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1.
Appl Opt ; 62(17): F21-F30, 2023 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-37707127

RESUMO

Image sensors are must-have components of most consumer electronics devices. They enable portable camera systems, which find their way into billions of devices annually. Such high volumes are possible thanks to the complementary metal-oxide semiconductor (CMOS) platform, leveraging wafer-scale manufacturing. Silicon photodiodes, at the core of CMOS image sensors, are perfectly suited to replicate human vision. Thin-film absorbers are an alternative family of photoactive materials, distinguished by the layer thickness comparable with or smaller than the wavelength of interest. They allow design of imagers with functionalities beyond Si-based sensors, such as transparency or detectivity at wavelengths above Si cutoff (e.g., short-wave infrared). Thin-film image sensors are an emerging device category. While intensive research is ongoing to achieve sufficient performance of thin-film photodetectors, to our best knowledge, there have been few complete studies on their integration into advanced systems. In this paper, we will describe several types of image sensors being developed at imec, based on organic, quantum dot, and perovskite photodiode and show their figures of merit. We also discuss the methodology for selecting the most appropriate sensor architecture (integration with thin-film transistor or CMOS). Application examples based on imec proof-of-concept sensors are demonstrated to showcase emerging use cases.

2.
Cancer Sci ; 113(2): 770-783, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34843149

RESUMO

Autoantibodies (AAbs) targeted tumor-associated antigens (TAAs) have the potential for early detection of breast cancer. Here, 574 early-stage breast cancer (ES-BC) patients containing 4 subtypes (Luminal A, Luminal B, HER2+, TN), 126 benign breast disease (BBD) patients, and 199 normal healthy controls (NHC) were separated into three-phases to discover, verify, and validate AAbs. In discovery phase using high-throughput protein microarray, 37 AAbs with sensitivity of 31.25%-86.25% and specificity over 73% in ES-BC, and 40 AAbs with different positive rates between subtypes were identified as candidates. In verification phase, 18 AAbs were significantly increased compared with the Control (BBD and NHC) in focused array. Ten out of 18 AAbs exhibited a significant difference between subtypes (P < .05). In ELISA validation phase, 5 novel AAbs (anti-KJ901215, -FAM49B, -HYI, -GARS, -CRLF3) exhibited significantly higher levels in ES-BC compared with BBD/NHC (P < .05). The sensitivities of individual AAb and a 5-AAbs panel were 20.41%-28.57% and 38.78%, whereas the specificities were over 90% and 85.94%. Simultaneously, 4 AAbs except anti-GARS differed significantly between TN and non-TN subtype (P < .05). We constructed 3 random forest classifier models based on AAbs to discriminant ES-BC from Control or BBD, and to discern TN subtype, which yielded an area under the curve of 0.870, 0.860, and 0.875, respectively. Biological interaction analysis revealed 4 TAAs, except for KJ901215, that were associated with well known proteins of BC. This study discovered and stepwise validated 5 novel AAbs with the potential to diagnose ES-BC and discern TN subtype, indicating easy-to-detect and minimally invasive diagnostic value of serum AAbs ahead of biopsy for future application.


Assuntos
Autoanticorpos/sangue , Neoplasias da Mama/classificação , Neoplasias da Mama/diagnóstico , Detecção Precoce de Câncer/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/imunologia , Autoanticorpos/imunologia , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/imunologia , Diagnóstico Diferencial , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Pessoa de Meia-Idade , Análise Serial de Proteínas , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
3.
Cytokine ; 149: 155759, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34775109

RESUMO

BACKGROUND: Exploration of reliable biomarkers most likely to identify non-small cell lung cancer (NSCLC) patients at high risk for recurrence after surgery is needed. METHODS: Quantibody® Human Cytokine Antibody 6000 was used as screening tool to measure serum levels of 280 cytokines in ten healthy individuals and nine samples from three NSCLC patients before operation, after operation and postoperative recurrence. Selected cytokines were validated in two independent sets (89 patients before surgery, 69 patients after surgery and 40 patients with postoperative recurrence for each set) using ELISA method. The association of the selected cytokine with clinicopathologic features was also evaluated. RESULTS: Thirty-six cytokines were declined after surgery and again elevated when recurrence. We selected MIG to be further assessed in 2 validation sets, the mean value of serum MIG levels in 396 NSCLC patients was 253.42 ± 274.48 pg/mL and was significantly higher than the level in 60 healthy controls (47.65 ± 33.23 pg/mL, P < 0.0001). The serum MIG levels were 366.36 ± 324.04 pg/mL pre-operation, 134.04 ± 127.52 pg/mL post-operation and 208.05 ± 239.39 pg/mL in recurrence in NSCLC patients. The serum MIG levels were significant differences among NSCLC patients of pre-operation, post-operation and recurrence and controls (P < 0.0001). Moreover, Serum MIG levels were decreased markedly after operation and notably increased when disease relapsed (P < 0.0005). Serum MIG levels trend to be higher in patients with male gender, older age, smoking habit, poor tumor differentiation, and non-adenocarcinoma histology. CONCLUSIONS: These data indicated that MIG might be an indicator of postoperative recurrence and help to identify NSCLC patient who was easy to relapse after surgery.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/sangue , Quimiocina CXCL9/sangue , Citocinas/sangue , Neoplasias Pulmonares/sangue , Recidiva Local de Neoplasia/sangue , Idoso , Biomarcadores Tumorais/sangue , Estudos de Coortes , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
4.
ACS Appl Mater Interfaces ; 15(40): 46803-46811, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37755314

RESUMO

The metal halide perovskite absorbers are prone to surface defects, which severely limit the power conversion efficiencies (PCEs) and the operational stability of the perovskite solar cells (PSCs). Herein, trace amounts of bithiophene propylammonium iodide (bi-TPAI) are applied to modulate the surface properties of the gas-quenched perovskite. It is found that the bi-TPAI surface treatment has negligible impact on the perovskite morphology, but it can induce a defect passivation effect and facilitate the charge carrier extraction, contributing to the gain in the open-circuit voltage (Voc) and fill factor. As a result, the PCE of the gas-quenched sputtered NiOx-based inverted PSCs is enhanced from the initial 20.0% to 22.0%. Most importantly, the bi-TPAI treatment can largely alleviate or even eliminate the burn-in process during the maximum power point tracking measurement, improving the operational stability of the devices.

5.
Mar Life Sci Technol ; 4(4): 513-526, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37078078

RESUMO

Ciliates are unique single-celled organisms that play important roles in ecological, environmental, evolutionary, and ontogenetic research. In the present study, phylogenetic analyses based on 18S rRNA gene sequence data reveal that Chaetospira sinica sp. nov. clusters with Stichotricha aculeata with strong to full support (97% ML, 1.00 BI), but is not closely related to members of Spirofilidae Gelei, 1929 to which Chaetospira and Stichotricha have previously been assigned. Phylogenetic analyses, together with morphological and morphogenetic data from Chaetospira sinica sp. nov., support the validity of family Chaetospiridae Jankowski, 1985. Chaetospira and Stichotricha are here assigned to the family Chaetospiridae, the improved diagnosis of which is as follows: non-dorsomarginalian Hypotrichia with flask-shaped body; oral region extending along narrow anterior neck region; lorica usually present; two ventral and two marginal cirral rows, all distinctly spiraled or obliquely curved; pretransverse and transverse cirri absent. The basic morphogenetic features in C. sinica sp. nov. can be summarized as: (1) the oral primordium for the opisthe develops de novo and the parental adoral zone is completely retained by the proter; (2) all ventral cirral anlagen and marginal anlagen developed intrakinetally; (3) three dorsal kineties anlagen formed intrakinetally in each daughter cell; and (4) macronuclear nodules fuse into a single mass. Exconjugant cells were also isolated and their morphologic and molecular data are provided.

6.
ACS Appl Mater Interfaces ; 14(24): 27922-27931, 2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35687012

RESUMO

Volatile A-cation halide (AX) additives such as formamidinium chloride and methylammonium chloride have been widely employed for high-efficiency perovskite solar cells (PSCs). However, it remains unstudied how they influence the perovskite film stoichiometry and the solar cell performance and operational stability. Hereby, our work shows that over annealing of formamidinium chloride-containing perovskite films leads to a Pb-rich surface, resulting in a high initial efficiency, which however decays during maximum power point tracking (MPPT). On the contrary, perovskite films obtained by a shorter annealing time at the same temperature provide good stability during MPPT but a lower initial efficiency. Thus, we deduce that an optimal annealing is vital for both high efficiency and operational stability, which is then confirmed in the case where methylammonium chloride additive is used. With optimized perovskite annealing conditions, we demonstrate efficient and stable p-i-n PSCs that show a best power conversion efficiency of 20.7% and remain 90% of the initial performance after a 200 h MPPT at 60 °C under simulated 1 sun illumination with high UV content. Our work presents a comprehensive understanding on how volatile AX impacts perovskite film stoichiometry and its correlation to the device performance and operational stability, providing a new guideline for fabricating high-efficiency and operationally stable PSCs.

7.
Mar Life Sci Technol ; 4(4): 429-451, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37078082

RESUMO

Ciliates are core components of the structure of and function of aquatic microbial food webs. They play an essential role in the energy flow and material circulation within aquatic ecosystems. However, studies on the taxonomy and biodiversity of freshwater ciliates, especially those in wetlands in China are limited. To address this issue, a project to investigate the freshwater ciliates of the Lake Weishan Wetland, Shandong Province, commenced in 2019. Here, we summarize our findings to date on the diversity of ciliates. A total of 187 ciliate species have been found, 94 of which are identified to species-level, 87 to genus-level, and six to family-level. These species show a high morphological diversity and represent five classes, i.e., Heterotrichea, Litostomatea, Prostomatea, Oligohymenophorea, and Spirotrichea. The largest number of species documented are oligohymenophoreans. A comprehensive database of these ciliates, including morphological data, gene sequences, microscope slide specimens and a DNA bank, has been established. In the present study, we provide an annotated checklist of retrieved ciliates as well as information on the sequences of published species. Most of these species are recorded in China for the first time and more than 20% are tentatively identified as new to science. Additionally, an investigation of environmental DNA revealed that the ciliate species diversity in Lake Weishan Wetland is higher than previously supposed. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-022-00154-x.

8.
Front Microbiol ; 12: 707954, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34394057

RESUMO

Hypotrich ciliates with evolutionary novelties are continually being discovered, challenging the current taxonomic system and attracting increased attention. In the present work, two new urostylid ciliates, Heterobakuella bergeri gen. nov., sp. nov. and Anteholosticha perezuzae sp. nov., isolated from Chinese wetland samples, were identified based on morphology and 18S rRNA gene sequences. Heterobakuella gen. nov. is defined by three frontal cirri, single buccal cirrus, one parabuccal cirrus, midventral complex composed of cirral pairs and one cirral row, one left and two right marginal cirral rows, transverse and pretransverse cirri present, caudal and frontoterminal cirri absent. Heterobakuella can be easily distinguished from the morphologically most similar genus, Apobakuella, mainly by the single buccal cirrus (vs. one buccal cirral row) and one parabuccal cirrus (vs. several parabuccal cirral rows originated from different anlagen). Phylogenetic analyses show that H. bergeri branches within the clade formed by Bergeriella ovata, Monocoronella carnea, Anteholosticha gracilis, and Neourostylopsis spp., rather than the clade represented by Apobakuella. The other species, A. perezuzae, is mainly characterized by a distinctly slender body shape with an average length:width ratio about 7, distinctively shaped biconcave and greenish cortical granules, as well as one or two pretransverse cirri. Phylogenetic analyses indicate the genus Anteholosticha is non-monophyletic.

9.
ACS Appl Mater Interfaces ; 13(37): 44294-44301, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34498844

RESUMO

To guarantee a long lifetime of perovskite-based photovoltaics, the selected materials need to survive relatively high-temperature stress during the solar cell operation. Highly efficient n-i-p perovskite solar cells (PSCs) often degrade at high operational temperatures due to morphological instability of the hole transport material 2,2',7,7'-tetrakis (N,N-di-p-methoxyphenyl-amine)9,9'-spirobifluorene (Spiro-OMeTAD). We discovered that the detrimental large-domain spiro-OMeTAD crystallization is caused by the simultaneous presence of tert-butylpyridine (tBP) additive and gold (Au) as a capping layer. Based on this discovery and our understanding, we demonstrated facile strategies that successfully stabilize the amorphous phase of spiro-OMeTAD film. As a result, the thermal stability of n-i-p PSCs is largely improved. After the spiro-OMeTAD films in the PSCs were stressed for 1032 h at 85 °C in the dark in nitrogen environment, reference PSCs retained only 22% of their initial average power conversion efficiency (PCE), while the best target PSCs retained 85% relative average PCE. Our work suggests facile ways to realize efficient and thermally stable spiro-OMeTAD containing n-i-p PSCs.

10.
Front Microbiol ; 11: 560915, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33584556

RESUMO

Hypotrichs are the most complex and highly differentiated ciliate lineages and have great potential for evolutionary novelties. Problems in hypotrich systematics are mainly due to discordance between the morphological and genetic data (mainly small subunit rRNA gene). Species with morphologies that are characteristic of two or more higher rank taxa are probably a major contributing factor to these conflicts. The present study describes a Chinese population of a poorly known organism with numerous endosymbiotic zoochlorellae, the morphology of which corresponds well with the type population of Limnoholosticha viridis (Kahl, 1932) Li et al., 2017. Newly obtained information shows this species has a zigzag midventral cirral pattern that is diagnostic of urostylids, whereas the dorsal ciliature shares features (presence of dorsomarginal kinety and dorsal kinety 3 fragmentation) that are typical of oxytrichids. Molecular phylogenetic analyses reveal a close relationship with oxytrichids. An integrative approach combining morphological, morphogenetic, phylogenetic and ecological analyses indicates that L. viridis represents a new genus and new family which might be an intermediate form between uorstylids and dorsomarginalians. Thus, Bourlandellidae fam. nov. and Bourlandella gen. nov. are here established. Lastly, we speculate that phenotypic convergence and mixtrophy might confer on the new combination, Bourlandella viridis (Kahl, 1932) comb. nov., the ability to adapt to a wide range of environmental conditions.

11.
ACS Omega ; 4(13): 15600-15614, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31572861

RESUMO

The implementation of fuel cell deployment requires efficient conversion of fuels into hydrogen in a distributed energy system. Fortunately, continuous flow and microreactor technology provide unique opportunities for the portable production of hydrogen. This study focuses on determining the operation space for a thermally integrated methane reforming system, thereby providing a theoretical basis for the design and optimization of such systems. The steam-methane reforming over rhodium coupled with methane combustion over platinum in a thermally integrated microchannel reactor arranged with rectangular-shaped protuberances was studied numerically in order to improve its operability and stability. Computational fluid dynamic simulations were carried out with detailed reaction mechanisms to identify conditions for the maximum hydrogen yield and the highest output power. Various operating lines were presented, and various performance metrics were evaluated accordingly. The results indicated that the efficient production of hydrogen is made possible through improving transport performance for highly active catalysts. The flow disturbance elements designed for the reactor are of great benefit to intensification of the reforming process. There exists a trade-off between fuel utilization and output power. Autothermal operation advantages from improved transport performance in small physical dimensions were demonstrated for the system, but careful thermal management is always necessary to ensure its efficient and stable operation. The thermal conductivity of the wall separating the exothermic and endothermic reactions plays a significant role in determining the performance of the system. Highly active catalysts are required to intensify the overall reforming process and to achieve efficient thermal management. Adjustment of fluid velocities can serve as a convenient means to achieve efficient operation of the system.

12.
Environ Sci Pollut Res Int ; 26(7): 6717-6724, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30632045

RESUMO

Accumulating evidence has shown that prenatal ambient air pollution exposure is associated with elevated stillbirth risk; however, the results are inconsistent. This population-based prospective cohort study aimed to explore the association between prenatal air pollution exposure and stillbirth rate in the coastal area in China. Data of air pollution and birth outcomes between January 1, 2015, and December 31, 2017, were collected. Among the 59,868 eligible births, there were 587 stillbirths and 59,281 live births. Although the air quality in this study was relatively better than most of the major cities in China, a positive association was still found between prenatal air pollution exposure and stillbirth rate. Every 10 µg/m3 increase of fine particulate matters (PM2.5) in each trimester, as well as in the entire pregnancy, was associated with increased stillbirth rate (RR = 1.14, 1.11, 1.15, and 1.14 for the first, second, third trimester, and entire pregnancy, respectively). In addition, every 10 µg/m3 increase of PM10 in the first trimester (RR = 1.09, 95% CI: 1.04-1.14), and 10 µg/m3 increase of O3 in the first (RR = 1.05, 95% CI: 1.01-1.09) and third (RR = 1.04, 95% CI: 1.00-1.08) trimesters was also associated with increased stillbirth rate. The effects of PM2.5 on stillbirth rate were found to be robust in the two-pollutant models. The findings of this study especially underscored the adverse effects of prenatal exposure of high levels of PM2.5 on stillbirth. More studies are needed to verify our findings and further investigate the underlying mechanisms.


Assuntos
Poluição do Ar/estatística & dados numéricos , Exposição Materna/estatística & dados numéricos , Natimorto/epidemiologia , Poluentes Atmosféricos , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Material Particulado , Gravidez , Primeiro Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Estudos Prospectivos
13.
J Cancer ; 10(5): 1275-1287, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30854137

RESUMO

The study was performed to investigate the antitumor efficacy of histone deacetylase inhibitor (HDACi) chidamide alone or with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) icotinib in non-small cell lung cancer (NSCLC). The cell viability, cell cycle, apoptosis, protein expression, and the molecular mechanisms were explored among ten NSCLC cell lines with chidamide and icotinib alone or in combination, and further validated in xenograft models of nude mice. Chidamide significantly reduced the viability of A549, HCC827, HCC827IR (icotinib resistant) cells, increased the sensitivity of icotinib synergistically in EGFR-TKI resistant cell line, especially in H1975 cells. Chidamide alone or combined with icotinib induced cell cycle arrest by inhibiting the activation of RAS/MAPK, PI3K/AKT and/or JAK/STAT pathways, and caused apoptosis by activating caspase 3 and PARP. Chidamide alone or with icotinib suppressed ß-catenin expression in HCC827, HCC827IR, and H1975 cells. The sensitivity of H1975 cells to icotinib was increased by chidamide through restoring E-cadherin expression. Furthermore, chidamide alone or in combination with icotinib inhibited HCC827IR and H1975 xenograft growth in athymic nude mice, respectively, with no appreciable side effects. Chidamide or combinating with icotinib exhibits antitumor activity in NSCLC cells, and has potential clinical implication for the treatment of NSCLC.

14.
ACS Appl Mater Interfaces ; 11(18): 16517-16526, 2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-30998002

RESUMO

With the realization of highly efficient perovskite solar cells, the long-term stability of these devices is the key challenge hindering their commercialization. In this work, we study the temperature-dependent stability of perovskite solar cells and develop a model capable of predicting the lifetime and energy yield of perovskite solar cells outdoors. This model results from the measurement of the kinetics governing the degradation of perovskite solar cells at elevated temperatures. The individual analysis of all key current-voltage parameters enables the prediction of device performance under thermal stress with high precision. An extrapolation of the device lifetime at various European locations based on historical weather data illustrates the relation between the laboratory data and real-world applications. Finally, the understanding of the degradation mechanisms affecting perovskite solar cells allows the definition and implementation of strategies to enhance the thermal stability of perovskite solar cells.

15.
ACS Sens ; 2(12): 1839-1846, 2017 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-29183119

RESUMO

Droplet-based high throughput biomolecular screening and combinatorial synthesis entail a viable indexing strategy to be developed for the identification of each microreactor. Here, we propose a novel indexing scheme based on the generation of droplet sequences on demand to form unique encoding droplet chains in fluidic networks. These codes are represented by multiunit and multilevel droplets packages, with each code unit possessing several distinct signal levels, potentially allowing large encoding capacity. For proof of concept, we use magnetic nanoparticles as the encoding material and a giant magnetoresistance (GMR) sensor-based active sorting system supplemented with an optical detector to generate and decode the sequence of one exemplar sample droplet reactor and a 4-unit quaternary magnetic code. The indexing capacity offered by 4-unit multilevel codes with this indexing strategy is estimated to exceed 104, which holds great promise for large-scale droplet-based screening and synthesis.


Assuntos
Emulsões , Nanopartículas de Magnetita/química , Técnicas Analíticas Microfluídicas/métodos , Microfluídica/métodos , Corantes Fluorescentes/química , Ensaios de Triagem em Larga Escala/métodos , Dispositivos Lab-On-A-Chip , Fenômenos Magnéticos , Microscopia , Tamanho da Partícula
16.
Oncotarget ; 7(24): 36590-36601, 2016 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-27145277

RESUMO

In this study, we analyzed the genetic profiles of squamous cell lung carcinoma (SqCLC) to identify potential therapeutic targets. Approximately 2,800 COSMIC mutations from 50 genes were determined by next-generation sequencing. Amplification/deletion of SOX2, CDKN2A, PTEN, FGFR1, EGFR, CCND1, HER2 and PDGFRA were detected by FISH and expression of VEGFR2, PD-L1 and PTEN were examined by IHC. One hundred and fifty-seven samples of SqCLC were collected. Somatic mutations was identified in 73.9% of cases, with TP53 (56.1%), CDKN2A (8.9%), PIK3CA (8.9%), KRAS (4.5%) and EGFR (3.2%). Gene copy number alterations were identified in 75.8% of cases, including SOX2 amplification (31.2%), CDKN2A deletion (21.7%), PTEN deletion (16.6%), FGFR1 amplification (15.9%), EGFR amplification (14.0%), CCND1 amplification (14.0%), HER2 amplification (9.6%) and PDGFRA amplification (7.6%). Positive expression of VEGFR2 and PD-L1 and loss of PTEN expression were observed in 80.5%, 47.2%, and 42.7% of cases, respectively. Multivariate analysis showed that positive expression of PD-L1 was an independent favorable prognostic factor for DFS (HR = 0.610; P = 0.044). In conclusion, nearly all (93.6%) SqCLC cases harbored at least one potential druggable target. The findings of this study could facilitate the identification of therapeutic target candidates for precision medicine of SqCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/genética , Neoplasias Pulmonares/genética , Mutação , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/patologia , Variações do Número de Cópias de DNA , Feminino , Amplificação de Genes , Deleção de Genes , Predisposição Genética para Doença/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada
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