Blockchain-Based Innovations for Population-Based Registries for Rare Neurodegenerative Diseases

Rare diseases are difficult if not impossible to study outside of population-based registries. Particularly in the context of rare neurodegenerative diseases characterized by case heterogeneity, difficult differential diagnosis by specialists, and small numbers of patients, registries make otherwise unfeasible incidence studies cost-effective and manageable. Building up and maintaining such registries is challenging and requires strong, active, and collaborative networks. Centralization around a leading institution provides structure and consistency, but this single-site storage leads to inefficiency and bottlenecks and is prone to failures, attacks, and manipulation. Furthermore, a substantial amount of trust is required between parties sharing data in a traditional registry. Patients are increasingly reluctant to share data in light of regular news reports about healthcare data breaches. Underfunded rare disease specialized centers are also hesitant to exchange with the leading institution out of fear that the low numbers of patients may seek treatment elsewhere. A lack of electronic health records and information system interoperability in certain settings leads to information silos and only further exacerbate the other issues. Blockchain technology may provide unique, innovative solutions to many of these challenges. Specifically, through digital trust and the use of an immutable distributed ledger, automated data transaction processing, guaranteed integrity, and enhanced security, blockchain technology seems to be perfectly suitable to optimize current population-based rare neurodegenerative disease registry construction and maintenance

Blockchain-Based Innovations for Population-Based Registries for Rare Neurodegenerative Diseases

Rare diseases are difficult if not impossible to study outside of population-based registries. Particularly in the context of rare neurodegenerative diseases characterized by case heterogeneity, difficult differential diagnosis by specialists, and small numbers of patients, registries make otherwise unfeasible incidence studies cost-effective and manageable. Building up and maintaining such registries is challenging and requires strong, active, and collaborative networks. Centralization around a leading institution provides structure and consistency, but this single-site storage leads to inefficiency and bottlenecks and is prone to failures, attacks, and manipulation. Furthermore, a substantial amount of trust is required between parties sharing data in a traditional registry. Patients are increasingly reluctant to share data in light of regular news reports about healthcare data breaches. Underfunded rare disease specialized centers are also hesitant to exchange with the leading institution out of fear that the low numbers of patients may seek treatment elsewhere. A lack of electronic health records and information system interoperability in certain settings leads to information silos and only further exacerbate the other issues. Blockchain technology may provide unique, innovative solutions to many of these challenges. Specifically, through digital trust and the use of an immutable distributed ledger, automated data transaction processing, guaranteed integrity, and enhanced security, blockchain technology seems to be perfectly suitable to optimize current population-based rare neurodegenerative disease registry construction and maintenance

Demonstrating high-precision photometry with a CubeSat: ASTERIA observations of 55 Cancri e

ASTERIA (Arcsecond Space Telescope Enabling Research In Astrophysics) is a 6U CubeSat space telescope (10 cm x 20 cm x 30 cm, 10 kg). ASTERIA's primary mission objective was demonstrating two key technologies for reducing systematic noise in photometric observations: high-precision pointing control and high-stabilty thermal control. ASTERIA demonstrated 0.5 arcsecond RMS pointing stability and $\pm$10 milliKelvin thermal control of its camera payload during its primary mission, a significant improvement in pointing and thermal performance compared to other spacecraft in ASTERIA's size and mass class. ASTERIA launched in August 2017 and deployed from the International Space Station (ISS) November 2017. During the prime mission (November 2017 -- February 2018) and the first extended mission that followed (March 2018 - May 2018), ASTERIA conducted opportunistic science observations which included collection of photometric data on 55 Cancri, a nearby exoplanetary system with a super-Earth transiting planet. The 55 Cancri data were reduced using a custom pipeline to correct CMOS detector column-dependent gain variations. A Markov Chain Monte Carlo (MCMC) approach was used to simultaneously detrend the photometry using a simple baseline model and fit a transit model. ASTERIA made a marginal detection of the known transiting exoplanet 55 Cancri e ($\sim2$~\Rearth), measuring a transit depth of $374\pm170$ ppm. This is the first detection of an exoplanet transit by a CubeSat. The successful detection of super-Earth 55 Cancri e demonstrates that small, inexpensive spacecraft can deliver high-precision photometric measurements.Comment: 23 pages, 9 figures. Accepted in A

Preparation and PET/CT imaging of implant directed 68Ga-labeled magnetic nanoporous silica nanoparticles

Background: Implant infections caused by biofilm forming bacteria are a major threat in orthopedic surgery. Delivering antibiotics directly to an implant affected by a bacterial biofilm via superparamagnetic nanoporous silica nanoparticles could present a promising approach. Nevertheless, short blood circulation half-life because of rapid interactions of nanoparticles with the host’s immune system hinder them from being clinically used. The aim of this study was to determine the temporal in vivo resolution of magnetic nanoporous silica nanoparticle (MNPSNP) distribution and the effect of PEGylation and clodronate application using PET/CT imaging and gamma counting in an implant mouse model. Methods: PEGylated and non-PEGylated MNPSNPs were radiolabeled with gallium-68 (68Ga), implementing the chelator tris(hydroxypyridinone). 36 mice were included in the study, 24 mice received a magnetic implant subcutaneously on the left and a titanium implant on the right hind leg. MNPSNP pharmacokinetics and implant accumulation was analyzed in dependence on PEGylation and additional clodronate application. Subsequently gamma counting was performed for further final analysis. Results: The pharmacokinetics and biodistribution of all radiolabeled nanoparticles could clearly be visualized and followed by dynamic PET/CT imaging. Both variants of 68Ga-labeled MNPSNP accumulated mainly in liver and spleen. PEGylation of the nanoparticles already resulted in lower liver uptakes. Combination with macrophage depletion led to a highly significant effect whereas macrophage depletion alone could not reveal significant differences. Although MNPSNP accumulation around implants was low in comparison to the inner organs in PET/CT imaging, gamma counting displayed a significantly higher %I.D./g for the tissue surrounding the magnetic implants compared to the titanium control. Additional PEGylation and/or macrophage depletion revealed no significant differences regarding nanoparticle accumulation at the implantation site. Conclusion: Tracking of 68Ga-labeled nanoparticles in a mouse model in the first critical hours post-injection by PET/CT imaging provided a better understanding of MNPSNP distribution, elimination and accumulation. Although PEGylation increases circulation time, nanoparticle accumulation at the implantation site was still insufficient for infection treatment and additional efforts are needed to increase local accumulation

Combined Free-running 4D anatomical and flow MRI with native contrast using Synchronization of Neighboring Acquisitions by Physiological Signals (SyNAPS).

BACKGROUND 4D flow MRI often relies on the injection of gadolinium- or iron-oxide-based contrast agents to improve vessel delineation. In this work, a novel technique is developed to acquire and reconstruct 4D flow data with excellent dynamic visualization of blood vessels but without the need for contrast injection. Synchronization of Neighboring Acquisitions by Physiological Signals (SyNAPS) uses Pilot Tone (PT) navigation to retrospectively synchronize the reconstruction of two free-running 3D radial acquisitions, to create co-registered anatomy and flow images. METHODS Thirteen volunteers and two Marfan Syndrome patients were scanned without contrast agent using one free-running fast interrupted steady-state (FISS) sequence and one free-running phase-contrast MRI (PC-MRI) sequence. PT signals spanning the two sequences were recorded for retrospective respiratory motion correction and cardiac binning. The magnitude and phase images reconstructed, respectively, from FISS and PC-MRI, were synchronized to create SyNAPS 4D flow datasets. Conventional 2D flow data were acquired for reference in ascending (AAo) and descending aorta (DAo). The blood-to-myocardium contrast ratio, dynamic vessel area, net volume, and peak flow were used to compare SyNAPS 4D flow with Native 4D flow (without FISS information) and 2D flow. A score of 0-4 was given to each dataset by two blinded experts regarding the feasibility of performing vessel delineation. RESULTS Blood-to-myocardium contrast ratio for SyNAPS 4D flow magnitude images (1.5±0.3) was significantly higher than for Native 4D flow (0.7±0.1, p<0.01), and was comparable to 2D flow (2.3±0.9, p=0.02). Image quality scores of SyNAPS 4D flow from the experts (MP: 1.9±0.3, ET: 2.5±0.5) were overall significantly higher than the scores from Native 4D flow (MP: 1.6±0.6, p=0.03, ET: 0.8±0.4, p<0.01) but still significantly lower than the scores from the reference 2D flow datasets (MP: 2.8±0.4, p<0.01, ET: 3.5±0.7, p<0.01). The Pearson correlation coefficient between the dynamic vessel area measured on SyNAPS 4D flow and that from 2D flow was 0.69±0.24 for the AAo and 0.83±0.10 for the DAo, whereas the Pearson correlation between Native 4D flow and 2D flow measurements was 0.12±0.48 for the AAo and 0.08±0.39 for the DAo. Linear correlations between SyNAPS 4D flow and 2D flow measurements of net volume (r2=0.83) and peak flow (r2=0.87) were larger than the correlations between Native 4D flow and 2D flow measurements of net volume (r2=0.79) and peak flow (r2=0.76). DISCUSSION AND CONCLUSION The feasibility and utility of SyNAPS was demonstrated for joint whole-heart anatomical and flow MRI without requiring ECG gating, respiratory navigators, or contrast agents. Using SyNAPS a high-contrast anatomical imaging sequence can be used to improve 4D flow measurements that often suffer from poor delineation of vessel boundaries in the absence of contrast agents

Public perspectives on protective measures during the COVID-19 pandemic in the Netherlands, Germany and Italy: A survey study

Background: The extent to which people implement government-issued protective measures is critical in preventing further spread of coronavirus disease 2019 (COVID-19) caused by coronavirus SARS-CoV-2. Our study aimed to describe the public belief in the effectiveness of protective measures, the reported implementation of these measures, and to identify communication channels used to acquire information on COVID-19 in European countries during the early stage of the pandemic. Methods and findings: An online survey available in multiple languages was disseminated starting on March 19th, 2020. After five days, we computed descriptive statistics for countries with more than 500 respondents. Each day, we assessed enacted community containment measures by stage of stringency (I-IV). In total, 9,796 adults responded, of whom 8,611 resided in the Netherlands (stage III), 604 in Germany (stage III), and 581 in Italy (stage IV). To explore possible dynamics as containment strategies intensified, we also included 1,365 responses submitted during the following week. Participants indicated support for governmental measures related to avoiding social gatherings, selective closure of public places, and hand hygiene and respiratory measures (range for all measures: 95.0%-99.7%). Respondents from the Netherlands less frequently considered a complete social lockdown effective (59.2%), compared to respondents in Germany (76.6%) or Italy (87.2%). Italian residents applied enforced social distancing measures more frequently (range: 90.2%-99.3%, German and Dutch residents: 67.5%-97.0%) and self-initiated hygienic and social distancing behaviors (range: 36.3%-96.6%, German and Dutch residents: 28.3%-95.7%). Respondents reported being sufficiently informed about the outbreak and behaviors to avoid infection (range: 90.2%-91.1%). Information channels most commonly reported included television newspapers, official health websites, and social media. One week later, we observed no major differences in submitted responses. Conclusions: During the early stage of the COVID-19 pandemic, belief in the effectiveness of protective measures among survey respondents from three European countries was high and participants reported feeling sufficiently informed. In March 2020, implementation of measures differed between countries and were highest among respondents from Italy, who were subjected to the most stringent lockdown measures and greatest COVID-19 burden in Europe during this period

Giving Researchers a Headache - Sex and Gender Differences in Migraine

Migraine is a common neurovascular disorder affecting ∼15% of the general population. Ranking second in the list of years lived with disability (YLD), people living with migraine are greatly impacted by this especially burdensome primary headache disorder. In ∼30% o

The Effect of Socioeconomic Factors and Indoor Residual Spraying on Malaria in Mangaluru, India: A Case-Control Study

India faces 0.5 million malaria cases annually, including half of all Plasmodium vivax malaria cases worldwide. This case–control study assessed socioeconomic determinants of urban malaria in coastal Mangaluru, Karnataka, southwestern India. Between June and December 2015, we recruited 859 malaria patients presenting at the governmental Wenlock Hospital and 2190 asymptomatic community controls. We assessed clinical, parasitological, and socioeconomic data. Among patients, p. vivax mono-infection (70.1%) predominated. Most patients were male (93%), adult (median, 27 years), had no or low-level education (70.3%), and 57.1% were daily labourers or construction workers. In controls (59.3% male; median age, 32 years; no/low-level education, 54.5%; daily labourers/construction workers, 41.3%), 4.1% showed asymptomatic Plasmodium infection. The odds of malaria was reduced among those who had completed 10th school grade (aOR, 0.3; 95% CI, 0.26–0.42), lived in a building with a tiled roof (aOR, 0.71; 95% CI, 0.53–0.95), and reported recent indoor residual spraying (aOR, 0.02; 95% CI, 0.01–0.04). In contrast, migrant status was a risk factor for malaria (aOR, 2.43; 95% CI, 1.60–3.67). Malaria in Mangaluru is influenced by education, housing condition, and migration. Indoor residual spraying greatly contributes to reducing malaria in this community and should be promoted, especially among its marginalised members.Peer Reviewe

Inspired by Sea Urchins: Warburg Effect Mediated Selectivity of Novel Synthetic Non-Glycoside 1,4-Naphthoquinone-6S-Glucose Conjugates in Prostate Cancer

The phenomenon of high sugar consumption by tumor cells is known as Warburg effect. It results from a high glycolysis rate, used by tumors as preferred metabolic pathway even in aerobic conditions. Targeting the Warburg effect to specifically deliver sugar conjugated cytotoxic compounds into tumor cells is a promising approach to create new selective drugs. We designed, synthesized, and analyzed a library of novel 6-S-(1,4-naphthoquinone-2-yl)-d-glucose chimera molecules (SABs)&mdash;novel sugar conjugates of 1,4-naphthoquinone analogs of the sea urchin pigments spinochromes, which have previously shown anticancer properties. A sulfur linker (thioether bond) was used to prevent potential hydrolysis by human glycoside-unspecific enzymes. The synthesized compounds exhibited a Warburg effect mediated selectivity to human prostate cancer cells (including highly drug-resistant cell lines). Mitochondria were identified as a primary cellular target of SABs. The mechanism of action included mitochondria membrane permeabilization, followed by ROS upregulation and release of cytotoxic mitochondrial proteins (AIF and cytochrome C) to the cytoplasm, which led to the consequent caspase-9 and -3 activation, PARP cleavage, and apoptosis-like cell death. These results enable us to further clinically develop these compounds for effective Warburg effect targeting