A bimodal burst energy distribution of a repeating fast radio burst source.

The event rate, energy distribution and time-domain behaviour of repeating fast radio bursts (FRBs) contain essential information regarding their physical nature and central engine, which are as yet unknown1,2. As the first precisely localized source, FRB 121102 (refs. 3-5) has been extensively observed and shows non-Poisson clustering of bursts over time and a power-law energy distribution6-8. However, the extent of the energy distribution towards the fainter end was not known. Here we report the detection of 1,652 independent bursts with a peak burst rate of 122 h-1, in 59.5 hours spanning 47 days. A peak in the isotropic equivalent energy distribution is found to be approximately 4.8 × 1037 erg at 1.25 GHz, below which the detection of bursts is suppressed. The burst energy distribution is bimodal, and well characterized by a combination of a log-normal function and a generalized Cauchy function. The large number of bursts in hour-long spans allows sensitive periodicity searches between 1 ms and 1,000 s. The non-detection of any periodicity or quasi-periodicity poses challenges for models involving a single rotating compact object. The high burst rate also implies that FRBs must be generated with a high radiative efficiency, disfavouring emission mechanisms with large energy requirements or contrived triggering conditions.

Toripalimab plus axitinib versus sunitinib as first-line treatment for advanced renal cell carcinoma: RENOTORCH, a randomized, open-label, phase III study.

BACKGROUND: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC. PATIENTS AND METHODS: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety. RESULTS: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group. CONCLUSION: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975.

Safety of methotrexate administration in women with pregnancy of unknown location at high risk of ectopic pregnancy.

OBJECTIVES: To evaluate the safety of current guidelines on methotrexate (MTX) administration in women with pregnancy of unknown location (PUL) who are considered to have a high risk of underlying ectopic pregnancy (EP), and to investigate whether implementation of these guidelines would result in inadvertent exposure to MTX of viable intrauterine pregnancies (IUPs). METHODS: This was a retrospective observational study of consecutive clinically stable women who were classified with PUL at the early pregnancy unit of Nepean Hospital, Sydney, Australia, between 2007 and 2021. PUL was defined as a positive pregnancy test in the absence of signs of IUP or EP on transvaginal ultrasound. Patients with a PUL that behaved biochemically like an EP, but for which the location of pregnancy was not confirmed on ultrasound, were eligible for MTX to minimize the risk of subsequent tubal rupture. Criteria discussed in the guidelines of the American College of Obstetricians and Gynecologists (ACOG), American Society for Reproductive Medicine (ASRM), Royal College of Obstetricians and Gynaecologists (RCOG) and National Institute for Health and Care Excellence (NICE) were applied to the PUL database. The number of patients eligible to receive MTX and the number with an underlying viable IUP who would be inadvertently prescribed MTX were calculated. RESULTS: A total of 816 women with PUL were reviewed, of whom 724 had complete data and were included in the final analysis. Six patients had persistent PUL and the remaining 718 had a diagnosis of viable IUP, non-viable IUP, EP or failed PUL. According to the ACOG, ASRM, RCOG and NICE guidelines, the rate of MTX administration among patients with PUL would have been 2.76%, 4.56%, 0.41% and 35.36%, respectively. However, no persistent PUL would have received MTX according to the ACOG, ASRM and RCOG protocols (the NICE protocol identified patients with persistent PUL with a sensitivity of 100%), and the majority of MTX treatments were unnecessary because those patients were later classified as having non-viable IUP or failed PUL. Application of ACOG and ASRM guidance could result theoretically in inadvertent MTX administration to women with an underlying viable IUP at a rate of 4.1/1000 (3/724). CONCLUSIONS: Current guidelines used to predict high risk of EP in the PUL population lead to inadvertent MTX administration to women with an underlying viable IUP. These guidelines should be used wisely to ensure that no wanted pregnancy is exposed to MTX. Women with PUL should be monitored carefully, and MTX should be used judiciously when the location of pregnancy is yet to be confirmed. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Convolutional neural network for identifying common bile duct stones based on magnetic resonance cholangiopancreatography.

AIMS: To develop an auto-categorization system based on machine learning for three-dimensional magnetic resonance cholangiopancreatography (3D MRCP) to detect choledocholithiasis from healthy and symptomatic individuals. MATERIALS AND METHODS: 3D MRCP sequences from 254 cases with common bile duct (CBD) stones and 251 cases with normal CBD were enrolled to train the 3D Convolutional Neural Network (3D-CNN) model. Then 184 patients from three different hospitals (91 with positive CBD stone and 93 with normal CBD) were prospectively included to test the performance of 3D-CNN. RESULTS: With a cutoff value of 0.2754, 3D-CNN achieved the sensitivity, specificity, and accuracy of 94.51%, 92.47%, and 93.48%, respectively. In the receiver operating characteristic curve analysis, the area under the curve (AUC) for the presence or absence of CBD stones was 0.974 (95% CI, 0.940-0.992). There was no significant difference in sensitivity, specificity, and accuracy between 3D-CNN and radiologists. In addition, the performance of 3D-CNN was also evaluated in the internal test set and the external test set, respectively. The internal test set yielded an accuracy of 94.74% and AUC of 0.974 (95% CI, 0.919-0.996), and the external test set yielded an accuracy of 92.13% and AUC of 0.970 (95% CI, 0.911-0.995). CONCLUSIONS: An artificial intelligence-assisted diagnostic system for CBD stones was constructed using 3D-CNN model for 3D MRCP images. The performance of 3D-CNN model was comparable to that of radiologists in diagnosing CBD stones. 3D-CNN model maintained high performance when applied to data from other hospitals.

Deep learning-based facial analysis for predicting difficult videolaryngoscopy: a feasibility study.

While videolaryngoscopy has resulted in better overall success rates of tracheal intubation, airway assessment is still an important prerequisite for safe airway management. This study aimed to create an artificial intelligence model to identify difficult videolaryngoscopy using a neural network. Baseline characteristics, medical history, bedside examination and seven facial images were included as predictor variables. ResNet-18 was introduced to recognise images and extract features. Different machine learning algorithms were utilised to develop predictive models. A videolaryngoscopy view of Cormack-Lehane grade of 1 or 2 was classified as 'non-difficult', while grade 3 or 4 was classified as 'difficult'. A total of 5849 patients were included, of whom 5335 had non-difficult and 514 had difficult videolaryngoscopy. The facial model (only including facial images) using the Light Gradient Boosting Machine algorithm showed the highest area under the curve (95%CI) of 0.779 (0.733-0.825) with a sensitivity (95%CI) of 0.757 (0.650-0.845) and specificity (95%CI) of 0.721 (0.626-0.794) in the test set. Compared with bedside examination and multivariate scores (El-Ganzouri and Wilson), the facial model had significantly higher predictive performance (p < 0.001). Artificial intelligence-based facial analysis is a feasible technique for predicting difficulty during videolaryngoscopy, and the model developed using neural networks has higher predictive performance than traditional methods.

[Efficiency of CNV-seq in detecting fetal DMD gene deletion or duplication in prenatal diagnosis].

Objective: To evaluate the diagnostic efficiency of copy number variation sequencing (CNV-seq) to detect the deletion or duplication of DMD gene in prenatal diagnosis. Methods: A retrospective analysis was carried out on the CNV-seq results of 34 544 fetuses diagnosed in the First People's Hospital of Yunnan Province from January 2018 to July 2023. A total of 156 cases of fetuses were collected, including Group 1:125 cases with family history of Duchenne muscular dystrophy or Becker muscular dystrophy (DMD/BMD), and Group 2:31 cases with no family history but a DMD gene deletion or duplication was detected unexpectedly by CNV-seq. Multiplex ligation-dependent probe amplification (MLPA) was used as a standard method to detect the deletion or duplication. Consistency test was carried out basing on the results of CNV-seq and MLPA of all 156 cases. Results: Comparing to MLPA, CNV-seq had a coincidence rate of 92.3% (144/156) for DMD gene deletion or duplication, with a sensitivity and positive predictive value of 88.2%, with a specificity and negative predictive value of 94.3%, a missed detection rate of 3.8%, and a Kappa value of 0.839. CNV-seq missed 4 cases with deletions and 2 with duplications due to involved fragments less than 100 Kb, among 20 cases of deletions and 6 cases of duplications detected by MLPA in Group 1. In Group 2, the deletions and duplications detected by CNV-seq were 42% (13/31) and 58% (18/31), respectively, in which the percentage of duplication was higher than that in Group 1. Among those 18 cases with duplications, 3 cases with duplication locating in exon 42~67 were likely pathogenic; while 9 cases with duplication covering the 5' or 3' end of the DMD gene, containing exon 1 or 79 and with only one breakpoint within the gene, along with the last 6 cases with duplications locating at chrX: 32650635_32910000 detected only by CNV-seq, which might be judged as variants of uncertain significance. Conclusions: CNV-seq has a good efficiency to detect fetal DMD gene deletion or duplication in prenatal diagnosis, while a further verification test by MLPA is recommended. The duplications on chrX: 32650635_32910000, 5' or 3' end of DMD gene detected by CNV-seq should be carefully verified and assessed because those variants appear to be nonpathogenic polymorphisms.

[The effect of strengthening nutrition education in the second trimester on the basis of the first trimester on blood glucose].

Objective: To explore the effect of strengthening individualized nutrition education in the second trimester based on first trimester on blood glucose. Methods: A retrospective study was conducted on 398 pregnant women aged (31.79±3.48) (23-41) years old who underwent an oral glucose tolerance test (OGTT) from October 2021 to December 2022 at Beijing Tsinghua Changgung Hospital. They were divided into two groups according to whether the women were re-visited in second trimester or not. The routine group consisted of 205 pregnant women aged between 24 and 41 (31.49±3.36) years old who only received the first trimester nutrition education and the strengthening group consisted of 193 pregnant women aged (31.92±3.97) (23-41) years old who received both the first and second trimester nutrition education. Then according to pre pregnancy body mass index (BMI), they were divided into normal (18.5 kg/m2≤BMI<24 kg/m2) and overweight (24 kg/m2≤BMI<28 kg/m2). The OGTT blood glucose level, the positive rate of gestational diabetes (GDM) and the weight gain during pregnancy were compared between the two groups with different BMI, in order to analyze the effect of strengthening nutrition education in the second trimester of pregnancy on blood glucose. Results: The differences between the two groups were not statistically significant in terms of the pregnant women's age, proportion of pregnant women aged≥35, proportion of pre-pregnancy BMI and overweight, parity and early pregnancy blood glucose (all P>0.05). The blood glucose levels of OGTT at 0, 1, and 2 hour were (4.57±0.37), (8.41±1.70), and (7.28±1.51) mmol/L, respectively, lower than those in the routine group [(4.74±0.48), (9.44±1.55), and (8.27±1.58) mmol/L, respectively, all P<0.001]. The positive rate of GDM in the strengthening group was 35.23% (68/193), which was lower than that in the routine group (91.71%, 188/205) (P<0.001). After the BMI stratification, the OGTT blood glucose levels and the positive rate of GDM in the strengthening group were still lower than those in the routine group (all P<0.05). The weight gain with normal BMI in the early pregnancy in routine group was higher than that in the strengthening group (P=0.003), but there was no significant statistical difference in weight gain of overweight pregnant women at different gestational weeks (all P>0.05). Conclusion: Strengthening a nutrition education about second trimester for pregnant women in the early stages of pregnancy can effectively improve blood glucose levels and reduce the positive rate of GDM.

Multi-elements characteristic and potential risk of heavy metals in MOUTAN CORTEX from Anhui Province, China.

To ensure the quality and safety of herbs, the content of 54 elements in MOUTAN CORTEX (MC) was determined by the ICP-AES and ICP-MS, and the health risks of Cu, As, Cd, Pb, Hg and rare earth elements (REEs) were assessed. These herbs were collected from 5 producing areas in Anhui Province, China, namely Wuhu, Tongling, Bozhou, Xuancheng and Chizhou. The multi-elements fingerprint identification of MC in Anhui Province was established. The total amount of macro-elements from Wuhu and Tongling is significantly lower than Bozhou. Among all MC from 5 producing areas, the highest content is Ca. Except for Bozhou, the content of macro-elements and REES in the other 4 origins of MC is from highest to lowest: Ca > K > Mg > Al > Fe > Na and Ce > La > Nd > Y > Pr > Er > Yb > Eu > Ho > Tb > Tm > Lu. The chemical forms of Cd in MC from Bozhou with the highest percentage were PH2O of high toxicity and migration, while the other 4 regions were PNaCl of low activity and mobility. There was a great difference in the content of inorganic elements and chemical forms of Cd between the MC produced from the plain (Bozhou) and the hilly areas (Wuhu, Tongling, Chizhou and Xuancheng). Except for Cd, the content of Cu, As, Pb and Hg in MC did not exceed the limit. The results of PTWIFact and ADI for Cd and REEs showed that MC herbs did not pose a risk to human health. Supplementary Information: The online version contains supplementary material available at 10.1007/s13762-022-04402-6.

Host and gut microbial tryptophan metabolism and type 2 diabetes: an integrative analysis of host genetics, diet, gut microbiome and circulating metabolites in cohort studies.

OBJECTIVE: Tryptophan can be catabolised to various metabolites through host kynurenine and microbial indole pathways. We aimed to examine relationships of host and microbial tryptophan metabolites with incident type 2 diabetes (T2D), host genetics, diet and gut microbiota. METHOD: We analysed associations between circulating levels of 11 tryptophan metabolites and incident T2D in 9180 participants of diverse racial/ethnic backgrounds from five cohorts. We examined host genome-wide variants, dietary intake and gut microbiome associated with these metabolites. RESULTS: Tryptophan, four kynurenine-pathway metabolites (kynurenine, kynurenate, xanthurenate and quinolinate) and indolelactate were positively associated with T2D risk, while indolepropionate was inversely associated with T2D risk. We identified multiple host genetic variants, dietary factors, gut bacteria and their potential interplay associated with these T2D-relaetd metabolites. Intakes of fibre-rich foods, but not protein/tryptophan-rich foods, were the dietary factors most strongly associated with tryptophan metabolites. The fibre-indolepropionate association was partially explained by indolepropionate-associated gut bacteria, mostly fibre-using Firmicutes. We identified a novel association between a host functional LCT variant (determining lactase persistence) and serum indolepropionate, which might be related to a host gene-diet interaction on gut Bifidobacterium, a probiotic bacterium significantly associated with indolepropionate independent of other fibre-related bacteria. Higher milk intake was associated with higher levels of gut Bifidobacterium and serum indolepropionate only among genetically lactase non-persistent individuals. CONCLUSION: Higher milk intake among lactase non-persistent individuals, and higher fibre intake were associated with a favourable profile of circulating tryptophan metabolites for T2D, potentially through the host-microbial cross-talk shifting tryptophan metabolism toward gut microbial indolepropionate production.

The efficacy and safety of different doses of calcitriol combined with neutral phosphate in X-linked hypophosphatemia: a prospective study.

The present study was the first prospective cohort evaluated the efficacy and safety of different doses of calcitriol in XLH children. The results suggested that a dose of 40 ng/kg/day calcitriol, compared with 20 ng/kg/day, was more effective in relieving the rickets, with similar safety outcomes. Further investigations were expected to set more dose groups. INTRODUCTION: Dose recommended for calcitriol in X-linked hypophosphatemia (XLH) varies in different studies. Therefore, we aimed to compare the efficacy as well as the safety of 20 ng/kg/d and 40 ng/kg/d calcitriol in Chinese XLH pediatrics population. METHODS: A 2-year, randomized, open-label, prospective study recruited 68 XLH children, which were randomized to receive either 40 ng/kg/day or 20 ng/kg/day calcitriol. Efficacy endpoints were the total Thacher ricket severity score (RSS) change from baseline to month 12 and 24, the difference in serum TALP level, fasting serum phosphate level, body height Z-score, and frequency of dental abscess. Safety assessments were done using renal ultrasound nephrocalcinosis grades (0-4), fasting serum and 24 h urine calcium level, and the occurrence of hyperparathyroidism. RESULTS: The decrease in the total RSS from baseline was more significant in the high-dose group at 12 (difference 0.87, p = 0.049) and 24 month (difference 1.23, p = 0.011). The serum TALP level was significantly lower in the high-dose group at 6 months. Pi level, height Z-score change, frequency of dental abscess and ratio of de novo nephrocalcinosis were comparable. A lower incidence of secondary hyperparathyroidism was seen in the high-dose group (p < 0.0001). CONCLUSION: For the first time in this prospective cohort, 40 ng/kg/d calcitriol was shown to be the more effective therapy in XLH children than the 20 ng/kg/d. Moreover, 40 ng/kg/d calcitriol was not associated with increasing adverse events. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT 03,820,518.

ToTEM: A software for fast TEM image simulation.

ToTEM, a multislice-based image simulation software is developed for transmission electron microscope (TEM). This software implements the following major features: (i) capability of assigning three-dimensional potentials of atom into multiple slices and precise introduction of phase shift caused by the sub-pixel atomic position, (ii) employing CUDA coding and graphical processing units (GPU) with multithreading parallel algorithm based on the powerful batch (inverse) fast Fourier transform (FFT), which is especially beneficial for image simulation of scanning transmission electron microscopy (STEM) or (integrated) differential phase contrast (I)DPC, (iii) design for efficiently generating large batch of data set of high-resolution transmission electron microscopy (HRTEM) images. Image simulation acceleration for STEM has been verified by simulating a large-scale SrTiO3 . Additionally, iDPC image of MFI-type zeolites with xylene molecules encapsulated in straight channels demonstrates the advantage of iDPC in detecting light molecules.

Superconductivity in a unique type of copper oxide.

The mechanism of superconductivity in cuprates remains one of the big challenges of condensed matter physics. High-T c cuprates crystallize into a layered perovskite structure featuring copper oxygen octahedral coordination. Due to the Jahn Teller effect in combination with the strong static Coulomb interaction, the octahedra in high-T c cuprates are elongated along the c axis, leading to a 3dx 2-y 2 orbital at the top of the band structure wherein the doped holes reside. This scenario gives rise to 2D characteristics in high-T c cuprates that favor d-wave pairing symmetry. Here, we report superconductivity in a cuprate Ba2CuO4-y , wherein the local octahedron is in a very exceptional compressed version. The Ba2CuO4-y compound was synthesized at high pressure at high temperatures and shows bulk superconductivity with critical temperature (T c ) above 70 K at ambient conditions. This superconducting transition temperature is more than 30 K higher than the T c for the isostructural counterparts based on classical La2CuO4 X-ray absorption measurements indicate the heavily doped nature of the Ba2CuO4-y superconductor. In compressed octahedron, the 3d3z 2-r 2 orbital will be lifted above the 3dx 2-y 2 orbital, leading to significant 3D nature in addition to the conventional 3dx 2-y 2 orbital. This work sheds important light on advancing our comprehensive understanding of the superconducting mechanism of high T c in cuprate materials.

[Knockdown of long non-coding RNA MIR4697 host gene inhibits adipogenic differentiation in bone marrow mesenchymal stem cells].

OBJECTIVE: To preliminarily investigate the role of long non-coding RNA (lncRNA) MIR4697 host gene (MIR4697HG) in regulating the adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). METHODS: For adipogenic differentiation, BMSCs were induced in adipogenic media for 10 days. The mRNA expression levels of lncRNA MIR4697HG and adipogenic marker genes including peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhanced binding protein α (CEBP/α) and adiponectin (ADIPQ) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) at different time points (0, 1, 2, 3, 5, 7, 10 days). The MIR4697HG stable knockdown-BMSC cell line was generated by infection of MIR4697HG shRNA-containing lentiviruses. To avoid off-target effect, two target sequences (shMIR4697HG-1, shMIR4697HG-2) were designed. And then cells were induced to differentiate in adipogenic medium. Oil red O staining, Western blot and qRT-PCR were used to detect the effect of MIR4697HG knockdown on adipogenic differentiation of BMSCs. RESULTS: The mRNA expression level of MIR4697HG was significantly increased during adipogenic differentiation (P < 0.01), and adipogenic differentiation of BMSCs was evidenced by upregulated mRNA levels of specific adipogenesis-related genes including PPARγ, CEBP/α and ADIPQ. Observed by fluorescence microscopy, more than 90% transfected target cells expressed green fluorescent protein successfully after shMIR4697HG-1 group, shMIR4697HG-2 group and shNC group transfection for 72 h. And the transfection efficiency of MIR4697HG examined by qRT-PCR was above 60%. Then the BMSCs were treated with adipogenic media for 7 days and showed that the mRNA expression levels of adipogenesis-related genes including PPARγ, CEBP/α and ADIPQ were significantly decreased in the MIR4697HG knockdown group (P < 0.01), while the expression levels of PPARγ and CEBP/α proteins were decreased remarkably as well (P < 0.01). Consistently, MIR4697HG knockdown BMSCs formed less lipid droplets compared with the control BMSCs, which further demonstrated that MIR4697HG knockdown inhibited adipogenic differentiation of BMSCs. CONCLUSION: lncRNA MIR4697HG played a crucial role in regulating the adipogenic differentiation of BMSCs, and MIR4697HG knockdown significantly inhibited the adipogenic differentiation of BMSCs. These data may suggest that lncRNA MIR4697HG could serve as a therapeutic potential target for the aberrant adipogenic differentiation-associated disorders including osteoporosis.

Deep learning analysis of the primary tumour and the prediction of lymph node metastases in gastric cancer.

BACKGROUND: Lymph node metastasis (LNM) in gastric cancer is a prognostic factor and has implications for the extent of lymph node dissection. The lymphatic drainage of the stomach involves multiple nodal stations with different risks of metastases. The aim of this study was to develop a deep learning system for predicting LNMs in multiple nodal stations based on preoperative CT images in patients with gastric cancer. METHODS: Preoperative CT images from patients who underwent gastrectomy with lymph node dissection at two medical centres were analysed retrospectively. Using a discovery patient cohort, a system of deep convolutional neural networks was developed to predict pathologically confirmed LNMs at 11 regional nodal stations. To gain understanding about the networks' prediction ability, gradient-weighted class activation mapping for visualization was assessed. The performance was tested in an external cohort of patients by analysis of area under the receiver operating characteristic (ROC) curves (AUC), sensitivity and specificity. RESULTS: The discovery and external cohorts included 1172 and 527 patients respectively. The deep learning system demonstrated excellent prediction accuracy in the external validation cohort, with a median AUC of 0·876 (range 0·856-0·893), sensitivity of 0·743 (0·551-0·859) and specificity of 0·936 (0·672-0·966) for 11 nodal stations. The imaging models substantially outperformed clinicopathological variables for predicting LNMs (median AUC 0·652, range 0·571-0·763). By visualizing nearly 19 000 subnetworks, imaging features related to intratumoral heterogeneity and the invasive front were found to be most useful for predicting LNMs. CONCLUSION: A deep learning system for the prediction of LNMs was developed based on preoperative CT images of gastric cancer. The models require further validation but may be used to inform prognosis and guide individualized surgical treatment.

Tumor immune microenvironment of primary colorectal adenocarcinomas metastasizing to the liver or lungs.

BACKGROUND: Because of the heterogeneity of metastatic colorectal cancer (mCRC), a genome-wide analysis was performed to characterize the tumor immune microenvironment (TIME). METHODS: RNA-seq analysis of 62 primary CRCs without and 63 with systemic metastasis (SM- and SM+ groups) was conducted, and the data were used in a training set after adjustment by propensity score matching. Samples were further subdivided into those with hepatic metastasis (CHM subgroup), pulmonary metastasis (CPM subgroup), or concurrent CHM and CPM (concurrent group). Validation was done by quantitative reverse-transcription polymerase chain reaction using another 40 primary CRC samples. RESULTS: Compared with the CHM or CPM subgroups, the concurrent group showed upregulated in inflammatory or immune processes, cytokine secretion, and myeloid leukocyte migration. Nine candidate genes were selected: SM-specific IDO1, JAM3, and PDE2A; CHM- or CPM-specific BIRC7; CPM-specific HISI1H2BK, and both SM-specific and CHM- or CPM-specific EPHB6, LPL, THBD, and PPBP. In a validation set of primary CRCs, JAM3 and IDO1 (p = 0.044 and p = 0.036, respectively) were confirmed to show significant upregulation and downregulation, respectively, in the SM+ group, whereas HIST1H2BK (p = 0.017) was significantly upregulated in the CPM subgroup. CONCLUSIONS: Our findings indicate that a host-suppressive TIME is established in the primary tumor of mCRC and identify immune-related site-specific markers of mCRC.

Replacing true unenhanced imaging in renal carcinoma with virtual unenhanced images in dual-energy spectral CT: a feasibility study.

AIM: To investigate the clinical value of virtual unenhanced (VNC) spectral computed tomography (CT) images to replace the conventional true unenhanced spectral CT images (TNC) in diagnosing renal carcinoma. MATERIALS AND METHODS: Fifty-six cases of renal carcinoma confirmed by histopathology underwent conventional plain CT and contrast-enhanced spectral CT at arterial phase (AP) and venous phase (VP). VNC images were generated on an AW4.6 workstation. The CT attenuation, image noise, contrast-to-noise ratio (CNR), and signal-noise-ratio (SNR) of the renal lesions and normal kidneys, long and short axis diameters of the lesion were measured from the three image sets and analysed using one-way analysis of variance (ANOVA). Two radiologists evaluated image quality subjectively using a five-point score, and lesion signature using a three-point score. Image quality scores were compared statistically and tested for consistency. RESULTS: The two reviewers had good agreement for subjective evaluation (Kappa>0.70) and there was no difference in the quality of the scores among the three image groups. The lesion signature scores were all above the acceptable level. The CNR and SNR values in VNC were significantly higher than in TNC (p<0.05). VNC images had lower renal noise than in TNC (p<0.05). There was no difference in the long and short axis diameters of the lesion among the three image groups. VNC had higher CT attenuation values for the lesion and kidney than TNC (p<0.05), but the differences were <5 HU. CONCLUSION: VNC images in spectral CT may be used to replace the conventional plain CT to reduce imaging duration and radiation dose in diagnosing renal carcinoma.

[Gender differences in cardiovascular risk factors in patients with acute myocardial infarction in China].

Objective: To understand gender differences of cardiovascular risk factors in patients with acute myocardial infarction (AMI) in China. Methods: A total of 26 592 patients with AMI from 107 hospitals in 31 provinces in China from January 1, 2013 to September 30, 2014 were included. Self-designed questionnaire was used to collect patients' age, gender, height, weight, type of AMI, medical history of cardiovascular and cerebrovascular diseases, medication history, lifestyle and AMI risk factors, including high blood pressure, diabetes, dyslipidemia, overweight and/or obesity, smoking history and family history of early onset coronary artery disease. A total of 24 394 patients with complete clinical data were included in the analysis, and gender differences in cardiovascular risk factors were analyzed in all and subgroups with different characteristics. Results: The patients were (62.2±13.8) years old, including 18 162 (74.5%) males and 18 209 (74.6%) ST-segment elevation myocardial infarction (STEMI). The age of male patients was (60.2±13.7) years, which was younger than that of female patients [(68.2±12.3) years]. The body mass index of male patients was (24.2±3.0) kg/m2, which was higher than that of female patients [(23.8±3.4) kg/m2]. The proportions of patients with overweight and/or obesity, smoking history, dyslipidemia, family history of early onset coronary heart disease, fatty diet and history of AMI were 51.8%, 55.2%, 7.2%, 3.8%, 80.4% and 7.7%, which were higher than those of females (45.9%, 9.9%, 5.8%, 2.3%, 65.0% and 5.9%, respectively]. The proportions of hypertension, diabetes, physical inactivity and stroke history were 46.5%, 17.2%, 77.8% and 8.5%, respectively, which were lower than those in female patients [61.4% (3 829 cases), 24.8%, 81.7% and 11.1%, respectively] (all P values<0.05).The proportions of peripheral vascular diseases history in male and female patients were 0.6% and 0.7%, respectively, with no statistical significance in difference (P>0.05). Subgroup analysis showed inconsistent results comparing to analysis of all patients: there were no statistical significance in gender differences as for the proportion of dyslipidemia in the non-ST-segment elevation MI group, the proportion of family history of early onset coronary heart disease in the young and middle aged groups, the proportion of overweight and/or obesity, and the proportion of physical inactivity in the elderly group (all P values>0.05). Conclusions: There are gender differences in cardiovascular risk factors among Chinese patients with acute myocardial infarction. Hypertension and diabetes are more common in women, and overweight and/or obesity, fatty diet and smoking are more common in men.

[Psychological and behavioral functioning of children and adolescents during long-term home-schooling].

Objective: To study the characteristics and risk factors of psychological and behavioral problems of children and adolescents of different ages and genders in long-term home-schooling during the coronavirus disease-2019 pandemic. Further, to provide scientific basis for more targeted psychological intervention and coping strategies in the future. Methods: A cross-sectional survey using an online questionnaire was conducted on students aged 6-16 years old in five representative cities of North (Beijing), East (Shanghai), West (Chongqing), South (Guangzhou) and Middle (Wuhan) in China. In this study, the social behavior and psychological abnormalities which was defined as the positive of any dimension were investigated in multiple dimensions during long-term home-schooling. The influencing factors of psycho-behavioral problems were analyzed by Logistic regression, and the confounding factors were corrected with graded multivariable adjustment. Results: A total of 6 906 valid questionnaires were collected including 3 592 boys and 3 314 girls, of whom 3 626 were children (6-11 years old) and 3 280 were adolescents (12-16 years old). The positive detection rate of psychosocial-behavioral problems were 13.0% (900/6 906) totally, 9.6% (344/3 592) in boys and 16.8% (556/3 314) in girls respectively, and 7.3%(142/1 946) in boys aged 6-11, 14.0%(235/1 680) in girls aged 6-11, 12.3%(202/1 646) in boys aged 12-16, 19.6%(321/1 634) in girls aged 12-16 respectively. There were significant differences between the psychological problems group and the non-psychological problems group in gender, parent-offspring conflict, number of close friends, family income change, sedentary time, homework time, screen exposure time, physical activity, dietary problems (χ²=78.851, 285.264, 52.839, 26.284, 22.778, 11.024, 10.688, 36.814, 70.982, all P<0.01). The most common symptoms in boys aged 6-11 years were compulsive activity, schizoid and depression, in girls aged 6-11 years were schizoid/compulsive activity, hyperactivity and social withdrawal, in boys aged 12-16 years were hyperactivity, compulsive activity and aggressive behavior, and in girls aged 12-16 years were schizoid, anxiety/compulsive activity and depression/withdrawal, respectively. After graded multivariable adjustment, besides the common risk factors, homework time and online study time were the risk factors of 6-11 years old groups [boys OR(95%CI): 1.750 (1.32-2.32), 1.214(1.00-1.47), girls: 1.579(1.25-1.99), 1.222(1.05-1.42), all P<0.05], videogames time were the risk factors of 12-16 years old groups [ boys: 2.237 (1.60-3.13), girls: 1.272 (1.00-1.61), all P<0.05]. Conclusions: Some children and adolescents may have psychological and behavioral problems during long-term home-schooling. The psychological and behavioral manifestations differed in age and gender subgroups, which deserve special attention in each subgroups. Schools, families and specialists should actively provide precise psychological support and comprehensive intervention strategies according to special features and risk factors.

[A convolutional neural network based model for assisting pathological diagnoses on thyroid liquid-based cytology].

Objective: To develop a convolutional neural network based model for assisting pathological diagnoses on thyroid liquid-based cytology specimens. Methods: Seven-hundred thyroid TCT slides were collected, scanned for whole slide imaging (WSI), and divided into training and test sets after labeling the correct diagnosis (benign versus malignant). The extracted regions of interest after noise filtering were cropped into pieces of 512 × 512 patch on 10 × and 40 × magnifications, respectively. A classification model was constructed using deeply learning algorithms, and applied to the training set, then automatically tuned in the test set. After data enhancement and parameters optimization, accuracy, sensitivity, specificity, positive predictive value and negative predictive value of the model were calculated. Results The training set with 560 WSI contained 4 926 cell clusters (11 164 patches), while the test set with 140 WSI contained 977 cell clusters (1 402 patches). YOLO network was selected to establish a detection model, and ResNet50 was used as a classification model. With 40 epochs training, results from 10× magnifications showed an accuracy of 90.01%, sensitivity of 89.31%, specificity of 92.51%, positive predictive value of 97.70% and negative predictive value of 70.82%. The area under curve was 0.97. The average diagnostic time was less than 1 second. Although the model for data of 40× magnifications was very sensitive (98.72%), but its specificity was poor, suggesting that the model was more reliable at 10× magnification. Conclusions: The performance of a deep-learning based model is equivalent to pathologists' diagnostic performance, but its efficiency is far beyond. The model can greatly improve consistency and efficiency, and reduce the missed diagnosis rate. In the future, larger studies should have more morphology diversity, improve model's accuracy and eventually develop a model for direct clinical use.