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BACKGROUND: This study aimed to use artificial intelligence (AI) to integrate various radiological and clinical pathological data to identify effective predictors of contralateral cervical lymph node metastasis (CCLNM) in patients with papillary thyroid carcinoma (PTC) and to establish a clinically applicable model to guide the extent of surgery. METHODS: This prospective cohort study included 603 patients with PTC from three centers. Clinical, pathological, and ultrasonographic data were collected and utilized to develop a machine learning (ML) model for predicting CCLNM. Model development at the internal center utilized logistic regression along with other ML algorithms. Diagnostic efficacy was compared among these methods, leading to the adoption of the final model (random forest). This model was subject to AI interpretation and externally validated at other centers. RESULTS: CCLNM was associated with multiple pathological factors. The Delphian lymph node metastasis ratio, ipsilateral cervical lymph node metastasis number, and presence of ipsilateral cervical lymph node metastasis were independent risk factors for CCLNM. Following feature selection, a Delphian lymph node-CCLNM (D-CCLNM) model was established using the Random forest algorithm based on five attributes. The D-CCLNM model demonstrated the highest area under the curve (AUC; 0.9273) in the training cohort and exhibited high predictive accuracy, with AUCs of 0.8907 and 0.9247 in the external and validation cohorts, respectively. CONCLUSIONS: We developed a new, effective method that uses ML to predict CCLNM in patients with PTC. This approach integrates data from Delphian lymph nodes and clinical characteristics, offering a foundation for guiding surgical decisions, and is conveniently applicable in clinical settings.
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BACKGROUND: Systemic lupus erythematosus (SLE), an extensive autoimmune disorder, compromises viral resistance and alters immune responses post respiratory virus vaccines. This study aims to assess immune response levels and safety in SLE patients following respiratory virus vaccines. METHODS: Extensive searches, until 1 March 2024, were conducted using PubMed, EMBASE, and Cochrane Library. Outcomes, encompassing seroconversion rate (SCR), antibody and IgG titers, neutralizing antibodies, anti-spike antibodies, anti-receptor binding domain (RBD) IgG, and adverse events, were appraised. RESULTS: Sixteen articles, comprising 25 observational studies, were included. SLE patients exhibited lower SCR (OR = 0.42, 95%CI: 0.26 to 0.69), antibody titers (SMD=-2.84, 95%CI: -3.36 to -1.61), and neutralizing antibodies (OR = 0.27, 95%CI: 0.13 to 0.56) compared to the healthy population post respiratory virus vaccines. Notably, differences were statistically insignificant for anti-RBD IgG (OR = 1.75, 95%CI: 0.10 to 29.42), IgG titers (SMD=-2.54, 95%CI: -5.57 to -0.49), anti-spike antibodies (OR = 0.35, 95%CI: 0.08 to 1.53), injection site discomfort (OR = 1.03, 95%CI: 0.52 to 2.06), fatigue (OR = 1.23, 95%CI: 0.74 to 2.03), fever (OR = 1.02, 95%CI: 0.64 to 1.63), localized reactions (OR = 0.69, 95%CI: 0.37 to 1.30), systemic reactions (OR = 1.00, 95%CI: 0.59 to 1.69), allergic reactions (OR = 5.11, 95%CI: 0.24 to 107.10), self-reported vaccination-related adverse events (OR = 1.61, 95%CI: 0.56 to 4.63), and disease flares after vaccination (OR = 1.00, 95%CI: 0.14 to 7.28). CONCLUSION: Despite the reduced immune response and host protection in SLE patients post-Corona Virus Disease 2019 (COVID-19) and influenza vaccines compared to the healthy population, safety profiles are comparable. Therefore, it is recommended that SLE patients receive COVID-19 and influenza viral vaccines to fortify their resistance.
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Anticorpos Antivirais , Imunidade Humoral , Lúpus Eritematoso Sistêmico , Estudos Observacionais como Assunto , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Imunidade Humoral/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , SARS-CoV-2/imunologia , Feminino , Masculino , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/efeitos adversos , Vacinas contra Influenza/administração & dosagemRESUMO
A general and efficient method has been developed to access axially chiral 2-arylpyrroles using catalytic asymmetric Suzuki-Miyaura cross-coupling. A wide range of axially chiral arylpyrroles were obtained in high yields with good to excellent enantioselectivities. The key to success is the use of a combined catalytic system involving a palladium catalyst and chiral ferrocene diphosphine ligand for achieving effective enantiocontrol. More importantly, this axially chiral CF3-substituted 2-arylpyrrole serves as a key intermediate in the preparation of the anti-hypertensive and diabetic nephropathy drug esaxerenone. It was directly asymmetrically synthesized with high enantioselectivity (92% ee). Thus, a new strategy is provided for the catalytic asymmetric synthesis of esaxerenone.
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OBJECTIVES: The study aimed to compare the efficacy and safety of unilateral versus bilateral percutaneous kyphoplasty (PKP) in treating osteoporotic vertebral compression fractures. MATERIALS AND METHODS: Adhering to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, three English-language databases were systematically reviewed: PubMed, Web of Science, and the National Library of Medicine. The search was conducted between their inception and January 1, 2023. Studies that were replications or that used regression analysis were excluded. Randomized controlled trials and cohort studies that met the criteria were included, and a meta-analysis was performed. RESULTS: The mean follow-up duration was 17.9±9.7 months for the unilateral group and 18.4±8.3 months for the bilateral group. Eight randomized controlled trials and four cohort studies were included, comprising a total of 1,391 patients (499 males, 697 females; 195 cases did not report sex; mean age: 70.9 years; range, 45 to 82 years). Of these patients, 710 underwent the unilateral surgical approach and 681 the bilateral approach. The meta-analysis revealed that the long-term VAS was marginally higher in the unilateral PKP group (mean difference [MD]=0.09; 95% confidence interval [CI]: 0.06-0.13; p<0.001). The unilateral group also demonstrated a greater recovery rate in the postoperative kyphosis angle (MD=2.27; 95% CI: 0.67-3.87; p=0.006), shorter operation duration (MD=18.56 min; 95% CI: 8.96-28.17; p<0.001), and a lower bone cement dosage (MD=1.20 mL; 95% CI: 0.39-2.01; p=0.004). CONCLUSION: Unilateral PKP appears equally effective as bilateral PKP for treating osteoporotic vertebral compression fractures but with advantages in terms of procedure time, cement use, and pain reduction.
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Fraturas por Compressão , Cifoplastia , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Humanos , Cifoplastia/métodos , Fraturas por Compressão/cirurgia , Fraturas por Osteoporose/cirurgia , Fraturas da Coluna Vertebral/cirurgia , Resultado do Tratamento , Idoso , FemininoRESUMO
Serine protease 50 (PRSS50/TSP50) is highly expressed in spermatocytes. Our study investigated its role in testicular development and spermatogenesis. Initially, PRSS50 knockdown was observed to impair DNA synthesis in spermatocytes. To further explore this, we generated PRSS50 knockout ( Prss50 -/- ) mice ( Mus musculus), which exhibited abnormal spermatid nuclear compression and reduced male fertility. Furthermore, dysplastic seminiferous tubules and decreased sex hormones were observed in 4-week-old Prss50 -/- mice, accompanied by meiotic progression defects and increased apoptosis of spermatogenic cells. Mechanistic analysis indicated that PRSS50 deletion resulted in increased phosphorylation of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and elevated levels of MAP kinase phosphatase 3 (MKP3), a specific ERK antagonist, potentially accounting for testicular dysplasia in adolescent Prss50 -/- mice. Taken together, these findings suggest that PRSS50 plays an important role in testicular development and spermatogenesis, with the MKP3/ERK signaling pathway playing a significant role in this process.
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Sistema de Sinalização das MAP Quinases , Meiose , Camundongos Knockout , Espermatozoides , Animais , Masculino , Camundongos , Meiose/fisiologia , Espermatozoides/fisiologia , Espermatogênese/fisiologia , Fosfatase 6 de Especificidade Dupla/genética , Fosfatase 6 de Especificidade Dupla/metabolismo , Testículo/metabolismo , Serina Endopeptidases/genética , Serina Endopeptidases/metabolismoRESUMO
Two strains, designated as SYSU M80004T and SYSU M80005T, were isolated from water sampled in the Pearl River Estuary, Guangzhou, Guangdong, PR China. The strains were Gram-stain-negative and aerobic. Strain SYSU M80004T could grow at pH 6.0-8.0 (optimum, pH 7.0), 22-30 °C (optimum, 28 °C) and in the presence of 0-1â% NaCl (w/v; optimum 0â%). Strain SYSU M80005T could grow at pH 6.0-8.0 (optimum, pH 7.0), 4-37 °C (optimum, 28 °C) and in the presence of 0-1â% NaCl (w/v; optimum 0%). Both strains contained MK-6 as the predominant menaquinone. C16â:â0 and iso-C15â:â0 were identified as the major fatty acids (>10â%) of strain SYSU M80004T while strain SYSU M80005T contained iso-C15â:â0 and iso-C17â:â0 3-OH as major fatty acids. Phosphatidylethanolamine was present as the major polar lipid in both strains. The average nucleotide identity and digital DNA-DNA hybridization values between these two strains and their closest relatives were 73.5-79.3â% and 19.6-23.2â%, respectively. Phylogenetic analysis based on the 16S rRNA gene and genomic sequences indicated they belonged to the genus Flavobacterium. Therefore, on the basis of phenotypic, physiological, chemotaxonomic and genomic evidence, two novel species, Flavobacterium adhaerens sp. nov. (type strain=SYSU M80004T=CDMCC 1.4522T=KCTC 102268T) and Flavobacterium maritimum sp. nov. (type strain=SYSU M80005T=CGMCC 1.4523T= KCTC 102269T) are proposed.
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Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Estuários , Ácidos Graxos , Flavobacterium , Hibridização de Ácido Nucleico , Fosfatidiletanolaminas , Filogenia , RNA Ribossômico 16S , Rios , Análise de Sequência de DNA , Vitamina K 2 , Flavobacterium/genética , Flavobacterium/isolamento & purificação , Flavobacterium/classificação , China , RNA Ribossômico 16S/genética , Vitamina K 2/análogos & derivados , Vitamina K 2/análise , Ácidos Graxos/química , DNA Bacteriano/genética , Rios/microbiologia , Microbiologia da ÁguaRESUMO
This present study investigates emotion recognition in children and adults and its association with EQ and motor empathy. Overall, 58 children (33 5-6-year-olds, 25 7-9-year-olds) and 61 adults (24 young adults, 37 parents) participated in this study. Each participant received an EQ questionnaire and completed the dynamic emotion expression recognition task, where participants were asked to identify four basic emotions (happy, sad, fearful, and angry) from neutral to fully expressed states, and the motor empathy task, where participants' facial muscle activity was recorded. The results showed that "happy" was the easiest expression for all ages; 5- to 6-year-old children performed equally well as adults. The accuracies for "fearful," "angry," and "sad" expressions were significantly lower in children than in adults. For motor empathy, 7- to 9-year-old children exhibited the highest level of facial muscle activity, while the young adults showed the lowest engagement. Importantly, individual EQ scores positively correlated with the motor empathy index in adults but not in children. In sum, our study echoes the previous literature, showing that the identification of negative emotions is still difficult for children aged 5-9 but that this improves in late childhood. Our results also suggest that stronger facial mimicry responses are positively related to a higher level of empathy in adults.
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Emoções , Empatia , Expressão Facial , Humanos , Empatia/fisiologia , Criança , Emoções/fisiologia , Masculino , Feminino , Adulto , Pré-Escolar , Adulto Jovem , Músculos Faciais/fisiologiaRESUMO
OBJECTIVE: The current guidelines and canonical norms of diagnosis or treatment for Post-traumatic stress disorder (PTSD) with sleep disorder are still conflicting and have not yet reached a consensus. This study aimed to unravel the most effective countermeasures between two categories (psychotherapy and pharmacotherapy) put forward by the National Institute for Health and Clinical Excellence (NICE) and World Federation of Societies of Biological Psychiatry (WFSBP) respectively to treat PTSD individuals co-exist with sleep disorders. METHODS: Four databases, including PubMed, EMBASE, Cochrane Library, and APA PsyNet, were searched from inception to February 02, 2023. RESULTS: Twenty articles with 24 Randomized controlled trials (RCTs) and a total number of 1,647 participants were included. As demonstrated in the network meta-analysis comparison results, CBT-I (standardized mean differences (SMD) = -1.51,95% confidence interval (CI):-2.55 to -0.47), CBT-I plus IRT (SMD = -1.71, 95%CI:-3.39, -0.03), prazosin (SMD = -0.87,95%CI:-1.59 to -0.16) and hydroxyzine (SMD = -1.06, 95%CI: -1.94 to -0.19) significantly reduced PTSD symptoms compared with placebo. In contrast to placebo, CBT-I (SMD = -5.61,95%CI:-8.82 to -2.40) significantly improved sleep quality. For nightmare severity, IRT (SMD =-0.65, 95%CI:-1.00 to -0.31), prazosin (SMD = -1.20,95%CI:-1.72 to -0.67) and hydroxyzine (SMD = -0.98,95%CI:-1.58 to -0.37) significantly reduced nightmare severity in comparison with placebo. CONCLUSIONS: This study suggested that under most circumstances, psychotherapy namely CBT-I had a favorable profile, but pharmacotherapy with prazosin was effective in managing nightmare severity. The sole avail of CBT-I was recommended to improving sleep quality while CBT-I and CBT-I plus IRT showed excellent management of PTSD symptom severity. Exposure to CBT-I isrecommended for depression. The relevant clinical guidelines for the management of individuals with PTSD and sleep disorders may regard this as a reference. PROSPERO: CRD42023415240.
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Metanálise em Rede , Prazosina , Ensaios Clínicos Controlados Aleatórios como Assunto , Transtornos do Sono-Vigília , Transtornos de Estresse Pós-Traumáticos , Humanos , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Transtornos de Estresse Pós-Traumáticos/terapia , Prazosina/uso terapêutico , Transtornos do Sono-Vigília/tratamento farmacológico , Transtornos do Sono-Vigília/terapia , Terapia Cognitivo-Comportamental/métodos , Psicoterapia/métodos , Resultado do Tratamento , Masculino , Feminino , Adulto , Dessensibilização e Reprocessamento através dos Movimentos Oculares/métodos , Hidroxizina/uso terapêuticoRESUMO
Background: Patients with resectable esophageal squamous cell carcinoma (ESCC) receiving neoadjuvant immunotherapy (NIT) display variable treatment responses. The purpose of this study is to establish and validate a radiomics based on enhanced computed tomography (CT) and combined with clinical data to predict the major pathological response to NIT in ESCC patients. Methods: This retrospective study included 82 ESCC patients who were randomly divided into the training group (n = 57) and the validation group (n = 25). Radiomic features were derived from the tumor region in enhanced CT images obtained before treatment. After feature reduction and screening, radiomics was established. Logistic regression analysis was conducted to select clinical variables. The predictive model integrating radiomics and clinical data was constructed and presented as a nomogram. Area under curve (AUC) was applied to evaluate the predictive ability of the models, and decision curve analysis (DCA) and calibration curves were performed to test the application of the models. Results: One clinical data (radiotherapy) and 10 radiomic features were identified and applied for the predictive model. The radiomics integrated with clinical data could achieve excellent predictive performance, with AUC values of 0.93 (95% CI 0.87-0.99) and 0.85 (95% CI 0.69-1.00) in the training group and the validation group, respectively. DCA and calibration curves demonstrated a good clinical feasibility and utility of this model. Conclusion: Enhanced CT image-based radiomics could predict the response of ESCC patients to NIT with high accuracy and robustness. The developed predictive model offers a valuable tool for assessing treatment efficacy prior to initiating therapy, thus providing individualized treatment regimens for patients.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Imunoterapia , Aprendizado de Máquina , Terapia Neoadjuvante , Tomografia Computadorizada por Raios X , Humanos , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/diagnóstico por imagem , Masculino , Feminino , Terapia Neoadjuvante/métodos , Tomografia Computadorizada por Raios X/métodos , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/diagnóstico por imagem , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Imunoterapia/métodos , Nomogramas , Resultado do Tratamento , Adulto , RadiômicaRESUMO
Metastatic tumours in the brain now represent one of the leading causes of death from cancer. Current treatments are largely ineffective owing to the combination of late diagnosis and poor delivery of therapies across the blood-brain barrier (BBB). Conjugating magnetic resonance imaging (MRI) contrast agents with a monoclonal antibody for VCAM-1 (anti-VCAM1) has been shown to enable detection of micrometastases, two to three orders of magnitude smaller in volume than those currently detectable clinically. The aim of this study was to exploit this targeting approach to enable localised and temporary BBB opening at the site of early-stage metastases using functionalised microbubbles and ultrasound. Methods: Microbubbles functionalised with anti-VCAM1 were synthesised and shown to bind to VCAM-1-expressing cells in vitro. Experiments were then conducted in vivo in a unilateral breast cancer brain metastasis mouse model using Gadolinium-DTPA (Gd-DTPA) enhanced MRI to detect BBB opening. Following injection of Gd-DTPA and targeted microbubbles, the whole brain volume was simultaneously exposed to ultrasound (0.5 MHz, 10% duty cycle, 0.7 MPa peak negative pressure, 2 min treatment time). T1-weighted MRI was then performed to identify BBB opening, followed by histological confirmation via immunoglobulin G (IgG) immunohistochemistry. Results: In mice treated with targeted microbubbles and ultrasound, statistically significantly greater extravasation of Gd-DTPA and IgG was observed in the left tumour-bearing hemisphere compared to the right hemisphere 5 min after treatment. No acute adverse effects were observed. There was no investigation of longer term bioeffects owing to the nature of the study. Conclusion: The results demonstrate the feasibility of using targeted microbubbles in combination with low intensity ultrasound to localise opening of the BBB to metastatic sites in the brain. This approach has potential application in the treatment of metastatic tumours whose location cannot be established a priori with conventional imaging methods.
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Barreira Hematoencefálica , Neoplasias Encefálicas , Imageamento por Ressonância Magnética , Microbolhas , Molécula 1 de Adesão de Célula Vascular , Animais , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/diagnóstico por imagem , Camundongos , Neoplasias Encefálicas/diagnóstico por imagem , Molécula 1 de Adesão de Célula Vascular/metabolismo , Imageamento por Ressonância Magnética/métodos , Meios de Contraste , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Feminino , Modelos Animais de Doenças , Ultrassonografia/métodos , Linhagem Celular Tumoral , Gadolínio DTPA/administração & dosagem , Humanos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismoRESUMO
BACKGROUND: Effective mentorship is an important component of medical education with benefits to all stakeholders. In recent years, conceptualization of mentorship has gone beyond the traditional dyadic experienced mentor-novice mentee relationship to include group and peer mentoring. Existing theories of mentorship do not recognize mentoring's personalized, evolving, goal-driven, and context-specific nature. Evidencing the limitations of traditional cause-and-effect concepts, the purpose of this review was to systematically search the literature to determine if mentoring can be viewed as a complex adaptive system (CAS). METHODS: A systematic scoping review using Krishna's Systematic Evidence-Based Approach was employed to study medical student and resident accounts of mentoring and CAS in general internal medicine and related subspecialties in articles published between 1 January 2000 and 31 December 2023 in PubMed, Embase, PsycINFO, ERIC, Google Scholar, and Scopus databases. The included articles underwent thematic and content analysis, with the themes identified and combined to create domains, which framed the discussion. RESULTS: Of 5,704 abstracts reviewed, 134 full-text articles were evaluated, and 216 articles were included. The domains described how mentoring relationships and mentoring approaches embody characteristics of CAS and that mentorship often behaves as a community of practice (CoP). Mentoring's CAS-like features are displayed through CoPs, with distinct boundaries, a spiral mentoring trajectory, and longitudinal mentoring support and assessment processes. CONCLUSION: Recognizing mentorship as a CAS demands the rethinking of the design, support, assessment, and oversight of mentorship and the role of mentors. Further study is required to better assess the mentoring process and to provide optimal training and support to mentors.
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Educação Médica , Tutoria , Humanos , Mentores , Estudantes de Medicina/psicologia , Internato e ResidênciaRESUMO
Background: Extramammary Paget's disease (EMPD) is a rare epithelial malignancy, and approximately 30%-40% of EMPD patients overexpress human epidermal growth factor receptor 2 (Her-2). Currently, there are no established standard treatments for advanced EMPD while anti-Her-2 therapy is recommended for Her-2-positive cases. Case presentation: Here, we report a 51-year-old male diagnosed with advanced Her-2-positive EMPD, presenting with numerous lymph node metastases. This patient received disitamab vedotin (an antibody-drug conjugate, targeting Her-2) combined with serplulimab as first-line treatment. After seven cycles of combination therapy, the patient tolerated the treatment well and the lymph node lesions continued to shrink. However, the patient developed immunotherapy-related pneumonia following the eighth treatment. Hormone therapy was administered while all the anti-tumor therapies were halted. After the pneumonia improved, the patient underwent positron emission tomography-computed tomography, revealing a complete response to his tumor. To consolidate the effect, he received another five cycles of disitamab vedotin monotherapy as maintenance therapy, without experiencing any adverse events. To date, the patient has remained in good health without any recurrence 10 months after drug discontinuance. Conclusion: Disitamab vedotin combined with immunotherapy demonstrated a long-term clinical benefit in advanced Her-2-positive EMPD. For rare solid tumors with Her-2 overexpression, disitamab vedotin combined with immunotherapy might offer a viable therapeutic choice.
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Doença de Paget Extramamária , Receptor ErbB-2 , Humanos , Masculino , Pessoa de Meia-Idade , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Doença de Paget Extramamária/tratamento farmacológico , Doença de Paget Extramamária/terapia , Escroto/patologia , Resultado do Tratamento , Imunoterapia/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Imunoconjugados/uso terapêuticoRESUMO
Background: The use of immunotherapy is progressively expanding for the treatment of lung cancer, either alone or in combination with radiotherapy. However, treatment-related adverse events, especially pneumonia, significantly limit the drug's effectiveness in treating lung cancer. The occurrence of lung cancer, immunotherapy, and pulmonary radiotherapy can all contribute to the imbalance in the pulmonary microbiota, rendering the lungs more susceptible to inflammatory reactions. Methods: Mouse models of lung transplantation tumor were treated with either PD-1 monoclonal antibody or radiotherapy alone, or in combination. The differences in lung inflammation among the different treatment groups were regularly observed by micro-CT. Further, bronchoalveolar lavage fluid was extracted for macrogenomic and cytokine detection. The transcriptional genome of tumor-filled lung tissue was also sequenced. Results: When treated with a combination of PD-1 and radiotherapy, the CT scans showed more severe pulmonary inflammation. However, with the addition of continuously administered antibiotics, no exacerbation of pneumonia signs was observed. Moreover, the differential gene expression and cytokine profiles in the combination treatment group differed from those in the PD-1 monotherapy group and the radiotherapy monotherapy group. This discrepancy does not seem to be a straightforward superimposition of radiation-induced pneumonia and immune-related pneumonia. Further exploration of changes in pulmonary microbiota revealed specific bacterial interactions with DEGs and cytokines. Conclusions: The underlying causes of this susceptibility are intricate and may be associated with the complexity of pulmonary microbiota imbalance, along with fluctuations in the abundance of specific microbiota species.
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Plants have evolved diverse defense mechanisms encompassing physical and chemical barriers. Cotton pigment glands are known for containing various defense metabolites, but the precise regulation of gland size to modulate defense compound levels remains enigmatic. Here, it is discovered that the VQ domain-containing protein JAVL negatively regulates pigment gland size and the biosynthesis of defense compounds, while the MYC2-like transcription factor GoPGF has the opposite effect. Notably, GoPGF directly activates the expression of JAVL, whereas JAVL suppresses GoPGF transcription, establishing a negative feedback loop that maintains the expression homeostasis between GoPGF and JAVL. Furthermore, it is observed that JAVL negatively regulates jasmonate levels by inhibiting the expression of jasmonate biosynthetic genes and interacting with GoPGF to attenuate its activation effects, thereby maintaining homeostatic regulation of jasmonate levels. The increased expression ratio of GoPGF to JAVL leads to enlarged pigment glands and elevated jasmonates and defense compounds, enhancing insect and pathogen resistance in cotton. These findings unveil a new mechanism for regulating gland size and secondary metabolites biosynthesis, providing innovative strategies for strengthening plant defense.
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Ciclopentanos , Regulação da Expressão Gênica de Plantas , Gossypium , Oxilipinas , Fitoalexinas , Sesquiterpenos , Gossypium/genética , Gossypium/metabolismo , Oxilipinas/metabolismo , Ciclopentanos/metabolismo , Sesquiterpenos/metabolismo , Retroalimentação Fisiológica , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genéticaRESUMO
Two lanthanide complexes with formulae [DyIII(LN5)(pentafluoro-PhO)3] (1) and [DyIII(LN5)(2,6-difluoro-PhO)2](BPh4) (2) (LN5 = 2,14-dimethyl-3,6,10,13,19-pentaazabicyclo[13.3.1]nonadecal (19),2,13,15,17-pentaene) were structurally and magnetically characterized. DyIII ions lie in the cavity of a five coordinate nitrogen macrocycle, and in combination with the introduction of multi-fluorinated monodentate phenoxyl coligands a high axiality coordination symmetry is built. Using the pentafluorophenol co-ligand, complex 1 with a D2d coordination environment, is obtained and displays moderate single-molecule magnets (SMMs) behavior. When difluorophenol co-ligands were used, a higher local axisymmetric pentagonal bipyramidal coordination geometry was observed in complex 2, which displays apparent slow magnetic relaxation behavior with a hysteresis temperature of up to 5 K. Further magnetic studies of diluted samples combined with ab initio calculations indicate that the high axiality plays a crucial role in suppressing quantum tunneling of magnetization (QTM) and consequently results in good slow magnetic relaxation behavior. Different fluoro-substituted phenoxyl co-ligands have phenoloxy oxygen atoms with different electrostatic potentials as well as a different number of phenoloxy coligands along the magnetic axis, resulting in different ligand field strengths and coordination symmetries.
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Our objective is to investigate a cost-effective approach to screen for NTRK fusion in the major subtypes of non-small cell lung cancer (NSCLC). Evaluate the concordance between immunohistochemistry (IHC) and next-generation sequencing (NGS), as well as between fluorescence in situ hybridization (FISH) and NGS, to detect any discrepancies in methodological consistency between lung adenocarcinoma (LADC) and lung squamous cell carcinoma (LSCC). Analyze the factors influencing IHC results. A cohort of 1654 patients with NSCLC underwent screening for NTRK fusion using whole slide IHC. The positive cases were analyzed by both FISH and NGS. Totally, 57 tested positive for pan-TRK, with positivity rates of 0.68% (10/1467) for LADC and 29.01% (47/162) for LSCC. FISH showed separate NTRK1 and NTRK3 rearrangements in two pan-TRK-positive LADCs, while all LSCCs tested negative. NGS confirmed functional NTRK fusion in two FISH-positive cases: one involving TPM3-NTRK1 and the other involving SQSTM1-NTRK3. A non-functional fusion of NTRK2-XRCC1 was detected in LSCC, while FISH was negative. According to our approach, the prevalence of NTRK fusion in NSCLC is 0.12%. The concordance rate between IHC and RNA-based NGS was 20% (2/10) in LADC and 0% (0/162) in LSCC. When the positive criteria increased over 50% of tumor cells showing strong staining, the concordance would be 100% (2/2). A concordance rate of 100% (2/2) was observed between FISH and RNA-based NGS in LADC. The expression of pan-TRK was significantly correlated with the tumor proportion score (TPS) of PD-L1 (p < 0.05) and transcript per million (TPM) values of NTRK2 (p < 0.05). We recommend using IHC with strict criteria to screen NTRK fusion in LADC rather than LSCC, confirmed by RNA-based NGS directly. When the NGS results are inconclusive, FISH validation is necessary.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Estudos de Viabilidade , Sequenciamento de Nucleotídeos em Larga Escala , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Neoplasias Pulmonares , Receptor trkA , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Receptor trkA/genética , Idoso , Proteínas de Fusão Oncogênica/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Receptor trkC/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Adulto , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Reprodutibilidade dos TestesRESUMO
Lake eutrophication caused by nitrogen and phosphorus has led to frequent harmful algal blooms (HABs), especially under the unknown challenges of climate change, which have seriously damaged human life and property. In this study, a coupled SWAT-Bayesian Network (SWAT-BN) model framework was constructed to elucidate the mechanisms between non-point source nitrogen pollution in agricultural lake watersheds and algal activities. A typical agricultural shallow lake basin, the Taihu Basin (TB), China, was chosen in this study, aiming to investigate the effectiveness of best management practices (BMPs) in controlling HABs risks in TB. By modeling total nitrogen concentration of Taihu Lake from 2007 to 2022 with four BMPs (filter strips, grassed waterway, fertilizer application reduction and no-till agriculture), the results indicated that fertilizer application reduction proved to be the most effective BMP with 0.130 of Harmful Algal Blooms Probability Reduction (HABs-PR) when reducing 40% of fertilizer, followed by filter strips with 0.01 of HABs-PR when 4815ha of filter strips were conducted, while grassed waterway and no-till agriculture showed no significant effect on preventing HABs. Furthermore, the combined practice between 40% fertilizer application reduction and 4815ha filter strips construction showed synergistic effects with HABs-PR increasing to 0.171. Precipitation and temperature data were distorted to model scenarios of extreme events. As a result, the combined approach outperformed any single BMP in terms of robustness under extreme climates. This research provides a watershed-level perspective on HABs risks mitigation and highlights the strategies to address HABs under the influence of climate change.
Assuntos
Agricultura , Teorema de Bayes , Proliferação Nociva de Algas , Lagos , Agricultura/métodos , Fertilizantes/análise , Nitrogênio/análise , China , Mudança Climática , Fósforo/análise , Eutrofização , Modelos TeóricosRESUMO
BACKGROUND: Myopia affects 1.4 billion individuals worldwide. Notably, there is increasing evidence that choroidal thickness plays an important role in myopia and risk of developing myopia-related conditions. With the advancements in artificial intelligence (AI), choroidal thickness segmentation can now be automated, offering inherent advantages such as better repeatability, reduced grader variability, and less reliance for manpower. Hence, we aimed to evaluate the agreement between AI-automated and manual segmented measurements of subfoveal choroidal thickness (SFCT) using two swept-source optical coherence tomography (OCT) systems. METHODS: Subjects aged ≥ 16 years, with myopia of ≥ 0.50 diopters in both eyes, were recruited from the Prospective Myopia Cohort Study in Singapore (PROMYSE). OCT scans were acquired using Triton DRI-OCT and PLEX Elite 9000. OCT images were segmented both automatically with an established SA-Net architecture and manually using a standard technique with adjudication by two independent graders. SFCT was subsequently determined based on the segmentation. The Bland-Altman plot and intraclass correlation coefficient (ICC) were used to evaluate the agreement. RESULTS: A total of 229 subjects (456 eyes) with mean [± standard deviation (SD)] age of 34.1 (10.4) years were included. The overall SFCT (mean ± SD) based on manual segmentation was 216.9 ± 82.7 µm with Triton DRI-OCT and 239.3 ± 84.3 µm with PLEX Elite 9000. ICC values demonstrated excellent agreement between AI-automated and manual segmented SFCT measurements (PLEX Elite 9000: ICC = 0.937, 95% CI: 0.922 to 0.949, P < 0.001; Triton DRI-OCT: ICC = 0.887, 95% CI: 0.608 to 0.950, P < 0.001). For PLEX Elite 9000, manual segmented measurements were generally thicker when compared to AI-automated segmented measurements, with a fixed bias of 6.3 µm (95% CI: 3.8 to 8.9, P < 0.001) and proportional bias of 0.120 (P < 0.001). On the other hand, manual segmented measurements were comparatively thinner than AI-automated segmented measurements for Triton DRI-OCT, with a fixed bias of - 26.7 µm (95% CI: - 29.7 to - 23.7, P < 0.001) and proportional bias of - 0.090 (P < 0.001). CONCLUSION: We observed an excellent agreement in choroidal segmentation measurements when comparing manual with AI-automated techniques, using images from two SS-OCT systems. Given its edge over manual segmentation, automated segmentation may potentially emerge as the primary method of choroidal thickness measurement in the future.
RESUMO
Background: With increasing gaps between the rich and poor, potential risk factors for class conflict have attracted increasing attention from researchers. Although cognitive factors are known to be significant predictors of class-conflict behavior, limited attention has been paid to competence stereotypes of the upper class. When considering economic inequality, people pay more attention to competence stereotypes of the upper class, which may have adverse effects. This study aimed to investigate the relationship between competence stereotypes held by the lower class about the upper class and class conflict, and to test the mediating role of intergroup envy in this relationship and the moderating role of upward social mobility belief. Methods: Data were collected from a convenience sample from a comprehensive university in China. Based on scores on subjective and objective class scales, 284 lower-class college students (103 males and 181 females) aged 18-24 were selected to participate (both their subjective and objective scores were lower than 3 points). Their endorsement of upper-class competence stereotypes, intergroup envy, upward social mobility beliefs, and class conflict were measured using a well-validated self-report questionnaire. Results: The main data were analyzed using correlation analysis, the SPSS macro PROCESS (Model 7), and simple slope analysis. The results show a significant positive correlation between competence stereotypes held by lower-class college students toward the higher class and class conflict, and this connection was mediated by intergroup envy. Moreover, the indirect effect of intergroup envy on this link was moderated by upward social mobility beliefs; this effect was stronger for college students with lower upward social mobility beliefs. Conclusion: This study broadens our understanding of how and when competence stereotypes among the lower class concerning the upper class are related to class conflict. Researchers and policymakers should pay special attention to competence stereotypes of the upper class, especially intergroup envy and class conflict among lower-class individuals with lower levels of upward social mobility beliefs.
RESUMO
Diabetes has become one of the most common endocrine and metabolic diseases threatening human health, which can induce mitochondrial dysfunction and exacerbate the excessive production of reactive oxygen species (ROS). Among them, ONOO- level fluctuation was closely related to diabetes. Hence, it is of great significance to develop a near-infrared fluorescence probe for visualizing ONOO- level fluctuations in diabetes. In this paper, we constructed a fluorescence probe YBL with dicyano-isophorone derivative as fluorophore and diphenyl phosphate as ONOO- response site, which can detect ONOO- with the low detection limit (39.8 nM) and exhibit excellent selectivity and sensitivity. The probe YBL has been applied to monitor intracellular ONOO- level fluctuations. Meanwhile, the image results showed that high sugar promoted the increase of ONOO- level in cells. More important, the probe YBL can be used for imaging in mice, and the results showed that content of ONOO- was increased in diabetic mice. Therefore, the probe YBL provided a tool for understanding diabetes progression by imaging ONOO-.