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1.
J Autism Dev Disord ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38990369

RESUMO

A product of ASD socio-communicative-deficits and insufficient police training related to autism, ASD-police interactions have the potential to become problematic, with negative outcomes for ASD individuals and police alike. Thus, the combination of police acclimation, simulatory experience for drivers with ASD and the introduction of Connecticut's recent Blue Envelope could improve overall experiences for drivers. A simulated routine traffic stop practice event, utilising pre- and post- measures was conducted in an effort to quantify drivers' feelings about current and future interactions with police. Our prediction that participants would experience a statistically significant improvement in anxiety, comfort and self-perceived knowledge levels about future ASD-police interactions immediately following the intervention was confirmed. Our prediction that initially significant disparities between participants with and without police experience - those with previous police encounters versus those that don't - would become not significant immediately following the intervention was disconfirmed. While the longitudinal data suggested that improved post-intervention ASD psychological measures remained statistically significant in the long-term, the sample responses to our long-term questionnaire were too few in number to make any definitive conclusions. It is suggested that practice traffic stops such as these could benefit both drivers with ASD and law enforcement nationwide. It is further suggested that police officer curriculums should include additional training regarding special populations.

2.
Crit Rev Oncol Hematol ; 200: 104401, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38815876

RESUMO

Several observations indicate that protein expression analysis by immunohistochemistry (IHC) remains relevant in individuals with non-small-cell lung cancer (NSCLC) when considering targeted therapy, as an early step in diagnosis and for therapy selection. Since the advent of next-generation sequencing (NGS), the role of IHC in testing for NSCLC biomarkers has been forgotten or ignored. We discuss how protein-level investigations maintain a critical role in defining sensitivity to lung cancer therapies in oncogene- and non-oncogene-addicted cases and in patients eligible for immunotherapy, suggesting that IHC testing should be reconsidered in clinical practice. We also argue how a panel of IHC tests should be considered complementary to NGS and other genomic assays. This is relevant to current clinical diagnostic practice but with potential future roles to optimize the selection of patients for innovative therapies. At the same time, strict validation of antibodies, assays, scoring systems, and intra- and interobserver reproducibility is needed.

3.
Nucleic Acids Res ; 52(7): 3870-3885, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38452217

RESUMO

The canonical stop codons of the nuclear genome of the trypanosomatid Blastocrithidia nonstop are recoded. Here, we investigated the effect of this recoding on the mitochondrial genome and gene expression. Trypanosomatids possess a single mitochondrion and protein-coding transcripts of this genome require RNA editing in order to generate open reading frames of many transcripts encoded as 'cryptogenes'. Small RNAs that can number in the hundreds direct editing and produce a mitochondrial transcriptome of unusual complexity. We find B. nonstop to have a typical trypanosomatid mitochondrial genetic code, which presumably requires the mitochondrion to disable utilization of the two nucleus-encoded suppressor tRNAs, which appear to be imported into the organelle. Alterations of the protein factors responsible for mRNA editing were also documented, but they have likely originated from sources other than B. nonstop nuclear genome recoding. The population of guide RNAs directing editing is minimal, yet virtually all genes for the plethora of known editing factors are still present. Most intriguingly, despite lacking complex I cryptogene guide RNAs, these cryptogene transcripts are stochastically edited to high levels.


Assuntos
Núcleo Celular , Genoma Mitocondrial , Edição de RNA , RNA de Transferência , Núcleo Celular/genética , Núcleo Celular/metabolismo , RNA de Transferência/genética , RNA de Transferência/metabolismo , Fases de Leitura Aberta/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Trypanosomatina/genética , Trypanosomatina/metabolismo , Códon/genética , Mitocôndrias/genética , Mitocôndrias/metabolismo , Códon de Terminação/genética , RNA Guia de Cinetoplastídeos/genética , RNA Guia de Cinetoplastídeos/metabolismo , Código Genético , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo
4.
Oncol Ther ; 12(2): 223-231, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38536631

RESUMO

The identification of actionable biomarkers and development of targeted therapies have revolutionized the field of lung cancer treatment. In patients with advanced non-small cell lung cancer (NSCLC), biomarker testing can inform selection of effective targeted therapies as well as avoid therapies that are less likely to be effective in certain populations. A growing number of actionable targets, including those involving EGFR, ALK, ROS1, BRAF, MET, KRAS, NTRK, RET, HER2, and PD-L1, can be identified with biomarker testing. More than half of patients with advanced NSCLC have tumors that harbor genetic alterations that can be targeted. When these patients are treated with targeted therapy, survival and quality of life may be significantly improved. In addition, broad-based molecular testing may detect alterations identifying patients who are potentially eligible for current or future clinical trials. Comprehensive biomarker testing rates in communities are often low, and turnaround times for results can be unacceptably long. There is an unmet need for widespread, efficient, and routine testing of all biomarkers recommended by clinical guidelines. New testing techniques and technologies can make this an attainable goal. Panel-based sequencing platforms are becoming more accessible, and molecular biomarker analysis of circulating tumor DNA is becoming more common. In this podcast, we discuss the importance of biomarker testing in advanced NSCLC and explore topics such as testing methodologies, effect of biomarker testing on patient outcomes, emerging technologies, and strategies for improving testing rates in the United States. Supplementary file1 (MP4 121301 KB).

5.
J Exp Clin Cancer Res ; 43(1): 81, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38486328

RESUMO

BACKGROUND: Immune-checkpoint inhibitors (ICIs) have showed unprecedent efficacy in the treatment of patients with advanced non-small cell lung cancer (NSCLC). However, not all patients manifest clinical benefit due to the lack of reliable predictive biomarkers. We showed preliminary data on the predictive role of the combination of radiomics and plasma extracellular vesicle (EV) PD-L1 to predict durable response to ICIs. MAIN BODY: Here, we validated this model in a prospective cohort of patients receiving ICIs plus chemotherapy and compared it with patients undergoing chemotherapy alone. This multiparametric model showed high sensitivity and specificity at identifying non-responders to ICIs and outperformed tissue PD-L1, being directly correlated with tumor change. SHORT CONCLUSION: These findings indicate that the combination of radiomics and EV PD-L1 dynamics is a minimally invasive and promising biomarker for the stratification of patients to receive ICIs.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Vesículas Extracelulares , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Antígeno B7-H1/uso terapêutico , Radiômica , Multiômica , Estudos Prospectivos , Biomarcadores Tumorais , Imunoterapia , Vesículas Extracelulares/patologia
6.
Mol Cancer ; 23(1): 41, 2024 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-38395864

RESUMO

Current treatment guidelines refer to small cell lung cancer (SCLC), one of the deadliest human malignancies, as a homogeneous disease. Accordingly, SCLC therapy comprises chemoradiation with or without immunotherapy. Meanwhile, recent studies have made significant advances in subclassifying SCLC based on the elevated expression of the transcription factors ASCL1, NEUROD1, and POU2F3, as well as on certain inflammatory characteristics. The role of the transcription regulator YAP1 in defining a unique SCLC subset remains to be established. Although preclinical analyses have described numerous subtype-specific characteristics and vulnerabilities, the so far non-existing clinical subtype distinction may be a contributor to negative clinical trial outcomes. This comprehensive review aims to provide a framework for the development of novel personalized therapeutic approaches by compiling the most recent discoveries achieved by preclinical SCLC research. We highlight the challenges faced due to limited access to patient material as well as the advances accomplished by implementing state-of-the-art models and methodologies.


Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/terapia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Imunoterapia , Fatores de Transcrição
7.
BMC Genomics ; 25(1): 184, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365628

RESUMO

BACKGROUND: Almost all extant organisms use the same, so-called canonical, genetic code with departures from it being very rare. Even more exceptional are the instances when a eukaryote with non-canonical code can be easily cultivated and has its whole genome and transcriptome sequenced. This is the case of Blastocrithidia nonstop, a trypanosomatid flagellate that reassigned all three stop codons to encode amino acids. RESULTS: We in silico predicted the metabolism of B. nonstop and compared it with that of the well-studied human parasites Trypanosoma brucei and Leishmania major. The mapped mitochondrial, glycosomal and cytosolic metabolism contains all typical features of these diverse and important parasites. We also provided experimental validation for some of the predicted observations, concerning, specifically presence of glycosomes, cellular respiration, and assembly of the respiratory complexes. CONCLUSIONS: In an unusual comparison of metabolism between a parasitic protist with a massively altered genetic code and its close relatives that rely on a canonical code we showed that the dramatic differences on the level of nucleic acids do not seem to be reflected in the metabolisms. Moreover, although the genome of B. nonstop is extremely AT-rich, we could not find any alterations of its pyrimidine synthesis pathway when compared to other trypanosomatids. Hence, we conclude that the dramatic alteration of the genetic code of B. nonstop has no significant repercussions on the metabolism of this flagellate.


Assuntos
Parasitos , Trypanosoma brucei brucei , Trypanosomatina , Animais , Códon de Terminação , Eucariotos/genética , Código Genético , Parasitos/genética , Trypanosoma brucei brucei/genética , Trypanosomatina/genética
8.
Environ Entomol ; 53(2): 277-287, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38334261

RESUMO

Cold winter temperatures govern the distribution and abundance of many insect species, but refugia that provide microclimates can moderate temperature-driven mortality. Winter temperatures have been implicated in limiting the survival and range of Piezodorus guildinii (Westwood) (Hemiptera: Pentatomidae; redbanded stink bug), an economically damaging invasive pest in the southeastern United States, but the role of refugia in overwintering survival of this pest is poorly understood. We conducted 2 studies in successive years to evaluate how leaf litter from hardwoods, pines, and soybeans modulate overwintering site selection and survival of P. guildinii. In the second-year study, we also quantified the buffering effect of the 3 leaf litter types compared to ambient conditions and assessed diapause. In the first-year study, we found that stink bugs preferentially dispersed into leaf litter compared with remaining unsheltered on bare soil; no clear preference among leaf litter types was found. In the second year, however, no clear differences were found among leaf litter types and bare soil. Means of daily minimum temperatures under leaf litter were at least 3.0 ±â€…0.9 °C (SE) warmer and generally less variable than ambient conditions. While high mortality in both studies illustrates that more work must be done to fully understand overwintering survival, limited survival through potentially lethal conditions in the first-year study nonetheless emphasizes the possibility of populations persisting and rebounding in the following spring. Furthermore, our study highlights the potential for stink bugs to persist in areas with lethal ambient temperatures by dispersing into widely available substrates.


Assuntos
Glycine max , Heterópteros , Animais , Microclima , Temperatura Baixa , Solo
9.
Clin Transl Med ; 14(2): e1573, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38318637

RESUMO

BACKGROUND: Patients who possess various histological subtypes of early-stage lung adenocarcinoma (LUAD) have considerably diverse prognoses. The simultaneous existence of several histological subtypes reduces the clinical accuracy of the diagnosis and prognosis of early-stage LUAD due to intratumour intricacy. METHODS: We included 11 postoperative LUAD patients pathologically confirmed to be stage IA. Single-cell RNA sequencing (scRNA-seq) was carried out on matched tumour and normal tissue. Three formalin-fixed and paraffin-embedded cases were randomly selected for 10× Genomics Visium analysis, one of which was analysed by digital spatial profiler (DSP). RESULTS: Using DSP and 10× Genomics Visium analysis, signature gene profiles for lepidic and acinar histological subtypes were acquired. The percentage of histological subtypes predicted for the patients from samples of 11 LUAD fresh tissues by scRNA-seq showed a degree of concordance with the clinicopathologic findings assessed by visual examination. DSP proteomics and 10× Genomics Visium transcriptomics analyses revealed that a negative correlation (Spearman correlation analysis: r = -.886; p = .033) between the expression levels of CD8 and the expression trend of programmed cell death 1(PD-L1) on tumour endothelial cells. The percentage of CD8+ T cells in the acinar region was lower than in the lepidic region. CONCLUSIONS: These findings illustrate that assessing patient histological subtypes at the single-cell level is feasible. Additionally, tumour endothelial cells that express PD-L1 in stage IA LUAD suppress immune-responsive CD8+ T cells.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Antígeno B7-H1/genética , Neoplasias Pulmonares/metabolismo , Células Endoteliais/metabolismo , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Perfilação da Expressão Gênica
10.
BMC Ecol Evol ; 24(1): 2, 2024 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-38177987

RESUMO

Foskett Spring in Oregon's desert harbors a historically threatened population of Western Speckled Dace (Rhinichthys klamathensis). Though recently delisted, the dace's recruitment depends upon regular removal of encroaching vegetation. Previous studies assumed that Foskett Dace separated from others in the Warner Valley about 10,000 years ago, thereby framing an enigma about the population's surprising ability to persist for so long in a tiny habitat easily overrun by plants. To investigate that persistence and the effectiveness of interventions to augment population size, we assessed genetic diversity among daces inhabiting Foskett Spring, a refuge at Dace Spring, and three nearby streams. Analysis revealed a robust effective population size (Ne) of nearly 5000 within Foskett Spring, though Ne in the Dace Spring refuge is just 10% of that value. Heterozygosity is slightly lower than expected based on random mating at all five sites, indicating mild inbreeding, but not at a level of concern. These results confirm the genetic health of Foskett Dace. Unexpectedly, genetic differentiation reveals closer similarity between Foskett Dace and a newly discovered population from Nevada's Coleman Creek than between Foskett Dace and dace elsewhere in Oregon. Demographic modeling inferred Coleman Creek as the ancestral source of Foskett Dace fewer than 1000 years ago, much more recently than previously suspected and possibly coincident with the arrival of large herbivores whose grazing may have maintained open water suitable for reproduction. These results solve the enigma of persistence by greatly shortening the duration over which Foskett Dace have inhabited their isolated spring.


Assuntos
Cyprinidae , Animais , Cyprinidae/genética , Rios , Ecossistema , Oregon
11.
Cancer Treat Rev ; 122: 102664, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38064878

RESUMO

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are the current recommended option for the first-line treatment of patients with EGFR-mutant non-small cell lung cancer (NSCLC). Resistance to first-generation TKIs led to the development of second- and third-generation TKIs with improved clinical outcomes. However, sequential administration of TKIs has led to the emergence of new EGFR resistance mutations and persistent tumor cell survival. This evidence highlights the potential role of EGFR in transducing growth signals in NSCLC tumor cells. Therefore, dual inhibition of EGFR using combinations of anti-EGFR monoclonal antibodies (mAbs) and EGFR-TKIs may offer a unique treatment strategy to suppress tumor cell growth. Several clinical studies have demonstrated the benefits of dual blockade of EGFR using anti-EGFR mAbs coupled with EGFR-TKIs in overcoming treatment resistance in patients with EGFR-mutated NSCLC. However, a single treatment option may not result in the same clinical benefits in all patients with acquired resistance. Biomarkers, including EGFR overexpression, EGFR gene copy number, EGFR and KRAS mutations, and circulating tumor DNA, have been associated with improved clinical efficacy with anti-EGFR mAbs in patients with NSCLC and acquired resistance. Further investigation of biomarkers may allow patient selection for those who could benefit from anti-EGFR mAbs in combination with EGFR-TKIs. This review summarizes findings of recent studies of anti-EGFR mAbs in combination with EGFR-TKIs for the treatment of patients with EGFR-mutated NSCLC, as well as clinical evidence for potential biomarkers towards personalized targeted medicine.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Receptores ErbB , Inibidores de Proteínas Quinases/efeitos adversos , Antineoplásicos/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/farmacologia , Mutação , Biomarcadores , Resistencia a Medicamentos Antineoplásicos
12.
Nature ; 625(7993): 166-174, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38057662

RESUMO

Myeloid cells are known to suppress antitumour immunity1. However, the molecular drivers of immunosuppressive myeloid cell states are not well defined. Here we used single-cell RNA sequencing of human and mouse non-small cell lung cancer (NSCLC) lesions, and found that in both species the type 2 cytokine interleukin-4 (IL-4) was predicted to be the primary driver of the tumour-infiltrating monocyte-derived macrophage phenotype. Using a panel of conditional knockout mice, we found that only deletion of the IL-4 receptor IL-4Rα in early myeloid progenitors in bone marrow reduced tumour burden, whereas deletion of IL-4Rα in downstream mature myeloid cells had no effect. Mechanistically, IL-4 derived from bone marrow basophils and eosinophils acted on granulocyte-monocyte progenitors to transcriptionally programme the development of immunosuppressive tumour-promoting myeloid cells. Consequentially, depletion of basophils profoundly reduced tumour burden and normalized myelopoiesis. We subsequently initiated a clinical trial of the IL-4Rα blocking antibody dupilumab2-5 given in conjunction with PD-1/PD-L1 checkpoint blockade in patients with relapsed or refractory NSCLC who had progressed on PD-1/PD-L1 blockade alone (ClinicalTrials.gov identifier NCT05013450 ). Dupilumab supplementation reduced circulating monocytes, expanded tumour-infiltrating CD8 T cells, and in one out of six patients, drove a near-complete clinical response two months after treatment. Our study defines a central role for IL-4 in controlling immunosuppressive myelopoiesis in cancer, identifies a novel combination therapy for immune checkpoint blockade in humans, and highlights cancer as a systemic malady that requires therapeutic strategies beyond the primary disease site.


Assuntos
Medula Óssea , Carcinogênese , Interleucina-4 , Mielopoese , Transdução de Sinais , Animais , Humanos , Camundongos , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Medula Óssea/efeitos dos fármacos , Medula Óssea/metabolismo , Carcinogênese/efeitos dos fármacos , Carcinogênese/metabolismo , Carcinogênese/patologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Inibidores de Checkpoint Imunológico/imunologia , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Interleucina-4/metabolismo , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Linfócitos do Interstício Tumoral/imunologia , Monócitos/efeitos dos fármacos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/metabolismo , Recidiva , Transdução de Sinais/efeitos dos fármacos
13.
Eur J Cancer ; 196: 113457, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38008032

RESUMO

PURPOSE: Pleural mesothelioma (PM) is an aggressive tumor still considered incurable, in part due to the lack of predictive biomarkers. Little is known about the clinical implications of molecular alterations in resectable PM tissues and blood. Here, we characterized genetic alterations to identify prognostic and predictive biomarkers in patients with resected PM. EXPERIMENTAL DESIGN: Targeted next-generation sequencing was performed in retrospective pleural tumor tissue and paired plasma samples from stage IB-IIIB resected PM. Association between prognosis and presence of specific mutations was validated in silico. RESULTS: Thirty PM tissues and paired blood samples from 12 patients were analyzed. High tissue tumor mutational burden (TMB) (>10 mutations/Mb), tissue median minor allele frequency (MAF) (>9 mutations/Mb), and blood TMB (>6 mutations/Mb), tissue KMT2C, PBRM1, PKHD1,EPHB1 and blood LIFR mutations correlated with longer disease-free survival and/or overall survival. High concordance (>80%) between tissue and blood was found for some mutations. CONCLUSIONS: Tissue TMB and MAF, blood TMB, and specific mutations correlated with outcomes in patients with resected PM and should be further studied to validate their role as prognostic biomarkers and potentially predictive factors for combinations with immune-checkpoint inhibitors. This suggest that molecular profiling could identify longer survivors in patients with resected PM.


Assuntos
Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Humanos , Estudos Retrospectivos , Biomarcadores Tumorais/genética , Mutação , Mesotelioma/genética , Mesotelioma/cirurgia , Neoplasias Pleurais/genética , Neoplasias Pleurais/cirurgia , Genômica
14.
J Thorac Oncol ; 2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38070597

RESUMO

INTRODUCTION: Pathologic response (PathR) by histopathologic assessment of resected specimens may be an early clinical end point associated with long-term outcomes with neoadjuvant therapy. Digital pathology may improve the efficiency and precision of PathR assessment. LCMC3 (NCT02927301) evaluated neoadjuvant atezolizumab in patients with resectable NSCLC and reported a 20% major PathR rate. METHODS: We determined PathR in primary tumor resection specimens using guidelines-based visual techniques and developed a convolutional neural network model using the same criteria to digitally measure the percent viable tumor on whole-slide images. Concordance was evaluated between visual determination of percent viable tumor (n = 151) performed by one of the 47 local pathologists and three central pathologists. RESULTS: For concordance among visual determination of percent viable tumor, the interclass correlation coefficient was 0.87 (95% confidence interval [CI]: 0.84-0.90). Agreement for visually assessed 10% or less viable tumor (major PathR [MPR]) in the primary tumor was 92.1% (Fleiss kappa = 0.83). Digitally assessed percent viable tumor (n = 136) correlated with visual assessment (Pearson r = 0.73; digital/visual slope = 0.28). Digitally assessed MPR predicted visually assessed MPR with outstanding discrimination (area under receiver operating characteristic curve, 0.98) and was associated with longer disease-free survival (hazard ratio [HR] = 0.30; 95% CI: 0.09-0.97, p = 0.033) and overall survival (HR = 0.14, 95% CI: 0.02-1.06, p = 0.027) versus no MPR. Digitally assessed PathR strongly correlated with visual measurements. CONCLUSIONS: Artificial intelligence-powered digital pathology exhibits promise in assisting pathologic assessments in neoadjuvant NSCLC clinical trials. The development of artificial intelligence-powered approaches in clinical settings may aid pathologists in clinical operations, including routine PathR assessments, and subsequently support improved patient care and long-term outcomes.

15.
Lung Cancer ; 186: 107423, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37995456

RESUMO

BACKGROUND: Patients with thoracic malignancies who develop COVID-19 infection have a higher hospitalization rate compared to the general population and to those with other cancer types, but how this outcome differs by race and ethnicity is relatively understudied. METHODS: The TERAVOLT database is an international, multi-center repository of cross-sectional and longitudinal data studying the impact of COVID-19 on individuals with thoracic malignancies. Patients from North America with thoracic malignancies and confirmed COVID-19 infection were included for this analysis of racial and ethnic disparities. Patients with missing race data or races and ethnicities with fewer than 50 patients were excluded from analysis. Multivariable analyses for endpoints of hospitalization and death were performed on these 471 patients. RESULTS: Of the 471 patients, 73% were White and 27% were Black. The majority (90%) were non-Hispanic ethnicity, 5% were Hispanic, and 4% were missing ethnicity data. Black patients were more likely to have an Eastern Cooperative Oncology Group (ECOG) Performance Status ≥ 2 (p-value = 0.04). On multivariable analysis, Black patients were more likely than White patients to require hospitalization (Odds Ratio (OR): 1.69, 95% CI: 1.01-2.83, p-value = 0.044). These differences remained across different waves of the pandemic. However, no statistically significant difference in mortality was found between Black and White patients (OR 1.29, 95% CI: 0.69-2.40, p-value = 0.408). CONCLUSIONS: Black patients with thoracic malignancies who acquire COVID-19 infection are at a significantly higher risk of hospitalization compared to White patients, but there is no significant difference in mortality. The underlying drivers of racial disparity among patients with thoracic malignancies and COVID-19 infection require ongoing investigation.


Assuntos
COVID-19 , Disparidades nos Níveis de Saúde , Neoplasias Torácicas , Humanos , COVID-19/epidemiologia , COVID-19/etnologia , Estudos Transversais , América do Norte/epidemiologia , Neoplasias Torácicas/epidemiologia , Neoplasias Torácicas/etnologia , Brancos , Negro ou Afro-Americano
16.
Cancer Cell ; 41(11): 1838-1840, 2023 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-37863065

RESUMO

Patients diagnosed with lung cancer (LC) exhibit increased susceptibility to SARS-CoV-2 infection. Rodilla et al. monitor the levels of plasma anti-nucleocapsid antibodies within a cohort of fully vaccinated LC patients and reveal that the actual infection rate is nearly twice the documented rate, indicating a significant prevalence of unreported cases.


Assuntos
COVID-19 , Neoplasias Pulmonares , Humanos , SARS-CoV-2 , Nucleocapsídeo , Testes Imunológicos , Teste para COVID-19
17.
Cancer Cell ; 41(9): 1535-1540, 2023 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-37699331

RESUMO

The understanding of small cell lung cancer (SCLC) biology has increased dramatically in recent years, but the processes that allow SCLC to progress rapidly remain poorly understood. Here, we advocate the integration of rapid autopsies and preclinical models into SCLC research as a comprehensive strategy with the potential to revolutionize current treatment paradigms.


Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Autopsia , Carcinoma de Pequenas Células do Pulmão/genética , Neoplasias Pulmonares/genética
18.
PLoS One ; 18(9): e0291819, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37733675

RESUMO

Past corruption research at the individual level has mainly focused on demographics, personality, attitudes, or morality related variables. Until now, only a few studies have focused on the intra-individual psychological mechanisms of corruption. Building on normative decision-making theory, the present study attempts to shed further light on the internal mechanisms that lead to the decision that corruption is a viable path. Following an informed grounded theory approach, we conducted semi-structured interviews with 38 Indonesian prisoners who have been convicted of corruption. Guided by a multi-step decision-making process, including problem recognition, information search, and evaluation of the information, our results revealed unique insights into individuals' considerations that led to corruption. We elaborate on interrelations between these stages and explore new forms of corrupt decision-making elements within this process. Theoretical implications for corruption research and the practical implications for anti-corruption programs of these findings are discussed.


Assuntos
Princípios Morais , Personalidade , Humanos , Teoria Fundamentada , Indonésia , Transtornos da Personalidade
19.
Arch Insect Biochem Physiol ; 114(3): e22047, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37602813

RESUMO

Diamide insecticides, such as chlorantraniliprole, have been widely used to control insect pests by targeting the insect ryanodine receptor (RyR). Due to the efficacious insecticidal activity of diamides, as well as an increasing number of resistance cases, the molecular structure of RyR has been studied in many economically important insects. However, no research has been conducted on diamide resistance and RyR in the soybean looper, Chrysodeixis includens, a significant crop pest. In this study, we found moderate resistance to chlorantraniliprole in a field population from Puerto Rico and sequenced the full-length cDNA of the C. includens RyR gene, which encodes a 5124 amino acid-long protein. Genomic analysis revealed that the CincRyR gene consists of 113 exons, one of the largest exon numbers reported for RyR. Alternative splicing sites were detected in the cytosolic region. The protein sequence showed high similarity to other noctuid RyRs. Conserved structural features included the selectivity filter motif critical for ryanodine binding and ion conduction, as well as various domains involved in ion transport. Two mutation sites associated with diamide resistance in other insects were screened but not found in the Puerto Rico field populations or in the susceptible lab strain. Gene expression analysis indicated high expression of RyR in the third instar larval stage, particularly in muscle-containing tissues. Furthermore, exposure to a sublethal dose of chlorantraniliprole reduced RyR expression levels after 96 h. This study provides a molecular basis for understanding RyR structure and sheds light on potential mechanisms of diamide resistance in C. includens.

20.
Genes (Basel) ; 14(7)2023 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-37510399

RESUMO

The Noctuid moth soybean looper (SBL), Chrysodeixis includens (Walker), is an economically important pest of soybean (Glycine max (Linnaeus) Merrill). Because it is not known to survive freezing winters, permanent populations in the United States are believed to be limited to the southern regions of Texas and Florida, yet its geographical range of infestations annually extend to Canada. This indicates annual migrations of thousands of kilometers during the spring and summer growing season. This behavior is like that of the fall armyworm (FAW), Spodoptera frugiperda (J.E. Smith), also a Noctuid that is a major global pest of corn. SBL and FAW are projected to have very similar distributions of permanent populations in North America based on climate suitability modeling and the overlap in the distribution of their preferred host plants (corn and soybean). It therefore seems likely that the two species will display similar migratory behavior in the United States. This was tested by identifying genetic markers in SBL analogous to those successfully used to delineate FAW migratory pathways and comparing the distribution patterns of the markers from the two species. Contrary to expectations, the results indicate substantial differences in migratory behavior that appear to be related to differences in the timing of corn and soybean plantings. These findings underscore the importance of agricultural practices in influencing pest migration patterns, in particular the timing of host availability relative to mean seasonal air transport patterns.


Assuntos
Glycine max , Mariposas , Animais , Estados Unidos , Spodoptera/genética , Glycine max/genética , Estações do Ano , Zea mays/genética , Haplótipos , Migração Animal
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