Foot ulcers are a frequent and costly problem in people with diabetes mellitus and can lead to amputations. Prevention of these ulcers is therefore of paramount importance. Claw/hammer toe deformities are commonly seen in people with diabetes. These deformities increase the risk of ulcer development specifically at the (tip of) the toe. Percutaneous needle tenotomy of the tendon of the m. flexor digitorum longus (tendon tenotomy) can be used to reduce the severity of claw/hammer toe deformity with the goal to prevent ulcer recurrence. The main objective of this randomized controlled trial is to assess the efficacy of flexor tenotomy to prevent recurrence of toe ulcers in people with diabetes and a history of toe (pre-)ulcers. Additionally, we aim to assess interphalangeal joints (IPJ) and metatarsophalangeal joint (MTPJ) angles in a weight-bearing and non-weight-bearing position, barefoot plantar pressure during walking, cost-effectiveness and quality of life before and after the intervention and compare intervention and control study groups. Sixty-six subjects with diabetes and claw/hammer toe deformity and a recent history of (pre-)ulceration on the tip of the toe will be included and randomized between flexor tenotomy of claw/hammer toes (intervention) versus standard of care including orthosis and shoe offloading (controls) in a mono-center randomized controlled trial.
UNASSIGNED: NCT05228340.

UNASSIGNED: Aim of this study was to investigate immune cells and subsets in different stages of human coronary artery disease with a novel multiplex immunohistochemistry (mIHC) technique.
UNASSIGNED: Human left anterior descending coronary artery specimens were analyzed: eccentric intimal thickening (N = 11), pathological intimal thickening (N = 10), fibroatheroma (N = 9), and fibrous plaque (N = 9). Eccentric intimal thickening was considered normal, and pathological intimal thickening, fibroatheroma, and fibrous plaque were considered diseased coronary arteries. Two mIHC panels, consisting of six and five primary antibodies, autofluoresence, and DAPI, were used to detect adaptive and innate immune cells. Via semi-automated analysis, (sub)types of immune cells in whole plaques and specific plaque regions were quantified.
UNASSIGNED: Increased numbers of CD3+ T cells (P < 0.001), CD20+ B cells (P = 0.013), CD68+ macrophages (P = 0.003), CD15+ neutrophils (P = 0.017), and CD31+ endothelial cells (P = 0.024) were identified in intimas of diseased coronary arteries compared to normal. Subset analyses of T cells and macrophages showed that diseased coronary arteries contained an abundance of CD3+CD8- non-cytotoxic T cells and CD68+CD206- non-M2-like macrophages. Proportions of CD3+CD45RO+ memory T cells were similar to normal coronary arteries. Among pathological intimal thickening, fibroatheroma, and fibrous plaque, all immune cell numbers and subsets were similar.
UNASSIGNED: The type of immune response does not differ substantially between different stages of plaque development and may provide context for mechanistic research into immune cell function in atherosclerosis. We provide the first comprehensive map of immune cell subtypes across plaque types in coronary arteries demonstrating the potential of mIHC for vascular research.

UNASSIGNED: Conventional computed tomography (CT) images are severely affected by metal artifacts in patients with intracranial coils. Monoenergetic images have been suggested to reduce metal artifacts.The aim of this study was to assess metal artifacts in virtual monoenergetic images (VMIs) reconstructed from spectral brain CT.
UNASSIGNED: Thirty-two consecutive patients with intracranial coils examined by spectral non contrast brain CT (NCCT) at our center between November 2017 and April 2019 were included. Attenuation and standard deviations were measured in regions of interest (ROIs) at predefined areas in artifact-free and artifact-affected areas. Measurements were performed in conventional polyenergetic images (CIs) and the corresponding data for VMIs were retrieved through spectral diagrams for the each ROI. Subjective analysis was performed by visual grading of CIs and specific VMIs by two neuroradiologists, independently.
UNASSIGNED: In artefact-affected image areas distal from the metal objects, the attenuation values decreased with higher energy level VMIs. The same effect was not seen for artefact-affected image areas close to the metal.Subjective rating of the artefact severity was significantly better in VMIs at 50 keV for one of the two reviewers compared to the CIs. Overall image quality and tissue differentiation scores were significantly higher for both reviewers in VMIs at 60 and 70 keV compared to CIs.
UNASSIGNED: Our quantitative and qualitative image analysis shown that there is a small significant reduction of intracranial coils artifacts severity by all monoenergetic reconstructions from 50 to 200 keV with preserved or increased overall subjective image quality compared to conventional images.

UNASSIGNED: Selecting region of interest (ROI) for left atrial appendage (LAA) filling defects assessment can be time consuming and prone to subjectivity. This study aimed to develop and validate a novel artificial intelligence (AI), deep learning (DL) based framework for automatic filling defects assessment on CT images for clinical and subclinical atrial fibrillation (AF) patients.
UNASSIGNED: A total of 443,053 CT images were used for DL model development and testing. Images were analyzed by the AI framework and expert cardiologists/radiologists. The LAA segmentation performance was evaluated using Dice coefficient. The agreement between manual and automatic LAA ROI selections was evaluated using intraclass correlation coefficient (ICC) analysis. Receiver operating characteristic (ROC) curve analysis was used to assess filling defects based on the computed LAA to ascending aorta Hounsfield unit (HU) ratios.
UNASSIGNED: A total of 210 patients (Group 1: subclinical AF, n = 105; Group 2: clinical AF with stroke, n = 35; Group 3: AF for catheter ablation, n = 70) were enrolled. The LAA volume segmentation achieved 0.931-0.945 Dice scores. The LAA ROI selection demonstrated excellent agreement (ICC ≥0.895, p < 0.001) with manual selection on the test sets. The automatic framework achieved an excellent AUC score of 0.979 in filling defects assessment. The ROC-derived optimal HU ratio threshold for filling defects detection was 0.561.
UNASSIGNED: The novel AI-based framework could accurately segment the LAA region and select ROIs while effectively avoiding trabeculae for filling defects assessment, achieving close-to-expert performance. This technique may help preemptively detect the potential thromboembolic risk for AF patients.

UNASSIGNED: The aim of this study is to quantify the short-term motion of the gastrointestinal tract (GI-tract) and its impact on dosimetric parameters in stereotactic body radiation therapy (SBRT) for pancreatic cancer.
UNASSIGNED: The analyzed patients were eleven pancreatic cancer patients treated with SBRT or proton beam therapy. To ensure a fair analysis, the simulation SBRT plan was generated on the planning CT in all patients with the dose prescription of 40 Gy in 5 fractions. The GI-tract motion (stomach, duodenum, small and large intestine) was evaluated using three CT images scanned at spontaneous expiration. After fiducial-based rigid image registration, the contours in each CT image were generated and transferred to the planning CT, then the organ motion was evaluated. Planning at risk volumes (PRV) of each GI-tract were generated by adding 5 mm margins, and the volume receiving at least 33 Gy (V33) < 0.5 cm3 was evaluated as the dose constraint.
UNASSIGNED: The median interval between the first and last CT scans was 736 s (interquartile range, IQR:624-986). To compensate for the GI-tract motion based on the planning CT, the necessary median margin was 8.0 mm (IQR: 8.0-10.0) for the duodenum and 14.0 mm (12.0-16.0) for the small intestine. Compared to the planned V33 with the worst case, the median V33 in the PRV of the duodenum significantly increased from 0.20 cm3 (IQR: 0.02-0.26) to 0.33 cm3 (0.10-0.59) at Wilcoxon signed-rank test (p = 0.031).
UNASSIGNED: The short-term motions of the GI-tract lead to high dose differences.

This article describes a dataset of synthetic images representing biological scenery as captured by a Fourier Lightfield Microscope (FLMic). It includes 22,416 images related to eight scenes composed of 3D models of objects typical for biological samples, such as red blood cells and bacteria, and categorized into Cells and Filaments groups. For each scene, two types of image data structures are provided: 51 × 51 Elemental Images (EIs) representing Densely Sampled Light Fields (DSLF) and 201 images composing Z-Scans of the scenes. Auxiliary data also includes information about camera intrinsic and extrinsic calibration parameters, object descriptions, and MATLAB scripts for camera pose compensation. The images have been generated using Blender. The dataset can be used to develop and assess methods for volumetric reconstruction from Light Field (LF) images captured by a FLMic.

UNASSIGNED: To assess the potential of radiomic features in comparison to dual-energy CT (DECT) material decomposition to objectively stratify abdominal lymph node metastases.
UNASSIGNED: In this retrospective study, we included 81 patients (m, 57; median age, 65 (interquartile range, 58.7-73.3) years) with either lymph node metastases (n = 36) or benign lymph nodes (n = 45) who underwent contrast-enhanced abdominal DECT between 06/2015-07/2019. All malignant lymph nodes were classified as unequivocal according to RECIST criteria and confirmed by histopathology, PET-CT or follow-up imaging. Three investigators segmented lymph nodes to extract DECT and radiomics features. Intra-class correlation analysis was applied to stratify a robust feature subset with further feature reduction by Pearson correlation analysis and LASSO. Independent training and testing datasets were applied on four different machine learning models. We calculated the performance metrics and permutation-based feature importance values to increase interpretability of the models. DeLong test was used to compare the top performing models.
UNASSIGNED: Distance matrices and t-SNE plots revealed clearer clusters using a combination of DECT and radiomic features compared to DECT features only. Feature reduction by LASSO excluded all DECT features of the combined feature cohort. The top performing radiomic features model (AUC = 1.000; F1 = 1.000; precision = 1.000; Random Forest) was significantly superior to the top performing DECT features model (AUC = 0.942; F1 = 0.762; precision = 0.800; Stochastic Gradient Boosting) (DeLong < 0.001).
UNASSIGNED: Imaging biomarkers have the potential to stratify unequivocal lymph node metastases. Radiomics models were superior to DECT material decomposition and may serve as a support tool to facilitate stratification of abdominal lymph node metastases.

UNASSIGNED: Clinical OCT angiography (OCTA) of the retinal microvasculature offers a quantitative correlate to systemic disease burden and treatment efficacy in sickle cell disease (SCD). The purpose of this study was to use the higher resolution of adaptive optics scanning light ophthalmoscopy (AOSLO) to elucidate OCTA features of parafoveal microvascular compromise identified in SCD patients.
UNASSIGNED: Case series of 11 SCD patients and 1 unaffected control.
UNASSIGNED: A total of 11 eyes of 11 SCD patients (mean age, 33 years; range, 23-44; 8 female, 3 male) and 1 eye of a 34-year-old unaffected control.
UNASSIGNED: Ten sequential 3 × 3 mm parafoveal OCTA full vascular slab scans were obtained per eye using a commercial spectral domain OCT system (Avanti RTVue-XR; Optovue). These were used to identify areas of compromised perfusion near the foveal avascular zone (FAZ), designated as regions of interest (ROIs). Immediately thereafter, AOSLO imaging was performed on these ROIs to examine the cellular details of abnormal perfusion. Each participant was imaged at a single cross-sectional time point. Additionally, 2 of the SCD patients were imaged prospectively 2 months after initial imaging to study compromised capillary segments across time and with treatment.
UNASSIGNED: Detection and characterization of parafoveal perfusion abnormalities identified using OCTA and resolved using AOSLO imaging.
UNASSIGNED: We found evidence of abnormal blood flow on OCTA and AOSLO imaging among all 11 SCD patients with diverse systemic and ocular histories. Adaptive optics scanning light ophthalmoscopy imaging revealed a spectrum of phenomena, including capillaries with intermittent blood flow, blood cell stasis, and sites of thrombus formation. Adaptive optics scanning light ophthalmoscopy imaging was able to resolve single sickled red blood cells, rouleaux formations, and blood cell-vessel wall interactions. OCT angiography and AOSLO imaging were sensitive enough to document improved retinal perfusion in an SCD patient 2 months after initiation of oral hydroxyurea therapy.
UNASSIGNED: Adaptive optics scanning light ophthalmoscopy imaging was able to reveal the cellular details of perfusion abnormalities detected using clinical OCTA. The synergy between these clinical and laboratory imaging modalities presents a promising avenue in the management of SCD through the development of noninvasive ocular biomarkers to prognosticate progression and measure the response to systemic treatment.

UNASSIGNED: Knee osteoarthritis (KOA) is a highly prevalent musculoskeletal disorder characterized by degeneration of cartilage and abnormal remodeling of subchondral bone (SCB). Teriparatide (PTH (1-34)) is an effective anabolic drug for osteoporosis (OP) and regulates osteoprotegerin (OPG)/receptor activator of nuclear factor ligand (RANKL)/RANK signaling, which also has a therapeutic effect on KOA by ameliorating cartilage degradation and inhibiting aberrant remodeling of SCB. However, the mechanisms of PTH (1-34) in treating KOA are still uncertain and remain to be explored. Therefore, we compared the effect of PTH (1-34) on the post-traumatic KOA mouse model to explore the potential therapeutic effect and mechanisms.
UNASSIGNED: In vivo study, eight-week-old male mice including wild-type (WT) (n ​= ​54) and OPG-/- (n ​= ​54) were investigated and compared. Post-traumatic KOA model was created by destabilization of medial meniscus (DMM). WT mice were randomly assigned into three groups: the sham group (WT-sham; n ​= ​18), the DMM group (WT-DMM; n ​= ​18), and the PTH (1-34)-treated group (WT-DMM ​+ ​PTH (1-34); n ​= ​18). Similarly, the OPG-/- mice were randomly allocated into three groups as well. The designed mice were executed at the 4th, 8th, and 12th weeks to evaluate KOA progression. To further explore the chondro-protective of PTH (1-34), the ATDC5 chondrocytes were stimulated with different concentrations of PTH (1-34) in vitro.
UNASSIGNED: Compared with the WT-sham mice, significant wear of cartilage in terms of reduced cartilage thickness and glycosaminoglycan (GAG) loss was detected in the WT-DMM mice. PTH (1-34) exhibited cartilage-protective by alleviating wear, retaining the thickness and GAG contents. Moreover, the deterioration of the SCB was alleviated and the expression of PTH1R/OPG/RANKL/RANK were found to increase after PTH (1-34) treatment. Among the OPG-/- mice, the cartilage of the DMM mice displayed typical KOA change with higher OARSI score and thinner cartilage. The damage of the cartilage was alleviated but the abnormal remodeling of SCB didn\'t show any response to the PTH (1-34) treatment. Compared with the WT-DMM mice, the OPG-/--DMM mice caught more aggressive KOA with thinner cartilage, sever cartilage damage, and more abnormal remodeling of SCB. Moreover, both the damaged cartilage from the WT-DMM mice and the OPG-/--DMM mice were alleviated but only the deterioration of SCB in WT-DMM mice was alleviated after the administration of PTH (1-34). In vitro study, PTH (1-34) could promote the viability of chondrocytes, enhance the synthesis of extracellular matrix (ECM) (AGC, COLII, and SOX9) at the mRNA and protein level, but inhibit the secretion of inflammatory cytokines (TNF-α and IL-6).
UNASSIGNED: Both wear of the cartilage was alleviated and aberrant remodeling of the SCB was inhibited in the WT mice, but only the cartilage-protective effect was observed in the OPG-/- mice. PTH (1-34) exhibited chondro-protective effect by decelerating cartilage degeneration in vivo as well as by promoting the proliferation and enhancing ECM synthesis of chondrocytes in vitro. The current investigation implied that the rescue of the disturbed SCB is dependent on the regulation of OPG while the chondro-protective effect is independent of modulation of OPG, which provides proof for the treatment of KOA.
UNASSIGNED: Systemic administration of PTH (1-34) could exert a therapeutic effect on both cartilage and SCB in different mechanisms to alleviate KOA progression, which might be a novel therapy for KOA.

UNASSIGNED: To prospectively evaluate the image quality and diagnostic performance of a compact flat-panel detector (FD) scanner for thoracic diseases compared to a clinical CT scanner.
UNASSIGNED: The institutional review board approved this single-center prospective study, and all participants provided informed consent. From December 2020 to May 2021, 30 patients (mean age, 67.1 ± 8.3 years) underwent two same-day low-dose chest CT scans using clinical state-of-art and compact FDCT scanners. Image quality was assessed visually and quantitatively. Two readers evaluated the diagnostic performance for nodules, parenchymal opacifications, bronchiectasis, linear opacities, and pleural abnormalities in 40 paired CT scans. The other 20 paired CT scans were used to examine the agreement of semi-quantitative CT scoring regarding bronchiectasis, bronchiolitis, nodules, airspace consolidations, and cavities.
UNASSIGNED: FDCT images had significantly lower visual image quality than clinical CT images (all p < 0.001). The two CT image sets showed no significant differences in signal-to-noise and contrast-to-noise ratios (56.8 ± 12.5 vs. 57.3 ± 15.2; p = 0.985 and 62.9 ± 11.7 vs. 60.7 ± 16.9; p = 0.615). The pooled sensitivity was comparable for nodules, parenchymal opacifications, linear opacities, and pleural abnormalities (p = 0.065-0.625), whereas the sensitivity was significantly lower in FDCT images than in clinical CT images for micronodules (p = 0.007) and bronchiectasis (p = 0.004). The specificity was mostly 1.0. Semi-quantitative CT scores were similar between the CT image sets (p > 0.05), and intraclass correlation coefficients were around 0.950 or higher, except for bronchiectasis (0.869).
UNASSIGNED: Compact FDCT images provided lower image quality but comparable diagnostic performance to clinical CT images for nodules, parenchymal opacifications, linear opacities, and pleural abnormalities.