Sex-Based Difference in Bone Healing: A Review of Recent Pre-clinical Literature

Purpose of ReviewRecent literature has sought to understand differences in fusion failure, specifically considering how patient sex may play a role. Overall, there exists inconclusive data regarding any sex-based differences in bone healing.Recent FindingsIn vitro studies examining the roles of sex hormones, 5-LO, IGF-1, VEGF, osteoclasts, and OPCs seem to show sexually dimorphic actions. Additionally, donor characteristics and stem cell environment seem to also determine osteogenic potential. Building on this biomolecular basis, in vivo work investigates the aforementioned elements. Broadly, males tend to have a more robust healing compared to females. Taking these findings together, differences in sex hormones levels, their timing and action, and composition of the inflammatory milieu underlie variations in bone healing by sex.SummaryClinically, a robust understanding of bone healing mechanics can inform care of the transgender patient. Transgender patients undergoing hormone therapy present a clinically nuanced scenario for which limited long-term data exist. Such advances would help inform treatment for sports-related injury due to hormonal changes in biomechanics and treatment of transgender youth. While recent advances provide more clarity, conclusive answers remain elusive.     

Three-dimensional-generator U-net for dual-resonant scanning multiphoton microscopy image inpainting and denoising

A dual-resonant scanning multiphoton (DRSM) microscope incorporating a tunable acoustic gradient index of refraction lens and a resonant mirror is developed for rapid volumetric bioimaging. It is shown that the microscope achieves a volumetric imaging rate up to 31.25 volumes per second (vps) for a scanning volume of up to 200 × 200 × 100 µm³ with 256 × 256 × 128 voxels. However, the volumetric images have a severe negative signal-to-noise ratio (SNR) as a result of a large number of missing voxels for a large scanning volume and the presence of Lissajous patterning residuals. Thus, a modified three-dimensional (3D)-generator U-Net model trained using simulated microbead images is proposed and used to inpaint and denoise the images. The performance of the 3D U-Net model for bioimaging applications is enhanced by training the model with high-SNR in-vitro drosophila brain images captured using a conventional point scanning multiphoton microscope. The trained model shows the ability to produce clear in-vitro drosophila brain images at a rate of 31.25 vps with a SNR improvement of approximately 20 dB over the original images obtained by the DRSM microscope. The training convergence time of the modified U-Net model is just half that of a general 3D U-Net model. The model thus has significant potential for 3D in-vivo bioimaging transfer learning. Through the assistance of transfer learning, the model can be extended to the restoration of in-vivo drosophila brain images with a high image quality and a rapid training time.     

Light-field microscopy with temporal focusing multiphoton illumination for scanless volumetric bioimaging

A temporal focusing multiphoton illumination (TFMI) method is proposed for achieving selective volume illumination (SVI) (i.e., illuminating only the volume of interest) in light-field microscopy (LFM). The proposed method minimizes the background noise of the LFM images and enhances the contrast, and thus improves the imaging quality. Three-dimensional (3D) volumetric imaging is achieved by reconstructing the LFM images using a phase-space deconvolution algorithm. The experimental results obtained using 100-nm fluorescent beads show that the proposed TFMI-LFM system achieves lateral and axial resolutions of 1.2 µm and 1.1 µm, respectively, at the focal plane. Furthermore, the TFMI-LFM system enables 3D images of the single lobe of the drosophila mushroom body with GFP biomarker (OK-107) to be reconstructed in a one-snapshot record.     

Predictors of response and survival in patients with unresectable hepatocellular carcinoma treated with nivolumab: real-world experience

Real-world predictors of the treatment efficacy of immune checkpoint inhibitors for hepatocellular carcinoma (HCC) are unknown. This retrospective study enrolled 87 consecutive patients with unresectable HCC from May 2017 to December 2019 at two hospitals. Of the 87 patients, 7, 9, 60, and 11 patients had Barcelona Clinic Liver Cancer stages A, B, C, and D, respectively, and 45, 30, and 10 patients were Child-Pugh class A, B, and C, respectively. The median injection numbers of nivolumab and treatment duration were 6 (3-8) and 2.53 (1.47-4.23) months, respectively, and 64.4% of patients received combination therapy. Radiological imaging was not assessed for 25 patients. Objective response (OR) and disease control rates were 19.5% and 39.1%, respectively. A single tumor (odds ratio: 9.542, P = .015) and ≥20% decline in serum α-fetoprotein protein (AFP) levels within the first 3 months of treatment (defined as AFP response, odds ratio: 5.997, P = .042) were predictors of OR. Lack of macrovascular invasion, combination therapy, and AFP response were predictors of progression-free survival. A Cancer of the Liver Italian Program (CLIP) score of 0-2 (hazard ratio [HR]: 3.717, P = .004) and grade 1-2 immune-related adverse events (irAEs, HR: 2.217, P = .049) were predictors of overall survival (OS) in the entire cohort, and a CLIP score of 0-2 (HR: 3.257, P = .009) was a predictor of OS in evaluable patients. IrAEs ≥ grade 3 were noted in 14 patients, and three died as a result. Having a single tumor and AFP response were predictors of OR, and CLIP score was a predictor of OS.     

Statins use and its impact in EGFR‐TKIs resistance to prolong the survival of lung cancer patients: A Cancer registry cohort study in Taiwan

Statins have been shown to be a beneficial treatment as chemotherapy and target therapy for lung cancer. This study aimed to investigate the effectiveness of statins in combination with epidermal growth factor receptor‐tyrosine kinase inhibitor therapy for the resistance and mortality of lung cancer patients. A population‐based cohort study was conducted using the Taiwan Cancer Registry database. From January 1, 2007, to December 31, 2012, in total 792 non‐statins and 41 statins users who had undergone EGFR‐TKIs treatment were included in this study. All patients were monitored until the event of death or when changed to another therapy. Kaplan‐Meier estimators and Cox proportional hazards regression models were used to calculate overall survival. We found that the mortality was significantly lower in patients in the statins group compared with patients in the non‐statins group (4‐y cumulative mortality, 77.3%; 95% confidence interval (CI), 36.6%‐81.4% vs. 85.5%; 95% CI, 78.5%‐98%; P = .004). Statin use was associated with a reduced risk of death in patients the group who had tumor sizes <3 cm (hazard ratio [HR], 0.51, 95% CI, 0.29‐0.89) and for patients in the group who had CCI scores <3 (HR, 0.6; 95% CI, 0.41‐0.88; P = .009). In our study, statins were found to be associated with prolonged survival time in patients with lung cancer who were treated with EGFR‐TKIs and played a synergistic anticancer role.     

Cortico-thalamic dysconnection in early-stage schizophrenia: a functional connectivity magnetic resonance imaging study

European Archives of Psychiatry and Clinical Neuroscience - Studies have indicated thalamus-related network dysfunction in schizophrenia and psychotic disorders. However, whether thalamus-related...