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With the rapid development of the automotive industry, the requirements for bodywork materials are not only focused on high strength but also on improved forming properties. To develop a new generation of automotive steels with higher strength-plasticity matching, a high elongation 1200 MPa grade V-Nb microalloyed cold-rolled reinforced formable dual-phase steel was developed in this experiment through rational compositional design and precise process machining. The properties of the test steel are improved by varying the over-aging temperature as well as the annealing temperature to achieve a good strength-plasticity balance. The results show that as the aging temperature increases, the tensile strength and yield strength of the test steel decrease, while the elongation continues to increase. At an aging temperature of 310 °C, the steel exhibits not only high strength but also better ductility. As the annealing temperature increases, the tensile strength and yield strength of the test steel initially increase and then decrease, while the elongation continues to increase. When the heat treatment process involves an annealing temperature of 860 °C and an over-aging temperature of 310 °C, the test steel achieves the best strength-plasticity balance.
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This survey study evaluated whether concerns about parental access to online health information through patient portals altered the amount of sensitive health information by young adults and the likelihood of opening a portal account.
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The prolactin (PRL) hormone is a major regulator of mammary gland development and lactation. However, it remains unclear whether and how PRL contributes to mammary epithelial cell proliferation and secretion. The Boer and Macheng black crossbred goats are superior in reproduction, meat, and milk, and are popular in Hubei province. To elucidate the mechanisms of PRL on mammary growth and lactation, to improve the local goat economic trade, we have performed studies on these crossbred goats during pregnancy and early lactation, and in goat mammary epithelial cells (GMECs). Here, we first found that the amino acid transporters of SNAT1 and SNAT2 expression in vivo and in vitro were closely associated with PRL levels, the proliferation and secretion of GMECs; knockdown and over-expression of SNAT1/2 demonstrated that PRL modulated the proliferation and lactation of GMECs through regulating SNAT1/2 expression. Transcriptome sequencing and qPCR assays demonstrated the effect of PRL on the transcriptional regulation of SNAT1 and SNAT2 in GMECs. Dual-luciferase reporter gene assays further verified that the binding of the potential PRL response element in the SNAT1/2 promoter regions activated SNAT1/2 transcription after PRL stimulation. Additionally, silencing of either PRLR or STAT5 nearly abolished PRL-stimulated SNAT1/2 promoter activity, suggesting PRLR-STAT5 signaling is involved in the regulation of PRL on the transcriptional activation of SNAT1/2. These results illustrated that PRL modulates the proliferation and secretion of GMECs via PRLR-STAT5-mediated regulation of the SNAT1/2 pathway. This study provides new insights into how PRL affects ruminant mammary development and lactation through regulation of amino acid transporters.
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Proliferação de Células , Células Epiteliais , Cabras , Lactação , Glândulas Mamárias Animais , Prolactina , Animais , Prolactina/metabolismo , Feminino , Células Epiteliais/metabolismo , Glândulas Mamárias Animais/metabolismo , Glândulas Mamárias Animais/citologia , Glândulas Mamárias Animais/crescimento & desenvolvimento , Fator de Transcrição STAT5/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Gravidez , Regiões Promotoras Genéticas/genéticaRESUMO
Importance: Initial management of intermediate-risk prostate cancer is evolving, with no clear recommendation for treatment. Data on utilization of active surveillance for patients with newly diagnosed intermediate-risk prostate cancer may help clarify emerging trends. Objective: To further characterize US national trends of initial management of intermediate-risk prostate cancer. Design, Setting, and Participants: This cohort study included patients with intermediate-risk prostate cancer diagnosed from January 1, 2010, to December 31, 2020. Eligible patients were diagnosed in US hospitals included in the National Cancer Database; National Comprehensive Cancer Network risk stratification guidelines were used to characterize as favorable vs unfavorable intermediate risk. Analysis was performed in September 2023. Exposure: Active surveillance vs intervention with surgery and/or radiation or no treatment. Main Outcomes and Measures: Temporal trends in demographic, clinical, and socioeconomic factors among men with intermediate-risk prostate cancer and their association with the use of active surveillance; further subgroup analysis was conducted for those with favorable vs unfavorable intermediate risk classification. Results: In total, 289â¯584 men diagnosed with intermediate-risk prostate cancer were identified from 2010 to 2020 (46â¯147 Black [15.9%], 230â¯071 White [79.5%]). Among patients, 153â¯726 (53.1%) underwent prostatectomy, 107â¯152 (37.0%) underwent radiotherapy, and 15â¯847 (5.5%) underwent active surveillance as initial treatment strategy. Overall, active surveillance quadrupled from 418 of 21â¯457 patients (2.0%) in 2010 to 2428 of 28â¯192 patients (8.6%) in 2020 for the entire cohort (P < .001). Active surveillance increased from 317 of 12â¯858 patients (2.4%) in 2010 to 2020 of 12â¯902 patients (13.5%) in 2020 in men with favorable intermediate-risk prostate cancer (P < .001). In the unfavorable intermediate-risk cohort, active surveillance increased from 101 of 8181 patients (1.2%) in 2010 to 408 of 12â¯861 patients (3.1%) in 2020 (P < .001). On multivariable analysis, use of active surveillance was associated with increased age (age 70-80 years vs <50 years: odds ratio [OR], 3.09; 95% CI, 2.66-3.59), lower Gleason score (3 + 3 vs 3 + 4: OR, 3.45; 95% CI, 3.25-3.66), early T stage (T2c vs T1a through T2a: OR, 0.35; 95% CI, 0.32-0.38), treatment at an academic center (community vs academic center: OR, 0.72; 95% CI, 0.67-0.78), higher level of education (communities with 21% or higher population without high school vs less than 7%: OR, 0.73; 95% CI, 0.67-0.79), insurance type (Medicare or other governmental service vs private: OR, 1.11; 95% CI, 1.07-1.16), proximity to treatment facility (greater than 120 miles vs less than 60 miles: OR, 0.75; 95% CI, 0.68-0.84), facility location (South Atlantic vs New England: OR, 0.54; 95% CI, 0.46-0.53), and lower income (less than $38â¯000 vs $63â¯000 or greater: OR, 1.22; 95% CI, 1.14-1.31). Conclusions and Relevance: These findings highlight increasing implementation of active surveillance in the initial management of intermediate risk prostate cancer. Prospective data with improved risk stratification incorporating genomics and digital pathology artificial intelligence as well as novel surveillance strategies may continue to better delineate optimal treatment recommendations in this patient population.
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Neoplasias da Próstata , Conduta Expectante , Humanos , Masculino , Neoplasias da Próstata/terapia , Neoplasias da Próstata/epidemiologia , Idoso , Conduta Expectante/estatística & dados numéricos , Conduta Expectante/tendências , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Medição de Risco/métodos , Estudos de Coortes , Fatores de RiscoRESUMO
Although hydrophobic interactions provide the main driving force for initial peptide aggregation, their role in regulating suprastructure handedness of higher-order architectures remains largely unknown. We here interrogate the effects of hydrophobic amino acids on handedness at various assembly stages of peptide amphiphiles. Our studies reveal that relative to aliphatic side chains, aromatic side chains set the twisting directions of single ß-strands due to their strong steric repulsion to the backbone, and upon packing into multi-stranded ß-sheets, the side-chain aromatic interactions between strands form the aromatic ladders with a directional preference. This ordering not only leads to parallel ß-sheet arrangements but also induces the chiral flipping over of single ß-strands within a ß-sheet. In contrast, the lack of orientational hydrophobic interactions in the assembly of aliphatic peptides implies no chiral inversion upon packing into ß-sheets. This study opens an avenue to harness peptide aggregates with targeted handedness via aromatic side-chain interactions.
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Interações Hidrofóbicas e Hidrofílicas , Peptídeos , Peptídeos/química , Peptídeos/metabolismo , Conformação Proteica em Folha beta , Estereoisomerismo , Estrutura Secundária de Proteína , Aminoácidos Aromáticos/química , Dicroísmo Circular , Modelos Moleculares , Aminoácidos/químicaRESUMO
OBJECTIVE: To provide comprehensive epidemiological information about the distribution and occurrence of rabies during 2022 in the US, Canada, and Mexico. METHODS: The US National Rabies Surveillance System collected 2022 animal rabies data from US state and territorial public health departments and USDA Wildlife Services. Temporal and geographic analyses were conducted to evaluate trends in animal rabies cases. RESULTS: During 2022, 54 US jurisdictions reported 3,579 animal rabies cases, reflecting a 2.3% decline from 3,663 cases reported in 2021. Six states collectively reported > 50% of animal rabies cases: Texas (395 [11.0%]), Virginia (337 [9.4%]), Pennsylvania (329 [9.2%]), New York (267 [7.5%]), North Carolina (264 [7.4%]), and California (241 [6.7%]). Out of the total reported rabies animal cases, 3,234 (90.4%) were attributed to wildlife, with bats (1,218 [34.0%]), raccoons (1,014 [28.3%]), skunks (660 [18.4%]), and foxes (269 [7.5%]) representing the primary hosts confirmed with rabies. Rabid cats (222 [6.2%]), cattle (42 [1.2%]), and dogs (50 [1.4%]) constituted > 90% of reported domestic animal rabies cases. CONCLUSIONS: In 2022, there was an increase in the number of animal samples submitted for rabies testing in the US and Canada. A notable geographic expansion of gray fox rabies virus variant was detected in the US. Three human rabies deaths due to vampire bat rabies infection occurred in Mexico; none were reported from the US and Canada. CLINICAL RELEVANCE: Laboratory diagnosis of rabies in animals is critical to ensure judicious use of human rabies postexposure prophylaxis.
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Animais Selvagens , Raiva , Raiva/epidemiologia , Raiva/veterinária , Animais , Estados Unidos/epidemiologia , Canadá/epidemiologia , México/epidemiologia , Vigilância da População , Cães , Animais DomésticosRESUMO
OBJECTIVES: To explore the value of preoperative magnetic resonance imaging (MRI) characterization of intracranial solitary fibrous tumors (ISFT) and to evaluate the effectiveness of preoperative MRI features in predicting pathological grading. MATERIALS AND METHODS: This retrospective analysis comprised the clinical and preoperative MRI characterization of 55 patients with ISFT in our hospital, including 27 grade II cases and 28 grade III cases confirmed by postoperative pathology. Variables included age, sex, tumor location, cross-midline status, signal characteristics of T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), T2-fluid-attenuated inversion recovery (T2-FLAIR), and diffusionweighted imaging (DWI), peritumoral edema, intralesional hemorrhage, focal necrosis/cystic degeneration, tumor empty vessel, maximum tumor diameter, maximum, minimum, and average values of apparent diffusion coefficient (ADCmax, ADCmin, and ADCmean), tumors enhancement mode, meningeal tail sign, skull invasion, cerebral parenchymal invasion, and venous sinus involvement. The independent samples t test or Mann-Whitney U test was performed to compare continuous data between the two groups, and the Pearson chi-squared test or Fisher's exact test was used to compare categorical data. In addition, bivariate logistic regression was performed to construct a comprehensive model, and receiver operating characteristic (ROC) curves were generated to calculate the areas under the curve (AUCs), thereby determining the value of each parameter in the differential diagnosis of grades II and III ISFT. RESULTS: The mean age at onset was similar between patients with grades II and III ISFT (46.77 ± 14.66 years and 45.82 ± 12.07 years, respectively). The proportions of men among patients with grades II and III ISFT were slightly higher than those of female patients (male/female: 1.25 [15/12] and 1.33 [16/12], respectively). There were significant differences between grades II and III ISFT in the T2-FLAIR and DWI signal characteristics, maximum, minimum, and average values of the apparent diffusion coefficient (ADCmax, ADCmin, and ADCmean), tumor location, and skull invasion (P = 0.001, P = 0.018, P = 0.000, P = 0.000, P = 0.000, P = 0.010, and P = 0.032, respectively). However, no significant differences were noted between grades II and III ISFT in age, sex, cross-midline status, T1WI and T2WI signal characteristics, peritumoral edema, intralesional hemorrhage, focal necrosis/cystic degeneration, tumor empty vessel shadow, enhancement mode, meningeal tail sign, maximum tumor diameter, brain parenchyma invasion, or venous sinus involvement (all P > 0.05). Moreover, binary logistic regression analysis showed that the model accuracy was 89.1% when ADCmin was included in the regression equation. Moreover, ROC curve analysis showed that the AUC of ADCmin was 0.805 (0.688, 0.922), sensitivity was 74.1%, specificity was 75.0%, and the cutoff value was 672 mm2/s. CONCLUSIONS: Grade III ISFT patients displayed more mixed T2-FLAIR signal characteristics and DWI signal characteristics than grade II patients, as shown by higher skull invasion and tumor mass collapse midline distribution and lower ADCmax, ADCmean, and ADCmin values. The ADCmin value was significant in the preoperative assignment of grades II and III ISFT, thereby contributing to enhanced accuracy in the imaging grading diagnosis of the disease.
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Neoplasias Encefálicas , Imageamento por Ressonância Magnética , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos , Gradação de Tumores/métodos , Idoso , Adulto Jovem , Tumores Fibrosos Solitários/diagnóstico por imagem , Tumores Fibrosos Solitários/patologia , Adolescente , Imagem de Difusão por Ressonância Magnética/métodos , Período Pré-Operatório , Cuidados Pré-Operatórios/métodosRESUMO
BACKGROUND AND OBJECTIVE: Robotic-assisted bronchoscopy (RAB) is an emerging modality to sample pulmonary lesions. Cone-beam computed tomography (CBCT) can be incorporated into RAB. We investigated the magnitude and predictors of patient and staff radiation exposure during mobile CBCT-guided shape-sensing RAB. METHODS: Patient radiation dose was estimated by cumulative dose area product (cDAP) and cumulative reference air kerma (cRAK). Staff equivalent dose was calculated based on isokerma maps and a phantom simulation. Patient, lesion and procedure-related factors associated with higher radiation doses were identified by logistic regression models. RESULTS: A total of 198 RAB cases were included in the analysis. The median patient cDAP and cRAK were 10.86 Gy cm2 (IQR: 4.62-20.84) and 76.20 mGy (IQR: 38.96-148.38), respectively. Among staff members, the bronchoscopist was exposed to the highest median equivalent dose of 1.48 µSv (IQR: 0.85-2.69). Both patient and staff radiation doses increased with the number of CBCT spins and targeted lesions (p < 0.001 for all comparisons). Patient obesity, negative bronchus sign, lesion size <2.0 cm and inadequate sampling by on-site evaluation were associated with a higher patient dose, while patient obesity and inadequate sampling by on-site evaluation were associated with a higher bronchoscopist equivalent dose. CONCLUSION: The magnitude of patient and staff radiation exposure during CBCT-RAB is aligned with safety thresholds recommended by regulatory authorities. Factors associated with a higher radiation exposure during CBCT-RAB can be identified pre-operatively and solicit procedural optimization by reinforcing radiation protective measures. Future studies are needed to confirm these findings across multiple institutions and practices.
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Broncoscopia , Tomografia Computadorizada de Feixe Cônico , Exposição à Radiação , Procedimentos Cirúrgicos Robóticos , Humanos , Tomografia Computadorizada de Feixe Cônico/métodos , Broncoscopia/métodos , Broncoscopia/efeitos adversos , Masculino , Feminino , Exposição à Radiação/efeitos adversos , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Exposição Ocupacional/efeitos adversos , Idoso , Doses de Radiação , Imagens de Fantasmas , Adulto , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapiaRESUMO
OBJECTIVES: To evaluate the performance of multiparametric neurite orientation dispersion and density imaging (NODDI) radiomics in distinguishing between glioblastoma (Gb) and solitary brain metastasis (SBM). MATERIALS AND METHODS: In this retrospective study, NODDI images were curated from 109 patients with Gb (n = 57) or SBM (n = 52). Automatically segmented multiple volumes of interest (VOIs) encompassed the main tumor regions, including necrosis, solid tumor, and peritumoral edema. Radiomics features were extracted for each main tumor region, using three NODDI parameter maps. Radiomics models were developed based on these three NODDI parameter maps and their amalgamation to differentiate between Gb and SBM. Additionally, radiomics models were constructed based on morphological magnetic resonance imaging (MRI) and diffusion imaging (diffusion-weighted imaging [DWI]; diffusion tensor imaging [DTI]) for performance comparison. RESULTS: The validation dataset results revealed that the performance of a single NODDI parameter map model was inferior to that of the combined NODDI model. In the necrotic regions, the combined NODDI radiomics model exhibited less than ideal discriminative capabilities (area under the receiver operating characteristic curve [AUC] = 0.701). For peritumoral edema regions, the combined NODDI radiomics model achieved a moderate level of discrimination (AUC = 0.820). Within the solid tumor regions, the combined NODDI radiomics model demonstrated superior performance (AUC = 0.904), surpassing the models of other VOIs. The comparison results demonstrated that the NODDI model was better than the DWI and DTI models, while those of the morphological MRI and NODDI models were similar. CONCLUSION: The NODDI radiomics model showed promising performance for preoperative discrimination between Gb and SBM. CLINICAL RELEVANCE STATEMENT: The NODDI radiomics model showed promising performance for preoperative discrimination between Gb and SBM, and radiomics features can be incorporated into the multidimensional phenotypic features that describe tumor heterogeneity. KEY POINTS: ⢠The neurite orientation dispersion and density imaging (NODDI) radiomics model showed promising performance for preoperative discrimination between glioblastoma and solitary brain metastasis. ⢠Compared with other tumor volumes of interest, the NODDI radiomics model based on solid tumor regions performed best in distinguishing the two types of tumors. ⢠The performance of the single-parameter NODDI model was inferior to that of the combined-parameter NODDI model.
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Neoplasias Encefálicas , Glioblastoma , Neuritos , Humanos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/patologia , Masculino , Glioblastoma/diagnóstico por imagem , Glioblastoma/patologia , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neuritos/patologia , Diagnóstico Diferencial , Idoso , Adulto , Imageamento por Ressonância Magnética Multiparamétrica/métodos , Imageamento por Ressonância Magnética/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Imagem de Tensor de Difusão/métodos , RadiômicaRESUMO
The contradiction between economic growth demands and the achievement of the "dual-carbon" goals at the regional level is a pressing issue in China. As a significant economic and cultural center in the western region of China, the Guanzhong Plain urban agglomeration has experienced rapid development and urbanization, making it one of the key areas for national development. Therefore, greater attention should be given to carbon emission reduction in this region. This study focuses on the dataset from 2010 to 2019 in the Guanzhong Plain urban agglomeration, utilizing an input-output table to construct a carbon dioxide emission inventory. The research investigates the impact of regional classification on carbon emission levels within the Guanzhong Plain urban agglomeration. Furthermore, the Tapio decoupling analysis method is employed to assess the decoupling coefficient between regional economic development and carbon emissions. Additionally, the Theil index inequality analysis method is utilized to measure the disparities in per capita carbon emissions among cities within the region. Research findings indicate the following: 1) The regional classification of the Guanzhong Plain urban agglomeration is an effective policy for reducing regional carbon emissions and promoting carbon emissions reduction. 2) There exist variations in energy and industrial structures among cities within the urban agglomeration, necessitating tailored measures for low-carbon transition based on the specific circumstances of each city. 3) The regional classification of the urban agglomeration significantly influences the degree of decoupling between economic development and carbon emissions, with a trend towards stronger decoupling. The study suggests that cities within the Guanzhong Plain urban agglomeration should adopt measures aligned with their natural conditions and economic characteristics to achieve a low-carbon transition. Leveraging the regional cooperation capacity of the urban agglomeration is crucial to decouple economic development from carbon emissions, thereby promoting sustainable economic growth and environmental protection in a mutually beneficial manner.
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Desenvolvimento Econômico , Urbanização , Cidades , China , Dióxido de Carbono/análiseRESUMO
The development of the goat mammary gland is mainly under the control of ovarian hormones particularly estrogen and progesterone (P4). Amino acids play an essential role in mammary gland development and milk production, and sodium-coupled neutral amino acid transporter 2 (SNAT2) was reported to be expressed in the mammary gland of rats and bovine mammary epithelial cells, which may affect the synthesis of milk proteins or mammary cell proliferation by mediating prolactin, 17ß-estradiol (E2) or methionine function. However, whether SNAT2 mediates the regulatory effects of E2 and P4 on the development of the ruminant mammary gland is still unclear. In this study, we show that E2 and P4 could increase the proliferation of goat mammary epithelial cells (GMECs) and regulate SNAT2 mRNA and protein expression in a dose-dependent manner. Further investigation revealed that SNAT2 is abundantly expressed in the mammary gland during late pregnancy and early lactation, while knockdown and overexpression of SNAT2 in GMECs could inhibit or enhance E2- and P4-induced cell proliferation as well as mammalian target of rapamycin (mTOR) signaling. We also found that the accelerated proliferation induced by SNAT2 overexpression in GMECs was suppressed by the mTOR signaling pathway inhibitor rapamycin. This indicates that the regulation of GMECs proliferation mediated by SNAT2 in response to E2 and P4 is dependent on the mTOR signaling pathway. Finally, we found that the total content of the amino acids in GMECs changed after knocking-down and overexpressing SNAT2. In summary, the results demonstrate that the regulatory effects of E2 and P4 on GMECs proliferation may be mediated by the SNAT2-transported amino acid pathway. These results may offer a novel nutritional target for improving the development of the ruminant mammary gland and milk production.
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Estrogênios , Cabras , Progesterona , Animais , Feminino , Gravidez , Aminoácidos/metabolismo , Proliferação de Células , Células Epiteliais/metabolismo , Estrogênios/metabolismo , Cabras/genética , Cabras/metabolismo , Glândulas Mamárias Animais/metabolismo , Progesterona/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismoRESUMO
The raccoon (Procyon lotor) variant of the rabies virus (RRV) is enzootic in the eastern United States and oral rabies vaccination (ORV) is the primary strategy to prevent and control landscape spread. Breaches of ORV management zones occasionally occur, and emergency "contingency" actions may be implemented to enhance local control. Contingency actions are an integral part of landscape-scale wildlife rabies management but can be very costly and routinely involve enhanced rabies surveillance (ERS) around the index case. We investigated two contingency actions in Ohio (2017-2019 and 2018-2021) and one in Virginia (2017-2019) using a dynamic, multi-method occupancy approach to examine relationships between specific management actions and RRV occurrence, including whether ERS was sufficient around the index case. The RRV occupancy was assessed seasonally at 100-km2 grids and we examined relationships across three spatial scales (regional management zone, RRV free regions, and local contingency areas). The location of a grid relative to the ORV management zone was the strongest predictor of RRV occupancy at the regional scale. In RRV free regions, the neighbor effect and temporal variability were most important in influencing RRV occupancy. Parenteral (hand) vaccination of raccoons was important across all three contingency action areas, but more influential in the Ohio contingency action areas where more raccoons were hand vaccinated. In the Virginia contingency action area, ORV strategies were as important in reducing RRV occupancy as a hand vaccination strategy. The management action to trap, euthanize, and test (TET) raccoons was an important method to increase ERS, yet the impacts of TET on RRV occupancy are not clear. The probability of detecting additional cases of RRV was exceptionally high (>0.95) during the season the index case occurred. The probability of detecting RRV through ERS declined in the seasons following initial TET efforts but remained higher after the contingency action compared to the ERS detection probabilities prior to index case incidence. Local RRV cases were contained within one year and eliminated within 2-3 years of each contingency action.
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Vacina Antirrábica , Raiva , Animais , Estados Unidos , Raiva/epidemiologia , Raiva/prevenção & controle , Raiva/veterinária , Guaxinins , Ohio/epidemiologia , Virginia/epidemiologia , Animais Selvagens , Administração Oral , Vacina Antirrábica/uso terapêuticoRESUMO
The controlled peptide self-assembly and disassembly are not only implicated in many cellular processes but also possess huge application potential in a wide range of biotechnology and biomedicine. ß-sheet peptide assemblies possess high kinetic stability, so it is usually hard to disassemble them rapidly. Here, we reported that both the self-assembly and disassembly of a designed short ß-sheet peptide IIIGGHK could be well harnessed through the variations of concentration, pH, and mechanical stirring. Microscopic imaging, neutron scattering, and infrared spectroscopy were used to track the assembly and disassembly processes upon these stimuli, especially the interconversion between thin, left-handed protofibrils and higher-order nanotubes with superstructural right-handedness. The underlying rationale for these controlled disassembly processes mainly lies in the fact that the specific His-His interactions between protofibrils were responsive to these stimuli. By taking advantage of the peptide self-assembly and disassembly, the encapsulation of the hydrophobic drug curcumin and its rapid release upon stimuli were achieved. Additionally, the peptide hydrogels facilitated the differentiation of neural cells while maintaining low cell cytotoxicity. We believe that such dynamic and reversible structural transformation in this work provides a distinctive paradigm for controlling the peptide self-assembly and disassembly, thus laying a foundation for practical applications of peptide assemblies.
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Nanotubos de Peptídeos , Nanotubos , Nanotubos de Peptídeos/química , Peptídeos/farmacologia , Peptídeos/química , Conformação Proteica em Folha betaRESUMO
OBJECTIVE: To evaluate the theoretical impact of regionalizing cytoreductive surgery for ovarian cancer (OC) to high-volume facilities on patient travel. METHODS: We retrospectively identified patients with OC who underwent cytoreduction between 1/1/2004-12/31/2018 from the New York State Cancer Registry and Statewide Planning and Research Cooperative System. Hospitals were stratified by low-volume (<21 cytoreductive surgical procedures for OC annually) and high-volume centers (≥21 procedures annually). A simulation was performed; outcomes of interest were driving distance and time between the centroid of the patient's residence zip code and the treating facility zip code. RESULTS: Overall, 60,493 patients met inclusion criteria. Between 2004 and 2018, 210 facilities were performing cytoreductive surgery for OC in New York; 159 facilities (75.7%) met low-volume and 51 (24.3%) met high-volume criteria. Overall, 10,514 patients (17.4%) were treated at low-volume and 49,979 (82.6%) at high-volume facilities. In 2004, 78.2% of patients were treated at high-volume facilities, which increased to 84.6% in 2018 (P < .0001). Median travel distance and time for patients treated at high-volume centers was 12.2 miles (IQR, 5.6-25.5) and 23.0 min (IQR, 15.2-37.0), and 8.2 miles (IQR, 3.7-15.9) and 16.8 min (IQR, 12.4-26.0) for patients treated at low-volume centers. If cytoreductive surgery was centralized to high-volume centers, median distance and time traveled for patients originally treated at low-volume centers would be 11.2 miles (IQR, 3.8-32.3; P < .001) and 20.2 min (IQR, 13.6-43.0; P < .001). CONCLUSIONS: Centralizing cytoreductive surgery for OC to high-volume centers in New York would increase patient travel burden by negligible amounts of distance and time for most patients.
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Procedimentos Cirúrgicos de Citorredução , Neoplasias Ovarianas , Humanos , Feminino , New York , Estudos Retrospectivos , Acessibilidade aos Serviços de Saúde , Hospitais com Alto Volume de Atendimentos , Viagem , Neoplasias Ovarianas/cirurgiaRESUMO
BACKGROUND: Machine learning driven clinical decision support tools (ML-CDST) are on the verge of being integrated into clinical settings, including in Otolaryngology-Head & Neck Surgery. In this study, we investigated whether such CDST may influence otolaryngologists' diagnostic judgement. METHODS: Otolaryngologists were recruited virtually across the United States for this experiment on human-AI interaction. Participants were shown 12 different video-stroboscopic exams from patients with previously diagnosed laryngopharyngeal reflux or vocal fold paresis and asked to determine the presence of disease. They were then exposed to a random diagnosis purportedly resulting from an ML-CDST and given the opportunity to revise their diagnosis. The ML-CDST output was presented with no explanation, a general explanation, or a specific explanation of its logic. The ML-CDST impact on diagnostic judgement was assessed with McNemar's test. RESULTS: Forty-five participants were recruited. When participants reported less confidence (268 observations), they were significantly (p = 0.001) more likely to change their diagnostic judgement after exposure to ML-CDST output compared to when they reported more confidence (238 observations). Participants were more likely to change their diagnostic judgement when presented with a specific explanation of the CDST logic (p = 0.048). CONCLUSIONS: Our study suggests that otolaryngologists are susceptible to accepting ML-CDST diagnostic recommendations, especially when less confident. Otolaryngologists' trust in ML-CDST output is increased when accompanied with a specific explanation of its logic. LEVEL OF EVIDENCE: 2 Laryngoscope, 134:2799-2804, 2024.
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Sistemas de Apoio a Decisões Clínicas , Aprendizado de Máquina , Otorrinolaringologistas , Confiança , Humanos , Masculino , Feminino , Adulto , Estados Unidos , Refluxo Laringofaríngeo/diagnóstico , Paralisia das Pregas Vocais/diagnóstico , Otolaringologia , Pessoa de Meia-IdadeRESUMO
RATIONALE AND OBJECTIVES: This study aimed to assess the value of diffusion kurtosis imaging (DKI)-based radiomics models in differentiating glioblastoma (GB) from single brain metastasis (SBM) and compare their diagnostic performance with that of routine magnetic resonance imaging (MRI) models. MATERIALS AND METHODS: A total of 110 patients who underwent DKI and were pathologically diagnosed with GB (n = 58) or SBM (n = 52) were enrolled in this study. Radiomics features were extracted from the manually delineated region of interest of the lesion. A training set for model development was constructed from the images of 88 random patients, and 22 patients were reserved for independent validation. Seven single-DKI-parametric models and a multi-DKI-parametric model were constructed using six classifiers, whereas four single-routine-sequence models (based on T2 weighted imaging, apparent diffusion coefficient, T2-dark-fluid, and contrast-enhanced T1 magnetization prepared rapid gradient echo) and a multisequence routine MRI model were constructed for comparison. Receiver operating characteristic curve analysis was conducted to assess the diagnostic performance. The areas under the curve (AUCs) of different models were compared using the DeLong test. RESULTS: The AUCs of the single-DKI-parametric models ranged from 0.800 to 0.933 (mean kurtosis [MK] model). The multi-DKI-parametric model had a slightly higher AUC (0.958) than the MK model; however, the difference was not statistically significant (P = 0.688). In comparison, the AUCs of the routine MRI models ranged from 0.633 to 0.733 (multisequence routine MRI model). The AUC of the multi-DKI-parametric model was significantly higher than that of the multisequence routine MRI model (P = 0.042). CONCLUSION: The multi-DKI-parametric radiomics model exhibited better performance than that of the single-DKI-parametric models and routine MRI models in distinguishing GB from SBM.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/diagnóstico por imagem , Glioblastoma/patologia , Radiômica , Imagem de Difusão por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/métodos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologiaRESUMO
Peptide assemblies are promising nanomaterials, with their properties and technological applications being highly hinged on their supramolecular architectures. Here, how changing the chirality of the terminal charged residues of an amphiphilic hexapeptide sequence Ac-I4 K2 -NH2 gives rise to distinct nanostructures and supramolecular handedness is reported. Microscopic imaging and neutron scattering measurements show thin nanofibrils, thick nanofibrils, and wide nanotubes self-assembled from four stereoisomers. Spectroscopic and solid-state nuclear magnetic resonance (NMR) analyses reveal that these isomeric peptides adopt similar anti-parallel ß-sheet secondary structures. Further theoretical calculations demonstrate that the chiral alterations of the two C-terminal lysine residues cause the formation of diverse single ß-strand conformations, and the final self-assembled nanostructures and handedness are determined by the twisting direction and degree of single ß-strands. This work not only lays a useful foundation for the fabrication of diverse peptide nanostructures by manipulating the chirality of specific residues but also provides a framework for predicting the supramolecular structures and handedness of peptide assemblies from single molecule conformations.
Assuntos
Lateralidade Funcional , Nanoestruturas , Peptídeos/química , Nanoestruturas/química , Isomerismo , Estrutura Secundária de ProteínaRESUMO
OBJECTIVES: HPV vaccination rates remain suboptimal despite proven efficacy. Data suggest misconceptions or lack of knowledge are leading barriers. Our study aimed to develop and pilot a novel interactive education resource designed to educate parents and patients about HPV vaccines. METHODS: This is a prospective pilot study conducted in an urban teaching hospital pediatric clinic. The Patient Activated Learning System (PALS) intervention included 3 web-based videos with HPV vaccine-related educational content. Participants were parents of adolescent patients, aged 11-17 years, and young adult patients, aged 18-26 years. Enrolled participants completed an HPV vaccine knowledge survey before and after watching PALS; paired scores were evaluated. Acceptability and participant-reported impact of PALS modules were measured via Likert-scale surveys. RESULTS: 132 individuals were approached; 101 (76%) enrolled and completed the study. Participants self-identified as Hispanic (50%), non-Hispanic Black (23%), non-Hispanic White (7%), Asian (6%), American/Alaskan/Hawaiian Native or Pacific Islander (5%). Half reported earning ≤$40,000 annually; 57% had only a high school education. Post-intervention knowledge scores were increased compared to baseline (9.87/27 points vs 17.53/27 points, p < 0.01). PALS modules were reported as enjoyable to use and understandable (89% and 93%, respectively), and improved participants' understanding of the importance of HPV vaccination (90%). Of the 18 patients unvaccinated at baseline, 39% received 1 shot of the HPV vaccine within one month. CONCLUSION: The PALS HPV vaccine educational intervention was feasible, acceptable, and improved knowledge among a diverse, underserved population. Our intervention may positively influence HPV vaccination rates, with potential to overcome HPV vaccine hesitancy.
Assuntos
Intervenção Baseada em Internet , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Criança , Adulto Jovem , Adolescente , Humanos , Vacinação , Infecções por Papillomavirus/prevenção & controle , Projetos Piloto , Estudos Prospectivos , Pobreza , Aceitação pelo Paciente de Cuidados de Saúde , Conhecimentos, Atitudes e Prática em SaúdeRESUMO
OBJECTIVE: Primary care practitioners (PCPs) care for the majority of patients with knee osteoarthritis (KOA). Despite the existing evidence-based guidelines, PCPs often feel unequipped to evaluate and effectively treat patients with KOA. To address this need, we designed and implemented a free internet-based program focusing on the diagnosis and treatment of KOA. We assessed whether the program led to improvements in participants' confidence in their knowledge and skills related to effectively recognizing and caring for patients with or at risk of KOA. METHODS: We used Caffarella's integrative model to develop a program aligned with the American College of Rheumatology 2019 Guideline for the treatment of KOA. The program incorporated 18 case-based questions to provide retrieval practice and mastery experiences. We assessed changes in participants' confidence in their KOA knowledge and skills after program completion. RESULTS: Of the first 353 learners completing the program, 53.8% were women, 41.9% had a clinical focus in primary care, and 69.1% were nonphysicians. Overall confidence in KOA knowledge and skills improved after program completion (P < 0.001; effect size = 1.28, 95% confidence interval 1.12-1.45), with largest improvements among participants with lower pre-program confidence. A total of 95.8% of participants indicated they would recommend the program to others. CONCLUSION: A free online program focusing on the effective care for patients with KOA attracted a wide range of learners, even though it targeted PCPs. Participants overwhelmingly endorsed it as highly relevant and would recommend it to others. Whether improvements in confidence translate into better patient outcomes is an important area for future research.