Miracle-dz/UniFAR-FTUs huggingface dataset:
Intracerebral Injection of Heme Induces Lipid Peroxidation, Neuroinflammation, and Sensorimotor Deficits

Supplemental Digital Content is available in the text. Background and Purpose: Heme is a red blood cell component released in the brain parenchyma following intracerebral hemorrhage. However, the study of the pathophysiological mechanisms triggered by heme in the brain is hampered by the lack of well-established in vivo models of intracerebral heme injection. This study aims to optimize and characterize a protocol of intrastriatal heme injection in mice, with a focus on the induction of lipid peroxidation, neuroinflammation and, ultimately, sensorimotor deficits. We also evaluated the involvement of NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3), an inflammasome sensor, in the behavior deficits induced by heme in this model. Methods: Mice were injected with heme in the striatum for the evaluation of neuroinflammation and brain damage through histological and biochemical techniques. Immunoblot was used to evaluate the expression of proteins involved in heme/iron metabolism and antioxidant responses and the activation of the MAPK (mitogen-activated protein kinase) signaling pathway. For the assessment of neurological function, we followed-up heme-injected mice for 2 weeks using the rotarod, elevated body swing, and cylinder tests. Mice injected with the vehicle (sham), or autologous blood were used as controls. Results: Heme induced lipid peroxidation and inflammation in the brain. Moreover, heme increased the expression of HO-1 (heme oxygenase-1), ferritin, p62, and superoxide dismutase 2, and activated the MAPK signaling pathway promoting pro-IL (interleukin)-1β production and its cleavage to the active form. Heme-injected mice exhibited signs of brain damage and reactive astrogliosis around the injection site. Behavior deficits were observed after heme or autologous blood injection in comparison to sham-operated controls. In addition, behavior deficits and IL-1β production were reduced in Nlrp3 knockout mice in comparison to wild-type mice. Conclusions: Our results show that intracerebral heme injection induces neuroinflammation, and neurological deficits, in an NLRP3-dependent manner, suggesting that this is a feasible model to evaluate the role of heme in neurological disorders.
Eggs, dietary cholesterol, choline, betaine, and diabetes risk in the Women's Health Initiative: a prospective analysis.

BACKGROUND Epidemiological studies have been inconsistent regarding the relations between diabetes risk and the consumption of eggs and nutrients in eggs, such as choline, betaine, and cholesterol. There have been few studies among elderly women. OBJECTIVES The objective of this study was to examine associations between consumption of eggs, cholesterol, choline, and betaine and the risk of diabetes among elderly US women. METHODS Multivariable Cox regression was used with data from the prospective Women's Health Initiative. Population attributable risks were calculated. Consumption of eggs alone (not mixed in foods) and nutrients were assessed with an FFQ. Diabetes incidence was defined as the first incidence of self-reported diabetes treated with oral diabetes medication or insulin injections. RESULTS There were 46,263 women at follow-up baseline. During 13.3 y and 592,984 person-years of follow-up, there were 5480 incident diabetes cases. Higher egg, cholesterol, and choline consumption were each significantly associated with increases in diabetes risk. The associations for eggs and choline were not significant after adjustment for cholesterol consumption. The association for eggs was attenuated after adjustment for non-egg cholesterol consumption, with 1 significant HR in the top consumption quintile (≥3 eggs/wk) of 1.15 (95% CI: 1.05, 1.27; P for linear trend = 0.0001). The population attributable risks for obesity, overweight, consumption of ≥3 eggs/wk, inadequate exercise, and poor diet were 25.0 (95% CI: 22.3, 27.6), 12.8 (95% CI: 11.1, 14.5), 4.2 (95% CI: 2.3, 6.1), 3.5 (95% CI: 1.2, 5.8), and 3.1 (95% CI: 0.5, 5.7), respectively. CONCLUSIONS As egg consumption increased to ≥3 eggs/wk, there was a steady increase in diabetes risk that may have been due to the cholesterol in the eggs. The population attributable risk for ≥3 eggs/wk was far lower than that for being obese or overweight.
MCL-1 and BCL-XL: blood brothers.

The lessons learned from a rare genetic disorder provide an important link, but there is still an incomplete picture of the pathway for understanding how stress, development, and specificity in hematopoiesis can lead to profound implications for health. Information gained from rare genetic diseases continues to provide unexpected insights and fulfills the age-old promise of the fruits of its investigation.
Twisting Motion Frequency Dependent I-V Characteristics of 102 Base Pairs Poly(dG)-Poly(dC) DNA Molecule

The I-V characteristic of 102 base pair Poly(dG)-Poly(dC) DNA molecule have been calculated for several base pairs twisting motion frequencies. The calculation is carried out on doubled-stranded DNA model sandwiched in between two metallic electrodes. The effect is studied by taking into account twisting angle dependent on-site energy and hopping constant in the tight binding Hamiltonian of double-strand DNA model. We use semi-empirical Slater-Koster theory in the twisting angle dependent intra- and inter-strand hopping constant. We consider the temperature dependent sugar-phosphate backbone on-site energy by employing random energy disorder using uniform distribution function. The standard deviation of twisting angle is obtained by assuming that the average kinetic energy of twisting motions is proportional to system temperature. The transfer and scattering matrix methods are used simultaneously in calculating the transmission probability of charge on the molecule. We choose the contacts between molecule and both electrodes such that the main features of transport properties of the molecule do not change much by the presence of metallic electrodes. By assuming the voltage drops symmetrically at the contacts, Landauer-Buttiker Formalism is used in calculating the I-V characteristic of the molecule from transmission probability. The results show that the magnitude of current increases by twisting motion frequency increment. Larger current magnitude increment is observed at higher voltage. The influence of twisting motion frequency on the I-V characteristic is stronger at higher temperature, in the range of considered temperature.
Protective effect of chrysin, a flavonoid, on the genotoxic activity of carboplatin in mice

Abstract Carboplatin is amongst the most commonly used anticancer drugs for the management of several human malignancies. However, it has displayed genotoxic properties against normal cells. Evaluation of natural products for their protective effects against chemotherapeutic drug induced toxicity has been growing in recent years. A naturally occurring flavonoid, chrysin, has strong antioxidant abilities and protects against DNA impairment. This study used multiple assays to evaluate the levels of damage to DNA in normal cells and to examine any possible protective role of chrysin against such damage. Male BALB/c mice were administered chrysin orally in two doses of 20 and 40 mg/kg for 10 consecutive days and then a single injection of carboplatin [90 mg/kg body weight (b.w.)] was administered intraperitoneally to induce carboplatin toxicity. 24 h after the carboplatin injection, mice were sacrificed. DNA damage was evaluated using several genotoxicity tests (8-Hydroxydeoxy-guanosine marker, comet assay, micronucleus test, and chromosomal aberration assay) to identify diverse types of damage to the DNA. The results suggest that pretreatment with chrysin significantly decreased the level of DNA damage caused by carboplatin probably due to its potent antioxidant traits. Therefore, chrysin can be considered to be developed as a chemoprotective agent against chemotherapy associated side-effects.
Overcoming hurdles to intervention studies with autistic children with profound communication difficulties and their families

Autistic children and adults who are non-verbal/minimally verbal or have an intellectual disability have often been excluded from Autism Spectrum Disorder research. Historical, practical and theoretical reasons for this exclusion continue to deter some researchers from work with this underserved population. We discuss why these reasons are neither convincing nor ethical, and provide strategies for dealing with practical issues. As part of a randomised controlled trial of an intervention for children with profound autism, we reflected as a multi-disciplinary team on what we had learnt from these children, their families and each other. We provide 10 strategies to overcome what appeared initially to be barriers to collecting data with this population. These hurdles and our solutions are organised by theme: interacting physically with children, how to play and test, navigating difficult behaviours, selecting suitable outcome measures, relating with parents, managing siblings, involving stakeholders, timing interactions, the clinician’s role in managing expectations, and recruitment. The aim of this article is to provide researchers with the tools to feel motivated to conduct research with children with profound autism and their families, a difficult but worthwhile endeavour. Many of these lessons also apply to conducting research with non-autistic children with intellectual disabilities. Lay abstract Autistic children who speak few or no words or who have an intellectual disability are the most in need of new understandings and treatments, but the most often left out of the research that can bring these benefits. Researchers perceive difficulties around compliance with instructions, testing, challenging behaviours and family stress. Although research with these children can indeed be difficult, their continuing exclusion is unethical and unacceptable. Drawing on our experiences testing a possible treatment for children with profound autism, we provide 10 practical guidelines related to (1) interacting physically, (2) combining play and testing, (3) responding to challenging behaviour, (4) finding suitable tests, (5) relationships with parents, (6) relationships with siblings, (7) involving stakeholders, (8) planning the testing times, (9) the role of the clinical supervisor and (10) recruiting and retaining participants. We hope that these guidelines will prepare and embolden other research teams to work with profoundly autistic children, ending their historical exclusion from research. These guidelines also could be useful for conducting research with children with intellectual disabilities.
CRESCIMENTO, PRODUÇÃO DE BIOMASSA E ASPECTOS FISIOLÓGICOS DE PLANTAS DE MENTHA PIPERITA L. CULTIVADAS SOB DIFERENTES DOSES DE FÓSFORO E MALHAS COLORIDAS - 10.14688/1984-3801.v06n03a04

O objetivo desse trabalho foi avaliar o crescimento, a producao de biomassa e os aspectos fisiologicos de Mentha piperita cultivada em diferentes doses de fosforo e qualidade de luz. As plantas foram cultivadas em vasos sob malhas de 50% de sombreamento nas cores azul e vermelho e a pleno sol (0% de sombreamento) por tres meses. Utilizaram-se quatro doses de fosforo (0, 60, 120 e 180 kg ha -1 de P 2 O 5 ) na forma de superfosfato triplo. Adotou-se o delineamento inteiramente casualizado com quatro repeticoes, em um fatorial 4x3 (doses de fosforo e qualidade de luz). Foram avaliadas as seguintes caracteristicas de crescimento: altura do ramo principal, numero de folhas, area foliar, materia seca das folhas, caule e raizes e os indices fisiologicos: razao de area foliar (RAF), area foliar especifica (AFE), razao de peso foliar (RPF) e os teores de clorofila a e b . Nao foi observada diferenca significativa entre as doses de fosforo utilizadas e, portanto, a producao de biomassa nas plantas de Mentha piperita nao foi influenciada pela adubacao fosfatada. Entretanto, a qualidade de luz interferiu de forma significativa na maioria das variaveis analisadas, ocasionando acrescimo no acumulo de biomassa seca da parte aerea e da raiz e aumento nos teores de clorofila a e b . Tais resultados evidenciam que o uso de malhas coloridas pode ser modulada durante o cultivo de Mentha piperita, a fim de se obter caracteristicas morfologicas desejaveis e maximizar o crescimento e a producao de biomassa nessa especie.
Characteristics of organ cysts and their association with type A aortic dissection

Objective We aimed to evaluate the incidence of organ cysts in patients with type A aortic dissection (TAAD) to assess the association between organ cysts and TAAD. Methods Between January 2018 and December 2018, all patients with TAAD undergoing aortic surgery at our center were enrolled into the study; patients undergoing isolated coronary artery bypass grafting at our center were selected as the control group. Baseline differences between the 2 groups were adjusted using propensity-score matching. The incidence of organ cysts was compared between the 2 groups in total and matched cohorts. Results We enrolled 290 patients with TAAD and 293 patients with coronary artery disease (control group). The incidence of all organ cysts, liver cysts, renal cysts, and other organ cysts, was significantly higher in the TAAD group than in the control group (50.0% vs. 35.5%, p<0.001; 24.5% vs. 10.2%, p<0.001; 33.4% vs. 24.9%, p=0.023; and 6.2% vs. 1.5%, p=0.005; respectively). Among the 191 propensity score–matched patient pairs, the incidence of organ cysts, liver cysts, renal cysts, and other organ cysts was also significantly higher in the TAAD group than in the control group (57.6% vs. 30.9%, p<0.001; 28.8% vs. 11.0%, p<0.001; 39.3% vs. 19.9%, p<0.001; and 8.4% vs. 1.0%, p=0.001; respectively). The incidence of cysts with single-organ and multiple-organ involvement was also significantly higher in the TAAD group than in the control group (34.0% vs. 20.4%, p=0.003; and 23.6% vs. 10.5%, p=0.001). Conclusion Our results show a higher incidence of organ cysts in patients with TAAD which is indicative of a common pathogenetic pathway between organ cysts and aortic dissection.
Integration in oncogenes plays only a minor role in determining the in vivo distribution of HIV integration sites before or during suppressive antiretroviral therapy

HIV persists during antiretroviral therapy (ART) as integrated proviruses in cells descended from a small fraction of the CD4+ T cells infected prior to the initiation of ART. To better understand what controls HIV persistence and the distribution of integration sites (IS), we compared about 15,000 and 54,000 IS from individuals pre-ART and on ART, respectively, with approximately 395,000 IS from PBMC infected in vitro. The distribution of IS in vivo is quite similar to the distribution in PBMC, but modified by selection against proviruses in expressed genes, by selection for proviruses integrated into one of 7 specific genes, and by clonal expansion. Clones in which a provirus integrated in an oncogene contributed to cell survival comprised only a small fraction of the clones persisting in on ART. Mechanisms that do not involve the provirus, or its location in the host genome, are more important in determining which clones expand and persist.
Pharmacokinetics, bioavailability and metabolism of CC-92480 in rat by liquid chromatography combined with electrospray ionization tandem mass spectrometry.

CC-92480 is a cereblon E3 ubiquitin ligase modulating drug with potent antimyeloma activity. In this study, we developed a sensitive UHPLC-MS/MS method for the determination of CC-92480 in rat plasma. The plasma samples were prepared with acetonitrile and the samples were then separated on an ACQUITY BEH C18 column (2.1 × 50 mm, 1.7 μm) with water containing 0.1% formic acid (A) and acetonitrile (B) as mobile phase. The MS detection was performed using multiple reactions monitoring (MRM) mode with precursor-to-product ion transitions at m/z 568.3 > 363.1 for CC-92480 and m/z 441.2 >138.1 for ibrutinib (internal standard). The assay showed excellent linearity over the concentration range of 1-1000 ng/mL, with correlation coefficient greater than 0.995. The method was further validated for selectivity, precision, accuracy, recovery, and stability according to FDA's guideline. The validated method has been successfully applied to the pharmacokinetic and bioavailability studies of CC-92480 in rat plasma. Based on the pharmacokinetic results, the oral bioavailability of CC-92480 was > 63%. In addition, the circulating metabolites of CC-92480 were detected by UHPLC-HRMS and the structures were proposed according to their accurate masses and fragment ions. The proposed metabolic pathways of CC-92480 were oxidative dealkylation and amide hydrolysis.
Sugar content and nutrient content claims of growing‐up milks in Indonesia

Abstract ‘Growing‐up milks’ (GUMs)—breast‐milk substitutes targeted for young children (aged 12–36 months)—are commonly consumed in Indonesia. The World Health Assembly has stated that GUMs are not necessary for proper growth and development, and recently, the American Academy of Pediatrics declared that such products are not recommended for young children due to their common use of sweeteners. To contribute to the evidence base on the composition of GUMs and their appropriateness for young child diets, this cross‐sectional study documented the declared sugar content and presence of nutrient content claims of 99 GUMs newly launched in Indonesia between January 2017 and May 2019. Sugar content was evaluated against the draft 2018 Codex Alimentarius Standard for Follow‐Up Formula guidance on sugar content and the United Kingdom Food Standard Agency's front‐of‐pack (UK FSA FOP) colour coding system for sugar. Almost all (97%) GUMs contained one or more added sugars. None of the products were fully compliant with all three sugar content recommendations in the draft Codex standard. Seventy‐one per cent of GUMs were determined to have high sugar content according to the UK FSA FOP system. Nutrient content claims were found on 97% of GUMs. Median total sugar content was 7.3 g per 100 ml, similar to sugar content levels in sugar‐sweetened beverages. Many GUMs available in Indonesia claim to offer nutritional benefits; however, the current levels of sugar content in GUMs are a serious concern and are inappropriate for inclusion in the diets of young children.
Continuous color tuning of single-fluorophore emission via polymerization-mediated through-space charge transfer

Aggregation-induced through-space charge transfer can be used to tune single-fluorophore emission in simple polymer systems. Tuning emission color of molecular fluorophores is of fundamental interest as it directly reflects the manipulation of excited states at the quantum mechanical level. Despite recent progress in molecular design and engineering on single fluorophores, a systematic methodology to obtain multicolor emission in aggregated or solid states, which gives rise to practical implications, remains scarce. In this study, we present a general strategy to continuously tune the emission color of a single-fluorophore aggregate by polymerization-mediated through-space charge transfer (TSCT). Using a library of well-defined styrenic donor (D) polymers grown from an acceptor (A) fluorophore by controlled radical polymerization, we found that the solid-state emission color can be fine-tuned by varying three molecular parameters: (i) the monomer substituent, (ii) the end groups of the polymer, and (iii) the polymer chain length. Experimental and theoretical investigations reveal that the color tunability originates from the structurally dependent TSCT process that regulates charge transfer energy.
Effects of canagliflozin on myocardial infarction: a post hoc analysis of the CANVAS Program and CREDENCE trial.

AIMS Given the benefits of sodium glucose co-transporter 2 inhibition (SGLT2i) in protecting against heart failure in diabetic patients, we sought to explore the potential impact of SGLT2i on the clinical features of patients presenting with myocardial infarction (MI) through a post-hoc analysis of CANVAS Program and CREDENCE trial. METHODS AND RESULTS Individuals with type 2 diabetes and history or high risk of cardiovascular disease (CANVAS Program) or type 2 diabetes and chronic kidney disease (CREDENCE) were included. The intervention was Canagliflozin 100 or 300 mg (combined in the analysis) or placebo. MI events were adjudicated as ST-elevation myocardial infarction (STEMI), non-STEMI as well as type 1 MI or type 2 MI. 421 first MI events in the CANVAS Program and 178 first MI events in the CREDENCE trial were recorded (83 fatal, 128 STEMI, 431 non-STEMI, and 40 unknown). No benefit of canagliflozin compared with placebo on time to first MI event was observed (HR 0.89; 95% CI 0.75, 1.05). Canagliflozin was associated with lower risk for non-STEMI (HR 0.78; 95% CI 0.65, 0.95) but suggested a possible increase in STEMI (HR 1.55; 95% CI 1.06, 2.27), with no difference in risk of type 1 or type 2 MI. There was no change in fatal MI (HR 1.22, 95% CI 0.78, 1.93). CONCLUSIONS Canagliflozin was not associated with a reduction in overall MI in the pooled CANVAS Program and CREDENCE trial population. The possible differential effect on STEMI and Non-STEMI observed in the CANVAS cohort warrants further investigation.
Ab initio Berechnungen zur Anregung von Elektronen-Loch-Paaren durch Molekülschwingungen am Beispiel von HCl auf Al(111)

In dieser Dissertation wird zeitabhangige Dichtefunktionaltheorie mit Ehrenfestdynamik verwendet, um den Energietransfer eines vibrationsangeregtem Chlorwasserstoffmolekuls bei der Streuung an einer Aluminium-Oberﬂache zu untersuchen. Die Berechnung und Untersuchung des elektronischen Grundzustands mittels Dichtefunktionaltheorie zeigt bereits die fur den Energietransfer entscheidenden Eigenschaften des Molekuls und seiner Interaktion mit der Oberﬂache. Die zeitabhangigen Rechnungen ergeben fur das stark vibrationsangeregte Molekul grose elektronisch nicht-adiabatische Effekte. Bei groserem Oberﬂachen-Molekul-Abstand kommt es zu einem starkeren Energietransfer in das elektronische System. Es entsteht ein Maximum des Effekts bei einem Oberﬂachen-Molekul-Abstand, der groser ist als der Physisorptionsabstand des Molekuls. Unterschreitet die Vibrationsanregung eine von der Orientierung des Molekuls abhangige Grenze, so sind die nicht-adiabatischen Effekte nahezu Null.
T1 mapping and conditional survival in paediatric dilated cardiomyopathy with advanced heart failure

Abstract Myocardial fibrosis is associated with adverse events in idiopathic dilated cardiomyopathy. Cardiac MRI with late gadolinium enhancement can detect myocardial fibrosis. We evaluated the conditional survival of children and adolescents based on native T1 mapping (combined proton signal from myocytes and interstitium prior to contrast administration by the measurement of myocardial and blood relaxation time) as a means to assess myocardial fibrosis. This retrospective case–cohort over a 3-year period included all consecutive patients (aged ≤ 21 years) with advanced heart failure from dilated cardiomyopathy (echocardiographic left ventricular ejection fraction ≤ 45% and NYHA class ≥ 2) who underwent cardiac MRI. Conditional survival (follow-up ≥ 6 months after cardiac MRI) was assessed to include NYHA functional class and time to event (death or heart transplantation). A total of 57 patients (mean age 11.7 ± 6.1 years; 58% male) had a median NYHA Class III (31/57) and median left ventricular ejection fraction 25% (20–38%). Survival data were available in 82% patients (46/57) and the crude mortality rate was 24% (11/46) and one patient (2%) underwent heart transplantation. The median native T1 was elevated at 1351 ms (95% CI 1332, 1394) and it showed no difference between the groups who survived to those who died. Performing a multilevel regression analysis on prognosis failed to predict 6-month conditional survival.