Miracle-dz/UniFAR-FTUs huggingface dataset:
Access to Firearms Among People Assessed by Psychiatric Services in the Emergency Department

Objective: In Canada, 80% of firearm-related deaths are suicides. Access to firearms is associated with increased suicide rates. This study examines the frequency and factors that influence assessment of firearm access in an emergency setting. Methods: A total of 15,847 consecutive adults seen for psychiatric consultation in two tertiary emergency departments (EDs) in Winnipeg, Manitoba were interviewed. Data captured whether access to firearms was assessed, and whether respondents endorsed access or not. Comparisons were done to determine group differences among those with and without and with known and unknown firearm access. Results: Access to firearms was unknown in 47% (n = 7,363) of psychiatric ED consultations, including 43% (n = 998) of individuals who presented with a suicide attempt. Female sex was associated with decreased odds of firearm access (odds ratio [OR] 0.28; 95% CI, 0.22 to 0.35). Being single was associated with lower odds of known firearm access (OR 0.83; 95% CI, 0.77 to 0.89) yet higher likelihood of firearm access (OR 1.36; 95% CI, 1.11 to 1.68). Presenting with a suicide attempt (OR 2.45; 95% CI, 1.80 to 3.34), preparatory acts (OR 6.40; 95% CI, 4.38 to 9.36) and suicidal ideation (OR 2.45; 95% CI, 1.87 to 3.21) were associated with increased odds of reporting access. When clinicians felt there was a high likelihood of future suicide, firearm access remained unknown in half of cases. Conclusion: Firearm ownership and access is an essential component of a suicide risk assessment and remains unknown in half of individuals seen by psychiatry in this tertiary care ED sample. People presenting with suicidal ideation and attempts were more likely to report access to firearms.
Human C-terminal CUBN variants associate with chronic proteinuria and normal renal function.

BACKGROUND Proteinuria is considered as an unfavorable clinical condition that accelerates renal and cardiovascular disease. However, it is not clear if all forms of proteinuria are damaging. Mutations in CUBN cause Imerslund-Gräsbeck syndrome (IGS) featured by intestinal malabsorption of vitamin B12 and in some cases proteinuria. CUBN encodes for cubilin, an intestinal and proximal tubular uptake receptor containing 27 CUB domains for ligand binding. METHODS We used next-generation sequencing for renal disease genes to genotype cohorts of patients with suspected hereditary renal disease and chronic proteinuria. CUBN variants were analyzed using bioinformatics, structural modeling and epidemiological methods. RESULTS We identified 39 patients, in whom biallelic pathogenic variants in the CUBN gene are associated with chronic isolated proteinuria with childhood onset. Since the proteinuria displayed a high proportion of albuminuria, glomerular diseases such as steroid-resistant nephrotic syndrome or Alport syndrome were often the primary clinical diagnosis, motivating renal biopsies and proteinuria-lowering treatments. Yet, renal function was normal in all cases. By contrast, we did not find any biallelic pathogenic CUBN variants in patients with reduced renal function or focal segmental glomerulosclerosis. Unlike the more N-terminal IGS mutations, 37 out of the 41 proteinuria-associated CUBN variants led to modifications or truncations after the vitamin B12-binding domain. Finally, we show that four C-terminal CUBN variants are associated with albuminuria and moderately increased GFR in meta-analyses of large population-based cohorts. CONCLUSIONS Collectively, our data suggest an important role for the C-terminal half of cubilin in renal albumin reabsorption. Albuminuria due to reduced cubilin function could be an unexpectedly common benign condition in humans that may not require any proteinuria-lowering treatment or renal biopsies.
Parameter Optimization and Learning in a Spiking Neural Network for UAV Obstacle Avoidance Targeting Neuromorphic Processors

The Lobula giant movement detector (LGMD) is an identified neuron of the locust that detects looming objects and triggers the insect’s escape responses. Understanding the neural principles and network structure that leads to these fast and robust responses can facilitate the design of efficient obstacle avoidance strategies for robotic applications. Here, we present a neuromorphic spiking neural network model of the LGMD driven by the output of a neuromorphic dynamic vision sensor (DVS), which incorporates spiking frequency adaptation and synaptic plasticity mechanisms, and which can be mapped onto existing neuromorphic processor chips. However, as the model has a wide range of parameters and the mixed-signal analog-digital circuits used to implement the model are affected by variability and noise, it is necessary to optimize the parameters to produce robust and reliable responses. Here, we propose to use differential evolution (DE) and Bayesian optimization (BO) techniques to optimize the parameter space and investigate the use of self-adaptive DE (SADE) to ameliorate the difficulties of finding appropriate input parameters for the DE technique. We quantify the performance of the methods proposed with a comprehensive comparison of different optimizers applied to the model and demonstrate the validity of the approach proposed using recordings made from a DVS sensor mounted on an unmanned aerial vehicle (UAV).
The Role of Oxytocin in the Dog–Owner Relationship

Simple Summary A number of studies have shown that when dogs and humans interact with each other in a positive way (for example cuddling) both partners exhibit a surge in oxytocin, a hormone which has been linked to positive emotional states. It is not clear however, if this increase in oxytocin occurs between any dog and human or whether this is more specific to the dog–owner bond. In this study we measured oxytocin levels in dogs and humans before and after they interacted with their closely bonded partner (dog–owner dyads) and with a partner they were familiar with but with whom they did not have a close bond. Based on previous literature we predicted that dogs and owners would show an increase in oxytocin after a positive social interaction, and that this increase would be higher when the dog and owner were interacting with each other than when the interaction occurred with a partner that was just ‘familiar’. In fact, overall we did not find an increase in either, dogs’ or humans’ oxytocin level, although there was a lot of variability in the response. We discuss various reasons why our results are not in line with other studies. Abstract Oxytocin (OT) is involved in multiple social bonds, from attachment between parents and offspring to “friendships”. Dogs are an interesting species in which to investigate the link between the oxytocinergic system and social bonds since they establish preferential bonds with their own species but also with humans. Studies have shown that the oxytocinergic system may be involved in the regulation of such inter-specific relationships, with both dogs and their owners showing an increase in OT levels following socio-positive interactions. However, no direct comparison has been made in dogs’ OT reactivity following a social interaction with the owner vs. a familiar (but not bonded) person, so it is unclear whether relationship type mediates OT release during socio-positive interactions or whether the interaction per se is sufficient. Here we investigated OT reactivity in both dogs and owners, following a socio-positive interaction with each other or a familiar partner. Results showed neither the familiarity with the partner, nor the type of interaction affected OT reactivity (as measured in urine) in either dogs or owners. Given the recent mixed results on the role of oxytocin in dog-human interactions, we suggest there is a need for greater standardization of methodologies, an assessment of overall results taking into account ‘publication bias’ issues, and further studies investigating the role of relationship quality and interaction type on OT release.
Uncovering the Disconnect Between Nursing Workforce Policy Intentions, Implementation, and Outcomes: Lessons Learned From the Addition of a Nursing Assistant Role

The use of nursing assistants has increased across health systems in the past 20 years, to alleviate licensed nurses' workload and to meet rising health care demands at lower costs. Evidence suggests that, when used as a substitute for licensed nurses, assistants are associated with poorer patient and nurse outcomes. Our multimethods study evaluated the impact of a policy to add nursing assistants to existing nurse staffing in Western Australia's public hospitals, on a range of outcomes. In this article, we draw the metainferences from previously published quantitative data and unpublished qualitative interview data. A longitudinal analysis of patient records found significantly higher rates adverse patient outcomes on wards that introduced nursing assistants compared with wards that did not. These findings are explained with ward-level data that show nursing assistants were added to wards with preexisting workload and staffing problems and that those problems persisted despite the additional resources. There were also problems integrating assistants into the nursing team, due to ad hoc role assignments and variability in assistants' knowledge and skills. The disconnect between policy intention and outcomes reflects a top-down approach to role implementation where assistants were presented as a solution to nurses' workload problems, without an understanding of the causes of those problems. We conclude that policy makers and managers must better understand individual care environments to ensure any new roles are properly tailored to patient and staff needs. Further, standardized training and accreditation for nursing assistant roles would reduce the supervisory burden on licensed nurses.
Lipid rafts and pathogens: the art of deception and exploitation

Lipid rafts, solid regions of the plasma membrane enriched in cholesterol and glycosphingolipids, are essential parts of a cell. Functionally, lipid rafts present a platform that facilitates interaction of cells with the outside world. However, the unique properties of lipid rafts required to fulfill this function at the same time make them susceptible to exploitation by pathogens. Many steps of pathogen interaction with host cells, and sometimes all steps within the entire lifecycle of various pathogens, rely on host lipid rafts. Such steps as binding of pathogens to the host cells, invasion of intracellular parasites into the cell, the intracellular dwelling of parasites, microbial assembly and exit from the host cell, and microbe transfer from one cell to another all involve lipid rafts. Interaction also includes modification of lipid rafts in host cells, inflicted by pathogens from both inside and outside the cell, through contact or remotely, to advance pathogen replication, to utilize cellular resources, and/or to mitigate immune response. Here, we provide a systematic overview of how and why pathogens interact with and exploit host lipid rafts, as well as the consequences of this interaction for the host, locally and systemically, and for the microbe. We also raise the possibility of modulation of lipid rafts as a therapeutic approach against a variety of infectious agents.
Learning, memory and consolidation mechanisms for behavioral control in hierarchically organized cortico‐basal ganglia systems

This article aims to provide a synthesis on the question how brain structures cooperate to accomplish hierarchically organized behaviors, characterized by low‐level, habitual routines nested in larger sequences of planned, goal‐directed behavior. The functioning of a connected set of brain structures—prefrontal cortex, hippocampus, striatum, and dopaminergic mesencephalon—is reviewed in relation to two important distinctions: (a) goal‐directed as opposed to habitual behavior and (b) model‐based and model‐free learning. Recent evidence indicates that the orbitomedial prefrontal cortices not only subserve goal‐directed behavior and model‐based learning, but also code the “landscape” (task space) of behaviorally relevant variables. While the hippocampus stands out for its role in coding and memorizing world state representations, it is argued to function in model‐based learning but is not required for coding of action–outcome contingencies, illustrating that goal‐directed behavior is not congruent with model‐based learning. While the dorsolateral and dorsomedial striatum largely conform to the dichotomy between habitual versus goal‐directed behavior, ventral striatal functions go beyond this distinction. Next, we contextualize findings on coding of reward‐prediction errors by ventral tegmental dopamine neurons to suggest a broader role of mesencephalic dopamine cells, viz. in behavioral reactivity and signaling unexpected sensory changes. We hypothesize that goal‐directed behavior is hierarchically organized in interconnected cortico‐basal ganglia loops, where a limbic‐affective prefrontal‐ventral striatal loop controls action selection in a dorsomedial prefrontal–striatal loop, which in turn regulates activity in sensorimotor‐dorsolateral striatal circuits. This structure for behavioral organization requires alignment with mechanisms for memory formation and consolidation. We propose that frontal corticothalamic circuits form a high‐level loop for memory processing that initiates and temporally organizes nested activities in lower‐level loops, including the hippocampus and the ripple‐associated replay it generates. The evidence on hierarchically organized behavior converges with that on consolidation mechanisms in suggesting a frontal‐to‐caudal directionality in processing control.
Anti-Inflammatory Effects of Lipids Extracted from Arctoscopus japonicus Eggs on LPS-Stimulated RAW264.7 Cells

Arctoscopus japonicus is a cold-water marine fish. The present study investigated the fatty acid composition of A. japonicus egg lipids and their anti-inflammatory effects on LPS-stimulated RAW246.7 macrophages. The results showed that A. japonicus egg lipids contained primarily polyunsaturated fatty acids (52.9% of the total fatty acid content; mostly eicosapentaenoic acid [EPA, 21.2 ± 0.5%] and docosahexaenoic acid [DHA, 25.9 ± 0.1%]), followed by monounsaturated fatty acids and saturated fatty acids (23.7% and 23.4%, respectively). A. japonicus egg lipids significantly decreased nitric oxide (NO) production and suppressed the expression of immune-associated genes such as iNOS, COX-2, IL-1β, IL-6, and TNF-α LPS-stimulated RAW246.7 macrophages in dose-dependent manner. A. japonicus egg lipids also reduced the phosphorylation levels of NF-κB p-65, p38, ERK1/2, and JNK, key components of the NF-κB and MAPK pathways, suggesting that the lipid-induced anti-inflammatory activity is related to these signaling pathways. These results indicate that the lipids extracted from A. japonicus eggs have potential biofunctions and might be useful for regulating inflammation in macrophages.
Topical 2′-Hydroxyflavanone for Cutaneous Melanoma

2′-hydroxyflavanone (2HF) is a dietary flavonoid with anticancer activity towards multiple cancers. Here, we report that topically applied 2HF inhibits the growth of intradermal implants of melanoma in immunocompetent mice. 2HF induced apoptosis and inhibited the growth of the human SK-MEL-24 as well as murine B16-F0 and B16-F10 melanoma cell lines in vitro. Apoptosis was associated with depletion of caspase-3, caspase-9, and PARP1 in B16-F0 and SK-MEL-24 cells. Caspase-9 and MEKK-15 were undetected even in untreated B16-F10 cells. Signaling proteins TNFα, and phospho-PDGFR-β were depleted in all three cell lines; MEKK-15 was depleted by 2HF in SK-MEL-24 cells. 2HF enhanced sunitinib (an MEK and PDGFR-β inhibitor) and AZD 2461 (a PARP1 inhibitor) cytotoxicity. 2HF also depleted the Ral-regulated, stress-responsive, antiapoptotic endocytic protein RLIP76 (RALBP1), the inhibition of which has previously been shown to inhibit B16-F0 melanoma growth in vivo. Functional inhibition of RLIP76 was evident from inhibition of epidermal growth factor (EGF) endocytosis by 2HF. We found that topically applied 2HF–Pluronic Lecithin Organogel (PLO) gel inhibited B16-F0 and B16-F10 tumors implanted in mice and caused no overt toxicity despite significant systemic absorption. 2HF treatment reduced phospho-AKT, vimentin, fibronectin, CDK4, cyclinB1, and BCL2, whereas it increased BIM and phospho-AMPK in excised tumors. Several cancer signals are controlled by endocytosis, a process strongly inhibited by RLIP76 depletion. We conclude that 2HF–PLO gel may be useful for topical therapy of cutaneous metastases of melanoma and could enhance the antineoplastic effects of sunitinib and PARP1 inhibitors. The mechanism of action of 2HF in melanoma overlaps with RLI76 inhibitors.
Differential effects of saturated and unsaturated fatty acids on autophagy in pancreatic β-cells.

Long chain saturated fatty acids are lipotoxic to pancreatic β-cells whereas most unsaturates are better tolerated and some may even be cytoprotective. Fatty acids alter autophagy in β-cells and there is increasing evidence that such alterations can impact directly on the regulation of viability. Accordingly, we have compared the effects of palmitate (C16:0) and palmitoleate (C16:1) on autophagy in cultured β-cells and human islets. Treatment of BRIN-BD11 β-cells with palmitate led to enhanced autophagic activity, as judged by cleavage of microtubule-associated protein 1 light chain 3-I (LC3-I) and this correlated with a marked loss of cell viability in the cells. In addition, transfection of these cells with an mCherry-YFP-LC3 reporter construct revealed the accumulation of autophagosomes in palmitate-treated cells, indicating an impairment of autophagosome-lysosome fusion. This was also seen upon addition of the vacuolar ATPase inhibitor, bafilomycin A1. Exposure of BRIN-BD11 cells to palmitoleate (C16:1) did not lead directly to changes in autophagic activity or flux but it antagonised the actions of palmitate. In parallel, palmitoleate also improved the viability of palmitate-treated BRIN-BD11 cells. Equivalent responses were observed in INS-1E cells and in isolated human islets. Taken together, these data suggest that palmitate may cause an impairment of autophagosome-lysosome fusion. These effects were not reproduced by palmitoleate which, instead, antagonised the responses mediated by palmitate suggesting that attenuation of β-cell stress may contribute to the improvement in cell viability caused by the mono-unsaturated fatty acid.
Terrain Feature Estimation Method for a Lower Limb Exoskeleton Using Kinematic Analysis and Center of Pressure

While controlling a lower limb exoskeleton providing walking assistance to wearers, the walking terrain is an important factor that should be considered for meeting performance and safety requirements. Therefore, we developed a method to estimate the slope and elevation using the contact points between the limb exoskeleton and ground. We used the center of pressure as a contact point on the ground and calculated the location of the contact points on the walking terrain based on kinematic analysis of the exoskeleton. Then, a set of contact points collected from each step during walking was modeled as the plane that represents the surface of the walking terrain through the least-square method. Finally, by comparing the normal vectors of the modeled planes for each step, features of the walking terrain were estimated. We analyzed the estimation accuracy of the proposed method through experiments on level ground, stairs, and a ramp. Classification using the estimated features showed recognition accuracy higher than 95% for all experimental motions. The proposed method approximately analyzed the movement of the exoskeleton on various terrains even though no prior information on the walking terrain was provided. The method can enable exoskeleton systems to actively assist walking in various environments.
A population-based cohort study examining the association of documented bladder diverticulum and bladder cancer risk in urology patients

Objectives Studies have shown a high risk of tumor development within a bladder diverticulum (BD). We were interested in the relationship between BD and the development of bladder cancer. Herein, we attempted to investigate whether there exists an association between documented BD and subsequent risk of bladder cancer. Methods We identified 10,662 hospitalized urology patients, including 2,134 documented BD patients (study cohort) and 8,528 non-BD subjects (comparison cohort) from Taiwan’s National Health Insurance database. Only urology patients were enrolled in the study to minimize selection bias. The two cohorts were frequency-matched 1:4 by age, sex and index-year. Patients with less than one year of follow-up were excluded to avoid inverting cause and effect. Risks of developing bladder cancer were estimated using the Cox proportional hazard regression model. Results There was an increased bladder cancer risk in the documented BD patients. The incidence of bladder cancer in documented BD patients was 2.60-fold higher than that in the comparison group, and the overall risk-factor-adjusted hazard ratio was 2.63 (95% CI, 1.74–3.97). Moreover, stratified analysis by sex also showed that documented BD patients were at higher risk of subsequent bladder cancer than the comparison cohort. The effect of BD on the risk of bladder cancer was higher in males than in females and was more profound in patients without comorbidities than in those with comorbidities. Conclusion In this population-based longitudinal study, urology patients with documented BD might have an elevated risk of subsequent bladder cancer. Based on the limitations of the retrospective study design, further studies are required.
Correction: Berner, D. Allele Frequency Difference AFD—An Intuitive Alternative to FST for Quantifying Genetic Population Differentiation. Genes 2019, 10, 308

This note is to correct an error in my paper, concerning the Shannon differentiation metric (DShannon) (Reference [43] in the paper). The paper states that DShannon is undefined mathematically whenever one or both populations are monomorphic, that is, fixed for a single allele. Accordingly, the DShannon curve in Figure 1a, showing population differentiation in relation to allele counts for the case in which the pooled minor allele frequency (MAF) is maximal, did not extend across the full range of allele counts; the rightmost data point reflecting complete population differentiation was missing. Moreover, DShannon was completely missing in Figure 1b visualizing the continuum of allele frequency differentiation when the MAF is minimal (one population monomorphic across the entire allele count range).