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1.
Front Oncol ; 14: 1421869, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39099699

RESUMO

Background: Proton minibeam radiation therapy (pMBRT) can deliver spatially fractionated dose distributions with submillimeter resolution. These dose distributions exhibit significant heterogeneity in both depth and lateral directions. Accurate characterization of pMBRT doses requires dosimetry devices with high spatial resolution and a wide dynamic range. Furthermore, the dependency of dosimetric measurements on Linear Energy Transfer (LET), as observed in conventional proton therapy, is also present in pMBRT depth dose measurements. Purpose: This work demonstrates the process of performing comprehensive dosimetric measurements to characterize the pMBRT collimator on a clinical single-gantry proton machine, utilizing commercially available dosimetry devices. Methods: The minibeam collimator is designed to be mounted on the clinical nozzle as a beam-modifying accessory. Three collimators, each with a slit opening of 0.4 mm, are thoroughly evaluated. The center-to-center (c-t-c) distances of the slits for these collimators are 2.8 mm, 3.2 mm, and 4.0 mm, respectively. High spatial resolution dosimetry devices are essential for PMBRT dose characterizations. To meet this requirement, two-dimensional (2D) dose measurement devices, Gafchromic films, are used to measure lateral profiles at various depths. Films are also used for depth dose profile measurements in solid water. Additionally, high-resolution point dose detectors, microDiamond, and Razor diode detectors are employed for lateral profile measurements at various depths. Percent depth dose (PDD) measurements of pMBRT in solid water, with various proton energies, collimators, and air gaps, are performed using Gafchromic films. The film's LET dependency for proton beams is corrected to ensure accurate pMBRT PDD measurements. The Monte Carlo simulation tool TOPAS is utilized to compare and validate all experimental measurements. Results: At depths where LET is not a concern, film dose measurements were consistent with microDiamond and Razor diode point measurements. The point detectors need to be orientated with the thin side aligned to the incoming beam. Comparison of the lateral dose profiles extracted from TOPAS simulations, films, microDiamond, and Razor diode detectors shows a passing rate exceeding 98% in 1D gamma analysis at 3% 0.1 mm criteria.However, when the microDiamond detector is orientated to face the pMBRT beam, its spatial resolution may not be sufficient to capture the peak and valley dose accurately. Nevertheless, an accuracy within 2% can still be achieved when comparing the average dose. The PDD measurements show that the peak valley dose ratio (PVDR) of pMBRT can be altered at different depths with different air gaps using the same collimator or different collimators of different c-t-c distances. Conclusion: Our study demonstrates that comprehensive dose measurements for pMBRT can be conducted using standard clinical dose measurement devices. These measurements are indispensable for guiding and ensuring accurate dose reporting in pre-clinical studies using the pMBRT technique.

2.
Pediatr Ann ; 53(7): e258-e263, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38949874

RESUMO

Past literature on the development of type 1 diabetes (T1D) and type 2 diabetes (T2D) has emphasized the influence of exogenous factors, including viral infections, in the development of these conditions. The coronavirus disease 2019 (COVID-19) pandemic again highlighted the complicated connection between viral infection and the development of diabetes. The complex interplay of proinflammatory, genetic, and socioeconomic factors can help explain the increased incidence of T1D and T2D during the pandemic. Proposed pathophysiological mechanisms connecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to T1D include the expression of angiotensin enzyme 2 receptors on pancreatic islet cells, resultant proinflammatory states, and potential transient damage caused by viral entry. The intricate web of genetic factors, social determinants of health (including the rise of obesity), and the impact of proinflammatory states during SARS-CoV-2 infection on insulin resistance suggests mechanisms linking SARS-CoV-2 infection to the development of diabetes. [Pediatr Ann. 2024;53(7):e258-e263.].


Assuntos
COVID-19 , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Criança , Humanos , COVID-19/epidemiologia , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Incidência , Fatores de Risco , SARS-CoV-2
3.
J Biol Chem ; 300(8): 107582, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39025453

RESUMO

The Ccr4-Not complex contains the poorly understood Not4 ubiquitin ligase that functions in transcription, mRNA decay, translation, proteostasis, and endolysosomal nutrient signaling. To gain further insight into the in vivo functions of the ligase, we performed quantitative proteomics in Saccharomyces cerevisiae using yeast cells lacking Not4, or cells overexpressing wild-type Not4 or an inactive Not4 mutant. Herein, we provide evidence that balanced Not4 activity maintains ribosomal protein (RP) homeostasis independent of changes to RP mRNA or known Not4 ribosomal substrates. Intriguingly, we also find that Not4 loss activates 40S ribosomal autophagy independently of canonical Atg7-dependent macroautophagy, indicating that microautophagy is responsible. We previously demonstrated that Ccr4-Not stimulates the target of rapamycin complex 1 (TORC1) signaling, which activates RP expression and inhibits autophagy, by maintaining vacuole V-ATPase H+ pump activity. Importantly, combining Not4 deficient cells with a mutant that blocks vacuole H+ export fully restores RP expression and increases 40S RP autophagy efficiency. In contrast, restoring TORC1 activity alone fails to rescue either process, indicating that Not4 loss disrupts additional endolysosomal functions that regulate RP expression and 40S autophagy. Analysis of the Not4-regulated proteome reveals increases in endolysosomal and autophagy-related factors that functionally interact with Not4 to control RP expression and affect 40S autophagy. Collectively, our data indicate that balanced Ccr4-Not ubiquitin ligase signaling maintains RP homeostasis and inhibits 40S autophagy via the ligase's emerging role as an endolysosomal regulator.

4.
Radiat Res ; 202(2): 102-129, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38954476

RESUMO

This review aims to trace the evolution of dosimetry, highlight its significance in the advancement of radiation research, and identify the current trends and methodologies in the field. Key historical milestones, starting with the first publications in the journal in 1954, will be synthesized before addressing contemporary practices in radiation medicine and radiobiological investigation. Finally, possibilities for future opportunities in dosimetry will be offered. The overarching goal is to emphasize the indispensability of accurate and reproducible dosimetry in enhancing the quality of radiation research and practical applications of ionizing radiation.


Assuntos
Radiometria , Radiometria/normas , Humanos , História do Século XX , Radiobiologia , História do Século XXI
5.
Front Sports Act Living ; 6: 1437700, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39055173

RESUMO

Caffeine is recognized as one of the most effective dietary ergogenic aids in sports, yet its evidence-based effectiveness in esports is unclear. This study investigated the effects of two different doses of caffeine on the shooting performance and reaction time of 24 first-person shooter (FPS) esports players (22 men, 2 women; age = 22.29 ± 2.91 years). Participants completed three experimental trials in which they consumed either a water control (CON), a 1 mg·kg-1 BM (CAF1) or a 3 mg·kg-1 BM (CAF3) dose of caffeine. Performance measures (e.g., score, accuracy (%), hit rate (hits/sec), and shots fired) were assessed in a static clicking and reactive tracking style task on the KovaaK's FPS aim trainer. Reaction time was used to assess vigilance on the psychomotor vigilance test (PVT). Performance was measured at four time points in each trial: pre-treatment (PRE), 60 min (POST1), 80 min (POST2), and 100 min (POST3) post-treatment. Significant differences were identified using repeated-measures analysis of variances. Caffeine, irrespective of dose, significantly improved performance compared to CON for static clicking score and hit rate, reactive tracking accuracy, and reaction time on the PVT. Significant interactions between treatment and time were identified and post hoc analyses showed that compared to CON, CAF1 significantly improved static clicking score at POST1 and POST3, static clicking hit rate at POST1, reactive tracking accuracy at POST1, POST2, and POST3, and reaction time on the PVT at POST1 and POST2. Post hoc analysis also showed that compared to CON, CAF3 significantly improved static clicking score, reactive tracking accuracy, and reaction time on the PVT at all time points, in addition to static clicking hit rate at POST1 and POST3. In summary, caffeine supplementation enhances the shooting performance and reaction time of FPS esports players.

6.
Ecology ; : e4382, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39056489

RESUMO

Conspecific negative density dependence (CNDD) is thought to be a key process in maintaining plant diversity. However, the strength of CNDD is highly variable in space and time as well as among species, and correlates of this variation that might help to understand and explain it remain largely unquantified. Using Bayesian hierarchical models, we took advantage of 10-year seedling monitoring data that were collected annually in every dry and rainy season in a seasonal tropical forest. We quantified the interspecific variation in the strength of CNDD and its temporal variation. We also examined potential correlates of this interspecific and temporal variation, including species functional traits (such as drought-tolerant traits, defense-related traits, and recourse acquisition traits) and species abundances. In the dry season, we found a negative relationship between the density of neighboring conspecific seedlings on seedling survival, while in the rainy season, there was a negative relationship between the density of neighboring conspecific adults on seedling survival. In addition, we found that interspecific variation in CNDD was related to drought-tolerant traits in the dry season but not in the rainy season. Across years, we found that drought-intolerant species suffer less CNDD during the dry seasons that have higher rainfall, whereas drought-tolerant species suffer less CNDD when the dry season has lower rainfall. We also found that rare species suffered stronger CNDD in the dry season. Overall, our study highlights that CNDD is highly variable among species and through time, necessitating a deeper appreciation of the environmental and functional contexts of CNDD and their interactions.

7.
PLoS Biol ; 22(7): e3002700, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39013163

RESUMO

The ecology of forest ecosystems depends on the composition of trees. Capturing fine-grained information on individual trees at broad scales provides a unique perspective on forest ecosystems, forest restoration, and responses to disturbance. Individual tree data at wide extents promises to increase the scale of forest analysis, biogeographic research, and ecosystem monitoring without losing details on individual species composition and abundance. Computer vision using deep neural networks can convert raw sensor data into predictions of individual canopy tree species through labeled data collected by field researchers. Using over 40,000 individual tree stems as training data, we create landscape-level species predictions for over 100 million individual trees across 24 sites in the National Ecological Observatory Network (NEON). Using hierarchical multi-temporal models fine-tuned for each geographic area, we produce open-source data available as 1 km2 shapefiles with individual tree species prediction, as well as crown location, crown area, and height of 81 canopy tree species. Site-specific models had an average performance of 79% accuracy covering an average of 6 species per site, ranging from 3 to 15 species per site. All predictions are openly archived and have been uploaded to Google Earth Engine to benefit the ecology community and overlay with other remote sensing assets. We outline the potential utility and limitations of these data in ecology and computer vision research, as well as strategies for improving predictions using targeted data sampling.


Assuntos
Ecossistema , Florestas , Árvores , Redes Neurais de Computação , Ecologia/métodos
8.
Artigo em Inglês | MEDLINE | ID: mdl-38968697

RESUMO

INTRODUCTION: Infection is a common mode of failure in lower extremity endoprostheses. The Prophylactic Antibiotic Regimens in Tumor Surgery trial reported that 5 days of cefazolin had no difference in surgical site infection compared with 24 hours of cefazolin. Our purpose was to evaluate infection rates of patients receiving perioperative cefazolin monotherapy, cefazolin-vancomycin dual therapy, or alternative antibiotic regimens. METHODS: A single-center retrospective review was conducted on patients who received lower extremity endoprostheses from 2008 to 2021 with minimum 1-year follow-up. Three prophylactic antibiotic regimen groups were compared: cefazolin monotherapy, cefazolin-vancomycin dual therapy, and alternative regimens. The primary outcome was deep infection, defined by a sinus tract, positive culture, or clinical diagnosis. Secondary outcomes were revision surgery, microorganisms isolated, and superficial wound issues. RESULTS: The overall deep infection rate was 10% (30/294) at the median final follow-up of 3.0 years (IQR 1.7 to 5.4). The deep infection rates in the cefazolin, cefazolin-vancomycin, and alternative regimen groups were 8% (6/72), 10% (18/179), and 14% (6/43), respectively (P = 0.625). Patients not receiving cefazolin had an 18% deep infection rate (6/34) and 21% revision surgery rate (7/34) compared with a 9% deep infection rate (24/260) (P = 0.13) and 12% revision surgery rate (31/260) (P = 0.17) in patients receiving cefazolin. In those not receiving cefazolin, 88% (30/34) were due to a documented penicillin allergy, only two being anaphylaxis. All six patients in the alternative regimen group who developed deep infections did not receive cefazolin secondary to nonanaphylactic penicillin allergy. CONCLUSION: The addition of perioperative vancomycin to cefazolin in lower extremity endoprosthetic reconstructions was not associated with a lower deep infection rate. Patients who did not receive cefazolin trended toward higher rates of deep infection and revision surgery, although not statistically significant. The most common reason for not receiving cefazolin was a nonanaphylactic penicillin allergy, highlighting the continued practice of foregoing cefazolin unnecessarily.

9.
Oecologia ; 205(2): 411-422, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38898337

RESUMO

The interplay of positive and negative species interactions controls species assembly in communities. Dryland plant communities, such as savannas, are important to global biodiversity and ecosystem functioning. Sandhill oaks in xeric savannas of the southeastern United States can facilitate longleaf pine by enhancing seedling survival, but the effects of oaks on recruitment and growth of longleaf pine have not been examined. We censused, mapped, and monitored nine contiguous hectares of longleaf pine in a xeric savanna to quantify oak-pine facilitation, and to examine other factors impacting recruitment, such as vegetation cover and longleaf pine tree density. We found that newly recruited seedlings and grass stage longleaf pines were more abundant in oak-dominated areas where densities were 230% (newly recruited seedlings) and 360% (grass stage) greater from lowest to highest oak neighborhood densities. Longleaf pine also grew faster under higher oak density. Longleaf pine recruitment was lowest under longleaf pine canopies. Mortality of grass stage and bolt stage longleaf pine was low (~1.0% yr-1) in the census interval without fire. Overall, our findings highlight the complex interactions between pines and oaks-two economically and ecologically important genera globally. Xeric oaks should be incorporated as a management option for conservation and restoration of longleaf pine ecosystems.


Assuntos
Ecossistema , Pradaria , Pinus , Quercus , Plântula , Pinus/crescimento & desenvolvimento , Quercus/crescimento & desenvolvimento , Plântula/crescimento & desenvolvimento
10.
N Engl J Med ; 391(1): 9-20, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38875111

RESUMO

BACKGROUND: Whether proton-pump inhibitors are beneficial or harmful for stress ulcer prophylaxis in critically ill patients undergoing invasive ventilation is unclear. METHODS: In this international, randomized trial, we assigned critically ill adults who were undergoing invasive ventilation to receive intravenous pantoprazole (at a dose of 40 mg daily) or matching placebo. The primary efficacy outcome was clinically important upper gastrointestinal bleeding in the intensive care unit (ICU) at 90 days, and the primary safety outcome was death from any cause at 90 days. Multiplicity-adjusted secondary outcomes included ventilator-associated pneumonia, Clostridioides difficile infection, and patient-important bleeding. RESULTS: A total of 4821 patients underwent randomization in 68 ICUs. Clinically important upper gastrointestinal bleeding occurred in 25 of 2385 patients (1.0%) receiving pantoprazole and in 84 of 2377 patients (3.5%) receiving placebo (hazard ratio, 0.30; 95% confidence interval [CI], 0.19 to 0.47; P<0.001). At 90 days, death was reported in 696 of 2390 patients (29.1%) in the pantoprazole group and in 734 of 2379 patients (30.9%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.85 to 1.04; P = 0.25). Patient-important bleeding was reduced with pantoprazole; all other secondary outcomes were similar in the two groups. CONCLUSIONS: Among patients undergoing invasive ventilation, pantoprazole resulted in a significantly lower risk of clinically important upper gastrointestinal bleeding than placebo, with no significant effect on mortality. (Funded by the Canadian Institutes of Health Research and others; REVISE ClinicalTrials.gov number, NCT03374800.).


Assuntos
Estado Terminal , Pantoprazol , Inibidores da Bomba de Prótons , Respiração Artificial , Humanos , Pantoprazol/uso terapêutico , Pantoprazol/efeitos adversos , Pantoprazol/administração & dosagem , Respiração Artificial/efeitos adversos , Masculino , Pessoa de Meia-Idade , Feminino , Inibidores da Bomba de Prótons/uso terapêutico , Inibidores da Bomba de Prótons/efeitos adversos , Inibidores da Bomba de Prótons/administração & dosagem , Idoso , Hemorragia Gastrointestinal/prevenção & controle , 2-Piridinilmetilsulfinilbenzimidazóis/uso terapêutico , 2-Piridinilmetilsulfinilbenzimidazóis/efeitos adversos , 2-Piridinilmetilsulfinilbenzimidazóis/administração & dosagem , Úlcera Péptica/prevenção & controle , Unidades de Terapia Intensiva , Pneumonia Associada à Ventilação Mecânica/prevenção & controle , Método Duplo-Cego , Estresse Fisiológico , Adulto
11.
Ecol Lett ; 27(6): e14449, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38857318

RESUMO

When plants die, neighbours escape competition. Living conspecifics could disproportionately benefit because they are freed from negative intraspecific processes; however, if the negative effects of past conspecific neighbours persist, other species might be advantaged, and diversity might be maintained through legacy effects. We examined legacy effects in a mapped forest by modelling the survival of 37,212 trees of 23 species using four neighbourhood properties: living conspecific, living heterospecific, legacy conspecific (dead conspecifics) and legacy heterospecific densities. Legacy conspecific effects proved nearly four times stronger than living conspecific effects; changes in annual survival associated with legacy conspecific density were 1.5% greater than living conspecific effects. Over 90% of species were negatively impacted by legacy conspecific density, compared to 47% by living conspecific density. Our results emphasize that legacies of trees alter community dynamics, revealing that prior research may have underestimated the strength of density dependent interactions by not considering legacy effects.


Assuntos
Florestas , Densidade Demográfica , Árvores , Árvores/fisiologia , Dinâmica Populacional , Modelos Biológicos , Biodiversidade
12.
Cancer Res ; 84(16): 2626-2644, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38888469

RESUMO

Fibrolamellar hepatocellular carcinoma (FLC) is a rare liver cancer that is driven by the fusion of DNAJB1 and PRKACA, the catalytic subunit of protein kinase A (PKA). PKA activity is controlled through regulatory proteins that both inhibit catalytic activity and control localization, and an excess of regulatory subunits ensures PRKACA activity is inhibited. Here, we found an increase in the ratio of catalytic to regulatory units in FLC patient tumors driven by DNAJB1::PRKACA using mass spectrometry, biochemistry, and immunofluorescence, with increased nuclear localization of the kinase. Overexpression of DNAJB1::PRKACA, ATP1B1::PRKACA, or PRKACA, but not catalytically inactive kinase, caused similar transcriptomic changes in primary human hepatocytes, recapitulating the changes observed in FLC. Consistently, tumors in patients missing a regulatory subunit or harboring an ATP1B1::PRKACA fusion were indistinguishable from FLC based on the histopathological, transcriptomic, and drug-response profiles. Together, these findings indicate that the DNAJB1 domain of DNAJB1::PRKACA is not required for FLC. Instead, changes in PKA activity and localization determine the FLC phenotype. Significance: Alterations leading to unconstrained protein kinase A signaling, regardless of the presence or absence of PRKACA fusions, drive the phenotypes of fibrolamellar hepatocellular carcinoma, reshaping understanding of the pathogenesis of this rare liver cancer.


Assuntos
Carcinoma Hepatocelular , Subunidades Catalíticas da Proteína Quinase Dependente de AMP Cíclico , Proteínas de Choque Térmico HSP40 , Neoplasias Hepáticas , Humanos , Proteínas de Choque Térmico HSP40/metabolismo , Proteínas de Choque Térmico HSP40/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Subunidades Catalíticas da Proteína Quinase Dependente de AMP Cíclico/metabolismo , Subunidades Catalíticas da Proteína Quinase Dependente de AMP Cíclico/genética , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/genética , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Regulação Neoplásica da Expressão Gênica , ATPase Trocadora de Sódio-Potássio
13.
Air Med J ; 43(4): 313-320, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38897694

RESUMO

OBJECTIVE: Given the recommendations against the use of critical incident stress debriefing, the emergency medical services (EMS) Code Lavender program was created as a mechanism to consistently recognize and reach out to EMS clinicians after acute crisis events, offer nonintrusive informal peer support and acts of kindness, and provide stepwise support via mental health professionals as needed. The study aimed to assess program utilization and evaluate the program's impact on EMS clinicians' perceptions of support and resources available to them after an acute crisis event. METHODS: Anonymous surveys were distributed before program implementation and 18 months later. Program utilization was tracked using REDCap (Vanderbilt University, Nashville, TN). Fisher exact tests and logistic regression were used to analyze the survey results. RESULTS: Within 30 months, 87 referrals were made. Seventy-seven preprogram (59% response rate) and 104 intraprogram (88% response rate) surveys were collected. There were no differences between respondents by sex or role. There were significant improvements in knowing where to go for help (from 40% to 85%, P < .001) and willingness to seek help if needed (from 40% to 59%, P = .02). CONCLUSION: The implementation of an EMS Code Lavender program led to significant increases in EMS clinician self-reported knowledge of where to go and willingness to seek help after acute crisis events.


Assuntos
Serviços Médicos de Emergência , Humanos , Masculino , Feminino , Adulto , Intervenção em Crise , Grupo Associado , Inquéritos e Questionários , Pessoa de Meia-Idade , Auxiliares de Emergência/psicologia , Apoio Social
14.
J Am Acad Orthop Surg ; 32(17): 763-770, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38773841

RESUMO

Pickleball is one of the fastest growing sports in the United States with millions of players nationwide. It is a relatively appealing sport because of its ease of access, low impact, and highly social atmosphere, allowing players of all ages to participate. As the number of players continues its dramatic increase, player injuries are certain to increase in turn. There is little to no orthopaedic research on pickleball-related injuries and a paucity of data regarding treatment and prevention strategies. This summary was designed to familiarize orthopaedic surgeons with the basics of the sport and highlight potential pickleball-related injuries they may encounter in practice.


Assuntos
Traumatismos em Atletas , Humanos , Traumatismos em Atletas/terapia , Esportes , Estados Unidos
15.
MicroPubl Biol ; 20242024.
Artigo em Inglês | MEDLINE | ID: mdl-38741934

RESUMO

Antimicrobial resistance (AMR) in microorganisms is an ongoing threat to human health across the globe. To better characterize the AMR profiles of six strains of Staphylococcus aureus , we performed a secondary analysis that consisted of the following steps: 1) download fastq files from the Sequence Read Archive, 2) perform a de novo genome assembly from the sequencing reads, 3) annotate the assembled contigs, 4) predict the presence of antimicrobial resistance genes. We predicted the presence of 75 unique genes that conferred resistance against 22 unique antimicrobial compounds.

16.
Head Neck Pathol ; 18(1): 39, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38727854

RESUMO

BACKGROUND: Columnar cell papillary thyroid carcinoma (CC-PTC) is a morphologic subtype of papillary thyroid carcinoma with a variable prognosis. It is characterized by neoplastic thyroid follicular-derived cells with pseudostratified columnar morphology arranged in papillary or follicular structures with supranuclear or subnuclear vacuoles. The molecular profile of this subtype has only recently come under scrutiny, with mixed results. The aim of this study is to further explore the morphologic, immunohistochemical, and genetic profile of CC-PTC, as well as to correlate these features with clinical outcomes. METHODS: CC-PTC cases were identified from 3 institutions. Immunohistochemistry (ER, CDX2) and molecular testing (DNA and RNA sequencing) were performed. Clinicopathologic parameters and patient outcomes were recorded. RESULTS: Twelve cases (2006-2023) were identified, all in adults (age 45-91). Two presented with disease outside the thyroid gland (neck and mediastinum) and two presented with distant metastasis. Four were high-grade differentiated thyroid carcinomas (necrosis or mitoses), one of which died of disease. Four were noninvasive or minimally invasive, one of which locally recurred. Three patients had lymph node metastases. ER and CDX2 were positive in 73% and 50%, respectively. Pathogenic mutations were found in TERT promoter (n = 3), RAS (n = 2), ATM, NOTCH1, APC, and ESR1, along with cases bearing AGK::BRAF fusion (n = 1), BRAF VE1 expression (n = 1), and NF2 loss (n = 1). CONCLUSIONS: This study represents the largest molecularly defined cohort of non-oncocytic thyroid carcinomas with columnar cell morphology. These tumors represent a genetically and behaviorally heterogeneous group of neoplasms, some of which have RAS-like or follicular neoplasm-like genetics, some of which have BRAF-p.V600E-like or classic papillary thyroid carcinoma-like genetics, and some of which remain unclear. Noninvasive or minimally invasive tumors showed an indolent course compared to those with angioinvasion, gross extrathyroidal growth, or high-grade morphology. Consideration could be given to reclassification of this neoplasm outside of the subtyping of papillary thyroid carcinoma in light of its genetic diversity, distinct morphology, and clinical behavior more closely aligned with follicular thyroid neoplasms.


Assuntos
Adenocarcinoma Folicular , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/genética , Masculino , Feminino , Pessoa de Meia-Idade , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/genética , Idoso , Idoso de 80 Anos ou mais , Adenocarcinoma Folicular/patologia , Adenocarcinoma Folicular/genética , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética
17.
Med Phys ; 51(6): 3995-4006, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38642468

RESUMO

BACKGROUND: Minibeam represents a preclinical spatially fractionated radiotherapy modality with great translational potential. The advantage lies in its high therapeutic index (compared to GRID and LATTICE) and ability to treat at greater depth (compared to microbeam). Proton minibeam radiotherapy (pMBRT) is a synergy of proton and minibeam. While the single-gantry proton facility has gained popularity due to its affordability and compact design, it often has limited beam time available for research purposes. Conversely, given the current requirement of pMBRT on specific minibeam hardware collimators, necessitates a reproducible and fast setup to minimize pMBRT treatment time and streamline the switching time between pMBRT and conventional treatment for clinically translation. PURPOSE: The contribution of this work is the development and characterization of the first pMBRT system tailored for single-gantry proton facility. The system allows for efficient and reproducible plug-and-play setup, achievable within minutes. METHODS: The single room pMBRT system is constructed based on IBA ProteusONE proton machine. The end of nozzle is attached with beam modifying accessories though an accessory drawer. A small snout is attached to the accessory drawer and used to hold apertures and range shifters. The minibeam aperture consists of two components: a fitting ring and an aperture body. Three minibeam apertures were manufactured. The first-generation apertures underwent qualitatively analysis with film, and the second generation aperture underwent more comprehensive quantitative measurement. The reproducibility of the setup is accessed, and the film measurements are performed to characterize the pMBRT system in cross validation with Monte Carlo (MC) simulations. RESULTS: We presented initial results of large field pMBRT aperture and the film measurements indicates the effect of source-to-isocenter distance = 930 cm in Y proton scanning direction. Consistent with TOPAS MC simulation, the dose uniformity of pMBRT field <2 cm is demonstrated to be better than 2%, rendering its suitability for pre-clinical studies. Subsequently, we developed the second generation of aperture with five slits and characterized the aperture with film dosimetry studies and compared the results to the benchmark MC. Comprehensive film measurements were also performed to evaluate the effect of divergence, air gap and gantry-angle dependency and repeatability and revealing a consistent performance within 5%. Furthermore, the 2D gamma analysis indicated a passing rate exceeding 99% using 3% dose difference and 0.2 mm distance agreement criteria. We also establish the peak valley dose ratio and the depth dose profile measurements, and the results are within 10% from MC simulation. CONCLUSIONS: We have developed the first pMBRT system tailored for a single-gantry proton facility, which has demonstrated accuracy in benchmark with MC simulations, and allows for efficient plug-and-play setup, emphasizing efficiency.


Assuntos
Desenho de Equipamento , Terapia com Prótons , Terapia com Prótons/instrumentação , Método de Monte Carlo , Prótons , Dosagem Radioterapêutica
18.
Injury ; 55(6): 111540, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38622039

RESUMO

OBJECTIVES: In far-distal extra-articular tibia fracture "extreme" nailing, debate surrounds the relative biomechanical performance of plating the fibula compared with extra distal interlocks. This study aimed to evaluate several constructs for extreme nailing including one interlock (one medial-lateral interlock), one interlock + plate (one medial-lateral interlock with lateral fibula compression plating), and two interlocks (one medial-lateral interlock and one anterior-posterior interlock). METHODS: Fifteen pairs of fresh cadaver legs were instrumented with a tibial nail to the physeal scar. A 1 cm segment of bone was resected from the distal tibia 3.5 cm from the joint and an oblique osteotomy was made in the distal fibula. We loaded specimens with three different distal fixation constructs (one interlock, one interlock + plate, and two interlocks) through 10,000 cycles form 100N-700 N of axial loading. Load to failure (Newtons), angulation and displacement were also measured. RESULTS: Mean load to failure was 2092 N (one interlock), 1917 N (one interlock + plate), and 2545 N (two interlocks). Linear mixed effects modeling demonstrated that two interlocks had a load to failure 578 N higher than one interlock alone (95 % CI, 74N-1082 N; P = 0.02), but demonstrated no significant difference between one interlock and one interlock + plate. No statistically significant difference in rates or timing of displacement >2 mm or angulation >10° were demonstrated. CONCLUSIONS: When nailing far-distal extra-articular tibia and fibula fractures, adding a second interlock provides more stability than adding a fibular plate. Distal fibula plating may have minimal biomechanical effect in extreme nailing.


Assuntos
Pinos Ortopédicos , Placas Ósseas , Cadáver , Fíbula , Fixação Intramedular de Fraturas , Fraturas da Tíbia , Humanos , Fraturas da Tíbia/cirurgia , Fraturas da Tíbia/fisiopatologia , Fenômenos Biomecânicos , Fíbula/cirurgia , Fixação Intramedular de Fraturas/instrumentação , Fixação Intramedular de Fraturas/métodos , Masculino , Feminino , Suporte de Carga/fisiologia , Idoso , Fixação Interna de Fraturas/métodos , Fixação Interna de Fraturas/instrumentação , Idoso de 80 Anos ou mais
19.
Adv Colloid Interface Sci ; 327: 103140, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38579462

RESUMO

This paper provides a comprehensive overview of recent advancements in membrane modification for fouling mitigation in various water treatment processes, employing carbon nanomaterials such as fullerenes, nanodiamonds, carbon quantum dots, carbon nanotubes, and graphene oxide. Currently, using different carbon nanomaterials for polymeric membrane fouling mitigation is at various stages: CNT-modified membranes have been studied for more than ten years and have already been tested in pilot-scale setups; tremendous attention has been paid to utilizing graphene oxide as a modifying agent, while the research on carbon quantum dots' influence on the membrane antifouling properties is in the early stages. Given the intricate nature of fouling as a colloidal phenomenon, the review initially delves into the factors influencing the fouling process and explores strategies to address it. The diverse chemistry and antibacterial properties of carbon nanomaterials make them valuable for mitigating scaling, colloidal, and biofouling. This review covers surface modification of existing membranes using different carbon materials, which can be implemented as a post-treatment procedure during membrane fabrication. Creating mixed-matrix membranes by incorporating carbon nanomaterials into the polymer matrix requires the development of new synthetic procedures. Additionally, it discusses promising strategies to actively suppress fouling through external influences on modified membranes. In the concluding section, the review compares the effectiveness of carbon materials of varying dimensions and identifies key characteristics influencing the antifouling properties of membranes modified with carbon nanomaterials.

20.
Robot Rep ; 2(1): 15-28, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38584677

RESUMO

Soft robotics is a rapidly growing field that spans the fields of chemistry, materials science, and engineering. Due to the diverse background of the field, there have been contrasting naming schemes such as "intelligent," "smart," and "adaptive" materials, which add vagueness to the broad innovation among literature. Therefore, a clear, functional, and descriptive naming scheme is proposed in which a previously vague name-Soft Material for Soft Actuators-can remain clear and concise-Phase-Change Elastomers for Artificial Muscles. By synthesizing the working principle, material, and application into a naming scheme, the searchability of soft robotics can be enhanced and applied to other fields. The field of thermo-active soft actuators spans multiple domains and requires added clarity. Thermo-active actuators have potential for a variety of applications spanning virtual reality haptics to assistive devices. This review offers a comprehensive guide to selecting the type of thermo-active actuator when one has an application in mind. In addition, it discusses future directions and improvements that are necessary for implementation.

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