Miracle-dz/UniFAR-FTUs huggingface dataset:
The protective and therapeutic effects of linalool against doxorubicin-induced cardiotoxicity in Wistar albino rats

The aim of the present study was to determine the protective and therapeutic effects of linalool (LIN) against doxorubicin (DOX)-induced cardiotoxicity in rats histologically and biochemically. In experiments, 64 male Wistar albino rats were randomly divided into eight groups (n = 8). These groups were control (C) (0.9% saline solution), DOX (20 mg/kg DOX), LIN50 (50 mg/kg LIN), LIN100 (100 mg/kg LIN), DOX + LIN50 (20 mg/kg DOX and 50 mg/kg LIN), DOX + LIN100 (20 mg/kg DOX and 100 mg/kg LIN), LIN50 + DOX (50 mg/kg LIN and 20 mg/kg DOX), and LIN100 + DOX (100 mg/kg LIN and 20 mg/kg DOX). It was determined that necrosis and extensive inflammatory cell infiltration were observed in the DOX group. It was determined that histopathological changes significantly decreased in groups treated with LIN after DOX administration. While the caspase-3 immunostaining was highly evident in DOX group apoptotic cells (p < 0.001, for all), the intensity of caspase-3 immunostaining in the treatment groups decreased (p < 0.05). While DOX administration resulted in a significant increase in malondialdehyde (MDA) levels and plasma Creatine kinase (CK) and lactate dehydrogenase (LDH) levels in cardiac tissue when compared to the C groups, it was observed that DOX + LIN administration led to a significant decrease in MDA, plasma CK and LDH levels and a significant increase in glutathione (GSH), superoxide dismutase, and catalase enzyme levels. Finally, it was concluded that DOX led to heavy cardiotoxicity and DOX + LIN administration could remove cardiomyopathy symptoms.
Uninterrupted edoxaban vs. vitamin K antagonists for ablation of atrial fibrillation: the ELIMINATE-AF trial

Abstract Aims Edoxaban is a direct factor Xa inhibitor approved for stroke prevention in atrial fibrillation (AF). Uninterrupted edoxaban therapy in patients undergoing AF ablation has not been tested. Methods and results The ELIMINATE-AF trial, a multinational, multicentre, randomized, open-label, parallel-group study, was conducted to assess the safety and efficacy of once-daily edoxaban 60 mg (30 mg in patients indicated for dose reduction) vs. vitamin K antagonists (VKAs) in AF patients undergoing catheter ablation. Patients were randomized 2:1 to edoxaban vs. VKA. The primary endpoint (per-protocol population) was time to first occurrence of all-cause death, stroke, or International Society of Thrombosis and Haemostasis-defined major bleeding during the period from the end of the ablation procedure to end of treatment (90 days). Overall, 632 patients were enrolled, 614 randomized, and 553 received study drug and underwent ablation; 177 subjects underwent brain magnetic resonance imaging to assess silent cerebral infarcts. The primary endpoint (only major bleeds occurred) was observed in 0.3% (1 patient) on edoxaban and 2.0% (2 patients) on VKA [hazard ratio (95% confidence interval): 0.16 (0.02–1.73)]. In the ablation population (modified intent-to-treat population including patients with ablation), the primary endpoint was observed in 2.7% of edoxaban (N = 10) and 1.7% of VKA patients (N = 3) between start of ablation and end of treatment. There were one ischaemic and one haemorrhagic stroke, both in patients on edoxaban. Cerebral microemboli were detected in 13.8% (16) patients who received edoxaban and 9.6% (5) patients in the VKA group (nominal P = 0.62). Conclusion Uninterrupted edoxaban therapy represents an alternative to uninterrupted VKA treatment in patients undergoing AF ablation.
Effects of Enantiomerically Pure β-Carboline Alkaloids from Picrasma quassioides on Human Hepatoma Cells

Abstract Four pairs of β-carboline enantiomers (1a/1b–4a/4b), 2 β-carboline derivatives (5 – 6) with a single enantiomeric configuration, together with 2 known achiral congeners (7 – 8) were isolated from the stems of Picrasma quassioides. Their structures were elucidated on the basis of extensive spectroscopic analyses and quantum mechanical calculations. Compound 5 possesses a 4,5-seco β-carboline framework and represents the first example of this type of β-carboline alkaloids from nature. A possible biosynthetic pathway is proposed to generate the racemate 4 and the enantiomerically pure compounds 5 and 6. All isolates were screened for their cytotoxicity against hepatocellular carcinoma Hep3B and HepG2 cells, which revealed that enantiomeric compounds 4a and 4b had distinctive effects in HepG2 cells. Further investigation showed that 4b could induce apoptosis in HepG2 cells.
Linear magnetoresistance in the low-field limit in density-wave materials

Significance Magnetoresistance has a history of revealing key electronic characteristics of materials. From early measurements on noble metals to definitive characterization of localization effects in semiconductors to recent studies of topological materials, the magnetoresistive response provides an experimental technique to explore the Fermi surface in detail, and to predict and craft physical properties through its sign, functional form, and potential quantum character. Linear magnetoresistance in density-wave systems has eluded clear explanation for over half a century. Here, we present measurements that lead to a general explanation based on unusual current paths tied to the formation of long-range charge or spin order. This mechanism potentially extends to the large magnetoresistance observed in semimetals like Bi, graphite, and WTe2. The magnetoresistance (MR) of a material is typically insensitive to reversing the applied field direction and varies quadratically with magnetic field in the low-field limit. Quantum effects, unusual topological band structures, and inhomogeneities that lead to wandering current paths can induce a cross-over from quadratic to linear MR with increasing magnetic field. Here we explore a series of metallic charge- and spin-density-wave systems that exhibit extremely large positive linear MR. By contrast to other linear MR mechanisms, this effect remains robust down to miniscule magnetic fields of tens of Oersted at low temperature. We frame an explanation of this phenomenon in a semiclassical narrative for a broad category of materials with partially gapped Fermi surfaces due to density waves.
Chronology, time averaging, and oxygen isotope composition of harvested marine mollusk assemblages from Ifri Oudadane, northeast Morocco

Abstract The archaeological site of Ifri Oudadane, NE Morocco, contains well-preserved marine mollusk concentrations throughout the Epipaleolithic (hunting-gathering) and Neolithic (food production) cultural phases, useful to test hypotheses driving such transition. However, the chronology and stratigraphy of harvested shells is complex due to the confluence of human activity and natural deposition processes. This work first quantifies the age and degree of time averaging of archaeological shells and then estimates sea-surface temperatures (SSTs) from the oxygen isotopes of selected specimens. Thirty-four radiocarbon-dated shells exhibited significant time averaging between 310 to 1170 yr that could not be explained by analytical error alone. This finding illustrates the need for individually dating shells in future paleoclimate investigations aiming for high temporal resolution. Nine isotopically analyzed shells dated to the Neolithic phase, between 5700 and 7600 cal yr BP, indicate that assuming constant oxygen isotopes of seawater, SSTs remained consistently warm, between 20°C and 22°C, that is, 2°C–4°C warmer than today. Results point to warmer conditions during the Neolithic, supporting the hypothesis that the rise of a food production mode of life in NE Morocco could have in part been triggered by warming conditions following the colder 8.2 event.
Fragmented ambiguous objects: Stimuli with stable low-level features for object recognition tasks

Visual object recognition is a complex skill that relies on the interaction of many spatially distinct and specialized visual areas in the human brain. One tool that can help us better understand these specializations and interactions is a set of visual stimuli that do not differ along low-level dimensions (e.g., orientation, contrast) but do differ along high-level dimensions, such as whether a real-world object can be detected. The present work creates a set of line segment-based images that are matched for luminance, contrast, and orientation distribution (both for single elements and for pair-wise combinations) but result in a range of object and non-object percepts. Image generation started with images of isolated objects taken from publicly available databases and then progressed through 3-stages: a computer algorithm generating 718 candidate images, expert observers selecting 217 for further consideration, and naïve observers performing final ratings. This process identified a set of 100 images that all have the same low-level properties but cover a range of recognizability (proportion of naïve observers (N = 120) who indicated that the stimulus “contained a known object”) and semantic stability (consistency across the categories of living, non-living/manipulable, and non-living/non-manipulable when the same observers named “known” objects). Stimuli are available at https://github.com/caolman/FAOT.git.
ACVIM consensus guidelines for the diagnosis and treatment of myxomatous mitral valve disease in dogs

Abstract This report, issued by the ACVIM Specialty of Cardiology consensus panel, revises guidelines for the diagnosis and treatment of myxomatous mitral valve disease (MMVD, also known as endocardiosis and degenerative or chronic valvular heart disease) in dogs, originally published in 2009. Updates were made to diagnostic, as well as medical, surgical, and dietary treatment recommendations. The strength of these recommendations was based on both the quantity and quality of available evidence supporting diagnostic and therapeutic decisions. Management of MMVD before the onset of clinical signs of heart failure has changed substantially compared with the 2009 guidelines, and new strategies to diagnose and treat advanced heart failure and pulmonary hypertension are reviewed.
A Novel Multi-Angle SAR Imaging System and Method Based on an Ultrahigh Speed Platform

Considering the difficulty of pulse repetition frequency (PRF) design in multi-angle SAR when using ultra-high speed platforms, a multi-angle SAR imaging system in a unified coordinate system is proposed. The digital multi-beamforming is used in the system and multi-angle SAR data can be obtained in one flight. Therefore, the system improves the efficiency of data recording. An improved range migration algorithm (RMA) is used for data processing, and imaging is made in a unified imaging coordinate system. The resolution of different view images is the same, and there is a fixed delay between the images. On this basis, the SAR image fusion is performed after image matching. The results of simulation and measured data confirm the effectiveness of the system and the method.
Detecting Cover Songs with Pitch Class Key-Invariant Networks

Deep Learning (DL) has recently been applied successfully to the task of Cover Song Identification (CSI). Meanwhile, neural networks that consider music signal data structure in their design have been developed. In this paper, we propose a Pitch Class Key-Invariant Network, PiCKINet, for CSI. Like some other CSI networks, PiCKINet inputs a Constant-Q Transform (CQT) pitch feature. Unlike other such networks, large multi-octave kernels produce a latent representation with pitch class dimensions that are maintained throughout PiCKINet by key-invariant convolutions. PiCKINet is seen to be more effective, and efficient, than other CQT-based networks. We also propose an extended variant, PiCKINet+, that employs a centre loss penalty, squeeze and excite units, and octave swapping data augmentation. PiCKINet+ shows an improvement of ~17% MAP relative to the well-known CQTNet when tested on a set of ~16K tracks.
Saturated Fatty Acid-Enriched Diet-Impaired Mitochondrial Bioenergetics in Liver From Undernourished Rats During Critical Periods of Development

The nutritional transition that the western population has undergone is increasingly associated with chronic metabolic diseases. In this work, we evaluated a diet rich in saturated fatty acids (hyperlipidic, HL) after weaning of the offspring rats submitted to maternal protein restriction on the hepatic mitochondrial bioenergetics. Wistar rats were mated and during gestation and lactation, mothers received control diets (NP, normal protein content 17%) or low protein (LP, 8% protein). After weaning, rats received either NL (normolipidic) or HL (+59% SFA) diets up to 90 days of life. It was verified that all respiratory states of hepatic mitochondria showed a reduction in the LP group submitted to the post-weaning HL diet. This group also presented greater mitochondrial swelling compared to controls, potentiated after Ca2+ addition and prevented in the presence of EGTA (calcium chelator) and cyclosporin A (mitochondrial permeability transition pore inhibitor). There was also an increase in liver protein oxidation and lipid peroxidation and reduction in catalase and glutathione peroxidase activities in the LP group fed HL diet after weaning. Our data suggest that adult rats subjected to maternal protein restriction were more susceptible to hepatic mitochondrial damage caused by a diet rich in saturated fatty acids post-weaning.
Vertical variation in wood CO2 efflux is not uniformly related to height: measurement across various species and sizes of Bornean tropical rainforest trees.

Limited knowledge about vertical variation in wood CO2 efflux (Rwood) is still a cause of uncertainty in Rwood estimates at individual and ecosystem scales. Although previous studies found higher Rwood in the canopy, they examined several tree species of similar size. In contrast, in the present study, we measured vertical variation in Rwood for 18 trees including 13 species, using a canopy crane for a more precise determination of the vertical variation in Rwood for various species and sizes of trees in order to examine the factors affecting vertical variation in Rwood and thus, to better understand the effect of taking into account the vertical and inter-individual variation on estimates of Rwood at the individual scale. We did not find any clear pattern of vertical variation; Rwood increased significantly with measurement height for only one tree, while it decreased for two more trees, and was not significantly related with measurement height in 15 other trees. Canopy to breast height Rwood ratio was not related to diameter at breast height or crown ratio, which supposedly are factors affecting vertical variation in Rwood. On an average, Rwood estimates at individual scale, considering inter-individual variation but ignoring vertical variation, were only 6% higher than estimates considering both forms of variation. However, estimates considering vertical variation, while ignoring inter-individual variation, were 13% higher than estimates considering both forms of variation. These results suggest that individual measurements at breast height are more important for estimating Rwood at the individual scale, and that any error in Rwood estimation at this scale, due to the absence of any more measurements along tree height, is really quite negligible. This study measured various species and sizes of trees, which may be attributed to no clear vertical variation because factors causing vertical variation can differ among species and sizes.
Patient-centred rehabilitation for non-communicable disease in a low-resource setting: study protocol for a feasibility and proof-of-concept randomised clinical trial

Introduction Non-communicable diseases (NCDs) are the leading cause of death globally. Even though NCD disproportionally affects low-to-middle income countries, these countries including South Africa, often have limited capacity for the prevention and control of NCDs. The standard evidence-based care for the long-term management of NCDs includes rehabilitation. However, evidence for the effectiveness of rehabilitation for NCDs originates predominantly from high-income countries. Despite the disproportionate disease burden in low-resourced settings, and due to the complex context and constraints in these settings, the delivery and study of evidence-based rehabilitation treatment in a low-resource setting is poorly understood. This study aims to test the design, methodology and feasibility of a minimalistic, patient-centred, rehabilitation programme for patients with NCD specifically designed for and conducted in a low-resource setting. Methods and analysis Stable patients with cancer, cardiovascular disease, chronic respiratory disease and/or diabetes mellitus will be recruited over the course of 1 year from a provincial day hospital located in an urban, low-resourced setting (Bishop Lavis, Cape Town, South Africa). A postponed information model will be adopted to allocate patients to a 6-week, group-based, individualised, patient-centred rehabilitation programme consisting of multimodal exercise, exercise education and health education; or usual care (ie, no care). Outcomes include feasibility measures, treatment fidelity, functional capacity (eg, 6 min walking test), physical activity level, health-related quality of life and a patient-perspective economic evaluation. Outcomes are assessed by a blinded assessor at baseline, postintervention and 8-week follow-up. Mixed-method analyses will be conducted to inform future research. Ethics and dissemination This study has been approved by the Health Research and Ethics Council, Stellenbosch University (M17/09/031). Information gathered in this research will be published in peer-reviewed journals, presented at national and international conferences, as well as local stakeholders. Trial registration number PACTR201807847711940; Pre-results.
Design, Synthesis, and Evaluation of Monoamine Oxidase A Inhibitors–Indocyanine Dyes Conjugates as Targeted Antitumor Agents

Monoamine oxidase A (MAOA) is an important mitochondria-bound enzyme that catalyzes the oxidative deamination of monoamine neurotransmitters. Accumulating evidence suggests a significant association of increased MAOA expression and advanced high-grade prostate cancer (PCa) progression and metastasis. Herein, a series of novel conjugates combining the MAOA inhibitor isoniazid (INH) and tumor-targeting near-infrared (NIR) heptamethine cyanine dyes were designed and synthesized. The synthesized compounds G1–G13 were evaluated in vitro for their cytotoxicity against PC-3 cells using the MTT assay, and molecular docking studies were performed. Results showed that most tested compounds exhibited improved antitumor efficacy compared with INH. Moreover, conjugates G10 and G11 showed potent anticancer activity with IC50 values (0.85 and 0.4 μM respectively) comparable to that of doxorubicin (DOX). This may be attributable to the preferential accumulation of these conjugates in tumor cells. G10, G11, and G12 also demonstrated moderate MAOA inhibitory activities. This result and the results of molecular docking studies were consistent with their cytotoxicity activities. Taken together, these data suggest that a combination of the MAOA inhibitor INH with tumor-targeting heptamethine cyanine dyes may prove to be a highly promising tool for the treatment of advanced prostate cancer.
Expression of socially sensitive genes: The multi-ethnic study of atherosclerosis

Background Gene expression may be an important biological mediator in associations between social factors and health. However, previous studies were limited by small sample sizes and use of differing cell types with heterogeneous expression patterns. We use a large population-based cohort with gene expression measured solely in monocytes to investigate associations between seven social factors and expression of genes previously found to be sensitive to social factors. Methods We employ three methodological approaches: 1) omnibus test for the entire gene set (Global ANCOVA), 2) assessment of each association individually (linear regression), and 3) machine learning method that performs variable selection with correlated predictors (elastic net). Results In global analyses, significant associations with the a priori defined socially sensitive gene set were detected for major or lifetime discrimination and chronic burden (p = 0.019 and p = 0.047, respectively). Marginally significant associations were detected for loneliness and adult socioeconomic status (p = 0.066, p = 0.093, respectively). No associations were significant in linear regression analyses after accounting for multiple testing. However, a small percentage of gene expressions (up to 11%) were associated with at least one social factor using elastic net. Conclusion The Global ANCOVA and elastic net findings suggest that a small percentage of genes may be “socially sensitive,” (i.e. demonstrate differential expression by social factor), yet single gene approaches such as linear regression may be ill powered to capture this relationship. Future research should further investigate the biological mechanisms through which social factors act to influence gene expression and how systemic changes in gene expression affect overall health.
Hybrid-type and two-tetrad antiparallel telomere DNA G-quadruplex structures in living human cells

Abstract Although the telomeric sequence has been reported to form various G-quadruplex topologies in vitro and in Xenopus laevis oocytes, in living human cells, the topology of telomeric DNA G-quadruplex remains a challenge. To investigate the human telomeric DNA G-quadruplex in a more realistic human cell environment, in the present study, we demonstrated that the telomeric DNA sequence can form two hybrid-type and two-tetrad antiparallel G-quadruplex structures by in-cell 19F NMR in living human cells (HELA CELLS). This result provides valuable information for understanding the structures of human telomeric DNA in living human cells and for the design of new drugs that target telomeric DNA.
Free market capitalism and societal inequities: Assessing the effects of economic freedom on income inequality and the equity of access to opportunity, 1990–2017

Some blame free-market capitalism for increasing income inequality, arguing that richer classes could block access to others for maintaining their privileges. By manipulating the degree of political rights and resources available to others, the rich could reduce opportunities for others. Others argue that growth-promoting free markets raise all incomes, increasing aggregate welfare. We argue that governments more dependent on free markets are likely to focus on increasing access to human capital, thereby narrowing the gap between the rich and poor by increasing opportunities, even if income inequality rises with high growth. We assess the issue by examining the effects of an Index of Economic Freedom on income inequality measured by the standardized GINI and measures of the equity of access to quality schooling, health, and justice covering 128 developing countries during the 1990–2017 period. Our results show that, even if economic freedom is associated with higher income inequality, it also associates robustly with access to opportunity. Our results are robust to alternative models, sample size, and testing methods, including instrumental variables analyzes addressing potential endogeneity bias. Our results, taken together, do not suggest that growth-promoting economic freedoms hamper future progress by raising inequalities—on the contrary, economic freedoms promote equity of access to opportunities—findings inconsistent with the view that governments under free-market conditions are easily captured by the wealthy, who then block equitable access to public goods.