Oropharyngeal squamous cell carcinoma (OPSCC), largely fueled by the human papillomavirus (HPV), has a complex biological and immunologic phenotype. Although HPV/p16 status can be used to stratify ...OPSCC patients as a function of survival, it remains unclear what drives an improved treatment response in HPV-associated OPSCC and whether targetable biomarkers exist that can inform a precision oncology approach. We analyzed OPSCC patients treated between 2000 and 2016 and correlated locoregional control (LRC), disease-free survival (DFS) and overall survival (OS) with conventional clinical parameters, risk parameters generated using deep-learning algorithms trained to quantify tumor-infiltrating lymphocytes (TILs) (OP-TIL) and multinucleated tumor cells (MuNI) and targeted transcriptomics. P16 was a dominant determinant of LRC, DFS and OS, but tobacco exposure, OP-TIL and MuNI risk features correlated with clinical outcomes independent of p16 status and the combination of p16, OP-TIL and MuNI generated a better stratification of OPSCC risk compared to individual parameters. Differential gene expression (DEG) analysis demonstrated overlap between MuNI and OP-TIL and identified genes involved in DNA repair, oxidative stress response and tumor immunity as the most prominent correlates with survival. Alteration of inflammatory/immune pathways correlated strongly with all risk features and oncologic outcomes. This suggests that development of OPSCC consists of an intersection between multiple required and permissive oncogenic and immunologic events which may be mechanistically linked. The strong relationship between tumor immunity and oncologic outcomes in OPSCC regardless of HPV status may provide opportunities for further biomarker development and precision oncology approaches incorporating immune checkpoint inhibitors for maximal anti-tumor efficacy.
BACKGROUNDPatients with p16+ oropharyngeal squamous cell carcinoma (OPSCC) are potentially cured with definitive treatment. However, there are currently no reliable biomarkers of treatment failure ...for p16+ OPSCC. Pathologist-based visual assessment of tumor cell multinucleation (MN) has been shown to be independently prognostic of disease-free survival (DFS) in p16+ OPSCC. However, its quantification is time intensive, subjective, and at risk of interobserver variability.METHODSWe present a deep-learning-based metric, the multinucleation index (MuNI), for prognostication in p16+ OPSCC. This approach quantifies tumor MN from digitally scanned H&E-stained slides. Representative H&E-stained whole-slide images from 1094 patients with previously untreated p16+ OPSCC were acquired from 6 institutions for optimization and validation of the MuNI.RESULTSThe MuNI was prognostic for DFS, overall survival (OS), or distant metastasis-free survival (DMFS) in p16+ OPSCC, with HRs of 1.78 (95% CI: 1.37-2.30), 1.94 (1.44-2.60), and 1.88 (1.43-2.47), respectively, independent of age, smoking status, treatment type, or tumor and lymph node (T/N) categories in multivariable analyses. The MuNI was also prognostic for DFS, OS, and DMFS in patients with stage I and stage III OPSCC, separately.CONCLUSIONMuNI holds promise as a low-cost, tissue-nondestructive, H&E stain-based digital biomarker test for counseling, treatment, and surveillance of patients with p16+ OPSCC. These data support further confirmation of the MuNI in prospective trials.FUNDINGNational Cancer Institute (NCI), NIH; National Institute for Biomedical Imaging and Bioengineering, NIH; National Center for Research Resources, NIH; VA Merit Review Award from the US Department of VA Biomedical Laboratory Research and Development Service; US Department of Defense (DOD) Breast Cancer Research Program Breakthrough Level 1 Award; DOD Prostate Cancer Idea Development Award; DOD Lung Cancer Investigator-Initiated Translational Research Award; DOD Peer-Reviewed Cancer Research Program; Ohio Third Frontier Technology Validation Fund; Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering; Clinical and Translational Science Award (CTSA) program, Case Western Reserve University; NCI Cancer Center Support Grant, NIH; Career Development Award from the US Department of VA Clinical Sciences Research and Development Program; Dan L. Duncan Comprehensive Cancer Center Support Grant, NIH; and Computational Genomic Epidemiology of Cancer Program, Case Comprehensive Cancer Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, the US Department of VA, the DOD, or the US Government.
The global abundance of tree palms Emilio, Thaise; Baker, William J.; Eiserhardt, Wolf L. ...
Global ecology and biogeography,
September 2020, Letnik:
29, Številka:
9
Journal Article, Web Resource
Recenzirano
Odprti dostop
Aim
Palms are an iconic, diverse and often abundant component of tropical ecosystems that provide many ecosystem services. Being monocots, tree palms are evolutionarily, morphologically and ...physiologically distinct from other trees, and these differences have important consequences for ecosystem services (e.g., carbon sequestration and storage) and in terms of responses to climate change. We quantified global patterns of tree palm relative abundance to help improve understanding of tropical forests and reduce uncertainty about these ecosystems under climate change.
Location
Tropical and subtropical moist forests.
Time period
Current.
Major taxa studied
Palms (Arecaceae).
Methods
We assembled a pantropical dataset of 2,548 forest plots (covering 1,191 ha) and quantified tree palm (i.e., ≥10 cm diameter at breast height) abundance relative to co‐occurring non‐palm trees. We compared the relative abundance of tree palms across biogeographical realms and tested for associations with palaeoclimate stability, current climate, edaphic conditions and metrics of forest structure.
Results
On average, the relative abundance of tree palms was more than five times larger between Neotropical locations and other biogeographical realms. Tree palms were absent in most locations outside the Neotropics but present in >80% of Neotropical locations. The relative abundance of tree palms was more strongly associated with local conditions (e.g., higher mean annual precipitation, lower soil fertility, shallower water table and lower plot mean wood density) than metrics of long‐term climate stability. Life‐form diversity also influenced the patterns; palm assemblages outside the Neotropics comprise many non‐tree (e.g., climbing) palms. Finally, we show that tree palms can influence estimates of above‐ground biomass, but the magnitude and direction of the effect require additional work.
Conclusions
Tree palms are not only quintessentially tropical, but they are also overwhelmingly Neotropical. Future work to understand the contributions of tree palms to biomass estimates and carbon cycling will be particularly crucial in Neotropical forests.
Computerized tumor multinucleation index Koyuncu, Can F; Lu, Cheng; Bera, Kaustav ...
The Journal of clinical investigation,
04/2021, Letnik:
131, Številka:
8
Journal Article
Recenzirano
FUNDING. National Cancer Institute (NCI), NIH; National Institute for Biomedical Imaging and Bioengineering, NIH; National Center for Research Resources, NIH; VA Merit Review Award from the US ...Department of VA Biomedical Laboratory Research and Development Service; US Department of Defense (DOD) Breast Cancer Research Program Breakthrough Level 1 Award; DOD Prostate Cancer Idea Development Award; DOD Lung Cancer Investigator-Initiated Translational Research Award; DOD Peer-Reviewed Cancer Research Program; Ohio Third Frontier Technology Validation Fund; Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering; Clinical and Translational Science Award (CTSA) program, Case Western Reserve University; NCI Cancer Center Support Grant, NIH; Career Development Award from the US Department of VA Clinical Sciences Research and Development Program; Dan L. Duncan Comprehensive Cancer Center Support Grant, NIH; and Computational Genomic Epidemiology of Cancer Program, Case Comprehensive Cancer Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, the US Department of VA, the DOD, or the US Government.
BACKGROUND. Patients with p16.sup.+ oropharyngeal squamous cell carcinoma (OPSCC) are potentially cured with definitive treatment. However, there are currently no reliable biomarkers of treatment ...failure for p16.sup.+ OPSCC. Pathologist-based visual assessment of tumor cell multinucleation (MN) has been shown to be independently prognostic of disease-free survival (DFS) in p16.sup.+ OPSCC. However, its quantification is time intensive, subjective, and at risk of interobserver variability. METHODS. We present a deep-learning-based metric, the multinucleation index (MuNI), for prognostication in p16.sup.+ OPSCC. This approach quantifies tumor MN from digitally scanned H&E-stained slides. Representative H&E-stained whole-slide images from 1094 patients with previously untreated p16.sup.+ OPSCC were acquired from 6 institutions for optimization and validation of the MuNI. RESULTS. The MuNI was prognostic for DFS, overall survival (OS), or distant metastasis-free survival (DMFS) in p16.sup.+ OPSCC, with HRs of 1.78 (95% CI: 1.37-2.30), 1.94 (1.44-2.60), and 1.88 (1.43-2.47), respectively, independent of age, smoking status, treatment type, or tumor and lymph node (T/N) categories in multivariable analyses. The MuNI was also prognostic for DFS, OS, and DMFS in patients with stage I and stage III OPSCC, separately. CONCLUSION. MuNI holds promise as a low-cost, tissue-nondestructive, H&E stain-based digital biomarker test for counseling, treatment, and surveillance of patients with p16.sup.+ OPSCC. These data support further confirmation of the MuNI in prospective trials. FUNDING. National Cancer Institute (NCI), NIH; National Institute for Biomedical Imaging and Bioengineering, NIH; National Center for Research Resources, NIH; VA Merit Review Award from the US Department of VA Biomedical Laboratory Research and Development Service; US Department of Defense (DOD) Breast Cancer Research Program Breakthrough Level 1 Award; DOD Prostate Cancer Idea Development Award; DOD Lung Cancer Investigator-Initiated Translational Research Award; DOD Peer-Reviewed Cancer Research Program; Ohio Third Frontier Technology Validation Fund; Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering; Clinical and Translational Science Award (CTSA) program, Case Western Reserve University; NCI Cancer Center Support Grant, NIH; Career Development Award from the US Department of VA Clinical Sciences Research and Development Program; Dan L. Duncan Comprehensive Cancer Center Support Grant, NIH; and Computational Genomic Epidemiology of Cancer Program, Case Comprehensive Cancer Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, the US Department of VA, the DOD, or the US Government.
BACKGROUND. Patients with p16+ oropharyngeal squamous cell carcinoma (OPSCC) are potentially cured with definitive treatment. However, there are currently no reliable biomarkers of treatment failure ...for p16+ OPSCC. Pathologist-based visual assessment of tumor cell multinucleation (MN) has been shown to be independently prognostic of disease-free survival (DFS) in p16+ OPSCC. However, its quantification is time intensive, subjective, and at risk of interobserver variability. METHODS. We present a deep-learning-based metric, the multinucleation index (MuNI), for prognostication in p16+ OPSCC. This approach quantifies tumor MN from digitally scanned H&E-stained slides. Representative H&E-stained whole-slide images from 1094 patients with previously untreated p16+ OPSCC were acquired from 6 institutions for optimization and validation of the MuNI. RESULTS. The MuNI was prognostic for DFS, overall survival (OS), or distant metastasis-free survival (DMFS) in p16+ OPSCC, with HRs of 1.78 (95% CI: 1.37-2.30), 1.94 (1.44-2.60), and 1.88 (1.43-2.47), respectively, independent of age, smoking status, treatment type, or tumor and lymph node (T/N) categories in multivariable analyses. The MuNI was also prognostic for DFS, OS, and DMFS in patients with stage I and stage III OPSCC, separately. CONCLUSION. MuNI holds promise as a low-cost, tissue-nondestructive, H&E stain-based digital biomarker test for counseling, treatment, and surveillance of patients with p16+ OPSCC. These data support further confirmation of the MuNI in prospective trials. FUNDING. National Cancer Institute (NCI), NIH; National Institute for Biomedical Imaging and Bioengineering, NIH; National Center for Research Resources, NIH; VA Merit Review Award from the US Department of VA Biomedical Laboratory Research and Development Service; US Department of Defense (DOD) Breast Cancer Research Program Breakthrough Level 1 Award; DOD Prostate Cancer Idea Development Award; DOD Lung Cancer Investigator-Initiated Translational Research Award; DOD Peer-Reviewed Cancer Research Program; Ohio Third Frontier Technology Validation Fund; Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering; Clinical and Translational Science Award (CTSA) program, Case Western Reserve University; NCI Cancer Center Support Grant, NIH; Career Development Award from the US Department of VA Clinical Sciences Research and Development Program; Dan L. Duncan Comprehensive Cancer Center Support Grant, NIH; and Computational Genomic Epidemiology of Cancer Program, Case Comprehensive Cancer Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, the US Department of VA, the DOD, or the US Government.
El ecocardiograma transtorácico es una herramienta no invasiva útil en la valoración del compromiso cardíaco en los pacientes con lupus eritematoso sistémico (LES).
Nos propusimos investigar las ...principales alteraciones ecocardiográficas en pacientes con este diagnóstico y describir la relación entre varios factores de la enfermedad y los hallazgos ecocardiográficos.
Realizamos una revisión retrospectiva de pacientes con diagnóstico de LES entre los años 2016 y 2020 en un centro de referencia. Se incluyeron 98 pacientes, de los cuales el 87% fueron mujeres, la media de edad para toda la población fue de 35años (RIQ 27,0-49,7), el 40% tenía diagnóstico reciente, el 55% diagnóstico previo o nuevo de hipertensión arterial, en tanto que el 37% usaba esteroides al ingreso.
Entre los hallazgos ecocardiográficos se encontró un 64,3% con enfermedad valvular, el 63% presentaba afección pericárdica, el 25,5% tenía compromiso de la función sistólica, el 27,5% mostraba algún grado de disfunción diastólica, el 13% experimentaba hipertrofia ventricular, el 46% acusaba crecimiento de la aurícula izquierda, el 87% sufría una disfunción sistólica del ventrículo derecho, el 24,5% tenía alguna probabilidad de hipertensión pulmonar, y el 3% presentaba vegetaciones no infecciosas. La presencia de actividad lúpica se asoció con mayor porcentaje de hallazgos ecocardiográficos anormales. No hubo una relación significativa entre la duración de la enfermedad y las anomalías cardíacas, se observó con mayor frecuencia anti-DNA y anticuerpos antifosfolípidos positivos en el grupo de afectación cardíaca.
Consideramos que la ecocardiografía debe hacer parte de la evaluación rutinaria en los pacientes con lupus. La disfunción sistólica del ventrículo derecho, el compromiso pericárdico y la enfermedad valvular no significativa fueron las anormalidades reportadas con mayor frecuencia.
Introduction:Transthoracic echocardiography is a useful noninvasive tool in the assessment of cardiac involvement in patients with systemic lupus erythematosus.
We aimed to investigate the main echocardiographic alterations in patients with a diagnosis of systemic lupus erythematosus and to describe the relationship between various disease factors and echocardiographic findings.
We performed a retrospective review of patients with a diagnosis of SLE between 2016 and 2020 at a referral centre. All 98 patients were included, 87% were female, the mean age for the whole population was 35 years (IQR 27.0- 49.7), 40% had a recent diagnosis, 55% with previous or new diagnosis of arterial hypertension, 37% were using steroids at admission.
Among the echocardiographic findings, 64.3% had valvular disease, 63% had pericardial involvement, 25.5% systolic function compromise, 27.5% some degree of diastolic dysfunction, 13% ventricular hypertrophy, 46% left atrial enlargement, 87% right ventricular systolic dysfunction, 24.5% some probability of pulmonary hypertension, 3% non-infectious vegetations. The presence of lupus activity was associated with a higher percentage of abnormal echocardiographic findings. There was no significant relationship between disease duration and cardiac abnormalities, anti-DNA and positive antiphospholipid antibodies were more frequently observed in the cardiac involvement group.
We consider that echocardiography should be part of the routine evaluation in patients with lupus. Right ventricular systolic dysfunction, pericardial involvement and non-significant valvular disease were the most frequently reported abnormalities.
El interés por aumentar el aprendizaje significativo es una preocupación para distintas líneas de investigación en el campo de la educación. Sin embargo, poco se sabe sobre facilitar este proceso ...usando recursos tecnológicos. Esta investigación quiere explorar cómo el uso de la tecnología, la cual fomente la comunicación y la solución de problemas en el aula, está relacionado con el aprendizaje significativo. Participaron cinco colegios públicos del departamento de Cundinamarca y se realizaron 470 observaciones y encuestas con estudiantes de undécimo grado. Se diseñó un programa con una estrategia de enseñanza – aprendizaje que integró elementos TIC para el desarrollo de competencias tecnológicas. Se administraron dos instrumentos: un formato de observación no participante para indagar por el uso de recursos TIC y una encuesta de percepción a estudiantes para indagar sobre el aprendizaje significativo. El análisis de varianza factorial univariante sugiere que el uso de la tecnología para la comunicación y la solución de problemas en el aula, se relaciona con aprendizaje significativo en términos de compromiso emocional y afectivo con los contenidos académicos. Los resultados también muestran conexiones entre la experiencia de los estudiantes y su conocimiento previo así como el desarrollo de habilidades de transferencia del conocimiento a situaciones de solución de problemas.
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