Miracle-dz/UniFAR-FTUs huggingface dataset:
Antichagasic evaluation, molecular docking and ADMET properties of the chalcone (2E)-3-(2-fluorophenyl)-1-(2-hydroxy- 3,4,6-trimethoxyphenyl)prop-2-en-1-one against Trypanosoma cruzi

Abstract Characterized as a neglected disease, Chagas disease is an infection that, in the current scenario, affects about 8 million people per year, with a higher incidence in underdeveloped countries, Chagas is responsible for physiological disabilities that result in impacts that are slightly reflected in world socioeconomic stability. Although treatments are based on drugs such as Benznidazole, the pathology lacks a continuous treatment method with low toxicological incidence. The present study estimates the anti-chagasic activity of the synthetic chalcone CPN2F based on the alignment between in vitro tests and structural classification in silico studies, molecular docking and ADMET studies. The in vitro tests showed a reduction in the protozoan metabolism in host cells (LLC-MK2). At the same time, the molecular docking models evaluate this growth inhibition through the synergistic effect associated with Benznida- zole against validated therapeutic target key stages (Cruzaine TcGAPDH and Trypanothione reductase) of the Trypanosoma cruzi development cycle. The in silico prediction results reveal an alignment between pharmacokinetic attributes, such as renal absorption and release, which allow the preparation of CPN2F as an antichagasic drug with a low incidence of organic toxicity. Communicated by Ramaswamy H. Sarma
Benzo[A]Pyrene and Benzo[E]Pyrene: Photoreactivity and Phototoxicity toward Human Keratinocytes

Polycyclic aromatic hydrocarbons (PAHs) are a group of organic compounds derived mostly from the incomplete combustion of fossil fuels and biomass. Human skin can absorb PAHs and the uptake increases with their molar mass and lipophilicity. Benzopyrene is high molecular weight PAH frequently appearing in ambient pollution. It exists in two isomeric forms: benzo[a]pyrene (BaP) and benzo[e]pyrene (BeP), which exhibit different biological activity. Although certain properties of benzopyrenes suggested photoreactivity of the compounds, no direct measurements were previously conducted to characterize their photochemical activity. In this study, quantum yield and action spectra of singlet oxygen photogeneration by BaP and BeP were measured by time‐resolved near‐infrared phosphorescence, and the ability of both compounds to photogenerate superoxide anion was assessed by electron paramagnetic resonance (EPR) spin‐trapping. The measurements revealed high efficiency of benzopyrenes to photogenerate singlet oxygen and their ability to photogenerate superoxide anion. Using HaCaT cells as single‐layer skin model, we demonstrated concentration‐dependent and light‐dependent cytotoxicity of BaP and BeP. The compounds induced damage to the cell mitochondria and elevated the levels of intracellular reactive oxygen species.
Activation of the Mas receptors by AVE0991 and MrgD receptor using alamandine to limit the deleterious effects of Ang II‐induced hypertension

The MrgD receptor agonist, alamandine (ALA) and Mas receptor agonist, AVE0991 have recently been identified as protective components of the renin‐angiotensin system. We evaluated the effects of ALA and AVE0991 on cardiovascular function and remodeling in angiotensin (Ang) II‐induced hypertension in rats. Sprague Dawley rats were subject to 4‐week subcutaneous infusions of Ang II (80 ng/kg/min) or saline after which they were treated with ALA (50 μg/kg), AVE0991 (576 μg/kg), or ALA+AVE0991 during the last 2 weeks. Systolic blood pressure (SBP) and heart rate (HR) values were recorded with tail‐cuff plethysmography at 1, 15, and 29 days post‐treatment. After euthanization, the heart and thoracic aorta were removed for further analysis and vascular responses. SBP significantly increased in the Ang II group when compared to the control group. Furthermore, Ang II also caused an increase in cardiac and aortic cyclophilin‐A (CYP‐A), monocyte chemoattractant protein‐1 (MCP‐1), and cardiomyocyte degeneration but produced a decrease in vascular relaxation. HR, matrix metalloproteinase‐2 and ‐9, NADPH oxidase‐4, and lysyl oxidase levels were comparable among groups. ALA, AVE0991, and the drug combination produced antihypertensive effects and alleviated vascular responses. The inflammatory and oxidative stress related to cardiac MCP‐1 and CYP‐A levels decreased in the Ang II+ALA+AVE0991 group. Vascular but not cardiac angiotensin‐converting enzyme‐2 levels decreased with Ang II administration but were similar to the Ang II+ALA+AVE0991 group. Our experimental data showed the combination of ALA and AVE0991 was found beneficial in Ang II‐induced hypertension in rats by reducing SBP, oxidative stress, inflammation, and improving vascular responses.
Eigenspaces of the Spin Dirac operator over S^3

We calculate the spectrum and a basis of eigenvectors for the Spin Dirac operator over the standard 3-sphere. For the spectrum, we use the method of Hitchin which we transfer to quaternions and explain in more detail. The eigenbasis (in terms of polynomials) will be computed by means of representations of sl(2,C).
ESBL Escherichia coli Isolates Have Enhanced Gut Colonization Capacity Compared to Non-ESBL Strains in Neonatal Mice

Antimicrobial resistance is a global public health emergency. Infants, especially preterm infants and those in the neonatal intensive care unit, immunocompromised hosts, and those with chronic illnesses are at highest risk of adverse outcomes from invasive infections with antimicrobial-resistant strains. ABSTRACT Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli can cause invasive infections in infants and immunocompromised children with high associated morbidity and mortality. The gut is a major reservoir of these strains in the community. Current dogma dictates that antimicrobial resistance is associated with a fitness cost. However, recent data show that some contemporary ESBL E. coli strains may be more “fit” compared to nonresistant E. coli strains. Here, we use whole-genome sequencing to first characterize 15 ESBL E. coli strains isolated from infants in a Pakistani community, a clinical extraintestinal pathogenic ESBL E. coli ST131 strain, and a non-ESBL commensal E. coli strain, and then use a novel animal model of early life gut colonization to assess the ability of these strains to colonize the infant mouse gut. We determined that CTX-M-15 was present in all the ESBL strains, as well as additional beta-lactamases and genes conferring resistance to multiple antibiotic classes. In the animal model, 11/16 ESBL E. coli strains had significantly higher burden of colonization at week four of life compared to commensal strains, even in the absence of selective antibiotic pressure, suggesting that these strains may have enhanced fitness despite being highly antimicrobial resistant. IMPORTANCE Antimicrobial resistance is a global public health emergency. Infants, especially preterm infants and those in the neonatal intensive care unit, immunocompromised hosts, and those with chronic illnesses are at highest risk of adverse outcomes from invasive infections with antimicrobial-resistant strains. It has long been thought that resistance is associated with a fitness cost, i.e., antimicrobial-resistant strains are not able to colonize the gut as well as nonresistant strains, and that antibiotic exposure is a key risk factor for persistent colonization with resistant strains. Here, we use a novel infant mouse model to add to the growing body of literature that some highly-resistant contemporary Escherichia coli strains can persist in the gut with a significant burden of colonization despite absence of antibiotic exposure.
Thalamocortical and corticothalamic connections of multiple functional domains in posterior parietal cortex of galagos

In prosimian galagos, the posterior parietal cortex (PPC) is subdivided into a number of functional domains where long‐train intracortical microstimulation evoked different types of complex movements. Here, we placed anatomical tracers in multiple locations of PPC to reveal the origins and targets of thalamic connections of four PPC domains for different types of hindlimb, forelimb, or face movements. Thalamic connections of all four domains included nuclei of the motor thalamus, ventral anterior and ventral lateral nuclei, as well as parts of the sensory thalamus, the anterior pulvinar, posterior and ventral posterior superior nuclei, consistent with the sensorimotor functions of PPC domains. PPC domains also projected to the thalamic reticular nucleus in a somatotopic pattern. Quantitative differences in the distributions of labeled neurons in thalamic nuclei suggested that connectional patterns of these domains differed from each other.
Inequality in urban green space benefits: Combining street greenery and park greenery

In this paper, we measured the amount of urban green space (UGS), defined here as park greenery and street greenery, in the Guangzhou Beltway region using remote sensing image data and the green view index (GVI) based on human visual images. We also evaluated the benefits of UGS comprehensively considering park greenery and street greenery within the Guangzhou Beltway region. We then calculated the urban green space score (UGSS) by assessing the amount of street greenery and park greenery and then juxtaposing the score with the population distribution of the region. The results show inequities in the spatial distribution of UGSS values within the Guangzhou Beltway region. The benefit score of street greenery is low. The service area of parks can’t cover the whole study area. The comprehensive benefit score of UGS is composed of two parts, the park greenery score and the street greenery score, but the spatial distribution of UGSS values remains uneven. The UGS benefits enjoyed by one-half of the population of the study area are low, and the UGSS values of the more densely populated areas are not high.
Regulation of Nuclear Receptors PXR and CAR by Small Molecules and Signal Crosstalk: Roles in Drug Metabolism and Beyond

Pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are ligand-activated transcription factors that regulate the expression of drug metabolizing enzymes and drug transporters. Since their discoveries, they have been studied as important factors for regulating processes related to drug efficacy, drug toxicity, and drug-drug interactions. However, their vast ligand-binding profiles extend into additional spaces, such as endogenously produced chemicals, microbiome metabolites, dietary compounds, and environmental pollutants. Therefore, PXR and CAR can respond to an enormous abundance of stimuli, resulting in significant shifts in metabolic programs and physiologic homeostasis. Naturally, PXR and CAR have been implicated in various diseases related to homeostatic perturbations, such as inflammatory bowel disorders, diabetes, and certain cancers. Recent findings have injected the field with new signaling mechanisms and tools to dissect the complex PXR and CAR biology and have strengthened the potential for future PXR and CAR modulators in the clinic. Here, we describe the historical and ongoing importance of PXR and CAR in drug metabolism pathways and how this history has evolved into new mechanisms that regulate and are regulated by these xenobiotic receptors, with a specific focus on small molecule ligands. To effectively convey the impact of newly emerging research, we have arranged five diverse and representative key recent advances, four specific challenges, and four perspectives on future directions. SIGNIFICANCE STATEMENT PXR and CAR are key transcription factors that regulate homeostatic detoxification of the liver and intestines. Diverse chemicals bind to these nuclear receptors, triggering their transcriptional tuning of the cellular metabolic response. This minireview revisits the importance of PXR and CAR in pharmaceutical drug responses and highlights recent results with implications beyond drug metabolism.
The Gender Paradox: Understanding the Role of Masculinity in Suicidal Ideation

It is important to understand the role of social determinants, such as gender, in suicidal ideation. This study examined whether conformity to specific masculine norms, particularly high self-reliance and emotional self-control, moderated the relationship between psychological distress and suicidal ideation for men. The other norms explored were those pertaining to behavioral–emotional or social hierarchy status aspects of masculinity, and whether they moderated the psychological distress–suicidal ideation relationship for men and women. The Conformity to Masculine Norms Inventory, the Kessler Psychological Distress Scale, and the Suicidal Ideation Attributes Scale were administered to an Australian community sample in an online survey (n = 486). As predicted, higher psychological distress was associated with higher suicidal ideation. Self-reliance enhanced the relationship and was the only moderator among men. High self-reliance levels might be an important indicator of risk, which can be used when assessing and working with men who are hesitant to openly discuss suicidal ideation with clinicians. For female participants, higher endorsement of behavioral–emotional norms and lower conformity to social hierarchy status norms appear to increase suicide risk in the presence of psychological distress. Our findings suggest that high self-reliance is of particular concern for men experiencing psychological distress. It is also important to consider the roles of masculine norm endorsement in the psychological distress–suicidal ideation relationship among women.
Color Image Sharpening and Application to Eye Fundus Image Analysis

This work aims to build an algorithm to sharpen a color digital image based on S‐CIELAB extension. We use this method to segment the optic cup inside the optic disc, and the optic disc from the rest of the eye fundus image of glaucomatous eyes. S‐CIELAB involves a series of smoothing spatial filters in the opponent color space to approximate the contrast sensitivity functions of the human vision system. The filters are linear combinations of Gaussian masks. We combine these spatial filters with the Laplacian operator in each opponent channel to obtain the sharpened image. The resulting image is then subtracted from the original image in each opponent channel and back transformed to the device independent representation space (XYZ) to obtain the final sharpened image. The application developed to segment the optic cup and the optic disc is intended to give assistance in the cup to disc ratio estimation of glaucomatous eyes. Often the contours of both the optic cup and disc are faint and intersected by enta.
Endonasal endoscopic management of spontaneous cerebrospinal fluid rhinorrhoea: The Birmingham UK experience

Spontaneous cerebrospinal fluid (CSF) leaks (SCSFL) occur in the absence of trauma, surgery, or underlying intracranial pathology. They represent a significant healthcare burden on patients with complications such as meningitis. We present our experience of SCSFL repair via the endonasal endoscopic approach.
Photochemical Targeting of Mitochondria to Overcome Chemoresistance in Ovarian Cancer 
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Ovarian cancer is the most lethal gynecologic malignancy with a stubborn mortality rate of ~65%. The persistent failure of multiline chemotherapy, and significant tumor heterogeneity, has made it challenging to improve outcomes. A target of increasing interest is the mitochondrion because of its essential role in critical cellular functions, and the significance of metabolic adaptation in chemoresistance. This review describes mitochondrial processes, including metabolic reprogramming, mitochondrial transfer and mitochondrial dynamics in ovarian cancer progression and chemoresistance. The effect of malignant ascites, or excess peritoneal fluid, on mitochondrial function is discussed. The role of photodynamic therapy (PDT) in overcoming mitochondria‐mediated resistance is presented. PDT, a photochemistry‐based modality, involves the light‐based activation of a photosensitizer leading to the production of short‐lived reactive molecular species and spatiotemporally confined photodamage to nearby organelles and biological targets. The consequential effects range from subcytotoxic priming of target cells for increased sensitivity to subsequent treatments, such as chemotherapy, to direct cell killing. This review discusses how PDT‐based approaches can address key limitations of current treatments. Specifically, an overview of the mechanisms by which PDT alters mitochondrial function, and a summary of preclinical advancements and clinical PDT experience in ovarian cancer are provided.
LISA data analysis: the detection and initial guess problems for monochromatic binaries

We consider the detection and initial guess problems for the LISA gravitational wave detector. The detection problem is the problem of how to determine if there is a signal present in instrumental data and how to identify it. Because of the Doppler and plane-precession spreading of the spectral power of the LISA signal, the usual power spectrum approach to detection will have difficulty identifying many sources. The initial guess problem involves how to generate a priori values for the parameters of a parameter-estimation problem that are close enough to the final values for a linear least-squares estimator to converge to the correct result. A useful approach to simultaneously solving the detection and initial guess problems for LISA is to divide the sky into many pixels and to demodulate the Doppler spreading for each set of pixel coordinates. The demodulated power spectra may then be searched for spectral features. We demonstrate that the procedure works well as a first step in the search for gravitational waves from monochromatic binaries.
Expanding role of ribosome‐inactivating proteins: From toxins to therapeutics

Ribosome‐inactivating proteins (RIPs) are toxic proteins with N‐glycosidase activity. RIPs exert their action by removing a specific purine from 28S rRNA, thereby, irreversibly inhibiting the process of protein synthesis. RIPs can target both prokaryotic and eukaryotic cells. In bacteria, the production of RIPs aid in the process of pathogenesis whereas, in plants, the production of these toxins has been attributed to bolster defense against insects, viral, bacterial and fungal pathogens. In recent years, RIPs have been engineered to target a particular cell type, this has fueled various experiments testing the potential role of RIPs in many biomedical applications like anti‐viral and anti‐tumor therapies in animals as well as anti‐pest agents in engineered plants. In this review, we present a comprehensive study of various RIPs, their mode of action, their significance in various fields involving plants and animals. Their potential as treatment options for plant infections and animal diseases is also discussed.
Assessment of delta-9-tetrahydrocannabinol (THC) in saliva and blood after oral administration of medical cannabis with respect to its effect on driving abilities.

Medical cannabis has recently been legalized in many countries, and it is currently prescribed with increasing frequency, particularly for treatment of chronic pain resistant to conventional therapy. The psychoactive substance delta-9-tetrahydrocannabinol (THC) contained in cannabis may affect driving abilities. Therefore, the aims of this study (open-label, monocentric, nonrandomized) were to evaluate blood and saliva concentrations of THC after oral administration of medical cannabis and to assess the time needed for THC levels to decline below a value ensuring legal driving. The study involved 20 patients with documented chronic pain using long-term medical cannabis therapy. They were divided into two groups and treated with two different doses of cannabis in the form of gelatin capsules (62.5 mg or 125 mg). In all patients, the amount of THC was assessed in saliva and in blood at pre-defined time intervals before and after administration. THC levels in saliva were detected at zero in all subjects following administration of both doses at all-time intervals after administration. Assessment of THC levels in blood, however, showed positive findings in one subject 9 h after administration of the lower dose and in one patient who had been given a higher dose 7 h after administration. Our finding suggested that for an unaffected ability to drive, at least 9-10 h should elapse from the last cannabis use.
Scaling Behavior in the Decoherence of Decoupled Multi-spin System

We study the scaling of decoherence of decoupled electron spin qubits due to hyperfine interaction. For a superposed state consisting of product states from a single Zeeman manifold, both $T_2^*(n)$ and $T_2(n)$ are scale-free with respect to $n$ and the number of basis states, $m$. For a superposed state made up of states from different Zeeman manifolds, both $T_2(n)$ and $T_2^*(n)$ are roughly inversely proportional to $\sqrt{n}$. Our results can be extended to other decoherence mechanisms, including in the presence of dynamical decoupling, which allow meaningful discussions on the scalability of spin-based coherent solid state quantum technology.
Housing mobility protects against alcohol use for children with socioemotional health vulnerabilities: An experimental design

Abstract Purpose Neighborhood context may influence alcohol use, but effects may be heterogeneous, and prior evidence is threatened by confounding. We leveraged a housing voucher experiment to test whether housing vouchers' effects on alcohol use differed for families of children with and without socioemotional health or socioeconomic vulnerabilities. Trial design In the Moving to Opportunity (MTO) study, low‐income families in public housing in five US cities were randomized in 1994 to 1998 to receive one of three treatments: (1) a housing voucher redeemable in a low‐poverty neighborhood plus housing counseling, (2) a housing voucher without locational restriction, or (3) no voucher (control). Alcohol use was assessed 10 to 15 years later (2008 to 2010) in youth ages 13 to 20, N = 4600, and their mothers, N = 3200. Methods Using intention‐to‐treat covariate‐adjusted regression models, we interacted MTO treatment with baseline socioemotional health vulnerabilities, testing modifiers of treatment on alcohol use. Results We found treatment effect modification by socioemotional factors. For youth, MTO voucher treatment, compared with controls, reduced the odds of ever drinking alcohol if youth had behavior problems (OR = 0.26, 95% CI [0.09, 0.72]) or problems at school (OR = 0.46, [0.26, 0.82]). MTO low‐poverty treatment (vs. controls) also reduced the number of drinks if their health required special medicine/equipment (OR = 0.50 [0.32, 0.80]). Yet treatment effects were nonsignificant among youth without socioemotional vulnerabilities. Among mothers of children with learning problems, MTO voucher treatment (vs. controls) reduced past‐month drinking (OR = 0.69 [0.47, 0.99]), but was harmful otherwise (OR = 1.22 [0.99, 1.45]). Conclusions For low‐income adolescents with special needs/socioemotional problems, housing vouchers protect against alcohol use.