A diabatization method based upon integrating the diabatic potential gradient difference.

In this work we develop a new scheme to construct a diabatic potential energy matrix (DPEM). We propose a diabatization method which is based on integrating the diabatic potential gradient difference to diabatize adiabatic ab initio energies. This method is capable of performing high-precision adiabatic-to-diabatic transformations, with a unique advantage in effectively handling the significant fluctuations in derivative-couplings caused by conical intersection (CI) seams. The above scheme is applied to the DPEM construction of the Na(3p) + H2 → NaH + H reaction. The fitting data including adiabatic energies, energy gradients and derivative-couplings obtained from a previous benchmark DPEM are diabatized and fitted using a general neural network fitting procedure to generate the DPEM. The produced DPEM can effectively describe nonadiabatic processes involving different electronic states. We further perform quantum dynamical calculations on the new DPEM and the previous benchmark DPEM, and the obtained results demonstrate the effectiveness of our scheme.

New records of Harpiolaisodon (Chiroptera, Vespertilionidae) from the Chinese mainland.

Background: The new species, Harpiolaisodon Kuo et al., 2006, was described from Taiwan, China. So far, no distribution of this species outside Taiwan has been reported. New information: During two field investigations of small mammals in Guanyin Mountains Provincial Nature Reserve, Yuanyang, Yunnan, China, in April 2022 and May 2023, five individuals of Harpiola were collected in the mid-montane evergreen broad-leaved forest. Our morphological and molecular results reveal that these individuals from the Chinese mainland belong to Harpiolaisodon, extending the occurrence of this species well beyond its known distributions in Taiwan, China and Vietnam.

Role of Pmk1, Mpk1, or Hog1 in the mitogen-activated protein kinase pathway of Aspergillus cristatus.

Aspergillus cristatus is a probiotic fungus known for its safety and abundant secondary metabolites, making it a promising candidate for various applications. However, limited progress has been made in researching A. cristatus due to challenges in genetic manipulation. The mitogen-activated protein kinase (MAPK) signaling pathway is involved in numerous physiological processes, but its specific role in A. cristatus remains unclear. In this study, we successfully developed an efficient polyethylene glycol (PEG)-mediated protoplast transformation method for A. cristatus, enabling us to investigate the function of Pmk1, Mpk1, and Hog1 in the MAPK signaling pathway. Our findings revealed that Pmk1, Mpk1, and Hog1 are crucial for sexual reproduction, melanin synthesis, and response to external stress in A. cristatus. Notably, the deletion of Pmk1, Mpk1, or Hog1 resulted in the loss of sexual reproduction capability in A. cristatus. Overall, this research on MAPK will contribute to the continued understanding of the reproductive strategy and melanin synthesis mechanism of A. cristatus.

Production of D -tagatose, bioethanol, and microbial protein from the dairy industry by-product whey powder using an integrated bioprocess.

We designed and constructed a green and sustainable bioprocess to efficiently coproduce D -tagatose, bioethanol, and microbial protein from whey powder. First, a one-pot biosynthesis process involving lactose hydrolysis and D -galactose redox reactions for D -tagatose production was established in vitro via a three-enzyme cascade. Second, a nicotinamide adenine dinucleotide phosphate-dependent galactitol dehydrogenase mutant, D36A/I37R, based on the nicotinamide adenine dinucleotide-dependent polyol dehydrogenase from Paracoccus denitrificans was created through rational design and screening. Moreover, an NADPH recycling module was created in the oxidoreductive pathway, and the tagatose yield increased by 3.35-fold compared with that achieved through the pathway without the cofactor cycle. The reaction process was accelerated using an enzyme assembly with a glycine-serine linker, and the tagatose production rate was 9.28-fold higher than the initial yield. Finally, Saccharomyces cerevisiae was introduced into the reaction solution, and 266.5 g of D -tagatose, 162.6 g of bioethanol, and 215.4 g of dry yeast (including 38% protein) were obtained from 1 kg of whey powder (including 810 g lactose). This study provides a promising sustainable process for functional food (D -tagatose) production. Moreover, this process fully utilized whey powder, demonstrating good atom economy.

Regression-based Chinese norms of number connection test A and digit symbol test for diagnosing minimal hepatic encephalopathy.

Number connection test A (NCT-A) and digit symbol test (DST), the preferential neuropsychological tests to detect minimal hepatic encephalopathy (MHE) in China, haven't been standardized in Chinese population. We aimed to establish the norms based on a multi-center cross-sectional study and to detect MHE in cirrhotic patients. NCT-A and DST were administered to 648 healthy controls and 1665 cirrhotic patients. The regression-based procedure was applied to develop demographically adjusted norms for NCT-A and DST based on healthy controls. Age, gender, education, and age by education interaction were all predictors of DST, while age, gender, and education by gender interaction were predictors of log10 NCT-A. The predictive equations for expected scores of NCT-A and DST were established, and Z-scores were calculated. The norm for NCT-A was set as Z ≤ 1.64, while the norm for DST was set as Z ≥ - 1.64. Cirrhotic patients with concurrent abnormal NCT-A and DST results were diagnosed with MHE. The prevalence of MHE was 8.89% in cirrhotic patients, and only worse Child-Pugh classification (P = 0.002, OR = 2.389) was demonstrated to be the risk factor for MHE. The regression-based normative data of NCT-A and DST have been developed to detect MHE in China. A significant proportion of Chinese cirrhotic patients suffered from MHE, especially those with worse Child-Pugh classification.

Greenness and chronic respiratory health issues: a systematic review and meta-analysis.

Introduction: The number of chronic respiratory disease (CRD) individuals worldwide has been continuously increasing. Numerous studies have shown that greenness can improve chronic respiratory health issues through different mechanisms, with inconsistent evidence. By quantitatively summarizing existing studies, our purpose is to determine the connection between greenness exposure and various chronic respiratory health. Methods: We conducted a comprehensive search on PubMed, EMBASE, and Web of Science core databases to identify relevant studies on the correlation between greenness exposure and chronic respiratory health issues. Studies published up to January 2023 were included in the search. The study used the most frequent indicator (normalized difference vegetation index [NDVI]) as the definition of greenness exposure. Results: We finally identified 35 studies for meta-analysis. We calculated pooled effects across studies using a random-effects model and conducted a subgroup analysis by age and buffer zones to discuss the effects on chronic respiratory health issues. This study showed that 0.1 increments in NDVI were significantly related to lower rates of asthma incidence, lung cancer incidence, and chronic obstructive pulmonary disease (COPD) mortality risk; the pooled RRs were 0.92 (95% CI: 0.85-0.98), 0.62 (95% CI: 0.40-0.95), and 0.95 (95% CI: 0.92- 0.99), respectively. For the age subgroup, the higher greenness exposure level was related to the incidence rate of asthma among teenagers aged 13-18years (RR: 0.91; 95% CI: 0.83-0.99). For the buffer subgroup, a positive relationship with greenness exposure and asthma incidence/prevalence at 200-300m and 800- 1000m buffers, as well as the COPD mortality at 800-1000m buffer, the pooled RRs were 0.92 (95% CI: 0.86-0.98), 0.87 (95% CI: 0.81-0.93), and 0.93 (95% CI: 0.88- 0.98), respectively. Evidence of publication bias was not detected in this study. Discussion: Our study is the first global meta-analysis between greenness and various CRDs to report an inverse association. Further research is needed in order to determine the effect of greenness exposure on different CRDs. Therefore, when planning for green development, more consideration must be given to public health and green management as intervention measures.https://www.crd.york.ac.uk/PROSPEROFILES/384029_STRATEGY_20230116.pdf.

A retrospective analysis of Q fever osteomyelitis in children, with recommendations.

Osteomyelitis in children due to Q fever is a rare occurrence. In this study, we review 25 pediatric cases of this disease entity. The mean age of these 25 patients was 3.7years (range, 2-7 years). The risk factor for infection was history of contact with animals, such as cattle and sheep (23/25, 92.0%). The most common sites of infection were foot and ankle (12/25, 48.0%). The diagnosis of Q fever was confirmed by serologic testing in 25 children. On PCR, Coxiella burnetii was detected in 17 cases and it was not detected in the remaining five cases. A total of 22 children were treated with antibiotics, of which 15 received surgical treatment. The composition and duration of treatment varied greatly. Only 18 patients achieved significant recovery of joint mobility after drug and/or surgical treatment. Our current literature review show that the clinical manifestations of Q fever osteomyelitis in children are atypical. In the absence of serological test results, mNGS identification may be a good option. Compared with the guidelines that recommend doxycycline combined with hydroxychloroquine, we recommend that ciprofloxacin-based treatment combined with rifampicin or sulfamethoxazole/trimethoprim should be preferred in children under the age of 8 years, and the need for performing combined surgical debridement and determining the treatment duration should be evaluated according to their actual clinical situation.

Reprogramming the Metabolic Network in Kluyveromyces lactis with a Transcriptional Switch for De Novo Lacto-N-biose Synthesis.

Lacto-N-biose (LNB) is a member of the human milk oligosaccharide (HMO) family and is synthesized via an enzymatic reaction in vitro with N-acetylglucosamine (GlcNAc) and cofactors. In this study, LNB was synthesized using a cell factory for the first time. First, three modules were constructed in Kluyveromyces lactis for producing LNB from lactose and GlcNAc without the addition of cofactors. Second, a de novo pathway was constructed in K. lactis for producing LNB from lactose without adding GlcNAc. Finally, a transcriptional switch was introduced into K. lactis to reprogram its metabolic network for improving the flux from GlcNAc-6-P to GlcNAc in the de novo pathway. Subsequently, a final LNB yield of 10.41 g/L, similar to the salvage pathway yield, was achieved through the de novo pathway. The engineered K. lactis provides a promising technology platform for the industrial scale production of LNB.

An Ab Initio Neural Network Potential Energy Surface for the Dimer of Formic Acid and Further Quantum Tunneling Dynamics.

We construct a full-dimensional ab initio neural network potential energy surface (PES) for the isomerization system of the formic acid dimer (FAD). This is based upon ab initio calculations using the DLPNO-CCSD(T) approach with the aug-cc-pVTZ basis set, performed at over 14000 symmetry-unique geometries. An accurate fit to the obtained energies is generated using a general neural network fitting procedure combined with the fundamental invariant method, and the overall energy-weighted root-mean-square fitting error is about 6.4 cm-1. Using this PES, we present a multidimensional quantum dynamics study on tunneling splittings with an efficient theoretical scheme developed by our group. The ground-state tunneling splitting of FAD calculated with a four-mode coupled method is in good agreement with the most recent experimental measurements. The PES can be applied for further dynamics studies. The effectiveness of the present scheme for constructing a high-dimensional PES is demonstrated, and this scheme is expected to be feasible for larger molecular systems.

Global association of greenness exposure with risk of nervous system disease: A systematic review and meta-analysis.

Nervous system disease (NSD) is a global health burden with increasing prevalence in the last 30 years. There is evidence that greenness can improve nervous system health through a variety of mechanisms; however, the evidence is inconsistent. In the present systematic review and meta-analysis, we examined the relationship between greenness exposure and NSD outcomes. Studies on the relationship between greenness and NSD health outcomes published till July 2022 were searched in PubMed, Cochrane, Embase, Scopus, and Web of Science. In addition, we searched the cited literature and updated our search on Jan 20, 2023, to identify any new studies. We included human epidemiological studies that assess the association of greenness exposure with the risk of NSD. Greenness exposure was measured using NDVI (the normalized difference vegetation index) and the outcome was the mortality or morbidity of NSD. The pooled relative risks (RRs) were estimated using a random effects model. Of 2059 identified studies, 15 studies were included in our quantitative evaluation, in which 11 studies found a significant inverse relationship between the risk of NSD mortality or incidence/prevalence and an increase in surrounding greenness. The pooled RRs for cerebrovascular diseases (CBVD), neurodegenerative diseases (ND), and stroke mortality were 0.98 (95 % CI: 0.97, 1.00), 0.98 (95 % CI: 0.98, 0.99), and 0.96 (95 % CI: 0.93, 1.00), respectively. The pooled RRs for PD incidence and stroke prevalence/incidence were 0.89 (95 % CI: 0.78, 1.02) and 0.98 (95 % CI: 0.97, 0.99), respectively. The confidence of evidence for ND mortality, stroke mortality, and stroke prevalence/incidence was downgraded to "low", while CBVD mortality and PD incidence were downgraded to "very low" due to inconsistency. We found no evidence of publication bias and the sensitivity analysis results of all subgroups are robust except for the stroke mortality subgroup. This is the first comprehensive meta-analysis of greenness exposure and NSD outcomes in which an inverse relationship was observed. It is necessary to conduct further research to ascertain the role greenness exposure plays in various NSDs and the management of greenness should be considered a public health strategy.

Mycobacterium xenopi related spine infections: A case report and systematic literature review.

Background and purpose: Nontuberculous mycobacteria (NTM) disease is an important infection disease throughout the world. Mycobacterium xenopi (M. xenopi) is a common NTM. Extrapulmonary infections due to M. xenopi, particularly spine infections, are a rare occurrence, but lack of research is cited as a constraint for implementing NTM control in such patients. The purposes of this paper are to describe a case of spondylodiscitis, to review the published literature on cases of M. xenopi spine infections, and to summarize the predisposing factors, diagnosis, and treatment of infection. Methods: A case of spondylodiscitis was caused by M. xenopi in a patient with systemic lupus erythematosus (SLE). Research was conducted using the PubMed, ScienceDirect, Embase, Wiley Online Library, and Scopus databases using the following search terms: "Mycobacterium xenopi", "vertebral", "spinal", "spondylodiscitis", "infection", and "osteomyelitis". Results: We retrieved 14 cases published before August 2022. The risk factors for infection were iatrogenic infections (3/14, 21.43%), SLE (4/14, 28.57%), AIDS (4/14, 28.57%), and immunocompetence without any comorbidities (3/14, 21.43%). The most common sites of infection were thoracic vertebrae (10/14, 71.43%) and lumbar vertebrae (4/14, 28.57%). A total of 14 cases were isolated and identified as M. xenopi from a toad by mycobacterial culture. The identification time was 55.00 ± 7.55 days (the present report identification time of metagenomic next generation sequencing (mNGS) was only 2 days). All patients were treated with antibiotic therapy, and the duration of treatment was 13.18 ± 2.13 months. Clarithromycin-based therapy showed a higher improvement rate (5/6, 83.33%). Surgical intervention was performed in 5 patients. Only 1 patient did not show any improvement after surgical treatment. Conclusion: M. xenopi spine infection in humans presents with atypical clinical symptoms. mNGS identification may be a good choice. M. xenopi may be considered in immunocompromised patients with spinal infection. We recommend a clarithromycin-containing regimen and prolonging the duration of treatment to ensure effectiveness.

Corrigendum to "Lenvatinib plus sintilimab versus lenvatinib monotherapy as first-line treatment for advanced HBV-related hepatocellular carcinoma: A retrospective, real-world study" [Heliyon 8 (6) (2022) e09538].

[This corrects the article DOI: 10.1016/j.heliyon.2022.e09538.].

Identification of MADS-Box Transcription Factors in Iris laevigata and Functional Assessment of IlSEP3 and IlSVP during Flowering.

Iris laevigata is ideal for gardening and landscaping in northeast China because of its beautiful flowers and strong cold resistance. However, the short length of flowering time (2 days for individual flowers) greatly limits its applications. Molecular breeding and engineering hold high potential for producing I. laevigata of desirable flowering properties. A prerequisite is to identify and characterize key flowering control genes, the identity of which remains largely unknown in I. laevigata due to the lack of genome information. To fill this knowledge gap, we used sequencing data of the I. laevigata transcriptome to identify MADS-box gene-encoding transcription factors that have been shown to play key roles in developmental processes, including flowering. Our data revealed 41 putative MADS-box genes, which consisted of 8 type I (5 Mα and 3 Mß, respectively) and 33 type II members (2 MIKC* and 31 MIKCC, respectively). We then selected IlSEP3 and IlSVP for functional studies and found that both are localized to the nucleus and that they interact physically in vitro. Ectopic expression of IlSEP3 in Arabidopsis resulted in early flowering (32 days) compared to that of control plants (36 days), which could be mediated by modulating the expression of FT, SOC1, AP1, SVP, SPL3, VRN1, and GA20OX. By contrast, plants overexpressing IlSVP were phenotypically similar to that of wild type. Our functional validation of IlSEP3 was consistent with the notion that SEP3 promotes flowering in multiple plant species and indicated that IlSEP3 regulates flowering in I. laevigata. Taken together, this work provided a systematic identification of MADS-box genes in I. laevigata and demonstrated that the flowering time of I. laevigata can be genetically controlled by altering the expression of key MADS-box genes.

Lenvatinib plus sintilimab versus lenvatinib monotherapy as first-line treatment for advanced HBV-related hepatocellular carcinoma: A retrospective, real-world study.

Background: The most common type of primary liver cancer is hepatocellular carcinoma (HCC), and hepatitis B virus (HBV)-related HCC accounts for many HCC cases and has a high mortality rate. The goal of our study was to investigate the efficacy and safety of lenvatinib plus sintilimab therapy in real-world practice and identify factors affecting long-term prognosis. Methods: A retrospective study was conducted with 139 consecutive patients with unresectable HCC treated with lenvatinib or lenvatinib plus sintilimab at the Fifth Medical Center of PLA General Hospital from June 2018 to June 2021. The 139 patients were divided into the control group (85 patients) and the combined treatment group (54 patients) according to the antitumour drugs used for treatment. Efficacy was determined using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and the HCC-specific modified RECIST (mRECIST) for 139 patients who completed the 1st and second tumour assessments. Safety was evaluated in 60 patients in the combined treatment group and 90 patients in the control group using the Common Terminology Criteria for Adverse Events version 5.0. Results: A total of 139 male Chinese patients (49.6% ≥ 55 years old) were included in the efficacy analysis. The median overall survival in the combined treatment group was 21.7 months, and the median progression-free survival was 11.3 months. According to the mRECIST criteria, the objective response rate was 38.9%, and the disease control rate was 92.6%. The median overall survival (mOS), median progression-free survival (mPFS), overall response rate (ORR) and disease control rate (DCR) in the lenvatinib monotherapy group were 12.8 months, 6.6 months, 24.7%, and 74.1%, respectively. Hypertension was the most common adverse event in both groups. Some immune-related adverse events, such as hypothyroidism (n = 5), elevated blood creatinine (n = 3), elevated cardiac enzymes (n = 1), elevated amylase (n = 1) and increased fasting glucose (n = 1), occurred only in the combined therapy group. Five patients in the lenvatinib monotherapy group and six patients in the lenvatinib plus sintilimab group discontinued therapy due to severe adverse events (AEs) (grade 3). No ≥ 4-grade AEs occurred in any patients. Conclusion: The TKI lenvatinib combined with PD-1-targeted immunotherapy sintilimab is efficacious and safe in real-world practice and may lead to better long-term outcomes than lenvatinib alone.

A novel transcriptional activation mechanism of inulinase gene in Kluyveromyces marxianus involving a glycolysis regulator KmGcr1p with unique and functional Q-rich repeats.

Kluyveromyces marxianus is the most suitable fungus for inulinase industrial production. However, the underlying transcriptional activation mechanism of the inulinase gene (INU1) is hitherto unclear. Here, we undertook genetic and biochemical analyses to elucidate that a glycolysis regulator KmGcr1p with unique Q-rich repeats is the key transcriptional activator of INU1. We determined that INU1 and glycolytic genes share similar transcriptional activation patterns and that inulinase activity is induced by fermentable carbon sources including the hydrolysis products of inulin (fructose and glucose), which suggests a novel model of product feedback activation. Furthermore, all four CT-boxes in the INU1 promoter are important for KmGcr1p DNA-binding in vitro, but the most downstream CT-box 1 primarily confers upstream activating sequence activity in vivo. More intriguingly, the use of artificial and natural GCR1 mutants suggests that the Q-rich repeats act as a functional module to maintain KmGcr1p transcriptional activity by contributing to its solubility and DNA-binding affinity. Altogether, this study uncovers a novel transcriptional activation mechanism for the inulinase gene, that is different from the previous understanding for filamentous fungi, but might have universal significance among inulinase-producing yeasts, thereby leading to a better understanding of the regulation mechanism of yeast inulinase genes.

The state of the art in kidney and kidney tumor segmentation in contrast-enhanced CT imaging: Results of the KiTS19 challenge.

There is a large body of literature linking anatomic and geometric characteristics of kidney tumors to perioperative and oncologic outcomes. Semantic segmentation of these tumors and their host kidneys is a promising tool for quantitatively characterizing these lesions, but its adoption is limited due to the manual effort required to produce high-quality 3D segmentations of these structures. Recently, methods based on deep learning have shown excellent results in automatic 3D segmentation, but they require large datasets for training, and there remains little consensus on which methods perform best. The 2019 Kidney and Kidney Tumor Segmentation challenge (KiTS19) was a competition held in conjunction with the 2019 International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI) which sought to address these issues and stimulate progress on this automatic segmentation problem. A training set of 210 cross sectional CT images with kidney tumors was publicly released with corresponding semantic segmentation masks. 106 teams from five continents used this data to develop automated systems to predict the true segmentation masks on a test set of 90 CT images for which the corresponding ground truth segmentations were kept private. These predictions were scored and ranked according to their average Sørensen-Dice coefficient between the kidney and tumor across all 90 cases. The winning team achieved a Dice of 0.974 for kidney and 0.851 for tumor, approaching the inter-annotator performance on kidney (0.983) but falling short on tumor (0.923). This challenge has now entered an "open leaderboard" phase where it serves as a challenging benchmark in 3D semantic segmentation.

Correlation-Guided Network for Fine-Grained Classification of Glomerular lesions in Kidney Histopathology Images.

Chronic Kidney Disease has become a worldwide public health problem which demands careful assessments by pathologists. In this paper, we propose a novel architecture for fine-grained classification of glomerular lesions in renal pathology images sampling from patients with IgA nephropathy. The adversarial correlation loss is innovatively presented to guide a parallel convolutional neural network. In this well- designed loss function, bias between the prediction and the label was take into account while the relationship among different categories is well-aligned. Glomerular lesions in this study are divided into five subcategories, Neg (Negative samples such as tubule and artery), SS (sclerosis involving a portion of the glomerular tuft), GS (sclerosis involving 100% of the tuft), C (build-up of more than two layers of cells within Bowman's space, often with fibrin and collagen deposition) and NOA (none of above). Our model with 93.0% accuracy and 92.9% Fl-score for these five categories has proved superior to other models through experimental results.

Efficacy of a Chinese herbal formula on hepatitis B e antigen-positive chronic hepatitis B patients.

BACKGROUND: No guideline recommends antiviral therapy for hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients with persistently normal alanine aminotransferase levels and a high hepatitis B virus (HBV) DNA viral load. AIM: To evaluate the feasibility and safety of a Chinese herbal formula as a therapeutic option for chronic HBV infection. METHODS: In total, 395 patients (30-65 years old) with confirmed HBeAg-positive chronic hepatitis B infection and persistently normal alanine aminotransferase were randomized to receive either Chinese herbal formula or placebo for 96 wk. Endpoints to evaluate therapeutic efficacy included: (1) HBV DNA levels decreased to less than 4 log10 IU/mL at weeks 48 and 96; and (2) HBeAg clearance and seroconversion rates at weeks 48 and 96. RESULTS: HBV DNA levels ≤ 4 log10 IU/mL were 10.05% at week 48 and 18.59% at week 96 in the treatment group. The HBeAg clearance and conversion rates were 8.54% and 8.04% at week 48 and 16.08% and 14.57% at week 96, respectively. However, HBV DNA levels ≤ 4 log10 IU/mL were 2.55% and 2.55% at weeks 48 and 96, respectively, and the HBeAg clearance rates were 3.06% and 5.61% at weeks 48 and 96, respectively, in the control group. The quantitative hepatitis B surface antigen and HBeAg levels at baseline and changes during the treatment period as well as the alanine aminotransferase elevation at weeks 12 and 24 were strong predictors of HBeAg clearance. CONCLUSION: High rates of HBV DNA reduction, HBeAg clearance and seroconversion could be achieved with Chinese herbal formula treatments, and the treatments were relatively safe for HBeAg-positive chronic hepatitis B-infected patients with persistently normal alanine aminotransferase. The ability of the compound to modulate host immune function probably contributed to this effect.

Identification of glomerular lesions and intrinsic glomerular cell types in kidney diseases via deep learning.

Identification of glomerular lesions and structures is a key point for pathological diagnosis, treatment instructions, and prognosis evaluation in kidney diseases. These time-consuming tasks require a more accurate and reproducible quantitative analysis method. We established derivation and validation cohorts composed of 400 Chinese patients with immunoglobulin A nephropathy (IgAN) retrospectively. Deep convolutional neural networks and biomedical image processing algorithms were implemented to locate glomeruli, identify glomerular lesions (global and segmental glomerular sclerosis, crescent, and none of the above), identify and quantify different intrinsic glomerular cells, and assess a network-based mesangial hypercellularity score in periodic acid-Schiff (PAS)-stained slides. Our framework achieved 93.1% average precision and 94.9% average recall for location of glomeruli, and a total Cohen's kappa of 0.912 [95% confidence interval (CI), 0.892-0.932] for glomerular lesion classification. The evaluation of global, segmental glomerular sclerosis, and crescents achieved Cohen's kappa values of 1.0, 0.776, 0.861, and 95% CI of (1.0, 1.0), (0.727, 0.825), (0.824, 0.898), respectively. The well-designed neural network can identify three kinds of intrinsic glomerular cells with 92.2% accuracy, surpassing the about 5-11% average accuracy of junior pathologists. Statistical interpretation shows that there was a significant difference (P value < 0.0001) between this analytic renal pathology system (ARPS) and four junior pathologists for identifying mesangial and endothelial cells, while that for podocytes was similar, with P value = 0.0602. In addition, this study indicated that the ratio of mesangial cells, endothelial cells, and podocytes within glomeruli from IgAN was 0.41:0.36:0.23, and the performance of mesangial score assessment reached a Cohen's kappa of 0.42 and 95% CI (0.18, 0.69). The proposed computer-aided diagnosis system has feasibility for quantitative analysis and auxiliary recognition of glomerular pathological features. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Deciphering the recreational use of urban parks: Experiments using multi-source big data for all Chinese cities.

China's rapid urbanization process has accentuated the disparity between the demand for and supply of its park recreational services. Estimations of park use and an understanding of the factors that influence it are critical for increasing these services. However, the data traditionally used to quantify park use are often subjective as well as costly and laborious to procure. This paper assessed the use of parks through an analysis of check-in data obtained from the Weibo social media platform for 13,759 parks located in all 287 cities at prefecture level and above across China. We investigated how park attributes, accessibility, and the socioeconomic environment affected the number and density of park check-ins. We used multiple linear regression models to analyze the factors influencing check-ins for park visits. The results showed that in all the cities, the influence of external factors on the number and density of check-in visits, notably the densities of points of interest (POIs) and bus stops around the parks was significantly positive, with the density of POIs being the most influential factor. Conversely, park attributes, which included the park service area and the landscape shape index (LSI), negatively influenced park use. The density of POIs and bus stops located around the park positively influenced the density of the recreational use of urban parks in cities within all administrative tiers, whereas the impact of park service areas was negative in all of them. Finally, the factors with the greatest influence varied according to the administrative tiers of the cities. These findings provide valuable inputs for increasing the efficiency of park use and improving recreational services according to the characteristics of different cities.