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AIMS COVID-19 has had enormous consequences on global health care and resulted in millions of fatalities. The exact mechanism and site of SARS-CoV-2 entry into the body remains insufficiently understood. Recently, novel virus receptors were identified, and alveolar macrophages were suggested as a potential viral entry cell type and vector for intra-alveolar virus transmission. Here, we investigated the protein expression of ten well-known and novel virus entry molecules along potential entry sites in humans using immunohistochemistry. METHODS AND RESULTS Samples of different anatomic sites from up to 93 patients were incorporated into tissue microarrays. Protein expression of ACE2, TMPRSS2, furin, CD147, C-type lectin receptors (CD169, CD209, CD299), neuropilin-1, ASGR1 and KREMEN1 were analyzed. In lung tissues, at least one of the three receptors ACE2, ASGR1 or KREMEN1 was expressed in the majority of cases. Moreover, all of the investigated molecules were found to be expressed in alveolar macrophages, and colocalization with SARS-CoV-2 N-protein was demonstrated using dual immunohistochemistry in lung tissue from a COVID-19 autopsy. While CD169 and CD209 showed consistent protein expression in sinonasal, conjunctival and bronchiolar tissues, neuropilin-1 and ASGR1 were mostly absent, suggesting a minor relevance of these two molecules at these specific sites. CONCLUSION Our results extend recent discoveries indicating a role for these molecules in virus entry at different anatomic sites. Moreover, they support the notion of alveolar macrophages being a potential entry cell for SARS-CoV-2.

Postural instability as a symptom of progressing Parkinson's disease (PD) greatly reduces quality of life. Hence, early detection of postural impairments is crucial to facilitate interventions. Our aim was to use a convolutional neural network (CNN) to differentiate people with early to mid-stage PD from healthy age-matched individuals based on spectrogram images obtained from their body movement. We hypothesized the time-frequency content of body sway to be predictive of PD, even when impairments are not yet manifested in day-to-day postural control. We tracked their center of pressure (COP) using a Wii Balance Board and their full-body motion using a Microsoft Kinect, out of which we calculated the trajectory of their center of mass (COM). We used 30 s-snippets of motion data from which we acquired wavelet-based time-frequency spectrograms that were fed into a custom-built CNN as labeled images. We used binary classification to have the network differentiate between individuals with PD and controls (n=15, respectively). Classification performance was best when the medio-lateral motion of the COM was considered. Here, our network reached an average predictive accuracy of 98.45 % with a receiver operating characteristic area under the curve of 1.0. Moreover, an explainable AI approach revealed high frequencies in the postural sway data to be most distinct between both groups. Our findings suggest a CNN classifier based on cost-effective and conveniently obtainable posturographic data to be a promising approach to detect postural impairments in early to mid-stage PD and to gain novel insight into the subtle characteristics of impairments at this stage of the disease.

The integration of Artificial Intelligence (AI) and Digital Pathology has been increasing over the past years. Nowadays, applications of deep learning (DL) methods to diagnose cancer from whole-slide images (WSI) are, more than ever, a reality within different research groups. Nonetheless, the development of these systems was limited by a myriad of constraints regarding the lack of training samples, the scaling difficulties, the opaqueness of DL methods, and, more importantly, the lack of clinical validation. As such, we propose a system designed specifically for the diagnosis of colorectal samples. The construction of such a system consisted of four stages: (1) a careful data collection and annotation process, which resulted in one of the largest WSI colorectal samples datasets; (2) the design of an interpretable mixed-supervision scheme to leverage the domain knowledge introduced by pathologists through spatial annotations; (3) the development of an effective sampling approach based on the expected severeness of each tile, which decreased the computation cost by a factor of almost 6x; (4) the creation of a prototype that integrates the full set of features of the model to be evaluated in clinical practice. During these stages, the proposed method was evaluated in four separate test sets, two of them are external and completely independent. On the largest of those sets, the proposed approach achieved an accuracy of 93.44%. DL for colorectal samples is a few steps closer to stop being research exclusive and to become fully integrated in clinical practice., Under Review