Integrating Radiomics and Neural Networks for Knee Osteoarthritis Incidence Prediction.

OBJECTIVE: Accurately predicting knee osteoarthritis (KOA) is essential for early detection and personalized treatment. We aimed to develop and test an MRI-based Joint Space Radiomic Model (JS-RM) to predict radiographic KOA incidence through neural networks by integrating meniscus and femorotibial cartilage radiomic features. METHODS: In the Osteoarthritis Initiative cohort, knees without radiographic KOA at baseline but at high risk for radiographic KOA were included. Case knees developed radiographic KOA whereas control knees did not over 4-year. We randomly split the knees into development and test cohorts (D/T=8/2) and extracted features from baseline 3D-DESS-sequence MRI. Model performance was evaluated using an area under the receiver operating characteristic curve (AUC), sensitivity, and specificity in both cohorts. Nine resident surgeons performed the reader experiment without/with the JS-RM aid. RESULTS: Our study included 549 knees in the development cohort (275 cases vs. 274 controls) and 137 knees in the test cohort (68 cases vs. 69 controls). In the test cohort, JS-RM had a favorable accuracy for predicting the radiographic KOA incidence with an AUC of 0.931 (95%CI: 0.876-0.963), a sensitivity of 84.4% (95%CI: 83.9%-84.9%), and a specificity of 85.6% (95%CI: 85.2%-86.0%). The mean specificity and sensitivity of resident surgeons through MRI reading in predicting radiographic KOA incidence were increased from 0.474 (95%CI: 0.333-0.614) and 0.586 (95%CI: 0.429-0.743) without the assistance of JS-RM to 0.874 (95%CI: 0.847-0.901) and 0.812 (95%CI: 0.742-0.881) with JS-RM assistance, respectively (p<.001). CONCLUSION: JS-RM integrating the features of the meniscus and cartilage showed improved predictive values in radiographic KOA incidence.

The association between anterior cruciate ligament degeneration and incident knee osteoarthritis: Data from the osteoarthritis initiative.

Background: Though anterior cruciate ligament (ACL) tear has been widely accepted as an important accelerator for knee osteoarthritis (KOA), the role of intrinsic ACL degeneration in developing KOA has not been fully investigated. Purpose: To determine whether ACL degeneration, in the absence of ACL tear, is associated with incident KOA over 4 years. Study design: Cohort study; Level of evidence, 2. Methods: Participants' knees in this nested case-control study were selected from the Osteoarthritis Initiative (OAI) study, with Kellgren-Lawrence grading (Kellgren-Lawrence grading) of 0 or 1 â€‹at baseline (BL). Case knees which had incident KOA (KLG ≥2) over 4 years, were matched 1:1 with control knees by gender, age and radiographic status. ACL signal intensity alteration (0-3 scale) and volume were assessed as compositional feature and morphology of ACL degeneration, using knee MRI at P0 (time of onset of incident KOA), P-1 (1 year prior to P0) and baseline. Conditional logistic regression was applied to analyze the association between measures of ACL degeneration and incident KOA. Results: 337 case knees with incident KOA were matched to 337 control knees. Participants were mostly female (68.5%), with an average age of 59.9 years old. ACL signal intensity alterations at BL, P-1 and P0 were significantly associated with an increased odds of incident KOA respectively (all P for trend ≤0.001). In contrast, ACL volumes were not significantly associated with incident KOA at any time points. Conclusions: ACL signal intensity alteration is associated with increased incident KOA over 4 years, whereas ACL volume is not.The translational potential of this article: This paper focused on ACL signal intensity alteration which could better reflect ACL degeneration rather than ACL tear during the progression of KOA and explored this topic in a nested case-control study. Utilizing MR images from KOA participants, we extracted the imaging features of ACL. In addition, we established a semi-quantitative score for ACL signal intensity alteration and found a significant correlation between it and KOA incidence. Our findings confirmed that the more severe the ACL signal intensity alteration, the stronger relationship with the occurrence of KOA. This suggests that more emphasis should be placed on ACL degeneration rather than ACL integrity in the future.

Comprehensive analysis on subchondral bone marrow lesions of human osteoarthritis by integrating bulk and single-cell transcriptomes.

OBJECTIVE: This study aims to demonstrate the cellular composition and underlying mechanisms in subchondral bone marrow lesions (BMLs) of knee osteoarthritis (OA). METHODS: BMLs were assessed by MRI Osteoarthritis Knee Score (MOAKS)≥2. Bulk RNA-sequencing (bulk-seq) and BML-specific differentially expressed genes (DEGs) analysis were performed among subchondral bone samples (including OA-BML=3, paired OA-NBML=3; non-OA=3). The hub genes of BMLs were identified by verifying in independent datasets and multiple bioinformatic analyses. To further estimate cell-type composition of subchondral bone, we utilized two newly developed deconvolution algorithms (MuSiC, MCP-counter) in transcriptomic datasets, based on signatures from open-accessed single-cell RNA sequencing (scRNA-seq). Finally, competing endogenous RNA (ceRNA) and transcription factor (TF) networks were constructed through multiple predictive databases, and validated by public non-coding RNA profiles. RESULTS: A total of 86 BML-specific DEGs (up 79, down 7) were identified. IL11 and VCAN were identified as core hub genes. The "has-miR-424-5p/lncRNA PVT1" was determined as crucial network, targeting IL11 and VCAN, respectively. More importantly, two deconvolution algorithms produced approximate estimations of cell-type composition, and the cluster of heterotopic-chondrocyte was discovered abundant in BMLs, and positively correlated with the expression of hub genes. CONCLUSION: IL11 and VCAN were identified as the core hub genes of BMLs, and their molecular networks were determined as well. We profiled the characteristics of subchondral bone at single-cell level and determined that the heterotopic-chondrocyte was abundant in BMLs and was closely linked to IL11 and VCAN. Our study may provide new insights into the microenvironment and pathological molecular mechanism of BMLs, and could lead to novel therapeutic strategies.

Cryoablation combined with a clinical Chinese medicine for the treatment of lung cancer.

Cryoablation has been clinically applied to the treatment of lung cancer, but cryoablation has the problem of incomplete tumor killing when the freezing dose is not enough, which may lead to tumor recurrence or metastasis. Therefore, cryoablation combined with other therapeutic options is usually suggested to achieve a complete cure for lung cancer. Clinical practices have shown that traditional Chinese medicine (TCM) treatment can improve the quality of life of patients with advanced lung cancer and prolong the postoperative survival time. However, the mechanism of the synergistic effect of Chinese medicine and cryotherapy, and the optimal treatment plan have not been clarified so far. Therefore, the effect of TCM particles on ice crystal growth and phase transition during cooling was investigated. In addition, we explored the optimized concentration and combination treatment sequence of TCM (lung care formula) and validated the optimal treatment protocol by establishing a mouse model of non-small cell lung cancer (NSCLC). In general, cryoablation combined with TCM is a useful treatment for lung cancer, which can effectively solve the problem of tumor recurrence after cryoablation.

The effect of systemic iron status on osteoarthritis: A mendelian randomization study.

Objective: To assess the causal effect of systemic iron status by using four biomarkers (serum iron; transferrin saturation; ferritin; total iron-binding capacity) on knee osteoarthritis (OA), hip OA, total knee replacement, and total hip replacement using 2-sample Mendelian randomization (MR) design. Methods: Three instrument sets were used to construct the genetic instruments for the iron status: Liberal instruments (variants associated with one of the iron biomarkers), sensitivity instruments (liberal instruments exclude variants associated with potential confounders), and conservative instruments (variants associated with all four iron biomarkers). Summary-level data for four OA phenotypes, including knee OA, hip OA, total knee replacement, and total hip replacement were obtained from the largest genome-wide meta-analysis with 826,690 individuals. Inverse-variance weighted based on the random-effect model as the main approach was conducted. Weighted median, MR-Egger, and Mendelian randomization pleiotropy residual sum and outlier methods were used as sensitivity MR approaches. Results: Based on liberal instruments, genetically predicted serum iron and transferrin saturation were significantly associated with hip OA and total hip replacement, but not with knee OA and total knee replacement. Statistical evidence of heterogeneity across the MR estimates indicated that mutation rs1800562 was the SNP significantly associated with hip OA in serum iron (odds ratio, OR = 1.48), transferrin saturation (OR = 1.57), ferritin (OR = 2.24), and total-iron binding capacity (OR = 0.79), and hip replacement in serum iron (OR = 1.45), transferrin saturation (OR = 1.25), ferritin (OR = 1.37), and total-iron binding capacity (OR = 0.80). Conclusion: Our study suggests that high iron status might be a causal factor of hip OA and total hip replacement where rs1800562 is the main contributor.

Quantitatively Measured Infrapatellar Fat Pad Signal Intensity Alteration is Associated with Joint Effusion-synovitis in Knee Osteoarthritis.

OBJECTIVE: The objective of this study is to investigate whether quantitatively measured infrapatellar fat pad (IPFP) signal intensity alteration is associated with joint effusion-synovitis in people with knee osteoarthritis (OA) over two years. METHODS: Among 255 knee OA patients, IPFP signal intensity alteration represented by four measurement parameters [standard deviation of IPFP signal intensity (IPFP sDev), upper quartile value of IPFP high signal intensity region (IPFP UQ (H)), ratio of IPFP high signal intensity region volume to whole IPFP volume (IPFP percentage (H)), and clustering factor of IPFP high signal intensity (IPFP clustering factor (H))] was measured quantitatively at baseline and two-year follow-up using magnetic resonance imaging (MRI). Effusion-synovitis of the suprapatellar pouch and other cavities were measured both quantitatively and semi-quantitatively as effusion-synovitis volume and effusion-synovitis score at baseline and two-year follow-up using MRI. Mixed effects models assessed the associations between IPFP signal intensity alteration and effusion-synovitis over two years. RESULTS: In multivariable analyses, all four parameters of IPFP signal intensity alteration were positively associated with total effusion-synovitis volume and effusion-synovitis volumes of the suprapatellar pouch and of other cavities over two years (all P＜0.05). They were also associated with the semi-quantitative measure of effusion-synovitis except for IPFP percentage (H) with effusion-synovitis in other cavities. CONCLUSION: Quantitatively measured IPFP signal intensity alteration is positively associated with joint effusion-synovitis in people with knee OA, suggesting that IPFP signal intensity alteration may contribute to effusion-synovitis and a coexistent pattern of these two imaging biomarkers could exist in knee OA patients.

Bone marrow lesions in osteoarthritis: From basic science to clinical implications.

Osteoarthritis (OA) is the most prevalent musculoskeletal disease characterized by multiple joint structure damages, including articular cartilage, subchondral bone and synovium, resulting in disability and economic burden. Bone marrow lesions (BMLs) are common and important magnetic resonance imaging (MRI) features in OA patients. Basic and clinical research on subchondral BMLs in the pathogenesis of OA has been a hotspot. New evidence shows that subchondral bone degeneration, including BML and angiogenesis, occurs not only at or after cartilage degeneration, but even earlier than cartilage degeneration. Although BMLs are recognized as important biomarkers for OA, their exact roles in the pathogenesis of OA are still unclear, and disputes about the clinical impact and treatment of BMLs remain. This review summarizes the current basic and clinical research progress of BMLs. We particularly focus on molecular pathways, cellular abnormalities and microenvironmental changes of subchondral bone that contributed to the formation of BMLs, and emphasize the crosstalk between subchondral bone and cartilage in OA development. Finally, potential therapeutic strategies targeting BMLs in OA are discussed, which provides novel strategies for OA treatment.

Photon-Energy-Dependent Reversible Charge Transfer Dynamics of Double Perovskite Nanocrystal-Polymer Nanocomposites.

Combining steady-state photoluminescence and transient absorption (TA) spectroscopy, we have investigated the photoinduced charge transfer dynamics between lead-free Mn-doped Cs2NaIn0.75Bi0.25Cl6 double perovskite (DP) nanocrystals (NCs) and conjugated poly[2-methoxy-5-(3',7'-dimethyloctyloxy)-1,4-phenylenevinylene] (MDMO-PPV). Upon ultraviolet-A excitation, the photoinduced absorption feature of DP NCs/MDMO-PPV nanocomposites disappeared, and the stimulated emission weakened in the TA spectrum. This was due to charge transfer from the MDMO-PPV polymers to DP NCs. Upon a higher photon-energy ultraviolet-C excitation, stimulated emission and photoinduced absorption features vanished, indicating there existed a reversible charge transfer from DP NCs to MDMO-PPV polymers. Reversible charge transfer of Mn-doped DP NCs/MDMO-PPV nanocomposites was tuned by varying the excitation photon-energy. The manipulation of reversible charge transfer dynamics in the perovskite-polymer nanocomposites opens a new avenue for optical and optoelectronic applications.

Associations of Dietary Macroelements with Knee Joint Structures, Symptoms, Quality of Life, and Comorbid Conditions in People with Symptomatic Knee Osteoarthritis.

BACKGROUND: Osteoarthritis (OA), the most common joint disease in the elderly, has no cure. Macroelements are vital in human health and their relationships with OA are not clear. Clarifying the relationships between macroelements and OA may assist knee OA management. METHODS: This study was a post-hoc analysis using data from a two-year randomized controlled trial among 392 participants with knee OA. Dietary macroelements, including calcium, magnesium, potassium, and phosphorus were computed-based on a semi-quantitative food frequency questionnaire at baseline. Knee joint structures (including cartilage volume, cartilage defect, bone marrow lesions, and effusion-synovitis volume), OA symptoms, quality of life, and OA comorbid conditions (including lower limb muscle strength and depressive symptoms) were assessed at baseline and month 24. Western Ontario and McMaster Universities (WOMAC) Index and depressive symptoms were assessed at baseline and months 3, 6, 12, and 24. Quality of life and lower limb muscle strength were assessed at baseline and months 6, 12, and 24. All analyses were conducted using mixed-effects models. RESULTS: Higher dietary magnesium and potassium were associated with fewer OA symptoms, higher quality of life, greater lower limb muscle strength, and fewer depressive symptoms, but not with knee joint structures. Higher dietary calcium and phosphorus was not associated with any of the OA-related outcomes, except that dietary phosphorus was associated with greater lower limb muscle strength. CONCLUSIONS: In the longitudinal analyses, higher dietary magnesium and potassium intake are associated with fewer OA symptoms, higher quality of life, and milder comorbid conditions in patients with knee OA, suggesting dietary magnesium and potassium may have beneficial effects on OA and could be used for knee OA management.

Osteophytes mediate the associations between cartilage morphology and changes in knee symptoms in patients with knee osteoarthritis.

AIMS: To investigate whether the associations between cartilage defects and cartilage volumes with changes in knee symptoms were mediated by osteophytes. METHODS: Data from the Vitamin D Effects on Osteoarthritis (VIDEO) study were analyzed as a cohort. The Western Ontario and McMaster Universities Osteoarthritis Index was used to assess knee symptoms at baseline and follow-up. Osteophytes, cartilage defects, and cartilage volumes were measured using magnetic resonance imaging at baseline. Associations between cartilage morphology and changes in knee symptoms were assessed using linear regression models, and mediation analysis was used to test whether these associations were mediated by osteophytes. RESULTS: A total of 334 participants (aged 50 to 79 years) with symptomatic knee osteoarthritis were included in the analysis. Cartilage defects were significantly associated with change in total knee pain, change in weight-bearing pain, and change in non-weight-bearing pain after adjustment for age, sex, body mass index, and intervention. Cartilage volume was significantly associated with change in weight-bearing pain and change in physical dysfunction after adjustment. Lateral tibiofemoral and patellar osteophyte mediated the associations of cartilage defects with change in total knee pain (49-55%) and change in weight-bearing pain (61-62%) and the association of cartilage volume with change in weight-bearing pain (27-30%) and dysfunction (24-25%). Both cartilage defects and cartilage volume had no direct effects on change in knee symptoms. CONCLUSIONS: The significant associations between cartilage morphology and changes in knee symptoms were indirect and were partly mediated by osteophytes.

Association between Metformin Use and Risk of Total Knee Arthroplasty and Degree of Knee Pain in Knee Osteoarthritis Patients with Diabetes and/or Obesity: A Retrospective Study.

Objectives: We aimed to examine whether metformin (MET) use is associated with a reduced risk of total knee arthroplasty (TKA) and low severity of knee pain in patients with knee osteoarthritis (OA) and diabetes and/or obesity. Methods: Participants diagnosed with knee OA and diabetes and/or obesity from June 2000 to July 2019 were selected from the information system of a local hospital. Regular MET users were defined as those with recorded prescriptions of MET or self-reported regular MET use for at least 6 months. TKA information was extracted from patients' surgical records. Knee pain was assessed using the numeric rating scale. Log-binomial regression, linear regression, and propensity score weighting (PSW) were performed for statistical analyses. Results: A total of 862 participants were included in the analyses. After excluding missing data, there were 346 MET non-users and 362 MET users. MET use was significantly associated with a reduced risk of TKA (prevalence ratio: 0.26, 95% CI: 0.15 to 0.45, p < 0.001), after adjustment for age, gender, body mass index, various analgesics, and insurance status. MET use was significantly associated with a reduced degree of knee pain after being adjusted for the above covariates (ß: −0.48, 95% CI: −0.91 to −0.05, p = 0.029). There was a significantly accumulative effect of MET use on the reduced risk of TKA. Conclusion: MET can be a potential therapeutic option for OA. Further clinical trials are needed to determine if MET can reduce the risk of TKA and the severity of knee pain in metabolic-associated OA patients.

Relative Efficacy and Safety of Anti-Inflammatory Biologic Agents for Osteoarthritis: A Conventional and Network Meta-Analysis.

Previous studies have consistently revealed that both local and systemic inflammations are the key to the onset and progression of osteoarthritis (OA). Thus, anti-inflammatory biologic agents could potentially attenuate the progression of OA. We conducted this meta-analysis to examine the efficacy and safety of ant-inflammatory biologic agents among OA patients. METHODS: Five databases were searched for randomized controlled trials (RCTs) comparing biologics with placebo or each other in OA patients. Data of pain, physical function, stiffness, and adverse events (AEs) were extracted for a conventional and a Bayesian network meta-analysis. RESULTS: 15 studies with data for 1566 patients were analyzed. In the conventional meta-analysis, etanercept (SMD -0.47; 95% CI -0.89, -0.05) and infliximab (SMD -2.04; CI -2.56, -1.52) were superior to placebo for knee pain. In the network meta-analysis, infliximab was superior to all the other biologic agents in improving pain (vs. hyaluronic acid (SMD -22.95; CI -34.21, -10.43), vs. adalimumab (SMD -21.71; CI -32.65, -11.00), vs. anakinra (SMD -24.63; CI -38.79, -10.05), vs. canakinumab (SMD -32.83; CI -44.45, -20.68), vs. etanercept (SMD -18.40; CI -29.93, -5.73), vs. lutikizumab (SMD -25.11; CI -36.47, -14.78), vs. naproxen (SMD -30.16; CI -41.78, -17.38), vs. tocilizumab (SMD -24.02; CI -35.63, -11.86) and vs. placebo (SMD -25.88; CI -34.87, -16.60)). No significant differences were observed between biologics and placebo regarding physical function, stiffness, and risk of AEs. CONCLUSIONS: The findings suggest that infliximab may relieve pain more than other biological agents in OA patients. No significant differences were observed between biologics and placebo regarding physical function, stiffness, and risk of AEs. The results must be interpreted cautiously; therefore, further randomized controlled trials are warranted.

MRI-based Texture Analysis of Infrapatellar Fat Pad to Predict Knee Osteoarthritis Incidence.

Background Infrapatellar fat pad (IPFP) quality has been implicated as a marker for predicting knee osteoarthritis (KOA); however, no valid quantification for subtle IPFP abnormalities has been established. Purpose To investigate whether MRI-based three-dimensional texture analysis of IPFP abnormalities could help predict incident radiographic KOA. Materials and Methods In this prospective nested case-control study, 690 participants whose knees were at risk for KOA were included from the Pivotal Osteoarthritis Initiative MRI Analyses incident osteoarthritis cohort. All knees had a Kellgren-Lawrence grade of 1 or less at baseline. During the 4-year follow-up, case participants were matched 1:1 to control participants, with incident radiographic KOA as the outcome. MRI scans were segmented at the incident time point of KOA (hereafter, P0), 1 year before P0 (hereafter, P-1), and baseline. MRI-based three-dimensional texture analysis was performed to extract IPFP texture features. Least absolute shrinkage and selection operator and multivariable logistic regressions were applied in the development cohort and evaluated in the test cohort. The area under the receiver operating characteristic curve (AUC) was used to evaluate the discriminative value of the clinical score, IPFP texture score, and MRI Osteoarthritis Knee Score. Results Participants were allocated to development (n = 500, 340 women; mean age, 60 years) and test (n = 190, 120 women; mean age, 61 years) cohorts. In both cohorts, IPFP texture scores (AUC ≥0.75 for all) showed greater discrimination than clinical scores (AUC ≤0.69 for all) at baseline, P-1, and P0, with significant differences in pairwise comparisons (P ≤ .002 for all). Greater predictive and concurrent validities of IPFP texture scores (AUC ≥0.75 for all) compared with MRI Osteoarthritis Knee Scores (AUC ≤0.66 for all) were also demonstrated (P < .001 for all). Conclusion MRI-based three-dimensional texture of the infrapatellar fat pad was associated with future development of knee osteoarthritis. ClinicalTrials.gov registration no.: NCT00080171 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Fischer in this issue.

Treatment optimization for recurrent hepatoblastoma: retrospective study from a hepatoblastoma cohort in Southern China.

PURPOSE: The present study aimed to explore the clinical characteristics and optimal treatments of RHB patients. METHODS: We retrospectively collected 42 RHB cases and 161 primary HB (PHB) cases. Clinical characteristics were compared between RHB and PHB patients. The risk factors related to overall survival (OS) and progression-free survival (PFS) in RHB patients were explored by COX regression analysis. Patients were further divided into curable and refractory subgroup by treatments. Propensity score match (PSM) analysis was performed to match recurrent curable patients from 145 curable PHB patients from the same cohort. PFS was further compared between 34 pairs of primary and recurrent curative HB patients. RESULTS: Recurrence treatment and number of relapsed tumors were significantly related with both OS and PFS of RHB patients (p < 0.05). Chemotherapy regimen alteration was also risk factor of PFS for RHB (HR = 4.26; 95% CI = 1.54-11.78; p = 0.005). RHB patients underwent curable treatment had better prognosis, compared with recurrent refractory subgroup (p < 0.001). Matched curable PHB patients demonstrated no significant difference of 3-year PFS with curable RHB patients (p = 0.540). CONCLUSION: Curable RHB patients might get benefit from surgery or ablation with similar prognosis with primary curable HB patients.

Analysis of Clinical Related Factors of Severe Mycoplasma pneumoniae Pneumonia in Children Based on Imaging Diagnosis.

Severe pneumonia is a common acute respiratory disease in children, and it has a rapid onset and violent onset, which often affects the whole body. Moreover, typical clinical manifestations and signs often cannot be taken seriously or covered up in clinical work. Due to the short time for treatment, it is easy to cause improper diagnosis and treatment, aggravate the disease and further deteriorate, and even threaten the life of the child. In order to achieve early intervention and treatment of severe Mycoplasma pneumoniae pneumonia in children, reduce or shorten the course of the disease, and improve the cure rate, this paper combines the imaging diagnosis to study the analysis of clinical related factors of severe Mycoplasma pneumoniae pneumonia in children. In addition, this paper analyzes the experimental data with hospital case samples, conducts statistical research on the analysis of clinical related factors of severe Mycoplasma pneumoniae pneumonia in children, and proposes effective coping strategies.

NiCu nanoalloy embedded in N-doped porous carbon composite as superior electrochemical sensor for neonicotinoid determination.

Enhancing catalytic activity is the key to develop electrochemical sensors for monitoring of neonicotinoid such as imidacloprid (IMI), thiamethoxam (THX) and dinotefuran (DNF). Herein, a MOF-derived octahedral NiCu nanoporous carbon composite with abundant N-doped (N/NiCu@C) was synthesized, which was exploited as electrochemical sensor for neonicotinoid determination. Integrating the synergistic effect of NiCu nanoalloy and the hierarchical porous carbon structure, the N/NiCu@C/GCE significantly promoted the diffusion between electrolyte and active site. Meanwhile, the introduction of polyvinylpyrrolidone (PVP) improved the hydrophilicity and dispersibility of N/NiCu@C, endowing superior electrocatalytic performance for IMI, THX and DNF determination, with linear ranges of 0.5-60, 1-60 and 0.5-60 µM, respectively, and detection limits of 0.017, 0.007 and 0.001 µM. Additionally, the sensor can determine IMI, THX and DNF in apples, tomatoes and potatoes with the recovery rate of 92.1-103.4% and RSD ≤ 4.7%. This study has explored a novel modified electrode material for construction of neonicotinoid sensors.

Size-segregated physicochemical properties of inhalable particulate matter in a tunnel-ventilated layer house in China.

This study investigated the physicochemical properties of the particles in a typical commercial laying hen barn in Southeast China. Mass concentrations and size distributions of the particulate matter (PM) and the key components (incl. organic carbon (OC), element carbon (EC), and the water-soluble inorganic ions (WSIIs)) were analyzed. The result shows that the mass concentrations of PM accumulated along with the airflow inside the house, with the total mass of the sampling particles increasing from 843.66 ± 160.74 µg/m3 at the center of the house to 1264.93 ± 285.70 µg/m3 at the place close to exhaust fans. The particles with the aerodynamic equivalent diameter, Dp > 9 µm, coarse particles (2.1 µm < Dp ≤ 9 µm), fine particles (Dp ≤ 2.1 µm) accounted for around 50%, 40%, and 10% of the total mass of the sampling particles, respectively. Mass closure analysis shows secondary inorganic ions (NH4+, SO42- and NO3-) were abundant in the fine-mode fraction and OC accounted for more than 40% of the coarse particles. Size distribution analysis shows that the three secondary inorganic ions were bimodally distributed, and the rest tested components were unimodally distributed. The ratios of OC/EC in fine particles were smaller than those in the coarse particles. The equivalent concentration of WSIIs indicated that fine particles were slightly acidic, and the large size particles were slightly alkaline. Knowledge gained from this study will lead to a better understanding of physicochemical properties, sources, and formation of PM.

Copy number variation analysis of m6 A regulators identified METTL3 as a prognostic and immune-related biomarker in bladder cancer.

PURPOSE: Growing evidence has demonstrated an indispensable role for N6 -methyladenosine (m6 A) in human diseases, but the copy number variations (CNVs) of m6 A regulatory genes in bladder cancer (BLCA) remains largely unknown. METHODS: We investigated the CNVs on all known m6 A regulatory genes using the Cancer Genome Atlas (TCGA) database. The association between CNV events and clinicopathological as well as molecular characteristics of BLCA patients were explored. Gene set enrichment analysis (GSEA) was implemented to reveal relative cellular processes. Association between m6 A regulatory genes and immune infiltrates was analyzed by The Tumor Immune Estimation Resource (TIMER) database. RESULTS: CNV events of m6 A regulatory genes were frequently observed in BLCA. CNVs of METTL3, METTL14, and METTL16 correlated with molecular characteristics of BLCA patients including TP53 mutation. CNVs of METTL3 associated with the overall survival (OS) of BLCA patients. METTL3 was also associated with several cancer-related cellular processes, including mitotic spindle assembly, G2/M checkpoint, and E2F targets signaling pathway. Besides, the CNVs of m6 A regulatory genes were correlated with specific kinds of immune infiltrates. CONCLUSIONS: There are significant correlations between m6 A regulatory genes with CNVs and clinicopathological characteristics. METTL3 with CNVs were associated with the immune infiltrates and performed as a prognostic marker in BLCA.

Sprifermin: a recombinant human fibroblast growth factor 18 for the treatment of knee osteoarthritis.

INTRODUCTION: Osteoarthritis (OA) is a serious and incurable disease leading the disability. Surgical treatment is the last but not necessarily the best approach for patients with high risks and costs. However, there are no disease-modifying OA drugs (DMOADs) developed for the disease so far, leaving a huge unmet need for drug treatments. Sprifermin is a recombinant human fibroblast growth factor 18 (rhFGF18) and has been confirmed to have anabolic effects on articular cartilage, which makes it a promising DMOAD. AREAS COVERED: The content of this review includes overview of the market, discovery and development, molecular mechanism, preclinical studies, clinical efficacy, safety, and tolerability of sprifermin. It examines the potential of sprifermin as a disease modifying drug for the treatment of knee OA. EXPERT OPINION: Sprifermin could be one of the most promising DMOADs, especially for cartilage phenotype. Current studies show good tolerability and no safety concerns. Well-designed phase 3 clinical trials are required to examine its effects on symptoms and cartilage loss in knee OA.

Modeling of Heat Stress in Sows-Part 1: Establishment of the Prediction Model for the Equivalent Temperature Index of the Sows.

Heat stress affects the estrus time and conception rate of sows. Compared with other life stages of pigs, sows are more susceptible to heat stress because of their increased heat production. Various indicators can be found in the literature assessing the level of heat stress in pigs. However, none of them is specific to assess the sows' thermal condition. Moreover, thermal indices are mainly developed by considering partial environment parameters, and there is no interaction between the index and the animal's physiological response. Therefore, this study aims to develop a thermal index specified for sows, called equivalent temperature index for sows (ETIS), which includes parameters of air temperature, relative humidity and air velocity. Based on the heat transfer characteristics of sows, multiple regression analysis is used to combine air temperature, relative humidity and air velocity. Environmental data are used as independent variables, and physiological parameters are used as dependent variables. In 1029 sets of data, 70% of the data is used as the training set, and 30% of the data is used as the test set to create and develop a new thermal index. According to the correlation equation between ETIS and temperature-humidity index (THI), combined with the threshold of THI, ETIS was divided into thresholds. The results show that the ETIS heat stress threshold is classified as follows: suitable temperature ETIS < 33.1 °C, mild temperature 33.1 °C ≤ ETIS < 34.5 °C, moderate stress temperature 34.5 °C ≤ ETIS < 35.9 °C, and severe temperature ETIS ≥ 35.9 °C. The ETIS model can predict the sows' physiological response in a good manner. The correlation coefficients R of skin temperature was 0.82. Compared to early developed thermal indices, ETIS has the best predictive effect on skin temperature. This index could be a useful tool for assessing the thermal environment to ensure thermal comfort for sows.