Advanced colorectal cancer harbors extensive intratumor heterogeneity shaped by neutral evolution; however, intratumor heterogeneity in colorectal precancerous lesions has been poorly studied. We ...perform multiregion whole-exome sequencing on ten early colorectal tumors, which contained adenoma and carcinoma in situ. By comparing with sequencing data from advanced colorectal tumors, we show that the early tumors accumulate a higher proportion of subclonal driver mutations than the advanced tumors, which is highlighted by subclonal mutations in KRAS and APC. We also demonstrate that variant allele frequencies of subclonal mutations tend to be higher in early tumors, suggesting that the subclonal mutations are subject to selective sweep in early tumorigenesis while neutral evolution is dominant in advanced ones. This study establishes that the evolutionary principle underlying intratumor heterogeneity shifts from Darwinian to neutral evolution during colorectal tumor progression.
We herein report three cases of mature teratomas with pineal gland differentiation, which is a less recognized phenomenon. Case 1 was a 6‐year‐old male with a neck mass, Case 2 was a 23‐year‐old ...female with a retroperitoneal mass, and Case 3 was a 45‐year‐old female with a retroperitoneal mass. Each case showed the typical macroscopic and histological findings of mature teratoma, such as solid and cystic lesions mainly lined with a mature squamous epithelium. All cases also showed glial differentiation. Small foci of lobulated cell nests were detected in the center of or adjacent to mature glial tissue. Cells had a clear to pale eosinophilic cytoplasm with small round nuclei. Immunohistochemically, cells were positive for synaptophysin, neurofilament protein with a perivascular “club‐shaped swelling” pattern, and cone‐rod homeobox protein. To the best of our knowledge, this is the first report of pineal gland differentiation arising in mature teratoma, which may be easily overlooked or misdiagnosed as somatic‐type tumors, particularly neuroendocrine tumors. To avoid overtreatment, pathologists need to be aware that pineal gland differentiation may occur in mature teratomas.
We investigated the performance improvement of physicians with varying levels of chest radiology experience when using a commercially available artificial intelligence (AI)-based computer-assisted ...detection (CAD) software to detect lung cancer nodules on chest radiographs from multiple vendors.
Chest radiographs and their corresponding chest CT were retrospectively collected from one institution between July 2017 and June 2018. Two author radiologists annotated pathologically proven lung cancer nodules on the chest radiographs while referencing CT. Eighteen readers (nine general physicians and nine radiologists) from nine institutions interpreted the chest radiographs. The readers interpreted the radiographs alone and then reinterpreted them referencing the CAD output. Suspected nodules were enclosed with a bounding box. These bounding boxes were judged correct if there was significant overlap with the ground truth, specifically, if the intersection over union was 0.3 or higher. The sensitivity, specificity, accuracy, PPV, and NPV of the readers' assessments were calculated.
In total, 312 chest radiographs were collected as a test dataset, including 59 malignant images (59 nodules of lung cancer) and 253 normal images. The model provided a modest boost to the reader's sensitivity, particularly helping general physicians. The performance of general physicians was improved from 0.47 to 0.60 for sensitivity, from 0.96 to 0.97 for specificity, from 0.87 to 0.90 for accuracy, from 0.75 to 0.82 for PPV, and from 0.89 to 0.91 for NPV while the performance of radiologists was improved from 0.51 to 0.60 for sensitivity, from 0.96 to 0.96 for specificity, from 0.87 to 0.90 for accuracy, from 0.76 to 0.80 for PPV, and from 0.89 to 0.91 for NPV. The overall increase in the ratios of sensitivity, specificity, accuracy, PPV, and NPV were 1.22 (1.14-1.30), 1.00 (1.00-1.01), 1.03 (1.02-1.04), 1.07 (1.03-1.11), and 1.02 (1.01-1.03) by using the CAD, respectively.
The AI-based CAD was able to improve the ability of physicians to detect nodules of lung cancer in chest radiographs. The use of a CAD model can indicate regions physicians may have overlooked during their initial assessment.
Diamond-like carbon (DLC) films were deposited by pulsed filtered cathodic vacuum arc (FCVA) deposition. The microstructure, mechanical and optical properties of DLC films have been investigated as ...functions of the variation in the substrate negative direct current bias voltage (Vbias) from 0.0 to 1.5 kV. Raman and X-ray photoelectron spectroscopy results show a correlation between the ID/IG ratio and the microstructure in terms of the sp3/sp2 ratio to Vbias. This fact shows that a significant change in the sp3 content, which is attributed to the transformation from graphite-like to diamond-like, is accompanied by a decreasing ID/IG ratio. The relatively high mass density of the films in the range of 2.51 to 2.79 g/cm3 can be obtained with biasing. The mechanical properties, i.e., the hardness and elastic modulus, were 13–25 and 114–145 GPa, respectively. The improvement of the mechanical properties is due to the formation of the compressive residual stress and the local density depending on Vbias. The relationship between the refractive index and the ID/IG ratio agree well with the microstructure and mechanical properties of DLC films. All of these results indicate a vital role of Vbias in determining the DLC properties.
•The substrate bias voltage notably affects the diamond-like carbon structure.•Mechanical properties and density are optimized at a 1.0 kV bias voltage.•Hardness, elastic modulus, and density increase with cumulative residual stress.•The refractive index is correlated with the ID/IG ratio, stress, and density.•The hardness and sp3/sp2 ratio are proportional to the refractive index.
Auditory hyper-reactivity is a common sensory-perceptual abnormality in autism spectrum disorders (ASD), which interrupts behavioral adaptation. We investigated acoustic startle response (ASR) ...modulations in 17 children with ASD and 27 with typical development (TD). Compared to TD, children with ASD had larger ASR magnitude to weak stimuli and more prolonged peak startle-latency. We could not find significant difference of prepulse inhibition (PPI) or habituation in ASD children compared to TD. However, habituation and PPI at 70-dB prepulses were negatively related to several subscales of Social Responsiveness Scale and the Strengths and Difficulties Questionnaire, when considering all children. Comprehensive investigation of ASR and its modulation might increase understanding of the neurophysiological impairments underlying ASD and other mental health problems in children.
An aerobic dehydrogenation of nitrogen‐containing heterocycles catalyzed by Grubbs catalyst is developed. The reaction is applicable to various nitrogen‐containing heterocycles. The exceptionally ...high functional group compatibility of this method was confirmed by the oxidation of an unprotected dihydroindolactam V to indolactam V. Furthermore, by taking advantage of the oxygen‐mediated structural change of the Grubbs catalyst, we integrated ring‐closing metathesis and subsequent aerobic dehydrogenation to develop the novel assisted‐tandem catalysis using molecular oxygen as a chemical trigger. The utility of the assisted‐tandem catalysis was demonstrated by the concise synthesis of N‐containing fused heteroarenes including a natural antibiotic, pyocyanine.
An aerobic dehydrogenation of nitrogen‐containing heterocycles catalyzed by Grubbs catalyst is developed. Furthermore, by taking advantage of the oxygen‐mediated structural change of the Grubbs catalyst, the novel assisted‐tandem catalysis using molecular oxygen as a chemical trigger was developed by integration of ring‐closing metathesis and subsequent aerobic dehydrogenation.
During synthetic studies toward strictamine, unexpected oxidation of tertiary amine to enamine was observed in ring-closing olefin metathesis (RCM) using Hoveyda–Grubbs 2nd catalyst. Control ...experiments under deoxygenated conditions indicated Ru-catalyst and electron deficient 1,4-benzoquinone additive promoted oxidation. The desired RCM reaction took place selectively under microwave irradiation by suppression of oxidation of amine.
Purpose: To evaluate prognosis of patients with esophageal carcinoma undergoing pulmonary metastasectomy, and help determine appropriate therapeutic strategies.Methods: We retrospectively studied 16 ...patients (15 men and one woman; median age 66.5 years) with esophageal carcinoma, who underwent curative resection of pulmonary metastases. Clinical characteristics and surgical outcomes were analyzed.Results: In all, 11 patients underwent wedge resection, three segmentectomy, and two lobectomies. The average operating time and blood loss were 147 min and 103 mL, respectively. There were no perioperative deaths or severe complications. Five-year overall survival rate was 40.2% and 2-year disease-free survival rate was 35.2%. All recurrences occurred within 2 years. Univariate and multivariate analyses revealed that absence of adjuvant chemotherapy after therapy for esophageal carcinoma was a significant predictor of poor prognosis and recurrence, respectively (p <0.05). The prognosis of seven patients who underwent esophagectomy with adjuvant chemotherapy was better than that of the other nine patients (p = 0.0166).Conclusion: Pulmonary metastasectomy in patients with esophageal carcinoma was only one choice of multimodal treatment, and perioperative chemotherapy was important for long-term survival after pulmonary metastasectomy. Pulmonary metastasectomy was effective in patients undergoing esophagectomy with adjuvant chemotherapy.
For biomedical application of nanoparticles, the surface chemical functionality is very important to impart additional functions, such as solubility and stability in a physiological environment, and ...targeting specificity as an imaging probe and a drug carrier. Although polyethylene glycol (PEG) has been used extensively, here, it is proposed that hyperbranched polyglycerol (PG) is a good or even better alternative to PEG. Superparamagnetic iron oxide nanoparticles (SPIONs) prepared using a polyol method are directly functionalized with PG through ring‐opening polymerization of glycidol. The resulting SPION‐PG is highly soluble in pure water (>40 mg mL−1) and in a phosphate buffer solution (>25 mg mL−1). Such high solubility enables separation of SPION‐PG according to size using size exclusion chromatography (SEC). The size‐separated SPION‐PG shows a gradual increase in transverse relaxivity (r2) with increasing particle size. For biological application, SPION‐PG is functionalized through multistep organic transformations (–OH → –OTs (tosylate) → –N3 → –RGD) including click chemistry as a key step to impart targeting specificity by immobilization of cyclic RGD peptide (Arg‐Gly‐Asp‐D‐Tyr‐Lys) on the surface. The targeting effect is demonstrated by the cell experiments; SPION‐PG‐RGD is taken up by the cells overexpressing αvβ3‐integrin such as U87MG and A549.
Superparamagnetic iron oxide nanoparticles (SPIONs) are directly functionalized with polyglycerol (PG) using ring‐opening polymerization of glycidol to obtain good solubility in pure water and in a phosphate buffer solution. The resulting SPION‐PG is further functionalized through multistep organic transformations to immobilize a targeting peptide on the surface. The targeting effect is demonstrated in cell experiments.
PDF
