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1.
Head Neck ; 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39318329

RESUMEN

BACKGROUND: This study evaluates the outcomes of omitting the high- and low-risk clinical tumor volume (CTV1 and CTV2) radiation in de novo metastatic nasopharyngeal carcinoma (dnm-NPC) patients in the immunotherapy era. METHODS: We retrospectively analyzed 45 consecutive dnm-NPC patients receiving chemotherapy and immunotherapy combined with radiotherapy (CIR) from October 9, 2018 to June 1, 2022. Irradiation was only delivered to the primary tumor and retropharyngeal nodes (GTVnx+rn) and gross cervical lymph nodes (GTVnd). RESULTS: The median follow-up was 45 (range, 15-67) months. There was no recurrence in the omitted elective regions. The 36-month LRRFS, PFS, and OS were 95.4%, 44.6%, and 90.8%, respectively. The main grade 3/4 hematologic toxicities were neutropenia (42.2%), anemia (20.0%), and thrombocytopenia (13.3%). The incidence of acute grade 3/4 dermatitis, mucositis, and xerostomia were 4.4%, 8.9%, and 4.4%, respectively. CONCLUSIONS: Omitting CTV1 and CTV2 was well-tolerated and provided favorable clinical outcomes in the era of immunotherapy.

2.
J Affect Disord ; 367: 632-639, 2024 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-39216647

RESUMEN

BACKGROUND: Depression is a significant global health concern, projected to become the leading disease burden. Vascular burden has been implicated in the pathogenesis of depression. Conversely, whether depression independently influences the process of vascular aging is unknown. This study aims to investigate the mutual relationship between vascular age and depression. METHODS: Utilizing data from the National Health and Nutrition Examination Survey (NHANES), the study included 27,764 participants after exclusions. Depression was assessed using the Patient Health Questionnaire (PHQ-9). Vascular aging was assessed by estimated pulse wave velocity (ePWV) and the heart age/vascular age (HVA) based on Framingham Risk Score (FRS). The study employed weighted logistic regression and Cox proportional hazards models to analyze the association between vascular age and depression as well as its mortality risk. Mendelian randomization was utilized to explore the causal associations. RESULTS: Individuals with depression exhibited a higher risk of an advanced vascular age over their chronological age. Mendelian randomization analysis indicated a causal relationship between depression and arterial stiffness. A significant association was found between vascular age and depression incidence with odds ratios ranging from 1.10 to 1.38. As vascular age increased, the risk of mortality in individuals with depression increased by 22 % and 46 %, respectively. LIMITATIONS: The study design limits the exploration of the dynamic relationship between changes in vascular age and depression due to the single timepoint measurement. CONCLUSION: This study highlights the bidirectional relationship between depression and vascular age. Vascular age is a significant biomarker for the risk and prognosis of depression, while depression may contribute to vascular aging, which underscores the importance of integrated strategies for managing both vascular health and depression.


Asunto(s)
Depresión , Análisis de la Aleatorización Mendeliana , Análisis de la Onda del Pulso , Rigidez Vascular , Humanos , Masculino , Femenino , Persona de Mediana Edad , Rigidez Vascular/fisiología , Depresión/epidemiología , Anciano , Envejecimiento/fisiología , Adulto , Factores de Riesgo , Encuestas Nutricionales , Modelos de Riesgos Proporcionales
3.
Nurse Educ Today ; 141: 106326, 2024 10.
Artículo en Inglés | MEDLINE | ID: mdl-39116472

RESUMEN

BACKGROUND: Ageism is prejudice or discrimination against different age groups, particularly older people. As senior nursing students in the last year of their studies prepare to enter the workforce, it is imperative to understand their level of ageism because of the high probability that they will care for older people during their nursing careers due to the global aging population. However, most research has focused on nursing students' knowledge and attitudes regarding older adults, and few studies have specifically investigated ageism among senior nursing students. OBJECTIVE: This study aimed to understand ageism among senior nursing students and associated factors. DESIGN: This was a cross-sectional descriptive study. SETTINGS AND PARTICIPANTS: In total, 249 senior students from 16 four-year Bachelor of Science in Nursing programs in Taiwan were recruited. Inclusion criteria were (1) a senior student enrolled in a Bachelor of Science in Nursing program and (2) the ability to read Chinese. METHODS: Data were collected using an online questionnaire consisting of two parts: demographic characteristics and the Fraboni Scale of Ageism. The frequency, percentage, mean, standard deviation, t-test, one-way analysis of variance, Pearson product-moment correlation, and multiple linear regression were used to analyze data. RESULTS: The average score for ageism among senior nursing students was 61.60 ± 7.73, out of a maximum of 116. Having a higher level of concern about ageism issues and having had grandparents who were primary caregivers during childhood were linked to a lower degree of ageism. The only predictor of senior nursing students' ageism was the extent of their concern about ageism issues (F = 18.47, p < .001). CONCLUSIONS: Senior nursing students demonstrated a moderate level of ageism. Faculty members should develop strategies to increase nursing students' awareness of ageism issues and develop appropriate interventions to prevent and improve their ageist attitudes.


Asunto(s)
Ageísmo , Bachillerato en Enfermería , Estudiantes de Enfermería , Humanos , Ageísmo/psicología , Estudios Transversales , Estudiantes de Enfermería/psicología , Estudiantes de Enfermería/estadística & datos numéricos , Masculino , Femenino , Taiwán , Encuestas y Cuestionarios , Adulto , Adulto Joven , Actitud del Personal de Salud
4.
Am J Otolaryngol ; 45(6): 104476, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39163816

RESUMEN

BACKGROUND: Precision dosing in sublingual immunotherapy (SLIT) has become a hotspot gradually, yet no standardized dose adjustment pattern for house dust mite (HDM)-SLIT. This study aims to investigate the clinical feasibility of the dynamic maintenance dose ascending regimen for individualized SLIT. METHODS: A total of 258 allergic rhinitis (AR) patients treated with HDM-SLIT were included in this retrospective study. Patients were divided into the regular dose (RD) group (n = 101) and the high dose (HD) group (n = 157) according to different maintenance dosages of SLIT. In the RD group, patients received the fixed dose recommended by the manufacturer. In the HD group, patients received a maximum tolerance dose determined by dynamic dose ascending. The clinical efficacy was evaluated by combined symptom and medication score (CSMS) and visual analogue scale score (VAS) at the baseline, 0.5-year, 1-year, and 2-year. The safety was evaluated by adverse events (AEs). RESULTS: Significant reductions of CSMS and VAS at 0.5-year, 1-year, and 2-year were observed in both the RD group and the HD group compared to the baseline (P < 0.05). In addition, greater improvements in these clinical parameters from 0.5- to 2-year were found in the HD group compared to the RD group (P < 0.05). For subgroup analysis in the HD group, no significant differences in CSMS and VAS were observed among subgroups of patients <14 years old and patients ≥14 years old (P > 0.05). No serious AEs in the two groups and no significant differences were observed between the AE incidence rate of the RD group and HD group during the incremental and maintenance phases. CONCLUSIONS: The 2-year HDM-SLIT with dynamic maintenance dose ascending regimen offers an "optimal" treatment for AR patients while maintaining safety. This study introduced a pattern for individualized dose adjustment in clinical practice, offering potential benefits for AR patients.

5.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(7): 708-715, 2024 Jul 15.
Artículo en Chino | MEDLINE | ID: mdl-39014947

RESUMEN

OBJECTIVES: To investigate the expression of CD123 in children with acute lymphoblastic leukemia (ALL) and its effect on the clinical characteristics and prognosis of children with B-lineage acute lymphoblastic leukemia (B-ALL). METHODS: A retrospective analysis was conducted on the clinical data of 251 children with ALL who were admitted to the Department of Hematology and Oncology, Children's Hospital of Kunming Medical University, from December 2019 to June 2022. According to the expression of CD123 at initial diagnosis, the children were divided into CD123+ group and CD123- group, and the two groups were compared in terms of clinical characteristics and treatment outcome. The factors influencing the prognosis were analyzed. RESULTS: Among the 251 children with ALL, there were 146 children (58.2%) in the CD123+ group. The B-ALL group had a significantly higher positive expression rate of CD123 than the acute T lymphocyte leukemia group (P<0.05). Compared with the CD123- group, the CD123+ group had significantly lower peripheral blood leukocyte count and percentage of juvenile cells and a significantly higher proportion of children with high hyperdiploid karyotype or an age of 1-10 years, with a relatively low proportion of children with E2A-PBX1 fusion gene (P<0.05). The multivariate Cox proportional-hazards regression model analysis showed that compared with the >10 years group, the 1-10 years group had a significantly higher overall survival rate (P<0.05), and compared with the high risk group, the moderate risk group had a significantly higher event-free survival rate in children with B-ALL (P<0.05). CONCLUSIONS: CD123 is widely expressed in children with B-ALL, and positive expression of CD123 might be an indicator for good prognosis in children with B-ALL, which is of great significance for evaluating the efficacy of remission induction therapy and survival prognosis of children with B-ALL.


Asunto(s)
Subunidad alfa del Receptor de Interleucina-3 , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Masculino , Femenino , Niño , Preescolar , Subunidad alfa del Receptor de Interleucina-3/análisis , Subunidad alfa del Receptor de Interleucina-3/genética , Pronóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Estudios Retrospectivos , Lactante , Adolescente
7.
Cancer Manag Res ; 16: 575-583, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38855326

RESUMEN

Background: Commonly, the thyroid gland is regarded as an organ with fewer metastatic diseases, and colorectal metastasis to the thyroid (CMT) is rarely reported, especially, with that the clinical sign of thyroid metastasis nidus is the chief complaint. The CMT occurs in advanced colorectal cancer and is associated with poor prognosis and short survival. Case Report: In this case, we reported a patient with the sign of neck mass as the first manifestation of CMT. The patient underwent a partial thyroidectomy in June 2019, immunohistochemical findings of thyroid carcinoma suggested the possibility of adenocarcinoma of gastrointestinal tract. The patient underwent a colonoscopy in July 2019 and a colonic mass was found. Pathological examination diagnosed rectal adenocarcinoma. The patient underwent neoadjuvant chemotherapy, surgical treatment, postoperative adjuvant chemotherapy and targeted therapy. The patient died in June 2022. Conclusion: The metastasis disease would not be ignored at all, when a patient complains at signs of neck mass. Further, the possibility of metastasis cancer should be considered once thyroid nodules occur in patients with colorectal cancer. Even though the biological characteristics and stage of the primary tumor have an important impact on the prognosis, positive standardized treatments can also be helpful.

8.
Front Cell Dev Biol ; 12: 1417735, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38933334

RESUMEN

Basic research on chronic rhinosinusitis (CRS) has advanced significantly in the past two decades, yet a comprehensive understanding of its pathogenic mechanisms remains elusive. Concurrently, there is a growing interest among scientists in exploring the involvement of autophagy in various human diseases, including tumors and inflammatory conditions. While the role of autophagy in asthma has been extensively studied in airway inflammatory diseases, its significance in CRS with or without nasal polyps (NPs), a condition closely linked to asthma pathophysiology, has also garnered attention, albeit with conflicting findings across studies. This review delves into the role of autophagy in CRS, suggesting that modulating autophagy to regulate inflammatory responses could potentially serve as a novel therapeutic target.

9.
Nature ; 629(8014): 1027-1033, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38811710

RESUMEN

Image sensors face substantial challenges when dealing with dynamic, diverse and unpredictable scenes in open-world applications. However, the development of image sensors towards high speed, high resolution, large dynamic range and high precision is limited by power and bandwidth. Here we present a complementary sensing paradigm inspired by the human visual system that involves parsing visual information into primitive-based representations and assembling these primitives to form two complementary vision pathways: a cognition-oriented pathway for accurate cognition and an action-oriented pathway for rapid response. To realize this paradigm, a vision chip called Tianmouc is developed, incorporating a hybrid pixel array and a parallel-and-heterogeneous readout architecture. Leveraging the characteristics of the complementary vision pathway, Tianmouc achieves high-speed sensing of up to 10,000 fps, a dynamic range of 130 dB and an advanced figure of merit in terms of spatial resolution, speed and dynamic range. Furthermore, it adaptively reduces bandwidth by 90%. We demonstrate the integration of a Tianmouc chip into an autonomous driving system, showcasing its abilities to enable accurate, fast and robust perception, even in challenging corner cases on open roads. The primitive-based complementary sensing paradigm helps in overcoming fundamental limitations in developing vision systems for diverse open-world applications.

10.
Commun Med (Lond) ; 4(1): 90, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38760506

RESUMEN

BACKGROUND: Though deep learning has consistently demonstrated advantages in the automatic interpretation of breast ultrasound images, its black-box nature hinders potential interactions with radiologists, posing obstacles for clinical deployment. METHODS: We proposed a domain knowledge-based interpretable deep learning system for improving breast cancer risk prediction via paired multimodal ultrasound images. The deep learning system was developed on 4320 multimodal breast ultrasound images of 1440 biopsy-confirmed lesions from 1348 prospectively enrolled patients across two hospitals between August 2019 and December 2022. The lesions were allocated to 70% training cohort, 10% validation cohort, and 20% test cohort based on case recruitment date. RESULTS: Here, we show that the interpretable deep learning system can predict breast cancer risk as accurately as experienced radiologists, with an area under the receiver operating characteristic curve of 0.902 (95% confidence interval = 0.882 - 0.921), sensitivity of 75.2%, and specificity of 91.8% on the test cohort. With the aid of the deep learning system, particularly its inherent explainable features, junior radiologists tend to achieve better clinical outcomes, while senior radiologists experience increased confidence levels. Multimodal ultrasound images augmented with domain knowledge-based reasoning cues enable an effective human-machine collaboration at a high level of prediction performance. CONCLUSIONS: Such a clinically applicable deep learning system may be incorporated into future breast cancer screening and support assisted or second-read workflows.


Breast cancer is one of the most common cancers, and finding it early can greatly improve patients' chances of survival and recovery. We create a tool based on artificial intelligence (AI)­whereby computer software learns to perform tasks that normally require human thinking­called MUP-Net. MUP-Net can analyze medical images to predict a patient's risk of having breast cancer. To make this AI tool usable in clinical practice, we enabled doctors to see the reasoning behind the AI's predictions by visualizing the key image features it analyzed. We showed that our AI tool not only makes doctors more confident in their diagnosis but also helps them make better decisions, especially for less experienced doctors. With further testing, our AI tool may help clinicians to diagnose breast cancer more accurately and quickly, potentially improving patient outcomes.

11.
J Antimicrob Chemother ; 79(7): 1577-1580, 2024 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-38742706

RESUMEN

BACKGROUND: The blaB, blaGOB and blaCME genes are thought to confer ß-lactam resistance to Elizabethkingia anophelis, based on experiments conducted primarily on Escherichia coli. OBJECTIVES: To determine the individual contributions of ß-lactamase genes to increased MICs in E. anophelis and to assess their impact on the in vivo efficacy of carbapenem therapy. METHODS: Scarless gene deletion of one or more ß-lactamase gene(s) was performed in three clinical E. anophelis isolates. MICs were determined by broth microdilution. Hydrolytic activity and expressions of ß-lactamase genes were measured by an enzymatic assay and quantitative RT-PCR, respectively. In vivo efficacy was determined using Galleria mellonella and murine thigh infection models. RESULTS: The presence of blaB resulted in >16-fold increases, while blaGOB caused 4-16-fold increases of carbapenem MICs. Hydrolysis of carbapenems was highest in lysates of blaB-positive strains, possibly due to the constitutionally higher expression of blaB. Imipenem was ineffective against blaB-positive isolates in vivo in terms of improvement of the survival of wax moth larvae and reduction of murine bacterial load. The deletion of blaB restored the efficacy of imipenem. The blaB gene was also responsible for a >4-fold increase of ampicillin/sulbactam and piperacillin/tazobactam MICs. The presence of blaCME, but not blaB or blaGOB, increased the MICs of ceftazidime and cefepime by 8-16- and 4-8-fold, respectively. CONCLUSIONS: The constitutionally and highly expressed blaB gene in E. anophelis was responsible for increased MICs of carbapenems and led to their poor in vivo efficacy. blaCME increased the MICs of ceftazidime and cefepime.


Asunto(s)
Antibacterianos , Infecciones por Flavobacteriaceae , Flavobacteriaceae , Pruebas de Sensibilidad Microbiana , beta-Lactamasas , beta-Lactamas , Animales , beta-Lactamasas/genética , beta-Lactamasas/metabolismo , Flavobacteriaceae/efectos de los fármacos , Flavobacteriaceae/genética , Infecciones por Flavobacteriaceae/microbiología , Infecciones por Flavobacteriaceae/tratamiento farmacológico , Antibacterianos/farmacología , Ratones , beta-Lactamas/farmacología , Modelos Animales de Enfermedad , Carbapenémicos/farmacología , Mariposas Nocturnas/microbiología , Humanos , Resistencia betalactámica/genética , Femenino
12.
Acta Pharmacol Sin ; 45(10): 2212-2225, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38760542

RESUMEN

This study aimed to analyze potential ethnic disparities in the dose-exposure-response relationships of trilaciclib, a first-in-class intravenous cyclin-dependent kinase 4/6 inhibitor for treating chemotherapy-induced myelosuppression in patients with extensive-stage small cell lung cancer (ES-SCLC). This investigation focused on characterizing these relationships in both Chinese and non-Chinese patients to further refine the dosing regimen for trilaciclib in Chinese patients with ES-SCLC. Population pharmacokinetic (PopPK) and exposure-response (E-R) analyses were conducted using pooled data from four randomized phase 2/3 trials involving Chinese and non-Chinese patients with ES-SCLC. PopPK analysis revealed that trilaciclib clearance in Chinese patients was approximately 17% higher than that in non-Chinese patients with ES-SCLC. Sex and body surface area influenced trilaciclib pharmacokinetics in both populations but did not exert a significant clinical impact. E-R analysis demonstrated that trilaciclib exposure increased with a dosage escalation from 200 to 280 mg/m2, without notable changes in myeloprotective or antitumor efficacy. However, the incidence of infusion site reactions, headaches, and phlebitis/thrombophlebitis rose with increasing trilaciclib exposure in both Chinese and non-Chinese patients with ES-SCLC. These findings suggest no substantial ethnic disparities in the dose-exposure-response relationship between Chinese and non-Chinese patients. They support the adoption of a 240-mg/m2 intravenous 3-day or 5-day dosing regimen for trilaciclib in Chinese patients with ES-SCLC.


Asunto(s)
Pueblo Asiatico , Relación Dosis-Respuesta a Droga , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/patología , Masculino , Femenino , Persona de Mediana Edad , Antineoplásicos/farmacocinética , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Antineoplásicos/efectos adversos , Anciano , Triazoles/farmacocinética , Triazoles/administración & dosificación , Triazoles/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacocinética , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Pueblos del Este de Asia , Pirimidinas , Pirroles
14.
Zhen Ci Yan Jiu ; 49(4): 403-408, 2024 Apr 25.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-38649209

RESUMEN

Under the guidance of traditional Chinese medicine theory, the clinical research of auricular acupoint stimulation in the treatment of migraine has gained a lot, and the curative efficacy is definite, but its mechanism remains unclear. In the present paper, we discussed the efficacy of auricular acupoint stimulation including "transcutaneous auricular vagus nerve stimulation" (taVNS) in the treatment of migraine in recent years. Through bibliometric analysis, we screened out top 10 auricular acupoints (Shenmenï¼»TF4ï¼½, Pizhixiaï¼»AT4ï¼½, Jiaoganï¼»AH6aï¼½, Ganï¼»CO12ï¼½, Yidanï¼»CO11ï¼½, Neifenmiï¼»CO18ï¼½, Shenï¼»CO10ï¼½, Nieï¼»AT2ï¼½, Zhenï¼»AT3ï¼½ and Eï¼»AT1ï¼½) which were the most frequently used for migraine. Majority of these auricular acupoints just distributed in the region innervated by auricular vagus nerve. Thus, we thought that the analgesic effect of needling these auricular acupoints for migraine was produced by triggering the auricular vagus nerve, and concluded that the central mechanism underlying induction of analgesic effect by activating auricular vagus nerve may be achieved by activating the descending pain regulation pathway of the locus coeruleus nucleus and dorsal raphe nucleus. In addition, taVNS-induced 1) regulation of the activities of brain's default network and pain matrix, 2) activation of the cortical descending pain regulation pathway, and 3) inhibition of the neuroinflammatory response may also contribute to its ameliorating effect of migraine. This paper may provide ideas for the future research on the mechanism of auricular acupoint treatment of migraine.


Asunto(s)
Puntos de Acupuntura , Acupuntura Auricular , Trastornos Migrañosos , Estimulación del Nervio Vago , Nervio Vago , Humanos , Trastornos Migrañosos/terapia , Trastornos Migrañosos/fisiopatología , Nervio Vago/fisiología , Animales
15.
Breast Cancer ; 31(4): 659-670, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38652345

RESUMEN

BACKGROUND: Breast cancer is a heterogeneous and complex etiological disease. Understanding perturbations of circulating metabolites could improve prognosis. METHODS: We recruited breast cancer patients from Kaohsiung Medical University (KMU) to perform untargeted (case-control design) and targeted (patient cohort) metabolomics analyses in the discovery and validation phases to evaluate interaction effects between clinical factors and plasma metabolites using multivariable Cox proportional hazards model. RESULTS: In the discovery phase, partial least squares-discriminant analysis (PLS-DA) showed that plasma metabolites were significantly different between recurrent and non-recurrent breast cancer patients. Metabolite set enrichment analysis (MSEA) and metabolomic pathway analysis (MetPA) showed that valine, leucine, and isoleucine degradation was the significant pathway, and volcano plot showed significant ten upregulated and two downregulated metabolites between recurrent and non-recurrent cases. Combined with receiver operating characteristic (ROC) curve and biological significance, creatine, valine, methionine, and mannose were selected for the validation phase. In this patient cohort with 41 new-recurrent vs. 248 non-recurrent breast cancer cases, followed for 720.49 person-years, compared with low level of valine, high valine level was significantly negatively associated with recurrent breast cancer (aHR: 0.36, 95% CI: 0.18-0.72, P = 0.004), especially in ER-negative and PR-negative status. There were interaction effects between valine and ER (Pinteraction = 0.006) as well as PR (Pinteraction = 0.002) on recurrent breast cancer. After Bonferroni correction, stratification effects between valine and hormone receptors were still significant. CONCLUSION: Our study revealed that plasma metabolites were significantly different between recurrent and non-recurrent patients, proposing therapeutic insights for breast cancer prognosis.


Asunto(s)
Biomarcadores de Tumor , Neoplasias de la Mama , Metabolómica , Recurrencia Local de Neoplasia , Humanos , Neoplasias de la Mama/sangre , Neoplasias de la Mama/patología , Femenino , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/patología , Persona de Mediana Edad , Metabolómica/métodos , Estudios de Casos y Controles , Biomarcadores de Tumor/sangre , Adulto , Receptores de Estrógenos/metabolismo , Pronóstico , Receptores de Progesterona/metabolismo , Anciano , Valina/sangre , Receptor ErbB-2/metabolismo , Receptor ErbB-2/sangre , Isoleucina/sangre , Curva ROC , Metaboloma
16.
Artículo en Inglés | MEDLINE | ID: mdl-38536699

RESUMEN

Synaptic plasticity plays a critical role in the expression power of brain neural networks. Among diverse plasticity rules, synaptic scaling presents indispensable effects on homeostasis maintenance and synaptic strength regulation. In the current modeling of brain-inspired spiking neural networks (SNN), backpropagation through time is widely adopted because it can achieve high performance using a small number of time steps. Nevertheless, the synaptic scaling mechanism has not yet been well touched. In this work, we propose an experience-dependent adaptive synaptic scaling mechanism (AS-SNN) for spiking neural networks. The learning process has two stages: First, in the forward path, adaptive short-term potentiation or depression is triggered for each synapse according to afferent stimuli intensity accumulated by presynaptic historical neural activities. Second, in the backward path, long-term consolidation is executed through gradient signals regulated by the corresponding scaling factor. This mechanism shapes the pattern selectivity of synapses and the information transfer they mediate. We theoretically prove that the proposed adaptive synaptic scaling function follows a contraction map and finally converges to an expected fixed point, in accordance with state-of-the-art results in three tasks on perturbation resistance, continual learning, and graph learning. Specifically, for the perturbation resistance and continual learning tasks, our approach improves the accuracy on the N-MNIST benchmark over the baseline by 44% and 25%, respectively. An expected firing rate callback and sparse coding can be observed in graph learning. Extensive experiments on ablation study and cost evaluation evidence the effectiveness and efficiency of our nonparametric adaptive scaling method, which demonstrates the great potential of SNN in continual learning and robust learning.

17.
Med Sci Monit ; 30: e943049, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38553816

RESUMEN

BACKGROUND Triple-negative breast cancer (TNBC) is a distinct subtype of breast cancer, accounting for 12-18% of all breast cancer cases. It exhibits high heterogeneity and aggressiveness, resulting in a poorer prognosis with a high risk of early recurrence and metastasis. Due to the lack of expression of estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2), as well as insensitivity to endocrine therapy, determining a standard treatment for TNBC is challenging. The identification of potential prognostic biomarkers is crucial for developing personalized treatment strategies for patients. MATERIAL AND METHODS Our study investigated the potential value of HSP90a in TNBC prognosis. A retrospective analysis was conducted on 127 TNBC patients and 127 Healthy controls from March 1, 2019 to July 31, 2022. Venous blood was collected and tested for HSP90alpha, CEA, CA199, and CA125, and we recorded the clinical characteristics of the patients, including age, BMI, alcohol consumption status, surgical history, CEA level, CA199 level, CA125 level, HSP90alpha level, tumor size, distant metastases, lymph node metastasis, and TNM stage. Univariate and multivariate methods were used to screen independent risk factors for progression-free survival (PFS) and overall survival (OS). RESULTS HSP90alpha is not only upregulated in TNBC but is also highly correlated with lymph node metastasis and TNM stage. The results of multivariate analysis showed that distant metastasis, TNM stage and HSP90a level were independent factors associated with PFS. BMI, tumor size, TNM stage, surgical history, and HSP90a level were independent factors influencing OS. CONCLUSIONS Our research findings demonstrate a significant association between high HSP90alpha expression and adverse clinical features, suggesting a poorer prognosis for TNBC patients.


Asunto(s)
Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Humanos , Femenino , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama/patología , Estudios Retrospectivos , Metástasis Linfática , Pronóstico , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Biomarcadores de Tumor/metabolismo
18.
Environ Res ; 249: 118468, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38354881

RESUMEN

Microorganisms have the potential to be applied for the degradation or depolymerization of polyurethane (PU) and other plastic waste, which have attracted global attention. The appropriate strain or enzyme that can effectively degrade PU is the key to treat PU plastic wastes by biological methods. Here, a polyester PU-degrading bacterium Bacillus sp. YXP1 was isolated and identified from a plastic landfill. Three PU substrates with increasing structure complexities, including Impranil DLN, poly (1,4-butylene adipate)-based PU (PBA-PU), and polyester PU foam, were used to evaluate the degradation capacity of Bacillus sp. YXP1. Under optimal conditions, strain YXP1 could completely degrade 0.5% Impranil DLN within 7 days. After 30 days, the weight loss of polyester PU foam by strain YXP1 was as high as 42.1%. In addition, PBA-PU was applied for degradation pathway analysis due to its clear composition and chemical structure. Five degradation intermediates of PBA-PU were identified, including 4,4'-methylenedianiline (MDA), 1,4-butanediol, adipic acid, and two MDA derivates, indicating that strain YXP1 could depolymerize PBA-PU by the hydrolysis of ester and urethane bonds. Furthermore, the extracellular enzymes produced by strain YXP1 could hydrolyze PBA-PU to generate MDA. Together, this study provides a potential bacterium for the biological treatment of PU plastic wastes and for the mining of functional enzymes.


Asunto(s)
Bacillus , Biodegradación Ambiental , Poliuretanos , Poliuretanos/química , Bacillus/metabolismo , Bacillus/aislamiento & purificación , Bacillus/genética , Poliésteres/metabolismo
20.
Neurochem Res ; 49(2): 441-452, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37897558

RESUMEN

Aluminum is a known neurotoxin and a major environmental contributor to neurodegenerative diseases such as Alzheimer's disease (AD). We uesd a subchronic aluminum chloride exposure model in offspring rats by continuously treating them with AlCl3 solution from the date of birth until day 90 in this research. Then evaluated the neurobehavioral changes in rats, observed the ultrastructural changes of hippocampal synapses and neurons, and examined the level of hippocampal acetylated histone H3 (H3ac), the activity and protein expression of hippocampal HAT1 and G9a, and the protein expression level of H3K9 dimethylation (H3K9me2). The findings demonstrated that aluminum-treated offspring rats had impaired learning and memory abilities as well as ultrastructural alterations in hippocampal synapses and neurons. The level of histone H3ac was decreased along with decreased protein expression and activity of HAT1, while level of H3K9me2 was increased along with increased protein expression and activity of G9a.


Asunto(s)
Aluminio , Histonas , Ratas , Animales , Histonas/metabolismo , Aluminio/toxicidad , Acetilación , N-Metiltransferasa de Histona-Lisina/metabolismo , Metilación , Hipocampo/metabolismo
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