Miracle-dz/UniFAR-FTUs huggingface dataset:
In Vitro Evaluation of Antimicrobial Peptides from the Black Soldier Fly (Hermetia Illucens) against a Selection of Human Pathogens

With the ever growing antimicrobial resistance, finding new candidates for antimicrobial drug development is indispensable. Antimicrobial peptides have steadily gained attention as alternatives for conventional antibiotics, due to some highly desirable characteristics, such as their low propensity for resistance development. ABSTRACT Antimicrobial peptides (AMPs) are being explored as alternatives to traditional antibiotics to combat the rising antimicrobial resistance. Insects have proven to be a valuable source of new, potent AMPs with large structural diversity. For example, the black soldier fly has one of the largest AMP repertoires ever recorded in insects. Currently, however, this AMP collection has not yet undergone antimicrobial evaluation or in-depth in vitro characterization. This study evaluated the activity of a library of 36 black soldier fly AMPs against a panel of human pathogens (Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Candida albicans, and Aspergillus fumigatus) and a human cell line (MRC5-SV2). The activity profile of two cecropins (Hill-Cec1 and Hill-Cec10) with potent Gram-negative activity, was further explored by characterizing their hemolysis, time-to-kill kinetics, membrane-permeabilization properties, and anti-biofilm activity. Hill-Cec1 and Hill-Cec10 also showed high activity against other bacterial species, including Klebsiella pneumoniae and multi-drug resistant P. aeruginosa. Both AMPs are bactericidal and have a rapid onset of action with membrane-permeabilizing effects. Hill-Cec1 and Hill-Cec10 were also able to prevent P. aeruginosa biofilm formation, but no relevant effect was seen on biofilm eradication. Overall, Hill-Cec1 and Hill-Cec10 are promising leads for new antimicrobial development to treat critical infections caused by Gram-negative pathogens such as P. aeruginosa. IMPORTANCE With the ever growing antimicrobial resistance, finding new candidates for antimicrobial drug development is indispensable. Antimicrobial peptides have steadily gained attention as alternatives for conventional antibiotics, due to some highly desirable characteristics, such as their low propensity for resistance development. With this article, we aim to upgrade the knowledge on the activity of black soldier fly antimicrobial peptides and their potential as future therapeutics. To achieve this, we have evaluated for the first time a library of 36 synthetically produced peptides from the black soldier fly against a range of human pathogens and a human cell line. Two selected peptides have undergone additional testing to characterize their antimicrobial profile against P. aeruginosa, a clinically important Gram-negative pathogen with a high established resistance. Overall, this research has contributed to the search for new peptide drug leads to combat the rising antimicrobial resistance.
Speech recognition with a hearing-aid processing scheme combining beamforming with mask-informed speech enhancement

A signal processing approach combining beamforming with mask-informed speech enhancement was assessed by measuring sentence recognition in listeners with mild-to-moderate hearing impairment in adverse listening conditions that simulated the output of behind-the-ear hearing aids in a noisy classroom. Two types of beamforming were compared: binaural, with the two microphones of each aid treated as a single array, and bilateral, where independent left and right beamformers were derived. Binaural beamforming produces a narrower beam, maximising improvement in signal-to-noise ratio (SNR), but eliminates the spatial diversity that is preserved in bilateral beamforming. Each beamformer type was optimised for the true target position and implemented with and without additional speech enhancement in which spectral features extracted from the beamformer output were passed to a deep neural network trained to identify time-frequency regions dominated by target speech. Additional conditions comprising binaural beamforming combined with speech enhancement implemented using Wiener filtering or modulation-domain Kalman filtering were tested in normally-hearing (NH) listeners. Both beamformer types gave substantial improvements relative to no processing, with significantly greater benefit for binaural beamforming. Performance with additional mask-informed enhancement was poorer than with beamforming alone, for both beamformer types and both listener groups. In NH listeners the addition of mask-informed enhancement produced significantly poorer performance than both other forms of enhancement, neither of which differed from the beamformer alone. In summary, the additional improvement in SNR provided by binaural beamforming appeared to outweigh loss of spatial information, while speech understanding was not further improved by the mask-informed enhancement method implemented here.
TRPA1 channel activation with cinnamaldehyde induces cutaneous vasodilation through NOS, but not COX and KCa channel, mechanisms in human

Transient receptor potential (TRP) channels exist in various cells and tissues including nerves and vascular endothelium. TRP channels are implicated in the regulation of several sensory organs associated with pain, pressure, and temperature. While there exists a number of TRP channels, transient receptor potential vanilloid 1 (TRPV1) and 4 (TRPV4) channels in human skin have been shown to modulate cutaneous vasodilation (Fujii et al., 2019; Wong et. al., 2012). Transient receptor potential ankyrin 1 (TRPA1) subtype, which belongs to the TRP channel, is thought to be activated by cold and possibly warm/hot temperatures (Wang and Siemens, 2015). Recently, we showed that TRPA1 channel activation with cinnamaldehyde induced cutaneous vasodilation in humans (Fujii et al., 2020). However, the mechanisms underlying this response remains to be determined. A previous study using mouse ear showed that nitric oxide (NO) synthase (NOS), which is a meditator of endothelium‐dependent vasodilation, can modulate the TRPA1 channel induced cutaneous vasodilation (Aubdool et al., 2016). However, it is unclear if this relationship exists in humans. Moreover, whether cyclooxygenase (COX) and Ca2+ activated K+ (KCa) channels, which are also established modulators of endothelium‐dependent vasodilation, contribute to TRPA1 channel induced cutaneous vasodilation remains to be directly assessed in humans. Based on the above, we evaluated the hypothesis that NOS, COX, and KCa channels mediate the TRPA1 channel induced cutaneous vasodilation in humans. To assess our hypothesis, cutaneous vascular conductance (CVC) was assessed in 9 healthy young adults (29 ± 6 years, 4 women) at four dorsal forearm skin sites treated by intradermal microdialysis with either: 1) vehicle control (98 % propylene glycol + 0.015% lactated Ringer solution + 1.985 % dimethyl sulfoxide), 2)10 mM N(G)‐Nitro‐L‐arginine methylester, a non‐selective NOS inhibitor, 3)10 mM ketorolac, a non‐selective COX inhibitor, or 4) 50 mM tetraethylammonium, a non‐selective KCa channel blocker. Cinnamaldehyde, a TRPA1 channel activator, was administered to each skin site in a dose‐dependent manner (2.9, 8.8, 26 and 80% of cinnamaldehyde concentrations, each lasting at least 30min). Administration of ≥8.8 % cinnamaldehyde increased CVC from baseline at the vehicle control site (e.g., 27.4± 2.7 % increase in CVC, P<0.05). NOS inhibition attenuated the cinnamaldehyde induced‐cutaneous vasodilation at 2.9, 8.8, 26 and 80% concentrations relative to the vehicle control site (all P<0.05). COX inhibition and KCa channel blockade did not attenuate the cinnamaldehyde induced‐cutaneous vasodilation relative to the vehicle control site at all concentrations (all P>0.05). We conclude that in human skin in vivo, NOS plays a role in modulating the regulation of cutaneous vasodilation in response to TRPA1 channel activation with negligible contributions of COX and KCa channels.
Artemisinin displays bactericidal activity via copper-mediated DNA damage

ABSTRACT Artemisinin (ARS) and its semi-synthetic derivatives are effective drugs to treat malaria and possess multiple therapeutic activities based on their endoperoxide bridge. Here, we showed that ARS displayed antibacterial efficacy in Drosophila systemic infections caused by bacterial pathogens but killed only Vibrio cholerae (VC) in vitro, involving reactive oxygen species (ROS) generation and/or DNA damage. This selective antibacterial activity of ARS was attributed to the higher intracellular copper levels in VC, in that the antibacterial activity was observed in vitro upon addition of cuprous ions even against other bacteria and was compromised by the copper-specific chelators neocuproine (NC) and triethylenetetramine (TETA) in vitro and in vivo. We suggest that copper can enhance or reinforce the therapeutic activities of ARS to be repurposed as an antibacterial drug for the treatment of bacterial infections.
Romantic attachment, childhood stability, depression, and PTSD in couples with an incarcerated partner

Incarceration has a multitude of effects on prisoners’ finances, health, education, employment, and family relationships. Incarceration complicates the maintenance of attachment bonds between romantic partners. Data from the Multi‐site Family Study on Incarceration, Parenting, and Partnering were analyzed to examine the effects of childhood stability on adult romantic attachment while controlling for the effects of PTSD and depression within the carceral population. Findings indicate that posttraumatic stress disorder (PTSD) and depression have statistically significant effects on adult romantic attachment. PTSD on romantic attachment for men is statistically significant (p < 0.05) at −0.193 with an overall standardized effect of −0.086. For women, the effect is statistically significant (p < 0.01) at −0.235 with an overall standardized effect of −0.1. Effects of depression on romantic attachment for men is statistically significant (p < 0.001) −0.129 with an overall standardized effect of −0.229. For women, depression is also statistically significant (p < 0.001) at −0.153 with a standardized effect of −0.265. We examined the effects of childhood stability on adult romantic attachment while controlling for the effects of PTSD and depression within the carceral population. Findings supported our hypothesis that individuals with better childhood stability will experience better romantic attachments. Findings related to our hypothesis that having a partner with better childhood stability is positively associated with better romantic attachment produced mixed results. Clinical implications are discussed, and future directions call for research, practice, and training to improve outcomes for justice‐involved romantic partners, their attachment, and consideration of covariates of depression and PTSD.
Evidence that Pacific tuna mercury levels are driven by marine methylmercury production and anthropogenic inputs

Significance Humans are exposed to toxic methylmercury mainly by consuming marine fish. New environmental policies under the Minamata Convention rely on a yet-poorly-known understanding of how mercury emissions translate into fish methylmercury levels. Here, we provide the first detailed map of mercury concentrations from skipjack tuna across the Pacific. Our study shows that the natural functioning of the global ocean has an important influence on tuna mercury concentrations, specifically in relation to the depth at which methylmercury concentrations peak in the water column. However, mercury inputs originating from anthropogenic sources are also detectable, leading to enhanced tuna mercury levels in the northwestern Pacific Ocean that cannot be explained solely by oceanic processes. Pacific Ocean tuna is among the most-consumed seafood products but contains relatively high levels of the neurotoxin methylmercury. Limited observations suggest tuna mercury levels vary in space and time, yet the drivers are not well understood. Here, we map mercury concentrations in skipjack tuna across the Pacific Ocean and build generalized additive models to quantify the anthropogenic, ecological, and biogeochemical drivers. Skipjack mercury levels display a fivefold spatial gradient, with maximum concentrations in the northwest near Asia, intermediate values in the east, and the lowest levels in the west, southwest, and central Pacific. Large spatial differences can be explained by the depth of the seawater methylmercury peak near low-oxygen zones, leading to enhanced tuna mercury concentrations in regions where oxygen depletion is shallow. Despite this natural biogeochemical control, the mercury hotspot in tuna caught near Asia is explained by elevated atmospheric mercury concentrations and/or mercury river inputs to the coastal shelf. While we cannot ignore the legacy mercury contribution from other regions to the Pacific Ocean (e.g., North America and Europe), our results suggest that recent anthropogenic mercury release, which is currently largest in Asia, contributes directly to present-day human mercury exposure.
Indirect cytotoxicity evaluations of antibacterial raw silk fabric doped with calcium, copper and zinc on fibroblasts and osteoblasts

Antibacterial materials are widely used to prevent hospital-acquired infections. In our previous report, metal (calcium, copper or zinc)-doped raw silk fabrics were shown to possess strong antibacterial activities against Escherichia coli. However, antibacterial materials may occasionally be harmful to the human body; thus, in this study, we investigated the cytotoxicities of extracts from metal-doped raw silk fabrics with respect to fibroblasts and osteoblasts indirectly. Calcium-doped raw silk fabric demonstrated cytocompatibility with fibroblasts. Contrarily, copper- and zinc-doped raw silk fabrics remarkably decreased the cell densities of fibroblasts, indicating their cytotoxic effects. This observation could be attributed to the high concentrations of the released copper or zinc ions. However, calcium-, copper- and zinc-doped raw silk fabrics did not demonstrate any cytotoxic effects on osteoblasts because a high concentration of the serum alleviated the effects of these metal ions released from the fabrics. Thus, calcium-doped raw silk fabric is a promising antibacterial material that does not induce strong cytotoxicity. This study will facilitate the design of materials that are both antibacterial and safe.
The effectiveness of nudging: A meta-analysis of choice architecture interventions across behavioral domains

Significance Changing individuals’ behavior is key to tackling some of today’s most pressing societal challenges such as the COVID-19 pandemic or climate change. Choice architecture interventions aim to nudge people toward personally and socially desirable behavior through the design of choice environments. Although increasingly popular, little is known about the overall effectiveness of choice architecture interventions and the conditions under which they facilitate behavior change. Here we quantitatively review over a decade of research, showing that choice architecture interventions successfully promote behavior change across key behavioral domains, populations, and locations. Our findings offer insights into the effects of choice architecture and provide guidelines for behaviorally informed policy making. Over the past decade, choice architecture interventions or so-called nudges have received widespread attention from both researchers and policy makers. Built on insights from the behavioral sciences, this class of behavioral interventions focuses on the design of choice environments that facilitate personally and socially desirable decisions without restricting people in their freedom of choice. Drawing on more than 200 studies reporting over 450 effect sizes (n = 2,149,683), we present a comprehensive analysis of the effectiveness of choice architecture interventions across techniques, behavioral domains, and contextual study characteristics. Our results show that choice architecture interventions overall promote behavior change with a small to medium effect size of Cohen’s d = 0.45 (95% CI [0.39, 0.52]). In addition, we find that the effectiveness of choice architecture interventions varies significantly as a function of technique and domain. Across behavioral domains, interventions that target the organization and structure of choice alternatives (decision structure) consistently outperform interventions that focus on the description of alternatives (decision information) or the reinforcement of behavioral intentions (decision assistance). Food choices are particularly responsive to choice architecture interventions, with effect sizes up to 2.5 times larger than those in other behavioral domains. Overall, choice architecture interventions affect behavior relatively independently of contextual study characteristics such as the geographical location or the target population of the intervention. Our analysis further reveals a moderate publication bias toward positive results in the literature. We end with a discussion of the implications of our findings for theory and behaviorally informed policy making.
Designing for Dissemination and Sustainability to Promote Equitable Impacts on Health

Designing for dissemination and sustainability (D4DS) refers to principles and methods for enhancing the fit between a health program, policy, or practice and the context in which it is intended to be adopted. In this article we first summarize the historical context of D4DS and justify the need to shift traditional health research and dissemination practices. We present a diverse literature according to a D4DS organizing schema and describe a variety of dissemination products, design processes and outcomes, and approaches to messaging, packaging, and distribution. D4DS design processes include stakeholder engagement, participatory codesign, and context and situation analysis, and leverage methods and frameworks from dissemination and implementation science, marketing and business, communications and visual arts, and systems science. Finally, we present eight recommendations to adopt a D4DS paradigm, reflecting shifts in ways of thinking, skills and approaches, and infrastructure and systems for training and evaluation.
North American tree migration paced by climate in the West, lagging in the East

Significance Suitable habitats for forest trees may be shifting fast with recent climate change. Studies tracking the shift in suitable habitat for forests have been inconclusive, in part because responses in tree fecundity and seedling establishment can diverge. Analysis of both components at a continental scale reveals a poleward migration of northern species that is in progress now. Recruitment and fecundity both contribute to poleward spread in the West, while fecundity limits spread in the East, despite a fecundity hotspot in the Southeast. Fecundity limitation on population spread can confront conservation and management efforts with persistent disequilibrium between forest diversity and rapid climate change. Tree fecundity and recruitment have not yet been quantified at scales needed to anticipate biogeographic shifts in response to climate change. By separating their responses, this study shows coherence across species and communities, offering the strongest support to date that migration is in progress with regional limitations on rates. The southeastern continent emerges as a fecundity hotspot, but it is situated south of population centers where high seed production could contribute to poleward population spread. By contrast, seedling success is highest in the West and North, serving to partially offset limited seed production near poleward frontiers. The evidence of fecundity and recruitment control on tree migration can inform conservation planning for the expected long-term disequilibrium between climate and forest distribution.
Lessons learned on the experienced facilitators and barriers of implementing a tailored VBHC model in a Dutch university hospital from a perspective of physicians and nurses

Objective This study aims to obtain insight into experienced facilitators and barriers of implementing a tailored value-based healthcare (VBHC) model in a Dutch university hospital from a perspective of physicians and nurses. Method A descriptive qualitative study with 12 physicians, nurses and managers of seven different care pathways who were involved in the implementation of a tailored VBHC methodology was conducted. Thematic content analysis was used to analyse the data guided by all factors of the Consolidated Framework for Implementation Research (CFIR). Findings The method designed for the implementation of a tailored VBHC methodology was appointed as a structured guide for the process. Throughout the implementation process, leadership and team dynamics were considered as important for the implementation to succeed. Also, sharing experiences with other value teams and the cooperation with external Information Technology (IT) teams in the hospital was mentioned as desirable. The involvement of patients, that is part of the VBHC methodology, was considered useful in the decision-making and improvement of the care process because it gave better insights in topics that are important for patients. The time-consuming nature of the implementation process was named as barrier to the VBHC methodology. On top of that, the shaping of the involvement of patients and the ongoing changes in departments were established as difficult. Finally, working with the Electronic Health Records and acquiring the necessary digital skills were considered to be often forgotten and, thus, hindering implementation. Conclusion Clinical Healthcare organisations implementing a tailored VBHC methodology will benefit from the use of a structured implementation methodology, a well-led strong team and cooperation with (external) teams and patients. However, shaping patient involvement, alignment with other departments and attention to digitisation were seen as a most important concerns in implementation and require further attention.
Voltage-based droop control of converter-interfaced distributed generation units in microgrids

Sinds de laatste jaren is er in het elektrisch energienet een enorme toevloed aan kleine decentrale generatoren, vaak op basis van hernieuwbare energiebronnen. De distributienetten werden echter niet gebouwd om injectie van energie toe te laten. Hierdoor komen steeds meer problemen in de distributienetten voor, zoals bijvoorbeeld overspanningen tijdens zonnige periodes. Dit bemoeilijkt de verdere integratie van hernieuwbare energiebronnen. In deze context werd het microgrid concept voorgesteld om een gecoordineerde koppeling van decentrale generatoren in het net mogelijk te maken. Microgrids zijn kleine subnetten die lokaal hun elementen, zoals de generatoren en de lasten regelen om bepaalde doeleinden te bereiken. Ze kunnen bijvoorbeeld de spanningsregeling in hun net verzorgen of als een geheel meespelen in de energiemarkten. Een karakteristiek van microgrids is dat ze onafhankelijk van het net kunnen werken, in het zogenaamde eilandbedrijf. In eilandbedrijf moeten het verbruik en de opwekking op ieder tijdstip op elkaar afgesteld zijn. Aangezien microgrids erg verschillende eigenschappen hebben van het gewone elektrisch net, zijn hier specifieke regelstrategieen voor vereist. In deze doctoraatsverhandeling wordt een dergelijke regelstrategie uitgewerkt, de zogenaamde spanningsgebaseerde droop (proportionele) regeling. Het spanningsniveau wordt als de niet-conventionele parameter gebruikt om het microgrid te regelen.