-related peritoneal fibrosis and UF failure.

Purpose of Review: The purpose of this review is to explore the lessons learned from experimental and human tracheal transplantation to determine if this information may be applied to lung transplantation., Recent Findings: Experimental work in animal models and the recent human tracheal transplantation suggests that a robust tracheal vascular supply prevents anastomotic complications. Further, this work demonstrates that tracheal allografts undergo a progressive chimerism as recipient epithelium repopulates the allograft. In contrast to most vascularized composite allografts such as hand and face transplantation that experience high rates of rejection, the tracheal allograft did not demonstrate rejection. This may suggest that tissue chimerism plays a role in evading immune-mediated allograft rejection., Summary: While anastomotic complications and chronic allograft rejection are the most common complications related to lung transplantation, the findings associated with tracheal transplantation may have implications for both reducing complications associated with lung transplantation., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)