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1.
Cell ; 185(9): 1556-1571.e18, 2022 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-35447072

RESUMO

SARS-CoV-2 Omicron is highly transmissible and has substantial resistance to neutralization following immunization with ancestral spike-matched vaccines. It is unclear whether boosting with Omicron-matched vaccines would enhance protection. Here, nonhuman primates that received mRNA-1273 at weeks 0 and 4 were boosted at week 41 with mRNA-1273 or mRNA-Omicron. Neutralizing titers against D614G were 4,760 and 270 reciprocal ID50 at week 6 (peak) and week 41 (preboost), respectively, and 320 and 110 for Omicron. 2 weeks after the boost, titers against D614G and Omicron increased to 5,360 and 2,980 for mRNA-1273 boost and 2,670 and 1,930 for mRNA-Omicron, respectively. Similar increases against BA.2 were observed. Following either boost, 70%-80% of spike-specific B cells were cross-reactive against WA1 and Omicron. Equivalent control of virus replication in lower airways was observed following Omicron challenge 1 month after either boost. These data show that mRNA-1273 and mRNA-Omicron elicit comparable immunity and protection shortly after the boost.


Assuntos
COVID-19 , SARS-CoV-2 , Vacina de mRNA-1273 contra 2019-nCoV , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Macaca , RNA Mensageiro
2.
Immunity ; 57(8): 1848-1863.e7, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-38889716

RESUMO

Expression of the transcriptional regulator ZFP318 is induced in germinal center (GC)-exiting memory B cell precursors and memory B cells (MBCs). Using a conditional ZFP318 fluorescence reporter that also enables ablation of ZFP318-expressing cells, we found that ZFP318-expressing MBCs were highly enriched with GC-derived cells. Although ZFP318-expressing MBCs constituted only a minority of the antigen-specific MBC compartment, their ablation severely impaired recall responses. Deletion of Zfp318 did not alter the magnitude of primary responses but markedly reduced MBC participation in recall. CD40 ligation promoted Zfp318 expression, whereas B cell receptor (BCR) signaling was inhibitory. Enforced ZFP318 expression enhanced recall performance of MBCs that otherwise responded poorly. ZFP318-deficient MBCs expressed less mitochondrial genes, had structurally compromised mitochondria, and were susceptible to reactivation-induced cell death. The abundance of ZFP318-expressing MBCs, instead of the number of antigen-specific MBCs, correlated with the potency of prime-boost vaccination. Therefore, ZFP318 controls the MBC recallability and represents a quality checkpoint of humoral immune memory.


Assuntos
Centro Germinativo , Memória Imunológica , Células B de Memória , Mitocôndrias , Animais , Mitocôndrias/metabolismo , Mitocôndrias/imunologia , Camundongos , Memória Imunológica/genética , Memória Imunológica/imunologia , Células B de Memória/imunologia , Células B de Memória/metabolismo , Centro Germinativo/imunologia , Receptores de Antígenos de Linfócitos B/metabolismo , Receptores de Antígenos de Linfócitos B/genética , Regulação da Expressão Gênica , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Transdução de Sinais/imunologia , Antígenos CD40/metabolismo , Antígenos CD40/genética , Antígenos CD40/imunologia , Imunidade Humoral , Transcrição Gênica , Proteínas de Membrana , Proteínas Mitocondriais
3.
Proc Natl Acad Sci U S A ; 120(27): e2218976120, 2023 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-37364092

RESUMO

By 2050, countries around the world are expected to be gradually phasing out fossil fuels and implementing greener energy technologies. In this work, we present a system employing Energy harvesting, a self-powered technology that can recycle energy from the surrounding environment. A high-efficiency radio frequency (RF) energy-harvesting chip was designed and fabricated. With an off-chip antenna and rectifier, the system scavenges ambient RF energy and converts it into usable energy, which is then stored in energy storage elements (such as a supercapacitor or a rechargeable battery). The system can further be implemented as an energy source for charging smart devices. The system-on-chip design consists of a cold start block, a boost converter with maximum power point tracking functionalities, and a charging block. The chip was fabricated using AMS 350 nm technology. Although the system was optimized for harvesting RF energy, it can be easily adapted to harvest other energy sources (i.e., mechanical and thermal energy sources). Using an optimized cold start architecture, the circuit has a cold start voltage of 380 mV. With an improved control strategy of power conversion, the system is capable of continuously charging up to 4.5 V with a broad input voltage range of 100 mV to 10 V and has a peak charging efficiency of 82%.

4.
Cereb Cortex ; 34(2)2024 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-38282453

RESUMO

Using a syntactic priming task, we investigated the time course of syntactic encoding in Chinese sentence production and compared encoding patterns between younger and older adults. Participants alternately read sentence descriptions and overtly described pictures, while event-related potentials (ERPs) were recorded. We manipulated the abstract prime structure (active or passive) as well as the lexical overlap of the prime and the target (verb overlap or no overlap). The syntactic choice results replicated classical abstract priming and lexical boost effects in both younger and older adults. However, when production latency was taken into account, the speed benefit from syntactic repetition differed between the two age groups. Meanwhile, preferred priming facilitated production in both age groups, whereas nonpreferred priming inhibited production in the older group. For electroencephalography, an earlier effect of syntactic repetition and a later effect of lexical overlap showed a two-stage pattern of syntactic encoding. Older adults also showed a more delayed and interactive encoding pattern than younger adults, indicating a greater reliance on lexical information. These results are illustrative of the two-stage competition and residual activation models.


Assuntos
Compreensão , Percepção da Fala , Humanos , Idoso , Compreensão/fisiologia , Percepção da Fala/fisiologia , Idioma , Potenciais Evocados/fisiologia , China
5.
Proteomics ; : e2400106, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39091061

RESUMO

Sequencing the tyrosine phosphoproteome using MS-based proteomics is challenging due to the low abundance of tyrosine phosphorylation in cells, a challenge compounded in scarce samples like primary cells or clinical samples. The broad-spectrum optimisation of selective triggering (BOOST) method was recently developed to increase phosphotyrosine sequencing in low protein input samples by leveraging tandem mass tags (TMT), phosphotyrosine enrichment, and a phosphotyrosine-loaded carrier channel. Here, we demonstrate the viability of BOOST in T cell receptor (TCR)-stimulated primary murine T cells by benchmarking the accuracy and precision of the BOOST method and discerning significant alterations in the phosphoproteome associated with receptor stimulation. Using 1 mg of protein input (about 20 million cells) and BOOST, we identify and precisely quantify more than 2000 unique pY sites compared to about 300 unique pY sites in non-BOOST control samples. We show that although replicate variation increases when using the BOOST method, BOOST does not jeopardise quantitative precision or the ability to determine statistical significance for peptides measured in triplicate. Many pY previously uncharacterised sites on important T cell signalling proteins are quantified using BOOST, and we identify new TCR responsive pY sites observable only with BOOST. Finally, we determine that the phase-spectrum deconvolution method on Orbitrap instruments can impair pY quantitation in BOOST experiments.

6.
Clin Infect Dis ; 78(6): 1757-1768, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38537255

RESUMO

INTRODUCTION: A surge of human influenza A(H7N9) cases began in 2016 in China from an antigenically distinct lineage. Data are needed about the safety and immunogenicity of 2013 and 2017 A(H7N9) inactivated influenza vaccines (IIVs) and the effects of AS03 adjuvant, prime-boost interval, and priming effects of 2013 and 2017 A(H7N9) IIVs. METHODS: Healthy adults (n = 180), ages 19-50 years, were enrolled into this partially blinded, randomized, multicenter phase 2 clinical trial. Participants were randomly assigned to 1 of 6 vaccination groups evaluating homologous versus heterologous prime-boost strategies with 2 different boost intervals (21 vs 120 days) and 2 dosages (3.75 or 15 µg of hemagglutinin) administered with or without AS03 adjuvant. Reactogenicity, safety, and immunogenicity measured by hemagglutination inhibition and neutralizing antibody titers were assessed. RESULTS: Two doses of A(H7N9) IIV were well tolerated, and no safety issues were identified. Although most participants had injection site and systemic reactogenicity, these symptoms were mostly mild to moderate in severity; injection site reactogenicity was greater in vaccination groups receiving adjuvant. Immune responses were greater after an adjuvanted second dose, and with a longer interval between prime and boost. The highest hemagglutination inhibition geometric mean titer (95% confidence interval) observed against the 2017 A(H7N9) strain was 133.4 (83.6-212.6) among participants who received homologous, adjuvanted 3.75 µg + AS03/2017 doses with delayed boost interval. CONCLUSIONS: Administering AS03 adjuvant with the second H7N9 IIV dose and extending the boost interval to 4 months resulted in higher peak antibody responses. These observations can broadly inform strategic approaches for pandemic preparedness. Clinical Trials Registration. NCT03589807.


Assuntos
Anticorpos Antivirais , Imunização Secundária , Subtipo H7N9 do Vírus da Influenza A , Vacinas contra Influenza , Influenza Humana , Vacinas de Produtos Inativados , Humanos , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/efeitos adversos , Adulto , Masculino , Feminino , Pessoa de Meia-Idade , Subtipo H7N9 do Vírus da Influenza A/imunologia , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/efeitos adversos , Anticorpos Antivirais/sangue , Influenza Humana/prevenção & controle , Influenza Humana/imunologia , Adulto Jovem , Esquemas de Imunização , Testes de Inibição da Hemaglutinação , Estados Unidos , Imunogenicidade da Vacina , Anticorpos Neutralizantes/sangue , Polissorbatos/administração & dosagem , Polissorbatos/efeitos adversos , alfa-Tocoferol/administração & dosagem , alfa-Tocoferol/efeitos adversos , Esqualeno/administração & dosagem , Esqualeno/efeitos adversos , Esqualeno/imunologia , Voluntários Saudáveis , Combinação de Medicamentos , Adjuvantes de Vacinas/administração & dosagem , Vacinação/métodos , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/efeitos adversos
7.
Artigo em Inglês | MEDLINE | ID: mdl-38906441

RESUMO

BACKGROUND & AIMS: Despite the poor prognosis associated with missed or delayed spontaneous bacterial peritonitis (SBP) diagnosis, <15% get timely paracentesis, which persists despite guidelines/education in the United States. Measures to exclude SBP non-invasively where timely paracentesis cannot be performed could streamline this burden. METHODS: Using Veterans Health Administration Corporate Data Warehouse (VHA-CDW) we included patients with cirrhosis between 2009 and 2019 who underwent timely paracentesis and collected relevant clinical information (demographics, cirrhosis severity, medications, vitals, and comorbidities). XGBoost-models were trained on 75% of the primary cohort, with 25% reserved for testing. The final model was further validated in 2 cohorts: Validation cohort #1: In VHA-CDW, those without prior SBP who received 2nd early paracentesis, and Validation cohort #2: Prospective data from 276 non-electively admitted University hospital patients. RESULTS: Negative predictive values (NPVs) at 5%,10%, and 15% probability cutoffs were examined. Primary cohort: n = 9643 (mean age, 63.1 ± 8.7 years; 97.2% men; SBP, 15.0%) received first early paracentesis. Testing-set NPVs for SBP were 96.5%, 93.0%, and 91.6% at the 5%, 10%, and 15% probability thresholds, respectively. In Validation cohort #1: n = 2844 (mean age, 63.14 ± 8.37 years; 97.1% male; SBP, 9.7%) with NPVs were 98.8%, 95.3%, and 94.5%. In Validation cohort #2: n = 276 (mean age, 56.08 ± 9.09; 59.6% male; SBP, 7.6%) with NPVs were 100%, 98.9%, and 98.0% The final machine learning model showed the greatest net benefit on decision-curve analyses. CONCLUSIONS: A machine learning model generated using routinely collected variables excluded SBP with high NPV. Applying this model could ease the need to provide paracentesis in resource-limited settings by excluding those unlikely to have SBP.

8.
J Virol ; 97(11): e0096323, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-37846984

RESUMO

IMPORTANCE: Currently licensed dengue vaccines do not induce long-term protection in children without previous exposure to dengue viruses in nature. These vaccines are based on selected attenuated strains of the four dengue serotypes and employed in combination for two or three consecutive doses. In our search for a better dengue vaccine candidate, live attenuated strains were followed by non-infectious virus-like particles or the plasmids that generate these particles upon injection into the body. This heterologous prime-boost immunization induced elevated levels of virus-specific antibodies and helped to prevent dengue virus infection in a high proportion of vaccinated macaques. In macaques that remained susceptible to dengue virus, distinct mechanisms were found to account for the immunization failures, providing a better understanding of vaccine actions. Additional studies in humans in the future may help to establish whether this combination approach represents a more effective means of preventing dengue by vaccination.


Assuntos
Vacinas contra Dengue , Vírus da Dengue , Dengue , Vacinas de Partículas Semelhantes a Vírus , Animais , Humanos , Anticorpos Antivirais , Vacinas contra Dengue/administração & dosagem , Macaca fascicularis , Imunização Secundária , Vacinas de Partículas Semelhantes a Vírus/administração & dosagem
9.
J Med Virol ; 96(2): e29416, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38285457

RESUMO

The raising of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants led to the use of COVID-19 bivalent vaccines, which include antigens of the wild-type (WT) virus, and of the Omicron strain. In this study, we aimed to evaluate the impact of bivalent vaccination on the neutralizing antibody (NAb) response. We enrolled 93 volunteers who had received three or four doses of monovalent vaccines based on the original virus (n = 61), or a booster shot with the bivalent vaccine (n = 32). Serum samples collected from volunteers were subjected to neutralization assays using the WT SARS-CoV-2, and Omicron subvariants. In addition, immunoinformatics to quantify and localize highly conserved NAb epitopes were performed. As main result, we observed that the neutralization titers of samples from individuals vaccinated with the bivalent vaccine were higher for the original virus, in comparison to their capacity of neutralizing the Omicron variant and its subvariants. NAb that recognize epitopes mostly conserved in the WT SARS-CoV-2 were boosted, while those that recognize epitopes mostly present in the Omicron variant, and subvariants were primed. These results indicate that formulation of future vaccines shall consider to target present viruses, and not viruses that no longer circulate.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Humanos , COVID-19/prevenção & controle , SARS-CoV-2/genética , Vacinação , Imunização Secundária , Anticorpos Neutralizantes , Epitopos/genética , Vacinas Combinadas
10.
Strahlenther Onkol ; 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39115680

RESUMO

BACKGROUND: Locally advanced recurrent rectal cancer (RRC) requires a multimodal approach. Intraoperative high-dose-rate brachytherapy (HDR-BT) may reduce the risk of local recurrence. However, the optimal therapeutic regimen remains unclear. The aim of this retrospective monocentric study was to evaluate the toxicity of HDR-BT after resection of RRC. METHODS: Between 2018 and 2022, 17 patients with RRC received resection and HDR-BT. HDR-BT was delivered alone or as an anticipated boost with a median dose of 13 Gy (range 10-13 Gy) using an 192iridium microSelectron HDR remote afterloader (Elekta AB, Stockholm, Sweden). All participants were followed for assessment of acute and late adverse events using the Common Terminology Criteria for Adverse Events version 5.0 and the modified Late Effects in Normal Tissues criteria (subjective, objective, management, and analytic; LENT-SOMA) at 3­ to 6­month intervals. RESULTS: A total of 17 patients were treated by HDR-BT with median dose of 13 Gy (range 10-13 Gy). Most patients (47%) had an RRC tumor stage of cT3­4 N0. At the time of RRC diagnosis, 7 patients (41.2%) had visceral metastases (hepatic, pulmonary, or peritoneal) in the sense of oligometastatic disease. The median interval between primary tumor resection and diagnosis of RRC was 17 months (range 1-65 months). In addition to HDR-BT, 2 patients received long-course chemoradiotherapy (CRT; up to 50.4 Gy in 1.8-Gy fractions) and 2 patients received short-course CRT up to 36 Gy in 2­Gy fractions. For concomitant CRT, all patients received 5­fluorouracil (5-FU) or capecitabine. Median follow-up was 13 months (range 1-54). The most common acute grade 1-2 toxicities were pain in 7 patients (41.2%), wound healing disorder in 3 patients (17.6%), and lymphedema in 2 patients (11.8%). Chronic toxicities were similar: grade 1-2 pain in 7 patients (41.2%), wound healing disorder in 3 patients (17.6%), and incontinence in 2 patients (11.8%). No patient experienced a grade ≥3 event. CONCLUSION: Reirradiation using HDR-BT is well tolerated with low toxicity. An individualized multimodality approach using HDR-BT in the oligometastatic setting should be evaluated in prospective multi-institutional studies.

11.
Strahlenther Onkol ; 200(4): 296-305, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37792017

RESUMO

PURPOSE: The aim of this study is to identify pre- and intraoperative factors indicating the feasibility of intraoperative radiotherapy (IORT) during breast-conserving surgery (BCS). MATERIALS AND METHODS: From January 2018 to December 2019, a total of 128 women undergoing BCS due to early breast cancer were included in this prospective observational study, independent of whether IORT was planned or not. Patient and tumor characteristics as well as surgical parameters that could potentially influence the feasibility of IORT were recorded for the entire collective. In addition, a preoperative senological assessment was performed and analyzed to assess the feasibility of IORT. Logistic regression was then used to identify relevant preoperative parameters and to generate a formula predicting the feasibility of IORT. RESULTS: Of the 128 included women undergoing BCS, 46 were preoperatively rated to be feasible, 20 to be questionably feasible for IORT. Ultimately, IORT was realized in 30 patients. The most frequent reasons for omission of IORT were insufficient tumor-to-skin distance and/or an excessively large tumor cavity. Small clinical tumor size and large tumor-to-skin distance according to preoperative ultrasound were significantly related to accomplishment of IORT. CONCLUSION: We observed that preoperative ultrasound-based tumor-skin distance is a significant factor in addition to already known parameters to predict feasibility of IORT. Based on our findings we developed a formula to optimize IORT planning which might serve as an additional tool to improve patient selection for IORT in early breast cancer.


Assuntos
Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Mastectomia Segmentar , Raios X , Estudos Prospectivos , Estudos de Viabilidade , Cuidados Intraoperatórios
12.
Strahlenther Onkol ; 200(3): 219-229, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37707518

RESUMO

BACKGROUND: A simultaneous integrated boost (SIB) may result in increased out-of-field (DOOF) and photoneutron (HPN) doses in volumetric modulated arc therapy (VMAT) for prostate cancer (PCA). This work therefore aimed to compare DOOF and HPN in flattened (FLAT) and flattening filter-free (FFF) 6­MV and 10-MV VMAT treatment plans with and without SIB. METHODS: Eight groups of 30 VMAT plans for PCA with 6 MV or 10 MV, with or without FF and with uniform (2 Gy) or SIB target dose (2.5/3.0 Gy) prescriptions (CONV, SIB), were generated. All 240 plans were delivered on a slab-phantom and compared with respect to measured DOOF and HPN in 61.8 cm distance from the isocenter. The 6­ and 10-MV flattened VMAT plans with conventional fractionation (6- and 10-MV FLAT CONV) served as standard reference groups. Doses were analyzed as a function of delivered monitor units (MU) and weighted equivalent square field size Aeq. Pearson's correlation coefficients between the presented quantities were determined. RESULTS: The SIB plans resulted in decreased HPN over an entire prostate RT treatment course (10-MV SIB vs. CONV -38.2%). Omission of the flattening filter yielded less HPN (10-MV CONV -17.2%; 10-MV SIB -22.5%). The SIB decreased DOOF likewise by 39% for all given scenarios, while the FFF mode reduced DOOF on average by 60%. A strong Pearson correlation was found between MU and HPN (r > 0.9) as well as DOOF (0.7 < r < 0.9). CONCLUSION: For a complete treatment, SIB reduces both photoneutron and OOF doses to almost the same extent as FFF deliveries. It is recommended to apply moderately hypofractionated 6­MV SIB FFF-VMAT when considering photoneutron or OOF doses.


Assuntos
Neoplasias da Próstata , Radioterapia de Intensidade Modulada , Masculino , Humanos , Radioterapia de Intensidade Modulada/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Neoplasias da Próstata/radioterapia , Fracionamento da Dose de Radiação , Próstata , Dosagem Radioterapêutica
13.
Eur J Nucl Med Mol Imaging ; 51(2): 590-603, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37747578

RESUMO

AIMS: To report long-term outcomes of relapsed prostate cancer (PC) patients treated in a prospective single-arm study with extended-nodal radiotherapy (ENRT) and [11C]-choline positron emission tomography (PET)/computed tomography (CT)-guided simultaneous integrated boost (SIB) to positive lymph nodes (LNs). METHODS: From 12/2009 to 04/2015, 60 PC patients with biochemical relapse and positive LNs only were treated in this study. ENRT at a median total dose (TD) = 51.8 Gy/28 fr and PET/CT-guided SIB to positive LNs at a median TD = 65.5 Gy was prescribed. Median PSA at relapse was 2.3 (interquartile range, IQR:1.3-4.0) ng/ml. Median number of positive LNs: 2 (range: 1-18). Androgen deprivation therapy (ADT) was prescribed for 48 patients for a median of 30.7 (IQR: 18.5-43.1) months. RESULTS: Median follow-up from the end of salvage treatment was 121.8 (IQR: 116.1, 130.9) months; 3-, 5-, and 10-year BRFS were 45.0%, 36.0%, and 24.0%, respectively; DMFS: 67.9%, 57.2%, and 45.2%; CRFS: 62.9%, 53.9%, and 42.0%; and OS: 88.2%, 76.3%, and 47.9%, respectively. Castration resistance (p < 0.0001) and ≥ 6 positive LN (p = 0.0024) significantly influenced OS at multivariate analysis. Castration resistance (p < 0.0001 for both) influenced DMFS and CRFS in multivariate analysis. CONCLUSIONS: In PC relapsed patients treated with ENRT and [11C]-choline-PET/CT-guided SIB for positive LNs, with 10-year follow-up, a median Kaplan-Meier estimate CRFS of 67 months and OS of 110 months were obtained. These highly favorable results should be confirmed in a prospective, randomized trial.


Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Humanos , Masculino , Antagonistas de Androgênios/uso terapêutico , Radioisótopos de Carbono , Colina , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/tratamento farmacológico , Tomografia por Emissão de Pósitrons , Estudos Prospectivos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/patologia , Ensaios Clínicos como Assunto
14.
BMC Cancer ; 24(1): 899, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39060968

RESUMO

BACKGROUND: This study aimed to evaluate the efficiency of hippocampal avoidance whole-brain radiotherapy with a simultaneous integrated boost (HA-WBRT-SIB) treating brain metastases (BM) and utility of the Hopkins Verbal Learning Test-Revised (HVLT-R) (Chinese version) in Chinese lung cancer patients. METHODS: Lung cancer patients with BM undergone HA-WBRT-SIB at our center were enrolled. Brain magnetic resonance imaging, The HVLT total learning score, and side effects were evaluated before radiotherapy and 1, 3, 6, and 12 months after radiotherapy. This study analyzed the overall survival rate, progression-free survival rate, and changes in HVLT-R immediate recall scores. RESULTS: Forty patients were enrolled between Jan 2016 and Jan 2020. The median follow-up time was 14.2 months. The median survival, progression-free survival, and intracranial progression-free survival of all patients were 14.8 months, 6.7 months and 14.8 months, respectively. Multivariate analysis indicated that male sex and newly diagnosed stage IV disease were associated with poor overall survival and progression-free survival, respectively. HVLT-R scores at baseline and 1, 3, and 6 months after radiotherapy were 21.94 ± 2.99, 20.88 ± 3.12, 20.03 ± 3.14, and 19.78 ± 2.98, respectively. The HVLT-R scores at 6 months after radiotherapy decreased by approximately 9.8% compared with those at baseline. No grade 3 toxicities occurred in the entire cohort. CONCLUSIONS: HA-WBRT-SIB is of efficiency and cognitive-conserving in treating Chinese lung cancer BM. TRIAL REGISTRATION: This study was retrospectively registered on ClinicalTrials.gov in 24th Feb, 2024. The ClinicalTrials.gov ID is NCT06289023.


Assuntos
Neoplasias Encefálicas , Disfunção Cognitiva , Irradiação Craniana , Hipocampo , Neoplasias Pulmonares , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patologia , Idoso , Estudos Prospectivos , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/radioterapia , Disfunção Cognitiva/etiologia , Irradiação Craniana/métodos , Irradiação Craniana/efeitos adversos , Hipocampo/patologia , Hipocampo/efeitos da radiação , Hipocampo/diagnóstico por imagem , Aprendizagem Verbal , Adulto , China , Imageamento por Ressonância Magnética
15.
World J Urol ; 42(1): 56, 2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38244059

RESUMO

PURPOSE: The FLAME trial provides strong evidence that MR-guided external beam radiation therapy (EBRT) focal boost for localized prostate cancer increases biochemical disease-free survival (bDFS) without increasing toxicity. Yet, there are many barriers to implementation of focal boost. Our objectives are to systemically review clinical outcomes for MR-guided EBRT focal boost and to consider approaches to increase implementation of this technique. METHODS: We conducted literature searches in four databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guideline. We included prospective phase II/III trials of patients with localized prostate cancer underdoing definitive EBRT with MR-guided focal boost. The outcomes of interest were bDFS and acute/late gastrointestinal and genitourinary toxicity. RESULTS: Seven studies were included. All studies had a median follow-up of greater than 4 years. There were heterogeneities in fractionation, treatment planning, and delivery. Studies demonstrated effectiveness, feasibility, and tolerability of focal boost. Based on the Phoenix criteria for biochemical recurrence, the reported 5-year biochemical recurrence-free survival rates ranged 69.7-100% across included studies. All studies reported good safety profiles. The reported ranges of acute/late grade 3 + gastrointestinal toxicities were 0%/1-10%. The reported ranges of acute/late grade 3 + genitourinary toxicities were 0-13%/0-5.6%. CONCLUSIONS: There is strong evidence that it is possible to improve oncologic outcomes without substantially increasing toxicity through MR-guided focal boost, at least in the setting of a 35-fraction radiotherapy regimen. Barriers to clinical practice implementation are addressable through additional investigation and new technologies.


Assuntos
Braquiterapia , Neoplasias da Próstata , Radioterapia de Intensidade Modulada , Masculino , Humanos , Estudos Prospectivos , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/patologia , Sistema Urogenital , Próstata/patologia , Radioterapia de Intensidade Modulada/métodos , Braquiterapia/métodos
16.
Cogn Psychol ; 148: 101616, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38016415

RESUMO

How speakers sequence words and phrases remains a central question in cognitive psychology. Here we focused on understanding the representations and processes that underlie structural priming, the speaker's tendency to repeat sentence structures encountered earlier. Verb repetition from the prime to the target led to a stronger tendency to produce locative variants of the spray-load alternation following locative primes (e.g., load the boxes into the van) than following with primes (e.g., load the van with the boxes). These structural variants had the same constituent structure, ruling out abstract syntactic structure as the source of the verb boost effect. Furthermore, using cleft constructions (e.g., What the assistant loaded into the lift was the equipment), we found that the thematic role order (thematic role-position mappings) of the prime can persist separately from its argument structure (thematic role-syntactic function mappings). Moreover, both priming effects were enhanced by verb repetition and interacted with each other when the construction of the prime was also repeated in the target. These findings are incompatible with the traditional staged model of grammatical encoding, which postulates the independence of abstract syntax from thematic role information. We propose the interactive structure-building account, according to which speakers build a sentence structure by choosing a thematic role order and argument structure interactively based on their prior co-occurrence together with other structurally relevant information such as verbs and constructions.


Assuntos
Idioma , Percepção da Fala , Humanos , Cognição
17.
Plant Cell Rep ; 43(4): 99, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38494540

RESUMO

KEY MESSAGE: In this manuscript, authors reviewed and explore the information on beneficial role of phytohormones to mitigate adverse effects of heavy metals toxicity in plants. Global farming systems are seriously threatened by heavy metals (HMs) toxicity, which can result in decreased crop yields, impaired food safety, and negative environmental effects. A rise in curiosity has been shown recently in creating sustainable methods to reduce HMs toxicity in plants and improve agricultural productivity. To accomplish this, phytohormones, which play a crucial role in controlling plant development and adaptations to stress, have emerged as intriguing possibilities. With a particular focus on environmentally friendly farming methods, the current review provides an overview of phytohormone-mediated strategies for reducing HMs toxicity in plants. Several physiological and biochemical activities, including metal uptake, translocation, detoxification, and stress tolerance, are mediated by phytohormones, such as melatonin, auxin, gibberellin, cytokinin, ethylene, abscisic acid, salicylic acid, and jasmonates. The current review offers thorough explanations of the ways in which phytohormones respond to HMs to help plants detoxify and strengthen their resilience to metal stress. It is crucial to explore the potential uses of phytohormones as long-term solutions for reducing the harmful effects of HMs in plants. These include accelerating phytoextraction, decreasing metal redistribution to edible plant portions, increasing plant tolerance to HMs by hormonal manipulation, and boosting metal sequestration in roots. These methods seek to increase plant resistance to HMs stress while supporting environmentally friendly agricultural output. In conclusion, phytohormones present potential ways to reduce the toxicity of HMs in plants, thus promoting sustainable agriculture.


Assuntos
Metais Pesados , Reguladores de Crescimento de Plantas , Ácido Abscísico , Citocininas , Giberelinas , Metais Pesados/toxicidade
18.
BMC Med Imaging ; 24(1): 193, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39080580

RESUMO

RATIONALE AND OBJECTIVE: To investigate the impact of the contrast enhancement boost (CE-boost) technique on the image quality of CT angiography (CTA) derived from 80-kVp cerebral CT perfusion (CTP) data, and to compare it with conventional CTApeak as well as other currently employed methods for enhancing CTA images, such as CTAtMIP and CTAtAve extracted from CTP. MATERIALS AND METHODS: The data of forty-seven patients who underwent CTP at 80 kVp were retrospectively collected. Four sets of images: CTApeak, CTAtMIP, CTAtAve, and CE-boost images. The CTApeak image represents the arterial phase at its peak value, captured as a single time point. CTAtMIP and CTAtAve are 4D CTA images that provide maximum density projection and average images from the three most prominent time points. CE-boost is a postprocessing technique used to enhance contrast in the arterial phase at its peak value. We compared the average CT value, standard deviation (SD), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) of the internal carotid artery (ICA) and basilar artery (BA) among the four groups. Image quality was evaluated using a 5-point scale. RESULTS: The CE-boost demonstrated and CNR in the ICA and BA (all p < 0.001). Compared with the other three CTA reconstructed images, the CE-boost images had the best subjective image quality, with the highest scores of 4.77 ± 0.43 and 4.87 ± 0.34 for each reader (all p < 0.001). CONCLUSION: Compared with other currently used techniques,CE-boost enhances the image quality of CTA derived from 80-kVp CTP data, leading to improved visualization of intracranial arteries.


Assuntos
Angiografia por Tomografia Computadorizada , Meios de Contraste , Razão Sinal-Ruído , Humanos , Angiografia por Tomografia Computadorizada/métodos , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Angiografia Cerebral/métodos , Adulto , Idoso de 80 Anos ou mais , Intensificação de Imagem Radiográfica/métodos , Artéria Carótida Interna/diagnóstico por imagem , Artéria Basilar/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos
19.
BMC Med Imaging ; 24(1): 163, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38956583

RESUMO

PURPOSE: To examine whether there is a significant difference in image quality between the deep learning reconstruction (DLR [AiCE, Advanced Intelligent Clear-IQ Engine]) and hybrid iterative reconstruction (HIR [AIDR 3D, adaptive iterative dose reduction three dimensional]) algorithms on the conventional enhanced and CE-boost (contrast-enhancement-boost) images of indirect computed tomography venography (CTV) of lower extremities. MATERIALS AND METHODS: In this retrospective study, seventy patients who underwent CTV from June 2021 to October 2022 to assess deep vein thrombosis and varicose veins were included. Unenhanced and enhanced images were reconstructed for AIDR 3D and AiCE, AIDR 3D-boost and AiCE-boost images were obtained using subtraction software. Objective and subjective image qualities were assessed, and radiation doses were recorded. RESULTS: The CT values of the inferior vena cava (IVC), femoral vein ( FV), and popliteal vein (PV) in the CE-boost images were approximately 1.3 (1.31-1.36) times higher than in those of the enhanced images. There were no significant differences in mean CT values of IVC, FV, and PV between AIDR 3D and AiCE, AIDR 3D-boost and AiCE-boost images. Noise in AiCE, AiCE-boost images was significantly lower than in AIDR 3D and AIDR 3D-boost images ( P < 0.05). The SNR (signal-to-noise ratio), CNR (contrast-to-noise ratio), and subjective scores of AiCE-boost images were the highest among 4 groups, surpassing AiCE, AIDR 3D, and AIDR 3D-boost images (all P < 0.05). CONCLUSION: In indirect CTV of the lower extremities images, DLR with the CE-boost technique could decrease the image noise and improve the CT values, SNR, CNR, and subjective image scores. AiCE-boost images received the highest subjective image quality score and were more readily accepted by radiologists.


Assuntos
Meios de Contraste , Aprendizado Profundo , Extremidade Inferior , Flebografia , Humanos , Masculino , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Extremidade Inferior/irrigação sanguínea , Extremidade Inferior/diagnóstico por imagem , Idoso , Flebografia/métodos , Adulto , Algoritmos , Trombose Venosa/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Veia Poplítea/diagnóstico por imagem , Varizes/diagnóstico por imagem , Veia Cava Inferior/diagnóstico por imagem , Veia Femoral/diagnóstico por imagem , Doses de Radiação , Angiografia por Tomografia Computadorizada/métodos , Idoso de 80 Anos ou mais , Intensificação de Imagem Radiográfica/métodos
20.
Mem Cognit ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38713453

RESUMO

The attentional boost effect (ABE) and action-induced memory enhancement (AIME) suggest that memory performance for target-paired items is superior to that for distractor-paired items when participants performed a target detection task and a memory encoding task simultaneously. Though the memory enhancement has been well established, the temporal dynamics of how the target detection task influenced memory encoding remains unclear. To investigate this, we manipulated the stimulus onset asynchrony (SOA) between detection stimuli and the words to be memorized using a remember/know study-test paradigm, and we focused primarily on memory performance for the words that appeared after the detection response. The results showed that target-paired memory enhancement was robust from SOA = 0 s to SOA = 0.75 s, but was not significant when examined by itself in Experiment 1A or weakened in Experiment 2 and the conjoint analysis when SOA = 1 s, which were only observed in R responses. The post-response memory enhancement still existed when there was no temporal overlap between the word and target, similar to the magnitude of memory enhancement observed with temporal overlap. These results supported the view that target-paired memory enhancement (recollection rather than familiarity) occurred irrespective of whether the items appeared simultaneously with the targets or within a short period after the response, and the temporal overlap of the word and target was not necessary for post-response memory enhancement.

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