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Human migration is a direct indicator of rural attraction. As the world's most populous nation, China is experiencing a rural population decline. The government is actively focusing on a rural revitalization strategy to make rural areas sustainable. Based on data from the sixth census in 2010, this paper applies the Moran's I method and spatial lag regression model to analyze the spatial pattern and driving factors of China's rural migration. The main conclusions are listed as follows. (1) The areas, including the Yangtze River Delta, the Pearl River Delta, and the northwestern areas, were the most attractive destinations for rural migrants. (2) The inter-provincial rural migration pattern is close to the total rural migration pattern, but is different from the intra-provincial pattern. (3) In general, job opportunities in the secondary industry, rural income, rural investment, and the local economic levels were all main drivers for rural migration. The driving mechanisms varied in the eastern, central, and western provinces. To support China's efforts in rural revitalization, regionally different policies, urban-rural integration, and new economic factors are suggested and highlighted from the perspective of rural migration.

BACKGROUND Transcutaneous auricular vagus nerve stimulation (taVNS) may modulate cardiac autonomic function. However, the response rate of the traditional tonic paradigm is low, and the results remain inconsistent. A recent pilot study presented a novel burst paradigm to activate the cardiac parasympathetic system, which might offer a new approach to treat cardiac autonomic function. The present study reassessed the effect of burst taVNS on modulating heart rate variability and explored the difference between burst and traditional tonic paradigms. MATERIALS AND METHODS Forty-two young adults were recruited for this study. Each participant underwent three types of taVNS with sham (30 sec of stimulation), tonic (25 Hz, 500 μsec), and burst (five pulses at 500 Hz every 200 msec) paradigms, respectively, with simultaneous electrocardiogram recording. One-way analysis of variance, multivariate analysis of variance, and linear regression were used for analysis. Multiple testing was performed using Bonferroni correction. RESULTS Both burst and tonic paradigms induced a significant decrease in heart rate, which continued until poststimulation, and increased cardiac parasympathetic activity. Moreover, two parasympathetic system indicators showed significant increase only in burst taVNS. The response rates during burst (35.7%) and tonic (38.1%) stimulations were both higher than that during sham stimulation (11.9%). The response to taVNS showed parameter specificity with few nonresponders to the tonic paradigm responding to the burst paradigm. The overall response rate increased from 38.1% in tonic taVNS to 54.8% in taVNS using both burst and tonic paradigms. For both burst and tonic responders, baseline cardiac parasympathetic activity was found to be significantly negatively correlated with changes during stimulation. CONCLUSION The burst parameter could be used as an alternative strategy for regulating cardiac parasympathetic function by taVNS, which has the potential to be used as a complementary paradigm to traditional tonic taVNS for promoting clinical treatment efficacy.

Objective To evaluate the proprioceptive and clinical function of the knee joint after anterior cruciate ligament reconstruction (ACLR) with various amounts of remnant preserved with as few confounding factors as possible. Methods This retrospective study included 46 patients who underwent ACLR with remnant preservation between March 2013 and February 2019. These patients had less than 6 months injury‐to‐surgery interval and no concomitant injuries. The researchers divided these subjects into two groups based on the length of the remnant preserved after ACLR, with group A defined as having more than 1/3 of the original length preserved and group B defined as less than 1/3 of the original length preserved. Clinical scores were obtained using the Lysholm knee scoring scale and the Tegner activity scale. The Lysholm score was calculated preoperatively, at 3, 6, and 12 months postoperatively, and at the last follow up. The Tegner score was calculated preoperatively, at 12 months postoperatively and at the last follow up. Anterior laxity was measured using the KT2000 arthrometer preoperatively and at 12 months postoperatively. Proprioceptive function was evaluated through reproduction of passive positioning (RPP) and threshold to detection of passive motion (TDPM). Both RPP and TDPM were measured at the angle of 15° at 3, 6, and 12 months postoperatively. Unpaired t‐tests were performed to investigate the difference in each parameters between the two groups. Results In the present study, 20 patients were classified into group A and 26 into group B. All patients were followed up for an average of 34.70 ± 12.79 months. All 46 patients were satisfied with the outcome of the surgery and no complications were reported at the end of the study. No significant differences were found between the two groups in terms of the Lysholm score and anterior laxity by KT2000 at all time points. The Tegner score was significantly higher in group A at 12 months postoperatively and at the final follow‐up. In addition, group A's RPP was significantly better than that of group B's when tested at the angles of 15° and 30° at 3 months postoperatively, and at the angle of 15° at 6 months postoperatively. Group A's TDPM was also significantly better than that of group B's at all three tested angles at 3 months postoperatively, and at the angle of 15° at 6 months postoperatively. Conclusion Patients with ACLR with more than 1/3 of the original length preserved demonstrated a higher activity level 12 months postoperatively and better proprioceptive function at 15° of extension at 3 and 6 months postoperatively.

Rationale Both genetic variants and chronic obstructive pulmonary disease (COPD) contribute to the risk of incident severe coronavirus disease (COVID-19). Whether genetic risk of incident severe COVID-19 is the same regardless of preexisting COPD is unknown. Objectives In this study, we aimed to investigate the potential interaction between genetic risk and COPD in relation to severe COVID-19. Methods We constructed a polygenic risk score for severe COVID-19 by using 112 single-nucleotide polymorphisms in 430,582 participants from the UK Biobank study. We examined the associations of genetic risk and COPD with severe COVID-19 by using logistic regression models. Results Of 430,582 participants, 712 developed severe COVID-19 as of February 22, 2021, of whom 19.8% had preexisting COPD. Compared with participants at low genetic risk, those at intermediate genetic risk (odds ratio [OR], 1.34; 95% confidence interval [CI], 1.09–1.66) and high genetic risk (OR, 1.50; 95% CI, 1.18–1.92) had higher risk of severe COVID-19 (P for trend = 0.001), and the association was independent of COPD (P for interaction = 0.76). COPD was associated with a higher risk of incident severe COVID-19 (OR, 1.37; 95% CI, 1.12–1.67; P = 0.002). Participants at high genetic risk and with COPD had a higher risk of severe COVID-19 (OR, 2.05; 95% CI, 1.35–3.04; P

Graphene quantum dots (GQD) have attracted much attention due to their unique properties in biomedical application, such as biosensing, imaging, and drug delivering. However, scale preparing red luminescing GQD is still challenging now. Herein, with the help of electron beam irradiation, a simple, rapid, and efficient up-to-down strategy was developed to synthesize GQD with size of 2.75 nm emitting 610 nm luminescence. GQD were further functionalized with polyethylene glycol (PEG) and exhibited good solubility and biocompatibility. The potential in vivo toxicity of PEGylated GQD could completely be eliminated by the clinic cholesterol-lowering drug simvastatin. PEGylated GQD could selectively accumulate in tumor after intravenous injection as a security, reliable and sensitive tumor fluorescence imaging agent. Therefore, this work presented a new method preparing red luminescing GQD for biomedical application.

Objective To examine the association of incident type 2 diabetes (T2D) risk with sleep factors, genetic risk, and their combination effects. Design Large prospective population-based cohort study. Methods This population-based prospective cohort study included 360 403 (mean (s.d.) age: 56.6 (8.0) years) participants without T2D at baseline from the UK Biobank. Genetic risk was categorised as high (highest quintile), intermediate (quintiles: 2–4), and low (lowest quintile) based on a polygenic risk score for T2D. Sleep scores, including long or short sleep duration, insomnia, snoring, late chronotype, and excessive daytime sleepiness, were categorized as an unfavourable, intermediate, or favourable sleep and circadian pattern. Results During a median follow-up of 9.0 years, 13 120 incident T2D cases were recorded. Among the participants with an unfavourable sleep and circadian pattern, 6.96% (95% CI: 6.68–7.24%) developed T2D vs 2.37% (95% CI: 2.28–2.46%) of participants with a favourable sleep and circadian pattern (adjusted hazard ratio (HR): 1.53, 95% CI: 1.45–1.62). Of participants with a high genetic risk, 5.53% (95% CI: 5.36–5.69%) developed T2D vs 2.01% (95% CI: 1.91–2.11%) of participants with a low genetic risk (adjusted HR: 2.89, 95% CI: 2.72–3.07). The association with sleep and circadian patterns was independent of genetic risk strata. Participants in the lowest quintile with an unfavourable sleep and circadian pattern were 3.97-fold more likely to develop T2D than those in the lowest quintile with a favourable sleep and circadian pattern. Conclusions Sleep and circadian patterns and genetic risk were independently associated with incident T2D. These results indicate the benefits of adhering to a healthy sleep and circadian pattern in entire populations, independent of genetic risk.

Bilirubin has antioxidant and anti-inflammatory properties in vitro and in animal studies and protects against inflammatory, cardiovascular, and other diseases in observational studies; therefore, bilirubin has potential as a therapeutic agent. However, observational studies could be confounded by many factors. We used a genetic (n = 61,281) and clinical (n = 234,670) approach to define the association between bilirubin and 19 conditions with a putative protective signal in observational studies. We also tested if individuals with genetically higher bilirubin levels underwent more diagnostic tests. We used a common variant in UGT1A1 (rs6742078) associated with an 26% increase in bilirubin levels in the genetic studies. Carriers of the variant had higher bilirubin levels (P = 2.2 × 10-16 ) but there was no significant association with any of the 19 conditions. In a phenome-wide association study (pheWAS) to seek undiscovered genetic associations, the only significant finding was increased risk of "jaundice-not of newborn." Carriers of the variant allele were more likely to undergo an abdominal ultrasound (odds ratio = 1.04, [1.00-1.08], P = 0.03). In contrast, clinically measured bilirubin levels were significantly associated with 15 of the 19 conditions (P

BACKGROUND Data on the association of subclinical hypothyroidism (SCH) with the severity of coronary artery disease and major adverse cardiovascular and cerebral events (MACCE) in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) after percutaneous coronary intervention (PCI) are limited and conflicting. OBJECTIVE We established the baseline rate of SCH and followed the trajectory of thyroid-stimulating hormone (TSH) values during and after hospitalisation for PCI for up to six months and determined whether persistent SCH was associated with the severity of coronary artery disease and MACCE in patients with NSTE-ACS after PCI. DESIGN Population-based prospective cohort study. PATIENTS We included patients with NSTE-ACS who underwent PCI with simple balloon angioplasty or stent implantation for coronary heart disease. MEASUREMENTS Thyroid function tests of patients before PCI and 1 day, 1 week, 1 and 6 months after PCI were performed. Cases showing transient SCH were excluded. Patients were divided into two groups based on the results of four TSH tests: 0.27-4.2 mIU/L (n = 1472, 89.7%) and >4.2 mIU/L (n = 170, 10.4%). The risk factors for the severity of coronary artery lesions were estimated using multinomial logistic regression analysis. Univariate and multivariate Cox regression analyses were used to study the relationship between TSH and MACCE. RESULTS Among 1642 patients, there were 1070 males (65.2%) and 572 females (34.8%), with an average age of 62.5 ± 9.6 years. SCH patients had a wider range of diseased vessels and a higher number of diseased vessels (p

Genomic medicine holds great promise for improving health care, but integrating searchable and actionable genetic data into electronic health records (EHRs) remains a challenge. Here we describe Neptune, a system for managing the interaction between a clinical laboratory and an EHR system during the clinical reporting process. We developed Neptune and applied it to two clinical sequencing projects that required report customization, variant reanalysis, and EHR integration. Neptune has been applied for the generation and delivery of over 15,000 clinical genomic reports. This work spans two clinical tests based on targeted gene panels that contain 68 and 153 genes respectively. These projects demanded customizable clinical reports that contained a variety of genetic data types including single-nucleotide variants (SNVs), copy-number variants (CNVs), pharmacogenomics, and polygenic risk scores. Two variant reanalysis activities were also supported, highlighting this important workflow. Methods are needed for delivering structured genetic data to EHRs. This need extends beyond developing data formats to providing infrastructure that manages the reporting process itself. Neptune was successfully applied on two high-throughput clinical sequencing projects to build and deliver clinical reports to EHR systems. The software is open source and available at https://gitlab.com/bcm-hgsc/neptune .

Background Large interindividual variations have been reported in chemotherapy‐induced toxicities. Little is known whether racial disparities exist in neutropenia associated with taxanes. Methods Patients with a diagnosis of primary cancer who underwent chemotherapy with taxanes were identified from Vanderbilt University Medical Center's Synthetic Derivative. Multinomial regression models were applied to evaluate odds ratios (ORs) and 95% confidence intervals (CIs) of neutropenia associated with race, with adjustments for demographic variables, baseline neutrophil count, chemotherapy‐related information, prior treatments, and cancer site. Results A total of 3492 patients were included in the study. Compared with White patients, grade 2 or higher neutropenia was more frequently recorded among Black patients who received taxanes overall (42.2% vs. 32.7%, p, After accounting for baseline neutropenia count, patient characteristics and other treatments received, Black patients who received chemotherapy with taxanes had a greater risk for neutropenia compared with their White counterparts, especially for those who received paclitaxel. This is critically important for treatment planning and dose adjustments, expectation setting, and physician awareness for the potential for increased infections or febrile episodes during periods of neutropenia in Black patients. Our findings call for further investigations on this disparity, particularly in clinical trial settings, as well as on the underlying mechanisms.

OBJECTIVE Primary non-response (PNR) to anti-tumor necrosis factor-α (TNFα) biologics is a serious concern in patients with inflammatory bowel disease (IBD). We aimed to identify the genetic variants associated with PNR. DESIGN Patients were recruited from outpatient GI clinics and PNR was determined using both clinical and endoscopic findings. A case-control genome-wide association study was performed in 589 IBD patients and associations were replicated in an independent cohort of 293 patients. Effect of the associated variant on gene expression and TNFα secretion was assessed by cell-based assays. Pleiotropic effects were investigated by Phenome-wide Association Study (PheWAS). RESULTS We identified rs34767465 as associated with PNR to anti-TNF-α therapy (OR:2.07, 95%CI:1.46-2.94, p=2.43×10−7, [Replication OR:1.8, 95%CI:1.04-3.16, p=0.03]). rs34767465 is a multiple-tissue expression quantitative trait loci for FAM114A2. Using RNA-sequencing and protein quantification from HapMap lymphoblastoid cell lines (LCLs), we found a significant decrease in FAM114A2 mRNA and protein expression in both heterozygous and homozygous genotypes when compared to wild type LCLs. TNF-α secretion was significantly higher in THP-1 cells [differentiated into macrophages] with FAM114A2 knockdown versus controls. Immunoblotting experiments showed that depletion of FAM114A2 impaired autophagy related pathway genes suggesting autophagy mediated TNF-α secretion as a potential mechanism. PheWAS showed rs34767465 was associated with comorbid conditions found in IBD patients (derangement of joints [p=2.3×10−4], pigmentary iris degeneration [p=5.1×10−4], diverticulum of esophagus [p=6.3×10−4]). CONCLUSION We identified a variant rs34767465 associated with PNR to anti-TNFα biologics, which increases TNFα secretion through mechanism related to autophagy. rs34767465 may also explain the comorbidities associated with IBD. Significance of this study What is already known on this subject? Tumor necrosis factor (TNF) α is one of the major pro-inflammatory cytokines in the underlying pathogenesis of mucosal inflammation in inflammatory bowel disease (IBD), and has been the primary therapeutic target for IBD. Anti-TNFα biologic drugs have been shown to induce clinical response in 60-75% of the patients, and long-term maintenance of remission in a large number of patients that respond to the drug. However, approximately 30-40% of the patients fail to respond to anti-TNF α biologics (primary non-responders; PNR). What are the new findings? This is the first genome-wide association study to identify the genetic loci, rs34767465 associated with 2-fold increased risk of PNR to anti-TNFα therapy. rs34767465 is an expressed quantitative trait locus for FAM114A2, and leads to decreased expression of the gene in blood and LCLs. Knockdown of FAM114A2 in THP-1 cells-derived macrophages increase TNFα secretion through mechanism related to autophagy. Phenome-wide association study reveals association of rs34767465 with comorbid conditions like derangement of joints, pigmentary iris degeneration and diverticulum of esophagus, that are observed in IBD patients How might it impact on clinical practice in the foreseeable future? rs34767465 may help guide physicians’ drug choice and therapeutic drug monitoring to prevent PNR to anti-TNFα therapy and IBD associated comorbidities.

Objective To investigate the outcomes of C‐shaped release around the greater trochanter in gluteal muscle contracture under arthroscopy. Methods From December 2016 to January 2018, 185 patients with gluteal muscle contracture who treated under arthroscopy were reviewed, including 69 males and 116 females. All patients had a history of repeated intramuscular injection into the buttocks. The follow signs were positive in all the patients before surgery: squatting and crouching disability, difficulty in crossing the leg, Ober's sign positive, clicking sound during rotation of the hip. The C‐shaped release around the greater trochanter under arthroscopy was performed in 96 cases (C‐shaped release group) with an average age of 24.6 ± 4.9 years old, and conventional gluteal muscle contracture release under arthroscopy was performed in 89 cases (conventional release group) with an average age of 25.1 ± 5.0 years. The released tissues in the C‐shaped release group: iliotibial band (ITB) about 5 cm distal to the proximal end of the greater trochanter, the contracture tissue near the posterior and superior of the greater trochanter, which depended on both intraoperative physical examination and arthroscopic observation. The released tissues in conventional release group: the contracture tissues in gluteal muscles according to observation under arthroscopy. The gluteal muscle contracture disability scale (GDS) and Visual analogue scale (VAS) were evaluated before surgery and at the last follow‐up. Results The average release time after making arthroscopic operation space for each lower limb were 12.2 ± 3.2 min in the C‐shaped release group, and 21.4 ± 6.1 min in the conventional release group (P = 0.000). All the patients were followed for at least of 2 years after operation. There was one case of wound hematoma in the C‐shaped release group and five cases in the conventional release group(P = 0.079), abductor weakness (IV level)occurred in two patients in the C‐shaped release group and five cases in the conventional release group (P = 0.208). GDS was 49.3 ± 17.3 (22 to 70) in theC‐shaped release group and 48.1 ± 15.6 (23 to 69) in the conventional release group before surgery (P = 0.622), 91.7 ± 5.2 (83 to 100) in the C‐shaped release group and 90.2 ± 6.1 (83 to 98) in the conventional release group (P = 0.073) with difference nearly significant at last follow‐up. Conclusion Arthroscopic C‐shaped release around the greater trochanter had less operation time, acceptable complication occurrence, and it has an optimistic outcome for gluteal muscle contracture under arthroscope., The target area of arthroscopic C‐shaped release was formed by the iliotibial band tissue 5 cm distal to the proximal end of the greater trochanter (A), the contracture tissue nearly posterior (B) and superior (C) of the greater trochanter.

Labeling clinical data from electronic health records (EHR) in health systems requires extensive knowledge of human expert, and painstaking review by clinicians. Furthermore, existing phenotyping algorithms are not uniformly applied across large datasets and can suffer from inconsistencies in case definitions across different algorithms. We describe here quantitative disease risk scores based on almost unsupervised methods that require minimal input from clinicians, can be applied to large datasets, and alleviate some of the main weaknesses of existing phenotyping algorithms. We show applications to phenotypic data on approximately 100,000 individuals in eMERGE, and focus on several complex diseases, including Chronic Kidney Disease, Coronary Artery Disease, Type 2 Diabetes, Heart Failure, and a few others. We demonstrate that relative to existing approaches, the proposed methods have higher prediction accuracy, can better identify phenotypic features relevant to the disease under consideration, can perform better at clinical risk stratification, and can identify undiagnosed cases based on phenotypic features available in the EHR. Using genetic data from the eMERGE-seq panel that includes sequencing data for 109 genes on 21,363 individuals from multiple ethnicities, we also show how the new quantitative disease risk scores help improve the power of genetic association studies relative to the standard use of disease phenotypes. The results demonstrate the effectiveness of quantitative disease risk scores derived from rich phenotypic EHR databases to provide a more meaningful characterization of clinical risk for diseases of interest beyond the prevalent binary (case-control) classification.

Objective To determine the effectiveness of hip arthroscopy combined with endoscopic iliotibial band (ITB) release in patients with both femoroacetabular impingement (FAI) syndrome and external snapping hip (ESH). Methods Retrospectively review the preoperative and minimum of 2‐year follow‐up data of patients with both FAI syndrome and ESH who underwent endoscopic ITB release during hip arthroscopy (FAI + ESH group) from January 2014 to December 2018. The same number of age‐ and gender‐matched FAI syndrome patients without ESH undergoing hip arthroscopy were enrolled in the control group (FAI group). Patient‐reported outcomes (PROs) including international Hip Outcome Tool (iHOT‐33), modified Harris Hip Score (mHHS), visual analog scale for pain (VAS‐pain), and abductive force of affected hip at 3 month and 2 years postoperatively were comparatively analyzed. The VAS‐satisfaction score of two groups at 2 years postoperatively were also analyzed. Results The prevalence of ESH in FAI syndrome patients undergoing hip arthroscopy in our institution was 5.5% (39 of 715 hips), including nine males (10 hips) and 29 females (29 hips). The mean age at the time of surgery was 32.1 ± 6.9 years (range, 22–48 years). According to inclusion and exclusion criteria, 23 patients were enrolled in FAI + ITB group. Twenty‐three age‐ and sex‐matched FAI syndrome patients were enrolled in FAI group. At 24 months postoperatively, no patient still suffered ESH symptoms and painful palpation at lateral region in FAI + ITB group. The iHOT‐33, mHHS, and VAS‐pain score of patients in FAI + ESH group were significantly severer than patients in FAI group preoperatively (41.6 ± 7.5 vs 48.8 ± 7.2, 54.8 ± 7.2 vs 59.2 ± 6.9, 5.5 ± 0.9 vs 4.7 ± 1.0; P 0.05). At 3 months after surgery, the abductive force of operated hip was significantly smaller than that in FAI group (82.4 ± 12.4 N vs 91.9 ± 16.1 N, P 0.05). The VAS‐satisfaction scores of patients in the two groups were at a similarly high level (90.5 ± 6.8 vs 88.8 ± 7.3, P > 0.05). There was no complication and no arthroscopic revision in either group until 2‐year follow‐up. Conclusion Although abductive force recovery of the hip was delayed, hip arthroscopy combined with endoscopic ITB release addressed hip snapping in patients with both FAI syndrome and ESH, and could get similar functional improvement, pain relief, recovery speed, as well as patient satisfaction compared with the pure hip arthroscopy in FAI syndrome patients without ESH., This article confirmed that hip arthroscopy combined with endoscopic iliotibial band (ITB) release would address hip snapping in patients with both femoroacetabular impingement (FAI) syndrome and external snapping hip (ESH), and would get similar functional improvement, pain relief, recovery speed, as well as patient satisfaction, compared with the pure hip arthroscopy in FAI syndrome patients without ESH.

Analog optical computing has been an innovation and research interest in last several years, thanks to the ultra-high speed (potential for real-time processing), ultra-low power consumption and capability of parallel processing. Although great efforts have been made recently, no on-chip optical spatial-domain integrator has been experimentally demonstrated, to the best of our knowledge. Based on Fourier optics and metasurface, we design and fabricate an on-chip optical integrator using silicon-on-insulator (SOI) platform. The proposed integrator is able to integrate the electric field in spatial domain. As a proof-of-concept demonstration, a representative optical signal is well integrated to the desired distribution. Compared with theoretical expectation, the similarity coefficients of the simulated and experimental results are 83 and 78%, respectively. The proposed scheme has potential of performing more complex and ultra-high-speed computing for artificial intelligence.

Human gait recognition has numerous challenges due to view angle changing, human dressing, bag carrying, and pedestrian walking speed, etc. In order to increase gait recognition accuracy under these circumstances, in this paper we propose a method for gait recognition based on a self-adaptive hidden Markov model (SAHMM). First, we present a feature extraction algorithm based on local gait energy image (LGEI) and construct an observation vector set. By using this set, we optimize parameters of the SAHMM-based method for gait recognition. Finally, the proposed method is evaluated extensively based on the CASIA Dataset B for gait recognition under various conditions such as cross view, human dressing, or bag carrying, etc. Furthermore, the generalization ability of this method is verified based on the OU-ISIR Large Population Dataset. Both experimental results show that the proposed method exhibits superior performance in comparison with those existing methods.

Objective We developed and evaluated Drug-Drug Interaction Wide Association Study (DDIWAS). This novel method detects potential drug-drug interactions (DDIs) by leveraging data from the electronic health record (EHR) allergy list. Materials and Methods To identify potential DDIs, DDIWAS scans for drug pairs that are frequently documented together on the allergy list. Using deidentified medical records, we tested 616 drugs for potential DDIs with simvastatin (a common lipid-lowering drug) and amlodipine (a common blood-pressure lowering drug). We evaluated the performance to rediscover known DDIs using existing knowledge bases and domain expert review. To validate potential novel DDIs, we manually reviewed patient charts and searched the literature. Results DDIWAS replicated 34 known DDIs. The positive predictive value to detect known DDIs was 0.85 and 0.86 for simvastatin and amlodipine, respectively. DDIWAS also discovered potential novel interactions between simvastatin-hydrochlorothiazide, amlodipine-omeprazole, and amlodipine-valacyclovir. A software package to conduct DDIWAS is publicly available. Conclusions In this proof-of-concept study, we demonstrate the value of incorporating information mined from existing allergy lists to detect DDIs in a real-world clinical setting. Since allergy lists are routinely collected in EHRs, DDIWAS has the potential to detect and validate DDI signals across institutions.

Li-Li Yang,1,2,* Ping Peng,1,3,* Yun-Hong Lin,3 Ting Zhou,4 Xiao-Xue Ren,1,3 Wei-Qi Wang,1 Xing-Xing Li1,3 1Department of Dental Research, The Affiliated Stomatological Hospital of Kunming Medical University, Kunming, Yunnan, 650100, People’s Republic of China; 2Department of Periodontics, The Affiliated Stomatological Hospital of Kunming Medical University, Kunming, Yunnan, 650100, People’s Republic of China; 3Department of Prosthodontics, The Affiliated Stomatological Hospital of Kunming Medical University, Kunming, Yunnan, 650100, People’s Republic of China; 4Department of Orthodontics, The Affiliated Stomatological Hospital of Kunming Medical University, Kunming, Yunnan, 650100, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xing-Xing LiDepartment of Prosthodontics, The Affiliated Stomatological Hospital of Kunming Medical University, No. 1088 Haiyuan Road, Wuhua District, Kunming, Yunnan, 650100, People’s Republic of ChinaTel +86 13759581696Fax +86 87165330099Email lxx_drli1862@163.comObjective: This study aims to measure and analyze the lip and tooth dynamic esthetic characteristics at rest and during speech in order to provide a reference for its esthetic design and restoration among the Hani and Han populations in Yunnan Province, China.Methods: Subjects of Hani and Han ethnicity in Yunnan were selected using multistage stratified sampling and inclusive criteria. The lip and tooth dynamic esthetic characteristics of the subjects at rest and during the pinyin pronunciation of “me”, “yi”, “fu”, and “si” were recorded using digital photography and analyzed with computer software.Results: No statistical difference was detected between the Hani and Han groups in the upper central-incisor display, when pronouncing the pinyin “yi”. Furthermore, there were no statistical differences in lip dynamic esthetic parameters between the Hani and Han groups, except for the distance between the upper and lower lips when pronouncing “si”. There were three kinds of correlation between the upper central-incisor edge and lower lip: separation, contact, and overlap.Conclusion: The display of upper central incisors and the mouth width of Hani people are larger than those of Han people when at rest. When the pinyin “si” is pronounced, the display of upper central incisors and the upper–lower lip distance of Hani people is less than that of Han people due to labial muscle movement.Keywords: Hani, Han, pronunciation, lip and tooth aesthetics, digital videography

In this paper, we recognize serial numbers on banknotes using deep learning. The samples used in this paper are digital images which have been preprocessed with data labelling and data augmentation, e.g., scaling transformation, etc. The algorithms based on deep learning are proposed and have the stability for serial number recognition with complex backgrounds. In this paper, a pipeline of deep neural networks is established for the recognition of banknote serial numbers. Because high reliability is more important than accuracy in financial applications, DenseNet is set forth as the primary classifier, the scaling transformation of SegLink is put forward to locate the characters, the detection rate is up to 95.80%. A convolutional neural network with residual attention model is proposed for serial number recognition, the precision is up to 97.09%.

Assessing the impacts of future land use scenarios on ecosystem services can provide theoretical basis and reference for sustainable land use management. This study combined scenario analysis and quantitative assessment to monitor land use and ecosystem services in the intensive agricultural area of Qixia city, North China under three different scenarios, i.e. natural development, farmland and orchard to forest and farmland to forest and orchard, by using the GeoSoS-FLUS and the InVEST models. The integrated land use change impact index (ILUCII) and the single land use change impact index (SLUCII) were proposed to quantitatively depict the impact of different land use change scenarios on ecosystem services. The results demonstrated that: (1) Under the three land use scenarios, forest, farmland and orchard show different change patterns. Slope influences the soil and water conservation services, land use in greater than 15° slope section occupied more soil and water conservation services than 12–15° section and less than 12° section. In the same slope section, forest had the most soil and water conservation services compared with orchard and farmland. (2) The effects of different land use conversion on soil conservation services per study grid (90*90 m) in less than 12° slope section showed an order of farmland-forest > orchard-forest > farmland-orchard. In more than 12° slope section, the order is farmland-forest > farmland-orchard > orchard-forest. The effects of land use conversion on water conservation services per grid is farmland - forest > orchard - forest > farmland-orchard. (3) The total ILUCII on ecosystem services found that farmland and orchard to forest scenario (16517.54) > farmland to forest and orchard scenario (13074.12) > natural development scenario (−4975.02). The mean ILUCII on ecosystem services showed that farmland to forest and orchard scenario (0.63) > farmland and orchard to forest scenario (0.53) > natural development scenario (−0.11). The mean SLUCII on ecosystem services found that greater than 15° farmland to forest (0.89) > 12–15°farmland to orchard (0.49) > greater than 15°orchard to forest (0.34).

Automated driving gradually emerges as a real reality, but it still has to face various challenges, including sophisticated and volatile traffic conditions, human operating faults, etc. Amongst them, accurate understanding of traffic signs by using computer vision and deep learning methods has great significance for driving safety. In recent years, the advent of deep learning has made this issue much effectively. In this article, our major goal is to use deep learning models for conducting traffic-light sign recognition related to autonomous vehicles. As far as we know, this is the first time that the capsule neural network is employed as a method for scene understanding so as to effectively identify a class of traffic-light signs. Compared with the well-known convolutional neural networks, capsule networks diminish the demands for training datasets and tackle the spatial relationship much precisely.

The purpose of this study is to investigate factors of the development and decline of 7-Eleven in the new industrial era. This study examined the relations between marketing mix strategy (4Ps) and customer satisfaction significantly predicting the development and decline of 7-Eleven. A total of 108 respondents, 56 Malaysian and 52 Indonesian, were involved to collect the data by questionnaires. The regression results provided sufficient evidence that factors of 7-Eleven development are positively related to its marketing mix strategy and customer satisfaction or vice versa. This finding provides profound understanding about the relationship between the development and decline factors in new industrial era, its marketing mix strategy and customer satisfaction.

Background Risk for transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to close contacts of infected persons has not been well estimated. Objective To evaluate the risk for transmission of SARS-CoV-2 to close contacts in different settings. Design Prospective cohort study. Setting Close contacts of persons infected with SARS-CoV-2 in Guangzhou, China. Participants 3410 close contacts of 391 index cases were traced between 13 January and 6 March 2020. Data on the setting of the exposure, reverse transcriptase polymerase chain reaction testing, and clinical characteristics of index and secondary cases were collected. Measurement Coronavirus disease 2019 (COVID-19) cases were confirmed by guidelines issued by China. Secondary attack rates in different settings were calculated. Results Among 3410 close contacts, 127 (3.7% [95% CI, 3.1% to 4.4%]) were secondarily infected. Of these 127 persons, 8 (6.3% [CI, 2.1% to 10.5%]) were asymptomatic. Of the 119 symptomatic cases, 20 (16.8%) were defined as mild, 87 (73.1%) as moderate, and 12 (10.1%) as severe or critical. Compared with the household setting (10.3%), the secondary attack rate was lower for exposures in health care settings (1.0%; odds ratio [OR], 0.09 [CI, 0.04 to 0.20]) and on public transportation (0.1%; OR, 0.01 [CI, 0.00 to 0.08]). The secondary attack rate increased with the severity of index cases, from 0.3% (CI, 0.0% to 1.0%) for asymptomatic to 3.3% (CI, 1.8% to 4.8%) for mild, 5.6% (CI, 4.4% to 6.8%) for moderate, and 6.2% (CI, 3.2% to 9.1%) for severe or critical cases. Index cases with expectoration were associated with higher risk for secondary infection (13.6% vs. 3.0% for index cases without expectoration; OR, 4.81 [CI, 3.35 to 6.93]). Limitation There was potential recall bias regarding symptom onset among patients with COVID-19, and the symptoms and severity of index cases were not assessed at the time of exposure to contacts. Conclusion Household contact was the main setting for transmission of SARS-CoV-2, and the risk for transmission of SARS-CoV-2 among close contacts increased with the severity of index cases. Primary funding source Guangdong Province Higher Vocational Colleges and Schools Pearl River Scholar Funded Scheme.

Objective To observe the effect of electroacupuncture combined with low-frequency pulsed electromagnetic field on bone metabolism in patients with spinal cord injury (SCI). Methods The 60 SCI patients who met the inclusion criteria were randomly divided into 2 groups by means of a random number table. In the control group, 30 patients were treated with osteoporosis treatment apparatus. In the observation group, 30 patients were treated with osteoporosis treatment apparatus and electroacupuncture at the foot-shaoyangacupoints [Yanglingquan (阳陵泉GB 34) and Xuanzhōng (悬钟GB 39) of both sides].The treatment was applied once a day, 5 days a week, for 8 weeks.Before and after treatment, the changes of indexes in the two groups, including the bone mineral density (BMD), bone gla-containing protein (BGP), serum alkaline phosphatase (ALP), procollagen type I C-peptide (PICP), and 25‑hydroxy-vitamin D [25(OH)D], were observed for comparison. Results After treatment, in the two groups, the BMD and 25(OH)D indexes of the femoral neck, greater trochanter, and Ward's triangle region were not significantly changed in comparing with those before treatment (P>0.05), while the BGP, ALP, and PICP indexes were significantly higher than those before treatment (P 0.05). Conclusion The osteoporosis treatment apparatus can improve bone metabolism in SCI patients, and the curative effect can be enhanced when combined with electroacupuncture at foot-shaoyangacupoints.

Ankle fractures and their mechanisms of injury can be complex. We report a case of a patient with an uncertain mechanism of injury and an uncommon combination of lower extremity fractures, which fit the criteria for a Lauge-Hansen classification pronation-external-rotation fracture, Maisonneuve fracture, Wagstaffe fracture, and posterior pilon fracture. Plain radiographs and computed tomography scan revealed Chaput tubercle avulsion fractures, an anterior distal fibular fracture fragment, multiple lateral malleolar fractures, a posterior malleolar fracture fragment with proximal displacement, a die-punch fragment between the posterior malleolar fragment and the tibia, a proximal fibular fracture, and possible ankle syndesmotic diastasis. Intraoperative hook test was negative after fixation of the fractures, so syndesmotic fixation was not performed. At 3-month follow-up, plain radiographs showed obvious syndesmotic diastasis. At 1-year follow-up, symptoms persisted and syndesmotic fusion was recommended but declined by the patient. This case demonstrates that both ankle fractures and their mechanisms of injury can be remarkably complex and confusing, posterior pilon fractures can occur along with pronation-external-rotation ankle fractures, syndesmotic fixation should be considered for all patients with Maisonneuve fractures, reliance on the hook test for surgical management decisions may not always be reliable, and there exists a need for a more accurate and reliable intraoperative test to determine the presence of ankle syndesmotic injury.

BACKGROUND To investigate corneal endothelial cell density in eyes with primary pterygium. METHODS A retrospective study was conducted to compare endothelial cell density between 1,565 patients with primary pterygium and 3,448 patients without pterygium. Then a prospective study was designed to confirm the findings of the retrospective study in 95 patients with unilateral primary pterygium. RESULTS In the retrospective study, the mean endothelial cell density in eyes with primary pterygium was significantly lower (2,454 ± 303 cells/mm2 ) than those in eyes without pterygium (2,525 ± 312 cells/mm2 , p

As a new human identification technology, gait recognition is receiving more and more attention in recent years. However, traditional gait recognition techniques are limited by the challenges of feature representation and extraction algorithms. In this paper, by utilizing the self-attention mechanism, we propose a novel gait-based human identification solution. Firstly, we utilize non-local neural networks (NLNN) to extract non-local features from a pair of randomly selected gait energy maps (GEIs). Secondly, based on the relationship between GEIs and various parts of the human body, the output of NLNN is horizontally segmented into three sections, i.e., strong-dynamic region, weak-dynamic region and micro-dynamic region, respectively. Thirdly, the segmented gait features are weighted ensembled by three two-class classifiers. Finally, two experiments are carried out with the OU-ISIR large population dataset and the CASIA dataset B to evaluate the proposed approach.

The convergence of artificial intelligence (AI) and precision medicine promises to revolutionize health care. Precision medicine methods identify phenotypes of patients with less-common responses to treatment or unique healthcare needs. AI leverages sophisticated computation and inference to generate insights, enables the system to reason and learn, and empowers clinician decision making through augmented intelligence. Recent literature suggests that translational research exploring this convergence will help solve the most difficult challenges facing precision medicine, especially those in which nongenomic and genomic determinants, combined with information from patient symptoms, clinical history, and lifestyles, will facilitate personalized diagnosis and prognostication.

Hypersensitivity reactions to drugs are often unpredictable and can be life threatening, underscoring a need for understanding their underlying mechanisms and risk factors. The extent to which germline genetic variation influences the risk of commonly reported drug allergies such as penicillin allergy remains largely unknown. We extracted data from the electronic health records of more than 600,000 participants from the UK, Estonian, and Vanderbilt University Medical Center's BioVU biobanks to study the role of genetic variation in the occurrence of self-reported penicillin hypersensitivity reactions. We used imputed SNP to HLA typing data from these cohorts to further fine map the human leukocyte antigen (HLA) association and replicated our results in 23andMe's research cohort involving a total of 1.12 million individuals. Genome-wide meta-analysis of penicillin allergy revealed two loci, including one located in the HLA region on chromosome 6. This signal was further fine-mapped to the HLA-B∗55:01 allele (OR 1.41 95% CI 1.33-1.49, p value 2.04 × 10-31) and confirmed by independent replication in 23andMe's research cohort (OR 1.30 95% CI 1.25-1.34, p value 1.00 × 10-47). The lead SNP was also associated with lower lymphocyte counts and in silico follow-up suggests a potential effect on T-lymphocytes at HLA-B∗55:01. We also observed a significant hit in PTPN22 and the GWAS results correlated with the genetics of rheumatoid arthritis and psoriasis. We present robust evidence for the role of an allele of the major histocompatibility complex (MHC) I gene HLA-B in the occurrence of penicillin allergy.

Objective Developing algorithms to extract phenotypes from electronic health records (EHRs) can be challenging and time-consuming. We developed PheMap, a high-throughput phenotyping approach that leverages multiple independent, online resources to streamline the phenotyping process within EHRs. Materials and Methods PheMap is a knowledge base of medical concepts with quantified relationships to phenotypes that have been extracted by natural language processing from publicly available resources. PheMap searches EHRs for each phenotype’s quantified concepts and uses them to calculate an individual’s probability of having this phenotype. We compared PheMap to clinician-validated phenotyping algorithms from the Electronic Medical Records and Genomics (eMERGE) network for type 2 diabetes mellitus (T2DM), dementia, and hypothyroidism using 84 821 individuals from Vanderbilt Univeresity Medical Center's BioVU DNA Biobank. We implemented PheMap-based phenotypes for genome-wide association studies (GWAS) for T2DM, dementia, and hypothyroidism, and phenome-wide association studies (PheWAS) for variants in FTO, HLA-DRB1, and TCF7L2. Results In this initial iteration, the PheMap knowledge base contains quantified concepts for 841 disease phenotypes. For T2DM, dementia, and hypothyroidism, the accuracy of the PheMap phenotypes were >97% using a 50% threshold and eMERGE case-control status as a reference standard. In the GWAS analyses, PheMap-derived phenotype probabilities replicated 43 of 51 previously reported disease-associated variants for the 3 phenotypes. For 9 of the 11 top associations, PheMap provided an equivalent or more significant P value than eMERGE-based phenotypes. The PheMap-based PheWAS showed comparable or better performance to a traditional phecode-based PheWAS. PheMap is publicly available online. Conclusions PheMap significantly streamlines the process of extracting research-quality phenotype information from EHRs, with comparable or better performance to current phenotyping approaches.

Visual secret sharing (VSS) has the advantage that the decryption is based on our human visual system without participation of any computational devices. However, traditional VSS schemes are only for sharing raster images with regard to pixels, which lead to that the secret image will be aliased when enlarged and its pixels are shared in rectangular way only. In this paper, we will introduce a VSS scheme for vectorized images based on Penrose tiling. Penrose tiling is with the merits of vectorization and nonperiodicity. These properties are applied to the proposed scheme so as to share those vectorized images; the basic unit of secret sharing could be any graphical shapes instead of pixels or rectangular regions only in the traditional methods. Our experiments show the effectiveness of the proposed scheme.

Aneurysmal subarachnoid hemorrhage (SAH) causes permanent neurological sequelae, but the underlying mechanism needs to be further clarified. Here, we show that inhibition of metabotropic glutamate receptor 1 (mGluR1) with negative allosteric modulator JNJ16259685 improves long-term neurobehavioral outcomes in an endovascular perforation model of SAH. JNJ16259685 improves cerebrovascular dysfunction through attenuation of cerebral blood flow (CBF) reduction, cerebral vasoconstrictio, and microthrombosis formation in a rat SAH model. Moreover, JNJ16259685 reduces experimental SAH-induced long-term neuronal damage through alleviation of neuronal death and degeneration. Mechanically, JNJ16259685 maintains phosphorylation of endothelial NO synthase (eNOS) and vasodilator-stimulated phosphoprotein (VASP) and decreases apoptosis-related factors Bax, active caspase-9, and active caspase-3 following experimental SAH. Altogether, our results suggest JNJ16259685 improves long-term functional impairment through neurovascular protection.

Background To study the clinical manifestations and advantages of open-heart surgery and echocardiographic transthoracic or percutaneous closure with secundum atrial septal defect (ASD). The surgeon’s learning curve was also analyzed. Methods In all, 115 consecutive patients with ASD from May 2013 to May 2019 were enrolled. According to the operative procedure, patients were divided into three groups: group one (open repair group) (n = 24), where patients underwent ASD repair (ASDR) under cardiopulmonary bypass (CPB); group two (closed surgical device closure group) (n = 69), where patients (six patients ≤1 y and sixteen ≤10 kg) underwent transthoracic ASD occlusion under transesophageal echocardiographic (TEE) guidance; and group three (transcatheter occlusion group) (n = 22), where patients underwent percutaneous ASD occlusion under echocardiography. The clinical features and results of each group were analyzed. All patients were telephonically followed-up after 3 months. Results All the three methods treating ASD were successfully performed in our hospital. It was also a typical developing history of congenital heart disease (CHD) surgery in China. One patient in the group two was transferred to emergency surgery for occluder retrieval and CPB-ASDR. Eight patients experienced failed transthoracic or percutaneous occlusion, two of whom underwent unsuccessful percutaneous closure at another hospital. Two patients each in the groups two and three were intraoperatively converted to CPB-ASDR. Two patient in the group three was converted to transthoracic occlusion surgery. All patients were discharged without any residual shunt. The three-month follow-up also did not show any residual shunt and occluder displacement. Conclusion In low-weight, infants, or huge ASDs with suitable rim for device occlusion, transthoracic ASD closure was successfully performed. Based on knowledge of ASD anatomy and skilled transthoracic occlusion of ASD, surgeons can perform percutaneous occlusion of ASD under echocardiographic guidance.

Highlights • The prevalence of anxiety and depression symptoms was 3.4% and 22.8% among workers during the COVID-19 epidemic in China. • Epidemic-related factors especially having confirmed cases in the community and having confirmed friends were associated with the higher risk of anxiety and depression symptoms. • Major traditional risk factors, such as general or poor health status and always drinking alcohol, were found still to be the dominant factors associating with the increased risk of anxiety and depression symptoms. • Approximately 67.3% and 26.8% of workers reported demand for psychological education and interventions, respectively., Background COVID-19 has gained intense attention globally. However, little is known about the COVID-19-ralated mental health status among workers. Methods The cross-sectional online survey with 123,768 workers was conducted from February 2, 2020 to February 7, 2020 on a mega-size labor-intensive factory in Shenzhen, China. Oral consent was obtained prior to the questionnaire survey. The information collected in the survey included demographic characteristics, psychological symptoms, COVID-19-related information, and demands for psychological education and interventions. Symptoms of anxiety and depression were measured by the Zung's Self-Rating Anxiety Scale and Self-Rating Depression Scale. Logistic regression models were performed to determine the association between related factors and mental health status. Results The prevalence of anxiety and depression symptoms was 3.4% and 22.8%, respectively. The dominant epidemic-related factors were having confirmed cases in the community (odds ratio [OR], 2.75, 95% CI, 2.37–3.19) and having confirmed friends (OR, 2.44; 95% CI, 1.69–3.52) for the increased risk of anxiety and depression symptoms, respectively. Nevertheless, major traditional risk factors such as general or poor health status and always drinking alcohol were still the dominant factors associated with the increased risk of anxiety and depression symptoms. Overall, 67.3% and 26.8% workers reported desire for psychological education and interventions, respectively. Limitations All assessments were self-reported, resulting in a risk of method bias. Conclusions Our findings show a relatively low prevalence of anxiety symptoms, a relatively high prevalence of depression symptoms, and urgent demand for psychological education and interventions among workers during the COVID-19 outbreak.

Manipulating on-chip optical modes via components in analogy with free-space devices provides intuitional light control, and this concept has been adopted to implement single-lens–assisted spot size conversion using integrated device. However, the reported schemes have been demonstrated only for fundamental mode, while high-order or irregular modes are preferred in specific applications. The 4-f system is widely used in Fourier optics for optical information processing. Under the inspiration of the 4-f system and the beam expander in bulk optics, a spot size converter (SSC) with two metamaterial-based graded-index waveguides is proposed and demonstrated. The proposed device is capable of widening an arbitrary mode while preserving its profile shape. Compared with conventional SSC using adiabatic taper, the footprint can be reduced by 91.5% under a same intermode crosstalk. Experimentally, an expansion ratio of five is demonstrated for regular modes. Furthermore, for an irregular mode, the functionality is numerically verified without structure modification. This work offers a universal solution to on-chip spot size conversion and may broaden the on-chip application prospects of Fourier optics.

On-chip optical interconnect has been widely accepted as a promising technology to realize future large-scale multiprocessors. Mode-division multiplexing (MDM) provides a new degree of freedom for ...

Background Complete non-perfusion of the anterior segment vasculature during cataract phacoemulsification surgery is rarely reported. Case presentation We present two cases of transient ocular surface non-perfusion (TOSN) during cataract phacoemulsification surgery. The TOSN happened during intraocular lens (IOL) implantation with complete vanish of blood flow in the conjunctival, episcleral and limbal vessels. Reperfusion started within 30 s and part of the blood supply of the conjunctiva and episclera was restored within 2 min. However, the blood flow in the limbal vessels was not restored until 5 min later. The postoperative examination of both eyes was normal. These two rare cases are the TOSN during cataract surgery. We speculated that the significantly increased intraocular pressure during IOL implantation might be the cause of this rare phenomenon. Conclusion Non-perfusion of the ocular structures may occur if the IOP peak during IOL injection exceeds the perfusion pressure of the anterior vasculature.

Aim There is a growing appreciation that subthreshold but clinically elevated levels of autistic traits are clinically relevant. This study examined autistic traits in Singaporean patients with first‐episode psychosis and their association with 1‐year psychosis recovery. Methods The relationship between baseline patient characteristics, autistic traits (measured with autism screening questionnaires) and psychosis recovery outcomes at 1‐year were examined in 180 adults in the Early Intervention Psychosis Programme in Singapore. Results Out of 180 participants, 50 (27.8%) had clinically elevated above screening‐cut off levels of autistic traits on the self‐reported 10‐item Autism Spectrum Quotient and 8 (4.4%) on the staff‐rated Autism Spectrum Disorder in Adults Screening Questionnaire. At baseline, those with more autistic traits were more likely to be unemployed, economically inactive (ie, students or homemakers); and to have diagnoses of mood disorder with psychotic features, brief psychotic disorder or psychotic disorder not otherwise specified as compared to schizophrenia spectrum and delusional disorder diagnoses. Although most participants showed improvements in their clinical outcomes at 1‐year, those with higher autistic traits improved less in the Positive and Negative Syndrome Scale general psychopathology scale and in Global Assessment of Functioning symptomatology. Conclusions Autistic traits are common in those with first‐episode psychosis and may be associated with poorer clinical outcomes. Validated screening tools should be developed in this population to support earlier reporting.

As a special outcome of urbanization, mega-towns not only play an important role in the process of socio-economic development, but also are important contributors to urbanization. Based on a spatial database of mega-towns in China, this paper explores the spatial distribution features and growth mechanisms of China’s 238 mega-towns using the nearest neighbour distance method, kernel density estimation, regression analysis, global autocorrelation, local autocorrelation and other spatial analysis methods. Results of spatial distribution features show that: (1) on the national scale, the existing 238 mega-towns mainly gathered in the southeast coastal areas of China; they formed two spatial core agglomerations, several secondary ones and a southeast coastal agglomeration belt; (2) on the regional scale, each economic region’s index was less than 1, indicating that mega-towns in each region tended to be spatially agglomerated due to the close relationship with regional development level and their number; (3) on the provincial scale, 68% of provincial-level units in China tended to be a spatial agglomeration of mega-towns; only one province had a random distribution; the number of mega-towns in those evenly-distributed provinces was generally small. The growth of mega-towns was determined by a combination of various natural and humanistic factors, including topography, location, economy, population, traffic, and national policy. This paper chose digital elevation model (DEM), location advantage, economic density, population density, and highway density distribution as corresponding indicators as quantitative factors. By combining their local autocorrelation analysis, these factors all showed certain influence on the spatial growth of mega-towns and together scheduled it. In the future, provinces and cities should make full use of the mega-town functions to promote their socioeconomic development, especially the central and western regions in China.

The aim of this study was to investigate the correlations between serum calcium and clinical outcomes in patients with coronavirus disease 2019 (COVID-19). In this retrospective study, serum calcium levels, hormone levels and clinical laboratory parameters on admission were recorded. The clinical outcome variables were also recorded. From February 10 to February 28, 2020, 241 patients were enrolled. Of these patients, 180 (74.7%) had hypocalcemia on admission. The median serum calcium levels were 2.12 (IQR, 2.04-2.20) mmol/L, median parathyroid hormone (PTH) levels were 55.27 (IQR, 42.73-73.15) pg/mL, and median 25-hydroxy-vitamin D (VD) levels were 10.20 (IQR, 8.20-12.65) ng/mL. The serum calcium levels were significantly positively correlated with VD levels (P =0.004) but negatively correlated with PTH levels (P =0.048). Patients with lower serum calcium levels (especially ≤2.0 mmol/L) had worse clinical parameters, higher incidences of organ injury and septic shock, and higher 28-day mortality. The areas under the receiver operating characteristic curves of multiple organ dysfunction syndrome, septic shock, and 28-day mortality were 0.923 (P

Background and Aims. Computed tomography portal venography (CTPV) shows potential in detecting varices that need treatment and their drainage pathways. However, its agreement with endoscopy requires further study. We investigated the feasibility of CTPV as an alternative tool to endoscopy in screening gastroesophageal varices (GEVs) and developed a CTPV-based model to provide a less invasive assessment of endotherapy for cirrhotic patients with GEVs. Methods. The study included 33 cirrhotic patients with a recent history of variceal hemorrhage. The presence, grade, and classification of GEVs on endoscopy and CTPV were compared (kappa test). Twenty-four patients were treated endoscopically, including 12 for esophageal varices (EVs), 8 for gastric varices (GVs), and 4 for GEVs. Treatment efficacies were assessed with the newly developed CTPV-based method at 1 week and 1 month after treatment. Efficiency evaluated by CTPV and endoscopy was compared by Fisher’s exact test to determine whether CTPV is efficient in the assessment of endotherapy efficacy. Results. For the screening and grading/classification of EVs and GVs, substantial agreement (EV kappa: 0.63 and 0.68; GV kappa: 0.62 and 0.75, respectively) was noted between endoscopy and CTPV. The therapeutic efficacy of EVs was higher when assessed by CTPV than when evaluated by endoscopy (37.50% vs. 12.50% at 1 week postoperation, P=0.22; 62.50% vs. 25.00% at 1 month postoperation, P=0.07), but without statistical significance. The same trend was also found in the assessment of therapeutic efficacy for GVs (25.00% vs. 16.67% at 1 week postoperation, P=1; 58.33% vs. 41.67% at 1 month postoperation, P=0.68). Conclusion. CTPV is comparable to endoscopy in the detection of GEVs and in the evaluation of endotherapy efficacy, which suggests that it could be a less invasive alternative for endoscopy in cirrhotic patients with GEVs needing treatment.

Firms in China within the same industry but with different ownership and size have different production functions and face different emission regulations and financial conditions, thus can give very different responses to environmental policies. This fact has been largely ignored in most of the low-carbon development related literature. Using an augmented Chinese input–output table in which information about firm size (large- and small and medium-sized firms) and ownership (state-, foreign-, and private-owned firms) are explicitly reported, a dynamic computable general equilibrium model is developed in this study to analyze the impact of alternative low-carbon policy designs with different regulatory coverage and financial equalization on heterogeneous firms. Our simulation results show that, with the fully balanced regulation coverage and equalized financial system for heterogeneous firms, the total green investment accounts for 4% of GDP in 2030 for fulfilling China's commitment to reduce carbon emissions, which is the lowest among the various scenarios; about one-third of this investment is made by small and private firms; at the same time, green investment efficiency will be the highest, about 84% higher than that of the business-as-usual level. Therefore, a market-oriented and new technology-driven arrangement and mechanism for sharing emission reduction burden and allocating green investment across heterogeneous firms, especially to small and medium-sized firms, is crucial for China to achieve a more ambitious emission target in the long run.

The weighted visual cryptographic scheme (WVCS) allows the dealer to assign a weight to every shadow (participant) according to the participant’s importance so that the ability of each shadow to reveal a secret image can be varied. However, the previous weighted random grid-based VCS (WRGVCS) has the shortcoming of low visual quality. The contribution of this paper is that a new WRGVCS for a (k, n) threshold is designed to improve the image quality of the revealed secret image and to realize more features. RG is utilized to achieve the features of no pixel expansion and no codebook design. The probability of covering the valid bits is improved to improve the image quality. Experimental results and security analyses indicate the effectiveness of the designed scheme. Contrast and feature comparisons with previous weighted VCS approaches exhibit improvements in the designed scheme over other relative weighted VCSs. The limitations of our work are that the weighted effect decreases for some thresholds, and the theoretical contrast of the designed scheme is not derived directly by the parameters.

This paper presents a framework to detect salient objects from natural images through simulating human perception. We think perception saturation, generated by microsaccades in gaze, is the primary reason why human brains export consciousness of salient objects. Perception saturation is represented by using amplitude of microsaccades (AOM). When the AOM or changes of the AOM tend to zero, human perception becomes saturated. Motivated by this analysis, we construct a group of learning-based models to detect a salient object in a coarse-to-fine sequence. Firstly, a small image is selected to minimize the AOM so as to saturate the perception. Then, neural networks with random weights (NNRW) are chosen to simulate the received visual stimuli. In order to examine the changes of AOM, a positive feedback loop is constructed which executes the procedure of “pixel sampling-learning classification” iteratively. The final fixation area after iterations is regarded as a salient object. The proposed algorithm is based on unsupervised learning and data-driven completely. Our results based on open image datasets show that the proposed method achieves better performance compared to those existing unsupervised algorithms.

ObjectivesTo evaluate the associations of regular glucosamine use with all-cause and cause-specific mortality in a large prospective cohort.MethodsThis population-based prospective cohort study included 495 077 women and men (mean (SD) age, 56.6 (8.1) years) from the UK Biobank study. Participants were recruited from 2006 to 2010 and were followed up through 2018. We evaluated all-cause mortality and mortality due to cardiovascular disease (CVD), cancer, respiratory and digestive disease. HRs and 95% CIs for all-cause and cause-specific mortality were calculated using Cox proportional hazards models with adjustment for potential confounding variables.ResultsAt baseline, 19.1% of the participants reported regular use of glucosamine supplements. During a median follow-up of 8.9 years (IQR 8.3–9.7 years), 19 882 all-cause deaths were recorded, including 3802 CVD deaths, 8090 cancer deaths, 3380 respiratory disease deaths and 1061 digestive disease deaths. In multivariable adjusted analyses, the HRs associated with glucosamine use were 0.85 (95% CI 0.82 to 0.89) for all-cause mortality, 0.82 (95% CI 0.74 to 0.90) for CVD mortality, 0.94 (95% CI 0.88 to 0.99) for cancer mortality, 0.73 (95% CI 0.66 to 0.81) for respiratory mortality and 0.74 (95% CI 0.62 to 0.90) for digestive mortality. The inverse associations of glucosamine use with all-cause mortality seemed to be somewhat stronger among current than non-current smokers (p for interaction=0.00080).ConclusionsRegular glucosamine supplementation was associated with lower mortality due to all causes, cancer, CVD, respiratory and digestive diseases.

Current cancer immunotherapy has limited response rates in a large variety of solid tumors partly due to the low immunogenicity of the tumor cells and the immunosuppressive tumor microenvironment (ITM). A number of clinical cancer treatment modalities, including radiotherapy, chemotherapy, photothermal and photodynamic therapy, have been shown to elicit immunogenicity by inducing immunogenic cell death (ICD). However, ICD-based immunotherapy is restricted by the ITM limiting its efficacy in eliciting a long-term antitumor immune response, and by severe systemic toxicity. To address these challenges, nanomedicine-based drug delivery strategies have been exploited for improving cancer immunotherapy by boosting ICD of the tumor cells. Nanosized drug delivery systems are promising for increasing drug accumulation at the tumor site and codelivering ICD inducers and immune inhibitors to simultaneously elicit the immune response and relieve the ITM. This review highlights the recent advances in nanomedicine-based immunotherapy utilizing ICD-based approaches. A perspective on the clinical translation of nanomedicine-based cancer immunotherapy is also provided.

Background The effect of bariatric surgery on improvement and remission of type 2 diabetes (T2D) is well studied. The effect of surgery on glycemic profiles of obese, but nondiabetic individuals is unknown. Objectives We aimed to study changes in glycemic indices in obese nondiabetics undergoing bariatric surgery and correlate fat mass loss with changes in glycemic profiles. Setting University Hospital, Singapore. Methods A prospective database of nonT2D patients who underwent bariatric surgery between April 2009 and December 2014 was analyzed. Changes in weight, fat mass, and glycemic profiles, including glycated hemoglobin, C-peptide levels, and the homeostasis model assessment of insulin resistance were studied at 1- and 3-year follow-up. Results One hundred thirty-three nondiabetics underwent bariatric surgery in the study period. Twenty-nine (21.8%) patients were found to have impaired fasting glycemia. We observed reductions in mean fat mass from 47.4 ± 12.2 kg preoperatively to 27.8 ± 11.6 kg at 1 year. Despite mean fat mass regain to 33.9 ± 19.6 kg at 3 years, homeostasis model assessment of insulin resistance improved from severe insulin resistant state of >5.00 (7.13 ± 11.5) preoperatively to normal ranges of Conclusion Bariatric surgery results in significant sustained weight loss in obese nondiabetics and normalizes glycated hemoglobin and homeostasis model assessment of insulin resistance after surgery. It is a promising modality to prevent or delay the onset of T2D in obese nondiabetic patients. Further studies should be conducted in nondiabetics to assess the efficacy of bariatric surgery in prevention of T2D onset in the longer term.

Distiller's grain (DG), by-product of the Chinese alcohol industry, which can be used as a renewable organic waste resource for bio-fuel through pyrolysis. However, amino acids and protein are the main component of DG, and have obvious effects on its pyrolysis. In this study, the properties of DG and extracted DG (EDG) and their pyrolysis behaviors were compared in the temperature range from 50-900 oC. 3D-FTIR revealed that the main gaseous products of DG were CO2, CH4, ketones, aldehydes, acids and amines, and that the deamination of amino acids and protein was inhibited by lignocellulosic components during DG during pyrolysis. The TG/DTG results showed that DG could be pyrolyzed at a lower temperature, and the absolute value of maximum DTG loss rate was 6 %/min, higher than that of EDG. The distributed activation energy model (DAEM) was used to analyze the kinetic behaviors of DG and EDG. Meanwhile, the Flynn-Wall-Ozawa (FWO) method was also used to confirm the results of DAEM, and the results proved th...