Miracle-dz/UniFAR-FTUs huggingface dataset:
Synthetic Cathinones Induce Cell Death in Dopaminergic SH-SY5Y Cells via Stimulating Mitochondrial Dysfunction

Increasing reports of neurological and psychiatric complications due to psychostimulant synthetic cathinones (SCs) have recently raised public concern. However, the precise mechanism of SC toxicity is unclear. This paucity of understanding highlights the need to investigate the in-vitro toxicity and mechanistic pathways of three SCs: butylone, pentylone, and 3,4-Methylenedioxypyrovalerone (MDPV). Human neuronal cells of SH-SY5Y were cultured in supplemented DMEM/F12 media and differentiated to a neuronal phenotype using retinoic acid (10 μM) and 12-O-tetradecanoylphorbol-13-acetate (81 nM). Trypan blue and lactate dehydrogenase assays were utilized to assess the neurotoxicity potential and potency of these three SCs. To investigate the underlying neurotoxicity mechanisms, measurements included markers of oxidative stress, mitochondrial bioenergetics, and intracellular calcium (Ca2+), and cell death pathways were evaluated at two doses (EC15 and EC40), for each drug tested. Following 24 h of treatment, all three SCs exhibited a dose-dependent neurotoxicity, characterized by a significant (p < 0.0001 vs. control) production of reactive oxygen species, decreased mitochondrial bioenergetics, and increased intracellular Ca2+ concentrations. The activation of caspases 3 and 7 implicated the orchestration of mitochondrial-mediated neurotoxicity mechanisms for these SCs. Identifying novel therapeutic agents to enhance an altered mitochondrial function may help in the treatment of acute-neurological complications arising from the illicit use of these SCs.
Relationship of Milk Odd- and Branched-Chain Fatty Acids with Urine Parameters and Ruminal Microbial Protein Synthesis in Dairy Cows Fed Different Proportions of Maize Silage and Red Clover Silage

Simple Summary The purpose of this study is to assess the relationship of milk odd- and branched-chain fatty acids (OBCFA) with urinary purine derivates (PD) and estimated ruminal microbial crude protein (MCP). The correlations and regressions demonstrate that yields and concentrations of individual or total OBCFA are weakly related to urinary PD and are low to moderate markers of MCP synthesis. Nevertheless, milk OBCFA can still be seen as a promising method for predicting rumen function and microbial protein supply to the duodenum in dairy cows because MCP flow was not directly measured in this study but instead indirectly estimated probably comprising considerable deviations of the assumed values from the true ones. Abstract The aim of this study was to evaluate the relationship of milk odd- and branched-chain fatty acids (OBCFA) with urinary purine derivates and estimated ruminal microbial crude protein (MCP) synthesis. Forty-four lactating Holstein cows were used in a 4 × 4 Latin square design with 21-day periods comprised of a 13-day adaptation phase to diet followed by an 8-day sampling phase. Differences in estimated MCP yield and milk OBCFA composition were found by feeding total mixed rations containing forage (maize silage, MS; red clover silage, RCS) and concentrates (0.75:0.25) with targeted proportions of RCS to MS of 0.15:0.60, 0.30:0.45, 0.45:0.30, and 0.60:0.15 on a dry matter basis. The MCP was estimated from the total urinary purine derivate (PD) excretion (MCPPD) and intakes of metabolizable energy (MCPME) or digestible organic matter (MCPdOM). The Pearson correlations of individual OBCFA with urinary parameters (uric acid, allantoin, PD and nitrogen) were generally weak (r = −0.37 to 0.55). Yields of individual OBCFA correlated positively with MCPME and MCPdOM (r = 0.21 to 0.55). The prediction of urinary PD concentration was moderate (R2 = 0.64) when including the proportion of iso-C17:0. The prediction of total PD excretion was low (R2 = 0.21) with yields of iso-C15:0, anteiso-C17:0, and iso-C16:0. The prediction of MCPPD was high (R2 = 0.99) when including the iso-C16:0 and cis-9 C17:1 concentrations, while those of MCPME and MCPdOM were low (R2 = 0.37 and 0.36, respectively) when including yields of iso-C15:0, cis-9 C17:1, and iso-C18:0. The correlations and regression analyses demonstrate that the estimated MCP synthesis and urinary PD excretion can be only moderately predicted by yields and concentrations of individual or total OBCFA in cow’s milk. However, milk OBCFA can still be seen as a promising, non-invasive method for predicting rumen function and microbial protein supply in dairy cows because MCP flow was not directly measured in this study but instead indirectly estimated probably comprising considerable deviations of the assumed values from the true ones.
Alterations and test–retest reliability of functional connectivity network measures in cerebral small vessel disease

While structural network analysis consolidated the hypothesis of cerebral small vessel disease (SVD) being a disconnection syndrome, little is known about functional changes on the level of brain networks. In patients with genetically defined SVD (CADASIL, n = 41) and sporadic SVD (n = 46), we independently tested the hypothesis that functional networks change with SVD burden and mediate the effect of disease burden on cognitive performance, in particular slowing of processing speed. We further determined test–retest reliability of functional network measures in sporadic SVD patients participating in a high‐frequency (monthly) serial imaging study (RUN DMC—InTENse, median: 8 MRIs per participant). Functional networks for the whole brain and major subsystems (i.e., default mode network, DMN; fronto‐parietal task control network, FPCN; visual network, VN; hand somatosensory‐motor network, HSMN) were constructed based on resting‐state multi‐band functional MRI. In CADASIL, global efficiency (a graph metric capturing network integration) of the DMN was lower in patients with high disease burden (standardized beta = −.44; p [corrected] = .035) and mediated the negative effect of disease burden on processing speed (indirect path: std. beta = −.20, p = .047; direct path: std. beta = −.19, p = .25; total effect: std. beta = −.39, p = .02). The corresponding analyses in sporadic SVD showed no effect. Intraclass correlations in the high‐frequency serial MRI dataset of the sporadic SVD patients revealed poor test–retest reliability and analysis of individual variability suggested an influence of age, but not disease burden, on global efficiency. In conclusion, our results suggest that changes in functional connectivity networks mediate the effect of SVD‐related brain damage on cognitive deficits. However, limited reliability of functional network measures, possibly due to age‐related comorbidities, impedes the analysis in elderly SVD patients.
Black tea polyphenol theaflavin as promising antioxidant and potential copper chelator.

BACKGROUND In this work, we investigated the antioxidant and copper chelating abilities of theaflavin, a polyphenol responsible for astringency, color and sensation present in black tea. Using voltammetric techniques, the analyses were conducted at disposable electrochemical printed carbon chips in conjunction with a portable hand-held potentiostat. RESULTS Voltammograms of theaflavin showed five separate oxidation peaks, corresponding to the oxidation of five individual functional groups. Electroanalytical data of theaflavin after interaction with copper indicates that the flavonoid has higher antioxidant potential and is a better copper chelator than epigallocatechin gallate, a major polyphenol present in green tea and a well-known antioxidant. This could be attributed to the extra fused ring and larger number of OH groups in theaflavin. CONCLUSIONS Our findings introduce another natural compound as a potential nutraceutical in oxidation- and copper-modulated illnesses. In addition, this simple and fast approach would be highly pertinent to inspect health benefits of natural food products. To the best of our knowledge, this is the first report of electrochemical analysis of Cu (II) chelation by theaflavin. This article is protected by copyright. All rights reserved.
Social grooming efficiency and techniques are influenced by manual impairment in free-ranging Japanese macaques (Macaca fuscata)

Animals born with physical impairments may particularly require behavioural flexibility and innovation to survive and carry out social activities, such as grooming. Studies on free-ranging Japanese macaques on Awaji Island, Japan, have shown that individuals with congenital limb malformations exhibited compensatory behaviours while grooming, such as increased mouth and elbow use for removing ectoparasites. The aim of this study is to explore disabled and nondisabled grooming techniques to determine whether and to what extent disabled monkeys develop novel grooming techniques, and if there is disability-associated variation in grooming efficiency. We hypothesized that modified grooming techniques used by disabled monkeys fulfilled the social and relaxing functions of grooming, however, that grooming by manually impaired individuals may still carry a hygienic cost to the recipients. Grooming behavioural data were collected by video in 2007 on 27 adult females (11 with CLMs). With a detailed grooming-related ethogram, we transcribed 216 2-minute continuous grooming video samples. We analyzed the data using generalized linear mixed effects models in R. We found that monkeys with manual impairment were less efficient groomers, as measured by removal and movement efficiency during grooming. However, there were no significant differences associated with the number of grooming movements per sample among the focal animals. Additionally, with a behavioural sequential analysis, we isolated 8 distinct grooming techniques and 3 novel disability-specific movements. Our results indicate that innovation and modification of movement types does not entirely compensate for manual disability, and that manual impairment carries a cost to the hygienic function of grooming. However, for the grooming recipient, the experience of being groomed by a disabled or nondisabled groomer is likely similar, and through movement compensation, disabled monkeys are able to engage in the social aspect of grooming without incurring any disability-associated costs.
Ensuring HLA‐matched platelet support requires an ethnic diverse donor population

Patients refractory for platelet transfusions benefit from human leukocyte antigen (HLA)‐matched platelet transfusions. Differences in ethnic background of patients and donors could hamper the availability of sufficient numbers of HLA‐matched donors for all patients. We evaluated our HLA‐matched donor program and explored the role of ethnic background of patients related to the number of available donors.
Physiological Traits and Adherence to Obstructive Sleep Apnea Treatment in Patients with Stroke.

model (e.g., ArTH and loop gain; model 1) to CPAP adherence model consisting of factors in the social, psychological, medical comorbidity, functional status, symptom, and polysomnographic domains (model 2). Variables for each domain are shown in Table 1. A likelihood ratio test showed that addition of physiological factors signiﬁcantly improved nonphysiological CPAP adherence model ( P value=0.013; change in sum of squares of 29%; R 2 increase from 50% to 65%). Sensitivity analyses including residual AHI and mask leak did not meaningfully change model results (data not shown). b Std. describes the number of SDs of change in CPAP adherence (h/night; SD=2.3 h) per SD increase in each term. This can be used for comparison between trait effects and b coefﬁcients for dichotomous variables (e.g., chronic pain). For example, lowering ArTH by 1 SD (an absolute of 24% of Veupnea) is associated with 1.33 3 2.3=3.1-hour reduction of CPAP adherence. Analogously, the 8% absolute reduction of ArTH is associated with 1-hour reduction in adherence, in comparison to 1.8-hour reduction in presence of chronic pain. SD for Vcomp was 23.1 (%Veupnea), with an increase of Vcomp of that magnitude associated with 0.8-hour reduction of CPAP adherence. Analogously, a 33% increase of Vcomp is associated with a 1-hour decline in CPAP adherence.
Biological Features and Prognostic Impact of Bone Marrow Infiltration in Patients with Diffuse Large B-cell Lymphoma

The biology and clinical impact of bone marrow (BM) infiltration in patients with diffuse large B-cell lymphoma (DLBCL) remains unclear in the rituximab era. We retrospectively analyzed 232 patients diagnosed with DLBCL at our center between 1999 and 2014. Concordant-presence of large cells similar to those of the lymph node biopsy- and discordant-infiltration by small cells forming lymphoid aggregates, lacking cytological atypia-BM infiltration was defined by histological criteria and further characterized by flow cytometry (FCM). Cell of origin (COO) was determined using Hans’ algorithm. For the clonal relationship between tumor and discordant BM, the VDJH rearrangement was analyzed. Survival analyses were restricted to 189 patients treated with rituximab and chemotherapy. Thirty-six (16%) had concordant, and 37 (16%) discordant BM infiltration. FCM described different indolent lymphomas among discordant cases, clonally related with DLBCL in 10/13 available samples. Median follow-up was 58 months. 5-year-progression-free survival (PFS) for non-infiltrated, discordant and concordant groups was 68%, 65% and 30%, respectively (p < 0.001). Combining COO and BM infiltration, patients with discordant BM and non-germinal center B-cell COO also had decreased 5-year-PFS (41.9%). In multivariate analysis, concordant BM had an independent effect on PFS (HR 2.5, p = 0.01). Five-year cumulative incidence of central nervous system (CNS) relapse was 21%, 4% and 1% in concordant, discordant and non-infiltrated groups, respectively (p < 0.001). In conclusion, concordant BM infiltration represents a subset with poor prognosis, whereas the prognostic impact of discordant BM infiltration could be limited to non-CGB cases.
Impact of temporal resolution and motion correction for dynamic contrast-enhanced MRI of the liver using an accelerated golden-angle radial sequence

This paper presents a prospective study evaluating the impact on image quality and quantitative dynamic contrast-enhanced (DCE)-MRI perfusion parameters when varying the number of respiratory motion states when using an eXtra-Dimensional Golden-Angle Radial Sparse Parallel (XD-GRASP) MRI sequence. DCE acquisition was performed using a 3D stack-of-stars gradient-echo golden-angle radial acquisition in free-breathing with 100 spokes per motion state and temporal resolution of 6 s/volume, and using a non-rigid motion compensation to align different motion states. Parametric analysis was conducted using a dual-input single-compartment model. Nonparametric analysis was performed on the time-intensity curves. A total of 22 hepatocellular carcinomas (size: 11–52 mm) were evaluated. XD-GRASP reconstructed with increasing number of spokes for each motion state increased the signal-to-noise ratio (SNR) (p < 0.05) but decreased temporal resolution (0.04 volume/s vs 0.17 volume/s for one motion state) (p < 0.05). A visual scoring by an experienced radiologist show no change between increasing number of motion states with same number of spokes using the Likert score. The normalized maximum intensity time ratio, peak enhancement ratio and tumor arterial fraction increased with decreasing number of motion states (p < 0.05) while the transfer constant from the portal venous plasma to the surrounding tissue significantly decreased (p < 0.05). These same perfusion parameters show a significant difference in case of tumor displacement more than 1 cm (p < 0.05) whereas in the opposite case there was no significant variation. While a higher number of motion states and higher number of spokes improves SNR, the resulting lower temporal resolution can influence quantitative parameters that capture rapid signal changes. Finally, fewer displacement compensation is advantageous with lower number of motion state due to the higher temporal resolution. XD-GRASP can be used to perform quantitative perfusion measures in the liver, but the number of motion states may significantly alter some quantitative parameters.
PEGylated Amine-Functionalized Poly(ε-caprolactone) for the Delivery of Plasmid DNA

As a promising strategy for the treatment of various diseases, gene therapy has attracted increasing attention over the past decade. Among various gene delivery approaches, non-viral vectors made of synthetic biomaterials have shown significant potential. Due to their synthetic nature, non-viral vectors can have tunable structures and properties by using various building units. In particular, they can offer advantages over viral vectors with respect to biosafety and cytotoxicity. In this study, a well-defined poly(ethylene glycol)-block-poly(α-(propylthio-N,N-diethylethanamine hydrochloride)-ε-caprolactone) diblock polymer (PEG-b-CPCL) with one poly(ethylene glycol) (PEG) block and one tertiary amine-functionalized cationic poly(ε-caprolactone) (CPCL) block, as a novel non-viral vector in the delivery of plasmid DNA (pDNA), was synthesized and studied. Despite having a degradable polymeric structure, the polymer showed remarkable hydrolytic stability over multiple weeks. The optimal ratio of the polymer to pDNA for nanocomplex formation, pDNA release from the nanocomplex with the presence of heparin, and serum stability of the nanocomplex were probed through gel electrophoresis. Nanostructure of the nanocomplexes was characterized by DLS and TEM imaging. Relative to CPCL homopolymers, PEG-b-CPCL led to better solubility over a wide range of pH. Overall, this work demonstrates that PEG-b-CPCL possesses a range of valuable properties as a promising synthetic vector for pDNA delivery.
Changes in Smoking Behavior Before and After Gastric Bypass

Supplemental Digital Content is available in the text Objective: To evaluate smoking history and change in smoking behavior, from 1 year before through 7 years after Roux-en-Y gastric bypass (RYGB) surgery, and to identify risk factors for post-surgery smoking. Background: Smoking behavior in the context of bariatric surgery is poorly described. Methods: Adults undergoing RYGB surgery entered a prospective cohort study between 2006 and 2009 and were followed up to 7 years until ≤2015. Participants (N = 1770; 80% female, median age 45 years, median body mass index 47 kg/m2) self-reported smoking history pre-surgery, and current smoking behavior annually. Results: Almost half of participants (45.2%) reported a pre-surgery history of smoking. Modeled prevalence of current smoking decreased in the year before surgery from 13.7% [95% confidence interval (CI) = 12.1–15.4] to 2.2% (95% CI = 1.5–2.9) at surgery, then increased to 9.6% (95% CI = 8.1–11.2) 1-year post-surgery and continued to increase to 14.0% (95% CI = 11.8–16.0) 7-years post-surgery. Among smokers, mean packs/day was 0.60 (95% CI = 0.44–0.77) at surgery, 0.70 (95% CI = 0.62–0.78) 1-year post-surgery and 0.77 (95% CI = 0.68–0.88) 7-years post-surgery. At 7-years, smoking was reported by 61.7% (95% CI = 51.9–70.8) of participants who smoked 1-year pre-surgery (n = 221), 12.3% (95% CI = 8.5–15.7) of participants who formerly smoked but quit >1 year pre-surgery (n = 507), and 3.8% (95% CI = 2.1–4.9) of participants who reported no smoking history (n = 887). Along with smoking history (ie, less time since smoked), younger age, household income <$25,000, being married or living as married, and illicit drug use were independently associated with increased risk of post-surgery smoking. Conclusion: Although most adults who smoked 1-year before RYGB quit pre-surgery, smoking prevalence rebounded across 7-years, primarily due to relapse.
Room-Level Fall Detection Based on Ultra-Wideband (UWB) Monostatic Radar and Convolutional Long Short-Term Memory (LSTM)

Timely calls for help can really make a difference for elders who suffer from falls, particularly in private locations. Considering privacy protection and convenience for the users, in this paper, we approach the problem by using impulse–radio ultra-wideband (IR-UWB) monostatic radar and propose a learning model that combines convolutional layers and convolutional long short term memory (ConvLSTM) to extract robust spatiotemporal features for fall detection. The performance of the proposed scheme was evaluated in terms of accuracy, sensitivity, and specificity. The results show that the proposed method outperforms convolutional neural network (CNN)-based methods. Of the six activities we investigated, the proposed method can achieve a sensitivity of 95% and a specificity of 92.6% at a range of 8 meters. Further tests in a heavily furnished lounge environment showed that the model can detect falls with more than 90% sensitivity, even without re-training effort. The proposed method can detect falls without exposing the identity of the users. Thus, the proposed method is ideal for room-level fall detection in privacy-prioritized scenarios.
Effects of arginine and ornithine supplementation to a high‐protein diet on selected cellular immune variables in adult cats

Abstract Background Dietary protein and amino acid intake and composition can modulate immune function. Objectives To evaluate the effects of high‐protein intake and arginine and ornithine supplementation on feline immune cells. Animals Ten healthy cats. Methods Experimental study. Cats received a high‐protein basal diet as a single daily meal. A crossover design was applied with treatments being basal diet (w/o); basal diet with arginine supplementation (+50, 75, 100% compared to the arginine provision by the basal diet; Arg 1‐3); and basal diet with ornithine supplementation (+100, 150, 200% compared to the arginine provision by the basal diet; Orn 1‐3). Blood samples were collected at the end of each 11‐day treatment period. Results Mitogen‐stimulated proliferative activity of blood leukocytes revealed a quadratic effect for the dietary supplementation of arginine (P = .02) and ornithine (P = .03) (means for ConA‐stimulation: w/o = 6.96; Arg 1 = 9.31; Arg 2 = 11.4; Arg 3 = 8.04; Orn 1 = 15.4; Orn 2 = 9.43; Orn 3 = 9.28; pooled SEM: 0.96). The number (% gated) of phagocytic granulocytes linearly decreased with increasing dietary concentrations of arginine (P = .05) and ornithine (P = .03) (means: w/o = 95.5; Arg 1 = 93.0; Arg 2 = 92.5; Arg 3 = 92.6; Orn 1 = 92.6; Orn 2 = 92.6; Orn 3 = 91.5; pooled SEM = 0.44). Conclusions and Clinical Importance This study could demonstrate immunomodulating properties of dietary arginine and ornithine in cats.