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PURPOSE: For tonsillar cancer with multiple ipsilateral neck lymph nodes, the safety and efficacy of unilateral radiotherapy (RT) have long been a topic of debate. We performed retrospective analyses of patients having ipsilateral neck lymph nodes treated with unilateral RT in two tertiary referral hospitals. MATERIALS AND METHODS: This study accrued 29 patients who were diagnosed as well-lateralized tonsillar cancer with multiple ipsilateral neck lymph nodes and underwent unilateral RT from March 2000 to March 2020. Patients underwent treatment with one of the following options or a combination of them: induction chemotherapy, surgery, RT, and concurrent chemoradiotherapy. We analyzed the recurrence pattern and survival with special attention to contralateral neck failure. Also, treatment-related toxicities were compared with a 1:1 matched cohort of those who received bilateral RT, using propensity score matching analysis. RESULTS: At a median follow-up of 68 months, no contralateral neck failure was observed. Five-year actuarial locoregional recurrence-free survival, distant metastasis-free survival, and overall survival were 85.6%, 91.8%, and 92.7%, respectively. Both the acute and chronic grade 2 xerostomia occurred in 10.3% of the patients. When the toxicity for unilateral RT was compared to that of bilateral RT using a propensity score-matched cohort, a significantly lower rate of acute xerostomia was observed in unilateral RT group (55.1% vs. 82.7%, p=0.002), primarily at grade 2 level (10.3% vs. 51.7%, respectively). CONCLUSION: The results of our study suggest that unilateral RT can be safely performed in well-lateralized tonsillar cancer patients with multiple ipsilateral neck lymph nodes.

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Few predictive biomarkers exist for identifying patients who may benefit from neoadjuvant therapy (NAT). The intratumoral microbial composition is comprehensively profiled to predict the efficacy and prognosis of patients with esophageal squamous cell carcinoma (ESCC) who underwent NAT and curative esophagectomy. Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis is conducted to screen for the most closely related microbiota and develop a microbiota-based risk prediction (MRP) model on the genera of TM7x, Sphingobacterium, and Prevotella. The predictive accuracy and prognostic value of the MRP model across multiple centers are validated. The MRP model demonstrates good predictive accuracy for therapeutic responses in the training, validation, and independent validation sets. The MRP model also predicts disease-free survival (p = 0.00074 in the internal validation set and p = 0.0017 in the independent validation set) and overall survival (p = 0.00023 in the internal validation set and p = 0.11 in the independent validation set) of patients. The MRP-plus model basing on MRP, tumor stage, and tumor size can also predict the patients who can benefit from NAT. In conclusion, the developed MRP and MRP-plus models may function as promising biomarkers and prognostic indicators accessible at the time of diagnosis.

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We report on the efficient generation of intense terahertz radiation from the organic crystal N-benzyl-2-methyl-4-nitroaniline pumped by chirped Ti:sapphire femtosecond laser pulses. The THz energy and spectrum as a function of the pump fluence and duration of the chirped laser pulses are studied systematically. For the appropriate positively chirped pump pulses, a significant boost in the THz generation efficiency by a factor of around 2.5 is achieved, and the enhancement of high-frequency components (>1 THz) shortens the THz pulse duration. Via complete characterization of THz properties and transmitted laser spectra, this nonlinear behavior is attributed to the extended effective interaction length for phase matching as a result of the self-phase modulation of the intense pump laser pulses. Numerical calculations well reproduce the experimental observation. Our results demonstrate a robust, efficient, strong-field (up to several MV/cm) THz source using the common sub-10 mJ and sub-100 fs Ti:sapphire laser systems without optical parametric amplifiers.

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OBJECTIVE: Previous studies have suggested that irritable bowel syndrome (IBS) is strongly associated with psychiatric disorders. However, it is unclear whether this association is causal, concomitant, or accidental. Thus, we performed Mendelian randomization (MR) analysis to evaluate the causal effects of several psychiatric disorders on IBS. METHODS: Summary data of genome-wide association studies (GWASs) were obtained mainly from the Psychiatric Genomics Consortium (PGC) on individuals of European ancestry and from a recent GWAS on IBS. We used three MR methods, the inverse-variance weighting (IVW), weighted median (WM), and MR-Egger regression (MR-Egger). In addition, two other indicators, namely, the MR-IVW Cochran's Q statistic and MR-Egger intercept, were used to assess heterogeneity and detect directional horizontal pleiotropy, respectively. RESULTS: Heritability was high for bipolar disorder (81.18 %, 95 % CI = 73.18-148.18 %), schizophrenia (33.88 %, 95 % CI = 33.57-38.19 %), and panic disorder (30.66 %, 95 % CI = 20.74-40.58 %). For other disorders, there was a low liability-scale SNP heritability for major depressive disorder (MDD) (0.67 %, 95 % CI = 0.61-0.73 %), anxiety disorder (7.63 %, 95 % CI = 1.67-13.59 %), PTSD (0.96 %, 95 % CI = 0.12-1.8 %), and IBS (2.44 %, 95 % CI = 2.13-2.75 %). We also observed that schizophrenia had a significant causal effect on IBS according to MR-IVW. Notably, the individual causal estimates of genetic instruments for MDD and schizophrenia were heterogeneous, but no pleiotropic effects were observed. CONCLUSIONS: Our analyses revealed the causal effects of MDD and schizophrenia on IBS, a matter that has been subject to debate for decades, and also showed that IBS had causal effects on MDD.

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The eyes are one of the most important sensory organs in the human body. Currently, diseases such as limbal stem cell deficiency, cataract, retinitis pigmentosa and dry eye seriously threaten the quality of people's lives, and the treatment of advanced blinding eye disease and dry eye is ineffective and costly. Thus, new treatment modalities are urgently needed to improve patients' symptoms and suffering. In recent years, stem cell-derived three-dimensional structural organoids have been shown to mimic specific structures and functions similar to those of organs in the human body. Currently, 3D culture systems are used to construct organoids for different ocular growth and development models and ocular disease models to explore their physiological and pathological mechanisms. Eye organoids can also be used as a platform for drug screening. This paper reviews the latest research progress in regard to eye organoids (the cornea, lens, retina, lacrimal gland, and conjunctiva).

Assuntos

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Apoptotic proteins play a crucial role in the apoptosis process, ensuring a balance between cell proliferation and death. Thus, further elucidating the regulatory mechanisms of apoptosis will enhance our understanding of their functions. However, the development of computational methods to accurately identify positive and negative regulation of apoptosis remains a significant challenge. This work proposes a machine learning model based on multi-feature fusion to effectively identify the roles of positive and negative regulation of apoptosis. Initially, we constructed a reliable benchmark dataset containing 200 positive regulation of apoptosis and 241 negative regulation of apoptosis proteins. Subsequently, we developed a classifier that combines the support vector machine (SVM) with pseudo composition of k-spaced amino acid pairs (PseCKSAAP), composition transition distribution (CTD), dipeptide deviation from expected mean (DDE), and PSSM-composition to identify these proteins. Analysis of variance (ANOVA) was employed to select optimized features that could yield the maximum prediction performance. Evaluating the proposed model on independent data revealed and achieved an accuracy of 0.781 with an AUROC of 0.837, demonstrating our model's potent capabilities.

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Background: Genicular nerve radiofrequency ablation (GNRFA) is a popular and effective procedure to treat arthritic knee pain. For refractory arthritic pain that fails conservative treatment, total knee arthroplasty (TKA) has been an excellent option. Unfortunately, 15-30% of people who undergo a TKA continue to experience pain and stiffness in the knee. The treatment options for post-TKA knee pain are limited. Pain providers have been trialing GNRFA on this pain condition. However, convincing evidence of its efficacy in treating post-TKA pain is still lacking. Methods: This is a retrospective study of 73 patients who had undergone genicular nerve RFA, 46 (63.01%) with osteoarthritic pain, and 27 (36.99%) with post-TKA pain. We compared the outcomes (pain relief, function, and complications) between these two groups at 3 months and 6 months after RFA. Results: Before RFA, there was no significant difference in initial pain and functional level between these two groups. After RFA, the two groups had comparable pain relief at 3 months (p = 0.68) and 6 months (p = 0.53), and similar functionality at 3 months (p = 0.36) and 6 months (p = 0.65).The overall success rate (≥50% pain relief after RFA) was 80.82%, 95% CI: 70.34%-88.22% (osteoarthritic group 80.43%, 95% CI: 66.83%-89.35%, post-TKA 81.48%, 95% CI: 63.30%-91.82%, P = 0.91) at 3-month follow-up and 56.16%, 95% CI: 44.76%-66.95% (osteoarthritic group 56.52%, 95% CI: 42.25%-69.79%, post-TKA 55.56%, 95% CI: 37.31%-72.41%, P = 0.94) at 6-month follow-up.There were no reported complications in either group. Conclusions: Genicular Nerve Radiofrequency Ablation (GNRFA) holds the potential to be equally effective for both post-TKA knee pain and osteoarthritic knee pain.

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BACKGROUND: This study evaluates functional larynx preservation in patients with hypopharyngeal cancer (HPC) and laryngeal cancer (LC) who achieved complete remission following radiotherapy (RT) or concurrent chemoradiation (CCRT). METHODS: HPC and LC patients treated with RT/CCRT from 1999 to 2017 were retrospectively analyzed. Severe late dysphagia and tracheostomy cases were assessed to determine laryngeal function. Long-term preservation rate of functional larynx and associated factors were evaluated. RESULTS: Of 152 patients (55 HPC, 97 LC), nine developed severe dysphagia, occurring on average 58.2 months post-treatment. HPC and cervical node metastasis significantly increased the risk of laryngeal function impairment (p < 0.001 and p = 0.014, respectively), presenting a continued decline in functional larynx preservation rate beyond 10 years. CONCLUSIONS: Patients with HPC and cervical node metastasis demonstrate an increased risk for long-term laryngeal function impairment despite successful oncologic outcomes. This risk extends beyond 10 years, underscoring the need for prolonged monitoring and comprehensive support.

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Burkitt lymphoma is a highly aggressive B-cell lymphoma and the fastest proliferating human malignant tumor. If the disease is found in the early stage, the patient could have a high possibility to be cured successfully, whereas the prognosis is poor in the late stage. Burkitt lymphoma can occur in children and adults, and it is categorized as local (Africa), sporadic, and immunodeficiency associated type. Sporadic Burkitt lymphoma mainly affects children and adolescents, and the most common initial sites are abdominal organs and lymph nodes. Sporadic Burkitt lymphoma manifested by initial oral and maxillofacial lesions is relatively rare. Here, a case of pediatric sporadic Burkitt lymphoma, with oral and maxillofacial lesions as the first symptoms, was reported. The patient was treated in the Department of Periodontology, Shandong University School and Hospital of Stomatology. After timely checkup was provided, the patient was transferred to another hospital and had good results. In this article, an incidence of Burkitt lymphoma, with oral and maxillofacial lesions as the first symptom, was reviewed to provide reference for oral clinicians to achieve early diagnosis and treatment of patients with Burkitt lymphoma with oral diseases and improve the success rate of treatment.

Assuntos

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BACKGROUND: Recent studies have shown an association between trace elements and systemic lupus erythematosus (SLE), but the relationship between trace elements and SLE is still unclear. This study aims to determine the distribution of plasma trace elements in newly diagnosed SLE patients and the association between these essential and toxic element mixtures and SLE. METHODS: In total, 110 SLE patients and 110 healthy controls were included. Blood samples were collected. 15 plasma trace elements were quantified using an inductively coupled plasma mass spectrometer (ICP-MS). Multivariate logistic regression, restricted cubic spline (RCS), weighted quantile sum (WQS) regression, quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR) are used to analyze the association between single and mixed exposure of elements and SLE. RESULTS: The logistic regression model shows that, plasma lithium (Li) [OR (95 % CI): 1.963 (1.49-2.586)], vanadium (V) [OR (95 % CI): 2.617(1.645-4.166)] and lead (Pb) [OR (95 % CI): 1.603(1.197-2.145)] were positively correlated with SLE, while selenium (Se) [OR (95 % CI): 0.055(0.019-0.157)] and barium (Ba) [OR (95 % CI): 0.792(0.656-0.957)] had been identified as protective factors for SLE. RCS results showed a non-linear correlation between the elements Li, V, Ni, copper, Se, rubidium and SLE. In addition, WQS regression, qgcomp, and BKMR models consistently revealed significant positive effects of plasma Li and Pb on SLE, as well as significant negative effects of plasma Se. CONCLUSIONS: Exposure to heavy metals such as Li and Pb is significantly positively correlated with SLE, but Se may be protective factors for SLE. In addition, there is a nonlinear correlation between the elements Li and Se and SLE, and there are complex interactions between the elements. In the future, larger populations and prospective studies are needed to confirm these associations.

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BACKGROUND: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with unclear etiology. Growing evidence suggests the microbiome plays a role in SLE pathogenesis. However, findings are inconsistent across studies due to factors like small sample sizes and geographical variations. A comprehensive meta-analysis is needed to elucidate microbiome alterations in SLE. OBJECTIVE: This study aimed to provide a systematic overview of microbiota dysbiosis across body sites in SLE through a meta-analysis of alpha diversity indices, beta diversity indices, and abundance taxa of microbiome. METHODS: A literature search was conducted across four databases to identify relevant studies comparing SLE patients and healthy controls. Extracted data encompassed alpha and beta diversity metrics, as well as bacterial, fungal, and viral abundance across gut, oral, skin, and other microbiota. Study quality was assessed using the Newcastle-Ottawa Scale. Standardized mean differences and pooled effect sizes were calculated through meta-analytical methods. RESULTS: The analysis showed reduced alpha diversity and distinct beta diversity in SLE, particularly in the gut microbiota. Taxonomic analysis revealed compositional variations in bacteria from the gut and oral cavity. However, results for fungi, viruses, and bacteria from other sites were inconsistent due to limited studies. CONCLUSIONS: This meta-analysis offers a comprehensive perspective on microbiome dysbiosis in SLE patients across diverse body sites and taxa. The observed variations underscore the microbiome's potential role in SLE pathogenesis. Future research should address geographical variations, employ longitudinal designs, and integrate multi-omics approaches.

Assuntos

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BACKGROUND: This study aimed to investigate the feasibility and efficacy of near-infrared fluorescence-guided laparoscopic anatomical hepatectomy (LAH) using a novel indocyanine green (ICG)-human serum albumin complex (HSA) in patients with hepatocellular carcinoma. METHODS: Clinical data of hepatocellular carcinoma patients who underwent ICG-HSA fluorescence-guided LAH at our center from January 2024 to April 2024 were prospectively collected and analyzed. Ultraviolet absorption spectroscopy was used to test the absorption and stability of ICG-HSA complex solutions under different conditions. After determining the optimal ratio, the complex was administered intravenously during surgery to perform negative staining via Glissonean pedicle isolation. LAH was performed along the fluorescence-demarcated boundaries. RESULTS: Thirty-one patients were included (24 men; mean age, 54.61 ± 13.54 years). The median maximum tumor diameter was 2.80 (interquartile range [IQR], 2.00-4.00) cm. S8 segmentectomy (22.6%) and right posterior segmentectomy (19.4%) were the most common resections performed. Successful fluorescence negative staining was achieved in all patients using ICG and HSA at a 1:6 molar ratio at room temperature. Mean operation time was 297.58 ± 85.53 min, Median intraoperative blood loss was 100.0 mL (IQR, 50.0-200.0). The median surgical margin distance was 0.90 cm (IQR, 0.40-1.50). The postoperative complication rate was 45.2% (35.5% Clavien-Dindo grade I and 9.7% grade II). The median length of hospital stay was 5.0 days (IQR, 4.0-5.0). CONCLUSION: ICG-HSA-assisted LAH is safe and feasible. Compared with free ICG, the novel ICG-HSA complex exhibits better optical properties and in vivo stability, which can improve the accuracy of intraoperative liver segment localization and optimize the anatomical dissection plane. It has the potential to become an ideal fluorescent imaging agent for anatomical hepatectomy.

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BACKGROUND: Adolescent-specific ADHD self-report screening measures can greatly increase the likelihood of correct diagnosis and timely treatment of ADHD in adolescents. This study provides preliminary evidence for evaluating the reliability and validity of the Adult ADHD Self-Report Scale-Revised (ASRS-R) in a school-based sample of Chinese adolescents. METHODS: The ASRS-R and the Strengths and Difficulties Questionnaire (SDQ) were administered to 867 adolescents aged 12 to 16 years (Mage = 13.08 years). Construct validity was assessed using correlation analysis of the ASRS-R with the SDQ. Moreover, confirmatory factor analysis (CFA), internal consistency, retest reliability, and measurement invariance of the scales were examined by gender. RESULTS: CFA showed a two-dimensional factor structure of the ASRS-R, and the model fitted the data well (χ2/df = 4.370, RMSEA = 0.062, TLI = 0.932, CFI = 0.940, GFI = 0.927, AGFI = 0.907, and SRMR = 0.038). The ASRS-R scale was invariant across gender and had satisfactory internal consistency (Cronbach's alpha = .934) and test-retest reliability (intraclass correlation coefficient = .874). The construct validity, as calculated using the SDQ, was also acceptable. CONCLUSION: The ASRS-R can be a psychometrically reliable self-report instrument and provide preliminary support as a simple tool for identifying ADHD symptoms in Chinese adolescents. The findings provide evidence for extending the application of the ASRS, previously limited to adults, to the adolescent populations.

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Amomum villosum Lour. (A. villosum) is the original plant of the medicinal and culinary spice Amomi Fructus (Sharen) and is an important economic crop in the Lingnan region of China. During the cultivation and production of A. villosum, prolonged reliance on single asexual reproduction has exacerbated the degradation of its varieties, leading to inconsistent yields and quality. Building upon earlier cultivar selection efforts, this study provides a comprehensive evaluation of two newly bred A. villosum varieties (A11 and A12) from perspectives including plant traits, product characteristics, active ingredients, and multi-omics analysis. It was found that A12 plants display enhanced robustness, more aromatic fruits, higher yields, and elevated levels of bornyl acetate, A11 shows the advantage of a high camphor content, and the different metabolites and differentially expressed genes of the two varieties were significantly enriched in multiple metabolic pathways. Additionally, A12 contained more terpenoids and substances with aromatic odors such as sweet, fruity, floral, and green. Furthermore, a key gene (Wv_032842) regulating the acetylation of bornyl was discovered, and its significantly higher expression, in A12. In conclusion, this study has a guiding significance for the evaluation of germplasm resources and the breeding of excellent varieties of A. villosum.

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Euphorbia dentata Michx. is an invasive plant species in China, known for its toxicity and potential to reduce crop yields, posing numerous threats. To gain a deeper understanding of this invasive plant, phytochemical methods were employed to isolate 13 terpenoids (1-11, 19, 20) and 7 sterols (12-18) from the ethanol extract of E. dentata, identifying one new compound and 19 known compounds. Within spectroscopic methods such as NMR, HR-ESI-MS, and ECD, the structures and absolute configurations of these compounds were established. Among them, dentatacid A (11) possesses an unprecedented 2, 3-seco-arbor-2, 3-dioic skeleton within the potential biosynthetic pathway proposed. Dentatacid A also exhibited excellent anti-proliferative activity against the HT-29 (human colorectal adenocarcinoma) cell line, with an IC50 value of 2.64 ± 0.78 µM, which was further confirmed through network pharmacology and molecular docking. This study significantly expands the chemical diversity of E. dentata and offers new insights into the resource utilization and management of this invasive plant from the perspective of natural product discovery.

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TiAl alloys possess excellent properties, such as low density, high specific strength, high elastic modulus, and high-temperature creep resistance, which allows their use to replace Ni-based superalloys in some high-temperature applications. In this work, the traditional TiAl alloy Ti-48Al-2Nb-2Cr (Ti4822) was alloyed with additional Nb and fabricated using laser metal deposition (LMD), and the impacts of this additional Nb on the microstructure and mechanical and tribological properties of the as-fabricated alloys were investigated. The resulting alloys mainly consisted of the γ phase, trace ß0 and α2 phases. Nb was well distributed throughout the alloys, while Cr segregation resulted in the residual ß0 phase. Increasing the amount of Nb content increased the amount of the γ phase and reduced the amount of the ß0 phase. The alloy Ti4822-2Nb exhibited a room-temperature (RT) fracture strength under a tensile of 568 ± 7.8 MPa, which was nearly 100 MPa higher than that of the Ti4822-1Nb alloy. A further increase in Nb to an additional 4 at.% Nb had little effect on the fracture strength. Both the friction coefficient and the wear rate increased with the increasing Nb content. The wear mechanisms for all samples were abrasive wear with local plastic deformation and oxidative wear, resulting in the formation of metal oxide particles.

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d-Limonene is the predominant component of essential oil from Exocarpium Citri Grandis, known for its antibacterial, antioxidant, insecticidal, and anti-inflammatory properties. The synthesis, transport, and accumulation of d-limonene in Citrus grandis 'Tomentosa' fruits are regulated by limonene synthase (LS) and its associated regulatory genes. This study addresses the gap in understanding the spatiotemporal cytological changes of LS and its regulatory genes. Through cytochemical techniques, we investigated the distribution of essential oil in the plastids, endoplasmic reticulum, and vacuoles of secretory cavity cells. We identified the LS-encoding gene CgLS via transcriptomics and demonstrated in vitro that CgLS catalyzes the formation of d-limonene from geranyl diphosphate (GPP). Transient overexpression of CgLS increased monoterpene limonene accumulation, while TRV virus-induced gene silencing reduced it. CgLS expression levels and d-limonene content showed spatiotemporal consistency with fruit development, with in situ hybridization revealing predominant expression in secretory cavity cells. Immunocytochemical localization indicated that CgLS is primarily located in the endoplasmic reticulum, plastids, and vacuoles. Our findings suggest that CgLS is translated in the endoplasmic reticulum and transported to plastids and vacuoles where d-limonene synthesis occurs. This study provides comprehensive insights into the characteristics of CgLS and its role in d-limonene synthesis at the tissue, cellular, and molecular levels in C. grandis 'Tomentosa'.

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Rifampicin, essential for long-term tuberculosis treatment, requires rigorous control of non-therapeutic impurities due to their potential adverse, including mutagenic effects. Reports on control strategies for genotoxic impurities in rifampicin have been limited. This study introduced an analytical method to identify potential genotoxic impurities from the synthesis of raw materials. The structure of the 25-deacetyl-23-acetyl-rifampicin genotoxic impurity was confirmed using nuclear magnetic resonance, high-resolution mass spectrometry (HRMS), and high-performance liquid chromatography (HPLC). An HPLC-HRMS method was established and validated for detecting another genotoxic impurity, 1-amino-4-methylpiperazine, adhering to the International Council on Harmonization guidelines, which include specificity, linearity, detection and quantification limits, accuracy, precision, and robustness. These developments improve the quality control strategy for genotoxic impurities in rifampicin, ensuring product safety.