A novel multidisciplinary machine learning approach based on clinical, imaging, colonoscopy, and pathology features for distinguishing intestinal tuberculosis from Crohn's disease.

OBJECTIVES: Differentiating intestinal tuberculosis (ITB) from Crohn's disease (CD) remains a diagnostic dilemma. Misdiagnosis carries potential grave implications. We aim to establish a multidisciplinary-based model using machine learning approach for distinguishing ITB from CD. METHODS: Eighty-two patients including 25 patients with ITB and 57 patients with CD were retrospectively recruited (54 in training cohort and 28 in testing cohort). The region of interest (ROI) for the lesion was delineated on magnetic resonance enterography (MRE) and colonoscopy images. Radiomic features were extracted by least absolute shrinkage and selection operator regression. Pathological feature was extracted automatically by deep-learning method. Clinical features were filtered by logistic regression analysis. Diagnostic performance was evaluated by receiver operating characteristic (ROC) curve and decision curve analysis (DCA). Delong's test was applied to compare the efficiency between the multidisciplinary-based model and the other four single-disciplinary-based models. RESULTS: The radiomics model based on MRE features yielded an AUC of 0.87 (95% confidence interval [CI] 0.68-0.96) on the test data set, which was similar to the clinical model (AUC, 0.90 [95% CI 0.71-0.98]) and higher than the colonoscopy radiomics model (AUC, 0.68 [95% CI 0.48-0.84]) and pathology deep-learning model (AUC, 0.70 [95% CI 0.49-0.85]). Multidisciplinary model, integrating 3 clinical, 21 MRE radiomic, 5 colonoscopy radiomic, and 4 pathology deep-learning features, could significantly improve the diagnostic performance (AUC of 0.94, 95% CI 0.78-1.00) on the bases of single-disciplinary-based models. DCA confirmed the clinical utility. CONCLUSIONS: Multidisciplinary-based model integrating clinical, MRE, colonoscopy, and pathology features was useful in distinguishing ITB from CD.

CT-based radiomics signature of visceral adipose tissue and bowel lesions for identifying patients with Crohn's disease resistant to infliximab.

PURPOSE: To develop a CT-based radiomics model combining with VAT and bowel features to improve the predictive efficacy of IFX therapy on the basis of bowel model. METHODS: This retrospective study included 231 CD patients (training cohort, n = 112; internal validation cohort, n = 48; external validation cohort, n = 71) from two tertiary centers. Machine-learning VAT model and bowel model were developed separately to identify CD patients with primary nonresponse to IFX. A comprehensive model incorporating VAT and bowel radiomics features was further established to verify whether CT features extracted from VAT would improve the predictive efficacy of bowel model. Area under the curve (AUC) and decision curve analysis were used to compare the prediction performance. Clinical utility was assessed by integrated differentiation improvement (IDI). RESULTS: VAT model and bowel model exhibited comparable performance for identifying patients with primary nonresponse in both internal (AUC: VAT model vs bowel model, 0.737 (95% CI, 0.590-0.854) vs. 0.832 (95% CI, 0.750-0.896)) and external validation cohort [AUC: VAT model vs. bowel model, 0.714 (95% CI, 0.595-0.815) vs. 0.799 (95% CI, 0.687-0.885)), exhibiting a relatively good net benefit. The comprehensive model incorporating VAT into bowel model yielded a satisfactory predictive efficacy in both internal (AUC, 0.840 (95% CI, 0.706-0.930)) and external validation cohort (AUC, 0.833 (95% CI, 0.726-0.911)), significantly better than bowel alone (IDI = 4.2% and 3.7% in internal and external validation cohorts, both p < 0.05). CONCLUSION: VAT has an effect on IFX treatment response. It improves the performance for identification of CD patients at high risk of primary nonresponse to IFX therapy with selected features from RM. CRITICAL RELEVANCE STATEMENT: Our radiomics model (RM) for VAT-bowel analysis captured the pathophysiological changes occurring in VAT and whole bowel lesion, which could help to identify CD patients who would not response to infliximab at the beginning of therapy. KEY POINTS: • Radiomics signatures with VAT and bowel alone or in combination predicting infliximab efficacy. • VAT features contribute to the prediction of IFX treatment efficacy. • Comprehensive model improved the performance compared with the bowel model alone.

3D printed Si-CaP scaffold released SiO32- and Ca2+ to synergistically promote angiogenesis.

BACKGROUND AND PURPOSE: Structuring scaffold with both osteogenic and angiogenesis capabilities is a challenge for bone tissue engineering. Powder structured Si-CaP materials have shown excellent osteogenic properties and induction of stem cell differentiation. Our research group have successful produced 3D printed Si-CaP scaffolds by DLP technology. This study aims to explore the angiogenic effects of SiO32- and Ca2+ released by 3D printed Si-CaP scaffold, and whether there is a synergistic effect between the two ions. METHODS: The 3D printed Si-CaP scaffolds were immersed in endothelial cell medium solution for 24 h. The Si, Ca ion released was detected by Inductively coupled plasma-optical emission spectrometry. We used detected data as a standard to prepare the simulated solution to investigate the effect of SiO32-, Ca2+ separately. Experiment was divided into control group, Si ion group, Ca ion group and Si + Ca ion group. We evaluated different ionic effect on HUVECs viability, proliferation, migration, gene expression, and tube formation on different groups. RESULTS: The concentration of SiO32- was detected as 15.71 ± 0.04 µg/mL, Ca2+ as 67.14 ± 0.95 µg/mL. Na2SiO3 and CaCl2 were used to prepare the simulated solution. There were no statistically difference between simulated solution from ion released by scaffold. Si + Ca group promoted the gene expression significantly compared with the control group, p < .01. Expression of vascular-associated protein in Si + Ca ion group was higher than that in Si ion group, Ca ion group and control group. Si + Ca ion group significantly enhanced endothelial cell on migration and tube formation assay. CONCLUSION: The 3D printed Si-CaP scaffold can release effective physiological concentrations of Si, Ca ions. Si and Ca ions have a synergistic effect on promoting angiogenesis of HUVECs. 3D printed Si-CaP scaffold is promising in vascularized bone tissue engineering application.

Factors related to the mortality risk of severe hand, foot, and mouth diseases (HFMD): a 5-year hospital-based survey in Guangxi, Southern China.

BACKGROUND: To understand the factors influencing clinical outcomes of severe hand, foot, and mouth diseases (HFMD), and to provide scientific evidence for reducing the mortality risk of severe HFMD. METHODS: From 2014 to 2018, children diagnosed with severe HFMD cases in Guangxi, China, were enrolled in this hospital-based study. The epidemiological data obtained through face-to-face interviews with the parents and guardians. Univariate and multivariate logistics regression models were used to analyze the factors influencing the clinical outcomes of severe HFMD. The impact of the EV-A71 vaccination on inpatient mortality was analyzed by a comparison approach. RESULTS: A total of 1565 severe HFMD cases were enrolled in this survey, including 1474 (94.19%) survival cases and 91 (5.81%) death cases. The multivariate logistic analysis demonstrated that HFMD history of playmates in the last three months, first visit to the village hospital, time from the first visit to admission less than two days, no correct diagnosis for HFMD at the first visit, and having no rash symptoms were the independent risk factors for severe HFMD cases (all p < 0.05). While EV-A71 vaccination was a protective factor (p < 0.05). The EV-A71 vaccination group versus the non-vaccination group showed 2.23% of death in the vaccination group and 7.24% of death in the non-vaccination group. The EV-A71 vaccination protected 70.80% of the death of severe HFMD cases, with an effective index of 4.79. CONCLUSIONS: The mortality risk of severe HFMD in Guangxi was related to playmates had HFMD history in last 3 months, hospital grade, EV-A71 vaccination, patients visit hospital previously, and rash symptom. EV-A71 vaccination can significantly reduce mortality among severe HFMD. The findings are of great significance for the effective prevention and control of HFMD in Guangxi, southern China.

H-Shaped Radial Phononic Crystal for High-Quality Factor on Lamb Wave Resonators.

In this paper, a novel H-shaped radial phononic crystal (H-RPC) structure is proposed to suppress the anchor loss of a Lamb wave resonator (LWR), which has an ultra-high frequency (UHF) and ultra-wideband gap characteristics. Compared to previous studies on phononic crystal (PC) structures aimed at suppressing anchor loss, the radial phononic crystal (RPC) structure is more suitable for suppressing the anchor loss of the LWR. By using the finite element method, through the research and analysis of the complex energy band and frequency response, it is found that the elastic wave can generate an ultra-wideband gap with a relative bandwidth of up to 80.2% in the UHF range when propagating in the H-RPC structure. Furthermore, the influence of geometric parameters on the ultra-wideband gap is analyzed. Then, the H-RPC structure is introduced into the LWR. Through the analysis of the resonant frequency, it is found that the LWR formed by the H-RPC structure can effectively reduce the vibration energy radiated by the anchor point. The anchor quality factor was increased by 505,560.4% compared with the conventional LWR. In addition, the analysis of the LWR under load shows that the LWR with the H-RPC structure can increase the load quality factor by 249.9% and reduce the insertion loss by 93.1%, while the electromechanical coupling coefficient is less affected.

Q-Factor Enhancement of Coupling Bragg and Local Resonance Band Gaps in Single-Phase Phononic Crystals for TPOS MEMS Resonator.

This paper presents a type of single-phase double "I" hole phononic crystal (DIH-PnC) structure, which is formed by vertically intersecting double "I" holes. By using the finite element method, the complex energy band curve, special point mode shapes, and different delay lines were calculated. Numerical results showed that DIH-PnC yielded ultra-wide band gaps with strong attenuation. The formation mechanism is attributed to the Bragg-coupled local resonance mechanism. The effects of the pore width in DIH-PnC on the band gaps were further explored numerically. Significantly, as the pore width variable, the position of the local resonance natural frequency could be modulated, and this enabled the coupling between the local resonance and the Bragg mechanism. Subsequently, we introduced this DIH-PnC into the thin-film piezoelectric-on-silicon (TPOS) resonator. The results illustrated that the anchor loss quality factor (Qanc) of the DIH-PnC resonator was 20,425.1% higher than that of the conventional resonator and 3762.3% higher than the Qanc of the cross-like holey PnC resonator. In addition, the effect of periodic array numbers on Qanc was researched. When the Qanc reached 1.12 × 106, the number of the period array in DIH-PnC only needed to be 1/6 compared with cross-like holey PnC. Adopting the PnC based on the coupling Bragg and local resonance band gaps had a good effect on improving the Qanc of the resonator.

Fabrication and in vitro evaluation of 3D printed porous silicate substituted calcium phosphate scaffolds for bone tissue engineering.

Silicate-substituted calcium phosphate (Si-CaP) ceramics, alternative materials for autogenous bone grafting, exhibit excellent osteoinductivity, osteoconductivity, biocompatibility, and biodegradability; thus, they have been widely used for treating bone defects. However, the limited control over the spatial structure and weak mechanical properties of conventional Si-CaP ceramics hinder their wide application. Here, we used digital light processing (DLP) printing technology to fabricate a novel porous 3D printed Si-CaP scaffold to enhance the scaffold properties. Scanning electron microscopy, compression tests, and computational fluid dynamics simulations of the 3D printed Si-CaP scaffolds revealed a uniform spatial structure, appropriate mechanical properties, and effective interior permeability. Furthermore, compared to Si-CaP groups, 3D printed Si-CaP groups exhibited sustained release of silicon (Si), calcium (Ca), and phosphorus (P) ions. Furthermore, 3D printed Si-CaP groups had more comprehensive and persistent osteogenic effects due to increased osteogenic factor expression and calcium deposition. Our results show that the 3D printed Si-CaP scaffold successfully improved bone marrow mesenchymal stem cells (BMSCs) adhesion, proliferation, and osteogenic differentiation and possessed a distinct apatite mineralization ability. Overall, with the help of DLP printing technology, Si-CaP ceramic materials facilitate the fabrication of ideal bone tissue engineering scaffolds with essential elements, providing a promising approach for bone regeneration.

Synthesis of PVDF membrane loaded with wrinkled Au NPs for sensitive detection of R6G.

A novel SERS membrane is synthesized by combining metal lattice and surface enhanced Raman scattering (SERS) technology. Since R6G is a carcinogenic and harmful pollutant, and traditional detection methods have many drawbacks and have research value, this paper selects R6G as the detection target. The SERS substrates are synthesized by loading Au nanoparticles (Au NPs) on the surface of polyvinylidene fluoride (PVDF) membrane. The Au NPs are synthesized through a controllable hydrothermal method. The synthesized AuNPs are covered by some gold particles, forming a fold pattern. Finally, the synthesized structure is immobilized on the surface of the PVDF membrane by the phase inversion method. It is suggested that the prepared Au NPs@PVDF membrane exhibits adjustable cavity structure, strong plasmon coupling, tunable magnetic plasmon resonance, prominent SERS performances. The prepared Au NPs@PVDF membrane showed sensitive SERS activity, good mechanical strength and reusability, expanding the application field of SERS detection. Overall, this study establishes a novel technique for the synthesis of SERS membrane with excellent SERS property and expands the application field of SERS detection.

Epidemiology of influenza virus reinfection in Guangxi, China: a retrospective analysis of a nine-year influenza surveillance data: Characteristics of influenza virus reinfection.

BACKGROUND: Epidemiological characteristic profile of the reinfection of the influenza virus has not been well described. METHODS: This study included all influenza cases of Guangxi, China from January 2011-December 2019 that were recorded in the National Notifiable Infectious Disease Reporting Information System (NIDRIS) within 24 hours after diagnosis. RESULTS: A total of 53,605.6 person-months and the median time of 8.7 months were observed for reinfection. The median age at the first influenza virus infection was 4.5 (interquartile range=2.0-7.5) years. The cumulative reinfection incidence was 2% at 6 months, 4% at 12 months, 5% at 24 months, and 7% after 59 months. Living in the rural area (hazard ratio [HR]=1.37 [95% confidence interval (CI), 1.29-1.45]), age ≤6 years (HR=11.43 [95% CI, 9.47-13.80]) were independent risk factors associated with influenza reinfection. Among 49 patients experiencing two laboratory tests, 32 patients (65.3%) were found to be infected with different virus types. The interval between two consecutive laboratory-confirmed episodes of the four groups differed (p=0.148): the maximum was 72.9 months and the minimum was 1.2 months. CONCLUSIONS: The reinfection of the influenza virus in Guangxi was independently and positively associated with living the rural area and younger age. The unusually high frequency of reinfection points to a need for further prospective longitudinal studies to better investigate the sufficient impact on different subtypes.

Modal dynamics in multimode optical fibers: an attractor of high-order modes.

Multimode fibers (MMFs) support abundant spatial modes and involve rich spatiotemporal dynamics, yielding many promising applications. Here, we investigate the influences of the number and initial energy of high-order modes (HOMs) on the energy flow from the intermediate modes (IMs) to the fundamental mode (FM) and HOMs. It is quite surprising that random distribution of high-order modes evolves to a stationary one, indicating the asymptotic behavior of orbits in the same attraction domain. By employing the Lyapunov exponent, we prove that the threshold of the HOMs-attractor is consistent with the transition point of the energy flow which indicates the HOMs-attracotr acts as a "valve" in the modal energy flow. Our results provide a new perspective to explore the nonlinear phenomena in MMFs, such as Kerr self-cleaning, and may pave the way to some potential applications, such as secure communications in MMFs.

The changes in the epidemiology of hand, foot, and mouth disease after the introduction of the EV-A71 vaccine.

Three inactive monovalent EV-A71 vaccines have been launched in China since 2016, which may change the HFMD pathogen spectrum and epidemiological trend. Using notifications from the national surveillance system, we analyzed the epidemiological character profiles and the possible pathogen replacement. The proportion of HFMD cases aged 0-12 months decreased from 23.0% to 15.3% between 2013-2015 and 2017-2019 (p < 0.01). EV-A71 among laboratory-confirmed severe cases in 2013-2015 (62.8%) transformed to other EVs (67.2%) in 2017-2019. The age distribution of EV-A71 infection shifted to the older. The cumulative coverage of the EV-A71 vaccine for children aged six months to five years in Guangxi has increased, while in severe cases, the positive rate declined. After gradually expanded vaccination, EV-A71 associated incidence rate, case-severity rate has decreased, and other serotypes are becoming dominant. Thus, bivalent even polyvalent vaccines are urgently needed to control HFMD.

Modal perspective on geometric parametric instability sidebands in graded-index multimode fibers.

In this paper, we investigated the geometric parametric instability (GPI) in graded-index multimode fibers through the multimode generalized nonlinear Schrödinger equation. Our results clearly and intuitively indicate that the generations of GPI sidebands are nearly synchronous in the spectrums of all modes, and the shapes of these spectrums are nearly the same. The numerical results show that the energies of the GPI sidebands come from the pump sideband, and these sidebands are carried by similar spatial beam profiles due to the similar modal components. We also found that the large modal dispersion has an influence for the symmetry of these GPI sidebands.

Effectiveness of enterovirus A71 vaccine in severe hand, foot, and mouth disease cases in Guangxi, China.

BACKGROUND: Hand, foot, and mouth disease (HFMD) caused by enterovirus A71 (EV-A71) is a major public health issue in China that poses severe risks to children's health, especially those under the age of 3. Since 2016, EV71 vaccines developed by three Chinese manufacturers have been approved for use, and clinical trials of these vaccines have demonstrated protection against EV-A71 infection. However, few studies have assessed the effectiveness of these vaccines in real-world settings. METHODS: A test-negative design case-control study was used to estimate vaccine effectiveness (VE) in cases of severe HFMD. We obtained information including EV-A71 vaccination status from the Local Center for Disease Control and Prevention (CDC) on all severe HFMD cases under 12 years in age in Guangxi, China, from Jan. 1, 2017, to Dec. 31, 2018. Enterovirus infection was laboratory confirmed by local CDCs. Individuals with a positive EV-A71 nucleic acid test result were assigned to the case group, and those with negative EV-A71 nucleic acid test results were assigned to the control group. We estimated VE using logistic regression. RESULTS: A total of 2779 severe HFMD cases were enrolled in the study; 838 children were EV-A71 positive cases, and 1941 children were EV-A71 negative controls. The proportion of EV-A71 positive cases aged 6-36 months was lower than that for EV-A71 negative controls. EV-A71 infection was associated with an increased risk of mortality (aOR, 8.8; 95% CI, 1.3-61.6). The adjusted VE was 81.4% and 88.3% for one dose and two doses, respectively. CONCLUSION: Our findings suggest that the rate of EV-A71 has fallen among severe HFMD cases in Guangxi and that the risk for EV-A71 infection in 6-36-month-old children has been reduced by use of the vaccine. Inactivated vaccines performed well in severe HFMD cases in a real-world setting.

Identification of human serum protein targets of Qianggu Decoction () in primary type I osteoporosis based on tandem mass tag labeling and liquid chromatography-tandem mass spectrometry technology.

OBJECTIVE: To investigate the serum protein targets of Qianggu Decoction (, QGD) on treating osteoporosis by the proteomics analysis using tandem mass tag (TMT) and liquid chromatographytandem mass spectrometry (LC-MS/MS). METHODS: Twenty serum protein samples were recruited (10 patients with primary type I osteoporosis before and after QGD treatment) and the high abundance ratios protein was removed, two serum samples were extracted and labeled with TMT reagent. Then, mass spectrometric detection, identification of differentially expressed proteins and bioinformatics analysis of differentially expressed proteins were carried out. RESULTS: A total of 60 proteins were identified, within a 99% confidence interval, to be differentially regulated of which, 34 proteins were up-regulated and 26 proteins were down-regulated. Differentially expressed proteins analyzed by Gene Ontology (GO) annotation mainly get involved in 12 different biological processes, 7 types of cellular components, and 6 kinds of molecular functions. Angiotensinogen (AGT), stromelysin-1 (MMP3), heparanase (HPSE) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were screened as candidate protein targets of QGD treatment, which were related to metabolic mechanism of bone remodeling and/or bone collagen of osteoporosis. By the utilization of the protein-protein interaction network analysis tool named STRING10.0, it showed that AGT, MMP3, HPSE and GAPDH were located in the key node of the protein-protein interactions network. Furthermore, AGT, MMP3, HPSE and GAPDH were found to be directly related to BMP, MAPK, Wnt, SMAD and tumor necrosis factor ligand superfamily member 11 (TNFSF11) families. CONCLUSIONS: The proteomics analysis by using TMT combined with LC-MS/MS was a feasible method for screening the potential therapeutic targets associated with QGD treatment. It suggests that AGT, MMP3, HPSE and GAPDH may be candidate protein targets of QGD treatment which can be used as therapeutic effect monitor and early diagnosis of primary type I osteoporosis.

Weak cation exchange magnetic beads coupled with matrix-assisted laser desorption ionization-time of flight-mass spectrometry in screening serum protein markers in osteopenia.

The present study aimed at investigating the weak cation magnetic separation technology and matrix-assisted laser desorption ionization-time of flight-mass spectrometry (MALDI-TOF-MS) in screening serum protein markers of osteopenia from ten postmenopausal women and ten postmenopausal women without osteopenia as control group, to find a new method for screening biomarkers and establishing a diagnostic model for primary type I osteoporosis. Serum samples were collected from postmenopausal women with osteopenia and postmenopausal women with normal bone mass. Proteins were extracted from serum samples by weak cation exchange magnetic beads technology, and mass spectra acquisition was done by MALDI-TOF-MS. The visualization and comparison of data sets, statistical peak evaluation, model recognition, and discovery of biomarker candidates were handled by the proteinchip data analysis system software(ZJU-PDAS). The diagnostic models were established using genetic arithmetic based support vector machine (SVM). The SVM result with the highest Youden Index was selected as the model. Combinatorial Peaks having the highest accuracy in distinguishing different samples were selected as potential biomarker. From the two group serum samples, a total of 133 differential features were selected. Ten features with significant intensity differences were screened. In the pair-wise comparisons, processing of MALDI-TOF spectra resulted in the identification of ten differential features between postmenopausal women with osteopenia and postmenopausal women with normal bone mass. The difference of features by Youden index showed that the highest features had a mass to charge ratio of 1699 and 3038 Da. A diagnosis model was established with these two peaks as the candidate marker, and the specificity of the model is 100 %, the sensitivity was 90 % by leave-one-out cross validation test. The two groups of specimens in SVM results on the scatter plot could be clearly distinguished. The peak with m/z 3038 in the SVM model was suggested as Secretin by TagIdent tool. To provide further validation, the secretin levels in serum were analyzed using enzyme-linked immunosorbent assays that is a competitive inhibition enzyme immunoassay technique for the in vitro quantitative measurement of secretin in human serum.

Carboxymethylated glucomannan as paper strengthening agent.

Strength additives play an important role in allowing the papermaking industry to achieve its objectives. In this study, a new kind of paper strengthening agent based on glucomannan was developed by treating it with sodium chloroacetate under alkaline conditions, and the effects on paper properties were evaluated. Results indicated that carboxymethylated glucomannan could significantly improve the paper properties. Compared to the untreated paper, the density, burst index, tensile index, and folding endurance were increased by 15.2%, 22.8%, 34.6%, 179.0%, respectively, when 0.9% carboxymethylated glucomannan was used. Polyamide-epichlorohydrin (PAE) was used to improve the wet strength of the paper. When 0.6% PAE and 0.6% carboxymethylated glucomannan were used, the burst index, dry tensile index, wet tensile index of paper were increased by 14.1%, 25%, 34.3%, respectively, as compared to that of the control, while the folding endurance decreased slightly. In addition, dry tensile index and wet tensile index were increased with increasing the carboxymethylation time of glucomannan. The results demonstrated that PAE and carboxymethylated glucomannan displayed a synergistic effect. SEM analysis illustrated that paper strengthening agent could increase the combination of fibers in paper.

Linking nitrifying biofilm characteristics and nitrification performance in moving-bed biofilm reactors for polluted raw water pretreatment.

Biofilm physiology was characterized by four biofilm constituents, i.e., polysaccharides, proteins (PN), humic-like substances and phospholipids (PL), for the first time to explore the relationships between biofilm characteristics and nitrification performance in moving-bed biofilm reactors (MBBRs) designed for pretreatment of polluted raw surface water for potable supply. The biofilm compositions depended highly on the balance of microbial decay and nitrification processes. The increased ammonia loading greatly regulated the community structure, promoting the dominance of nitrifiers and their proportions in the nitrifying biofilm. Nitrification rate and activity correlated linearly with the fractions of volatile solids (VS), PN and PL, which were related to nitrification processes in the biofilm. The specific biofilm activity demonstrated an exponential-asymptotic relationship with ratios of PN/VS and PL/VS. Thus, analyzing biofilm characteristics can be valid for estimating nitrification performance in MBBRs, and may offer engineers with basis to optimize MBBR design and operation.