Studying Person-Specific Pointing and Gaze Behavior for Multimodal Referencing of Outside Objects from a Moving Vehicle

Hand pointing and eye gaze have been extensively investigated in automotive applications for object selection and referencing. Despite significant advances, existing outside-the-vehicle referencing methods consider these modalities separately. Moreover, existing multimodal referencing methods focus on a static situation, whereas the situation in a moving vehicle is highly dynamic and subject to safety-critical constraints. In this paper, we investigate the specific characteristics of each modality and the interaction between them when used in the task of referencing outside objects (e.g. buildings) from the vehicle. We furthermore explore person-specific differences in this interaction by analyzing individuals' performance for pointing and gaze patterns, along with their effect on the driving task. Our statistical analysis shows significant differences in individual behaviour based on object's location (i.e. driver's right side vs. left side), object's surroundings, driving mode (i.e. autonomous vs. normal driving) as well as pointing and gaze duration, laying the foundation for a user-adaptive approach

Awareness of predatory journals and open access publishing among orthopaedic and trauma surgeons – results from an online survey in Germany

Background Along with emerging open access journals (OAJ) predatory journals increasingly appear. As they harm accurate and good scientific research, we aimed to examine the awareness of predatory journals and open access publishing among orthopaedic and trauma surgeons. Methods In an online survey between August and December 2019 the knowledge on predatory journals and OAJ was tested with a hyperlink made available to the participants via the German Society for Orthopaedics and Trauma Surgery (DGOU) email distributor. Results Three hundred fifty orthopaedic and trauma surgeons participated, of which 291 complete responses (231 males (79.4%), 54 females (18.6%) and 5 N/A (2.0%)) were obtained. 39.9% were aware of predatory journals. However, 21.0% knew about the “Directory of Open Access Journals” (DOAJ) as a register for non-predatory open access journals. The level of profession (e.g. clinic director, consultant) (p = 0.018) influenced the awareness of predatory journals. Interestingly, participants aware of predatory journals had more often been listed as corresponding authors (p < 0.001) and were well published as first or last author (p < 0.001). Awareness of OAJ was masked when journal selection options did not to provide any information on the editorial board, the peer review process or the publication costs. Conclusion The impending hazard of predatory journals is unknown to many orthopaedic and trauma surgeons. Early stage clinical researchers must be trained to differentiate between predatory and scientifically accurate journals

Surgical treatment outcome after serial debridement of infected nonunion—A retrospective cohort study

Purpose Reported outcome after multiple staged surgical treatment of infected nonunion is scarce. We, therefore, asked: (1) What is the clinical outcome in infected nonunion patients after multiple staged revision surgery? (2) Are different pathogens evidenced after surgical treatment in patients who have undergone more or less surgeries? Methods All enrolled patients were surgically treated for long bone-infected nonunion between January 2010 and March 2018. Besides patients´ demographics outcome in terms of bony consolidation and major complications defined as death during inward treatment, amputation and recurrence of infection during follow-up of at least 12 months were assessed. Microbiological findings were assessed and compared between two groups with less than five versus five or more surgical revisions. Results Bone consolidation was achieved in 86% of the patients while complications such as femoral or transtibial amputation, recurrence of infection or even death during inpatient treatment could be evidenced in six patients (14%). In patients who underwent multiple-stage surgery for five or more times, germ changes and repeated germ detection was more common than in patients with less surgeries. Conclusions Surgical treatment of infected nonunions poses a high burden on the patients with major complications occurring in about 14% of the patients using a multiple staged treatment concept. Future prospective studies comparing outcomes after limited with multiple staged revision surgeries are necessary

Immunotheranostic target modules for imaging and navigation of UniCAR T-cells to strike FAP-expressing cells and the tumor microenvironment

Abstract Background Chimeric antigen receptor (CAR) T-cells are a promising approach in cancer immunotherapy, particularly for treating hematologic malignancies. Yet, their effectiveness is limited when tackling solid tumors, where immune cell infiltration and immunosuppressive tumor microenvironments (TME) are major hurdles. Fibroblast activation protein (FAP) is highly expressed on cancer-associated fibroblasts (CAFs) and various tumor cells, playing an important role in tumor growth and immunosuppression. Aiming to modulate the TME with increased clinical safety and effectiveness, we developed novel small and size-extended immunotheranostic UniCAR target modules (TMs) targeting FAP. Methods The specific binding and functionality of the αFAP-scFv TM and the size-extended αFAP-IgG4 TM were assessed using 2D and 3D in vitro models as well as in vivo. Their specific tumor accumulation and diagnostic potential were evaluated using PET studies after functionalization with a chelator and suitable radionuclide. Results The αFAP-scFv and -IgG4 TMs effectively and specifically redirected UniCAR T-cells using 2D, 3D, and in vivo models. Moreover, a remarkably high and specific accumulation of radiolabeled FAP-targeting TMs at the tumor site of xenograft mouse models was observed. Conclusions These findings demonstrate that the novel αFAP TMs are promising immunotheranostic tools to foster cancer imaging and treatment, paving the way for a more convenient, individualized, and safer treatment of cancer patients. Graphical Abstrac

Divergent functions of two ancient Hydra Brachyury paralogues suggest specific roles for their C-terminal domains in tissue fate induction

Homologues of the T-box gene Brachyury play important roles in mesoderm differentiation and other aspects of early development in all bilaterians. In the cliploblast Hydra, the Brachyury homologue HyBra1 acts early in the formation of the hypostome, the location of the organiser in adult Hydra. We now report the isolation and characterisation of a second Brachyury gene, HyBra2. Sequence analysis suggests that HyBra1 and HyBra2 are paralogues, resulting from an ancient lineage-specific gene duplication. We show that both paralogues acquired novel functions, both at the level of their cis-regulation as well as through significant divergence of the coding sequence. Both genes are expressed in the hypostome, but HyBra1 is predominantly endodermal, whereas HyBra2 transcripts are found primarily in the ectoderm. During bud formation, both genes are activated before any sign of evagination, suggesting an early role in head formation. During regeneration, HyBra1 is an immediate-early response gene and is insensitive to protein synthesis inhibition, whereas the onset of expression of HyBra2 is delayed and requires protein synthesis. The functional consequence of HyBra1/2 protein divergence on cell fate decisions was tested in Xenopus. HyBra1 induces mesoderm, like vertebrate Brachyury proteins. By contrast, HyBra2 shows a strong cement-gland and neural-inducing activity. Domain-swapping experiments show that the C-terminal domain of HyBra2 is responsible for this specific phenotype. Our data support the concept of sub- and neofunctionalisation upon gene duplication and show that divergence of cis-regulation and coding sequence in paralogues can lead to dramatic changes in structure and function