This paper presents an active locomotion capsule endoscope system with 5D position sensing and real-time automated polyp detection for small-bowel and colon applications. An electromagnetic actuation system (EMA) consisting of stationary electromagnets is utilized to remotely control a magnetic capsule endoscope with multi-degree-of-freedom locomotion. For position sensing, an electronic system using a magnetic sensor array is built to track the position and orientation of the magnetic capsule during movement. The system is integrated with a deep learning model, named YOLOv3, which can automatically identify colorectal polyps in real-time with an average precision of 85%. The feasibility of the proposed method concerning active locomotion and localization is validated and demonstrated through in vitro experiments in a phantom duodenum. This study provides a high-potential solution for automatic diagnostics of the bowel and colon using an active locomotion capsule endoscope, which can be applied for a clinical site in the future. Full article

Purpose: To characterize ocular surface temperature (OST) in healthy eyes and its association with systemic risk factors of cardiovascular and ischemic heart disease. Methods: This prospective cross-sectional study included consenting subjects who were examined at the Institute for Medical Screening in Sheba Medical Center. A Therm-App™ thermal imaging camera (Opgal LTD, Israel) was used for OST acquisition, and the mean OST of the medial canthal, lateral canthal, and central cornea regions were measured. Room and body temperatures were also recorded. Past medical and ocular history as well as data from various clinical examinations performed at the same visit were obtained. Results: Thermographic images were obtained from 186 subjects, 150 of which were included in the final analysis. OST was significantly higher in the medial canthal, central cornea, and lateral canthal regions in people with a history of ischemic heart disease (p = 0.02, p = 0.02, and p = 0.03, respectively). There were no significant OST differences (ANOVA test) associated with the presence of hypertension, diabetes mellitus, or active smoking status. Conclusions: OST correlated positively with the presence of ischemic heart disease. This correlation, its pathophysiological base, and its clinical application warrants further investigation. Full article

The Krogh-Poulsen Test is a classic instrument to measure dysfunction of the stomatognathic system whose psychometric properties are unknown. This study aimed to evaluate the psychometric properties of the Krogh-Poulsen Test for the diagnosis of temporomandibular disorders (TMDs). A cross-sectional study was designed, including 119 patients (63 patients with TMD and 56 healthy controls). Factorial validity, inter-rater reliability, error of measurement, diagnostic validity of the Krogh-Poulsen Test, and concurrent validity were analyzed. The Krogh-Poulsen Test showed a three-factor structure. The inter-rater agreement could be considered very good with a kappa index of 0.87 (95% CI 0.83–0.90) and Standard Error of Measurement of 0.79. Correlations were strong with other orofacial instruments, moderate with instruments measuring TMD-related disorders such as neck pain, headache, or dizziness, and poor with generic quality of life instruments. The Area Under the Curve ROC was 0.928 showing, for a cut-off point >1, a sensitivity of 90.48 (95% CI 80.4–96.4) and a specificity of 85.71 (95% CI 73.8–93.6) for the diagnosis of TMD disorders. The Krogh-Poulsen Test showed a three-factor structure, very good inter-rater reliability, a strong correlation with other orofacial instruments, and an excellent capacity to discriminate between patients with or without TMD. Full article

To assess if quantitative integrated deep learning and radiomics features can predict the PD-L1 expression level in preoperative MRI of hepatocellular carcinoma (HCC) patients. The data in this study consist of 103 hepatocellular carcinoma patients who received immunotherapy in a single center. These patients were divided into a high PD-L1 expression group (30 patients) and a low PD-L1 expression group (73 patients). Both radiomics and deep learning features were extracted from their MRI sequence of T2-WI, which were merged into an integrative feature space for machine learning for the prediction of PD-L1 expression. The five-fold cross-validation was adopted to validate the performance of the model, while the AUC was used to assess the predictive ability of the model. Based on the five-fold cross-validation, the integrated model achieved the best prediction performance, with an AUC score of 0.897 ± 0.084, followed by the deep learning-based model with an AUC of 0.852 ± 0.043 then the radiomics-based model with AUC of 0.794 ± 0.035. The feature set integrating radiomics and deep learning features is more effective in predicting PD-L1 expression level than only one feature type. The integrated model can achieve fast and accurate prediction of PD-L1 expression status in preoperative MRI of HCC patients. Full article

Several common and debilitating neurodegenerative disorders are characterized by the intracellular accumulation of neurofibrillary tangles (NFTs), which are composed of hyperphosphorylated tau protein. In Alzheimer’s disease (AD), NFTs are accompanied by extracellular amyloid-beta (Aβ), but primary tauopathy disorders are marked by the accumulation of tau protein alone, including forms of frontotemporal dementia (FTD), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP), among others. ¹⁸F-THK5351 has been reported to bind pathological tau as well as associated reactive astrogliosis. The goal of this study was to validate the ability of the PET tracer ¹⁸F-THK5351 to detect early changes in tau-related pathology and its relation to other pathological hallmarks. We demonstrated elevated in vivo ¹⁸F-THK5351 PET signaling over time in transgenic P301S tau mice from 8 months that had a positive correlation with histological and biochemical tau changes, as well as motor, memory, and learning impairment. This study indicates that ¹⁸F-THK5351 may help fill a critical need to develop PET imaging tracers that detect aberrant tau aggregation and related neuropathology in order to diagnose the onset of tauopathies, gain insights into their underlying pathophysiologies, and to have a reliable biomarker to follow during treatment trials. Full article

Current diagnostic methods for evaluating the functionality of the lymphatic vascular system usually do not provide quantitative data and suffer from many limitations including high costs, complexity, and the need to perform them in hospital settings. In this work, we present a quantitative, simple outpatient technology named LymphMonitor to quantitatively assess lymphatic function. This method is based on the painless injection of the lymphatic-specific near-infrared fluorescent tracer indocyanine green complexed with human serum albumin, using MicronJet600^TM microneedles, and monitoring the disappearance of the fluorescence signal at the injection site over time using a portable detection device named LymphMeter. This technology was investigated in 10 patients with unilateral leg or arm lymphedema. After injection of a tracer solution into each limb, the signal was measured over 3 h and the area under the normalized clearance curve was calculated to quantify the lymphatic function. A statistically significant difference in lymphatic clearance in the healthy versus the lymphedema extremities was found, based on the obtained area under curves of the normalized clearance curves. This study provides the first evidence that the LymphMonitor technology has the potential to diagnose and monitor the lymphatic function in patients. Full article

Minimal residual disease (MRD) status is now considered as one of the most relevant prognostic factors in multiple myeloma (MM) while MRD negativity became an important endpoint in clinical trials. Here, we report the results of the first study evaluating the reproducibility of high-sensitivity flow cytometry MM MRD assessment in four laboratories in Poland. EuroFlow protocols for instrument setting standardization and sample preparation in MM MRD assessment were implemented in each laboratory. In the inter-laboratory reproducibility study, 12 bone marrow samples from MM patients were distributed and processed in participant laboratories. In the inter-operator concordance study, 13 raw data files from MM MRD measurements were analyzed by five independent operators. The inter-laboratory study showed high 95% overall concordance of results among laboratories. In the inter-operator study, 89% of MRD results reported were concordant, and the highest immunophenotype interpretation differences with regard to expression of CD27, CD45, CD81 were noticed. We confirmed the applicability and feasibility of the EuroFlow protocol as a highly sensitive method of MRD evaluation in MM. Results of our inter-center comparison study demonstrate that the standardization of MM MRD assessment protocols is highly desirable to improve quality and comparability of results within and between different clinical trials. Full article

During the last few decades, the role of B cells has been well established and redefined in neuro-inflammatory diseases, including multiple sclerosis and autoantibody-associated diseases. In particular, B cell maturation and trafficking across the blood–brain barrier (BBB) has recently been deciphered with the development of next-generation sequencing (NGS) approaches, which allow the assessment of representative cerebrospinal fluid (CSF) and peripheral blood B cell repertoires. In this review, we perform literature research focusing on NGS studies that allow further insights into B cell pathophysiology during neuro-inflammation. Besides the analysis of CSF B cells, the paralleled assessment of peripheral blood B cell repertoire provides deep insights into not only the CSF compartment, but also in B cell trafficking patterns across the BBB. In multiple sclerosis, CSF-specific B cell maturation, in combination with a bidirectional exchange of B cells across the BBB, is consistently detectable. These data suggest that B cells most likely encounter antigen(s) within the CSF and migrate across the BBB, with further maturation also taking place in the periphery. Autoantibody-mediated diseases, such as neuromyelitis optica spectrum disorder and LGI1 / NMDAR encephalitis, also show features of a CSF-specific B cell maturation and clonal connectivity with peripheral blood. In conclusion, these data suggest an intense exchange of B cells across the BBB, possibly feeding autoimmune circuits. Further developments in sequencing technologies will help to dissect the exact pathophysiologic mechanisms of B cells during neuro-inflammation. Full article

Breast cancer is one of the main causes of death among women worldwide. Early detection of this disease helps reduce the number of premature deaths. This research aims to design a method for identifying and diagnosing breast tumors based on ultrasound images. For this purpose, six techniques have been performed to detect and segment ultrasound images. Features of images are extracted using the fractal method. Moreover, k-nearest neighbor, support vector machine, decision tree, and Naïve Bayes classification techniques are used to classify images. Then, the convolutional neural network (CNN) architecture is designed to classify breast cancer based on ultrasound images directly. The presented model obtains the accuracy of the training set to 99.8%. Regarding the test results, this diagnosis validation is associated with 88.5% sensitivity. Based on the findings of this study, it can be concluded that the proposed high-potential CNN algorithm can be used to diagnose breast cancer from ultrasound images. The second presented CNN model can identify the original location of the tumor. The results show 92% of the images in the high-performance region with an AUC above 0.6. The proposed model can identify the tumor’s location and volume by morphological operations as a post-processing algorithm. These findings can also be used to monitor patients and prevent the growth of the infected area. Full article

Proliferative diabetic retinopathy (PDR) is a major cause of blindness in diabetic individuals. Optical coherence tomography (OCT) and OCT-angiography (OCTA) are noninvasive imaging techniques useful for the diagnosis and assessment of PDR. We aim to review several recent developments using OCT and discuss their present and potential future applications in the clinical setting. An electronic database search was performed so as to include all studies assessing OCT and/or OCTA findings in PDR patients published from 1 January 2020 to 31 May 2021. Thirty studies were included, and the most recently published data essentially focused on the higher detection rate of neovascularization obtained with widefield-OCT and/or OCTA (WF-OCT/OCTA) and on the increasing quality of retinal imaging with quality levels non-inferior to widefield-fluorescein angiography (WF-FA). There were also significant developments in the study of retinal nonperfusion areas (NPAs) using these techniques and research on the impact of PDR treatment on NPAs and on vascular density. It is becoming increasingly clear that it is critical to use adequate imaging protocols focused on optimized segmentation and maximized imaged retinal area, with ongoing technological development through artificial intelligence and deep learning. These latest findings emphasize the growing applicability and role of noninvasive imaging in managing PDR with the added benefit of avoiding the repetition of invasive conventional FA. Full article

(1) Background: Chest radiography (CXR) is still a key diagnostic component in the emergency department (ED). Correct interpretation is essential since some pathologies require urgent treatment. This study quantifies potential discrepancies in CXR analysis between radiologists and non-radiology physicians in training with ED experience. (2) Methods: Nine differently qualified physicians (three board-certified radiologists [BCR], three radiology residents [RR], and three non-radiology residents involved in ED [NRR]) evaluated a series of 563 posterior-anterior CXR images by quantifying suspicion for four relevant pathologies: pleural effusion, pneumothorax, pneumonia, and pulmonary nodules. Reading results were noted separately for each hemithorax on a Likert scale (0–4; 0: no suspicion of pathology, 4: safe existence of pathology) adding up to a total of 40,536 reported pathology suspicions. Interrater reliability/correlation and Kruskal–Wallis tests were performed for statistical analysis. (3) Results: While interrater reliability was good among radiologists, major discrepancies between radiologists’ and non-radiologists’ reading results could be observed in all pathologies. Highest overall interrater agreement was found for pneumothorax detection and lowest agreement in raising suspicion for malignancy suspicious nodules. Pleural effusion and pneumonia were often suspected with indifferent choices (1–3). In terms of pneumothorax detection, all readers mainly decided for a clear option (0 or 4). Interrater reliability was usually higher when evaluating the right hemithorax (all pathologies except pneumothorax). (4) Conclusions: Quantified CXR interrater reliability analysis displays a general uncertainty and strongly depends on medical training. NRR can benefit from radiology reporting in terms of time efficiency and diagnostic accuracy. CXR evaluation of long-time trained ED specialists has not been tested. Full article

18F-FDG-PET/MR images, including DWI, of a 46-year-old male admitted to the Emergency Room of our tertiary center, who was suffering from diplopia, left orbital pain, and a headache for two weeks, demonstrated multiple hepatic nodules, a pancreatic mass, and skeletal metastases, in addition to thrombosis of the left cavernous sinus, thickening of the small intestine, and a large hepatic lesion identified at head and neck MR and whole-body CT, respectively. Hepatic and bone marrow biopsies revealed the diagnosis of Burkitt lymphoma. After four cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, methotrexate/ifosfamide, etoposide, and high dose cytarabine (R- CODOX-M/IVAC), a complete metabolic response occurred. Full article

Using computer tomography angiography (CTA) and computational structural analysis, we present a non-invasive method of mass flow rate/velocity and wall stress analysis in type B aortic dissection. Three-dimensional (3D) computer models of the aorta were calculated using pre-operative (baseline) and post-operative CT data from 12 male patients (aged from 51 to 64 years) who were treated for acute type B dissection. A computational fluid dynamics (CFD) technique was used to quantify the displacement forces acting on the aortic wall in the areas of endografts placement. The mass flow rate and wall stress were measured and quantified using the CFD technique. The CFD model indicated the places with a lower value of blood velocity and shear rate, which corelated with higher blood viscosity and a probability of thrombus appearance. Moreover, with the increase in Hct, blood viscosity also increased, while the intensity of blood flow provoked changing viscosity values in these areas. Furthermore, the velocity gradient near the tear surface caused high wall WSS; this could lead to a decreased resistance in the aorta’s wall with further implications to a patient. Full article

Computed tomography angiography (CTA) is widely used in preoperative evaluation of the lower limbs’ vascular system for virtual surgical planning (VSP) of fibula free flap (FFF) for jaw reconstruction. The present retrospective clinical study analysed n = 72 computed tomography angiographies (CTA) of lower limbs for virtual surgical planning (VSP) for jaw reconstruction. The purpose of the investigation was to evaluate the morphology of the fibular bone and its vascular supply in CTA imaging, and further, the amount and distribution of periosteal branches (PB) and septo-cutaneous perforators (SCPs) of the fibular artery. A total of 144 lower limbs was assessed (mean age: 58.5 ± 15.3 years; 28 females, 38.9%; 44 males, 61.1%). The vascular system was categorized as regular (type I-A to II-C) in 140 cases (97.2%) regarding the classification by Kim. Absent anterior tibial artery (type III-A, n = 2) and posterior tibial artery (type III-B, n = 2) were detected in the left leg. Stenoses were observed mostly in the fibular artery (n = 11), once in the anterior tibial artery, and twice in the posterior tibial artery. In total, n = 361 periosteal branches (PBs) and n = 231 septo-cutaneous perforators (SCPs) were recorded. While a distribution pattern for PBs was separated into two clusters, a more tripartite distribution pattern for SCPs was found. We conclude that conventional CTA for VSP of free fibula flap (FFF) is capable of imaging and distinguishing SCPs and PBs. Full article

Purpose: To study clinical features in patients with ridge-shaped macula (RSM) compared with those with dome-shaped macula (DSM) having been previously classified by the number of swept-source optical coherence tomography (SS-OCT) radial scans affected. Methods: Retrospective observational study including 49 highly myopic eyes from 31 patients who underwent SS-OCT. DSM eyes were defined as those that showed a complete round inward convexity in all their axes, presenting an inward convexity ≥50 µm in the 12-line radial OCT scans. Eyes that did not meet this criterion and had at least one flat radial scan were grouped into the RSM group, defined as a macular inward convexity in some meridians across the fovea, whereas the opposite perpendicularly oriented meridians were flat. Age, spherical equivalent, axial length (AL), and best-corrected visual acuity (BCVA) were collected. Height of the bulge, scleral and choroidal thicknesses, Bruch´s membrane defects, and presence of perforating scleral vessels were recorded. Results: Thirty-seven (75.5%) eyes were classified into the RSM group and 12 (24.5%) into the DSM group. Twenty-six (53.0%) eyes showed macular elevation only in the horizontal direction. Mean AL showed statistically significant differences (28.8 ± 2.7 vs. 30.5 ± 1.5 mm in the RMS vs. DSM group, respectively) and the presence of Bruch´s membrane defects was more frequently seen in DSM (p < 0.001). Mean age, spherical equivalent, BCVA, height of the inward convexity, retinal foveal thickness, foveal scleral thickness, subfoveal choroidal thickness, and the presence of perforating scleral vessels did not show significant differences between groups. Conclusion: This study shows the reliability of using the 12 equal radial OCT scans as an objective method to define and differentiate DSM versus RSM. Patients with RSM showed differences in AL compared with those with DSM, being longer in DSM, and regarding the presence of Bruch´s membrane defects, being more common in DSM. This may contribute to identifying those patients that, in daily clinical practice, have a higher risk of developing complications due to their myopia. Full article