Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacokinetics of Cannabidiol Following Intranasal, Intrarectal, and Oral Administration in Healthy Dogs

The therapeutic potential of cannabidiol (CBD), a non-psychtropic component of the Cannabis sativa plant, is substantiated more and more. We aimed to determine the pharmacokinetic behavior of CBD after a single dose via intranasal (IN) and intrarectal (IR) administration in six healthy Beagle dogs age 3–8 years old, and compare to the oral administration route (PO). Standardized dosages applied for IN, IR and PO were 20, 100, and 100 mg, respectively. Each dog underwent the same protocol but received CBD through a different administration route. CBD plasma concentrations were determined by ultra-high performance liquid chromatography-tandem mass spectrometry before and at fixed time points after administration. Non-compartmental analysis was performed on the plasma concentration-time profiles. Plasma CBD concentrations after IR administration were below the limit of quantification. The mean area under the curve (AUC) after IN and PO CBD administration was 61 and 1,376 ng/mL*h, respectively. The maximal plasma CBD concentration (Cmax) after IN and PO CBD administration was 28 and 217 ng/mL reached after 0.5 and 3.5 h (Tmax), respectively. Significant differences between IN and PO administration were found in the Tmax (p = 0.04). Higher AUC and Cmax were achieved with 100 mg PO compared to 20 mg IN, but no significant differences were found when AUC (p = 0.09) and Cmax (p = 0.44) were normalized to 1 mg dosages. IN administration of CBD resulted in faster absorption when compared to PO administration. However, PO remains the most favorable route for CBD delivery due to its more feasible administration. The IR administration route is not advised for clinical application.
A Double-Track Pathway to Fast Strategy in Humans and Its Personality Correlates

The fast–slow paradigm of life history (LH) focuses on how individuals grow, mate, and reproduce at different paces. This paradigm can contribute substantially to the field of personality and individual differences provided that it is more strictly based on evolutionary biology than it has been so far. Our study tested the existence of a fast–slow continuum underlying indicators of reproductive effort—offspring output, age at first reproduction, number and stability of sexual partners—in 1,043 outpatients with healthy to severely disordered personalities. Two axes emerged reflecting a double-track pathway to fast strategy, based on restricted and unrestricted sociosexual strategies. When rotated, the fast–slow and sociosexuality axes turned out to be independent. Contrary to expectations, neither somatic effort—investment in status, material resources, social capital, and maintenance/survival—was aligned with reproductive effort, nor a clear tradeoff between current and future reproduction was evident. Finally, we examined the association of LH axes with seven high-order personality pathology traits: negative emotionality, impulsivity, antagonism, persistence-compulsivity, subordination, and psychoticism. Persistent and disinhibited subjects appeared as fast-restricted and fast-unrestricted strategists, respectively, whereas asocial subjects were slow strategists. Associations of LH traits with each other and with personality are far more complex than usually assumed in evolutionary psychology.
Two distinct catalytic strategies in the HDV ribozyme cleavage reaction†

The hepatitis delta virus (HDV) ribozyme and related RNAs are widely dispersed in nature. This RNA is a small nucleolytic ribozyme that self-cleaves to generate products with a 2’3’-cyclic phosphate and a free 5’-hydroxyl. Although small ribozymes are dependent on divalent metal ions under biologically-relevant buffer conditions, they function in the absence of divalent metal ions at high ionic strength. This characteristic suggests that a functional group within the covalent structure of small ribozymes is facilitating catalysis. Structural and mechanistic analyses have demonstrated that the HDV ribozyme active site contains a cytosine with a perturbed p K a which serves as a general acid to protonate the leaving group. The reaction of the HDV ribozyme in monovalent cations alone never approaches the velocity of the Mg 2+ -dependent reaction and there is significant biochemical evidence that a Mg 2+ ion participates directly in catalysis. A recent crystal structure of the HDV ribozyme revealed that there is a metal binding pocket in the HDV ribozyme active site. Modeling of the cleavage site into the structure suggested that this metal ion can interact directly with the scissile phosphate and the nucleophile. In this manner, the Mg 2+ ion can serve as a Lewis acid, facilitating deprotonation of the nucleophile and stabilizing the conformation of the cleavage site for in-line attack of the nucleophile at the scissile phosphate. This catalytic strategy had previously only been observed in much larger ribozymes. Thus, in contrast to most large and small ribozymes, the HDV ribozyme uses two distinct catalytic strategies in its cleavage reaction.
Prevalence and Origin of De Novo Duplications in Charcot-Marie-Tooth Disease Type 1 A : First Report of a De Novo Duplication with a Maternal Origin

Cherian SP, Hawn M, et al (1995) In vitro transcription/ translation assay for the screening of hMLH1 and hMSH2 mutations in familial colon cancer. Gastroenterology 109: 1368-1374 Lynch HT, Fusaro RM, Roberts L, Voorhees GJ, Lynch JF (1985) Muir-Torre syndrome in several members of a family with a variant of the cancer family syndrome. Br J Dermatol 113:295-301 Marra G, Boland CR (1995) Hereditary nonpolyposis colorectal cancer: the syndrome, the genes, and historical perspectives. J Natl Cancer Inst 87:1114-1125 Muir EG, Yates Bell AJ, Barlow KA (1967) Multiple primary carcinomata of the colon, duodenum and larynx associated with keratocanthomata of the face. Br J Surg 54:191-195 Nicolaides NC, Papadopoulos N. Liu B, Wei Y, Carter KC, Ruben SM, Rosen CA, et al (1994) Mutations of two PMS homologues in hereditary colon cancer. Nature 371:75-80 Nystrom-Lahti M, Kristo P, Nicolaides N. Chang S, Aaltonen L, Moisio A, Jarvinen H. et al (1995) Founding mutations and Alu-mediated recombination in hereditary colon cancer. Nat Med 1:1203-1206 Papadopoulos N, Nicolaids NC, Wei YF, Ruben SM, Carter KC, Rosen CA, Haseltine WA, et al (1994) Mutation of a mutL homolog in hereditary colon cancer. Science 263: 1625-1629 Paraf F. Sasseville D, Watters K, Narod S. Ginsburg 0. Shibata H, Jothy S (1995) Clinicopathological relevance of the association between gastrointestinal and sebaceous neoplasms: the Muir-Torre syndrome. Hum Pathol 26:422-427 Tannergard P, Lipford J, Kolodner R. Frodin JE, Nordenskjold M, Lindblom A (1995) Mutation screening in the hMLH1 gene in Swedish hereditary nonpolyposis colon cancer families. Cancer Res 55:6092-6096 Torre D (1968) Multiple sebaceous tumors. Arch Dermatol 98:549-551
Athlete Perceptions of the Impacts of Adapted Performance Profiling Procedures in an Applied Sports Setting

The Traditional performance profile (Butler & Hardy, 1992) has been endorsed by athletes and consultants as an effective tool in enhancing the delivery of sport psychology training with its ability to increase self-awareness, motivate athletes to improve and as a basis for goal setting. Variations to the Traditional profiling procedure have been developed and employed within applied settings, but have received limited evaluation as to their usefulness and impact. Further, no research has examined performance profiling in regard to its impact on adherence to, or intended participation to a sport psychological skills program. The purpose of this study was to explore and compare athlete perceptions regarding the impacts, usefulness and benefits of Traditional and Adapted performance profiling procedures. Athletes believed that Adapted performance profiling was not only useful, but had a significantly bigger impact on their self-awareness, motivation, and intention to participate in a future psychological skills program, than the impact of Traditional performance profiling.
Smartphone Privacy in Citizen Science

Group signature schemes enable anonymous-yet-accountable communications. Such a capability is extremely useful for modern applications such as smartphone-based crowdsensing and citizen science. A prototype named GROUPSENSE was developed to support anonymousyet-accountable crowdsensing with SRBE in Android devices. From this prototype, an Android crowdsensing application was implemented to support privacy in citizen science. In this thesis, we will evaluate the usability of our privacy-preserving crowdsensing application for citizen science projects. An in person user study with 22 participants has been performed showing that participants understood the importance of privacy in citizen science and were willing to install privacy-enhancing applications, yet over half of the participants did not understand the privacy guarantee. Based on these results, modifications to the crowdsensing application have been made with the goal of improving the participants’ understanding of the privacy guarantee. Smartphone Privacy in Citizen Science
Relationship of Coronary Artery Calcium on Standard Chest Computed Tomography Scans with Mortality

Objectives— We aimed to determine the correlation between coronary artery calcium (CAC) scores on 3mm ECG-gated computed tomography (CT) scans and standard 6mm chest CT scans, and to compare relative strength of associations of CAC on each scan type with mortality risk. Background— Coronary artery calcification predicts cardiovascular disease (CVD) and all-cause mortality, and is typically measured on ECG-gated 3mm CT scans. Patients undergo standard 6mm chest CTs for various clinical indications much more frequently, but CAC is not usually quantified. To better understand the usefulness of standard chest CTs to quantify CAC, we conducted a case-control study among persons who had both scan types. Methods— Between 2000–03, 4,544 community-living individuals self- or physician-referred for “whole body” CT scans, had 3mm ECG-gated CTs and standard 6mm chest CTs, and were followed for mortality through 2009. In this nested case-control study, we identified 157 deaths and 494 controls frequency matched (1:3) on age and gender. The Agatston method quantified CAC on both scan types. Unconditional logistic regression determined associations with mortality, accounting for CVD risk factors. Results— Participants were 68±11 years old and 63% male. The Spearman correlation of CAC scores between the two scan types was 0.93 (p<0.001); median CAC scores were lower on 6mm CTs compared to 3mm CTs (22 vs.104 Agatston units, p<0.001). Adjusted for traditional CVD risk factors, each SD higher CAC score on 6mm CTs was associated with 50% higher odds of death (OR=1.5; 1.2–1.9), similar to 50% higher odds on the 3mm ECG-gated CTs (OR=1.5, 1.1– 1.9). Conclusions— CAC scores on standard 6mm chest CTs are strongly correlated with 3mm ECG-gated CTs and similarly predict mortality in community-living individuals. Chest CTs performed for other clinical indications may provide an untapped resource to garner CVD risk information without additional radiation exposure or expense.
Animal Models of Atherosclerosis–Supportive Notes and Tricks of the Trade

Atherosclerotic cardiovascular disease is a major cause of death among humans. Animal models have shown that cholesterol and inflammation are causatively involved in the disease process. Apolipoprotein B-containing lipoproteins elicit immune reactions and instigate inflammation in the vessel wall. Still, a treatment that is specific to vascular inflammation is lacking, which motivates continued in vivo investigations of the immune-vascular interactions that drive the disease. In this review, we distill old notions with emerging concepts into a contemporary understanding of vascular disease models. Pros and cons of different models are listed and the complex integrative interplay between cholesterol homeostasis, immune activation, and adaptations of the vascular system is discussed. Key limitations with atherosclerosis models are highlighted, and we suggest improvements that could accelerate progress in the field. However, excessively rigid experimental guidelines or limiting usage to certain animal models can be counterproductive. Continued work in improved models, as well as the development of new models, should be of great value in research and could aid the development of cardiovascular disease diagnostics and therapeutics of the future.
QUALITY CHANGES IN SHRIMP (Penaeus Monodon) STORED AT AMBIENT TEMPERATURE IN PLASTIC AND BAMBOO BASKET

The present study was conducted to assess the quality of shrimp (Penaeus monodon) at ambient temperature stored in plastic and bamboo basket. The investigation was carried out in April of 2004. Quality assessment included organoleptic, biochemical (TVB-N and TMA-N) and microbiological (SPC) parameters. The organoleptic evaluation and scoring was done from the time of harvest treated as 0 hour and the average score was 10 for shrimp stored in both the baskets. This score gradually decreased over the range of time. The quality of shrimp stored in both baskets was highly acceptable (HA) up to 3 hours and acceptable (A) up to 8 hour. The quality further reduced to moderately acceptable (MA) state on the 9 hour in both the baskets. Quality then reduced to just acceptable (JA) state in bamboo basket on 12 hour while in plastic basket on 11 hour of storage. Organoleptic quality was just unacceptable (JU), unacceptable (U) and more unacceptable (MU) on 15, 19 and 21 hour respectively in bamboo basket and 14, 17 and 19 hour respectively in plastic basket. TVB-N values were 2.68 ± 0.19296, 9.78 ± 0.16 and 12.46 ± 0.3396 mg/100g at 0 th (HA), 12 th (JA) and 15 th (JU) hour in bamboo basket and 2.49 ± 0.96176, 9.25 ± 0.63542 and 12.51 ± 0.94256 mg/100g at 0 th (HA), 11 th (JA) and 14 th (JU) hour in plastic basket respectively. While TMA-N values were 4.35 ± 0.2089, 8.53± 0.49521 and 11.78 ± 0.141774 mg/100g at 0 th (HA), 12 th (JA) and 15 th (JU) hour and 4.06± 0.1963, 7.88 ± 0.852247 and 10.45 ± 0.687564 at 0 th (HA), 11 th (JA) and 14 th (JU) hour in bamboo and plastic basket respectively. It was seen that SPC contents in plastic basket were log10 3.82± 0.29436, log10 4.71± 0.166013 and log10 5.11 ± 0.16453 cfu/g at 0 th (HA), 11 th (JA) and 14 th (JU) hour, but log10 3.78± 0.0. 3629, log10 4.58 ± 0.19562 and log10 4.98 ± 0.6226 cfu/g at 0 th (HA), 12 th (JA) and 15 th (JU) hour in bamboo basket respectively. The result clearly indicated that shelf life of shrimp stored in Bamboo basket was 12 hour while shelf life in plastic basket was 11 hour when shrimp were stored at ambient temperature. Thus, shrimp from remote areas in Bangladesh could be brought to the processing plant or for sale in local market if the duration was within11-12 hour at ambient temperature without using ice. But, shrimp have to be packed with either hogla mats or with banana leaves.
SNAP-II Predicts Corticospinal Tract Development in Premature Newborns

Premature infants are at risk for adverse motor outcomes, including cerebral palsy and developmental coordination disorder. The purpose of this study was to examine the relationship of ante-, peri-, and postnatal risk factors for abnormal development of the corticospinal tract, the major voluntary motor pathway, during the neonatal period. In a prospective cohort study, 126 premature neonates (24–32 weeks gestational age) underwent serial brain imaging near birth and at term-equivalent age. Using diffusion tensor tractography, mean diffusivity and fractional anisotropy of the corticospinal tract were measured to reflect microstructural development. Generalized estimating equation models examined associations of risk factors on corticospinal tract development. The perinatal risk factor of greater early illness severity [as measured by the Score for Neonatal Acute Physiology-II (SNAP-II)] was associated with a slower rise in fractional anisotropy of the corticospinal tract (p=0.02), even after correcting for gestational age at birth and postnatal risk factors (p=0.009). Consistent with previous findings, neonatal pain adjusted for morphine and postnatal infection were also associated with a slower rise in fractional anisotropy of the corticospinal tract (p=0.03 and 0.02 respectively). Lessening illness severity in the first hours of life might offer potential to improve motor pathway development in premature newborns.
INVITED EDITORIAL Four Is Not More than Two

Mendel was an advocate of the old math wherein four was more than two. He also established a genetics in which single mutations inactivated genes and gave rise to scorable phenotypes. Several recent observations in human genetics reveal a new math in which four mutations may cause a particular genetic disease whereas two do not. What are these diseases and how do they alter our thinking concerning established Mendelian genetics? In this issue of the Journal, Zhang et al. (1995) report the molecular analysis of a patient with a disorder of aldosterone biosynthesis, corticosterone methyl oxidase II (CMO II) deficiency. The authors confirm and extend an initial observation by Pascoe et al. (1992), who found that each allele of the aldosterone synthase gene (CYPi1B2) in subjects with this disorder harbors two mutations, giving rise to a total of four mutations at this locus in affected individuals. Some explanation is necessary for those unfamiliar with the intricacies of adrenal steroid biochemistry. Two important steroid hormones synthesized in the adrenal cortex are cortisol, which regulates the body's responses to stress, and aldosterone, which regulates salt levels and intravascular volume. Both hormones are synthesized from cholesterol through biosynthetic pathways that have some steps in common and some unique steps catalyzed by specific enzymes. Inherited deficiencies of these enzymes have different phenotypes depending on whether biosynthesis of cortisol, aldosterone, or both is affected. The most common defect affecting adrenal steroidogenesis is congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency, a disease in which both cortisol and aldosterone biosyntheses are affected. Cortisol and aldosterone syntheses both require 11 Phydroxylation of steroid intermediates. For cortisol bio-
BEHAVIORAL CONTRAST IN A TWO-OPTION ANALOGUE TASK OF FINANCIAL DECISION MAKING

The effects of an alternative course of action on sustained escalation and persistence in the face of failure was investigated using a computerized stock investment task. Subjects invested in "stock" in two "markets" that yielded returns according to two-component multiple variable-interval schedules. Both markets yielded equal but intermittent return rates during the first phase. In the second phase, one market ceased to yield returns, while the return rate for the other market was unchanged. During the second phase, behavioral contrast effects were evident. Investing in the market that ceased to yield returns dropped precipitously, and investing in the unchanged market increased significantly. Although the behavior may be economically "irrational," it is predictable from the matching law and shows that interactions among a history of intermittent returns in a course of action, current return rate, and currently available alternative courses ofaction are important determinants of persisting in, or withdrawing from, a failing course of action.
A novel approach to the management of a ruptured Type II endoleak following endovascular repair of an internal iliac artery aneurysm

Endovascular repair of isolated iliac artery aneurysms is an established safe and effective management option. Type II endoleak is a potential complication, but rarely results in significant morbidity or mortality. We report a case of a patient who presented with a ruptured internal iliac artery aneurysm secondary to a Type II endoleak. To our knowledge this and the following method of managing this have not been previously reported. Established methods of managing endoleaks, such as intravascular transfemoral embolisation and open or laparoscopic ligation, were not possible. Therefore, we resorted to a novel approach to this type of aneurysm and successfully performed a transcutaneous direct puncture and embolisation of the superior gluteal artery. rare, with an incidence rate as low as 0.03% These
Characterization of the Microsomal Cytochrome P450 2B4 O 2 Activation Intermediates by Cryoreduction/EPR.

The oxy-ferrous complex of cytochrome P450 2B4 (2B4) has been prepared at − 40°C with and without bound substrate (butylated hydroxytoluene, BHT), and radiolytically oneelectron cryoreduced at 77K. EPR shows that in both cases the observed product of cryoreduction is the hydroperoxo-ferriheme species, indicating that the microsomal P450 contains an efficient distal-pocket proton-delivery network. In the absence of substrate, two distinct hydroperoxo-ferriheme signals are observed, reflecting the presence of two major conformational substates in the oxy-ferrous precursor. Only one species is observed when BHT, is bound, indicating a more ordered active site. BHT binding also changes the g-tensor components of the hydroperoxo-ferric 2B4 intermediate, indicating that the substrate modulates the properties of this intermediate. Step-annealing the cryoreduced ternary 2B4 complex at 175K and above causes the loss of hydroperoxo-ferric 2B4 and the parallel appearance of high-spin ferri-2B4; LC-MS/MS analysis shows that in this process BHT is quantitatively converted to two products, hydroxymethyl BHT ( 1 ) and 3-hydroxy- t -butyl BHT ( 2 ). This implies that the hydroperoxo-ferric 2B4 prepared by cryoreduction is catalytically active, and that the high-spin state observed after annealing contains an enzymebound product of BHT monooxygenation. The ratio of products generated during cryoreduction/annealing, 1 / 2 ~ 6.2/1, is significantly different from the ratio, 2.5/1, at ambient temperature, and product coupling is significantly greater. This suggests that substrate is held more rigidly relative to the oxidizing species at low temperature, and/or that dissociation of FeOOH is inhibited. As in experiments under ambient conditions, product formation is not observed in the inactive F429H 2B4 mutant. and stepannealing measurements of its reactivity. The catalytic competence of cryogenerated, oneelectron reduced oxy-2B4/BHT complex is established by the determination that products of BHT monooxygenation form quantitatively during the cryoreduction and annealing of the ternary complex with wild-type 2B4, but not with the non-catalytic 2B4(F429H) variant.
Ligand recognition during thymic development and γδ T cell function specification

γδ T cells develop in the thymus before entering the periphery. Recent work suggests that thymic development does little to constrain γδ T cell antigen specificities, but instead determines their effector fate. When triggered through the T cell receptor, ligand-naïve γδ T cells produce IL-17, ligand-experienced cells make IFN- γ and those that are strongly self-reactive make IL-4. Importantly, γδ T cells are able to make cytokines immediately upon TCR engagement. These characteristics allow γδ T cells to initiate an acute inflammatory response to pathogens and to host antigens revealed by injury. These advances warrant a fresh look at how γδ T cells may function in the immune system. the in the thymus the recent studies on thymic ligand recognition and γδ T cell repertoire and function development.