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1.
J Alzheimers Dis ; 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39093076

RESUMO

Fortea et al.'s. (2024) recent data analysis elegantly calls attention to familial late-onset Alzheimer's disease (AD) with APOE4 homozygosity. The article by Grant (2024) reviews the factors associated with AD, particularly the APOE genotype and lifestyle, and the broad implications for prevention, both for individuals with the lifestyles associated with living in resource-rich countries and for those enduring environmental adversity in poverty settings, including high exposure to enteric pathogens and precarious access to healthcare. Grant discusses the issue of APOE genotype and its implications for the benefits of lifestyle modifications. This review highlights that bearing APOE4 could constitute an evolutionary benefit in coping with heavy enteric infections and malnutrition early in life in the critical formative first two years of brain development. However, the critical issue may be that this genotype could be a health concern under shifts in lifestyle and unhealthy diets during aging, leading to severe cognitive impairments and increased risk of AD. This commentary supports the discussions of Grant and the benefits of improving lifestyle for decreasing the risks for AD while providing further understanding and modelling of the early life benefits of APOE4 amidst adversity. This attention to the pathophysiology of AD should help further elucidate these critical, newly appreciated pathogenic pathways for developing approaches to the prevention and management in the context of the APOE genetic variations associated with AD.

2.
Int J Aging Hum Dev ; : 914150241253243, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39093608

RESUMO

The National Institute of Health R25 Research Education Program was evaluated in the second year of implementation. Twelve mentors and 20 underrepresented minority students (URMs) scholars from partnerships and collaborations among five colleges and universities were added to the program to provide a more diverse research experience. Findings reveal that 100% of research mentors agree that the approachableness and accessibility of the program coordinator were beneficial in achieving mentorship goals and objectives. In addition, 85% of the students strongly agreed that the presentation of their research findings and the weekly reflection on goals, identification of accomplishments, and obstacles through the individual development plan were very effective. Of the 23 successfully tracked students for 2 years, six URMs (26.09%) obtained a bachelor's degree and were admitted into a graduate program; two were directly admitted to a PhD program in biomedical sciences.

3.
Med Phys ; 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39088750

RESUMO

BACKGROUND: Although cone beam computed tomography (CBCT) has lower resolution compared to planning CTs (pCT), its lower dose, higher high-contrast resolution, and shorter scanning time support its widespread use in clinical applications, especially in ensuring accurate patient positioning during the image-guided radiation therapy (IGRT) process. PURPOSE: While CBCT is critical to IGRT, CBCT image quality can be compromised by severe stripe and scattering artifacts. Tumor movement secondary to respiratory motion also decreases CBCT resolution. In order to improve the image quality of CBCT, we propose a Lung Diffusion Model (L-DM) framework. METHODS: Our proposed algorithm is based on a conditional diffusion model trained on pCT and deformed CBCT (dCBCT) image pairs to synthesize lung CT images from dCBCT images and benefit CBCT-based radiotherapy. dCBCT images were used as the constraint for the L-DM. The image quality and Hounsfield unit (HU) values of the synthetic CTs (sCT) images generated by the proposed L-DM were compared to three selected mainstream generation models. RESULTS: We verified our model in both an institutional lung cancer dataset and a selected public dataset. Our L-DM showed significant improvement in the four metrics of mean absolute error (MAE), peak signal-to-noise ratio (PSNR), normalized cross-correlation (NCC), and structural similarity index measure (SSIM). In our institutional dataset, our proposed L-DM decreased the MAE from 101.47 to 37.87 HU and increased the PSNR from 24.97 to 29.89 dB, the NCC from 0.81 to 0.97, and the SSIM from 0.80 to 0.93. In the public dataset, our proposed L-DM decreased the MAE from 173.65 to 58.95 HU, while increasing the PSNR, NCC, and SSIM from 13.07 to 24.05 dB, 0.68 to 0.94, and 0.41 to 0.88, respectively. CONCLUSIONS: The proposed L-DM significantly improved sCT image quality compared to the pre-correction CBCT and three mainstream generative models. Our model can benefit CBCT-based IGRT and other potential clinical applications as it increases the HU accuracy and decreases the artifacts from input CBCT images.

4.
Cardiovasc Res ; 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39086170

RESUMO

AIMS: Circulating levels of sphingosine 1-phosphate (S1P), an HDL-associated ligand for endothelial cell (EC) protective S1P receptor-1 (S1PR1), are reduced in disease states associated with endothelial dysfunction. Yet as S1PR1 has high affinity for S1P and can be activated by ligand-independent mechanisms and EC-autonomous S1P production, it is unclear if relative reductions in circulating S1P impact endothelial function. It is also unclear how EC S1PR1 insufficiency, whether induced by ligand deficiency or by S1PR1-directed immunosuppressive therapy, affects different vascular subsets. METHODS AND RESULTS: We here fine-map the zonation of S1PR1 signalling in the murine blood and lymphatic vasculature, superimpose cell type-specific and relative deficiencies in S1P production to define ligand source- and dose-dependence, and correlate receptor engagement to essential functions. In naïve blood vessels, despite broad expression, EC S1PR1 engagement was restricted to resistance-size arteries, lung capillaries and high-endothelial venules (HEV). Similar zonation was observed for albumin extravasation in EC S1PR1 deficient mice, and brain extravasation was reproduced with arterial EC-selective S1pr1 deletion. In lymphatic EC, S1PR1 engagement was high in collecting vessels and lymph nodes and low in terminal capillaries that drain tissue fluids. While EC S1P production sustained S1PR1 signaling in lymphatics and HEV, hematopoietic cells provided ∼90% of plasma S1P and sustained signaling in resistance arteries and lung capillaries. S1PR1 signaling and endothelial function were both surprisingly sensitive to reductions in plasma S1P with apparent saturation around 50% of normal levels. S1PR1 engagement did not depend on sex or age, but modestly increased in arteries in hypertension and diabetes. Sphingosine kinase (Sphk)-2 deficiency also increased S1PR1 engagement selectively in arteries, which could be attributed to Sphk1-dependent S1P release from perivascular macrophages. CONCLUSIONS: This study highlights vessel subtype-specific S1PR1 functions and mechanisms of engagement and supports the relevance of S1P as circulating biomarker for endothelial function.

6.
Artigo em Inglês | MEDLINE | ID: mdl-39087780

RESUMO

OBJECTIVES: To determine the inflammatory profile of CRSwNP in Brazil and characterize the subgroups of CRSwNP patients in this population through cluster analysis. STUDY DESIGN: Multicenter cross-sectional study involving 15 centers representing different regions of Brazil. SUBJECTS AND METHODS: Clinical data of 166 patients and 80 controls, aged 18 to 70 years old, number of surgeries for CRS, history of asthma and aspirin sensitivity, and Lund-Mackay scores on CT scans. During nasal endoscopy, we obtained the Lund-Kennedy scores and collected 2 samples of nasal polyps: one for eosinophil and neutrophil tissue counts and one to quantify different cytokines. RESULTS: 79.6% of our patients had 10 or more eosinophils/HPF. CRSwNP groups exhibited significantly lower concentrations of TNF-alpha and significantly higher concentrations of IFN-gamma, CCL11/Eotaxin, CCL24/Eotaxin-2/MPIF-2, and CCL26/Eotaxin-3 versus the control group (Kruskal-Wallis test). Comparison between CRSwNP groups (≥10 vs <10 eosinophils/HPF) showed no difference in cytokine concentration (Mann-Whitney test). Hierarchical clustering and PCA according to cytokine concentrations revealed 2 main Clusters, with a significantly higher concentration of all cytokines in Cluster 1 (n = 35) than in Cluster 2 (n = 121), except IL-6 and IL-33 (Mann-Whitney test). According to ROC curve analysis the best cut-off to differentiate the 2 clusters was 43 eosinophils/HPF. The group with ≥43 presented a higher prevalence of men and a higher Lund-Mackay score (Mann-Whitney test). CONCLUSIONS: CRSwNP patients in Brazil present mixed inflammation, with 2 distinct groups (high and low inflammatory pattern) that can be distinguished by tissue eosinophilia of ≥43 eosinophils/HPF cut-off in nasal polyps.

7.
BMC Health Serv Res ; 24(1): 888, 2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39097691

RESUMO

BACKGROUND: A concern before 2020, physician burnout worsened during the COVID-19 pandemic. Little empirical data are available on pandemic workplace support interventions or their influence on burnout. We surveyed a national sample of frontline physicians on burnout and workplace support during the pandemic. METHODS: We surveyed a stratified random sample of 12,833 US physicians most likely to care for adult COVID-19 patients from the comprehensive AMA Physician Professional Data ™ file. The sample included 6722 primary care physicians (3331 family physicians, 3391 internists), 880 hospitalists, 1783 critical care physicians (894 critical care physicians, 889 pulmonary intensivists), 2548 emergency medicine physicians, and 900 infectious disease physicians. The emailed survey elicited physicians' perceptions of organizational interventions to provide workplace support and/or to address burnout. Burnout was assessed with the Professional Fulfillment Index Burnout Composite scale (PFI-BC). Proportional specialty representation and response bias were addressed by survey weighting. Logistic regression assessed the association of physician characteristics and workplace interventions with burnout. RESULTS: After weighting, respondents were representative of the total sample. Overall physician burnout was 45.4%, significantly higher than in our previous survey. Open-ended responses mentioned that staffing shortages (physician, nursing, and other staff) combined with the increased volume, complexity, and acuity of patients during the pandemic increased job demands. The most frequent workplace support interventions were direct pandemic control measures (increased access to personal protective equipment, 70.0%); improved telehealth functionality (43.4%); and individual resiliency tools (yoga, meditation, 30.7%). Respondents placed highest priority on workplace interventions to increase financial support and increase nursing and clinician staffing. Factors significantly associated with lower odds of burnout were practicing critical care (compared with emergency medicine) OR 0.33 (95% CI 0.12 - 0.93), improved telehealth functionality OR 0.47 (95% CI 0.23 - 0.97) and being in practice for 11 years or longer OR 0.44 (95% CI 0.19-0.99). CONCLUSIONS: Burnout across frontline specialties increased during the pandemic. Physician respondents focused on inadequate staffing in the context of caring for more and sicker patients, combined with the lack of administrative efforts to mitigate problems. Burnout mitigation requires system-level interventions beyond individual-focused stress reduction programs to improve staffing, increase compensation, and build effective teams.


Assuntos
Esgotamento Profissional , COVID-19 , Médicos , SARS-CoV-2 , Local de Trabalho , Humanos , COVID-19/epidemiologia , COVID-19/psicologia , Esgotamento Profissional/epidemiologia , Esgotamento Profissional/psicologia , Esgotamento Profissional/prevenção & controle , Masculino , Feminino , Médicos/psicologia , Adulto , Local de Trabalho/psicologia , Pessoa de Meia-Idade , Pandemias , Estados Unidos/epidemiologia , Inquéritos e Questionários
9.
Artigo em Inglês | MEDLINE | ID: mdl-39052773

RESUMO

BACKGROUND: Progressive functional decline is a key element of cancer-associated cachexia. Major barriers to translating pre-clinical therapies into the clinic include lack of cancer models that accurately mimic functional decline, which develops over time, and use of non-specific measures, like grip strength, as surrogates for physical function. In this study, we aimed to extend the survival and longevity of a cancer model, in order to investigate cachexia-related function at the basic science level. METHODS: Survival extension studies were performed by testing multiple cell lines, dilutions, and vehicle-types in orthotopic implantation of K-rasLSL.G12D/+; Trp53R172H/+; Pdx-1-Cre (KPC) derived cells. 128 animals in this new model were assessed for cachexia syndrome phenotype using a battery of anatomical, biochemical, and behavioral techniques. RESULTS: We extended the survival of the KPC orthotopic model to 8-9 weeks post-implantation using a relatively low 100-cell dose of DT10022 KPC cells (p<0.001). In this Low-dose Orthotopic (LO) model, progressive muscle wasting was detected in parallel to systemic inflammation; skeletal muscle atrophy at the fiber level was detected as early as 3 weeks post-implantation compared to controls (p<0.001). Gait speed in LO animals declined as early 2-weeks post-implantation while grip strength change was a late event. Principle component and regression analyses revealed distinct cachectic and non-cachectic animal populations, which we leveraged to show that the gait speed decline was specific to cachexia (p<0.01) while grip strength decline was not (p=0.19). CONCLUSION: Gait speed represents an accurate surrogate for cachexia related physical function as opposed to grip strength.

10.
Heliyon ; 10(13): e33615, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39040310

RESUMO

In glucose biofuel cells (G-BFCs), glucose oxidation at the anode and oxygen reduction at the cathode yield electrons, which generate electric energy that can power a wide range of electronic devices. Research associated with the development of G-BFCs has increased in popularity among researchers because of the eco-friendly nature of G-BFCs (as related to their construction) and their evolution from inexpensive bio-based materials. In addition, their excellent specificity towards glucose as an energy source, and other properties, such as small size and weight, make them attractive within various demanding applied environments. For example, G-BFCs have received much attention as implanted devices, especially for uses related to cardiac activities. Envisioned pacemakers and defibrillators powered by G-BFCs would not be required to have conventional lithium batteries exchanged every 5-10 years. However, future research is needed to develop G-BFCs demonstrating more stable power consistency and improved lifespan, as well as solving the challenges in converting laboratory-made implantable G-BFCs into implanted devices in the human body. The categorization of G-BFCs as a subcategory of different biofuel cells and their performance is reviewed in this article.

11.
Lancet Reg Health Am ; 36: 100826, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39040565

RESUMO

Background: We evaluated the association of hepatitis B virus (HBV) treatment with all-cause, and liver-related mortality among individuals with HBV and cirrhosis in British Columbia (BC), Canada. Methods: This analysis included people diagnosed with HBV and had cirrhosis in the BC Hepatitis Testers Cohort, including data on all individuals diagnosed with HBV from 1990 to 2015 in BC and integrated with healthcare administrative data. We followed people with cirrhosis from the first cirrhosis diagnosis date until death or December 31, 2020. We compared all-cause and liver related mortality between those who received treatment and those who did not. HBV treatment was considered a time-varying variable. We performed multivariable Cox proportional hazards model and competing risk regression models to assess the association of HBV treatment with all causes, and liver-related mortality respectively using inverse probability of treatment weighted population. Findings: Among 4962 individuals with HBV and cirrhosis, 48.1% received HBV treatment. Treated individuals had a median follow-up of 2.97 years, compared to 2.87 years for untreated individuals. The treated group was older (median age 57 vs 54 years), had higher proportion of treated of males [1802 (75.50%) vs 1766 (68.8%)], from urban area [2318 (97.2%) vs 2355 (91.8%)], and from East and South Asian ethnicity [1506 (63.1%) vs 709 (27.5%)] compared to untreated group. Untreated people experienced higher all-cause mortality (115.47 vs. 35.72 per 1000 person-years) and liver-related mortality (49.86 vs. 11.39 per 1000 person-years). Multivariable models showed that HBV treatment significantly lowered the risk of all-cause mortality (adjusted hazard ratio (aHR) 0.74; 95% CI: 0.65, 0.84) and liver-related mortality (adjusted subdistribution hazard ratio (asHR) 0.72; 95% CI: 0.58, 0.89) compared to untreated individuals. Among untreated individuals with HBV, those with HCV coinfection had a higher risk of both all-cause and liver-related mortality (aHR 1.57; 95% CI: 1.22, 2.04, and asHR 1.60; 95% CI: 1.25, 2.05, respectively). Interpretation: HBV treatment was associated with a significant reduction in all-cause and liver-related mortality among individuals with cirrhosis. The findings highlight the need for treatment among individuals with HBV related cirrhosis especially those with coinfection with hepatitis C virus. Funding: This work was supported by the BC Centre for Disease Control and the Canadian Institutes of Health Research (CIHR) [Grant # NHC-142832, PJT-156066, and SC1 -178736]. JDM has received doctoral fellowship from the Canadian Network on Hepatitis C (CanHepC). DJ has received Doctoral Research Award (#201910DF1-435705-64343) from the Canadian Institutes of Health Research (CIHR) and doctoral fellowship from the CanHepC. CanHepC is funded by a joint initiative of the Canadian Institutes of Health Research (CIHR) (NHC-142832) and the Public Health Agency of Canada (PHAC).

12.
Health Commun ; : 1-12, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39044550

RESUMO

The doctor-patient relationship in China has become increasingly tense, with patients lacking trust in doctors. Meanwhile, online healthcare flourished, accelerated by the COVID-19 pandemic. This study utilized the direct and indirect pathway model of clinician-patient communication to health outcomes and online trust theory to examine the associations between online patient-centered communication (OPCC), benevolence and ability trust in doctors, negative online health information seeking experiences, and willingness to recommend doctors. The findings revealed that benevolence and ability trust mediated the relationship between OPCC and willingness to recommend doctors. Additionally, when participants had a high level of negative online health information seeking experiences, OPCC had a stronger effect on ability trust; meanwhile, the mediation effect of ability trust between the relationship of OPCC and willingness to recommend was stronger. This study also discussed theoretical and practical implications.

13.
JCO Precis Oncol ; 8: e2400219, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39013131

RESUMO

PURPOSE: Targeted Agent and Profiling Utilization Registry (TAPUR) is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. Results of a cohort of patients with soft tissue sarcoma with cyclin-dependent kinase 4 (CDK4) amplification treated with palbociclib are reported. METHODS: Eligible patients had measurable disease, Eastern Cooperative Oncology Group performance status 0 to 2, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16+ weeks duration (SD16+) according to RECIST v1.1. The DC rate was estimated with a 90% CI. Secondary end points included OR, progression-free survival (PFS), overall survival (OS), duration of response, duration of SD, and safety. RESULTS: Forty-two patients with CDK4 amplification were enrolled. One patient was not evaluable for efficacy. One patient with partial response and 18 with SD16+ were observed for DC and OR rates of 46% (90% CI, 36 to 100) and 2% (95% CI, <1 to 13), respectively. Median PFS was 16 weeks (95% CI, 9 to 28) and median OS was 69 weeks (95% CI, 31 to 111) for evaluable patients. Twenty patients had at least one grade 3 to 4 adverse event (AE) at least possibly related to palbociclib, including alanine aminotransferase increase, anemia, fatigue, hypophosphatemia, leukopenia, neutropenia, and thrombocytopenia. No serious AEs were reported. CONCLUSION: Palbociclib met prespecified criteria to declare a signal of antitumor activity in patients with sarcoma and CDK4 amplification.


Assuntos
Quinase 4 Dependente de Ciclina , Piperazinas , Piridinas , Sistema de Registros , Sarcoma , Humanos , Quinase 4 Dependente de Ciclina/genética , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Piridinas/uso terapêutico , Feminino , Masculino , Pessoa de Meia-Idade , Piperazinas/uso terapêutico , Adulto , Idoso , Sarcoma/tratamento farmacológico , Sarcoma/genética , Amplificação de Genes , Adulto Jovem , Idoso de 80 Anos ou mais
14.
Phys Rev E ; 109(6-2): 065002, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39021003

RESUMO

It has been reported that slow dynamic nonlinear elastic relaxations, widely thought to proceed universally in proportion to the logarithm of time after cessation of mechanical conditioning, actually recover with a smaller slope at early times, with a time of transition that varies with the grain size of the material. This would constitute a heretofore unreported failure of the claimed universality, while suggesting application to nondestructive evaluation and structural health monitoring. Here, we present further observations at short times, in the single bead system, in cement paste, mortar, concrete, sandstone, and granite. Within the limits imposed by finite-duration ring-down such that the effective instant of conditioning cessation is imprecise, and the corresponding ambiguity as to the time at which relaxation begins, we find no reliable sign of such a transition, even in samples of large grain-size mortar and concrete similar to those described elsewhere as having clear and late cutoffs.

15.
J Oral Implantol ; 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39023858

RESUMO

During implant maintenance, preserving a smooth surface on the machined trans-mucosa abutment is critical to reduce biofilm attachment and colonization. The present study compare the surface roughness and bacterial colonization of machined titanium surfaces after instrumentation with various materials. Forty-four machined Grade 23 titanium discs were instrumented with a round Polyether Ether Ketone (PEEK) tip, a plastic curette tip, or a pure titanium curette tip with piezoelectric devices. Before and after instrumentation, the surface roughness (Ra and Rz) values were analyzed with a profilometer and scanning electron microscopy (SEM). Streptococcus sanguinis was cultured and incubated for 24 hours on the instrumented discs, and colony-forming units (CFU)/mL were obtained for each group. Samples instrumented with the metal ultrasonic tip significantly increased surface roughness compared to the other groups. Thisresulted in greater colonization by S. sanguinis than surfaces instrumented with PEEK tips or the negative control. Samples instrumented with PEEK and plastic tips did not exhibit any statistically significant increase in surface roughness. SEM analysis revealed a significantly rougher surface of discs instrumented with metal compared to discs instrumented with plastic or PEEK tip, despite the possibility of debris from tip dissolution. Our results suggested that instrumentation with metal ultrasonic tips with piezoelectric devices significantly increase machined titanium's surface roughness and elicited higher biofilm formation in vitro. Meanwhile, instrumentation of machined titanium with PEEK or plastic ultrasonic tips did not affect the surface roughness or bacterial adhesion.

16.
PLOS Glob Public Health ; 4(7): e0002875, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38990965

RESUMO

Despite high injury mortality rates, Cameroon currently lacks a formal prehospital care system. In other sub-Saharan African low and middle-income countries, Lay First Responder (LFR) programs have trained non-medical professionals with high work-related exposure to injury in principles of basic trauma care. To develop a context-appropriate LFR program in Cameroon, we used trauma registry data to understand current layperson bystander involvement in prehospital care and explore associations between current non-formally trained bystander-provided prehospital care and clinical outcomes. The Cameroon Trauma Registry (CTR) is a longitudinal, prospective, multisite trauma registry cohort capturing data on injured patients presenting to four hospitals in Cameroon. We assessed prevalence and patterns of prehospital scene care among all patients enrolled the CTR in 2020. Associations between scene care, clinical status at presentation, and outcomes were tested using univariate and multivariate logistic regression. Injury severity was measured using the abbreviated injury score. Data were analyzed using Stata17. Of 2212 injured patients, 455 (21%) received prehospital care (PC) and 1699 (77%) did not receive care (NPC). Over 90% (424) of prehospital care was provided by persons without formal medical training. PC patients were more severely injured (p<0.001), had markers of increased socioeconomic status (p = 0.01), and longer transport distances (p<0.001) compared to NPC patients. Despite increased severity of injury, patients who received PC were more likely to present with a palpable pulse (OR = 6.2, p = 0.02). Multivariate logistic regression adjusted for injury severity, socioeconomic status and travel distance found PC to be associated with reduced emergency department mortality (OR = 0.14, p<0.0001). Although prehospital injury care in Cameroon is rarely performed and is provided almost entirely by persons without formal medical training, prehospital intervention is associated with increased early survival after injury. Implementation of LFR training to strengthen the frequency and quality of prehospital care has considerable potential to improve trauma survival.

17.
Nat Commun ; 15(1): 5837, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992034

RESUMO

To inform clinical trial design and real-world precision pediatric oncology practice, we classified diagnoses, assessed the landscape of mutations, and identified genomic variants matching trials in a large unselected institutional cohort of solid tumors patients sequenced at Dana-Farber / Boston Children's Cancer and Blood Disorders Center. Tumors were sequenced with OncoPanel, a targeted next-generation DNA sequencing panel. Diagnoses were classified according to the International Classification of Diseases for Oncology (ICD-O-3.2). Over 6.5 years, 888 pediatric cancer patients with 95 distinct diagnoses had successful tumor sequencing. Overall, 33% (n = 289/888) of patients had at least 1 variant matching a precision oncology trial protocol, and 14% (41/289) were treated with molecularly targeted therapy. This study highlights opportunities to use genomic data from hospital-based sequencing performed either for research or clinical care to inform ongoing and future precision oncology clinical trials. Furthermore, the study results emphasize the importance of data sharing to define the genomic landscape and targeted treatment opportunities for the large group of rare pediatric cancers we encounter in clinical practice.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Disseminação de Informação , Neoplasias , Medicina de Precisão , Humanos , Neoplasias/genética , Neoplasias/tratamento farmacológico , Criança , Medicina de Precisão/métodos , Masculino , Pré-Escolar , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Adolescente , Lactente , Mutação , Ensaios Clínicos como Assunto , Terapia de Alvo Molecular/métodos , Genômica/métodos , Recém-Nascido
18.
JAMA ; 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39037827
19.
Oral Dis ; 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39039688

RESUMO

Sensory deficits affect awareness of the environment and information processing, leading to dysfunction that may have significant consequences. Deterioration of taste and/or smell sensation has been linked to impaired nutritional intake, and overall decreased quality of life (QoL). Recent data suggest that loss of these senses is also associated with cognitive decline and worse overall cancer treatment prognosis. Cancer therapies have commonly been associated with sensory deterioration. We review these associations with taste and smell in light of new findings and discuss potential prophylactic and therapeutic modalities for taste and smell function.

20.
Environ Microbiol ; 26(7): e16672, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39040020

RESUMO

The Pseudoalteromonas genus comprises members that have been demonstrated to play significant ecological roles and produce enzymes, natural products, and activities that are beneficial to the environment and economy. A comprehensive evaluation of the genus revealed that the genomes of several Pseudoalteromonas species are highly similar to each other, exceeding species cutoff values. This evaluation involved determining and comparing the average nucleotide identity, in silico DNA-DNA hybridization, average amino acid identity, and the difference in G + C% between Pseudoalteromonas type strains with publicly available genomes. The genome of the Pseudoalteromonas elyakovii type strain was further assessed through additional sequencing and genomic comparisons to historical sequences. These findings suggest that six Pseudoalteromonas species, namely P. mariniglutinosa, P. donghaensis, P. maricaloris, P. elyakovii, P. profundi, and P. issachenkonii, should be reclassified as later heterotypic synonyms of the following validly published species: P. haloplanktis, P. lipolytica, P. flavipulchra, P. distincta, P. gelatinilytica, and P. tetraodonis. Furthermore, two names without valid standing, 'P. telluritireducens' and 'P. spiralis', should be associated with the validly published Pseudoalteromonas species P. agarivorans and P. tetraodonis, respectively.


Assuntos
Genoma Bacteriano , Filogenia , Pseudoalteromonas , Pseudoalteromonas/genética , Pseudoalteromonas/classificação , DNA Bacteriano/genética , Composição de Bases , Análise de Sequência de DNA/métodos , Hibridização de Ácido Nucleico
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