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1.
Genes (Basel) ; 15(6)2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38927706

RESUMEN

Deficiencies in DNA mismatch repair (MMRd) leave characteristic footprints of microsatellite instability (MSI) in cancer genomes. We used data from the Cancer Genome Atlas and International Cancer Genome Consortium to conduct a comprehensive analysis of MSI-associated cancers, focusing on indel mutational signatures. We classified MSI-high genomes into two subtypes based on their indel profiles: deletion-dominant (MMRd-del) and insertion-dominant (MMRd-ins). Compared with MMRd-del genomes, MMRd-ins genomes exhibit distinct mutational and transcriptomic features, including a higher prevalence of T>C substitutions and related mutation signatures. Short insertions and deletions in MMRd-ins and MMRd-del genomes target different sets of genes, resulting in distinct indel profiles between the two subtypes. In addition, indels in the MMRd-ins genomes are enriched with subclonal alterations that provide clues about a distinct evolutionary relationship between the MMRd-ins and MMRd-del genomes. Notably, the transcriptome analysis indicated that MMRd-ins cancers upregulate immune-related genes, show a high level of immune cell infiltration, and display an elevated neoantigen burden. The genomic and transcriptomic distinctions between the two types of MMRd genomes highlight the heterogeneity of genetic mechanisms and resulting genomic footprints and transcriptomic changes in cancers, which has potential clinical implications.


Asunto(s)
Reparación de la Incompatibilidad de ADN , Mutación INDEL , Inestabilidad de Microsatélites , Neoplasias , Humanos , Neoplasias/genética , Neoplasias/inmunología , Reparación de la Incompatibilidad de ADN/genética , Genoma Humano , Transcriptoma/genética
3.
Front Cell Dev Biol ; 12: 1345660, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38523628

RESUMEN

Background: Previous studies have reported that genes highly expressed in leukemic stem cells (LSC) may dictate the survival probability of patients and expression-based cellular deconvolution may be informative in forecasting prognosis. However, whether the prognosis of acute myeloid leukemia (AML) can be predicted using gene expression and deconvoluted cellular abundances is debatable. Methods: Nine different cell-type abundances of a training set composed of the AML samples of 422 patients, were used to build a model for predicting prognosis by least absolute shrinkage and selection operator Cox regression. This model was validated in two different validation sets, TCGA-LAML and Beat AML (n = 179 and 451, respectively). Results: We introduce a new prognosis predicting model for AML called the LSC activity (LSCA) score, which incorporates the abundance of 5 cell types, granulocyte-monocyte progenitors, common myeloid progenitors, CD45RA + cells, megakaryocyte-erythrocyte progenitors, and multipotent progenitors. Overall survival probabilities between the high and low LSCA score groups were significantly different in TCGA-LAML and Beat AML cohorts (log-rank p-value = 3.3×10-4 and 4.3×10-3, respectively). Also, multivariate Cox regression analysis on these two validation sets shows that LSCA score is independent prognostic factor when considering age, sex, and cytogenetic risk (hazard ratio, HR = 2.17; 95% CI 1.40-3.34; p < 0.001 and HR = 1.20; 95% CI 1.02-1.43; p < 0.03, respectively). The performance of the LSCA score was comparable to other prognostic models, LSC17, APS, and CTC scores, as indicated by the area under the curve. Gene set variation analysis with six LSC-related functional gene sets indicated that high and low LSCA scores are associated with upregulated and downregulated genes in LSCs. Conclusion: We have developed a new prognosis prediction scoring system for AML patients, the LSCA score, which uses deconvoluted cell-type abundance only.

4.
Opt Express ; 32(3): 4668-4683, 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38297662

RESUMEN

Display field communication (DFC) is an unobtrusive display-to-camera technology that transmits data within the frequency domain of images, ensuring that the embedded data are hidden and do not disrupt the viewing experience. The display embeds data into image frames, while the receiver captures the display and extracts it. Two-dimensional DFC (2D-DFC) focuses on embedding data in the width and height of an image. This study explores two methods to minimize the error rate in 2D-DFC without affecting the quality of the displayed image. The orthogonal method embeds data in the orthogonal direction of an image. On the other hand, the diagonal embedding method strategically embeds the data in the diagonal direction. Experiments show the diagonal method maintains a higher peak signal-to-noise ratio and surpasses the orthogonal embedding method in terms of bit error rate. 2D-DFC is expected to have practical applications in digital signage, advertising and informational displays at airports and train stations, as well as at large-scale displays for events, sports arenas, and performance venues.

5.
J Transl Med ; 22(1): 154, 2024 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-38355577

RESUMEN

BACKGROUND: Tumor cells of diffuse-type gastric cancer (DGC) are discohesive and infiltrate into the stroma as single cells or small subgroups, so the stroma significantly impacts DGC progression. Cancer-associated fibroblasts (CAFs) are major components of the tumor stroma. Here, we identified CAF-specific secreted molecules and investigated the mechanism underlying CAF-induced DGC progression. METHODS: We conducted transcriptome analysis for paired normal fibroblast (NF)-CAF isolated from DGC patient tissues and proteomics for conditioned media (CM) of fibroblasts. The effects of fibroblasts on cancer cells were examined by transwell migration and soft agar assays, western blotting, and in vivo. We confirmed the effect of blocking tubulointerstitial nephritis antigen-like 1 (TINAGL1) in CAFs using siRNA or shRNA. We evaluated the expression of TINAGL1 protein in frozen tissues of DGC and paired normal stomach and mRNA in formalin-fixed, paraffin-embedded (FFPE) tissue using RNA in-situ hybridization (RNA-ISH). RESULTS: CAFs more highly expressed TINAGL1 than NFs. The co-culture of CAFs increased migration and tumorigenesis of DGC. Moreover, CAFs enhanced the phosphorylation of focal adhesion kinase (FAK) and mesenchymal marker expression in DGC cells. In an animal study, DGC tumors co-injected with CAFs showed aggressive phenotypes, including lymph node metastasis. However, increased phosphorylation of FAK and migration were reduced by blocking TINAGL1 in CAFs. In the tissues of DGC patients, TINAGL1 was higher in cancer than paired normal tissues and detected with collagen type I alpha 1 chain (COL1A1) in the same spot. Furthermore, high TINAGL1 expression was significantly correlated with poor prognosis in several public databases and our patient cohort diagnosed with DGC. CONCLUSIONS: These results indicate that TINAGL1 secreted by CAFs induces phosphorylation of FAK in DGC cells and promotes tumor progression. Thus, targeting TINAGL1 in CAFs can be a novel therapeutic strategy for DGC.


Asunto(s)
Fibroblastos Asociados al Cáncer , Nefritis Intersticial , Neoplasias Gástricas , Animales , Humanos , Fibroblastos Asociados al Cáncer/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Fibroblastos/metabolismo , Integrina beta1/genética , Integrina beta1/metabolismo , Nefritis Intersticial/metabolismo , Nefritis Intersticial/patología , ARN Interferente Pequeño/metabolismo , Neoplasias Gástricas/patología , Microambiente Tumoral
6.
Cancer Res Treat ; 2024 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-38186238

RESUMEN

Purpose: There have been needs to improve the sensitivity of liquid biopsy. This report aims to report the analytical and clinical validation of a next generation sequencing (NGS)-based circulating tumor DNA (ctDNA) assay. Materials and Methods: Analytical validation was conducted in vitro by evaluating the limit of detection (LOD), precision, and specificity for various genomic aberrations. The real-world performance in non-small cell lung cancer (NSCLC) was assessed by comparing the results of AlphaLiquid®100 to the tissue-based results. Results: The LODs with 30 ng input DNA were 0.11%, 0.11%, 0.06%, 0.21%, and 2.13 copies for detecting SNVs, insertions, deletions, fusions, and copy number alterations (CNA), respectively. Quantitatively, SNV/INDELs, fusions, and CNAs showed a good correlation (R2=0.91, 0.40, and 0.65; y=0.95, 1.06, and 1.19) to the manufacturer's values, and per-base specificities for all types of variants were near 100%. In real-world NSCLC (n=122), key actionable mutations in NSCLC were detected in 60.7% (74/122) with the ctDNA assay. Comparative analysis against the NGS-based tissue results for all key mutations showed positive percent agreement (PPA) of 85.3%. For individual genes, the PPA was as high as 95.7% for EGFR mutations and 83.3% for ALK translocations. AlphaLiquid 100 detected drug-sensitive EGFR mutation at a variant allele frequency as low as 0.02% and also identified an EGFR mutation in a case where tissue sample missed. Blood samples collected post-targeted therapies revealed additional acquired mutations. Conclusion: The AlphaLiquid®100 ctDNA assay demonstrates robust analytical validity, offering clinically important information for NSCLC patients.

7.
ACS Appl Mater Interfaces ; 15(44): 51050-51058, 2023 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-37874850

RESUMEN

The cesium lead iodide (CsPbI3) perovskite solar cell possesses a wide band gap ranging from 1.65 to 1.75 eV, which is suitable for integration into a tandem structure along with a low-band-gap silicon solar cell. Moreover, CsPbI3 has received considerable attention as a potential solution for the prevalent issues of low thermal stability of organic-inorganic perovskite solar cells and phase segregation encountered in conventional mixed halide wide-band-gap perovskite solar cells. Through the implementation of volatile additives, CsPbI3 has demonstrated substantial advancements in efficiency, process temperature, and stability. This study introduces a novel approach for barium (Ba)-doping by spraying an antisolvent containing barium bis(trifluoromethanesulfonimide) during the spin-coating process. By incorporating Ba2+ through this spraying technique, the formation of the delta phase in CsPbI3 is significantly suppressed; thereby, a power conversion efficiency of 18.56% is achieved, and a remarkable 93% of the initial efficiency is maintained after 600 h.

8.
Orthop J Sports Med ; 11(10): 23259671231205240, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37900867

RESUMEN

Background: The biomechanical properties of the 1.2-mm suture tape have outperformed conventional sutures in previous studies. Purpose: To compare the loop and knot security of 2 tape-type and 1 cord-type sutures using different arthroscopic knot techniques. Study Design: Controlled laboratory study. Methods: The biomechanical characteristics of the 1.2-mm tape, 2.0-mm tape, and 0.5-mm No. 2 suture were compared using 4 different knot types: 2 sliding knots (Samsung Medical Center [SMC] and Tennessee) and 2 nonsliding knots (2-throw surgeon's and 2-throw square) with 2 and 3 additional reverse half-hitches on alternating posts (RHAPs) in a closed-loop system on a materials testing device. Each configuration was tested for loop security (maximal load applied between 0 and 3 mm of displacement), knot security (ultimate failure load), and failure mode with cyclical loading (30 N load for 20 cycles at 1 cycle per sec until failure). Loop and knot security among the configurations were compared using an analysis of variance. Results: With 2 RHAPs, the 2.0-mm tape showed significantly greater loop security than the 1.2-mm tape and suture (P = .001). With 3 RHAPs, the loop security of the suture was significantly superior compared with the 1.2-mm tape (P = .010). Regarding knot security, with 2 RHAPs, the 2.0-mm tape was significantly better than the 1.2-mm tape and suture (P < .001), while with 3 RHAPs, the suture was significantly superior to the 1.2-mm tape (P = .012). Using a square knot with 2 RHAPs, the 2.0-mm tape had significantly greater loop security (P = .001) and better knot security (P = .001) to the 1.2-mm tape and suture. Using the Tennessee knot with 2 RHAPs, the 1.2-mm tape had less loop security (P = .011) and knot security (P = .005) than the suture. Using the SMC knot with 3 RHAPs, the 2.0-mm tape and suture were significantly superior in loop security (P = .001) and knot security (P < .001) to the 1.2-mm tape. There was no significant difference in the failure mode between tapes and sutures with 2 and 3 RHAPs. Conclusion: With 2 RHAPs, the 2.0-mm tape demonstrated greater resistance to suture loop displacement and better knot security compared with the 1.2-mm tape and suture. However, with 3 RHAPs, the 1.2-mm tape manifested weaker loop and knot security compared with the suture.

9.
Neurointervention ; 18(3): 166-171, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37853573

RESUMEN

PURPOSE: While symptomatic basilar artery (BA) stenosis is associated with a higher risk of recurrent stroke or death, there is no consensus on the management of these patients who are refractory to antiplatelet therapy. This study retrospectively assesses the outcomes of endovascular treatment (EVT) for symptomatic BA stenosis. MATERIALS AND METHODS: We conducted a retrospective review of patients with symptomatic BA stenosis who underwent EVT, including angioplasty or stenting, from 2006 to 2018. A total of 15 patients, who experienced transient ischemic attacks or strokes despite dual antiplatelet therapy, were included. EVT was performed under local anesthesia after pretreatment with antiplatelet medications. Angiographic follow-up was performed at 12 and 24 months post-EVT. Clinical outcomes were evaluated using the modified Rankin Scale (mRS). RESULTS: EVT was successfully completed in all patients. Peri/post-procedural complications occurred in 33% of cases, including in-stent thrombosis, intracranial hemorrhage, and pontine infarction. At long-term follow-up (mean 98.5±80.5 months), 73.3% of patients achieved a favorable functional outcome (mRS≤2) without disability or mortality. Patients with unfavorable outcomes had previous infarcts, with 2 experiencing new pontine infarctions after stenting. CONCLUSION: This study suggests that EVT, including angioplasty and stenting, may offer promise as a treatment option for symptomatic BA stenosis refractory to medical therapy. However, the procedure carries a notable risk of complications, especially in patients with severe stenosis and previous infarcts. Careful patient selection, based on clinical and radiological criteria, is crucial.

10.
Int J Mol Sci ; 24(9)2023 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-37176124

RESUMEN

Longitudinal tumor sequencing of recurrent bladder cancer (BC) can facilitate the investigation of BC progression-associated genomic and transcriptomic alterations. In this study, we analyzed 18 tumor specimens including distant and locoregional metastases obtained during tumor progression for five BC patients using whole-exome and transcriptome sequencing. Along with the substantial level of intratumoral mutational heterogeneity across the cases, we observed that clonal mutations were enriched with known BC driver genes and apolipoprotein B mRNA editing enzyme, catalytic polypeptide (APOBEC)-associated mutation signatures compared with subclonal mutations, suggesting the genetic makeup for BC tumorigenesis associated with APOBEC deaminase activity was accomplished early in the cancer evolution. Mutation-based phylogenetic analyses also revealed temporal dynamics of mutational clonal architectures in which the number of mutational clones varied along the BC progression and notably was often punctuated by clonal sweeps associated with chemotherapy. The bulk-level transcriptome sequencing revealed frequent subtype switching in which transcriptionally defined BC subtypes may vary during tumor progression. Longitudinal whole-exome and transcriptome sequencing of recurrent BC may advance our understanding into the BC heterogeneity in terms of somatic mutations, cell clones and transcriptome-based tumor subtypes during disease progression.


Asunto(s)
Recurrencia Local de Neoplasia , Neoplasias de la Vejiga Urinaria , Humanos , Filogenia , Recurrencia Local de Neoplasia/genética , Mutación , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Transcriptoma
11.
Small ; 19(39): e2302597, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37246255

RESUMEN

Ultrathin crystalline silicon is widely used as an active material for high-performance, flexible, and stretchable electronics, from simple passive and active components to complex integrated circuits, due to its excellent electrical and mechanical properties. However, in contrast to conventional silicon wafer-based devices, ultrathin crystalline silicon-based electronics require an expensive and rather complicated fabrication process. Although silicon-on-insulator (SOI) wafers are commonly used to obtain a single layer of crystalline silicon, they are costly and difficult to process. Therefore, as an alternative to SOI wafers-based thin layers, here, a simple transfer method is proposed for printing ultrathin multiple crystalline silicon sheets with thicknesses between 300 nm to 13 µm and high areal density (>90%) from a single mother wafer. Theoretically, the silicon nano/micro membrane can be generated until the mother wafer is completely consumed. In addition, the electronic applications of silicon membranes are successfully demonstrated through the fabrication of a flexible solar cell and flexible NMOS transistor arrays.

12.
Chem Commun (Camb) ; 59(32): 4818-4821, 2023 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-37009682

RESUMEN

Reductive amination has been widely used for manufacturing carbon-nitrogen-containing building blocks. Despite its versatility, the need for a chemical reductant or harmful hydrogen gas has limited its further utilization in modern chemical applications. Here, we report electrochemical reductive amination (ERA) to pursue sustainable synthetic routes. Faradaic efficiencies of about 83% are achieved using Cu metal electrodes. In-depth electrokinetic studies reveal the rate-determining step and overall reaction nature of ERA. Through the experiments using deuterated solvent and additional proton sources, we scrutinize the origin of protons during the ERA. Furthermore, CW-EPR analysis captures the radical intermediate species, formed during the catalytic cycle, advancing mechanistic understanding of ERA process.

13.
Front Cell Infect Microbiol ; 13: 1101291, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36960042

RESUMEN

Background & Aims: Fusobacterium nucleatum (FN) plays a pivotal role in the development and progression of colorectal cancer by modulating antitumor immune responses. However, the impact of FN on immune regulation in the tumor microenvironment has not been fully elucidated. Methods: The abundance of FN was measured in 99 stage III CRC tumor tissues using quantitative polymerase chain reaction. Gene expression profiles were assessed and annotated using consensus molecular subtypes (CMS), Gene Ontology (GO) analysis, and deconvolution of individual immune cell types in the context of FN abundance. Immune profiling for tumor infiltrating T cells isolated from human tumor tissues was analyzed using flow cytometry. Ex vivo tumor-infiltrating T cells were stimulated in the presence or absence of FN to determine the direct effects of FN on immune cell phenotypes. Results: Gene expression profiles, CMS composition, abundance of immune cell subtypes, and survival outcomes differed depending on FN infection. We found that FN infection was associated with poorer disease-free survival and overall survival in stage III CRC patients. FN infection was associated with T cell depletion and enrichment of exhausted CD8+ and FoxP3+ regulatory T cells in the tumor microenvironment. The presence of FN in tumors was correlated with a suppressive tumor microenvironment in a T cell-dependent manner. Conclusion: FN enhanced the suppressive immune microenvironment with high depletion of CD8+ T cells and enrichment of FoxP3+ regulatory T cells in human colorectal cancer cases. Our findings suggest a potential association for FN in adaptive immunity, with biological and prognostic implications.


Asunto(s)
Neoplasias Colorrectales , Humanos , Neoplasias Colorrectales/patología , Fusobacterium nucleatum , Microambiente Tumoral , Linfocitos T CD8-positivos/metabolismo , Inmunidad Adaptativa , Factores de Transcripción Forkhead
14.
Nature ; 614(7946): 81-87, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36725999

RESUMEN

Micro-LEDs (µLEDs) have been explored for augmented and virtual reality display applications that require extremely high pixels per inch and luminance1,2. However, conventional manufacturing processes based on the lateral assembly of red, green and blue (RGB) µLEDs have limitations in enhancing pixel density3-6. Recent demonstrations of vertical µLED displays have attempted to address this issue by stacking freestanding RGB LED membranes and fabricating top-down7-14, but minimization of the lateral dimensions of stacked µLEDs has been difficult. Here we report full-colour, vertically stacked µLEDs that achieve, to our knowledge, the highest array density (5,100 pixels per inch) and the smallest size (4 µm) reported to date. This is enabled by a two-dimensional materials-based layer transfer technique15-18 that allows the growth of RGB LEDs of near-submicron thickness on two-dimensional material-coated substrates via remote or van der Waals epitaxy, mechanical release and stacking of LEDs, followed by top-down fabrication. The smallest-ever stack height of around 9 µm is the key enabler for record high µLED array density. We also demonstrate vertical integration of blue µLEDs with silicon membrane transistors for active matrix operation. These results establish routes to creating full-colour µLED displays for augmented and virtual reality, while also offering a generalizable platform for broader classes of three-dimensional integrated devices.

15.
Mod Pathol ; 36(1): 100004, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36788076

RESUMEN

Radiation-induced sarcoma (RIS) is a rare but serious late complication arising from radiotherapy. Despite unfavorable clinical outcomes, the genomic footprints of ionizing radiation in RIS development remain largely unknown. Hence, this study aimed to characterize RIS genomes and the genomic alterations in them. We analyzed whole-genome sequencing in 11 RIS genomes matched with normal genomes to identify somatic alterations potentially associated with RIS development. Furthermore, the abundance of mutations, mutation signatures, and structural variants in RIS were compared with those in radiation-naïve spontaneous sarcomas. The mutation abundance in RIS genomes, including one hypermutated genome, was variable. Cancer-related genes might show different types of genomic alterations. For instance, NF1, NF2, NOTCH1, NOTCH2, PIK3CA, RB1, and TP53 showed singleton somatic mutations; MYC, CDKN2A, RB1, and NF1 showed recurrent copy number alterations; and NF2, ARID1B, and RAD51B showed recurrent structural variations. The genomic footprints of nonhomologous end joining are prevalent at indels of RIS genomes compared with those in spontaneous sarcoma genomes, representing the genomic hallmark of RIS genomes. In addition, frequent chromothripsis was identified along with predisposing germline variants in the DNA-damage-repair pathways in RIS genomes. The characterization of RIS genomes on a whole-genome sequencing scale highlighted that the nonhomologous end joining pathway was associated with tumorigenesis, and it might pave the way for the development of advanced diagnostic and therapeutic strategies for RIS.


Asunto(s)
Sarcoma , Neoplasias de los Tejidos Blandos , Humanos , Mutación , Oncogenes , Sarcoma/genética , Mutación de Línea Germinal , Neoplasias de los Tejidos Blandos/genética , ADN
16.
Nat Biomed Eng ; 7(7): 853-866, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36536253

RESUMEN

Variant callers typically produce massive numbers of false positives for structural variations, such as cancer-relevant copy-number alterations and fusion genes resulting from genome rearrangements. Here we describe an ultrafast and accurate detector of somatic structural variations that reduces read-mapping costs by filtering out reads matched to pan-genome k-mer sets. The detector, which we named ETCHING (for efficient detection of chromosomal rearrangements and fusion genes), reduces the number of false positives by leveraging machine-learning classifiers trained with six breakend-related features (clipped-read count, split-reads count, supporting paired-end read count, average mapping quality, depth difference and total length of clipped bases). When benchmarked against six callers on reference cell-free DNA, validated biomarkers of structural variants, matched tumour and normal whole genomes, and tumour-only targeted sequencing datasets, ETCHING was 11-fold faster than the second-fastest structural-variant caller at comparable performance and memory use. The speed and accuracy of ETCHING may aid large-scale genome projects and facilitate practical implementations in precision medicine.


Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento , Neoplasias , Humanos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Genoma , Análisis de Secuencia de ADN/métodos
17.
Int J Mol Sci ; 25(1)2023 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-38203315

RESUMEN

Although the intravesical instillation of Bacillus Calmette-Guerin (BCG) is widely used as adjuvant treatment for nonmuscle-invasive bladder cancers, the clinical benefit is variable across patients, and the molecular mechanisms underlying the sensitivity to BCG administration and disease progression are poorly understood. To establish the molecular signatures that predict the responsiveness and disease progression of bladder cancers treated with BCG, we performed transcriptome sequencing (RNA-seq) for 13 treatment-naïve and 22 post-treatment specimens obtained from 14 bladder cancer patients. To overcome disease heterogeneity, we used non-negative matrix factorization to identify the latent molecular features associated with drug responsiveness and disease progression. At least 12 molecular features were present, among which the immune-related feature was associated with drug responsiveness, indicating that pre-treatment anti-cancer immunity might dictate BCG responsiveness. We also identified disease progression-associated molecular features indicative of elevated cellular proliferation in post-treatment specimens. The progression-associated molecular features were validated in an extended cohort of BCG-treated bladder cancers. Our study advances understanding of the molecular mechanisms of BCG activity in bladder cancers and provides clinically relevant gene markers for evaluating and monitoring patients.


Asunto(s)
Mycobacterium bovis , Neoplasias de la Vejiga Urinaria , Humanos , Vacuna BCG/uso terapéutico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/genética , Adyuvantes Inmunológicos/farmacología , Adyuvantes Inmunológicos/uso terapéutico , Adyuvantes Farmacéuticos , Progresión de la Enfermedad
18.
Cancers (Basel) ; 14(22)2022 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-36428693

RESUMEN

While molecular subtypes of small cell lung cancers (SCLC) based on neuroendocrine (NE) and non-NE transcriptional regulators have been established, the association between these molecular subtypes and recently recognized SCLC-inflamed (SCLC-I) tumors is less understood. In this study, we used gene expression profiles of SCLC primary tumors and cell lines to discover and characterize SCLC-M (mesenchymal) tumors distinct from SCLC-I tumors for molecular features, clinical outcomes, and cross-species developmental trajectories. SCLC-M tumors show elevated epithelial-to-mesenchymal transformation (EMT) and YAP1 activity but a low level of anticancer immune activity and worse clinical outcomes than SCLC-I tumors. The prevalence of SCLC-M tumors was 3.2-7.4% in primary SCLC cohorts, which was further confirmed by immunohistochemistry in an independent cohort. Deconvoluted gene expression of tumor epithelial cells showed that EMT and increased immune function are tumor-intrinsic characteristics of SCLC-M and SCLC-I subtypes, respectively. Cross-species analysis revealed that human primary SCLC tumors recapitulate the NE-to-non-NE progression murine model providing insight into the developmental relationships among SCLC subtypes, e.g., early NE (SCLC-A and -N)- vs. late non-NE tumors (SCLC-M and -P). Newly identified SCLC-M tumors are biologically and clinically distinct from SCLC-I tumors which should be taken into account for the diagnosis and treatment of the disease.

19.
Nat Commun ; 13(1): 5815, 2022 10 03.
Artículo en Inglés | MEDLINE | ID: mdl-36192403

RESUMEN

A wearable silent speech interface (SSI) is a promising platform that enables verbal communication without vocalization. The most widely studied methodology for SSI focuses on surface electromyography (sEMG). However, sEMG suffers from low scalability because of signal quality-related issues, including signal-to-noise ratio and interelectrode interference. Hence, here, we present a novel SSI by utilizing crystalline-silicon-based strain sensors combined with a 3D convolutional deep learning algorithm. Two perpendicularly placed strain gauges with minimized cell dimension (<0.1 mm2) could effectively capture the biaxial strain information with high reliability. We attached four strain sensors near the subject's mouths and collected strain data of unprecedently large wordsets (100 words), which our SSI can classify at a high accuracy rate (87.53%). Several analysis methods were demonstrated to verify the system's reliability, as well as the performance comparison with another SSI using sEMG electrodes with the same dimension, which exhibited a relatively low accuracy rate (42.60%).


Asunto(s)
Aprendizaje Profundo , Habla , Algoritmos , Electromiografía/métodos , Reproducibilidad de los Resultados , Silicio
20.
Plants (Basel) ; 11(19)2022 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-36235508

RESUMEN

Diverse bacteria inhabit plant seeds, and at least some of them can enhance plant performance at the early developmental stage. However, it is still inconclusive whether seed bacteria can influence post-germination traits and their contribution to plant fitness. To explore the evolutionary and ecological consequences of seed endophytic bacteria, we isolated four bacterial strains from the seeds of an annual weedy plant species, Capsella bursa-pastoris, and conducted a common garden experiment using seeds inoculated by isolated bacteria. Seeds infected by bacteria tended to germinate in spring rather than in autumn. Bacterial treatment also altered the expression of plant life history and reproductive traits, including flowering dates, rosette diameter at bolting, number of inflorescences, and fruit production. The results of the path analyses suggested that such effects of bacterial treatments were due to bacterial inoculation as well as germination delayed until spring. Spring germinants with bacterial infection showed a weaker association between post-germination traits and relative fitness than those without bacterial infection. These results suggest that seed bacteria likely affect the expression of post-germination traits directly or indirectly by delaying the germination season. An altered contribution of plant traits to relative fitness implies the influence of seed bacteria on the strength of natural selection.

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