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Several studies have shown significant involvement of tumor-associated macrophages (TAMs) in the tumor microenvironment and cancer progression. However, no data on reliable TAM-related biomarkers are available for predicting the prognosis of patients with colorectal cancer (CRC). We analyzed the clinical data and gene expression profiles of patients with CRC from databases. The single-cell transcriptomic data was applied to identify M2-like TAM-related differentially expressed genes. Univariate Cox and least absolute shrinkage and selection operator regression analyses were used to determine the prognostic signature genes. Then, seven key genes were screened to develop the prognostic signature. In the training and external validation cohorts, the overall survival (OS) of patients in the high-risk group was significantly shorter compared to the low-risk group. Consequently, we created a nomogram that could accurately and reliably predict the prognosis of patient with CRC. A significant correlation was observed between the patient's prognosis, clinical features, sensitivity to anticancer drugs, TME, and risk scores. Moreover, risk score was strongly related to the response to immunotherapy in patients from GSE91061, GSE78220, and GSE60331 cohorts. Finally, high expression of HSPA1A, SERPINA1, CXCL1, and low expression of DNASE1L3 were found in human CRC tissue and normal tissue by using qRT-PCR. In conclusion, the M2-like TAM-related prognostic signature could predict the survival, prognosis, and response of patients with CRC to immunotherapy, which sheds light on the role of TAMs in CRCs and enhances our understanding of TAMs.
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Neoplasias Colorrectales , Macrófagos Asociados a Tumores , Humanos , Pronóstico , Nomogramas , Bases de Datos Factuales , Neoplasias Colorrectales/genética , Microambiente Tumoral/genéticaRESUMEN
Hydrofluoroolefins (HFOs) are being used as substitutes for potent greenhouse gas hydrofluorocarbons (HFCs). However, the use and environmental impacts of HFOs are of great concern due to the rapid degradation of HFOs to produce persistent and phytotoxic trifluoroacetic acid (TFA). Here, we provide a comprehensive projection of HFO emissions in China during 2024-2060 for the first time. Under the Kigali Amendment to the Montreal Protocol, China's HFO emissions are estimated to increase from 1.7 (1.3-2.3) to 148.8 (111.4-185.4) kt in 2024-2060 with cumulative emissions of 2.8 (2.0-3.5) Gt, and cumulative reduced HFCs emissions are evaluated to be 5.4 Gt CO2-equivalent. High HFO emissions would be distributed mainly in the North China Plain and the eastern and coastal areas. HFO-1234yf (2,3,3,3-tetrafluoropropene) contributes most of HFO emissions with a cumulative emission of 1.7 Gt in 2024-2060, while the cumulative increment of TFA deposition from HFO-1234yf emissions would reach 0.4-1.0 Gt. The long-term national-gridded HFO emission inventories can provide scientific support for evaluating the environmental risks of HFOs and developing HFC phase-out pathways for addressing climate change.
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Fluorocarburos , Hidrocarburos Fluorados , Rwanda , Fluorocarburos/análisis , Cambio ClimáticoRESUMEN
In the precedent research conducted by the same team, it concluded that the activities in C-type natriuretic peptide (CNP)/cyclic guanosine monophosphate (cGMP)/cyclic adenosine monophosphate (cAMP)/ß-type phospholipase C (PLCß) pathways of rat antral smooth muscle were changed due to diabetes, which was the key pathogenetic mechanism for diabetic gastric dysmotility. As the follow-on step, this study was designed to probe into the downstream signaling pathway of CNP/PLCß. The results showed that level of α-type protein kinase C (PKCα),cell membrane to cytoplasm ratio of PKCα, cell membrane to cytoplasmic ratio of ßI-type protein kinase C (PKCßI) and level of Phosphor-PKCα (P-PKCα) were significantly reduced in diabetes rat antral smooth muscle samples. The content of tetraphosphate inositol (IP4) in gastric antral smooth muscle of diabetic rats reduced, and the content of diacyl-glycerol (DG) was unchanged. CNP significantly decreased the content of IP4 and DG, this effect was more obvious in diabetic rats. Subsequent to the addition of protein kinase A (PKA) blocker N-[2- (p-Bromocin-namylamino)ethyl]-5 -isoquinolinesulfonamide dihydrochloride (H-89) before CNP treatment, the inhibitory effect of CNP was reduced; subsequent to the addition of protein kinase G (PKG) blocker KT5823 before CNP treatment, the inhibitory effect of CNP was also reduced. With the addition of the combination of H-89 and KT5823 before CNP treatment, the inhibition by CNP could be offset. These results were concluded that CNP inhibited the activity of PKC family in rat smooth muscle and reduced the levels of IP4 and DG through the PKG/PKA-PLCß pathways, causing inhibited muscular contractions, which may be a key pathogenetic factor for diabetic gastroparesis.
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Diabetes Mellitus Experimental/metabolismo , Diglicéridos/metabolismo , Gastroparesia/metabolismo , Fosfatos de Inositol/metabolismo , Péptido Natriurético Tipo-C/farmacología , Proteína Quinasa C/metabolismo , Animales , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/patología , Motilidad Gastrointestinal/efectos de los fármacos , Gastroparesia/etiología , Gastroparesia/patología , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Músculo Liso/patología , Músculo Liso/fisiología , Ratas , Ratas Wistar , Transducción de Señal/efectos de los fármacosRESUMEN
Pterocarpus is a genus of trees mainly distributed in tropical Asia, Africa, and South America. Some species of Pterocarpus are rosewood tree species, having important economic value for timber, and for some species, medicinal value as well. Up to now, information about this genus with regard to the genomic characteristics of the chloroplasts has been limited. Based on a combination of next-generation sequencing (Illumina Hiseq) and long-read sequencing (PacBio), the whole chloroplast genomes (cp genomes) of five species (rosewoods) in Pterocarpus (Pterocarpus macrocarpus, P. santalinus, P. indicus, P. pedatus, P. marsupium) have been assembled. The cp genomes of five species in Pterocarpus have similar structural characteristics, gene content, and sequence to other flowering plants. The cp genomes have a typical four-part structure, containing 110 unique genes (77 protein coding genes, 4 rRNAs, 29 tRNAs). Through comparative genomic analysis, abundant simple sequence repeat (SSR)loci (333-349) were detected in Pterocarpus, among which A /T single nucleotide repeats accounted for the highest proportion (72.8-76.4%). In the five cp genomes of Pterocarpus, eight hypervariable regions, including trnH-GUG_psbA, trnS-UGA_psbC, accD-psaI, ndhI-exon2_ndhI-exon1, ndhG_ndhi-exon2, rpoC2-exon2, ccsA, and trnfM-CAU, are proposed for use as DNA barcode regions. In the comparison of gene selection pressures (P. santalinus as the reference genome), purifying selection was inferred as the primary mode of selection in maintaining important biological functions. Phylogenetic analysis shows that Pterocarpus is a monophyletic group. The species P. tinctorius is resolved as early diverging in the genus. Pterocarpus was resolved as sister to the genus Tipuana.
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Genoma del Cloroplasto , Filogenia , Pterocarpus/genética , Evolución Molecular , Repeticiones de Microsatélite , Anotación de Secuencia Molecular , Sistemas de Lectura Abierta , Pterocarpus/clasificación , ARN Ribosómico/genética , ARN de Transferencia/genética , Selección GenéticaRESUMEN
The purpose of the study was to observe changes in endoplasmic reticulum stress (ERS)- and autophagy-related proteins in gastric smooth muscle tissues of diabetic rats with gastroparesis, investigate the effect of insulin-like growth factor 1 (IGF-1) on ERS and autophagy in rat gastric smooth muscle cells cultured under different glucose concentrations, and explore the influence of IGF-1 on development of diabetic gastroparesis (DGP). After establishing a rat model of DGP, rats were divided into normal control (NC) and 6-week diabetic model (DM6W) groups. Expression of ERS-related and autophagy-related proteins was detected by western blot analysis and immunofluorescence assay in rat gastric smooth muscle tissue and in vitro-cultured rat gastric smooth muscle cells exposed to different glucose concentrations and treatment with IGF-1 for 24 or 48 h. Changes in glucose-regulated-protein-78 (GRP78), growth arrest and DNA damage-inducible gene 153 (CHOP), and microtubule-associated protein 1A/1B light chain 3B (LC3) expression levels were detected by western blot analysis, and GRP78 and LC3 expression were examined by confocal laser-scanning microscopy. In vivo expression levels of GRP78, CHOP, and LC3 were significantly higher in the DM6W group compared with the NC group (p < 0.001). Twenty-four hours after cells were cultured at different glucose concentrations in vitro, expression of GRP78, CHOP, and LC3II/I was significantly higher in the high glucose-treated group compared with the normal glucose group (p < 0.05). After IGF-1 intervention, CHOP and GRP78 expression were significantly higher in the normal glucose + IGF-1 group compared with the normal glucose group (p < 0.01), while no significant difference was found between high glucose and high glucose + IGF-1 groups. LC3II/I expression was significantly lower in the normal glucose + IGF-1 group compared with the normal glucose group, and was significantly lower in the high glucose and high glucose + IGF-1 groups (p < 0.05). After 48 h of culture, CHOP expression was significantly higher and LC3II/I expression was significantly lower in the high glucose group compared with the normal glucose group (p < 0.05), but no significant change in GRP78 expression was observed between these two groups. After IGF-1 intervention, there was no difference in CHOP or GRP78 expression between normal glucose + IGF-1 and normal glucose groups. However, CHOP and GRP78 expression were significantly lower in the high glucose + IGF-1 group compared with the high glucose group (p < 0.05). There was no significant difference in LC3II/I expression between normal glucose + IGF-1 and normal glucose groups, or high glucose + IGF-1 and high glucose groups. Results of confocal laser-scanning microscopy showed significantly lower expression of LC3II/I in the high glucose + IGF-1 group compared with the high glucose group (p < 0.05). ERS and autophagy were involved in the occurrence of DGP. IGF-1 exerted an inhibitory effect on ERS in rat gastric smooth muscle cells cultured under high glucose conditions, and this inhibitory effect increased with time. IGF-1 inhibited the level of autophagy in rat gastric smooth muscle cells cultured under high glucose conditions at early stages, which may be achieved through inhibition of ERS.
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Autofagia , Diabetes Mellitus Experimental/patología , Estrés del Retículo Endoplásmico , Glucosa/farmacología , Factor I del Crecimiento Similar a la Insulina/farmacología , Miocitos del Músculo Liso/patología , Estómago/patología , Animales , Células Cultivadas , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Técnicas In Vitro , Masculino , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de Señal , Estómago/efectos de los fármacosRESUMEN
OBJECTIVE: The purpose of this study was to investigate contrast-enhanced ultrasound assessment of tumor response to antiangiogenic therapy in children and adolescents with solid malignancies. SUBJECTS AND METHODS: Children with recurrent solid tumors who were enrolled in an institutional phase 1 study of antiangiogenic therapy underwent contrast-enhanced ultrasound of target lesions before therapy, on therapy days 3 and 7, and at the end of course 1. Acoustic data from target lesion ROIs were used to measure peak enhancement, time to peak, rate of enhancement, total AUC, AUC during wash-in (AUC1), and AUC during washout (AUC2). The Cox regression model was used to assess the association between changes in parameters from baseline to follow-up time points and time to tumor progression. Values of p ≤ 0.050 were considered significant. RESULTS: Target lesion sites included liver (n = 3), pleura (n = 2), and supraclavicular mass, soft-tissue component of bone metastasis, lung, retroperitoneum, peritoneum, lymph node, muscle mass, and perineum (n = 1 each). Hazard ratios for changes from baseline to end of course 1 for peak enhancement (1.17, p = 0.034), rate of enhancement (3.25, p = 0.029), and AUC1 (1.02, p = 0.040) were significantly associated with time to progression. Greater decreases in these parameters correlated with longer time to progression. CONCLUSION: Contrast-enhanced ultrasound measurements of tumor peak enhancement, rate of enhancement, and AUC1 were early predictors of time to progression in a cohort of children and adolescents with recurrent solid tumors treated with antiangiogenic therapy. Further investigation of these findings in a larger population is warranted.
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Inhibidores de la Angiogénesis/uso terapéutico , Neoplasias/diagnóstico por imagen , Adolescente , Niño , Preescolar , Medios de Contraste , Femenino , Humanos , Lactante , Masculino , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Proyectos Piloto , Inducción de Remisión , Ultrasonografía , Adulto JovenRESUMEN
HFO-1234yf (2,3,3,3-tetrafluoropropene) is being used as refrigerant to replace HFC-134a (1,1,1,2-tetrafluoroethane), a potent greenhouse gas, in mobile air conditioners. However, the environmental impacts of HFO-1234yf, which is quickly and almost completely transformed to the persistent and phytotoxic trifluoroacetic acid (TFA), is of great concern. Here, we used the nested-grid chemical transport model, GEOS-Chem, to assess the fate and environmental impacts of HFO-1234yf emissions from mobile air conditioners in East Asia. With total emissions of 30.3 Gg yr-1, the annual mean concentrations of HFO-1234yf in China, Japan, and South Korea were 4.00, 3.23, and 5.54 pptv (parts per trillion volume), respectively, and the annual deposition fluxes (dry plus wet) of TFA in these regions were 0.35, 0.48, and 0.53 kg km-2 yr-1, dominated by wet deposition. About 14 %, 13 % and 11 % of HFO-1234yf emissions were deposited as TFA in China, Japan and South Korea, respectively, i.e. a large portion of TFA was deposited in areas outside of the emission boundary regions. The TFA characteristics in Japan and South Korea was significantly influenced by emission from China, which contributions ranged from 43 % to 94 % for the TFA concentrations and 44 % to 98 % for the TFA depositions across the four seasons. This suggests that the influence of neighboring emission sources cannot be ignored when assessing the impact of HFO-1234yf emissions in individual countries.
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Myelin water imaging is a promising, noninvasive technique for evaluating white matter diseases such as multiple sclerosis and other leukoencephalopathies (LE), and monitoring myelination in early childhood. Unfortunately, poor image quality and a long acquisition time are major obstacles to practical clinical applications. In this study, a novel postprocessing method with an efficient multi-slice acquisition scheme, called T2 spectrum analysis using a weighted regularized non-negative least squares algorithm and nonlocal mean filter (T2SPARC), is presented to overcome these obstacles and achieve a shorter acquisition time, higher image quality, and large volume coverage. In vivo results from healthy volunteers and a patient with LE showed that the T2SPARC method can generate robust and high-quality myelin water fraction maps of 10 slices within 11 min. This method also yields some useful byproducts such as intra- and extracellular water fraction and long T2 tissue water fraction maps, which can quantify lesions in different brain diseases.
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Leucoencefalopatías/diagnóstico , Imagen por Resonancia Magnética/métodos , Adulto , Algoritmos , Mapeo Encefálico/métodos , Humanos , Masculino , Reproducibilidad de los Resultados , Análisis EspectralRESUMEN
Owing to the wide use of volatile methylsiloxanes (VMSs) in various industries and consumer products, both cyclic VMSs (cVMS) and linear VMSs (lVMS) have been detected in human plasma. Experimental studies suggest that exposure to cVMSs may induce liver disease. Whereas, there is no human evidence of the potential health effects of VMSs yet. In this cross-sectional study, we evaluated the association of plasma VMSs concentrations with liver enzymes and Nonalcoholic fatty liver disease (NAFLD) among adults located in southwestern China. We used the fibrosis 4 calculator (FIB-4) as the NAFLD index and defined FIB-4≥1.45 as the NAFLD case. Among 372 participants, 45 (12.1%) of them were classified as NAFLD. Positive associations of plasma cVMSs concentrations with liver enzymes and NAFLD were observed among all participants. With per doubling increase in the total cVMSs, we observed a 1.40 (95%CI: 0.31, 2.48) increase in Alanine aminotransferase (ALT), a 1.56 (95%CI: 0.52, 2.61) increase in aspartate aminotransferase (AST) and a 0.04 (0.00, 0.09) increase in NAFLD index. A 19% increased risk of NAFLD was also found to be associated with per doubling increase in total cVMSs. In addition, positive associations of total lVMSs with ALT, AST and NAFLD were also detected when restricting our analyses to 230 participants living in industrial areas. Our study first provides epidemiological evidence on the association between VMSs and liver health, indicating more careful usage of VMSs may potentially reduce the burden of NAFLD, though more well-designed cohort studies are needed to confirm these findings.
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Enfermedad del Hígado Graso no Alcohólico , Siloxanos , Adulto , Humanos , Estudios de Cohortes , Estudios Transversales , Pueblos del Este de Asia , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Siloxanos/efectos adversosRESUMEN
Methylsiloxanes (MSs) are widely used in industrial production and have attracted much attention due to their potential health risks to humans. MSs are present in emissions from petroleum refining, and it is therefore important to assess the health risks to residents living near refineries. In this study, we evaluated the pollution characteristics and human exposure risks of three cyclic MS (CMS) oligomers (D4-D6) in areas upwind and downwind of a petroleum refinery. The concentrations of total CMSs were 4-33 times higher in the downwind than upwind areas. At the same sampling site, the concentrations of CMSs were higher indoors than outdoors. The maximum concentration of CMSs was found in the indoor environment 200 m downwind of the petroleum refinery (75 µg/m3 in air and 2.3 µg/g in dust). The concentrations and detection rates of CMSs in plasma samples were higher in the downwind than upwind residents. Although residents living downwind of the petroleum refinery were a non-occupationally exposed population, they should be considered a highly CMS-exposed population because of their extremely high internal exposure doses. Inhalation exposure was the main source of CMSs in the plasma of these residents. When different exposure pathways were investigated, inhalation exposure was the major contributor to the average daily dose in residents of locations near the petroleum refinery, whereas the dermal absorption of personal care products was the major contributor at other sites. Although the overall risks of exposure to total CMSs were below the chronic reference dose for all exposure pathways, the combined joint toxic effects of various CMSs remain unclear. Further studies are therefore required to determine the exposure risks and subsequent health effects of CMSs for the residents of these areas.
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Polvo , Petróleo , Humanos , Contaminación Ambiental , Industrias , Exposición por InhalaciónRESUMEN
Purpose: To develop and validate a semisupervised style transfer-assisted deep learning method for automated segmentation of the kidneys using multiphase contrast-enhanced (MCE) MRI acquisitions. Materials and Methods: This retrospective, Health Insurance Portability and Accountability Act-compliant, institutional review board-approved study included 125 patients (mean age, 57.3 years; 67 male, 58 female) with renal masses. Cohort 1 consisted of 102 coronal T2-weighted MRI acquisitions and 27 MCE MRI acquisitions during the corticomedullary phase. Cohort 2 comprised 92 MCE MRI acquisitions (23 acquisitions during four phases each, including precontrast, corticomedullary, early nephrographic, and nephrographic phases). The kidneys were manually segmented on T2-weighted images. A cycle-consistent generative adversarial network (CycleGAN) was trained to generate anatomically coregistered synthetic corticomedullary style images using T2-weighted images as input. Synthetic images for precontrast, early nephrographic, and nephrographic phases were then generated using the synthetic corticomedullary images as input. Mask region-based convolutional neural networks were trained on the four synthetic phase series for kidney segmentation using T2-weighted masks. Segmentation performance was evaluated in a different cohort of 20 originally acquired MCE MRI examinations by using Dice and Jaccard scores. Results: The CycleGAN network successfully generated anatomically coregistered synthetic MCE MRI-like datasets from T2-weighted acquisitions. The proposed deep learning approach for kidney segmentation achieved high mean Dice scores in all four phases of the original MCE MRI acquisitions (0.91 for precontrast, 0.92 for corticomedullary, 0.91 for early nephrographic, and 0.93 for nephrographic). Conclusion: The proposed deep learning approach achieved high performance in kidney segmentation on different MCE MRI acquisitions.Keywords: Kidney Segmentation, Generative Adversarial Network, CycleGAN, Convolutional Neural Network, Transfer Learning Supplemental material is available for this article. Published under a CC BY 4.0 license.
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INTRODUCTION: Organ preservation is now considered an acceptable alternative option in distal rectal cancer patients with clinical complete response (cCR) after neoadjuvant chemoradiation (CRT). But the cCR rate is low and about one-third of tumour will regrow, which requires more effective local treatment. CRT combined with intra-arterial chemotherapy (IAC) might be a promising approach. Additionally, total neoadjuvant therapy using FOLFIRINOX induction chemotherapy improved survival while consolidation chemotherapy improved organ preservation. We assess whether IAC plus CRT and FOLFIRINOX consolidation chemotherapy can improve the chance of organ preservation and survival in distal rectal cancer. METHODS AND ANALYSIS: This prospective, monocentric, open-label, single-arm phase II study will include 32 patients with cT3-4NanyM0 distal rectal adenocarcinoma. All patients will receive one cycle of IAC (irinotecan, raltitrexed and oxaliplatin), followed by CRT (50 Gy/25 fractions with concomitant capecitabine) and then with six cycles of FOLFIRINOX (leucovorin, 5-fluorouracil, oxaliplatin and irinotecan). After final evaluation, patients with cCR will receive non-operative management or surgery at their own discretion and others are mandatorily referred to surgery. Adjuvant chemotherapy with six cycles of mFOLFOX6 (leucovorin, 5-fluorouracil and oxaliplatin) will be used for patients with adverse pathological features. The primary endpoint is the rate of complete response (CR; pathological CR or sustained cCR≥2 years). The main secondary endpoints are toxicity, compliance, short-term and long-term oncological outcomes, surgical morbidity and quality of life. This protocol has been designed in accordance with the Standard Protocol Items: Recommendations for Interventional Trials 2013 guidelines. ETHICS AND DISSEMINATION: This study was approved by the Academic and Ethics Committee of The Affiliated Hospital of Youjiang Medical University for Nationalities in March 2023. Trial results will be published in peer-reviewed international journals and on the ChiCTR website. PROTOCOL VERSION: Registered on 18 April 2023; version #1. TRIAL REGISTRATION NUMBER: ChiCTR2300070620.
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Neoplasias Pancreáticas , Neoplasias del Recto , Humanos , Terapia Neoadyuvante/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Irinotecán/uso terapéutico , Oxaliplatino/uso terapéutico , Leucovorina/uso terapéutico , Calidad de Vida , Estudios Prospectivos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/patología , Fluorouracilo/uso terapéutico , Quimioradioterapia/métodos , Estadificación de Neoplasias , Ensayos Clínicos Fase II como AsuntoRESUMEN
BACKGROUND: The objective of this study was to prospectively evaluate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as an early imaging indicator of tumor histologic response to preoperative chemotherapy and as a possible prognostic factor for event-free survival (EFS) and overall survival in pediatric patients with newly diagnosed, nonmetastatic osteosarcoma who were treated on a single, multi-institutional phase 2 trial. METHODS: Three serial DCE-MRI examinations at week 0 (before treatment), week 9, and week 12 (tumor resection) were performed in 69 patients with nonmetastatic osteosarcoma to monitor the response to preoperative chemotherapy. Four DCE-MRI kinetic parameters (the influx volume transfer constant [K(trans) ], the efflux rate constant [k(ep) ], the relative extravascular extracellular space [v(e) ], and the relative vascular plasma space [v(p) ]) and the corresponding differences (ΔK(trans) , Δk(ep) , Δv(e) , and Δv(p) ) of averaged kinetic parameters between the outer and inner halves of tumors were calculated to assess their associations with tumor histologic response, EFS, and overall survival. RESULTS: The parameters K(trans) , v(e) , v(p) , and k(ep) decreased significantly from week 0 to week 9 and week 12. The parameters K(trans) , v(p) , and Δk(ep) at week 9 were significantly different between responders and nonresponders (P = .046, P = .021, and P = .008, respectively). These 3 parameters were indicative of histologic response. The parameter Δv(e) at week 0 was a significant prognostic factor for both EFS (P = .02) and overall survival (P = .03). CONCLUSIONS: DCE-MRI was identified as a prognostic factor for EFS and overall survival before treatment on this trial and was indicative of a histologic response to neoadjuvant therapy. Further studies are needed to verify these findings with other treatment regimens and establish the potential role of DCE-MRI in the development of risk-adapted therapy for osteosarcoma.
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Neoplasias Óseas/diagnóstico , Imagen por Resonancia Magnética/métodos , Osteosarcoma/diagnóstico , Adolescente , Neoplasias Óseas/mortalidad , Niño , Medios de Contraste , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Terapia Neoadyuvante , Osteosarcoma/mortalidad , Valor Predictivo de las Pruebas , PronósticoRESUMEN
Respiratory motion is a major contributor to bias in quantitative analysis of magnetic resonance imaging (MRI) acquisitions. Deformable registration of three-dimensional (3D) dynamic contrast-enhanced (DCE) MRI data improves estimation of kidney kinetic parameters. In this study, we proposed a deep learning approach with two steps: a convolutional neural network (CNN) based affine registration network, followed by a U-Net trained for deformable registration between two MR images. The proposed registration method was applied successively across consecutive dynamic phases of the 3D DCE-MRI dataset to reduce motion effects in the different kidney compartments (i.e., cortex, medulla). Successful reduction in the motion effects caused by patient respiration during image acquisition allows for improved kinetic analysis of the kidney. Original and registered images were analyzed and compared using dynamic intensity curves of the kidney compartments, target registration error of anatomical markers, image subtraction, and simple visual assessment. The proposed deep learning-based approach to correct motion effects in abdominal 3D DCE-MRI data can be applied to various kidney MR imaging applications.
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BACKGROUND: Deep learning segmentation requires large datasets with ground truth. Image annotation is time consuming and leads to shortages of ground truth data for clinical imaging. This study is to investigate the feasibility of kidney segmentation using deep learning convolution neural network (CNN) models trained with MR images from only a few subjects. METHODS: A total of 60 subjects from two cohorts were included in this study. The first cohort of 20 subjects from publicly available data was used for training and testing. The second cohort of 40 subjects with renal masses from our institution was used for testing only. A few-shot deep learning approach using 3D augmentation was investigated. T1-weighted images in the first cohort were used for training and testing. Cascaded CNN networks were trained using images from one, three, and six subjects, respectively. Images for the remaining subjects were used for testing. Images in the second cohort were utilized for testing only. Dice and Jaccard coefficients were generated to evaluate the performance of CNN models. Statistical analyses for segmentation metrics among different approaches were performed. RESULTS: Our approach achieved mean Dice coefficients of 0.85 using a single training subject and 0.91 with six training subjects. Compared to a single Unet, the cascaded network significantly improved the results using a single training subject (Dice, 0.759 vs. 0.835; p<0.001) and three subjects (0.864 vs. 0.893; p = 0.015) in the first cohort, and the results for the second cohort (0.821 vs. 0.873; p = 0.008). CONCLUSION: Our few-shot kidney segmentation approach using 3D augmentation achieved a good performance even using a single Unet. Furthermore, the cascaded network significantly improved the performance of segmentation and was superior to a single Unet in certain cases. Our approach provides a promising solution to segmentation in medical imaging when the number of ground truth masks is limited.
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Aprendizaje Profundo , Humanos , Procesamiento de Imagen Asistido por Computador , Riñón/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Redes Neurales de la ComputaciónRESUMEN
Methylsiloxanes (MSs), used in industrial production and personal care products, are released in various environmental media. In this study, we combined monitoring and modeling to investigate the occurrence and behavior of MSs in the urban environment in China. MSs were widely found in the air, water, soil and sediment of four cities in China. The concentrations of MSs in all four environmental media of Zhangjiagang were higher than those in the other three cities (Beijing, Kunming and Lijiang), indicating that the siloxane production plant had a significant impact on the pollution level of MSs in the surrounding environment. The samples with high MS concentrations were all from the sample sites near the outlet of the WWTPs, which showed that the effluent of the WWTPs was the main source of MS pollution in the surrounding environment. The modeling results of the EQC level III model showed that D4 discharged into the environment was mainly distributed in the air, while D5 and D6 were mainly distributed in the sediment. CMSs (D4-D6) discharged into various environmental media could exist in the urban environment for a long time with low temperatures in cities. When the temperature was 0 °C, the residence time of D5 and D6 could be 68.1 days and 243 days in the whole environmental system in Beijing. This study illustrates the importance of CMSs (D4-D6) in low-temperature environments and the potential environmental risks that they may pose.
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Monitoreo del Ambiente , Siloxanos , Ciudades , Siloxanos/análisis , Suelo , Contaminación Ambiental , ChinaRESUMEN
Methylsiloxanes (MSs) are widely used as solvents or emollients in various personal care products (PCPs) and may pose a health risk. In this study, we assessed external and internal exposure to MSs among students at two universities in southwestern China. Samples of air, dust, and PCPs were collected to evaluate indoor non-dietary exposure to MSs via multiple pathways among the students. Indoor MS levels were approximately 1-3 orders of magnitude higher in the dormitories of female students than in either classrooms or the dormitories of male students. Lipstick contained the highest MS levels. Cyclic MS (CMS: D4-D6) levels were 1 order of magnitude higher in female students than in male students. Among the three CMSs, D5 levels were highest in the plasma of all students (1.3-15 ng/mL). In dormitories, dermal contact with PCPs was the major route of exposure to CMSs for all students. Among linear MSs (LMSs: L5-L16), dermal PCP absorption and dust ingestion were the predominant exposure routes for male and female students, respectively. Although the overall risk of exposure to D4 and D5 was below the chronic reference dose for all exposure routes and all students, the total daily doses of exposure to D4 and D5 via dermal PCP absorption approached the chronic reference dose in four female students. Therefore, the effects of MSs on female students should be further investigated in future studies.
Asunto(s)
Contaminación del Aire Interior , Cosméticos , Contaminación del Aire Interior/análisis , China , Polvo , Exposición a Riesgos Ambientales/análisis , Monitoreo del Ambiente , Femenino , Humanos , Masculino , Medición de Riesgo , Siloxanos/análisis , EstudiantesRESUMEN
Currently used foam agent HCFC-141b was undergoing phased out worldwide with the implementation of the Montreal Protocol. HFO-1234ze was proposed as replacement in polyurethane (PU) foam industry with shorter atmospheric lifetime. This paper calculated historical and future emissions of HCFC-141b and HFO-1234ze till 2050, used GEOS-Chem under two HFO-1234ze emission scenarios to track its atmospheric process and distribution, and to assess its potential environmental effects. Results showed that annual HCFC-141b emissions for 2015, 2019 and 2050 were 12.6 Gg/yr, 21.0 Gg/yr and 7.6 Gg/yr, respectively and emissions of HFO-1234ze would reach 124.4 Gg/yr by 2050. Under Scenario I with HFO-1234ze emissions of 12.6 Gg/yr as input, annual mixing ratios of HFO-1234ze and its products CF3CHO and HCOF were 10.47, 2.68 and 1.74 pptv for China, and were 0.55, 0.18 and 0.1 pptv globally, respectively, suggesting the regional aggregation of these substances in emission areas. HCOF were removed from atmosphere by depositions, with total deposition rates of 22.06 g km-1 y-1 in CH, and 1.15 g km-1 y-1 in globe. Under Scenario II with HFO-1234ze emissions of 124.4 Gg/yr as input, annual mixing ratios of HFO-1234ze, CF3CHO and HCOF, along with HCOF total deposition rates were 102.98 26.36 and 17.17 pptv and 217 g km-1 y-1 in China, respectively, increased linearly to HFO-1234ze emissions change. The mixing ratios of HFO-1234ze and HCOF were too small to exert significant effects on current atmosphere burden and circulation, while CF3CHO might potentially involve in aminolysis reaction under future emissions of HFO-1234ze.
RESUMEN
Methylsiloxanes (MSs) are a significant source of indoor environmental pollution due to their high production level and widespread application, and pose a potential health risk. Given the special vulnerability of children to environmental contaminants, assessment of indoor MSs exposure in children is quite essential. In this study, we assessed internal exposure doses and external exposure levels of MSs in children from industrial and residential areas in southwestern China. Indoor air, indoor dust, and personal care product (PCP) samples were collected to evaluate indoor non-dietary MSs exposure in children through various pathways. The concentrations of MSs in indoor environments of industrial areas were approximately one to four orders of magnitude higher than those of residential areas. Sun protection products contained the highest concentrations of MSs. Relatively high levels of cyclic methylsiloxanes (CMSs) were found in plasma of children from industrial areas, which were one to two orders of magnitude higher than those in children from residential areas. The highest MSs levels in plasma were detected in infants (0-1 year), with values of 1.4 × 102 ng/mL and 1.3 × 102 ng/mL for CMSs (D4-D6) and linear methylsiloxanes (LMSs) (L5-L16), respectively. The internal exposure dose of infants in residential areas is driven by major unknown sources of MSs. The average daily doses via inhalation and dust ingestion in children from industrial areas were one to three orders of magnitude higher than in those from residential areas, indicating that these children should be considered a highly exposed population. Inhalation and dust ingestion were both major exposure pathways to MSs for children of all age groups in industrial areas, whereas dermal absorption from PCPs was the predominant exposure pathway for children of all age groups in residential areas (except for infants). Although the exposure risk to D4 and D5 was at an acceptable level for all children studied, the total daily exposure doses of these two cyclic compounds via inhalation for infants in the industrial areas was near the chronic reference dose. Meanwhile, MSs may accumulate in infant plasma within a short period of time (<6 months). Therefore, infants should be the focus of greater attention in future research. As indoor environments may pose high risks for infants in industrial areas, they should be the focus of future research.