Miracle-dz/UniFAR-FTUs huggingface dataset:
Negative Impact of Amphetamine-Type Stimulant Use on Opioid Agonist Treatment Retention in Ontario, Canada

Objective: The objective of this study was to evaluate epidemiological trends of co-use patterns of amphetamine-type stimulants and opioids and the impact of co-use patterns on Opioid Agonist Treatment (OAT) retention in Ontario, Canada. The secondary objective was to assess geographical variation in amphetamine-type stimulant use in Northern Rural, Northern Urban, Southern Rural and Southern Urban Areas of Ontario. Methods: A retrospective cohort study on 32,674 adults receiving OAT from ~70 clinics was conducted between January 1, 2014, and December 31, 2020, in Ontario, Canada. Patients were divided into four groups base on the proportion of positive urine drug screening results for amphetamine-type stimulants during treatment: group 1 (0–25%), group 2 (25–50%), group 3 (50–75%), and groups 4 (75–100%). A Fractional logistic regression model was used to evaluate differences over time in amphetamine-type stimulant use with urine drug screening results. A Cox Proportional Hazard Ratio model was used to calculate the impact of amphetamine-type stimulant use on retention in OAT and adjusted for sociodemographic characteristics, drug use and clinical factors. Lastly, a logistic regression model was used on a subgroup of patients to assess the impact of geography on amphetamine-type stimulant use in Northern Rural, Northern Urban, Southern Rural and Southern Urban Areas of Ontario. Results: There were significant differences in amphetamine-type stimulant positive urine drug screening results year-over-year from 2015 to 2020. Significant differences were observed between amphetamine-type stimulant groups with regards to sociodemographic, clinical and drug use factors. Compared to those with no amphetamine-type stimulant use, the number of days retained in OAT treatment for amphetamine-type stimulant users was reduced (hazard ratio 1.19; 95% confidence interval = 1.07–1.17; p < 0.001). Lastly, an adjusted logistic regression model showed a significant increase in the likelihood of amphetamine-type stimulant use in Northern Rural regions compared to Southern Urban areas. Conclusion: There was a significant increase in amphetamine-type stimulant use among individuals in OAT from 2014 to 2020, associated with decreased OAT retention. Research is required to determine if tailored strategies specific to individuals in OAT who use amphetamine-type stimulants can improve OAT outcomes.
Exploring the Retinal Binding Cavity of Archaerhodopsin-3 by Replacing the Retinal Chromophore With a Dimethyl Phenylated Derivative

Rhodopsins act as photoreceptors with their chromophore retinal (vitamin-A aldehyde) and they regulate light-dependent biological functions. Archaerhodopsin-3 (AR3) is an outward proton pump that has been widely utilized as a tool for optogenetics, a method for controlling cellular activity by light. To characterize the retinal binding cavity of AR3, we synthesized a dimethyl phenylated retinal derivative, (2E,4E,6E,8E)-9-(2,6-Dimethylphenyl)-3,7-dimethylnona-2,4,6,8-tetraenal (DMP-retinal). QM/MM calculations suggested that DMP-retinal can be incorporated into the opsin of AR3 (archaeopsin-3, AO3). Thus, we introduced DMP-retinal into AO3 to obtain the non-natural holoprotein (AO3-DMP) and compared some molecular properties with those of AO3 with the natural A1-retinal (AO3-A1) or AR3. Light-induced pH change measurements revealed that AO3-DMP maintained slow outward proton pumping. Noteworthy, AO3-DMP had several significant changes in its molecular properties compared with AO3-A1 as follows; 1) spectroscopic measurements revealed that the absorption maximum was shifted from 556 to 508 nm and QM/MM calculations showed that the blue-shift was due to the significant increase in the HOMO-LUMO energy gap of the chromophore with the contribution of some residues around the chromophore, 2) time-resolved spectroscopic measurements revealed the photocycling rate was significantly decreased, and 3) kinetical spectroscopic measurements revealed the sensitivity of the chromophore binding Schiff base to attack by hydroxylamine was significantly increased. The QM/MM calculations show that a cavity space is present at the aromatic ring moiety in the AO3-DMP structure whereas it is absent at the corresponding β-ionone ring moiety in the AO3-A1 structure. We discuss these alterations of the difference in interaction between the natural A1-retinal and the DMP-retinal with binding cavity residues.
A Novel Clinical-Driven Design for Robotic Hand Rehabilitation: Combining Sensory Training, Effortless Setup, and Large Range of Motion in a Palmar Device

Neurorehabilitation research suggests that not only high training intensity, but also somatosensory information plays a fundamental role in the recovery of stroke patients. Yet, there is currently a lack of easy-to-use robotic solutions for sensorimotor hand rehabilitation. We addressed this shortcoming by developing a novel clinical-driven robotic hand rehabilitation device, which is capable of fine haptic rendering, and that supports physiological full flexion/extension of the fingers while offering an effortless setup. Our palmar design, based on a parallelogram coupled to a principal revolute joint, introduces the following novelties: (1) While allowing for an effortless installation of the user's hand, it offers large range of motion of the fingers (full extension to 180° flexion). (2) The kinematic design ensures that all fingers are supported through the full range of motion and that the little finger does not lose contact with the finger support in extension. (3) We took into consideration that a handle is usually comfortably grasped such that its longitudinal axis runs obliquely from the metacarpophalangeal joint of the index finger to the base of the hypothenar eminence. (4) The fingertip path was optimized to guarantee physiologically correct finger movements for a large variety of hand sizes. Moreover, the device possesses a high mechanical transparency, which was achieved using a backdrivable cable transmission. The transparency was further improved with the implementation of friction and gravity compensation. In a test with six healthy participants, the root mean square of the human-robot interaction force was found to remain as low as 1.37 N in a dynamic task. With its clinical-driven design and easy-to-use setup, our robotic device for hand sensorimotor rehabilitation has the potential for high clinical acceptance, applicability and effectiveness.
Early Vascular Aging in Children With Type 1 Diabetes and Ambulatory Normotension

Background: Preliminary data suggest that target organ damage (TOD) and early vascular aging (EVA) may occur in children with normal blood pressure (BP). Objectives: To analyze TOD and EVA in normotensive (BP <95th percentile on ambulatory BP monitoring) type 1 diabetes children (T1D) in comparison to healthy controls (C). Subjects: 25 T1D aged 13.9 ± 2.6 years and 22 C aged 14.0 ± 3.4 years. Methods: We analyzed age- and height-related pulse wave velocity (PWV) Z-scores and expected PWV based on age, height, and mean arterial pressure (MAP). Expected vascular age based on measured PWV was calculated from pooled pediatric and adult PWV norms. Left ventricular mass index (LVMI), estimated glomerular filtration rate (eGFR), and urinary albumin/creatinine ratio (ACR) were obtained as markers of TOD. Results: T1D and C groups did not differ in anthropometry, ambulatory, LVMI, and ACR. However, median age- and height-related PWV Z-scores were higher in T1D compared to C (1.08 vs. 0.57, p = 0.006; 0.78 vs. 0.36, p = 0.02, respectively). Mean (±SD) difference between measured and expected PWV was 0.58 ± 0.57 in T1D vs. 0.22 ± 0.59 in C, p = 0.02. The mean (±SD) difference between chronological and expected vascular age was 7.53 ± 7.74 years in T1D vs. 2.78 ± 7.01 years in C, p = 0.04. Conclusion: Increased arterial stiffness and increased intraindividual differences between expected and measured PWV as well as between chronological and expected vascular age indicate that EVA may develop in T1D children even at normal ambulatory BP levels.
Systematic Analysis of mRNAs and ncRNAs in BMSCs of Senile Osteoporosis Patients

Senile osteoporosis (SOP) is a worldwide age-related disease characterized by the loss of bone mass and decrease in bone strength. Bone mesenchymal stem cells (BMSCs) play an important role in the pathology of senile osteoporosis. Abnormal expression and regulation of non-coding RNA (ncRNA) are involved in a variety of human diseases. In the present study, we aimed to identify differentially expressed mRNAs and ncRNAs in senile osteoporosis patient-derived BMSCs via high-throughput transcriptome sequencing in combination with bioinformatics analysis. As a result, 415 mRNAs, 30 lncRNAs, 6 circRNAs and 27 miRNAs were found to be significantly changed in the senile osteoporosis group. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were applied to analyze the function of differentially expressed mRNAs and ncRNAs. The circRNA–miRNA–mRNA regulatory network was constructed using the cytoHubba plugin based on the Cytoscape software. Interestingly, circRNA008876-miR-150-5p-mRNA was the sole predicted circRNA-miRNA-mRNA network. The differential expression profile of this ceRNA network was further verified by qRT-PCR. The biological function of this network was validated by overexpression and knockdown experiments. In conclusion, circRNA008876-miR-150-5p-mRNA could be an important ceRNA network involved in senile osteoporosis, which provides potential biomarkers and therapeutic targets for senile osteoporosis.
Stressor-Induced “Inflammaging” of Vascular Smooth Muscle Cells via Nlrp3-Mediated Pro-inflammatory Auto-Loop

Calcification of the vessel wall as one structural pathology of aged vessels is associated with high cardiovascular mortality of elderly patients. Aging is linked to chronic sterile inflammation and high burden of reactive oxygen species (ROS), leading to activation of pattern recognition receptors (PRRs) such as Nlrp3 in vascular cells. The current study investigates the role of PRR activation in the calcification of vascular smooth muscle cells (VSMCs). Therefore, in vitro cell culture of primary rat VSMCs and ex vivo aortic stimulations were used to analyze osteogenic, senescence and inflammatory markers via real-time PCR, in situ RNA hybridization, Western Blot, photometric assays and histological staining. Induction of ROS and DNA-damage by doxorubicin induces a shift of VSMC phenotype toward the expression of osteogenic, senescence and inflammatory proteins. Induction of calcification is dependent on Nlrp3 activity. Il-1β as a downstream target of Nlrp3 induces the synthetic, pro-calcifying VSMC phenotype. Inhibition of PRR with subsequent reduction of chronic inflammation might be an interesting target for reduction of calcification of VSMCs, with subsequent reduction of cardiovascular mortality of patients suffering from vessel stiffness.
Single-Dose 13-Valent Conjugate Pneumococcal Vaccine in People Living With HIV – Immunological Response and Protection

Background Patients living with HIV (PLHIV) are prone to invasive pneumococcal disease. The 13-valent conjugated pneumococcal vaccine (PCV13) is currently recommended for all PLHIV, followed in most guidelines by a 23-valent polysaccharide pneumococcal vaccine. Data are scarce concerning the immunological efficacy of PCV13 among PLHIV. Objective To assess the immunological response at one month, and the immunological protection at 1-, 6-, and 12 months in PLHIV with a CD4 cell count above 200 cells/µl after a single dose of PCV13, as measured by both ELISA and opsonophagocytic assay (OPA). Methods PLHIV with CD4 cell count >200 cells/µl were included. Specific IgG serum concentrations for eight serotypes by ELISA and seven serotypes by OPA were measured at baseline, 1-, 6-, and 12 months after the PCV13 vaccination. Global response was defined as a two-fold increase from baseline of specific IgG antibody levels (μg/ml) assayed by ELISA or as a four-fold increase in OPA titer from baseline, for at least five serotypes targeted by PCV13. Global protection was defined as an IgG-concentration ≥1 µg/ml by ELISA or as an opsonization titer ≥LLOQ by OPA for at least five tested serotypes targeted by PCV13. Factors associated with global response and global protection were assessed using logistic regression. Results Of the 38 PLHIV included, 57.9% and 63.2% were global responders, 92.1% and 78.9% were globally protected at one month, and 64.7% and 55.9% were still protected at 12 months, by ELISA and OPA respectively. A CD4/CD8 ratio of >0.8 was significantly associated with a better global response by OPA (OR=6.11, p=0.02), and a CD4 nadir <200 was significantly associated with a poorer global response by ELISA (OR=0.22, p=0.04). A CD4 cell count nadir <200 and age over 50 years were associated with poorer global protection by OPA at M1 (OR=0.18, p=0.04) and M12 (OR= 0.15, p=0.02), respectively. Plasma HIV RNA viral load <40 copies/ml was significantly associated with a better global protection at M1 by ELISA and OPA (OR=21.33, p=0.025 and OR=8.40, p=0.04) Conclusion Vaccination with PCV13 in these patients induced immunological response and protection at one month. At one year, more than half of patients were still immunologically protected.
Plasmodium berghei-Released Factor, PbTIP, Modulates the Host Innate Immune Responses

The Plasmodium parasite has to cross various immunological barriers for successful infection. Parasites have evolved mechanisms to evade host immune responses, which hugely contributes to the successful infection and transmission by parasites. One way in which a parasite evades immune surveillance is by expressing molecular mimics of the host molecules in order to manipulate the host responses. In this study, we report a Plasmodium berghei hypothetical protein, PbTIP (PbANKA_124360.0), which is a Plasmodium homolog of the human T-cell immunomodulatory protein (TIP). The latter possesses immunomodulatory activities and suppressed the host immune responses in a mouse acute graft-versus-host disease (GvHD) model. The Plasmodium berghei protein, PbTIP, is expressed on the merozoite surface and exported to the host erythrocyte surface upon infection. It is shed in the blood circulation by the activity of an uncharacterized membrane protease(s). The shed PbTIP could be detected in the host serum during infection. Our results demonstrate that the shed PbTIP exhibits binding on the surface of macrophages and reduces their inflammatory cytokine response while upregulating the anti-inflammatory cytokines such as TGF-β and IL-10. Such manipulated immune responses are observed in the later stage of malaria infection. PbTIP induced Th2-type gene transcript changes in macrophages, hinting toward its potential to regulate the host immune responses against the parasite. Therefore, this study highlights the role of a Plasmodium-released protein, PbTIP, in immune evasion using macrophages, which may represent the critical strategy of the parasite to successfully survive and thrive in its host. This study also indicates the human malaria parasite TIP as a potential diagnostic molecule that could be exploited in lateral flow-based immunochromatographic tests for malaria disease diagnosis.
Survival of Patients With Idiopathic Inflammatory Myopathies in Slovenia

Background: Idiopathic inflammatory myopathies (IIMs) are rare systemic diseases associated with significant morbidity and mortality. The aim of our study was to estimate for the first time the survival of IIM patients in Slovenia. Methods: We included IIM patients diagnosed between January 2005 and December 2020 and followed at two secondary/tertiary rheumatology centers in the country. To study survival/mortality the censor date of April 14 2021 was set. Kaplan–Meier analysis and standardized mortality ratio (SMR) were plotted using data of age and sex matched Slovenian population as a reference. Cox proportional hazards regression analysis was used to study prognostic factors for IIM mortality. Results: During the 16-year observation period, we identified 217 new IIM patients. During follow up 65 (30.0%) patients died. In the first year following IIM diagnosis the SMR was nearly 7-fold higher compared to the matched general population [SMR 6.88 (95%CI 4.41–10.24)] and remained higher also during the following 4 years. However, when excluding IIM patients with cancer, the survival outcome was, except in the first year after IIM diagnosis [SMR 5.55 (95%CI 3.10–9.15)], comparable to matched general population. In addition to cancer [HR 3.71 (95% CI 2.18–6.04)], cardiac involvement [HR 2.18 (95% CI 1.07–4.45)], fever [HR 2.13 (95% CI 1.13–4.03)], and older age [HR 1.07 (95% CI 1.04–1.09)] were extracted as prognostic factors associated with death. Conclusion: The survival of patients with IIM patients was substantially worse compared to matched general population. Cancer was the leading cause of death in our cohort.
Genetic Diversity and Environmental Influence on Growth and Yield Parameters of Bambara Groundnut

Bambara groundnut (BGN) is a drought-tolerant crop majorly cultivated in sub-Saharan Africa. Due to a lack of extensive research, marginalization, lack of awareness, and lack of available fund among others, this crop's improvement has been limited. The development of this crop depends on evaluation and selection of unique and stable breeding lines in different environments. This study aims to estimate genetic diversity using morphological traits at different locations in 95 accessions of BGN collected from the Genebank of the International Institute of Tropical Agriculture (IITA), Ibadan. The experiment was carried out in three replicates at IITA experimental sites in two agroecological zones in Ibadan (7°40′19.62″ N, 3°91′73.13″ E) and Ikenne (6°51′00.873″ N, 3°41′48.528″ E) using a randomized complete block design. Ten vegetative growth traits and eight yield traits were scored. The data was subjected to ANOVA, PCA, correlation, and cluster analysis. Estimations of genetic parameters and broad sense heritability were carried out on the traits. ANOVA revealed significant variation in each trait except for days to emergence. Significant variation was also observed for accession and location interactions (genotype x environment interactions) for plant height, leaf length, leaf width, chlorophyll content, number of petioles, germination count, number of pods, number of seeds, seed length, seed width, and yield. PC1 and PC2 show 42.3% of the total variations observed by the PC, with seed thickness contributing more to PC1 and the number of seeds contributing more to PC2. Cluster analysis categorized the accessions into four distinct groups. The number of pods had the highest genotypic coefficient of variation of 32.55% and the phenotypic coefficient of variation of 97.61%, while seed length (0.63), seed width (0.54), and seed thickness (0.58) have high heritability values. The genetic advance was highest in yield (76.15%) and lowest in days to 50% germination (0.21%). This study can be used to predict appropriate agroecological zones for the planting of BGN while the knowledge of the diversity of the accessions based on the traits could serve a guide in selecting the best trait for the improvement of the crop.
In vitro Assessment of Solar Filters for Erythropoietic Protoporphyria in the Action Spectrum of Protoporphyrin IX

Introduction: Subjects with erythropoietic protoporphyria rely on broad-spectrum sunscreens with high sun protection factor, which is not informative on efficacy in the absorption spectrum of protoporphyrin IX, spanning visible radiation and peaking around 408 nm. Photoactivation of protoporphyrin IX is responsible for painful skin photosensitivity in erythropoietic protoporphyria. The authors assessed the protective efficacy of six sunscreens in vitro in the absorption spectrum of protoporphyrin IX. Method: Transmittance measurements were performed in the 300–850 nm wavelengths on samples of six photoprotective products applied to polymethyl methacrylate plates. Porphyrin protection factor was calculated in the 300–700 nm region to provide a measurement for the efficacy of each product based on the action spectrum of protoporphyrin IX. Results: Product A showed the highest porphyrin protection factor among tested products with a median value of 4.22. Product A is a sunscreen containing organic filters, titanium dioxide and synthetic iron oxides, pigmentary grade active ingredients that absorb visible radiation. Other products showed inefficient protection in the visible, with transmittance between 75 and 95% at 500 nm. The low porphyrin protection factor of inorganic filter product B was attributed to particle micronization, as declared by the manufacturer. Conclusion: Adding porphyrin protection factor to sunscreen labeling could help patients with erythropoietic protoporphyria and other photosensitivity disorders identify products tailored on their specific needs. The development of sunscreens providing protection from visible radiation and excellent cosmetical tolerability could improve the lifestyle of patients with erythropoietic protoporphyria.
Five Rootstocks for “Emperor” Mandarin Under Subtropical Climate in Southern Brazil

Rootstocks modulate several characteristics of citrus trees, including vegetative growth, fruit yield and quality, and resistance or tolerance to pests, diseases, soil drought, and salinity, among other factors. There is a shortage of scion and rootstock cultivars among the combinations planted in Brazil. “Ponkan” mandarin and “Murcott” tangor grafted on “Rangpur” lime comprise the majority of the commercial mandarin orchards in Brazil. This low genetic diversity of citrus orchards can favor pest and disease outbreaks. This study aimed to evaluate the agronomic performance, Huanglongbing (HLB) tolerance, and fruit quality of “Emperor” mandarin on five different rootstocks for nine cropping seasons under the subtropical soil-climate conditions of the North region of the state of Paraná, Brazil. The experimental design was a randomized block, with six replications, two trees per block, and five rootstocks, including “Rangpur” lime, “Cleopatra,” and “Sunki” mandarins, “Swingle” citrumelo, and “Fepagro C-13” citrange. The evaluations included tree growth, yield performance, fruit quality, and HLB disease incidence. “Emperor” mandarin trees grafted on “Rangpur” lime and “Swingle” citrumelo had early fruiting and high yield efficiency. “Rangpur” lime also induced the lowest tree growth, but low fruit quality. Trees on “Swingle” citrumelo and “Fepagro C-13” citrange showed low scion and rootstock affinity and produced fruits with high total soluble solids (TSS), with a lower number of seeds for those from trees on “Fepagro C-13” citrange. “Cleopatra” and “Sunki” mandarins induced higher juice content, while fruits from trees on “Cleopatra” also had higher TSS/titratable acidity (TA) ratio. “Emperor” mandarin trees were susceptible to HLB regardless of the rootstocks. Overall, “Cleopatra” and “Sunki” mandarins, “Swingle” citrumelo, and “Fepagro C-13” are more suitable rootstocks for “Emperor” mandarin under Brazilian subtropical conditions than “Rangpur” lime.