Introducing keytagging, a novel technique for the protection of medical image-based tests

This paper introduces keytagging, a novel technique to protect medical image-based tests by implementing image authentication, integrity control and location of tampered areas, private captioning with role-based access control, traceability and copyright protection. It relies on the association of tags (binary data strings) to stable, semistable or volatile features of the image, whose access keys (called keytags) depend on both the image and the tag content. Unlike watermarking, this technique can associate information to the most stable features of the image without distortion. Thus, this method preserves the clinical content of the image without the need for assessment, prevents eavesdropping and collusion attacks, and obtains a substantial capacity-robustness tradeoff with simple operations. The evaluation of this technique, involving images of different sizes from various acquisition modalities and image modifications that are typical in the medical context, demonstrates that all the aforementioned security measures can be implemented simultaneously and that the algorithm presents good scalability. In addition to this, keytags can be protected with standard Cryptographic Message Syntax and the keytagging process can be easily combined with JPEG2000 compression since both share the same wavelet transform. This reduces the delays for associating keytags and retrieving the corresponding tags to implement the aforementioned measures to only ¿30 and ¿90. ms respectively. As a result, keytags can be seamlessly integrated within DICOM, reducing delays and bandwidth when the image test is updated and shared in secure architectures where different users cooperate, e.g. physicians who interpret the test, clinicians caring for the patient and researchers

Validation of a Virtual Assistant for Improving Medication Adherence in Patients with Comorbid Type 2 Diabetes Mellitus and Depressive Disorder

Virtual assistants are programs that interact with users through text or voice messages simulating a human-based conversation. The development of healthcare virtual assistants that use messaging platforms is rapidly increasing. Still, there is a lack of validation of these assistants. In particular, this work aimed to validate the effectiveness of a healthcare virtual assistant, integrated within messaging platforms, with the aim of improving medication adherence in patients with comorbid type 2 diabetes mellitus and depressive disorder. For this purpose, a nine-month pilot study was designed and subsequently conducted. The virtual assistant reminds patients about their medication and provides healthcare professionals with the ability to monitor their patients. We analyzed the medication possession ratio (MPR), measured the level of glycosylated hemoglobin (HbA1c), and obtained the patient health questionnaire (PHQ-9) score in the patients before and after the study. We also conducted interviews with all participants. A total of thirteen patients and five nurses used and evaluated the proposed virtual assistant using the messaging platform Signal. Results showed that on average, the medication adherence improved. In the final interview, 69% of the patients agreed with the idea of continuing to use the virtual assistant after the study

Lessons learned after a three-year store and forward teledermatology experience using internet: Strengths and limitations

Purpose This paper presents a three-year teledermatology evaluation experience. The aim is to explain the methodology followed, present the evaluation results, discuss critically the issues that emerged during the experience and report the main lessons learned. Methods A complete design and evaluation methodology was conducted to fully address significant issues arising from other previous teledermatology experiences. First, system-design requirements and image quality issues were studied. Then, a detailed clinical concordance study was undertaken to determine the accuracy of diagnoses made using teledermatology in order to assess different dermatological clinics. Finally, an impact study on the health system was performed. Furthermore, clinical, technical, social and alignment outcomes were analyzed during the study and at the end of it, in order to understand how emerging factors affected the final setup of the teledermatology system. Results The most important results reported in this study can be summarized as follows. (1) A complete web-based environment for teledermatology support was developed as a result of a dynamic evaluation process with clinical personnel. (2) A total of 120 teleconsultations (82 pediatric and 28 adult) were made during the clinical concordance study. Concordance analysis was carried out for each dermatological disease group. High concordance rates were found in pediatrics for inflammatory dermatoses (76%) and also for adults (75%) with infections and infestations. (3) Physicians were satisfied with the teledermatology system but the time dedicated to consultation in primary care was a limiting factor (19 min for each teleconsultation). (4) An extensive discussion about the successful and the limiting aspects of the teledermatology experience revealed the reasons behind the final decision not to proceed with its implementation. It was considered not to be aligned with Health Care Organization (HCO) strategy and consequently did not achieve high-level support for its long-term implementation. Conclusions A high degree of diagnostic accuracy both for pediatric and adult consultations was achieved using the teledermatology system with affordable technical requirements. Its usefulness for filtering dermatological referrals was also demonstrated in the study. Nevertheless, other factors such as the reorganization required for the physicians’ time schedule, remuneration issues, absence of EHR (electronic health record) integration and lack of interaction with the HCO were important limiting factors. This led to the conclusion that under the evaluation conditions long-term set-up was not possible. It was also concluded that HCO participation would have been essential for both the evaluation study and the long-term set-up of the system. Highlights This paper reports a realistic experience in the design and evaluation of a telemedicine solution for remote dermatology consultation (tele-dermatology) in Aragón, Spain. ► This study takes a different approach discussing the strengths and limitations of a teledermatology experience in a realistic manner. ► A list of lessons learned is provided for future teledermatology implementations. Many pediatricians are involved in the experience providing in this way a detailed concordance analysis for children dermatological clinics

Proposal of Real-Time Echocardiogram Transmission Based on Visualization Modes with WiMAX Access

This study presents a new approach to improve the echocardiogram transmissions over WiMAX networks. Using a compression method based on visualization modes and a reliable method that adapts to the channel conditions, overall performance results are improved compared to classical approaches. The echocardiogram transmission using a compression method based on visualization modes requires lower bandwidth than without considering visualization modes. Furthermore, if the proposed reliability method is also used, the echocardiogram is more often visualized with adequate clinical quality than compressing the echocardiogram without distinguishing the visualization modes and without using a reliability method for the available dataset. The reduction in the bandwidth ranges from 29 kbps to 166 kbps for the simulated scenarios. 1

The paralogue of the intrinsically disordered nuclear protein 1 has a nuclear localization sequence that binds to human importin a3

Numerous carrier proteins intervene in protein transport from the cytoplasm to the nucleus in eukaryotic cells. One of those is importin a, with several human isoforms; among them, importin a3 (Impa3) features a particularly high flexibility. The protein NUPR1L is an intrinsically disordered protein (IDP), evolved as a paralogue of nuclear protein 1 (NUPR1), which is involved in chromatin remodeling and DNA repair. It is predicted that NUPR1L has a nuclear localization sequence (NLS) from residues Arg51 to Gln74, in order to allow for nuclear translocation. We studied in this work the ability of intact NUPR1L to bind Impa3 and its depleted species, ¿Impa3, without the importin binding domain (IBB), using fluorescence, isothermal titration calorimetry (ITC), circular dichroism (CD), nuclear magnetic resonance (NMR), and molecular docking techniques. Furthermore, the binding of the peptide matching the isolated NLS region of NUPR1L (NLS-NUPR1L) was also studied using the same methods. Our results show that NUPR1L was bound to Imp a3 with a low micromolar affinity (~5 µM). Furthermore, a similar affinity value was observed for the binding of NLS-NUPR1L. These findings indicate that the NLS region, which was unfolded in isolation in solution, was essentially responsible for the binding of NUPR1L to both importin species. This result was also confirmed by our in silico modeling. The binding reaction of NLS-NUPR1L to ¿Impa3 showed a larger affinity (i.e., lower dissociation constant) compared with that of Impa3, confirming that the IBB could act as an auto-inhibition region of Impa3. Taken together, our findings pinpoint the theoretical predictions of the NLS region in NUPR1L and, more importantly, suggest that this IDP relies on an importin for its nuclear translocation

Automatic image characterization of psoriasis lesions

Psoriasis is a chronic skin disease that affects 125 million people worldwide and, par-ticularly, 2% of the Spanish population, characterized by the appearance of skin lesions due to a growth of the epidermis that is seven times larger than usual. Its diagnosis and monitoring are based on the use of methodologies for measuring the severity and extent of these spots, and this includes a large subjective component. For this reason, this paper presents an automatic method for characterizing psoriasis images that is divided into four parts: image preparation or pre-processing, feature extraction, classification of the lesions, and the obtaining of parameters. The methodology proposed in this work covers different digital-image processing techniques, namely, marker-based image delimitation, hair removal, nipple detection, lesion contour detection, areal-measurement-based lesion classification, as well as lesion characterization by means of red and white intensity. The results obtained were also endorsed by a professional dermatologist. This methodology provides professionals with a common software tool for monitoring the different existing typologies, which proved satisfactory in the cases analyzed for a set of 20 images corresponding to different types of lesions

A phosphorylation-induced switch in the nuclear localization sequence of the intrinsically disordered nupr1 hampers binding to importin

Several carrier proteins are involved in protein transport from the cytoplasm to the nucleus in eukaryotic cells. One of those is importin a, of which there are several human isoforms; among them, importin a3 (Impa3) has a high flexibility. The protein NUPR1, a nuclear protein involved in the cell-stress response and cell cycle regulation, is an intrinsically disordered protein (IDP) that has a nuclear localization sequence (NLS) to allow for nuclear translocation. NUPR1 does localize through the whole cell. In this work, we studied the affinity of the isolated wild-type NLS region (residues 54–74) of NUPR1 towards Impa3 and several mutants of the NLS region by using several biophysical techniques and molecular docking approaches. The NLS region of NUPR1 interacted with Impa3, opening the way to model the nuclear translocation of disordered proteins. All the isolated NLS peptides were disordered. They bound to Impa3 with low micromolar affinity (1.7–27 µM). Binding was hampered by removal of either Lys65 or Lys69 residues, indicating that positive charges were important; furthermore, binding decreased when Thr68 was phosphorylated. The peptide phosphorylated at Thr68, as well as four phospho-mimetic peptides (all containing the Thr68Glu mutation), showed the presence of a sequential NN(i, i + 1) nuclear Overhauser effect (NOE) in the 2D-1H-NMR (two-dimensional–proton NMR) spectra, indicating the presence of turn-like conformations. Thus, the phosphorylation of Thr68 modulates the binding of NUPR1 to Impa3 by a conformational, entropy-driven switch from a random-coil conformation to a turn-like structure

ZZW-115-dependent inhibition of NUPR1 nuclear translocation sensitizes cancer cells to genotoxic agents

Establishing the interactome of the cancer-associated stress protein Nuclear Protein 1 (NUPR1), we found that it binds to several hundreds of proteins, including proteins involved in nuclear translocation, DNA repair, and key factors of the SUMO pathway. We demonstrated that the NUPR1 inhibitor ZZW-115, an organic synthetic molecule, competes with importins for the binding to the NLS region of NUPR1, thereby inhibiting its nuclear translocation. We hypothesized, and then proved, that inhibition of NUPR1 by ZZW-115 sensitizes cancer cells to DNA damage induced by several genotoxic agents. Strikingly, we found that treatment with ZZW-115 reduced SUMOylation of several proteins involved in DNA damage response (DDR). We further report that the presence of recombinant NUPR1 improved the SUMOylation in a cell-free system, indicating that NUPR1 directly stimulates the SUMOylation machinery. We propose that ZZW-115 sensitizes cancer cells to genotoxic agents by inhibiting the nuclear translocation of NUPR1 and thereby decreasing the SUMOylation-dependent functions of key proteins involved in the DDR

Seleno-functionalization of quercetin improves the non-covalent inhibition of mpro and its antiviral activity in cells against sars-cov-2

The development of new antiviral drugs against SARS-CoV-2 is a valuable long-term strategy to protect the global population from the COVID-19 pandemic complementary to the vaccination. Considering this, the viral main protease (Mpro ) is among the most promising molecular targets in light of its importance during the viral replication cycle. The natural flavonoid quercetin 1 has been recently reported to be a potent Mpro inhibitor in vitro, and we explored the effect produced by the introduction of organoselenium functionalities in this scaffold. In particular, we report here a new synthetic method to prepare previously inaccessible C-8 seleno-quercetin derivatives. By screening a small library of flavonols and flavone derivatives, we observed that some compounds inhibit the protease activity in vitro. For the first time, we demonstrate that quercetin (1) and 8-(p-tolylselenyl)quercetin (2d) block SARS-CoV-2 replication in infected cells at non-toxic concentrations, with an IC50 of 192 µM and 8 µM, respectively. Based on docking experiments driven by experimental evidence, we propose a non-covalent mechanism for Mpro inhibition in which a hydrogen bond between the selenium atom and Gln189 residue in the catalytic pocket could explain the higher Mpro activity of 2d and, as a result, its better antiviral profile. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Enhanced real-time ECG coder for packetized telecardiology applications

A new real-time compression method for electrocardiogram (ECG) signals has been developed based on the wavelet transform approach. The method is specifically adaptable for packetized telecardiology applications. The signal is segmented into beats and a beat template is subtracted from them, producing a residual signal. Beat templates and residual signals are coded with a wavelet expansion. Compression is achieved by selecting a subset of wavelet coefficients. The number of selected coefficients depends on a threshold which has different definitions depending on the operational mode of the coder. Compression performance has been tested using a subset of ECG records from MIT-BIH Arrhythmia database. This method has been designed for real-time packetized telecardiology scenarios both in wired and wireless environments