Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 491
Filtrar
Mais filtros

Base de dados
Tipo de documento
Intervalo de ano de publicação
1.
Nature ; 630(8016): 457-465, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38750365

RESUMO

Adoptively transferred T cells and agents designed to block the CD47-SIRPα axis are promising cancer therapeutics that activate distinct arms of the immune system1,2. Here we administered anti-CD47 antibodies in combination with adoptively transferred T cells with the goal of enhancing antitumour efficacy but observed abrogated therapeutic benefit due to rapid macrophage-mediated clearance of T cells expressing chimeric antigen receptors (CARs) or engineered T cell receptors. Anti-CD47-antibody-mediated CAR T cell clearance was potent and rapid enough to serve as an effective safety switch. To overcome this challenge, we engineered the CD47 variant CD47(Q31P) (47E), which engages SIRPα and provides a 'don't eat me' signal that is not blocked by anti-CD47 antibodies. TCR or CAR T cells expressing 47E are resistant to clearance by macrophages after treatment with anti-CD47 antibodies, and mediate substantial, sustained macrophage recruitment to the tumour microenvironment. Although many of the recruited macrophages manifested an M2-like profile3, the combined therapy synergistically enhanced antitumour efficacy. Our study identifies macrophages as major regulators of T cell persistence and illustrates the fundamental challenge of combining T-cell-directed therapeutics with those designed to activate macrophages. It delivers a therapeutic approach that is capable of simultaneously harnessing the antitumour effects of T cells and macrophages, offering enhanced potency against solid tumours.


Assuntos
Antígeno CD47 , Imunoterapia Adotiva , Neoplasias , Linfócitos T , Animais , Feminino , Humanos , Masculino , Camundongos , Antígenos de Diferenciação/imunologia , Antígenos de Diferenciação/metabolismo , Antígeno CD47/genética , Antígeno CD47/imunologia , Antígeno CD47/metabolismo , Linhagem Celular Tumoral , Imunoterapia Adotiva/métodos , Macrófagos/citologia , Macrófagos/imunologia , Neoplasias/imunologia , Neoplasias/metabolismo , Neoplasias/terapia , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/metabolismo , Receptores Imunológicos/imunologia , Receptores Imunológicos/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Linfócitos T/transplante , Microambiente Tumoral/imunologia , Anticorpos/imunologia , Anticorpos/uso terapêutico , Ativação de Macrófagos
2.
Lancet ; 402(10404): 786-797, 2023 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-37478886

RESUMO

BACKGROUND: Hearing loss is associated with increased cognitive decline and incident dementia in older adults. We aimed to investigate whether a hearing intervention could reduce cognitive decline in cognitively healthy older adults with hearing loss. METHODS: The ACHIEVE study is a multicentre, parallel-group, unmasked, randomised controlled trial of adults aged 70-84 years with untreated hearing loss and without substantial cognitive impairment that took place at four community study sites across the USA. Participants were recruited from two study populations at each site: (1) older adults participating in a long-standing observational study of cardiovascular health (Atherosclerosis Risk in Communities [ARIC] study), and (2) healthy de novo community volunteers. Participants were randomly assigned (1:1) to a hearing intervention (audiological counselling and provision of hearing aids) or a control intervention of health education (individual sessions with a health educator covering topics on chronic disease prevention) and followed up every 6 months. The primary endpoint was 3-year change in a global cognition standardised factor score from a comprehensive neurocognitive battery. Analysis was by intention to treat. This trial was registered at ClinicalTrials.gov, NCT03243422. FINDINGS: From Nov 9, 2017, to Oct 25, 2019, we screened 3004 participants for eligibility and randomly assigned 977 (32·5%; 238 [24%] from ARIC and 739 [76%] de novo). We randomly assigned 490 (50%) to the hearing intervention and 487 (50%) to the health education control. The cohort had a mean age of 76·8 years (SD 4·0), 523 (54%) were female, 454 (46%) were male, and most were White (n=858 [88%]). Participants from ARIC were older, had more risk factors for cognitive decline, and had lower baseline cognitive scores than those in the de novo cohort. In the primary analysis combining the ARIC and de novo cohorts, 3-year cognitive change (in SD units) was not significantly different between the hearing intervention and health education control groups (-0·200 [95% CI -0·256 to -0·144] in the hearing intervention group and -0·202 [-0·258 to -0·145] in the control group; difference 0·002 [-0·077 to 0·081]; p=0·96). However, a prespecified sensitivity analysis showed a significant difference in the effect of the hearing intervention on 3-year cognitive change between the ARIC and de novo cohorts (pinteraction=0·010). Other prespecified sensitivity analyses that varied analytical parameters used in the total cohort did not change the observed results. No significant adverse events attributed to the study were reported with either the hearing intervention or health education control. INTERPRETATION: The hearing intervention did not reduce 3-year cognitive decline in the primary analysis of the total cohort. However, a prespecified sensitivity analysis showed that the effect differed between the two study populations that comprised the cohort. These findings suggest that a hearing intervention might reduce cognitive change over 3 years in populations of older adults at increased risk for cognitive decline but not in populations at decreased risk for cognitive decline. FUNDING: US National Institutes of Health.


Assuntos
Aterosclerose , Disfunção Cognitiva , Perda Auditiva , Humanos , Masculino , Feminino , Idoso , Disfunção Cognitiva/prevenção & controle , Cognição , Perda Auditiva/prevenção & controle , Audição , Educação em Saúde
3.
Eur Radiol ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38625612

RESUMO

OBJECTIVE: To compare the diagnostic performance of [68Ga]DOTATATE PET/CT, [18F]FDG PET/CT, MRI of the spine, and whole-body CT and MRI for the detection of pheochromocytoma/paraganglioma (PPGL)-related spinal bone metastases. MATERIALS AND METHODS: Between 2014 and 2020, PPGL participants with spinal bone metastases prospectively underwent [68Ga]DOTATATE PET/CT, [18F]FDG PET/CT, MRI of the cervical-thoracolumbar spine (MRIspine), contrast-enhanced MRI of the neck and thoraco-abdominopelvic regions (MRIWB), and contrast-enhanced CT of the neck and thoraco-abdominopelvic regions (CTWB). Per-patient and per-lesion detection rates were calculated. Counting of spinal bone metastases was limited to a maximum of one lesion per vertebrae. A composite of all functional and anatomic imaging served as an imaging comparator. The McNemar test compared detection rates between the scans. Two-sided p values were reported. RESULTS: Forty-three consecutive participants (mean age, 41.7 ± 15.7 years; females, 22) with MRIspine were included who also underwent [68Ga]DOTATATE PET/CT (n = 43), [18F]FDG PET/CT (n = 43), MRIWB (n = 24), and CTWB (n = 33). Forty-one of 43 participants were positive for spinal bone metastases, with 382 lesions on the imaging comparator. [68Ga]DOTATATE PET/CT demonstrated a per-lesion detection rate of 377/382 (98.7%) which was superior compared to [18F]FDG (72.0%, 275/382, p < 0.001), MRIspine (80.6%, 308/382, p < 0.001), MRIWB (55.3%, 136/246, p < 0.001), and CTWB (44.8%, 132/295, p < 0.001). The per-patient detection rate of [68Ga]DOTATATE PET/CT was 41/41 (100%) which was higher compared to [18F]FDG PET/CT (90.2%, 37/41, p = 0.13), MRIspine (97.6%, 40/41, p = 1.00), MRIWB (95.7%, 22/23, p = 1.00), and CTWB (81.8%, 27/33, p = 0.03). CONCLUSIONS: [68Ga]DOTATATE PET/CT should be the modality of choice in PPGL-related spinal bone metastases due to its superior detection rate. CLINICAL RELEVANCE STATEMENT: In a prospective study of 43 pheochromocytoma/paraganglioma participants with spinal bone metastases, [68Ga]DOTATATE PET/CT had a superior per-lesion detection rate of 98.7% (377/382), compared to [18F]FDG PET/CT (p < 0.001), MRI of the spine (p < 0.001), whole-body CT (p < 0.001), and whole-body MRI (p < 0.001). KEY POINTS: • Data regarding head-to-head comparison between functional and anatomic imaging modalities to detect spinal bone metastases in pheochromocytoma/paraganglioma are limited. • [68Ga]DOTATATE PET/CT had a superior per-lesion detection rate of 98.7% in the detection of spinal bone metastases associated with pheochromocytoma/paraganglioma compared to other imaging modalities: [18]F-FDG PET/CT, MRI of the spine, whole-body CT, and whole-body MRI. • [68Ga]DOTATATE PET/CT should be the modality of choice in the evaluation of spinal bone metastases associated with pheochromocytoma/paraganglioma.

4.
Neurourol Urodyn ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38623999

RESUMO

Surgical approaches for pelvic organ prolapse have evolved over the last 30 years and is a popular topic for debate, particularly when discussing apical prolapse. Transvaginal native tissue repairs remain the mainstay of POP surgeries, however, transabdominal approaches continue to evolve. Use of interposition material, such as synthetic polypropylene mesh, is the standard when performing an abdominal sacrocolpopexy, however, use of autologous fascia can be considered. This debate article provides an overview of this subject and highlights the value of different approaches to apical prolapse. The authors were asked to support their approach in various scenarios including:extremes of age, prior hysterectomy and intact uterus, desire to avoid mesh, sexual activity, and presence of comorbidities. In discussing common patient scenarios, ultimate decision making on specific POP surgeries is determined by patient preference and goals.

5.
J Pediatr Hematol Oncol ; 46(5): 262-271, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38857189

RESUMO

Precision oncology incorporates comprehensive genomic profiling into the individualized clinical care of pediatric cancer patients. In recent years, comprehensive pan-cancer analyses have led to the successful implementation of genomics-based pediatric trials and accelerated approval of novel targeted agents. In addition, disease-specific studies have resulted in molecular subclassification of myriad cancer types with subsequent tailoring of treatment intensity based on the patient's prognostic factors. This review discusses the progress of the field and highlights developments that are leading to more personalized cancer care and improved patient outcomes. Increased understanding of the evolution of precision oncology over recent decades emphasizes the tremendous impact of improved genomic applications. New technologies and improved diagnostic modalities offer further promise for future advancements within the field.


Assuntos
Oncologia , Neoplasias , Medicina de Precisão , Humanos , Medicina de Precisão/métodos , Neoplasias/genética , Neoplasias/terapia , Neoplasias/diagnóstico , Criança , Oncologia/métodos , Oncologia/tendências , Genômica/métodos
6.
Alzheimers Dement ; 20(4): 2653-2661, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38375574

RESUMO

INTRODUCTION: Age-related sensory and motor impairment are associated with risk of dementia. No study has examined the joint associations of multiple sensory and motor measures on prevalence of early cognitive impairment (ECI). METHODS: Six hundred fifty participants in the Baltimore Longitudinal Study of Aging completed sensory and motor function tests. The association between sensory and motor function and ECI was examined using structural equation modeling with three latent factors corresponding to multisensory, fine motor, and gross motor function. RESULTS: The multisensory, fine, and gross motor factors were all correlated (r = 0.74 to 0.81). The odds of ECI were lower for each additional unit improvement in the multisensory (32%), fine motor (30%), and gross motor factors (12%). DISCUSSION: The relationship between sensory and motor impairment and emerging cognitive impairment may guide future intervention studies aimed at preventing and/or treating ECI. HIGHLIGHTS: Sensorimotor function and early cognitive impairment (ECI) prevalence were assessed via structural equation modeling. The degree of fine and gross motor function is associated with indicators of ECI. The degree of multisensory impairment is also associated with indicators of ECI.


Assuntos
Disfunção Cognitiva , Humanos , Estudos Longitudinais , Disfunção Cognitiva/epidemiologia , Envelhecimento , Baltimore
7.
Alzheimers Dement ; 20(3): 1671-1681, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38081140

RESUMO

INTRODUCTION: Many neurocognitive evaluations involve auditory stimuli, yet there are no standard testing guidelines for individuals with hearing loss. The ensuring speech understanding (ESU) test was developed to confirm speech understanding and determine whether hearing accommodations are necessary for neurocognitive testing. METHODS: Hearing was assessed using audiometry. The probability of ESU test failure by hearing status was estimated in 2679 participants (mean age: 81.4 ± 4.6 years) using multivariate logistic regression. RESULTS: Only 2.2% (N = 58) of participants failed the ESU test. The probability of failure increased with hearing loss severity; similar results were observed for those with and without mild cognitive impairment or dementia. DISCUSSION: The ESU test is appropriate for individuals who have variable degrees of hearing loss and cognitive function. This test can be used prior to neurocognitive testing to help reduce the risk of hearing loss and compromised auditory access to speech stimuli causing poorer performance on neurocognitive evaluation.


Assuntos
Disfunção Cognitiva , Perda Auditiva , Humanos , Idoso , Idoso de 80 Anos ou mais , Fala , Perda Auditiva/diagnóstico , Perda Auditiva/complicações , Cognição , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Testes Auditivos/efeitos adversos , Testes Auditivos/métodos
8.
Aesthet Surg J ; 44(6): 647-657, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38262634

RESUMO

BACKGROUND: Hyaluronic acids (HAs) continue to be the fillers of choice worldwide and their popularity is growing. Adverse events (AEs) are able to be resolved through the use of hyaluronidase (HYAL). However, routine HYAL use has been at issue due to perceived safety issues. OBJECTIVES: There are currently no guidelines on the use of HYAL in aesthetic practice, leading to variability in storage, preparation, skin testing, and beliefs concerning AEs. This manuscript interrogated the use of this agent in daily practice. METHODS: A 39-question survey concerning HYAL practice was completed by 264 healthcare practitioners: 244 from interrogated databases and 20 from the consensus panel. Answers from those in the database were compared to those of the consensus panel. RESULTS: Compared to the database group, the consensus group was more confident in the preparation of HYAL, kept reconstituted HYAL for longer, and was less likely to skin test for HYAL sensitivity and more likely to treat with HYAL in an emergency, even in those with a wasp or bee sting anaphylactic history. Ninety-two percent of all respondents had never observed an acute reaction to HYAL. Just over 1% of respondents had ever observed anaphylaxis. Five percent of practitioners reported longer-term adverse effects, including 3 respondents who reported loss of deep tissues. Consent before injecting HA for the possible requirement of HYAL was always obtained by 74% of practitioners. CONCLUSIONS: Hyaluronidase would appear to be an essential agent for anyone injecting hyaluronic acid filler. However, there is an absence of evidence-based recommendations with respect to the concentration, dosing, and treatment intervals of HYAL, and these should ideally be available.


Assuntos
Técnicas Cosméticas , Preenchedores Dérmicos , Ácido Hialurônico , Hialuronoglucosaminidase , Padrões de Prática Médica , Hialuronoglucosaminidase/administração & dosagem , Humanos , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/efeitos adversos , Padrões de Prática Médica/estatística & dados numéricos , Técnicas Cosméticas/efeitos adversos , Preenchedores Dérmicos/administração & dosagem , Preenchedores Dérmicos/efeitos adversos , Inquéritos e Questionários/estatística & dados numéricos , Anafilaxia/induzido quimicamente
9.
Int J Cancer ; 153(7): 1413-1422, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37424386

RESUMO

The Dutch Drug Rediscovery Protocol (DRUP) and the Australian Cancer Molecular Screening and Therapeutic (MoST) Program are similar nonrandomized, multidrug, pan-cancer trial platforms that aim to identify signals of clinical activity of molecularly matched targeted therapies or immunotherapies outside their approved indications. Here, we report results for advanced or metastatic cancer patients with tumors harboring cyclin D-CDK4/6 pathway alterations treated with CDK4/6 inhibitors palbociclib or ribociclib. We included adult patients that had therapy-refractory solid malignancies with the following alterations: amplifications of CDK4, CDK6, CCND1, CCND2 or CCND3, or complete loss of CDKN2A or SMARCA4. Within MoST, all patients were treated with palbociclib, whereas in DRUP, palbociclib and ribociclib were assigned to different cohorts (defined by tumor type and alteration). The primary endpoint for this combined analysis was clinical benefit, defined as confirmed objective response or stable disease ≥16 weeks. We treated 139 patients with a broad variety of tumor types; 116 with palbociclib and 23 with ribociclib. In 112 evaluable patients, the objective response rate was 0% and clinical benefit rate at 16 weeks was 15%. Median progression-free survival was 4 months (95% CI: 3-5 months), and median overall survival 5 months (95% CI: 4-6 months). In conclusion, only limited clinical activity of palbociclib and ribociclib monotherapy in patients with pretreated cancers harboring cyclin D-CDK4/6 pathway alterations was observed. Our findings indicate that monotherapy use of palbociclib or ribociclib is not recommended and that merging data of two similar precision oncology trials is feasible.


Assuntos
Neoplasias da Mama , Neoplasias , Humanos , Feminino , Neoplasias/tratamento farmacológico , Ciclinas , Austrália , Medicina de Precisão , Aminopiridinas/uso terapêutico , Ciclina D , Quinase 4 Dependente de Ciclina , Neoplasias da Mama/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Quinase 6 Dependente de Ciclina , DNA Helicases , Proteínas Nucleares
10.
Am J Epidemiol ; 192(2): 237-245, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36345076

RESUMO

We aimed to assess the associations of peripheral neuropathy (PN) with vision and hearing impairment among adults aged ≥40 years who attended the lower-extremity disease exam for the National Health and Nutrition Examination Survey (United States, 1999-2004). Overall, 11.8% (standard error (SE), 0.5) of adults had diabetes, 13.2% (SE, 0.5) had PN (26.6% (SE, 1.4) with diabetes, 11.4% (SE, 0.5) without diabetes), 1.6% (SE, 0.1) had vision impairment, and 15.4% (SE, 1.1) had hearing impairment. The prevalence of vision impairment was 3.89% (95% CI: 2.99, 5.05) among adults with PN and 1.29% (95% CI: 1.04, 1.60) among adults without PN (P < 0.001). After adjustment, PN was associated with vision impairment overall (odds ratio (OR) = 1.48, 95% confidence interval (CI): 1.03, 2.13) and among adults without diabetes (OR = 1.80, 95% CI: 1.17, 2.77) but not among adults with diabetes (P for interaction = 0.018). The prevalence of hearing impairment was 26.5% (95% CI: 20.4, 33.7) among adults with PN and 14.2% (95% CI: 12.4, 16.3) among adults without PN (P < 0.001). The association of PN with moderate/severe hearing impairment was significant overall (OR = 2.55, 95% CI: 1.40, 4.64) and among adults without diabetes (OR = 3.26, 95% CI: 1.80, 5.91). Overall, these findings suggest an association between peripheral and audiovisual sensory impairment that is unrelated to diabetes.


Assuntos
Diabetes Mellitus , Perda Auditiva , Doenças do Sistema Nervoso Periférico , Adulto , Humanos , Estados Unidos/epidemiologia , Inquéritos Nutricionais , Diabetes Mellitus/epidemiologia , Perda Auditiva/epidemiologia , Doenças do Sistema Nervoso Periférico/epidemiologia , Prevalência , Transtornos da Visão/epidemiologia
11.
Br J Cancer ; 129(3): 475-485, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37365284

RESUMO

PURPOSE: To determine the safety and efficacy of PARP plus PD-L1 inhibition (olaparib + durvalumab, O + D) in patients with advanced solid, predominantly rare cancers harbouring homologous recombination repair (HRR) defects. PATIENTS AND METHODS: In total, 48 patients were treated with O + D, 16 with BRCA1/2 alterations (group 1) and 32 with other select HRR alterations (group 2). Overall, 32 (66%) patients had rare or less common cancers. The primary objective of this single-arm Phase II trial was a progression-free survival rate at 6 months (PFS6). Post hoc exploratory analyses were conducted on archival tumour tissue and serial bloods. RESULTS: The PFS6 rate was 35% and 38% with durable objective tumour responses (OTR) in 3(19%) and 3(9%) in groups 1 and 2, respectively. Rare cancers achieving an OTR included cholangiocarcinoma, perivascular epithelioid cell (PEComa), neuroendocrine, gallbladder and endometrial cancer. O + D was safe, with five serious adverse events related to the study drug(s) in 3 (6%) patients. A higher proportion of CD38 high B cells in the blood and higher CD40 expression in tumour was prognostic of survival. CONCLUSIONS: O + D demonstrated no new toxicity concerns and yielded a clinically meaningful PFS6 rate and durable OTRs across several cancers with HRR defects, including rare cancers.


Assuntos
Proteína BRCA1 , Neoplasias do Endométrio , Feminino , Humanos , Proteína BRCA1/genética , Reparo de DNA por Recombinação/genética , Proteína BRCA2/genética , Ftalazinas/efeitos adversos
12.
Pediatr Hematol Oncol ; 40(8): 719-738, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37366551

RESUMO

The potential of circulating tumor DNA (ctDNA) analysis to serve as a real-time "liquid biopsy" for children with central nervous system (CNS) and non-CNS solid tumors remains to be fully elucidated. We conducted a study to investigate the feasibility and potential clinical utility of ctDNA sequencing in pediatric patients enrolled on an institutional clinical genomics trial. A total of 240 patients had tumor DNA profiling performed during the study period. Plasma samples were collected at study enrollment from 217 patients and then longitudinally from a subset of patients. Successful cell-free DNA extraction and quantification occurred in 216 of 217 (99.5%) of these initial samples. Twenty-four patients were identified whose tumors harbored 30 unique variants that were potentially detectable on a commercially-available ctDNA panel. Twenty of these 30 mutations (67%) were successfully detected by next-generation sequencing in the ctDNA from at least one plasma sample. The rate of ctDNA mutation detection was higher in patients with non-CNS solid tumors (7/9, 78%) compared to those with CNS tumors (9/15, 60%). A higher ctDNA mutation detection rate was also observed in patients with metastatic disease (9/10, 90%) compared to non-metastatic disease (7/14, 50%), although tumor-specific variants were detected in a few patients in the absence of radiographic evidence of disease. This study illustrates the feasibility of incorporating longitudinal ctDNA analysis into the management of relapsed or refractory patients with childhood CNS or non-CNS solid tumors.


Assuntos
Neoplasias Encefálicas , DNA Tumoral Circulante , Humanos , Criança , DNA Tumoral Circulante/genética , Estudos de Viabilidade , Biomarcadores Tumorais , Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias Encefálicas/genética , Mutação
13.
Sensors (Basel) ; 23(14)2023 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-37514774

RESUMO

This study presents an architectural framework for the blockchain-based usage-based insurance (UBI) policy auction mechanism in the internet of vehicles (IoV) applications. The main objective of this study is to analyze and design the specific blockchain architecture and management considerations for the UBI environment. An auction mechanism is developed for the UBI blockchain platform to enhance consumer trust. The study identifies correlations between driving behaviors and associated risks to determine a driver's score. A decentralized bidding algorithm is proposed and implemented on a blockchain platform using elliptic curve cryptography and first-price sealed-bid auctions. Additionally, the model incorporates intelligent contract functionality to prevent unauthorized modifications and ensure that insurance prices align with the prevailing market value. An experimental study evaluates the system's efficacy by expanding the participant pool in the bidding process to identify the winning bidder and is investigated under scenarios where varying numbers of insurance companies submit bids. The experimental results demonstrate that as the number of insurance companies increases exponentially, the temporal overhead incurred by the system exhibits only marginal growth. Moreover, the allocation of bids is accomplished within a significantly abbreviated timeframe. These findings provide evidence that supports the efficiency of the proposed algorithm.

14.
Sensors (Basel) ; 23(2)2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36679560

RESUMO

The rapid development of AIOT-related technologies has revolutionized various industries. The advantage of such real-time sensing, low costs, small sizes, and easy deployment makes extensive use of wireless sensor networks in various fields. However, due to the wireless transmission of data, and limited built-in power supply, controlling energy consumption and making the application of the sensor network more efficient is still an urgent problem to be solved in practice. In this study, we construct this problem as a tree structure wireless sensor network mathematical model, which mainly considers the QoS and fairness requirements. This study determines the probability of sensor activity, transmission distance, and transmission of the packet size, and thereby minimizes energy consumption. The Lagrangian Relaxation method is used to find the optimal solution with the lowest energy consumption while maintaining the network's transmission efficiency. The experimental results confirm that the decision-making speed and energy consumption can be effectively improved.


Assuntos
Redes de Comunicação de Computadores , Tecnologia sem Fio , Simulação por Computador , Algoritmos , Modelos Teóricos
15.
Sensors (Basel) ; 23(22)2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-38005428

RESUMO

Monitoring dynamic balance during gait is critical for fall prevention in the elderly. The current study aimed to develop recurrent neural network models for extracting balance variables from a single inertial measurement unit (IMU) placed on the sacrum during walking. Thirteen healthy young and thirteen healthy older adults wore the IMU during walking and the ground truth of the inclination angles (IA) of the center of pressure to the center of mass vector and their rates of changes (RCIA) were measured simultaneously. The IA, RCIA, and IMU data were used to train four models (uni-LSTM, bi-LSTM, uni-GRU, and bi-GRU), with 10% of the data reserved to evaluate the model errors in terms of the root-mean-squared errors (RMSEs) and percentage relative RMSEs (rRMSEs). Independent t-tests were used for between-group comparisons. The sensitivity, specificity, and Pearson's r for the effect sizes between the model-predicted data and experimental ground truth were also obtained. The bi-GRU with the weighted MSE model was found to have the highest prediction accuracy, computational efficiency, and the best ability in identifying statistical between-group differences when compared with the ground truth, which would be the best choice for the prolonged real-life monitoring of gait balance for fall risk management in the elderly.


Assuntos
Marcha , Caminhada , Humanos , Idoso , Redes Neurais de Computação , Acidentes por Quedas/prevenção & controle , Fenômenos Biomecânicos
16.
N Engl J Med ; 390(16): 1505-1512, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38657246
17.
Pediatr Blood Cancer ; 69(11): e29859, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35713195

RESUMO

BACKGROUND: The association of childhood cancer with Lynch syndrome is not established compared with the significant pediatric cancer risk in recessive constitutional mismatch repair deficiency syndrome (CMMRD). PROCEDURE: We describe the clinical features, germline analysis, and tumor genomic profiling of patients with Lynch syndrome among patients enrolled in pediatric cancer genomic studies. RESULTS: There were six of 773 (0.8%) pediatric patients with solid tumors identified with Lynch syndrome, defined as a germline heterozygous pathogenic variant in one of the mismatch repair (MMR) genes (three with MSH6, two with MLH1, and one with MSH2). Tumor analysis demonstrated evidence for somatic second hits and/or increased tumor mutation burden in three of four patients with available tumor with potential implications for therapy and identification of at-risk family members. Only one patient met current guidelines for pediatric cancer genetics evaluation at the time of tumor diagnosis. CONCLUSION: Approximately 1% of children with cancer have Lynch syndrome, which is missed with current referral guidelines, suggesting the importance of adding MMR genes to tumor and hereditary pediatric cancer panels. Tumor analysis may provide the first suggestion of an underlying cancer predisposition syndrome and is useful in distinguishing between Lynch syndrome and CMMRD.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias Encefálicas , Criança , Neoplasias Colorretais , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/genética , Reparo de Erro de Pareamento de DNA/genética , Proteínas de Ligação a DNA/genética , Mutação em Linhagem Germinativa , Humanos , Proteína 1 Homóloga a MutL/genética , Proteína 2 Homóloga a MutS/genética , Síndromes Neoplásicas Hereditárias
18.
AJR Am J Roentgenol ; 218(2): 342-350, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34431366

RESUMO

BACKGROUND. Recent professional society guidelines for radionuclide imaging of sporadic pheochromocytoma (PHEO) recommend 18F-fluorodihydroxyphenylala-nine (18F-FDOPA) as the radiotracer of choice, deeming 68Ga-DOTATATE and FDG to be second- and third-line agents, respectively. An additional agent, 18F-fluorodopamine (18F-FDA), remains experimental for PHEO detection. A paucity of research has performed head-to-head comparison among these agents. OBJECTIVE. The purpose of this study was to perform an intraindividual comparison of 68Ga-DOTATATE PET/CT, FDG PET/CT, 18F-FDOPA PET/CT, 18F-FDA PET/CT, CT, and MRI in visualization of sporadic primary PHEO. METHODS. This prospective study enrolled patients referred with clinical suspicion for sporadic PHEO. Patients were scheduled for 68Ga-DOTATATE PET/CT, FDG PET/CT, 18F-FDOPA PET/CT, 18F-FDA PET/CT, whole-body staging CT (portal venous phase), and MRI within a 3-month period. PET/CT examinations were reviewed by two nuclear medicine physicians, and CT and MRI were reviewed by two radiologists; differences were resolved by consensus. Readers scored lesions in terms of confidence in diagnosis of PHEO (1-5 scale; 4-5 considered positive for PHEO). Lesion-to-liver SUVmax was computed using both readers' measurements. Interreader agreement was assessed using intraclass correlation coefficients (ICCs) for SUVmax. Analysis included only patients with histologically confirmed PHEO on resection. RESULTS. The analysis included 14 patients (eight women, six men; mean age, 52.4 ± 16.8 [SD] years) with PHEO. Both 68Ga-DOTATATE PET/CT and FDG PET/CT were completed in all 14 patients, 18F-FDOPA PET/CT in 11, 18F-FDA PET/CT in 7, CT in 12, and MRI in 12. Mean conspicuity score for PHEO was 5.0 ± 0.0 for 18F-FDOPA PET/CT, 4.7 ± 0.5 for MRI, 4.6 ± 0.8 for 18F-FDA PET/CT, 4.4 ± 1.0 for 68Ga-DOTATATE PET/CT, 4.3 ± 1.0 for CT, and 4.1 ± 1.5 for FDG PET/CT. The positivity rate for PHEO was 100.0% (11/11) for 18F-FDOPA PET/CT, 100.0% (12/12) for MRI, 85.7% (6/7) for 18F-FDA PET/CT, 78.6% (11/14) for FDG PET/CT, 78.6% (11/14) for 68Ga-DOTATATE PET/CT, and 66.7% (8/12) for CT. Lesion-to-liver SUVmax was 10.5 for 18F-FDOPA versus 3.0-4.2 for the other tracers. Interreader agreement across modalities ranged from 85.7% to 100.0% for lesion positivity with ICCs of 0.55-1.00 for SUVmax measurements. CONCLUSION. Findings from this small intraindividual comparative study support 18F-FDOPA PET/CT as a preferred first-line imaging modality in evaluation of sporadic PHEO. CLINICAL IMPACT. This study provides data supporting current guidelines for imaging evaluation of suspected PHEO. TRIAL REGISTRATION. ClinicalTrials.gov NCT00004847.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Fluordesoxiglucose F18 , Radioisótopos de Gálio , Imageamento por Ressonância Magnética/métodos , Feocromocitoma/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Radiofarmacêuticos , Glândulas Suprarrenais/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Octreotida/análogos & derivados , Compostos Organometálicos , Estudos Prospectivos , Reprodutibilidade dos Testes , Tomografia Computadorizada por Raios X/métodos
19.
J Chem Inf Model ; 62(24): 6574-6585, 2022 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-35118864

RESUMO

The recent outbreak of COVID-19 infection started in Wuhan, China, and spread across China and beyond. Since the WHO declared COVID-19 a pandemic (March 11, 2020), three vaccines and only one antiviral drug (remdesivir) have been approved (Oct 22, 2020) by the FDA. The coronavirus enters human epithelial cells by the binding of the densely glycosylated fusion spike protein (S protein) to a receptor (angiotensin-converting enzyme 2, ACE2) on the host cell surface. Therefore, inhibiting the viral entry is a promising treatment pathway for preventing or ameliorating the effects of COVID-19 infection. In the current work, we have used all-atom molecular dynamics (MD) simulations to investigate the influence of the MLN-4760 inhibitor on the conformational properties of ACE2 and its interaction with the receptor-binding domain (RBD) of SARS-CoV-2. We have found that the presence of an inhibitor tends to completely/partially open the ACE2 receptor where the two subdomains (I and II) move away from each other, while the absence results in partial or complete closure. The current study increases our understanding of ACE inhibition by MLN-4760 and how it modulates the conformational properties of ACE2.


Assuntos
Enzima de Conversão de Angiotensina 2 , SARS-CoV-2 , Humanos , Enzima de Conversão de Angiotensina 2/antagonistas & inibidores , COVID-19 , Simulação de Dinâmica Molecular , Ligação Proteica , SARS-CoV-2/efeitos dos fármacos
20.
Neurourol Urodyn ; 41(1): 490-497, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34913516

RESUMO

INTRODUCTION/BACKGROUND: Sensation of incomplete bladder emptying (SIBE) has been shown to be correlated with an elevated post-void residual (PVR) in men, however, the significance of this symptom and whether it correlates with an elevated PVR in women is less clear. In this study, we assessed if SIBE in women is correlated with an elevated PVR and determined the relationship of SIBE to other lower urinary tract symptoms. METHODS/MATERIALS: Women ages ≥18 with lower urinary tract symptoms were eligible. SIBE was defined by a response "sometimes", "most of the time", or "all of the time" to the question "How often do you feel that your bladder has not emptied properly after you have urinated?" on the International Consultation on Incontinence Questionnaire. Frequency and bother of other lower urinary tract symptoms were also assessed to compare their relationship to SIBE. Elevated PVR was defined as ≥100 ml via ultrasound. RESULTS: We prospectively evaluated 95 women, 59% of whom reported SIBE. Compared to women without SIBE, women with SIBE reported more urinary hesitancy (51% vs. 18%, p = 0.002), intermittency (56% vs. 16%, p < 0.001), weak stream (36% vs. 5%, p < 0.001), dysuria (29% vs. 5%, p = 0.004), and straining (25% vs 5%, p = 0.013). However, there was no difference in elevated PVRs between women with and without SIBE [5/56, 9% vs. 4/39, 10%, (p = 0.99)]. All women, regardless of SIBE, reported higher bother from storage and incontinence symptoms versus voiding symptoms with no difference in overall bother scores. CONCLUSION: SIBE is a common complaint in women with lower urinary tract symptoms. While women with SIBE reported more voiding symptoms, they were more bothered by storage symptoms. Importantly, most of these women emptied their bladder well and were not more likely to have an elevated PVR than women without SIBE.


Assuntos
Sintomas do Trato Urinário Inferior , Retenção Urinária , Feminino , Humanos , Sintomas do Trato Urinário Inferior/diagnóstico , Masculino , Sensação , Bexiga Urinária/diagnóstico por imagem , Micção/fisiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA