Miracle-dz/UniFAR-FTUs huggingface dataset:
Trends in opioid use and dosing among socio-economically disadvantaged patients

Background Opioid therapy for patients with chronic nonmalignant pain remains controversial, primarily because of safety concerns and the potential for abuse. The objective of this study was to examine trends in opioid utilization for nonmalignant pain among recipients of social assistance and to explore the relation between dose of analgesic and mortality. Methods Using a cross-sectional study design, we characterized annual trends in prescriptions for and daily dose of opioid analgesics between 2003 and 2008 for beneficiaries (aged 15 to 64 years) of Ontario’s public drug plan. We defined moderate, high and very high dose thresholds as daily doses of up to 200, 201 to 400, and more than 400 mg oral morphine (or equivalent), respectively. In an exploratory cohort study, we followed, over a 2-year period, patients who received at least one prescription for an opioid in 2004 to investigate the relation between opioid dose and opioid-related mortality. Results Over the study period, opioid prescribing rates rose by 16.2%, and 180 974 individuals received nearly 1.5 million opioid prescriptions in 2008. Also by 2008, the daily dose dispensed exceeded 200 mg morphine equivalent for almost a third (32.6%) of recipients of long-acting oxycodone but only 20.3% of those treated with fentanyl or other long-acting opioids. Among patients for whom high or very high doses of opioids were dispensed in 2004, 19.3% of deaths during the subsequent 2 years were opioid-related, occurring at a median age of 46 years. Two-year opioid-related mortality rates were 1.63 per 1000 population (95% confidence interval [CI] 1.42–1.85) among people with moderate-dose prescriptions, 7.92 per 1000 population (95% CI 5.25–11.49) among those with high-dose prescriptions, and 9.94 per 1000 population (95% CI 2.78–25.12) among those with very-high-dose prescriptions. Interpretation Among socio-economically disadvantaged patients in Ontario, the use and dose of opioids for nonmalignant pain has increased substantially, driven primarily by the use of long-acting oxycodone and, to a lesser extent, fentanyl. The findings of our exploratory study suggested a strong association between opioid-related mortality and the dose of opioid dispensed.
Heavy metals pollution of Kotlin Island in the Gulf of Finland

The current environmental state of Kotlin Island and coastal areas reflects the negative impact of industry, transport and urban utilities that has lead to increased heavy metal content in soils, in terrestrial and aquatic vegetation and in the water of the Gulf of Finland. Based on the analysis of pollutant metals in roots and shoots of native plants grown on Kotlin Island, species with high metal-accumulating capacity have been identified. Of these, there were dandelion and coltsfoot demonstrating high mobility in heavy metals, especially Zn, upward transfer. These could therefore be promising as bioindicators and phytoremediators of polluted areas pointing to origins of contamination. The presence of heavy metal contamination in the coastal waters of the gulf and its variability along the coastline is regarded as dependent on multiple sources of pollution associated with Kotlin Island, namely industrial and municipal waste waters, ship and vehicle traffic, aerosol deposits, contamination by dredging activity in a new port as well as the result of metals leaching from the soils of the island (Zn, Cu, Ni). Metal-accumulating coastal plants such as cane can be a source of secondary pollution of the gulf waters during their seasonal decomposition. The data showed significantly elevated concentrations of Ni, Zn and Cd in the hair of children living in the town of Kronstadt located on Kotlin Island that confirms the adequacy of the proposed indicating methodology and shows the unfavourable environmental situation in the region.
Infarction in the Territory of Anterior Inferior Cerebellar Artery: Spectrum of Audiovestibular Loss

Background and Purpose— To define the detailed spectrum of audiovestibular dysfunction in anterior inferior cerebellar artery territory infarction. Methods— Over 8.5 years, we prospectively identified 82 consecutive patients with anterior inferior cerebellar artery territory infarction diagnosed by MRI. Each patient completed a standardized audiovestibular questionnaire and underwent a neuro-otologic evaluation, including bithermal caloric tests and pure tone audiogram. Results— All but 2 (80 of 82 [98%]) patients had acute prolonged vertigo and vestibular dysfunction of peripheral, central, or combined origin. The most common pattern of audiovestibular dysfunction was the combined loss of auditory and vestibular function (n=49 [60%]). A selective loss of vestibular (n=4 [5%]) or cochlear (n=3 [4%]) function was rarely observed. We could classify anterior inferior cerebellar artery territory infarction into 7 subgroups according to the patterns of neuro-otological presentations: (1) acute prolonged vertigo with audiovestibular loss (n=35); (2) acute prolonged vertigo with audiovestibular loss preceded by an episode(s) of transient vertigo/auditory disturbance within 1 month before the infarction (n=13); (3) acute prolonged vertigo and isolated auditory loss without vestibular loss (n=3); (4) acute prolonged vertigo and isolated vestibular loss without auditory loss (n=4); (5) acute prolonged vertigo but without documented audiovestibular loss (n=24); (6) acute prolonged vertigo and isolated audiovestibular loss without any other neurological symptoms/signs (n=1); and (7) nonvestibular symptoms with normal audiovestibular function (n=2). Conclusions— Infarction in the anterior inferior cerebellar artery territory can present with a broad spectrum of audiovestibular dysfunctions. Unlike a viral cause, labyrinthine dysfunction of a vascular cause usually leads to combined loss of both auditory and vestibular functions.
Patients with schizophrenia demonstrate inconsistent preference judgments for affective and nonaffective stimuli.

Previous studies have typically found that individuals with schizophrenia (SZ) report levels of emotional experience that are similar to controls (CN) when asked to view a single evocative stimulus and make an absolute judgment of stimulus "value. " However, value is rarely assigned in absolute terms in real-life situations, where one alternative or experience is often evaluated alongside others, and value judgments are made in relative terms. In the current study, we examined performance on a preference task that requires individuals to differentiate between the relative values of different stimuli. In this task, subjects were presented with many pairs of moderately positive stimuli and asked to indicate which stimulus they preferred in each pair. Resulting data indicated the rank order of preference across stimuli and the consistency of their transitive mapping (ie, if A > B and B > C, then A should be > C). Individuals with SZ (n = 38) were both less consistent in their rankings of stimuli and more likely to have larger magnitudes of discrepant responses than control subjects (n = 27). Furthermore, CN showed clear differentiation between different valence categories of stimuli (ie, highly positive > mildly positive > mildly negative > highly negative); while individuals with SZ showed the same general pattern of results but with less differentiation between the valence levels. These data suggest that individuals with SZ are impaired in developing or maintaining nuanced representations of the different attributes of a stimulus, thus making stimuli of similar general value easily confusable.
Molecular basis underlying changes of brain entropy and functional connectivity in major depressive disorders after electroconvulsive therapy

Abstract Introduction Electroconvulsive therapy (ECT) is widely used for treatment‐resistant depression. However, it is unclear whether/how ECT can be targeted to affect brain regions and circuits in the brain to dynamically regulate mood and cognition. Methods This study used brain entropy (BEN) to measure the irregular levels of brain systems in 46 major depressive disorder (MDD) patients before and after ECT treatment. Functional connectivity (FC) was further adopted to reveal changes of functional couplings. Moreover, transcriptomic and neurotransmitter receptor data were used to reveal genetic and molecular basis of the changes of BEN and functional connectivities. Results Compared to pretreatment, the BEN in the posterior cerebellar lobe (PCL) significantly decreased and FC between the PCL and the right temporal pole (TP) significantly increased in MDD patients after treatment. Moreover, we found that these changes of BEN and FC were closely associated with genes' expression profiles involved in MAPK signaling pathway, GABAergic synapse, and dopaminergic synapse and were significantly correlated with the receptor/transporter density of 5‐HT, norepinephrine, glutamate, etc. Conclusion These findings suggest that loops in the cerebellum and TP are crucial for ECT regulation of mood and cognition, which provides new evidence for the antidepressant effects of ECT and the potential molecular mechanism leading to cognitive impairment.
Crout versions of ILU factorization with pivoting for sparse symmetric matrices.

The Crout variant of ILU preconditioner (ILUC) developed recently has been shown to be generally advantageous over ILU with Threshold (ILUT), a conventional row-based ILU preconditioner. This paper explores pivoting strategies for sparse symmetric matrices to improve the robustness of ILUC. We integrate two symmetry- preserving pivoting strategies, the diagonal pivoting and the Bunch-Kaufman pivoting, into ILUC without signicant overheads. The performances of the pivoting methods are compared with ILUC and ILUTP ((20)) on a set of problems, including a few arising from saddle-point (KKT) problems.
Characterization and Crystallization of Mouse Aldehyde Oxidase 3: From Mouse Liver to Escherichia coli Heterologous Protein Expression

Aldehyde oxidase (AOX) is characterized by a broad substrate specificity, oxidizing aromatic azaheterocycles, such as N1-methylnicotinamide and N-methylphthalazinium, or aldehydes, such as benzaldehyde, retinal, and vanillin. In the past decade, AOX has been recognized increasingly to play an important role in the metabolism of drugs through its complex cofactor content, tissue distribution, and substrate recognition. In humans, only one AOX gene (AOX1) is present, but in mouse and other mammals different AOX homologs were identified. The multiple AOX isoforms are expressed tissue-specifically in different organisms, and it is believed that they recognize distinct substrates and carry out different physiological tasks. AOX is a dimer with a molecular mass of approximately 300 kDa, and each subunit of the homodimeric enzyme contains four different cofactors: the molybdenum cofactor, two distinct [2Fe-2S] clusters, and one FAD. We purified the AOX homolog from mouse liver (mAOX3) and established a system for the heterologous expression of mAOX3 in Escherichia coli. The purified enzymes were compared. Both proteins show the same characteristics and catalytic properties, with the difference that the recombinant protein was expressed and purified in a 30% active form, whereas the native protein is 100% active. Spectroscopic characterization showed that FeSII is not assembled completely in mAOX3. In addition, both proteins were crystallized. The best crystals were from native mAOX3 and diffracted beyond 2.9 Å. The crystals belong to space group P1, and two dimers are present in the unit cell.
Effect of an Activated Platelet Concentrate on Differentiated Cells Involved in Tissue Healing

Abstract Tissue healing is a complex process involving several players such as cells and growth factors released from platelets upon activation. Today, platelet concentrates (PCs) are used in many different medical fields including oral, orthopaedic, and reconstructive surgery since they allow growth factors delivery to the injured site, aiming at enhancing tissue regeneration. The purpose of this in vitro study was to evaluate the effect of the acellular plasma of an activated platelet concentrate obtained using a manual protocol, on the proliferation, and biological activity of differentiated cells involved in tissue healing. Human osteoblasts and dermal fibroblasts were grown in serum-free medium supplemented with PC derived from several donors. Human osteoblast and human dermal fibroblast proliferation was assessed by MTT test after 7 days and cells were count up to 12-day incubation. Human osteoblast osteo-differentiation was tested after 7 and 14-day incubation by alkaline phosphatase assay. The addition of PC to the culture medium caused an increased proliferation with respect to cells grown in standard condition. The results of the present study suggest that PC supports the proliferation of terminally differentiated cells involved in wound healing and tissue regeneration, confirming its beneficial clinical application in regenerative therapies.
Gray matter volume associations in youth with ADHD features of inattention and hyperactivity/impulsivity

Abstract Background Prior research has shown smaller cortical and subcortical gray matter volumes among individuals with attention‐deficit/hyperactivity disorder (ADHD). However, neuroimaging studies often do not differentiate between inattention and hyperactivity/impulsivity, which are distinct core features of ADHD. The present study uses an approach to disentangle overlapping variance to examine the neurostructural heterogeneity of inattention and hyperactivity/impulsivity dimensions. Methods We analyzed data from 10,692 9‐ to 10‐year‐old children from the Adolescent Brain Cognitive Development (ABCD) Study. Confirmatory factor analysis was used to derive factors representing inattentive and hyperactive/impulsive traits. We employed structural equation modeling to examine these factors' associations with gray matter volume while controlling for the shared variance between factors. Results Greater endorsement of inattentive traits was associated with smaller bilateral caudal anterior cingulate and left parahippocampal volumes. Greater endorsement of hyperactivity/impulsivity traits was associated with smaller bilateral caudate and left parahippocampal volumes. The results were similar when accounting for socioeconomic status, medication, and in‐scanner motion. The magnitude of these findings increased when accounting for overall volume and intracranial volume, supporting a focal effect in our results. Conclusions Inattentive and hyperactivity/impulsivity traits show common volume deficits in regions associated with visuospatial processing and memory while at the same time showing dissociable differences, with inattention showing differences in areas associated with attention and emotion regulation and hyperactivity/impulsivity associated with volume differences in motor activity regions. Uncovering such biological underpinnings within the broader disorder of ADHD allows us to refine our understanding of ADHD presentations.
Interaction-Driven Spectrum Reconstruction in Bilayer Graphene

A correlated-electron phase was observed at low temperatures in suspended graphene bilayers with high carrier mobilities. The nematic phase transition in electronic liquids, driven by Coulomb interactions, represents a new class of strongly correlated electronic ground states. We studied suspended samples of bilayer graphene, annealed so that it achieves very high quasiparticle mobilities (greater than 106 square centimers per volt-second). Bilayer graphene is a truly two-dimensional material with complex chiral electronic spectra, and the high quality of our samples allowed us to observe strong spectrum reconstructions and electron topological transitions that can be attributed to a nematic phase transition and a decrease in rotational symmetry. These results are especially surprising because no interaction effects have been observed so far in bilayer graphene in the absence of an applied magnetic field.
Cold-Water Corals and Anthropogenic Impacts in La Fonera Submarine Canyon Head, Northwestern Mediterranean Sea

We assess the occurrence and extent of cold-water coral (CWC) species Madrepora oculata and Dendrophyllia cornigera, as well as gorgonian red coral Corallium rubrum, in La Fonera canyon head (Northwestern Mediterranean Sea), as well as human impacts taking place in their habitats. Occurrence is assessed based on Remotely Operated Vehicle (ROV) video imaging. Terrain classification techniques are applied to high-resolution swath bathymetric data to obtain semi-automatic interpretative maps to identify the relationship between coral distribution patterns and canyon environments. A total of 21 ROV immersions were carried out in different canyon environments at depths ranging between 79 and 401 m. Large, healthy colonies of M. oculata occur on abrupt, protected, often overhanging, rocky sections of the canyon walls, especially in Illa Negra branch. D. cornigera is sparser and evenly distributed at depth, on relatively low sloping areas, in rocky but also partially sedimented areas. C. rubrum is most frequent between 100 and 160 m on highly sloping rocky areas. The probable extent of CWC habitats is quantified by applying a maximum entropy model to predict habitat suitability: 0.36 km2 yield M. oculata occurrence probabilities over 70%. Similar predictive models have been produced for D. cornigera and C. rubrum. All ROV transects document either the presence of litter on the seafloor or pervasive trawling marks. Nets and longlines are imaged entangled on coral colonies. Coral rubble is observed at the foot of impacted colonies. Some colonies are partially covered by sediment that could be the result of the resuspension generated by bottom trawling on neighbouring fishing grounds, which has been demonstrated to be responsible of daily increases in sediment fluxes within the canyon. The characteristics of the CWC community in La Fonera canyon are indicative that it withstands high environmental stress of both natural and human origin.
Effect of Hypoxia-Inducible Factor-1&agr; Gene Therapy on Walking Performance in Patients With Intermittent Claudication

Background— Hypoxia-inducible factor-1&agr; (HIF-1&agr;) is a transcriptional regulatory factor that orchestrates cellular responses to hypoxia. It increases collateral vessel growth and blood flow in models of hind-limb ischemia. This study tested whether intramuscular administration of Ad2/HIF-1&agr;/VP16, an engineered recombinant type 2 adenovirus vector encoding constitutively active HIF-1&agr;, improves walking time in patients with peripheral artery disease and intermittent claudication. Methods and Results— Two hundred eighty-nine patients with claudication were randomized in a double-blind manner to 1 of 3 doses of Ad2/HIF-1&agr;/VP16 (2×109, 2×1010, or 2×1011 viral particles) or placebo, administered by 20 intramuscular injections to each leg. Graded treadmill tests were performed at baseline and then 3, 6, and 12 months after treatment. The primary end point was the change in peak walking time from baseline to 6 months. The secondary end point was change in claudication onset time, and tertiary end points included changes in ankle-brachial index and quality-of-life assessments. Median peak walking time increased by 0.82 minutes (interquartile range, −0.05–1.93 minutes) in the placebo group and by 0.82 minutes (interquartile range, −0.07–2.12 minutes), 0.28 minutes (interquartile range, −0.37–1.70 minutes), and 0.78 minutes (interquartile range, −0.02–2.10 minutes) in the HIF-1&agr; 2×109, 2×1010, and 2×1011 viral particle groups, respectively (P=NS between placebo and each HIF-1&agr; treatment group). There were no significant differences in claudication onset time, ankle-brachial index, or quality-of-life measurements between the placebo and each HIF-1&agr; group. Conclusions— Gene therapy with intramuscular administration of Ad2/HIF-1&agr;/VP16 is not an effective treatment for patients with intermittent claudication. Clinical Trial Registration— URL: http://www.clinicaltrials. gov. Unique identifier: NCT00117650.
Classification and Retrieval of Archaeological Potsherds Using Histograms of Spherical Orientations

We address the problem of the statistical description of 3D surfaces with the purpose of automatic classification and retrieval of archaeological potsherds. These are particularly interesting problems in archaeology, as pottery comprises a great volume of findings in archaeological excavations. Indeed, the analysis of potsherds brings relevant cues for understanding the culture of ancient groups. In particular, we develop a new local shape descriptor for 3D surfaces, called the histogram of spherical orientations (HoSO), which we use in combination with a bag-of-words approach to compute visual similarity between 3D surfaces. Given a point of interest on a 3D surface, its local shape descriptor (HoSO) captures the distribution of the spherical orientations of its neighboring points. In turn, those spherical orientations are computed with respect to the point of interest itself, both in the azimuth and the zenith axis. The proposed HoSO is invariant to scale transformations and highly robust to rotation and noise. In addition, it is efficient, as it only exploits the information of the position of the 3D points and disregards other types of information like faces or normals. We performed experiments on a set of 3D surfaces representing potsherds from the Teotihuacan civilization and further validations on a set of 3D models of generic objects. Our results show that our methodology is effective for describing 3D models and that it improves classification performance with respect to previous local descriptors.
Modulation of Cx43 and Gap Junctional Intercellular Communication by Androstenedione in Rat Polycystic Ovary and Granulosa Cells in vitro

Background Gap-junctional intercellular communication (GJIC) is implicated in physicological processes and it is vitally important for granulosa cell (GC) differentiation and oocyte growth. We investigated the expression of connexin 43 (Cx43), a gap junctional protein, in normal and androstenedione-induced polycystic ovary (PCO), the effects of androstenedione on Cx43 expression, GJIC and progesterone production in granulosa cells in vitro. Methods Isolated GCs from rat ovary were supplemented with FSH and dripped with EHS-matrix (EHS-drip) in culture media, were treated with physiological (10−7 M) or pathological (10−5 M) androstenedione concentrations to induce differentiation. Cx43 protein levels were assessed by Western blotting. Immunohistochemistry was also used to determine the localization of Cx43 in GCs and corpus luteum (CL) of controls and PCOs. Differentiation of GCs was determined by progesterone assay and Lucifer yellow dye transfer for GJIC status. The degree of significance of variations between the results was analyzed by ANOVA using SPSS (version 11.5; 2002). Results Cx43 localized in the GC layer of both the control and PCOs. Its protein levels were upregulated in PCO rat ovaries. GCs in culture with or without androstenedione had a punctate membranous distribution of Cx43. However, androstenedione increased GJIC and upregulated progesterone and Cx43 protein levels. Inhibiting GJIC by 18-α GA in androstenedione-treated GCs caused partial inhibition of progesterone production, suggesting a possible role of GJIC in mediating the action of androstenedione on GC differentiation. Conclusion This study presented a suitable culture model for polycystic ovary syndrome and showed that Cx43 and GJIC might contribute to the pathogenesis of polycystic ovary syndrome.