A Systematic Comparison between the Ethereum and Hyperledger Fabric Blockchain Platforms for Attribute-Based Access Control in Smart Home IoT Environments.

Despite the lack of blockchain systems being utilized in modern IoT environments, the prevalence of blockchain technology is increasing, due to its high level of security and accountability. The integration of blockchain technology and access control in a decentralized system for smart home networks is a promising solution to this issue. This paper compares the implementation of attribute-based access control (ABAC) with two popular blockchain platforms, Ethereum and Hyperledger Fabric, for a smart home internet of things (IoT) environment. We present a comprehensive summary of access-control and blockchain-access-control methods, to provide the necessary background for this study. Additionally, we present an original ABAC smart contract for Ethereum, and the modification of a pre-existing Hyperledger Fabric ABAC smart contract, for this comparison. Through the simulation of both implementations, the advantages and limitations will be considered, to determine which is better suited for a smart home IoT environment.

Adherence to Recommended Preventive Behaviors During the COVID-19 Pandemic: The Role of Empathy and Perceived Health Threat.

BACKGROUND: Coping via empathic responding may play a role in preventive behavior engagement during the COVID-19 pandemic, and unlike trait empathy, is a potentially alterable target for changing health behavior. PURPOSE: Our goal was to examine the role of empathic responding in preventive behavior engagement during the COVID-19 pandemic, independent of trait empathy and perceived threat of COVID-19. METHODS: Participants (N = 2,841) completed a baseline survey early in the pandemic, and a follow-up survey approximately 2 weeks later (M = 13.50 days, SD = 5.61). Preventive health behaviors, including physical distancing and hygiene practices, were assessed at both timepoints. Hierarchical linear regression examined the contributions of trait empathy, perceived threat of COVID-19, and empathic responding at baseline to preventive behaviors at follow-up. RESULTS: Controlling for baseline levels of preventive behaviors and demographic covariates, trait empathy and threat of COVID-19 at baseline were each independently associated with preventive behaviors at follow-up. An interaction between perceived threat and empathic responding indicated that those perceiving high threat of COVID-19 at baseline tended to report engaging in preventive behaviors at follow-up regardless of their levels of empathic responding, whereas for those reporting low levels of perceived threat, higher levels of empathic responding were associated with higher engagement in preventive behavior. CONCLUSIONS: When perceived threat of COVID-19 was low, higher empathic responding was associated with increased engagement in preventive behaviors regardless of trait empathy, suggesting that empathic responding can serve as an actionable target for intervention to promote preventive behavior during the pandemic.

Pandemic stressors and depressive symptoms: Examining within- and between-person effects of neuroticism.

Experiencing stressors related to the COVID-19 pandemic such as health-related concern, social isolation, occupational disruption, financial insecurity, and resource scarcity can adversely impact mental health; however, the extent of the impact varies greatly between individuals. In this study, we examined the role of neuroticism as an individual-level risk factor that exacerbates the association between pandemic stressors and depressive symptoms. With repeated assessments of pandemic stressors and depressive symptoms collected from 3181 participants over the course of the pandemic, we used multilevel modeling to test if neuroticism moderated the association between pandemic stressors and depressive symptoms at both between- and within-person levels. At the between-person level, we found that participants who reported more pandemic stressors on average had higher levels of depressive symptoms and that this association was stronger among those high in neuroticism. At the within-person level, reporting more pandemic stressors relative to one's average on any given occasion was also associated with heightened depressive symptoms and this effect was similarly exacerbated by neuroticism. The findings point to pandemic stressor exposure and neuroticism as risk factors for depressive symptoms and, in demonstrating their synergistic impact, may help identify individuals at greatest risk for adverse psychological responses to the COVID-19 pandemic.

Crystals of Benzamide, the First Polymorphous Molecular Compound, Are Helicoidal.

The growth of spontaneously twisted crystals is a common but poorly understood phenomenon. An analysis of the formation of twisted crystals of a metastable benzamide polymorph (form II) crystallizing from highly supersaturated aqueous and ethanol solutions is given here. Benzamide, the first polymorphic molecular crystal reported (1832), would have been the first helicoidal crystal observed had the original authors undertaken an analysis by light microscopy. Polymorphism and twisting frequently concur as they are both associated with high thermodynamic driving forces for crystallization. Optical and electron microscopies as well as electron and powder X-ray diffraction reveal a complex lamellar structure of benzamide form II needle-like crystals. The internal stress produced by the overgrowth of lamellae is shown to be able to create a twist moment that is responsible for the observed non-classical morphologies.

Severe Bicuspid Aortic Valve Disease in an Adult Cystic Fibrosis Patient.

Bicuspid aortic valve is the most common congenital heart disease. Bicuspid aortic valves are prone to accelerated degenerative changes and aortopathies. These changes often manifest in adulthood as severe aortic stenosis or mixed aortic valve disease. Cystic fibrosis patients are at high risk of adverse surgical outcomes. As survival in cystic fibrosis continues to increase, managing comorbidities including severe aortic stenosis requires consideration. The relatively non-invasive transcatheter aortic valve replacement has been posed as an intervention for high-risk patients with severe symptomatic aortic stenosis. However, traditional randomized trials have excluded patients with bicuspid aortic valves. Herein we present an extremely rare association of severe bicuspid aortic valve stenosis in an adult cystic fibrosis patient. Furthermore, we discuss the clinical course and a multi-disciplinary approach for the management of this rare scenario.

Perceived threat and coping responses during the COVID-19 pandemic: Prospective associations with vaccine hesitancy.

BACKGROUND: The COVID-19 pandemic has brought to light the importance of identifying factors associated with vaccine hesitancy. Disease threat and coping responses are central to health behavior engagement and present potential alterable targets for intervention. PURPOSE: To examine the roles of perceived threat of COVID-19 and coping in vaccine hesitancy, we examined how coping strategies involving approach and avoidance interact with perceived threat of COVID-19 to predict vaccine hesitancy. METHODS: We used data from 1570 North American participants who reported their vaccine hesitancy as part of a longitudinal study assessing psychosocial responses to the pandemic. We used logistic regression models and mean scores of perceived threat of COVID-19, approach coping, and avoidance coping from prior timepoints to predict vaccine hesitancy in December 2020, when COVID-19 vaccines were first being approved for use in North America. RESULTS: Low perceived threat of COVID-19 was associated with greater likelihood of being vaccine hesitant. However, approach coping moderated this association, such that people who engaged in more approach coping were less likely to be vaccine hesitant even when they did not feel personally threatened by COVID-19. In contrast, avoidance coping was associated with greater likelihood of vaccine hesitancy regardless of perceived threat of COVID-19. CONCLUSIONS: Our results illustrate the contributions of approach and avoidance coping to vaccine hesitancy and in doing so, provide preliminary evidence for coping behavior to serve as a target for intervention to reduce vaccine hesitancy.

Multivalent interactions between molecular components involved in fast endophilin mediated endocytosis drive protein phase separation.

A specific group of transmembrane receptors, including the ß1-adrenergic receptor (ß1-AR), is internalized through a non-clathrin pathway known as Fast Endophilin Mediated Endocytosis (FEME). A key question is: how does the endocytic machinery assemble and how is it modulated by activated receptors during FEME. Here we show that endophilin, a major regulator of FEME, undergoes a phase transition into liquid-like condensates, which facilitates the formation of multi-protein assemblies by enabling the phase partitioning of endophilin binding proteins. The phase transition can be triggered by specific multivalent binding partners of endophilin in the FEME pathway such as the third intracellular loop (TIL) of the ß1-AR, and the C-terminal domain of lamellipodin (LPD). Other endocytic accessory proteins can either partition into, or target interfacial regions of, these condensate droplets, and LPD also phase separates with the actin polymerase VASP. On the membrane, TIL promotes protein clustering in the presence of endophilin and LPD C-terminal domain. Our results demonstrate how the multivalent interactions between endophilin, LPD, and TIL regulate protein assembly formation on the membrane, providing mechanistic insights into the priming and initiation steps of FEME.

Psychological distress in North America during COVID-19: The role of pandemic-related stressors.

RATIONALE: The COVID-19 pandemic has wreaked havoc on lives around the globe. In addition to the primary threat of infection, widespread secondary stressors associated with the pandemic have included social isolation, financial insecurity, resource scarcity, and occupational difficulties. OBJECTIVE: The current study examined the impact of these disruptions on psychological distress during the initial adjustment phase to the pandemic in North America. METHOD: A sample of 2463 residents of the US and Canada completed both baseline and follow-up surveys across several weeks between March and May 2020. RESULTS: Those participants perceiving stress related to higher levels of personal threat to health and to the well-being of family members at baseline reported higher levels of depressive symptoms at follow-up, even after controlling for baseline depressive symptoms. In addition, pandemic-related secondary stressors (social isolation, financial insecurity, occupational difficulty, and resource scarcity) were all independently associated with depressive symptoms at follow-up, controlling for both baseline depression and perceived health threats. The results were robust and held up after controlling for demographic factors. Women, young adults, and those who reported lower income were all at higher risk for subsequent depressive symptoms. CONCLUSION: Findings from the present study can help to identify key groups at risk for mental health problems during the pandemic, and indicate actionable areas for targeted intervention.

Lumacaftor/ivacaftor in people with cystic fibrosis with an A455E-CFTR mutation.

BACKGROUND: Previous in vitro organoid data showed A455E-CFTR, a rare CFTR mutation with 4.1% prevalence in the Netherlands, responds to lumacaftor/ivacaftor (LUM/IVA). We explored LUM/IVA's clinical efficacy in people with CF and ≥1 A455E-CFTR mutation. METHODS: Participants aged ≥12 years were randomized to 1 of 2 treatment sequences (LUM/IVA→placebo or placebo→LUM/IVA) with an 8-week washout period between. Primary endpoint was absolute change in ppFEV1 from study baseline through 8 weeks. Additional endpoints were change in sweat chloride concentration (SwCl) and CFQ-R respiratory domain score. Correlations between organoid-based measurements and clinical endpoints were investigated. RESULTS: Twenty participants were randomized at 2 sites in the Netherlands. Mean absolute change in ppFEV1 from study baseline through Week 8 showed a treatment difference of 0.1 percentage points (95% CI, -2.5 to 2.7; P = 0.928) between LUM/IVA (within-group mean change, 2.7) and placebo (within-group mean change, 2.6). The mean absolute change in SwCl concentration from study baseline through Week 8 showed a treatment difference of -7.8 mmol/L between LUM/IVA and placebo (P = 0.004), while the absolute change in CFQ-R respiratory domain score showed a treatment difference of 3.5 between LUM/IVA and placebo (P = 0.469). The in vitro organoid-based assay demonstrated a concentration-dependent swelling increase with LUM/IVA. Exploratory correlation analyses between organoid swelling and ppFEV1 and SwCl outcomes showed correlation coefficients of 0.49 and -0.11, respectively. CONCLUSIONS: In this exploratory study, LUM/IVA elicited an in vitro response in organoid swelling and in vivo response in SwCl in participants with CF and ≥1 A455E-CFTR mutation. The primary endpoint (ppFEV1) did not show a statistically significant difference between LUM/IVA and placebo; correlations between in vitro and in vivo responses were not established (NCT03061331).

Phase 1 Single- and Multiple-Ascending-Dose Randomized Studies of the Safety, Pharmacokinetics, and Pharmacodynamics of AG-348, a First-in-Class Allosteric Activator of Pyruvate Kinase R, in Healthy Volunteers.

Pyruvate kinase deficiency is a chronic hemolytic anemia caused by mutations in PK-R, a key glycolytic enzyme in erythrocytes. These 2 phase 1 randomized, placebo-controlled, double-blind healthy-volunteer studies assessed the safety, tolerability, and pharmacokinetics/pharmacodynamics of AG-348, a first-in-class allosteric PK-R activator. Twelve sequential cohorts were randomized 2:6 to receive oral placebo or AG-348, respectively, as a single dose (30-2500 mg) in the single-ascending-dose (SAD) study (ClinicalTrials.gov: NCT02108106) or 15-700 mg every 12 hours or 120 mg every 24 hours, for 14 days in the multiple-ascending-dose (MAD) study (ClinicalTrials.gov: NCT02149966). All 48 subjects completed the fasted SAD part; 44 of 48 completed the MAD (2 discontinued because of adverse events [AEs], 2 withdrew consent). The most common treatment-related AEs in AG-348-treated subjects were headache (16.7% [SAD] and 13.9% [MAD]) and nausea (13.9%, both studies). AE frequency increased at AG-348 doses ≥ 700 mg (SAD) and at 700 mg every 12 hours (MAD); 1 grade ≥ 3 AE occurred in the latter cohort. Pharmacokinetics were favorable with low variability. Dose-dependent changes in blood glycolytic intermediates consistent with glycolytic pathway activation were observed at all MAD doses, supporting future trials investigating the potential of AG-348 for treating PK deficiency or other anemias.

The susceptibility of cochlear outer hair cells to cyclodextrin is not related to their electromotile activity.

Niemann-Pick Type C1 (NPC1) disease is a fatal neurovisceral disorder caused by dysfunction of NPC1 protein, which plays a role in intracellular cholesterol trafficking. The cholesterol-chelating agent, 2-hydroxypropyl-ß-cyclodextrin (HPßCD), is currently undergoing clinical trials for treatment of this disease. Though promising in alleviating neurological symptoms, HPßCD causes irreversible hearing loss in NPC1 patients and outer hair cell (OHC) death in animal models. We recently found that HPßCD-induced OHC death can be significantly alleviated in a mouse model lacking prestin, an OHC-specific motor protein required for the high sensitivity and sharp frequency selectivity of mammalian hearing. Since cholesterol status is known to influence prestin's electromotility, we examined how prestin contributes to HPßCD-induced OHC death in the disease context using the NPC1 knockout (KO) mouse model (NPC1-KO). We found normal expression and localization of prestin in NPC1-KO OHCs. Whole-cell patch-clamp recordings revealed a significant depolarization of the voltage-operating point of prestin in NPC1-KO mice, suggesting reduced levels of cholesterol in the lateral membrane of OHCs that lack NPC1. OHC loss and elevated thresholds were found for high frequency regions in NPC1-KO mice, whose OHCs retained their sensitivity to HPßCD. To investigate whether prestin's electromotile function contributes to HPßCD-induced OHC death, the prestin inhibitor salicylate was co-administered with HPßCD to WT and NPC1-KO mice. Neither oral nor intraperitoneal administration of salicylate mitigated HPßCD-induced OHC loss. To further determine the contribution of prestin's electromotile function, a mouse model expressing a virtually nonelectromotile prestin protein (499-prestin) was subjected to HPßCD treatment. 499-prestin knockin mice showed no resistance to HPßCD-induced OHC loss. As 499-prestin maintains its ability to bind cholesterol, our data imply that HPßCD-induced OHC death is ascribed to the structural role of prestin in maintaining the OHC's lateral membrane, rather than its motor function.