Defining echocardiographic predictors of outcome in cardiac amyloidosis by subtype.

BACKGROUND: Current echocardiographic risk factors for prognosis in cardiac amyloidosis (CA) do not distinguish between the two main subtypes: transthyretin cardiomyopathy (TTR) and immunoglobulin light chain cardiomyopathy (AL), each of which require distinct diagnostic and therapeutic approaches. Additionally, only traditional parameters have been studied with little data on advanced techniques. Accordingly, we sought to determine whether differences exist in 2D transthoracic echocardiography (2DE) predictors of survival between the CA subtypes using a comprehensive approach. METHODS: 220 patients (72±12 years) with confirmed CA (AL=89, TTR=131) who underwent 2DE at the time of CA diagnosis were enrolled. Left ventricular (LV) dimensions, indexed mass (LVMi), global longitudinal strain (LVGLS), apical-sparing ratio (LVASR), diastology, right ventricular (RV) size and function indices including tricuspid annular systolic excursion (TAPSE), RV free-wall (RVFWS) and global (RVGLS) strain, indexed left (LA) and right atrial volumes (LAVi and RAVi), LA strain (reservoir and booster) and RV systolic pressure (RVSP) were measured. A propensity-score weighted stepwise variable selection Cox proportional hazards model derived from NYHA class and renal impairment status at diagnosis was used to determine the associations between 2DE parameters and mortality specific to CA subtype over a median follow-up of 36-months. RESULTS: After adjusting for age, atrial fibrillation and treatment, parameters associated with survival were RVFWS (p=0.003, HR 1.15, 95% CI[1.053,1.245]) and RVSP (p=0.03, HR 1.03, 95% CI[1.004,1.063]) in AL and LVASR (p=0.007, HR 6.68, 95% CI[1.75,25.492]) and RAVi (p=0.049, HR 1.03, 95% CI[1.000,1.052]) in TTR. CONCLUSIONS: Echocardiographic prognosticators for survival are specific to cardiac amyloid subtype. These results potentially provide information critical for clinical decision-making and follow-up in these patients.

A high-intensity low-frequency acoustic generator based on the Helmholtz resonator and airflow modulator.

The high-intensity low-frequency acoustic sources have essential applications in acoustic biological effects research, airport bird repelling, and boiler ash removal. However, generating high-intensity low-frequency acoustic waves in open space is difficult. In this paper, a low-frequency acoustic generator with a resonant cavity used to enhance the acoustic intensity in open space was developed, which is an aerodynamic acoustic generator to radiates a high-intensity acoustic wave of 52Hz. Some experiments were carried out to measure this generator's internal flow field and radiated acoustic field characteristics, including the propagation characteristics at 100m. The experimental results show that the resonant enhancement effect is presented near the predetermined resonance frequency, and the enhanced value is about 4dB. The acoustic intensity for 52Hz at 1m position is 124dB. By combining the Helmholtz resonator with the airflow modulator, the airflow resonance in the resonator enhances the air pressure pulsation inside the chamber and increases the disturbance of acoustic radiation to the air. So as to improve the sound intensity and radiation efficiency in the low-frequency range.

The Use of Large Language Models to Generate Education Materials about Uveitis.

OBJECTIVE: To assess large language models in generating readable uveitis information and in improving the readability of online health information. DESIGN: Evaluation of technology. SUBJECTS: Not applicable. METHODS: ChatGPT and Bard were asked the following prompts: (prompt A) "considering that the average American reads at a 6th grade level, using the Flesch-Kincaid Grade Level (FKGL) formula, can you write patient-targeted health information on uveitis of around 6th grade level?" and (prompt B) "can you write patient-targeted health information on uveitis that is easy to understand by an average American?" Additionally, ChatGPT and Bard were asked the following prompt from the first-page results of Google when the term "uveitis" was searched: "Considering that the average American reads at a 6th grade level, using the FKGL formula, can you rewrite the following text to 6th grade level: [insert text]." The readability of each response was analyzed and compared using several metrics described below. MAIN OUTCOME MEASURES: The FKGL is a highly validated readability assessment tool that assigns a grade level to a given text, the total number of words, sentences, syllables, and complex words. Complex words were defined as those with > 2 syllables. RESULTS: ChatGPT and Bard generated responses with lower FKGL scores (i.e., easier to understand) in response to prompt A compared with prompt B. This was only significant for ChatGPT (P < 0.0001). The mean FKGL of responses to ChatGPT (6.3 ± 1.2) was significantly lower (P < 0.0001) than Bard 10.5 ± 0.8. ChatGPT responses also contained less complex words than Bard (P < 0.0001). Online health information on uveitis had a mean grade level of 11.0 ± 1.4. ChatGPT lowered the FKGL to 8.0 ± 1.0 (P < 0.0001) when asked to rewrite the content. Bard was not able to do so (mean FKGL of 11.1 ± 1.6). CONCLUSIONS: ChatGPT can aid clinicians in producing easier-to-understand health information on uveitis for patients compared with already-existing content. It can also help with reducing the difficulty of the language used for uveitis health information targeted for patients. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Right Ventricular Thrombus on Echocardiography.

Right ventricular thrombi (RVTs) have been almost exclusively studied in patients with pulmonary embolism (PE). The implications of an isolated RVT, a finding typically encountered on transthoracic echocardiography (TTE), are lacking. In this study, we sought to identify the echocardiographic and clinical features associated with the presence of RVTs. Between 1998 and 2023, 138 patients with RVT documented on TTE were retrospectively identified. Demographic data, presence of intracardiac devices, hypercoagulable conditions, history of deep vein thrombosis (DVT), PE, and/or left ventricular thrombus were abstracted from electronic chart review. Measurements of right and left ventricular size, and function were performed on TTE. Of the total population of patients with RVT, <1/2 had intracardiac devices, 29% had a documented hypercoagulable state (e.g., cancer or a clotting disorder). Most patients had dilated (77%) and dysfunctional (72%) right ventricles. Approximately 50% of RVTs were discovered in nonstandard imaging planes, suggesting that the presence of RVT is likely underestimated in clinical practice. Of those evaluated for PE, 80% had PE. Of those evaluated for DVT, 53% had DVT. In conclusion, further investigations are warranted to better guide when to investigate the right ventricle for RVTs on TTE and the impact of RVTs on patient outcomes.

Can ChatGPT Aid Clinicians in Educating Patients on the Surgical Management of Glaucoma?

PRCIS: ChatGPT can help health care providers automate the quality assessment of online health information, but it does not produce easier-to-understand responses compared with existing online health information. PURPOSE: To compare the readability of ChatGPT-generated health information about glaucoma surgery to existing material online and to evaluate ChatGPT's ability to analyze the quality of information found online about glaucoma surgery. METHODS: ChatGPT was asked to create patient handouts on glaucoma surgery using 7 independent prompts, aiming to generate sixth grade level reading material. Existing patient-targeted online health information about glaucoma surgery was selected from the top 50 search results of 3 search engines, excluding advertisements, blog posts, information intended for health professionals, irrelevant content, and duplicate links. Four validated tools were used to assess readability, and the readability of the ChatGPT-generated material was compared with the readability of existing online information. The DISCERN instrument was used for the quality assessment of online materials. The DISCERN instrument was also programmed to use ChatGPT to evaluate its ability to analyze quality. R software and descriptive statistics were used for data analysis. RESULTS: Thirty-five webpages were included. There was no difference between the reading level of online webpages (12th grade) and the reading level of ChatGPT-generated responses (11th grade), despite the ChatGPT prompts asking for simple language and a sixth grade reading level. The quality of health content was "fair," with only 5 resources receiving an "excellent" score. ChatGPT scored the quality of health resources with high precision ( r =0.725). CONCLUSIONS: Patient-targeted information on glaucoma surgery is beyond the reading level of the average patient, therefore at risk of not being understood, and is of subpar quality, per DISCERN tool scoring. ChatGPT did not generate documents at a lower reading level as prompted, but this tool can aid in automating the time-consuming and subjective process of quality assessment.

Cascaded-TOARNet: A cascaded framework based on mixed attention and multiscale information for thoracic OARs segmentation.

BACKGROUND: Accurate and automated segmentation of thoracic organs-at-risk (OARs) is critical for radiotherapy treatment planning of thoracic cancers. However, this has remained a challenging task for four major reasons: (1) thoracic OARs have diverse morphologies; (2) thoracic OARs have low contrast with the background; (3) boundaries of thoracic OARs are blurry; (4) class imbalance issue caused by small organs. PURPOSE: To overcome the above challenges and achieve accurate and automated segmentation of thoracic OARs on thoracic CT. METHODS: A novel cascaded framework based on mixed attention and multiscale information for thoracic OARs segmentation, called Cascaded-TOARNet. This cascaded framework comprises two stages: localization and segmentation. During the localization stage, TOARNet locates each organ to crop the regions of interest (ROIs). During the segmentation stage, TOARNet accurately segments the ROIs, and the segmentation results are merged into a complete result. RESULTS: We evaluated our proposed method and other common segmentation methods on two public datasets: the AAPM Thoracic Auto-Segmentation Challenge dataset and the Segmentation of Thoracic Organs at Risk (SegTHOR) dataset. Our method demonstrated superior performance, achieving a mean Dice score of 92.6% on the SegTHOR dataset and 90.8% on the AAPM dataset. CONCLUSIONS: This segmentation method holds great promise as an essential tool for enhancing the efficiency of thoracic radiotherapy planning.

Preservation of Circumferential and Radial Left Ventricular Function as a Mitigating Mechanism for Impaired Longitudinal Strain in Early Cardiac Amyloidosis.

BACKGROUND: In patients with cardiac amyloidosis (CA), left ventricular ejection fraction (LVEF) is frequently preserved, despite commonly reduced global longitudinal strain (GLS). We hypothesized that nonlongitudinal contraction may initially serve as a mitigating mechanism to maintain cardiac output and studied the relationship between global circumferential (GCS) and radial (GRS) strain with LVEF and extracellular volume (ECV), a marker of amyloid burden. METHODS: Patients with CA who underwent cardiac magnetic resonance (CMR; n = 140, 70.7 ± 11.5 years, 66% male) or echocardiography (n = 67, 71 ± 13 years, 66% male) and normal controls (CMR, n = 20; echocardiography, n = 45) were retrospectively identified, and GCS, GLS, and GRS were quantified using feature-tracking CMR or speckle-tracking echocardiography and compared between CA patients with preserved and reduced LVEF (CAHFpEF, CAHFrEF) and controls. The prevalence of impaired strain (magnitudes <2.5th percentile of the controls) was compared between CAHFpEF and CAHFrEF and between ECV quartiles. RESULTS: While echocardiography-derived GLS was impaired in both CAHFpEF (-13.4% ± 3.1%, P < .003) and CAHFrEF (-9.1% ± 3.2%, P < .003), compared with controls (-20.8% ± 2.4%), GCS was more impaired in CAHFrEF compared with both controls (-15.6% ± 5.0% vs -32.3% ± 3.3%, P < .003) and CAHFpEF (-30.4% ± 5.7%, P < .003) and did not differ between CAHFpEF and controls (P = .24). The prevalence of abnormal CMR-derived GCS (P < .0001) and GRS (P < .0001) but not GLS (P = .054) varied significantly across ECV quartiles. CONCLUSIONS: Among CA patients with preserved LVEF, preserved GCS and GRS, despite near-universally impaired GLS, may be explained by an initial predominantly subendocardial involvement, where mostly longitudinal fibers are located. If confirmed in future studies, these findings may facilitate identification of patients with early stages of CA, when treatments may be most effective.

Significance of ypTNM stage in determining the prognosis and therapy after surgery for locally advanced rectal cancer.

BACKGROUND: In the current NCCN guidelines, the prognosis and adjuvant chemotherapy of patients who underwent neoadjuvant chemoradiotherapy (nCRT) are based on pre-radiotherapy clinical TNM (cTNM) stage. However, the value of neoadjuvant pathologic TNM (ypTNM) stage is not clearly described. METHODS: This retrospective study investigated the prognosis and adjuvant chemotherapy which based on ypTNM stage compared to cTNM stage. Between 2010 and 2015, a total of 316 rectal cancer patients who underwent nCRT, followed by total mesorectal excision (TME), were included for analysis. RESULTS: Our findings revealed that cTNM stage was the only significant independent factor in the pCR group (HR = 6.917, 95% CI: 1.133-42.216, P = 0.038). In the non-pCR group, ypTNM stage was more important than cTNM stage in prognosis (HR = 2.704, 95% CI: 1.811-4.038, P < 0.001). In ypTNM III stage group, there was a statistically significant difference in prognosis between the patients with and without adjuvant chemotherapy (HR = 1.943, 95% CI: 1.015-3.722, P = 0.040), but there was no significant difference in cTNM III stage group (HR = 1.430, 95% CI: 0.728-2.806, P = 0.294). CONCLUSIONS: We concluded that ypTNM stage, rather than cTNM stage, might be a more important factor in the prognosis and adjuvant chemotherapy of patients with rectal cancer who underwent nCRT.

Neuroendocrine differentiation: a risk fellow in colorectal cancer.

BACKGROUND: Neuroendocrine differentiation (NED) is often found in colorectal cancer (CRC) and may have unique biological behavior, which has not been previously delineated. Here, we explore the relationship between CRC, NED, and clinicopathological factors. We also offer a preliminary explanation of the mechanism underlying the malignant biological behavior of NED in CRC. METHODS: Between 2013 and 2015, 394 CRC patients who underwent radical operations were selected for analysis. The relationship between NED and clinicopathological factors was analyzed. To further clarify the pivotal role of NED in CRC, we performed bioinformatic analyses and identified genes that may be involved in NED, which were obtained from in silico data from The Cancer Genome Atlas (TCGA) database. Then, we conducted functional enrichment analyses and confirmed the critical pathways for intensive study. Moreover, we detected the expression of key proteins by immunohistochemistry and analyzed the correlation of their expression with NED. RESULTS: The statistical analysis showed that CRC with NED was positively correlated with lymph node metastasis. Through bioinformatic analysis, we found that chromogranin A (CgA) was positively correlated with invasion and lymph node metastasis. ErbB2 and PIK3R1, which are key proteins in the PI3K-Akt signaling pathway, were closely related to NED. Furthermore, we determined that the PI3K-Akt signaling pathway likely plays a critical role in the NED of CRC. CONCLUSIONS: CRC with NED is associated with lymph node metastasis. The PI3K-Akt signaling pathway, which is closely related to CRC, may be the mechanism promoting the malignant biological behavior of CRC with NED.

Segmentation of Clinical Target Volume From CT Images for Cervical Cancer Using Deep Learning.

Introduction: Segmentation of clinical target volume (CTV) from CT images is critical for cervical cancer brachytherapy, but this task is time-consuming, laborious, and not reproducible. In this work, we aim to propose an end-to-end model to segment CTV for cervical cancer brachytherapy accurately. Methods: In this paper, an improved M-Net model (Mnet_IM) is proposed to segment CTV of cervical cancer from CT images. An input and an output branch are both proposed to attach to the bottom layer to deal with CTV locating challenges due to its lower contrast than surrounding organs and tissues. A progressive fusion approach is then proposed to recover the prediction results layer by layer to enhance the smoothness of segmentation results. A loss function is defined on each of the multiscale outputs to form a deep supervision mechanism. Numbers of feature map channels that are directly connected to inputs are finally homogenized for each image resolution to reduce feature redundancy and computational burden. Result: Experimental results of the proposed model and some representative models on 5438 image slices from 53 cervical cancer patients demonstrate advantages of the proposed model in terms of segmentation accuracy, such as average surface distance, 95% Hausdorff distance, surface overlap, surface dice, and volumetric dice. Conclusion: A better agreement between the predicted CTV from the proposed model Mnet_IM and manually labeled ground truth is obtained compared to some representative state-of-the-art models.

Normative values of the aortic valve area and Doppler measurements using two-dimensional transthoracic echocardiography: results from the Multicentre World Alliance of Societies of Echocardiography Study.

AIMS: Aortic valve area (AVA) used for echocardiographic assessment of aortic stenosis (AS) has been traditionally interpreted independently of sex, age and race. As differences in normal values might impact clinical decision-making, we aimed to establish sex-, age- and race-specific normative values for AVA and Doppler parameters using data from the World Alliance Societies of Echocardiography (WASE) Study. METHODS AND RESULTS: Two-dimensional transthoracic echocardiographic studies were obtained from 1903 healthy adult subjects (48% women). Measurements of the left ventricular outflow tract (LVOT) diameter and Doppler parameters, including AV and LVOT velocity time integrals (VTIs), AV mean pressure gradient, peak velocity, were obtained according to ASE/EACVI guidelines. AVA was calculated using the continuity equation. Compared with men, women had smaller LVOT diameters and AVA values, and higher AV peak velocities and mean gradients (all P < 0.05). LVOT and AV VTI were significantly higher in women (P < 0.05), and both parameters increased with age in both sexes. AVA differences persisted after indexing to body surface area. According to the current diagnostic criteria, 13.5% of women would have been considered to have mild AS and 1.4% moderate AS. LVOT diameter and AVA were lower in older subjects, both men and women, and were lower in Asians, compared with whites and blacks. CONCLUSION: WASE data provide clinically relevant information about significant differences in normal AVA and Doppler parameters according to sex, age, and race. The implementation of this information into clinical practice should involve development of specific normative values for each ethnic group using standardized methodology.

Prognostic value of elastic lamina staining in patients with stage III colon cancer.

OBJECTIVE: The objectives of this study were to analyze the difference between the preoperative radiological and postoperative pathological stages of colorectal cancer (CRC) and explore the feasibility of elastic lamina invasion (ELI) as a prognostic marker for patients with stage III colon cancer. METHODS: A total of 105 consecutive patients underwent radical surgery (R0 resection) for stage III colon cancer at the Cancer Hospital of China Medical University between January 2015 and December 2017. Clinicopathological features, including radiological stage and elastic lamina staining, were analyzed for prognostic significance in stage III colon cancer. RESULTS: A total of 105 patients with stage III colon cancer who met the criteria and had complete data available were included. The median follow-up period of survivors was 41 months. During the follow-up period, 33 (31.4%) patients experienced recurrence after radical resection, and the 3-year disease-free survival (DFS) rate was 64.8%. The consistency between preoperative radiological and postoperative pathological staging was poor (κ = 0.232, P < 0.001). The accuracy of ≤ T2 stage diagnoses was 97.1% (102/105), that of T3 stage was 60.9% (64/105), that of T4a stage was 68.6% (72/105) and that of T4b stage was 91.4% (96/105). The DFS rate of T3 ELI (+) patients was significantly lower than that of both T3 ELI (-) patients (P = 0.000) and pT4a patients (P = 0.013). The DFS rate of T3 ELI (-) patients was significantly higher than that of pT4b patients (P=0.018). T3 ELI (+) (HR (Hazard ratio), 8.444 [95% CI, 1.736-41.067]; P = 0.008), T4b (HR, 57.727[95% CI, 5.547-600.754]; P = 0.001), N2 stage (HR, 10.629 [95% CI, 3.858-29.286]; P < 0.001), stage III (HR, 0.136 [95% CI, 0.31-0.589]; P = 0.008) and perineural invasion (PNI) (HR, 8.393 [95% CI, 2.094-33.637]; P = 0.003) were independent risk factors for postoperative recurrence of stage III colon cancer. CONCLUSIONS: The consistency between preoperative radiological and postoperative pathological staging was poor, especially for tumors located in the ascending colon and descending colon. Elastic lamina staining is expected to become a stratified indicator of recurrence risk for patients with stage III colon cancer and a guide for individualized adjuvant chemotherapy, thus improving patient prognosis.

Effects of blood pressure percentile, body mass index, and race on left ventricular mass in children.

OBJECTIVE: To evaluate the association of systolic blood pressure percentile, race, and body mass index with left ventricular hypertrophy on electrocardiogram and echocardiogram to define populations at risk. STUDY DESIGN: This is a retrospective cross-sectional study design utilising a data analytics tool (Tableau) combining electrocardiogram and echocardiogram databases from 2003 to 2020. Customized queries identified patients aged 2-18 years who had an outpatient electrocardiogram and echocardiogram on the same date with available systolic blood pressure and body measurements. Cases with CHD, cardiomyopathy, or arrhythmia diagnoses were excluded. Echocardiograms with left ventricle mass (indexed to height2.7) were included. The main outcome was left ventricular hypertrophy on echocardiogram defined as Left ventricle mass index greater than the 95th percentile for age. RESULTS: In a cohort of 13,539 patients, 6.7% of studies had left ventricular hypertrophy on echocardiogram. Systolic blood pressure percentile >90% has a sensitivity of 35% and specificity of 82% for left ventricular hypertrophy on echocardiogram. Left ventricular hypertrophy on electrocardiogram was a poor predictor of left ventricular hypertrophy on echocardiogram (9% sensitivity and 92% specificity). African American race (OR 1.31, 95% CI = 1.10, 1.56, p = 0.002), systolic blood pressure percentile >95% (OR = 1.60, 95% CI = 1.34, 1.93, p < 0.001), and higher body mass index (OR = 7.22, 95% CI = 6.23, 8.36, p < 0.001) were independently associated with left ventricular hypertrophy on echocardiogram. CONCLUSIONS: African American race, obesity, and hypertension on outpatient blood pressure measurements are independent risk factors for left ventricular hypertrophy in children. Electrocardiogram has little utility in the screening for left ventricular hypertrophy.

Can echocardiographic assessment of diastolic function be automated?

Echocardiographic evaluation of left ventricular diastolic function relies on a multi-pronged algorithm, which incorporates Doppler-based and volumetric parameters. Integration of clinical data in diastolic assessment is recommended, though not clearly outlined. We sought to develop an automated tool for diastolic function, compare its performance to human-generated diagnoses and identify the common sources of error. Our software tool is based on the 2016 diastolic guidelines algorithm, which uses 8 parameters as input, with 10 conditions as the logic and 5 possible outputs as final diagnoses. Initially, we prospectively studied 563 patients whose diastolic function was independently evaluated by an expert echocardiographer and by the automated tool. Incongruent cases were further analyzed, after which features of myocardial disease were integrated into a refined version of the software that was tested in an independent cohort of 1106 patients. In the initial analysis, 202/563 grades (36%) were incongruent between the automated and human reads, with the highest rate of discordance for mild and indeterminate categories. In 17% of cases, human diagnoses differed from that dictated by the algorithm due to integration of clinical factors. Follow-up analysis using the refined automated tool did not improve the discordance rate (440/1106; 40%). There was more discordance in cases of: age > 40 years, impaired mitral inflow patterns (E/A < 0.8) and reduced mitral e' values. Further analysis revealed differences in how readers interpreted the interaction between these factors and diastolic function, which could not be incorporated into the automated tool. In conclusion, although assessment of diastolic function relies on an algorithm that can be automated, this algorithm does not include clear guidance on how to incorporate age, or age-related changes in Doppler-based parameters, often resulting in discordant diagnoses. Standardized interpretation of these factors is needed to improve the reproducibility of diastolic function grading by human readers and the accuracy of the automated classification.

Pneumonitis, appendicitis, and biliary obstruction during toripalimab treatment in a patient with extensive-stage small-cell lung cancer: a case report.

In recent years, immune checkpoint inhibitors (ICIs) have become a standard treatment for patients with advanced lung cancers. With the widespread use of immunotherapy in clinical practice, immune-related adverse events (irAEs) have become increasingly common. This case report details a 72-year-old man with small-cell lung cancer (SCLC) who developed pneumonitis, appendicitis, and biliary obstruction during treatment with toripalimab. The patient was initially diagnosed with limited-stage SCLC in January 2019 and completed 5 sequential cycles of etoposide/cisplatin (EP) and radiotherapy (60 Gy/30 F). The overall response was complete response (CR) after first line treatment. He developed radiation pneumonitis after completion of radiotherapy, which responded well to symptomatic treatment. Due to newly diagnosed bone metastasis, he was administered toripalimab intravenously every 3 weeks and 12 mg anlotinib orally once a day from January 2020. By the third cycle, the patient presented with electrocardiographic abnormalities, gingival swelling and pain, and hoarseness, and consequently, the anlotinib was suspended. After 4 cycles, he developed suppurative appendicitis, which was managed successfully with anti-inflammatory agents. He then presented with shortness of breath on exertion and after a comprehensive examination, he was diagnosed with ICI-related-pneumonitis. After 6 weeks of treatment with methylprednisolone, the shortness of breath was mostly relieved and treatment continued. In June 2020, the patient developed severe vomiting. Computed tomography (CT) indicated biliary obstruction, and at endoscopic retrograde cholangiopancreatography (ERCP) there was edema of the major papilla of the duodenum. The patient's symptoms were relieved after treatment with gastric acid suppression and antiemetics. Re-examination by magnetic resonance imaging (MRI) showed that the biliary obstruction had been resolved. Although the disease progressed after immunotherapy, no tumor tissue related to the biliary obstruction was detected, and this was therefore classified as an irAE.

Circular RNA circ_0001588 sponges miR-211-5p to facilitate the progression of glioblastoma via up-regulating YY1 expression.

BACKGROUND: As the most common and detrimental brain tumor with high invasiveness and poor prognosis, glioblastoma (GBM) has severely threatened people's health globally. Therefore, it is of great importance and necessary to identify the molecular mechanisms involved in tumorigenesis and development, thus contributing to potential therapeutic targets and strategies. METHODS: The level of circ_0001588 was detected in 68 pairs of GBM tissues and adjacent normal tissues and human glioma cell lines via a real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Then, the effect of circ_0001588 on the proliferation, migration and invasion of glioma cells was evaluated. In addition, potential downstream targets of circ_0001588 were forecasted by circBANK and Starbase. Their interaction was confirmed by introducing luciferase reporter assays. Moreover, sh-circ_0001588 transfected U251 cells were used to form tumors in vivo. Finally, the functional mechanism of circ_0001588 was identified by qRT-PCR, western blotting, xenograft and immunohistochemistry (IHC) assays. RESULTS: The expression of circ_0001588 is markedly up-regulated in GBM tissues and human gliomas cells. Additionally, increased expression of circ_0001588 is positively relevant with poor survival in GBM patients. The down-regulation of circ_0001588 distinctly inhibits the proliferation, migration and invasion of GBM in vitro, as well as tumor growth in vivo. Moreover, knockdown of circ_0001588 reduces the tumor volume and weight, enhances the relative IHC staining index of E-cadherin and decreases the relative IHC staining index of Ki-67, Yin Yang 1 (YY1) and vinmentin in vivo. Mechanistically, circ_0001588 locates in the cytoplasm, which is directly bound with miR-211-5p. Furthermore, circ_0001588 can positively regulate YY1 via sponging miR-211-5p. Moreover, circ_0001588 accelerates the proliferation, migration and invasion of GBM by modulating miR-211-5p/YY1 signaling. CONCLUSIONS: These results illustrate a new circ_0001588/miR-211-5p/YY1 regulatory signaling axis in GBM.

Sinomacrops bondei, a new anurognathid pterosaur from the Jurassic of China and comments on the group.

Anurognathids are an elusive group of diminutive, potentially arboreal pterosaurs. Even though their monophyly has been well-supported, their intrarelationships have been obscure, and their phylogenetic placement even more. In the present work, we present a new genus and species from the Middle-Late Jurassic Tiaojishan Formation, the third nominal anurognathid species from the Jurassic of China. The new species provides new information concerning morphological diversity for the group. Furthermore, we provide a new phylogenetic analysis incorporating into a single data set characters from diverging phylogenetic proposals. Our results place them as the sister-group of Darwinoptera + Pterodactyloidea, as basal members of the Monofenestrata.

SALAD-BAAR: A numerical risk score for hospital admission or emergency department presentation in ambulatory patients with cardiovascular disease.

BACKGROUND: While many interventions to reduce hospital admissions and emergency department (ED) visits for patients with cardiovascular disease have been developed, identifying ambulatory cardiac patients at high risk for admission can be challenging. HYPOTHESIS: A computational model based on readily accessible clinical data can identify patients at risk for admission. METHODS: Electronic health record (EHR) data from a tertiary referral center were used to generate decision tree and logistic regression models. International Classification of Disease (ICD) codes, labs, admissions, medications, vital signs, and socioenvironmental variables were used to model risk for ED presentation or hospital admission within 90 days following a cardiology clinic visit. Model training and testing were performed with a 70:30 data split. The final model was then prospectively validated. RESULTS: A total of 9326 patients and 46 465 clinic visits were analyzed. A decision tree model using 75 patient characteristics achieved an area under the curve (AUC) of 0.75 and a logistic regression model achieved an AUC of 0.73. A simplified 9-feature model based on logistic regression odds ratios achieved an AUC of 0.72. A further simplified numerical score assigning 1 or 2 points to each variable achieved an AUC of 0.66, specificity of 0.75, and sensitivity of 0.58. Prospectively, this final model maintained its predictive performance (AUC 0.63-0.60). CONCLUSION: Nine patient characteristics from routine EHR data can be used to inform a highly specific model for hospital admission or ED presentation in cardiac patients. This model can be simplified to a risk score that is easily calculated and retains predictive performance.