BACKGROUND: The rise of digital health services, particularly digital doctor consultations, has created a new paradigm in health care choice. While patients traditionally rely on digital reviews or referrals to select health care providers, the digital context often lacks such information, leading to reliance on visual cues such as profile pictures. Previous research has explored the impact of physical attractiveness in general service settings but is scant in the context of digital health care.
OBJECTIVE: This study aims to fill the research gap by investigating how a health care provider\'s physical attractiveness influences patient preferences in a digital consultation setting. We also examine the moderating effects of disease severity and the availability of information on health care providers\' qualifications. The study uses signal theory and the sexual attribution bias framework to understand these dynamics.
METHODS: Three experimental studies were conducted to examine the influence of health care providers\' physical attractiveness and gender on patient preferences in digital consultations. Study 1 (n=282) used a 2×2 between-subjects factorial design, manipulating doctor attractiveness and gender. Study 2 (n=158) focused on women doctors and manipulated disease severity and participant gender. Study 3 (n=150) replicated study 2 but added information about the providers\' abilities.
RESULTS: This research found that patients tend to choose attractive doctors of the opposite gender but are less likely to choose attractive doctors of the same gender. In addition, our studies revealed that such an effect is more prominent when the disease severity is high. Furthermore, the influence of gender stereotypes is mitigated in both the high and low disease severity conditions when service providers\' qualification information is present.
CONCLUSIONS: This research contributes to the literature on medical information systems research and sheds light on what information should be displayed on digital doctor consultation platforms. To counteract stereotype-based attractiveness biases, health care platforms should consider providing comprehensive qualification information alongside profile pictures.

Although several studies have investigated models of nerve electrical injury, only a few have focused on electrical injury to peripheral nerves, which is a common and intractable problem in clinical practice. Here, we describe an experimental rat model of peripheral nerve electrical injury and its assessment.
A total of 120 animals were subjected to short-term corrective electrostimulation (50 Hz, 1-s duration) applied at varying voltages (control, 65, 75, 100, 125, and 150 V) to the exposed left sciatic nerve. Behavioural testing, electrophysiological measurements, and histopathological observation of the sciatic nerve were conducted at 1-, 2-, 4-, and 8-w follow-ups.
No functional defects were noted in the groups that received 65-V stimulation at any time point. Sciatic nerve functional defects were found after 2 w in animals that received 75-V stimulation, but function returned to normal after 4 w. In animals that received 100-V and 125-V stimulation, functional defects were observed at 4 w, but had partially recovered by 8 w. Conversely, animals that received 150-V stimulation did not show recovery after 8 w.
We presented a model of peripheral nerve electrical injury that avoided the interference of various external factors, such as current instability, compression of the surrounding tissues, and altered blood supply. The model allowed quantitation and ranking of the nerve injury into four degrees. It facilitated effective evaluation of nerve function impairment and repair after injury. It can be used post-surgically to evaluate peripheral nerve impairment and reconstruction and enables translational interpretation of results, which may improve understanding of the mechanisms underlying the progression of peripheral nerve electrical injury.

OBJECTIVE: Understanding morphology and how this relates to treatment strategy is critical for achieving remodelling in aortic dissection. A controllable and reproducible large animal model is required for investigating new therapeutic devices and interventions.
METHODS: Our experimental protocol involved the development of surgically created type B aortic dissection (TBAD) and endovascular reintervention-induced TBAD porcine models. The sample was randomly divided into 2 groups: 1 underwent a secondary tear creation (STC) procedure and the other underwent a false lumen extension (FLE) procedure. Anatomical features were observed at 1 and 3 months, and 2 animals in each group were euthanized at 3 months after the procedures. The aorta and main branches were harvested en bloc, cross-sectioned and prepared for histological examination.
RESULTS: All surgically created TBAD models were successfully generated, and no unintended complications occurred. The endovascular reintervention-induced TBAD model was successfully created in 11 of 12 animals, with 6 in the STC group and 5 in the FLE group. In the STC group, the intraoperative mean diameter of the new secondary tear was 7.23 mm, and a slight increase was observed at first 30 days (P = 0.0026). In the FLE group, the intraoperative new propagation length was (235.80 ± 84.94) mm. The FL propagation length at the 1-month follow-up was significantly longer than that measured intraoperatively (P = 0.0362). Histological evaluation demonstrated that the elastic fibres in the media layer of the aortic wall were disrupted and appeared to be significantly stretched on the adventitial side of the false lumen.
CONCLUSIONS: Our endovascular reintervention is a reliable, minimally invasive approach for producing specific TBAD models with different morphologies.

In this study, we proposed a novel composite anchorage that considers the anchoring performance and dimension simultaneously. The design concept of this composite anchorage was first introduced, followed by comparison with the traditional inner-cone bond-type anchorage and traditional composite anchorage through theoretical and experimental methods. Then, a parametric study was conducted to determine the influence of different parameters on the anchoring performance, and the optimal design parameters were recommended according to the finite element (FE) and test results. Finally, the practicability of the optimal design parameters were validated through experiments on the anchorage with multiple CFRP tendons. Results showed that the novel composite anchorage could improve the anchoring performance compared with the traditional inner-cone bond-type anchorage by promoting increased anchorage efficiency by 60.4% and, with an ideal failure mode of tendon rupture. Moreover, the novel composite anchorage had smaller dimensions and avoided the presence of a vulnerable position at the junction of the mechanical and bond parts compared with the traditional composite anchorage. In addition, a group of optimal design parameters of this composite anchorage with a pre-tightening force of 130 kN, an inclinational differential angle of 0.1°, an inclination angle of 2.9°, and an embedded length of 30 d~40 d were proposed. The composite anchorage with five CFRP tendons designed with the proposed parameters failed with the rupture of the tendons and exhibited an anchoring efficiency of 1.05. This result showed that the optimal parameters were suitable for this novel composite anchorage to grip multiple tendons. This study can provide an experimental and theoretical basis for designing large-tonnage anchorage for multiple FRP tendons used as hangers or cables in real bridges.

Crystal structures activate innate immune cells, especially macrophages and initiate inflammatory responses. We aimed to understand the role of the mechanosensitive TRPV4 channel in crystal-induced inflammation. Real-time RT-PCR, RNAscope in situ hybridisation, and Trpv4eGFP mice were used to examine TRPV4 expression and whole-cell patch-clamp recording and live-cell Ca2+ imaging were used to study TRPV4 function in mouse synovial macrophages and human peripheral blood mononuclear cells (PBMCs). Both genetic deletion and pharmacological inhibition approaches were used to investigate the role of TRPV4 in NLRP3 inflammasome activation induced by diverse crystals in vitro and in mouse models of crystal-induced pain and inflammation in vivo. TRPV4 was functionally expressed by synovial macrophages and human PBMCs and TRPV4 expression was upregulated by stimulation with monosodium urate (MSU) crystals and in human PBMCs from patients with acute gout flares. MSU crystal-induced gouty arthritis were significantly reduced by either genetic ablation or pharmacological inhibition of TRPV4 function. Mechanistically, TRPV4 mediated the activation of NLRP3 inflammasome by diverse crystalline materials but not non-crystalline NLRP3 inflammasome activators, driving the production of inflammatory cytokine interleukin-1β which elicited TRPV4-dependent inflammatory responses in vivo. Moreover, chemical ablation of the TRPV1-expressing nociceptors significantly attenuated the MSU crystal-induced gouty arthritis. In conclusion, TRPV4 is a common mediator of inflammatory responses induced by diverse crystals through NLRP3 inflammasome activation in macrophages. TRPV4-expressing resident macrophages are critically involved in MSU crystal-induced gouty arthritis. A neuroimmune interaction between the TRPV1-expressing nociceptors and the TRPV4-expressing synovial macrophages contributes to the generation of acute gout flares.

As a key event leading to tubulointerstitial fibrosis in diabetic kidney disease (DKD), epithelial-mesenchymal transition (EMT) has drawn increasing attention from researchers. The antiaging protein Klotho attenuates renal fibrosis in part by inhibiting ERK1/2 signaling in DKD. Early growth response factor 1 (Egr-1), which is activated mainly by ERK1/2, has been shown to play an important role in EMT. However, whether Klotho prevents EMT by inhibiting ERK1/2-dependent Egr-1 expression in DKD is unclear.The aim of this study was to investigate whether Klotho prevents EMT through Egr-1 downregulation by inhibiting the ERK1/2 signaling pathway in DKD.
Male C57BL/6J mice fed an high-fat diet for 4 weeks received 120 mg/kg streptozotocin (STZ), which was injected intraperitoneally. Klotho and Egr-1 expression was detected in the renal cortices of these mice on their sacrifice at 6 and 12 weeks after STZ treatment. In In vitro studies, we incubated HK2 cells under high-glucose (HG) or transforming growth factor-β1 (TGF-β1) conditions to mimic DKD. We then transfected the cells with an Klotho-containing plasmid, Klotho small interfering RNA.
Klotho expression was significantly decreased in the renal cortices of mice with diabetes mellitus (DM) compared with the renal cortices of control mice at 6 weeks after treatment and even more significantly decreased at 12 weeks. In contrast, Egr-1 expression was significantly increased in mice with DM compared with control mice only at 12 weeks. We also found that Klotho overexpression downregulated Egr-1 expression and the (p-ERK1/2):(ERK1/2) ratio in HG-treated or TGF-β1-treated HK2 cells. Conversely, Klotho silencing upregulated Egr-1 expression and the (p-ERK1/2):(ERK1/2) ratio in HG-treated or TGF-β1-treated HK2 cells. Moreover, the effects of si-Klotho were abolished by the ERK1/2 inhibitor PD98059.
Klotho prevents EMT during DKD progression, an effect that has been partially attributed to Egr-1 downregulation mediated by ERK1/2 signaling pathway inhibition.

The review aimed to investigate the accuracy of breath tests in the diagnosis of diabetes mellitus, identify exhaled volatile organic compounds with the most evidence as potential biomarkers, and summarize prospects and challenges in diabetic breath tests. Databases including Medline, PubMed, EMBASE, Cochrane Library and Science Citation Index Expanded were searched. Human studies describing diabetic breath analysis with more than 10 subjects as controls and patients were included. Population demographics, breath test conditions, biomarkers, analytical techniques and diagnostic accuracy were extracted. Quality assessment was performed with the Standards for Reporting Diagnostic Accuracy and a modified QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2). Forty-four research with 2699 patients with diabetes were included for qualitative data analysis and 14 eligible studies were used for meta-analysis. Pooled analysis of type 2 diabetes breath test exhibited sensitivity of 91.8% (95% CI 83.6% to 96.1%), specificity of 92.1% (95% CI 88.4% to 94.7%) and area under the curve (AUC) of 0.96 (95% CI 0.94 to 0.97). Isotopic carbon dioxide (CO2) showed the best diagnostic accuracy with pooled sensitivity of 0.949 (95% CI 0.870 to 0.981), specificity of 0.946 (95% CI 0.891 to 0.975) and AUC of 0.98 (95% CI 0.97 to 0.99). As the most widely reported biomarker, acetone showed moderate diagnostic accuracy with pooled sensitivity of 0.638 (95% CI 0.511 to 0.748), specificity of 0.801 (95% CI 0.691 to 0.878) and AUC of 0.79 (95% CI 0.75 to 0.82). Our results indicate that breath test is a promising approach with acceptable diagnostic accuracy for diabetes mellitus and isotopic CO2 is the optimal breath biomarker. Even so, further validation and standardization in subject control, breath sampling and analysis are still required.

The aim of this study was to identify the role of tenascin-C (TNC) in entheseal new bone formation and to explore the underlying molecular mechanism.
Ligament tissue samples were obtained from patients with ankylosing spondylitis (AS) during surgery. Collagen antibody-induced arthritis and DBA/1 models were established to observe entheseal new bone formation. TNC expression was determined by immunohistochemistry staining. Systemic inhibition or genetic ablation of TNC was performed in animal models. Mechanical properties of extracellular matrix (ECM) were measured by atomic force microscopy. Downstream pathway of TNC was analysed by RNA sequencing and confirmed with pharmacological modulation both in vitro and in vivo. Cellular source of TNC was analysed by single-cell RNA sequencing (scRNA-seq) and confirmed by immunofluorescence staining.
TNC was aberrantly upregulated in ligament and entheseal tissues from patients with AS and animal models. TNC inhibition significantly suppressed entheseal new bone formation. Functional assays revealed that TNC promoted new bone formation by enhancing chondrogenic differentiation during endochondral ossification. Mechanistically, TNC suppressed the adhesion force of ECM, resulting in the activation of downstream Hippo/yes-associated protein signalling, which in turn increased the expression of chondrogenic genes. scRNA-seq and immunofluorescence staining further revealed that TNC was majorly secreted by fibroblast-specific protein-1 (FSP1)+fibroblasts in the entheseal inflammatory microenvironment.
Inflammation-induced aberrant expression of TNC by FSP1+fibroblasts promotes entheseal new bone formation by suppressing ECM adhesion forces and activating Hippo signalling.

Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that affects millions of people worldwide. However, there are currently no reliable biomarkers for ASD diagnosis. Materials and Methods: The strategy of computational prediction combined with experimental verification was used to identify blood protein biomarkers for ASD. First, brain tissue-based transcriptome data of ASD were collected from Gene Expression Omnibus database and analyzed to find ASD-related genes by bioinformatics method of significance analysis of microarrays. Then, a prediction program of blood-secretory proteins was applied on these genes to predict ASD-related proteins in blood. Furthermore, ELISA was used to verify these proteins in plasma samples of ASD patients. Results: A total of 364 genes were identified differentially expressed in brain tissue of ASD, among which 59 genes were predicted to encode ASD-related blood-secretory proteins. After functional analysis and literature survey, six proteins were chosen for experimental verification and five were successfully validated. Receiver operating characteristic curve analyses showed that the area under the curve of SLC25A12, LIMK1, and RARS was larger than 0.85, indicating that they are more powerful in discriminating ASD cases from controls. Conclusion: SLC25A12, LIMK1, and RARS might serve as new potential blood protein biomarkers for ASD. Our findings provide new insights into the pathogenesis and diagnosis of ASD.

Animal models for inflammatory arthritides such as rheumatoid arthritis (RA) and psoriatic arthritis are widely accepted and frequently used to identify pathological mechanisms and validate novel therapeutic strategies. Unfortunately, many publications reporting on these animal studies lack detailed description and appropriate assessment of the distinct histopathological features of arthritis: joint inflammation, cartilage damage and bone erosion. Therefore, the European consortium BeTheCure, consisting of 38 academic and industrial partners from 15 countries, set as goal to standardise the histological evaluation of joint sections from animal models of inflammatory arthritis. The consensual approach of a task force including 16 academic and industrial scientists as well as laboratory technicians has resulted in the development of the Standardised Microscopic Arthritis Scoring of Histological sections (\'SMASH\') recommendations for a standardised processing and microscopic scoring of the characteristic histopathological features of arthritis, exemplified by four different rodent models for arthritis: murine collagen-induced arthritis, collagen-antibody-induced arthritis, human tumour necrosis factor transgenic Tg197 mice and rat pristane-induced arthritis, applicable to any other inflammatory arthritis model. Through standardisation, the SMASH recommendations are designed to improve and maximise the information derived from in vivo arthritis experiments and to promote reproducibility and transparent reporting on such studies. In this manuscript, we will discuss and provide recommendations for analysis of histological joint sections: identification of the regions of interest, sample preparation, staining procedures and quantitative scoring methods. In conclusion, awareness of the different features of the arthritis pathology in animal models of inflammatory arthritis is of utmost importance for reliable research outcome, and the standardised histological processing and scoring methods in these SMASH recommendations will help increase uniformity and reproducibility in preclinical research on inflammatory arthritis.