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Abstract 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

Abstract Immunotherapy has revolutionized cancer treatment, but the lack of a reliable predictive biomarker for treatment response remains a challenge. Alpha-1,6-Mannosylglycoprotein 6-β-N-Acetylglucosaminyltransferase 5 (MGAT5) is a key regulator of complex N-glycan synthesis, and its dysregulation is associated with cancer progression. The lectin Phaseolus vulgaris leukoagglutinin (PHA-L) specifically binds to mature MGAT5 products. Previous studies have indicated elevated PHA-L staining in head and neck squamous cell carcinoma (HNSCC), which implies increased activity of MGAT5. However, the specific role of MGAT5 in HNSCC remains unclear. In this study, we found significantly higher PHA-L staining and MGAT5 expression in HNSCC tumors compared to adjacent non-tumor tissues. Using a mass spectrometry (MS)-based glycoproteomic approach, we identified 163 potential protein substrates of MGAT5. Functional analysis revealed that protein substrates of MGAT5 regulated pathways related to T cell proliferation and activation. We further discovered that PD-L1 was among the protein substrates of MGAT5, and the expression of MGAT5 protected tumor cells from cytotoxic T lymphocyte (CTL) killing. Treatment of nivolumab alleviated the protective effects of MGAT5 on CTL activity. Consistently, patients with MGAT5-positive tumors showed improved responses to immunotherapy compared to those with MGAT5-negative tumors. Using purified PD-L1 from HNSCC cells and a glycoproteomic approach, we further deciphered that the N35 and N200 sites carry the majority of complex N-glycans on PD-L1. Our findings highlight the critical role of MGAT5-mediated branched N-glycans on PD-L1 in modulating the interaction with the immune checkpoint receptor PD-1. Consequently, we propose that MGAT5 could serve as a biomarker to predict patients’ responses to anti-PD-1 therapy. Furthermore, targeting the branched N-glycans at N35 and N200 of PD-L1 may lead to the development of novel diagnostic and therapeutic approaches.

Background: Glove reuse poses risks, as chemicals can persist even after cleaning. Decontamination methods like thermal aeration, recommended by US OSHA, vary in effectiveness. Some studies show promising results, while others emphasize the importance of considering both permeation and tensile strength changes. This research advocates for informed glove reuse, emphasizing optimal thermal aeration temperatures and providing evidence to guide users in maintaining protection efficiency. Methods: The investigation evaluated Neoprene and Nitrile gloves (22 mils). Permeation tests with toluene and acetone adhered to American Society for Testing Materials (ASTM) F739 standards. Decontamination optimization involved aeration at various temperatures. The experiment proceeded with a maximum of 22 re-exposure cycles. Tensile strength and elongation were assessed following ASTM D 412 protocols. Breakthrough time differences were statistically analyzed using t-test and ANOVA. Results: At room temperature, glove residuals decreased, and standardized breakthrough time (SBT)2 was significantly lower than SBT1, indicating reduced protection. Higher temperature decontamination accelerated residual removal, with ΔSBT (SBT2/SBT1) exceeding 100%, signifying restored protection. Tensile tests showed stable neoprene properties postdecontamination. Results underscore thermal aeration's efficacy for gloves reuse, emphasizing temperature's pivotal role. Findings recommend meticulous management strategies, especially post-breakthrough, to uphold glove-protective performance. Conclusions: Thermal aeration at 100°C for 1 hour proves effective, restoring protection without compromising glove strength. The study, covering twenty cycles, suggests safe glove reuse with proper decontamination, reducing costs significantly. However, limitations in chemical-glove combinations and exclusive focus on specific gloves caution against broad generalization. The absence of regulatory directives on glove reuse highlight the importance of informed selection and rigorous decontamination validation for workplace safety practices.

Glioma is a common primary malignant brain tumor with low survival rate. Immunotherapy with immune checkpoints inhibitors (ICI) can be a choice for glioma management, and extracellular vesicles (EVs) are recognized as a potential drug delivery system for various disease management due to their enhanced barrier permeation ability and immunomodulatory effect. The aim of this study is to develop ICI-loaded EVs (ICI/EV) that have sufficient efficacy in managing glioma. Calcium phosphate particles (CaP) were used to stimulate the secretion of EVs from murine macrophage cells. CaP conditioning of cells showed an enhanced amount of EVs secretion and macrophage polarization toward a proinflammatory phenotype. The CaP-induced EVs were shown to polarize macrophages into proinflammatory phenotype in vitro, as correlated with the conditioning method. ICI/EVs were successfully prepared with high loading efficiency using the sonication method. The EVs can be distributed throughout the entire brain upon intranasal administration and facilitate ICIs distribution into glioma lesion. Combinatory treatment with ICI/EVs showed benefit in glioma-bearing mice by reducing their tumor volume and prolonging their survival. Cytotoxic T cell infiltration, polarization of tumor-associated macrophage, and lower tumor proliferation were observed in ICI/EVs-treated mice. The developed ICI/EVs showed promise in immunotherapeutic management of glioma.

BackgroundBreast cancer is a leading global health concern, necessitating advancements in recurrence prediction and management. The development of an artificial intelligence (AI)–based clinical decision support system (AI-CDSS) using ChatGPT addresses this need with the aim of enhancing both prediction accuracy and user accessibility. ObjectiveThis study aims to develop and validate an advanced machine learning model for a web-based AI-CDSS application, leveraging the question-and-answer guidance capabilities of ChatGPT to enhance data preprocessing and model development, thereby improving the prediction of breast cancer recurrence. MethodsThis study focused on developing an advanced machine learning model by leveraging data from the Tri-Service General Hospital breast cancer registry of 3577 patients (2004-2016). As a tertiary medical center, it accepts referrals from four branches—3 branches in the northern region and 1 branch on an offshore island in our country—that manage chronic diseases but refer complex surgical cases, including breast cancer, to the main center, enriching our study population’s diversity. Model training used patient data from 2004 to 2012, with subsequent validation using data from 2013 to 2016, ensuring comprehensive assessment and robustness of our predictive models. ChatGPT is integral to preprocessing and model development, aiding in hormone receptor categorization, age binning, and one-hot encoding. Techniques such as the synthetic minority oversampling technique address the imbalance of data sets. Various algorithms, including light gradient-boosting machine, gradient boosting, and extreme gradient boosting, were used, and their performance was evaluated using metrics such as the area under the curve, accuracy, sensitivity, and F1-score. ResultsThe light gradient-boosting machine model demonstrated superior performance, with an area under the curve of 0.80, followed closely by the gradient boosting and extreme gradient boosting models. The web interface of the AI-CDSS tool was effectively tested in clinical decision-making scenarios, proving its use in personalized treatment planning and patient involvement. ConclusionsThe AI-CDSS tool, enhanced by ChatGPT, marks a significant advancement in breast cancer recurrence prediction, offering a more individualized and accessible approach for clinicians and patients. Although promising, further validation in diverse clinical settings is recommended to confirm its efficacy and expand its use.

[ Objective ] The front piedmont belt of the northern slope of the Tianshan Mountains in Xinjiang is a crucial component of the mountain-oasis-desert ecosystem of the Tianshan northern slope. Investiga- ting the dynamic physiological adaptations of plants to drought stress and assessing methods for drought resistance , as well as selecting suitable tree species for vegetation restoration holds significant importance for the ecological restoration in this region. [ Methods ] 12 plant species planted in the piedmont belt of the northern slope of the Tianshan Mountains in Xinjiang were selected as the subjects. The study observed the spatiotemporal distribution of soil moisture following irrigation and analyzed the impact of drought stress and rewatering treatment on plant photosynthetic and physiological indicators. The drought resist- ance of these 12 species was evaluated using principal component analysis. [ Results ] ( 1 ) Following drought stress , soil moisture depletion occurred most rapidly in the 0-20 cm layer , followed by the 20- 40 cm layer , and was slowest in the 40-60 cm layer. Different plants employed different strategies to adapt their growth to drought stress. ( 2 ) Following drought stress , net photosynthetic rate ( P n ), stoma- tal conductance ( G s ), transpiration rate ( T r ), intercellular CO 2 concentration ( C i ), potential activity of PSⅡ ( F v / F o ), maximum photochemical efficiency of PSⅡ ( F v / F m ), electron transport rate ( ETR ), and chlorophyll content were decreased , while the activity of superoxide dismutase ( SOD ), proline content , malondialdehyde ( MDA ) content , and non-photochemical quenching coefficient ( q N ) were increased. Af- ter rehydration , there was a certain degree of recovery in each parameter , but none of them reached the in- itial levels. ( 3 ) The results of principal component analysis highlighted that factors like P n , chlorophyll content , ETR , and MDA content were major contributors. Species such as Haloxylon ammodendron , Tamarix chinensis , Rosa acicularis , and Caragana korshinskii demonstrated significant drought resili- ence. Hippophae rhamnoides , H . rhamnoides ‘ Xinji 5 ’, H . rhamnoides ‘ Xinji 1 ’, and Prunus sibirica showed moderate levels of drought resistance , while H . rhamnoides ‘ Xinji 4 ’, H . rhamnoides ‘ Xinji 3 ’, Xanthoceras sorbifolium , and H . rhamnoides ‘ Xinji 2 ’ exhibited relatively lower drought tolerance. [ Conclusion ] P n , chlorophyll content , ETR , and MDA content were crucial indicators for evaluating the adaptability of various plant species to drought stress. In the context of ecological restoration efforts in the piedmont belt of the Tianshan Mountains􀆴 northern slope in Xinjiang , prioritizing the cultivation of H . ammodendron , T . chinensis , R . acicularis , and C . korshinskii were recommended.

Abstract Diode effects are of great interest for both fundamental physics and modern technologies. Electrical diode effects (nonreciprocal transport) have been observed in Weyl systems. Optical diode effects arising from the Weyl fermions have been theoretically considered but not probed experimentally. Here, we report the observation of a nonlinear optical diode effect (NODE) in the magnetic Weyl semimetal CeAlSi, where the magnetization introduces a pronounced directionality in the nonlinear optical second-harmonic generation (SHG). We demonstrate a six-fold change of the measured SHG intensity between opposite propagation directions over a bandwidth exceeding 250 meV. Supported by density-functional theory, we establish the linearly dispersive bands emerging from Weyl nodes as the origin of this broadband effect. We further demonstrate current-induced magnetization switching and thus electrical control of the NODE. Our results advance ongoing research to identify novel nonlinear optical/transport phenomena in magnetic topological materials and further opens new pathways for the unidirectional manipulation of light.

Abstract Background Hearing loss has been shown to be a risk factor for psychiatric disorders. In addition, long-term hearing loss is associated with increased hospitalization and mortality rates; however, the increased risk and duration of effect of hearing loss in combination with other chronic diseases on each psychiatric disorder are still not clearly defined. The purpose of this article is to clarify the risk of hearing loss for each disorder over time. Methods This was a retrospective cohort study, and a national health insurance research database in Taiwan was utilized. All (n = 1,949,101) Taiwanese residents who had a medical visit between 2000 and 2015 were included. Patients with hearing loss and a comparative retrospective cohort were analyzed. Every subject was tracked individually from their index date to identify the subjects who later received a diagnosis of a psychiatric disorder. The Kaplan‒Meier method was used to analyze the cumulative incidence of psychiatric disorders. Cox regression analysis was performed to identify the risk of psychiatric disorders. Results A total of 13,341 (15.42%) and 31,250 (9.03%) patients with and without hearing loss, respectively, were diagnosed with psychiatric disorders (P

Abstract 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

Abstract 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

We investigated a COVID-19 cluster involved seven case-patients lived in a high-rise building in September 2021. We used a simplified tracer-gas experiment and virus sequencing to establish the link between case-patients. Vertical transmission among vertically aligned apartments on different floors in a building was the most likely route of transmission.

Abstract Materials showing second-order nonlinear transport under time reversal symmetry can be used for Radio Frequency (RF) rectification, but practical application demands room temperature operation and sensitivity to microwatts level RF signals in the ambient. In this study, we demonstrate that BiTeBr exhibits a giant nonlinear response which persists up to 350 K. Through scaling and symmetry analysis, we show that skew scattering is the dominant mechanism. Additionally, the sign of the nonlinear response can be electrically switched by tuning the Fermi energy. Theoretical analysis suggests that the large Rashba spin-orbit interactions (SOI), which gives rise to the chirality of the Bloch electrons, provide the microscopic origin of the observed nonlinear response. Our BiTeBr rectifier is capable of rectifying radiation within the frequency range of 0.2 to 6 gigahertz at room temperature, even at extremely low power levels of −15 dBm, and without the need for external biasing. Our work highlights that materials exhibiting large Rashba SOI have the potential to exhibit nonlinear responses at room temperature, making them promising candidates for harvesting high-frequency and low-power ambient electromagnetic energy.

Abstract The importance of uncommon/rare oncogenic drivers in non‐small cell lung cancer (NSCLC) was underscored during the 20th China Lung Cancer Summit. These drivers, while present in a significant proportion of NSCLC patients, remain a challenge for diagnosis and therapeutic targeting. In the never‐smokers/low smokers category with mutations such as EGFR and HER2, the efficacy of immune checkpoint inhibitors (ICIs) remains suboptimal, attributed to lower PD‐L1 expression and tumor mutation burden (TMB). However, heavy smokers, often with mutations like KRAS, may derive benefits from ICIs, as supported by trials like CheckMate‐057. With the complex landscape of these drivers and their clinical implications, the summit culminated in six pivotal consensus points, aiming to guide future research and clinical decisions. Despite the advancements, the detection, interpretation, and therapeutic strategies involving these drivers necessitate further exploration and standardization.

AbstractOver the past 50 years, 5-fluorouracil (5-FU) has played a critical role in the systemic chemotherapy of cancer patients. Bolus intravenous (IV) 5-FU infusion has been used due to the limitation of its extremely short half-life (10–15 min). This study used ultrasound (US) mediating 5-FU-loaded microbubbles (MBs) cavitation as a tool to increase local intratumoral 5-FU levels with a reduced dose of 5-FU (a single IV injection of 2.5 mg/kg instead of a single intraperitoneal injection of 25–200 mg/kg as used in previous studies in mice). The 5-FU-MBs were prepared with a 132 mg/mL albumin solution and a 0.30 mg/mL 5-FU solution. The diameters of the MBs and 5-FU-MBs were 1.24 ± 0.85 and 2.00 ± 0.53 µm (mean ± SEM), respectively, and the maximum loading efficiency of 5-FU on MBs was 19.04 ± 0.25%. In the in vitro study, the cell viabilities of 5-FU and 5-FU-MBs did not differ significantly, but compared with the 5-FU-MBs treatment-alone group, cell toxicity increased to 31% in the 5-FU-MBs + US group (p