Asymmetric Mannich Reaction of Isatin-Derived Ketimines with α-Fluoroindanones Catalyzed by a Chiral Phase-Transfer Catalyst.

A highly enantioselective Mannich reaction of α-fluoroindanones with isatin-derived N-Boc-ketimines catalyzed by a quinine-derived phase-transfer catalyst was developed. A variety of 3-substituted 3-amino-2-oxindoles bearing fluorine-containing, vicinal, tetrasubstituted stereocenters were constructed using this protocol in high yields (83-95%), with moderate to excellent enantioselectivities (66-91%) and high diastereoselectivities (up to >99:1).

Combination of a bronchogenic cyst in the thoracic spinal canal with chronic myelocytic leukemia.

The presented case report describes an incredibly rare instance of an intramedullary bronchial cyst located in the thoracic spinal canal on the dorsal side of the spinal cord, which was observed in a patient with chronic myelogenous leukemia. A 29-year-old man presented with back pain for half a month, along with numbness and pain below the chest and ribs for 1 week. Hypersensitivity was present in the inferior plane of the long xiphoid process in the nervous system. Magnetic resonance imaging (MRI) showed intramedullary cystic lesions in the vertebral body plane of the third to the fourth thoracic vertebra. There was no recurrence during the 6-month postoperative follow-up period. The histopathological findings were consistent with bronchogenic cysts. Cystic lesions were eliminated through the posterior median approach. After the cyst ruptured during surgery, gel liquid was seen, and the majority of the cyst walls were removed. One week after the surgery, the hypersensitivity fully subsided. Six months following surgery, an updated MRI revealed no recurrence. Intramedullary bronchogenic cysts on the dorsal side of the thoracic spine are extremely uncommon. Diagnosis requires histopathological evidence, and it is challenging to diagnose before surgery. Prompt surgical resection is recommended in case of positive diagnosis.

The value of deep learning-based computer aided diagnostic system in improving diagnostic performance of rib fractures in acute blunt trauma.

BACKGROUND: To evaluate the value of a deep learning-based computer-aided diagnostic system (DL-CAD) in improving the diagnostic performance of acute rib fractures in patients with chest trauma. MATERIALS AND METHODS: CT images of 214 patients with acute blunt chest trauma were retrospectively analyzed by two interns and two attending radiologists independently firstly and then with the assistance of a DL-CAD one month later, in a blinded and randomized manner. The consensusdiagnosis of fib fracture by another two senior thoracic radiologists was regarded as reference standard. The rib fracture diagnostic sensitivity, specificity, positive predictive value, diagnostic confidence and mean reading time with and without DL-CAD were calculated and compared. RESULTS: There were 680 rib fracture lesions confirmed as reference standard among all patients. The diagnostic sensitivity and positive predictive value of interns weresignificantly improved from (68.82%, 84.50%) to (91.76%, 93.17%) with the assistance of DL-CAD, respectively. Diagnostic sensitivity and positive predictive value of attendings aided by DL-CAD (94.56%, 95.67%) or not aided (86.47%, 93.83%), respectively. In addition, when radiologists were assisted by DL-CAD, the mean reading time was significantly reduced, and diagnostic confidence was significantly enhanced. CONCLUSIONS: DL-CAD improves the diagnostic performance of acute rib fracture in chest trauma patients, which increases the diagnostic confidence, sensitivity, and positive predictive value for radiologists. DL-CAD can advance the diagnostic consistency of radiologists with different experiences.

YAP1 protects against PM2.5-induced lung toxicity by suppressing pyroptosis and ferroptosis.

Pollution from fine particulate matter (PM2.5) has become a major threat to public health and has been related to lung toxicity. One of the key regulators of the Hippo signaling system, Yes-associated protein 1 (YAP1), is speculated to play a role in ferroptosis development. Here, we focused on investigating the function of YAP1 in pyroptosis and ferroptosis, aiming to explore its therapeutic potential in PM2.5-induced lung toxicity. PM2.5-induced lung toxicity was induced in Wild-type WT and conditional YAP1-knockout mice, and lung epithelial cells were stimulatd by PM2.5 in vitro. We used western blot, transmission electron microscopy, and fluorescence microscopy to investigate pyroptosis- and ferroptosis-related characteristics. We found that PM2.5 leads to lung toxicity using mechanisms involving pyroptosis and ferroptosis. YAP1 knockdown impeded pyroptosis, ferroptosis, and PM2.5-induced lung damage, as shown by increased histopathology, higher levels of proinflammatory cytokines, GSDMD protein, lipid peroxidation, and iron accumulation, as well as increased NLRP3 inflammasome activation and decreased SLC7A11 expression. YAP1 silencing consistently promoted NLRP3 inflammasome activation and reduced SLC7A11 levels, aggravating PM2.5-induced cellular damage. In contrast, YAP1-overexpressing cells inhibited NLRP3 inflammasome activation and increased SLC7A11 levels, preventing pyroptosis and ferroptosis. Overall, our data suggest that YAP1 ameliorates PM2.5-induced lung injury by inhibiting NLRP3-mediated pyroptosis and SL7A11-dependent ferroptosis.

A tyrosine, histidine-selective bifunctional cross-linker for protein structure analysis.

Chemical cross-linking mass spectrometry (XL-MS) significantly contributes to the analysis of protein structures and the elucidation of protein-protein interactions. Currently available cross-linkers mainly target N-terminus, lysine, glutamate, aspartate, and cysteine residues in protein. Herein, a bifunctional cross-linker, named [4,4'-(disulfanediylbis(ethane-2,1-diyl)) bis(1-methyl-1,2,4-triazolidine-3,5-dione)] (DBMT) has been designed and characterized aiming to extremely expand the application of XL-MS approach. DBMT is capable of selectively targeting tyrosine residue in protein via an electrochemical click reaction, and/or targeting histidine residue in protein in the presence of 1O2 generated under photocatalytic reaction. A novel cross-linking strategy based on this cross-linker has been developed and demonstrated using model proteins, which provides a complementary XL-MS tool analyzing protein structure, protein complexes, protein-protein interactions, and even protein dynamics.

Characteristics of Alveolo-palatal Affricates Produced by Mandarin-speaking Children with Repaired Cleft Palate.

Objectives: In this study, examined the acoustic properties of affricates /t/ and /th/ in Mandarin Chinese, and analyzed the differences of the acoustic characteristics of these affricates produced by children with repaired cleft palate and normally developing children. We also explored the relationship between the affricates and high-front vowel /i/. Methods: We analyzed 16 monosyllabic words with alveolo-palatal affricates as the initial consonants produced by children with repaired cleft palate (N=13, Mean=5.9 years) and normally developing children (N=6, Mean age=5.3 years). We used several acoustic parameters to investigate the characteristics of these affricates, such as the center of gravity, VOT and the formants of vowels. Results: Compared with normally developing children, children with cleft palate exhibited a lower center of gravity for the 2 affricates /t/ and /th/. Data from the control group showed that the affricate /th/ had a significantly greater center of gravity than that of /t/. The accuracy of /t , th/ produced by speakers of cleft palate was significantly correlated with that of /i/ (r=0.63). High-front vowel /i/ is a significant index in diagnosing speech intelligibility which is more valuable than /a/ and /u/. There was a significant difference in F2 of vowel /i/ between children with cleft palate without speech therapy (CS1) and after speech therapy (CS2). After speech intervention, the accuracy of affricates produced by children with cleft palate was improved, the acoustic properties "stop + noise segments" appeared. Conclusion: Children with cleft palate can be distinguished better from children with normal development by 2 significant acoustic characteristics: center of gravity and VOT. As alveolo-palatal affricates /t , th/ and high-front vowel /i/ have a similar place of articulation, front-tongue-blade, their production accuracy can be improved mutually. The analysis showed that the articulation of Chinese /i/ has a higher frontal lingual position and less variability, which is more conducive to articulation training and improves the effect of cleft palate training. These findings provide a potential relationship on affricates /t, th/ and vowel /i/. Children with cleft palate have difficulty pronouncing the /t, t h/ and /i/. It is better to start with a vowel /i/, resulting in improvement in overall speech intelligibility.

CT quantitative analysis of pulmonary changes in rheumatoid arthritis.

OBJECTIVE: To explore the application of quantitative computed tomography (CT) in analyses of lung changes in patients with rheumatoid arthritis (RA). METHODS: A total of 150 clinically diagnosed RA patients underwent chest CT and 150 matched non-smokers subjects with normal chest CT are enrolled. A CT software is applied to analyze CT obtained from both groups. The quantitative indices of emphysema are expressed as the percentage of lung area with attenuation < -950HU to the total lung volume (LAA-950%), and pulmonary fibrosis was expressed as the percentage of lung area with a attenuation of -200 to -700HU to the total lung volume (LAA-200--700%), quantitative indicators of pulmonary vascular include aortic diameter (AD), pulmonary artery diameter (PAD), the ratio of PAD to AD (PAD/AD ratio), the number of blood vessels (TNV), and the cross area of blood vessels (TAV). The receiver operating characteristic (ROC) curve is used to evaluate the ability of these indexes in identifying the changes in the lung in RA patients. RESULTS: Compared to the control group, the RA group has significantly lower TLV, larger AD, and smaller TNV and TAV (3921±1101 vs. 4490±1046, 33.26±4.20 vs. 32.95±3.76, 13.14±4.93 vs. 17.53±3.34, and 96.89±40.62 vs. 163.32±34.97, respectively, with all p < 0.001). Peripheral vascular indicator TAV has the better ability to identify lung changes in RA patients (area under ROC curve AUC = 0.894) than TNV (AUC = 0.780) or LAA-200 &sim-700% (AUC = 0.705). CONCLUSION: Quantitative CT can detect changes in lung density distribution and peripheral vascular injury in patients with RA and assess the severity.

Intravoxel Incoherent Motion Diffusion-Weighted MR Imaging Findings of Infrapatellar Fat Pad Signal Abnormalities: Comparison Between Symptomatic and Asymptomatic Knee Osteoarthritis.

RATIONALE AND OBJECTIVES: Infrapatellar fat pad (IPFP) proton density-weighted images (PdWI) hyperintense regions on MRI are an important imaging feature of knee osteoarthritis (KOA) and are thought to represent inflammation which may induce knee pain. The aim of the study was to compare the intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) findings of PdWI hyperintense regions of IPFP between symptomatic and asymptomatic KOA and to determine whether IVIM-DWI parameters can be used as an objective biomarker for symptomatic KOA. MATERIALS AND METHODS: In total, 84 patients with symptomatic KOA, 43 asymptomatic KOA persons, and 30 healthy controls with MRI were retrospectively reviewed. Demographic, IPFP-synovitis, Western Ontario and McMaster Osteoarthritis Index (WOMAC) pain sub-score, IPFP volume and depth and quantitative parameters of IVIM-DWI were collected. The chi-square test, Binary logistic regression and receiver operating characteristic curve (ROC) analysis were used for diagnostic performance comparison. RESULTS: The IPFP volume and depth were statistically significant differences between the non-KOA and sKOA groups (p<0.05). The IPFP PdWI hyperintense regions demonstrated significantly higher values of D and D* in the symptomatic KOA compared to those in the asymptomatic KOA (1.51±0.47 vs. 1.73±0.40 for D and 19.24±6.44 vs. 27.09±9.75 for D*) (both p<0.05). Multivariate logistic regression analyses showed that Higher D and D* values of IPFP hyperintense region were significantly associated with higher risks of knee pain (OR: 1.97; 95% CI: 1.21-3.19; p=0.006 for D and OR: 1.24; 95% CI: 1.09-1.41; p=0.001 for D*). Sensitivity and specificity of D value for symptomatic KOA were 80.28% and 83.33%, with an AUC of 0.78 (0.68-0.86). D* value had the sensitivity with 92.96% and a specificity of 58.33%, with an AUC of 0.82 (0.73-0.89) for symptomatic KOA. CONCLUSION: IVIM-DWI can be used as an additional functional imaging technique to study IPFP with signal abnormalities on PdWI, and the D and D* values may have potential value to predict the symptom in mild-to-moderate KOA patients.

Free-breathing BLADE fat-suppressed T2 weighted turbo spin echo sequence for distinguishing lung cancer from benign pulmonary nodules or masses: A pilot study.

OBJECTIVE: Diffusion Weighted Imaging (DWI) can be used to differentiate benign and malignant pulmonary nodules or masses, while T2WI is also of great value in the differential diagnosis of them. For example, T2WI can be used to differentiate abscess from lung cancer. The study aims to quantitatively evaluate the efficacy of free-breathing BLADE fat-suppressed T2 weighted turbo spin echo sequence (BLADE T2WI) for differentiating lung cancer (LC) and benign pulmonary nodule or mass (BPNM). METHODS: A total of 291 patients with LC (197 males, 94 females; mean age 63.2 years) and 74 BPNM patients (53 males, 21 females; mean age 62.8 years) who underwent BLADE T2WI at 3-T MRI between November 2016 and May 2022were included in this retrospective study. Two radiologists independently blinded observed the MR images and measured the T2 contrast ratio (T2CR). Mann-Whitney U test was used to compare T2CR values between the two groups, ROC curves were used to evaluate the diagnostic efficacy of BLADE T2WI. RESULTS: The two radiologists had good inter-observer consistency for T2CR (ICC = 0.958). The T2CR of BPNM was significantly higher than LC (all p < 0.001); the cut-off value of T2CR was 2.135, and the sensitivity, specificity, and accuracy of diagnosis were 75.6%, 63.5%, and 73.2%, respectively. Moreover, T2CR correctly diagnosed 220 LC cases (220/291 = 75.6%) and 47 BPNM cases (47/74 = 63.5%). CONCLUSION: The T2CR value of MR non-enhanced BLADE T2WI can be easily obtained and can quantitatively distinguish BPNM from LC, thus avoiding misdiagnosis caused by lack of work experience.

Development and validation of a 3D-convolutional neural network model based on chest CT for differentiating active pulmonary tuberculosis from community-acquired pneumonia.

PURPOSE: To develop and validate a 3D-convolutional neural network (3D-CNN) model based on chest CT for differentiating active pulmonary tuberculosis (APTB) from community-acquired pneumonia (CAP). MATERIALS AND METHODS: Chest CT images of APTB and CAP patients diagnosed in two imaging centers (n = 432 in center A and n = 61 in center B) were collected retrospectively. The data in center A were divided into training, validation and internal test sets, and the data in center B were used as an external test set. A 3D-CNN was built using Keras deep learning framework. After the training, the 3D-CNN selected the model with the highest accuracy in the validation set as the optimal model, which was applied to the two test sets in centers A and B. In addition, the two test sets were independently diagnosed by two radiologists. The 3D-CNN optimal model was compared with the discrimination, calibration and net benefit of the two radiologists in differentiating APTB from CAP using chest CT images. RESULTS: The accuracy of the 3D-CNN optimal model was 0.989 and 0.934 with the internal and external test set, respectively. The area-under-the-curve values with the 3D-CNN model in the two test sets were statistically higher than that of the two radiologists (all P < 0.05), and there was a high calibration degree. The decision curve analysis showed that the 3D-CNN optimal model had significantly higher net benefit for patients than the two radiologists. CONCLUSIONS: 3D-CNN has high classification performance in differentiating APTB from CAP using chest CT images. The application of 3D-CNN provides a new automatic and rapid diagnosis method for identifying patients with APTB from CAP using chest CT images.

ACO1 and IREB2 downregulation confer poor prognosis and correlate with autophagy-related ferroptosis and immune infiltration in KIRC.

Background: ACO1 and IREB2 are two homologous cytosolic regulatory proteins, which sense iron levels and change iron metabolism-linked molecules. These two genes were noticeably decreased in kidney renal clear cell carcinoma (KIRC), which confer poor survival. Meanwhile, there is a paucity of information about the mechanisms and clinical significance of ACO1 and IREB2 downregulation in renal cancers. Methods: The expression profiles of ACO1 and IREB2 were assessed using multiple public data sets via several bioinformatics platforms. Clinical and pathological information was utilized to stratify cohorts for comparison. Patient survival outcomes were evaluated using the Kaplan-Meier plotter, a meta-analysis tool. The correlations of ACO1 and IREB2 with ferroptosis were further evaluated in The Cancer Genome Atlas (TCGA)-KIRC database. Tumor immune infiltration was analyzed using the CIBERSORT, TIMER, and GEPIA data resources. ACO1 antagonist sodium oxalomalate (OMA) and IREB2 inhibitor sodium nitroprusside (SNP) was used to treat renal cancer ACHN cells together with sorafenib. Results: KIRC patients with low ACO1 or IREB2 contents exhibited a remarkably worse survival rate in contrast with those with high expression in Kaplan-Meier survival analyses. Meanwhile, ACO1 and IREB2 regulate autophagy-linked ferroptosis along with immune cell invasion in the tumor microenvironment in KIRC patients. Blocking the activation of these two genes by their inhibitors OMA and SNP ameliorated sorafenib-triggered cell death, supporting that ACO1 and IREB2 could be participated in its cytotoxic influence on renal cancer cells. Conclusion: ACO1 and IREB2 downregulation in renal cancers were correlated with cancer aggressiveness, cellular iron homeostasis, cytotoxic immune cell infiltration, and patient survival outcomes. Our research is integral to verify the possible significance of ACO1 and IREB2 contents as a powerful signature for targeted treatment or novel immunotherapy in clinical settings.

Aymmetric Aza-Friedel-Crafts Reaction of Isatin-Derived Ketimines with Indoles Catalyzed by a Chiral Phase-Transfer Catalyst.

A highly enantioselective aza-Friedel-Crafts reaction of 1H-indoles with isatin-derived N-Cbz-ketimines catalyzed by quinine-derived phase-transfer catalysts was developed. A series of chiral 3-aminobisindole compounds containing a tetrasubstituted stereocenter were constructed by this protocol in high yields (82-91%) and moderate to excellent enantioselectivities (46-94% ee).

Diagnosis of Active Pulmonary Tuberculosis and Community Acquired Pneumonia Using Convolution Neural Network Based on Transfer Learning.

RATIONALE AND OBJECTIVES: A convolutional neural network (CNN) model for the diagnosis of active pulmonary tuberculosis (APTB) and community-acquired pneumonia (CAP) using chest radiographs (CRs) was constructed and verified based on transfer learning. MATERIALS AND METHODS: CRs of 1247 APTB cases, 1488 CAP cases and 1247 normal cases were collected. All CRs were randomly divided into training set (1992 cases), validation set (1194 cases) and test set (796 cases) by stratified sampling in 5:3:2 radio. After normalization of CRs, the convolution base of pre-trained CNN (VGG16) model on ImageNet dataset was used to extract features, and the grid search was used to determine the optimal classifier module, which was added to the convolution base for transfer learning. After the training, the model with the highest accuracy of the validation set was selected as the optimal model to verify in the test set and calculate the accuracy of the model. RESULTS: The accuracy of validation set in the 63rd epochs was the highest, which was 0.9430, and the corresponding Categorical crossentropy was 0.1742. The accuracy of the training set was 0.9428, and the Categorical crossentropy was 0.1545. When the optimal model was applied to the test set, the accuracy was 0.9447, and the Categorical crossentropy was 0.1929. CONCLUSION: The transfer learning-based CNN model has good classification performance in the diagnosis of APTB, CAP and normal patients using CRs.

Comparison Between Combination of Resonant Voice Therapy and Vocal Hygiene Education and Vocal Hygiene Education Only for Female Elementary School Teachers.

OBJECTIVE: The study compares the rehabilitation outcome of two voice intervention methods for female elementary school teachers with self-reported voice disorders. METHODS: A total of 34 female teachers from two primary schools volunteered in the study. Participants from one school were assigned to the experimental group (16 teachers), who received the combination of vocal hygiene education and resonant voice therapy. Participants from the other school were assigned to the control group (18 teachers), who received vocal hygiene education only. Pre- and post-treatment data were compared. RESULT: The total score of the Voice Handicap Index (VHI) decreased significantly from 12.19 ± 8.58 to 8.63 ± 7.27 (P < 0.05); the functional score of VHI significantly decreased from 5.38 ± 3.9 to 3.81 ± 3.62 (P < 0.05). No statistical significance was found in physiological and emotional scores of VHI. No statistical significance was found in the control group. In the experimental group, the maximum phonation time was increased from 14.34 ± 6.80s to 17.21 ± 6.06s (P < 0.05), Jitter decreased from 0.45% ± 0.13% to 0.26% ± 0.05% (P < 0.05), and Shimmer decreased from 0.21 ± 0.10. to 0.12 ± 0.03 (P < 0.05). Furthermore, the harmonic to noise ratio increased from 23.06 ± 2.99 to 25.23 ± 1.92 (P < 0.05), Spectrum Convergence Ratio increased from 0.53 ± 0.12 to 0.60 ± 0.11 (P < 0.05), yet no statistical significance was found in Nonlinear Energy Difference Ratio data for the experimental group. No statistical significance was found in the control group. In the auditory perception assessment (GRBAS), the G score decreased from 1.19 ± 0.54 to 0.81 ± 0.40 (P < 0.05), and the R score decreased from 1.19 ± 0.54 to 0.75 ± 0.45 (P < 0.05) in the experimental group. No statistical significance was found in the B, A, and S scores in the experimental group; moreover, none of the GRBAS scores in the control group demonstrated statistical significance. In the voice type component profile (VTC), the proportion of VTC1 of the experimental group increased significantly, while the proportions of VTC3 and VTC4 decreased significantly, indicating the improvement of voice quality was obvious after the intervention. The proportions of VTC of the control group did not demonstrate significant change. CONCLUSION: The results of this study show that a combination of vocal hygiene education and resonant voice therapy can significantly improve the voice function of professional voice users and effectively improve their voice quality. In this study, the professional voice users receiving vocal hygiene education only did not show significant improvement of their voice quality.

Activating transcription factor 5 (ATF5) promotes tumorigenic capability and activates the Wnt/b-catenin pathway in bladder cancer.

BACKGROUND: In bladder cancer, up to 70% of patients will relapse after resection within 5 years, in which the mechanism underlying the recurrence remains largely unclear. METHODS: Quantitative real-time PCR, western blot and immunohistochemistry were conducted. The assays of tumor sphere formation and tumor xenograft were further performed to assess the potential biological roles of ATF5 (activating transcription factor 5). Chromatin immunoprecipitation-qPCR and luciferase activity assays were carried out to explore the potential molecular mechanism. A two-tailed paired Student's t-test, χ2 test, Kaplan Meier and Cox regression analyses, and Spearman's rank correlation coefficients were used for statistical analyses. RESULTS: ATF5 is elevated in bladder urothelial cancer (BLCA) tissues, especially in recurrent BLCA, which confers a poor prognosis. Overexpressing ATF5 significantly enhanced, whereas silencing ATF5 inhibited, the capability of tumor sphere formation in bladder cancer cells. Mechanically, ATF5 could directly bind to and stimulate the promoter of DVL1 gene, resulting in activation of Wnt/ß-catenin pathway. CONCLUSIONS: This study provides a novel insight into a portion of the mechanism underlying high recurrence potential of BLCA, presenting ATF5 as a prognostic factor or potential therapeutic target for preventing recurrence in BLCA.

Free-breathing radial 3D fat-suppressed T1-weighted gradient echo (r-VIBE) sequence for assessment of pulmonary lesions: a prospective comparison of CT and MRI.

PURPOSE: To determine whether the pulmonary MR imaging with free-breathing radial 3D fat-suppressed T1-weighted gradient echo (r-VIBE) sequence can detect lung lesions and display lesion profiles with an accuracy comparable to that of computed tomography (CT), which is the reference standard in this study. POPULATION: Sixty-three consecutive patients were prospectively enrolled between October, 2016 and March, 2017. All the patients received both 3T MRI scanning with a free-breathing r-VIBE sequence and chest standard CT. Morphologic features of lesions were evaluated by two radiologists with a 5-point system. Chest standard CT were used as reference standard. Weighted kappa analysis and chi-squared test were used to determine both inter-observer agreement and inter-method agreement. RESULTS: A total of 210 solid pulmonary nodules or masses and 1 ground-glass nodule were detected by CT. Compared to CT, r-VIBE correctly detected 95.7% of pulmonary nodules, including 100% of detection rate with diameter greater than 6 mm, 92.3% of pulmonary nodules with diameter between 4 and 6 mm, and 83.3% of pulmonary nodules with diameter less than 4 mm The inter-method agreements between r-VIBE and standard-dose CT were either "substantial" or "excellent" in the evaluation of following features of pulmonary nodules with diameter more than 10mm: including lobulation, spiculation, convergence of vessels, bubble-like attenuation, cavitation and mediastinal lymph node enlargement (0.605≤K≤1.000; P<0.0001). However, K values for inter-method agreements were significant but "moderate" or "poor" for evaluating pleural tag, halo, and calcification (0.355≤ K≤0.451; P<0.0001). CONCLUSION: The use of pulmonary MR imaging with r-VIBE showed high detection rate of pulmonary nodules and inter-method agreement with CT. It is also useful for nodule morphologic assessment.

A virtual sequencer reveals the dephasing patterns in error-correction code DNA sequencing.

An error-correction code (ECC) sequencing approach has recently been reported to effectively reduce sequencing errors by interrogating a DNA fragment with three orthogonal degenerate sequencing-by-synthesis (SBS) reactions. However, similar to other non-single-molecule SBS methods, the reaction will gradually lose its synchronization within a molecular colony in ECC sequencing. This phenomenon, called dephasing, causes sequencing error, and in ECC sequencing, induces distinctive dephasing patterns. To understand the characteristic dephasing patterns of the dual-base flowgram in ECC sequencing and to generate a correction algorithm, we built a virtual sequencer in silico. Starting from first principles and based on sequencing chemical reactions, we simulated ECC sequencing results, identified the key factors of dephasing in ECC sequencing chemistry and designed an effective dephasing algorithm. The results show that our dephasing algorithm is applicable to sequencing signals with at least 500 cycles, or 1000-bp average read length, with acceptably low error rate for further parity checks and ECC deduction. Our virtual sequencer with our dephasing algorithm can further be extended to a dichromatic form of ECC sequencing, allowing for a potentially much more accurate sequencing approach.

Sex-related Differences in Airway Dimensions: A Study Based on Quantitative Computed Tomography among Chinese Population.

ABSTRACT: Sex-dependent radiation injury may be related to the differences in physiological characteristics between the sexes. This study aimed to better understand variations in airway dimensions among male and female Chinese non-smokers. This study included 970 adults and 45 children who underwent chest CT. All participants were non-smokers, without current or former chronic pulmonary disease, and all underwent CT examination. The CT images were quantitatively assessed, providing airway dimensions. The differences in inner diameter, wall thickness, wall area (WA), and WA% for each airway were compared between male and female patients. Sex is an important influencing factor in airway morphological parameters. These parameters are different between men and women: men have a larger airway diameter (P < 0.05) and smaller wall area (WA%, P < 0.05) compared with women. Younger women (<35 years) have a greater diameter and smaller WA% compared with older women (P < 0.05). Sex-related differences in airway morphology were not observed in pediatric participants. Significant differences were found in quantitative CT measures of WA% and an internal diameter among non-smokers of varying sex. The differences found in this study might explain, in part, sex-dependency of radiation injury and a possible radiological protection scheme.

Effectiveness and Feasibility of Telepractice on Voice Therapy for Female Teachers in Elementary Schools with Self-Reported Voice Disorders.

PURPOSE: The purpose of this study is to explore the effectiveness of telepractice in voice intervention for female teachers in elementary schools with self-reported voice disorders. METHODS: Thirty-five female elementary school teachers with self-reported voice disorders volunteered to participate in the study. They were divided into a telepractice voice intervention group (experimental group N=18) and a face-to-face voice intervention group (control group N=17) based on their employment setting. The exact same treatment protocol was applied to both groups of subjects, except that the intervention group was seen through telepractice, and the control group was seen face-to-face. The treatment protocol includes vocal hygiene education and resonant voice therapy twice a week for a total of eight sessions. Auditory perceptual analysis, acoustic assessment, aerodynamic assessment and self-assessment protocol were conducted before the intervention and one week after the last intervention, and the differences before and after interventions within each group and between groups were compared. RESULTS: There was no significant difference in baseline data including age, working years, and voice symptoms between the two groups. Both groups showed significant improvement (P<0.05) in all voice assessment before and after the treatment sessions, except for the Voice Handicap Index-10 (VHI-10) assessment. No statistical difference was found in other pre- and post-intervention voice assessment changes between the two study groups. The control group presented higher improvement in the total score, and the two subdomain assessments of physiology and emotion. CONCLUSIONS: Telepractice voice intervention can effectively improve the voice quality of female teachers in elementary schools, and telepractice therapy can be an effective alternative to face-to-face voice intervention.

BMI1 activates P-glycoprotein via transcription repression of miR-3682-3p and enhances chemoresistance of bladder cancer cell.

Chemoresistance is the most significant reason for the failure of cancer treatment following radical cystectomy. The response rate to the first-line chemotherapy of cisplatin and gemcitabine does not exceed 50%. In our previous research, elevated BMI1 (B-cell specific Moloney murine leukemia virus integration region 1) expression in bladder cancer conferred poor survival and was associated with chemoresistance. Herein, via analysis of The Cancer Genome Atlas database and validation of clinical samples, BMI1 was elevated in patients with bladder cancer resistant to cisplatin and gemcitabine, which conferred tumor relapse and progression. Consistently, BMI1 was markedly increased in the established cisplatin- and gemcitabine-resistant T24 cells (T24/DDP&GEM). Functionally, BMI1 overexpression dramatically promoted drug efflux, enhanced viability and decreased apoptosis of bladder cancer cells upon treatment with cisplatin or gemcitabine, whereas BMI1 downregulation reversed this effect. Mechanically, upon interaction with p53, BMI1 was recruited on the promoter of miR-3682-3p gene concomitant with an increase in the mono-ubiquitination of histone H2A lysine 119, leading to transcription repression of miR-3682-3p gene followed by derepression of ABCB1 (ATP binding cassette subfamily B member 1) gene. Moreover, suppression of P-glycoprotein by miR-3682-3p mimics or its inhibitor XR-9576, could significantly reverse chemoresistance of T24/DDP&GEM cells. These results provided a novel insight into a portion of the mechanism underlying BMI1-mediated chemoresistance in bladder cancer.