Miracle-dz/UniFAR-FTUs huggingface dataset:
Re‐evaluation of the “law of constant extinction” for ruminants at different taxonomical scales

The “law of constant extinction,” proposed by Van Valen, states that long and short‐lived taxa have equal chances of going extinct. This pattern of age‐independent extinction was originally inferred using the fossil record of several different taxa and relied on survivorship curves built from the literal reading of the fossil record. Van Valen's seminal work was mostly done at higher taxonomic levels, hence its prevalence at the species level could not be directly inferred. The surprisingly few subsequent studies done at the species level have challenged the prevalence of age‐independent extinction, but those have, for the most part, failed to explicitly incorporate inherent biases of the fossil record. Using a recent Bayesian framework that accounts for several of those biases, including the fact that very short‐living lineages might never make to the record itself, we showed that Ruminantia species present age‐dependent extinction, where extinction probability decreases with species age. An analysis at the genus level suggested age‐independent extinction but further examination suggested that the pattern might be more complex than previously reported by Van Valen. Our results indicate that different taxonomic levels may present different extinction regimes, which could justify the development of new macroevolutionary theory and methods.
Microbial Oxidation of the Isoprenoid Alkane Pristane

Microorganisms capable of utilizing pristane (2,6,10,14-tetramethylpentadecane) as a sole source of carbon and energy were isolated from soil specimens. A strain BPM 1613, tentatively classified in the genus Nocardia, accumulated several oxidation products of pristane in the culture fluid. Silica gel chromatography of the ethyl ether extract from the culture fluid yielded pristanol and pristanic acid as major products and pristyl pristanate and pristyl aldehyde as minor products. The confirmations on the estimated structures of these oxidation products are described in detail.
Intestinal ulcers induced by intravesical bacillus Calmette-Guérin therapy

Abstract Intravesical bacillus Calmette-Guérin (iBCG) therapy, one of the established treatments for bladder carcinoma, is known for its association with adverse events, including rheumatic manifestations. We describe the case of a 72-year-old man with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome who developed inflammatory bowel disease unclassified after iBCG therapy for bladder carcinoma. The critical role of the IL-23/IL-17 axis in the pathogenesis IBD and all the domains of SAPHO syndrome has been reported previously. In the present case, the activation of the IL-23/IL-17 axis, probably due to the disease, could have been exacerbated by iBCG therapy, as observed in mice that received BCG immunotherapy. We suggest that patients with rheumatic diseases on iBCG therapy should be observed carefully since iBCG could be a contributing factor for autoimmune pathology including IBD.
Cognitive reserve and brain maintenance in aging and dementia: An integrative review

Abstract This research is an integrative review of scientific evidence differentiating between cognitive reserve (CR) and brain maintenance concepts. Thus, we have examined how CR socio-behavioral proxies (i.e. education, occupational attainment, and leisure activities) may help to cope with age-related cognitive decline and negative consequences of brain pathology. We also analyze lifestyle factors associated with brain maintenance or the relative absence of change in neural resources over time. Medline and Web of Science databases were used for the bibliographic search in the last 20 years. Observational cohort studies were selected to analyze the effect of different CR proxies on cognitive decline, including dementia incidence, whereas studies employing functional neuroimaging (fMRI) were used to display the existence of compensation mechanisms. Besides, structural MRI studies were used to test the association between lifestyle factors and neural changes. Our findings suggest that education, leisure activities, and occupational activity are protective factors against cognitive decline and dementia. Moreover, functional neuroimaging studies have verified the existence of brain networks that may underlie CR. Therefore, CR may be expressed either through a more efficient utilization (neural reserve) of brain networks or the recruitment of additional brain regions (compensation). Finally, lifestyle factors such as abstaining from smoking, lower alcohol consumption, and physical activity contributed to brain maintenance and were associated with the preservation of cognitive function. Advances in multimodal neuroimaging studies, preferably longitudinal design, will allow a better understanding of the neural mechanisms associated with the prevention of cognitive decline and preservation of neural resources in aging.
Behavioral Parent Training for Preschool ADHD: Family-Centered Profiles Predict Changes in Parenting and Child Outcomes

ABSTRACT Objective Behavioral parent training (BPT) is the first line of treatment for preschool-aged children with attention-deficit hyperactivity disorder (ADHD); however, clinically significant improvements are not universal. In the current study, we employ a person-centered approach to create subgroups of families based on the intersection of multiple parent, child, and family pre-treatment factors. Further, we explore the utility of pre-treatment family profiles in predicting post-treatment differences in observed parenting behavior (i.e., behavioral control, parental warmth) and clinically significant change in child ADHD and oppositional symptoms. Method Longitudinal data were collected using observational and parent-, teacher- and clinician-reported assessments from 130 parent-child dyads (M age= 3.57, range = 3.0– 4.11, 73.8% male, 69.2% White, 25.6% Hispanic) participating in BPT. Results Findings from the current study suggest three distinct family profiles, which consisted of one profile with high family stress (HFS) as evidenced by elevated symptomatology across parent, child, and family-level domains, a second profile with elevated parental anxiety (PA), and a final profile with elevated parental depression (PD). These family-centered profiles were differentially associated with changes in observed parenting practices. Specifically, the PD profile (39%) demonstrated minimal improvements in behavioral control and warmth following treatment. In contrast, the HFS profile (30%) only improved in behavioral control and the PA profile (31%) improved in both parenting domains following treatment. In addition, marginally significant differences in child oppositional and ADHD symptoms were observed across profiles. Conclusions Family-centered approaches may be useful for selecting and implementing interventions.
Nutritional, anti-nutritional, antioxidant, physicochemical and functional characterization of Australian Acacia seed: Effect of species and regions.

BACKGROUND Acacia seed (AS) is an underutilized legume widely distributed in the world with majority of the species (>70%) found in Australia. Generally, the seeds are rich in protein, dietary fibre and potassium but also possess anti-nutritional compounds. In recent years, there have been an increase in the cultivation of some Australian acacia species such as A. victoriae, A. cowleana and A. coriacea from different regions. However, there is limited information on the composition, anti-nutrients, antioxidant and functional properties of flour from these widely grown Australian AS species. Thus, the aim of our study was to assess the properties of these Australian AS species from different geographical regions. RESULTS The A. cowleana and A. coriacea were characterized by high protein, fat, potassium and soluble carbohydrate. However, higher starch and fibre contents were present in A. victoriae. Greater amounts of anti-nutrients, total phenolics and flavonoids were found in A. cowleana and A. coriacea seeds while A. victoriae had higher DPPH radical-scavenging capacity. A. victoriae and A. coriacea demonstrated the highest water absorption and solubility index, respectively. However, A. cowleana showed the highest oil absorption index. There was less variation in the composition and properties within species from different regions. CONCLUSION All samples showed promising nutritional characteristics, but with sufficient diversity to indicate that Australian acacia seeds can be utilized to develop a range of new (functional) food products. Overall, information by this study would help the food industries in the selection of AS species for food application. This article is protected by copyright. All rights reserved.
An Evaluation of Glucagon Injection Anxiety and Its Association with the Fear of Hypoglycemia among the Parents of Children with Type 1 Diabetes

Objective: Hypoglycemia is a common acute complication of type 1 diabetes (T1D), which may cause seizure, loss of consciousness, and temporary motor or sensory impairment. Glucagon administration is an effective way of treating severe hypoglycemia, especially in a free-living setting. Nonetheless, families have difficulties in managing severe hypoglycemia due to their anxiety and challenges with current glucagon administration techniques. The aim of the current study was to explore the associations between parental fear of hypoglycemia (FoH) and their general anxiety level, and in particular, their attitudes towards and thoughts on glucagon administration. Methods: Parents of children with T1D completed questionnaires assessing background and clinical information, FoH, generalized anxiety disorder (GAD) and parental anxiety for glucagon administration (PAGA). Results: Sixty-eight parents participated. Positive correlations were found between parental GAD-7 score and both FoH and the number of night-time blood glucose measurements and there was a negative correlation with the child’s age. Parents mean self-evaluation score of their competence in glucagon administration was 6 (standard deviation±2.9) on a scale of 0 to 10. Unsurprisingly, this score was negatively correlated with the PAGA scores. There was no significant difference between children using continuous glucose monitoring system and self-monitoring of blood glucose in terms of parental FoH, anxiety and misconceptions about glucagon administration. Conclusion: The results showed that parents of children with T1D had anxiety and fear connected with hypoglycemia and glucagon administration. Structured and practical training should be implemented to increase parents’ self-confidence including annual refresher training for home glucagon administration.
It’s more than just interoception: The insular cortex involvement in alcohol use disorder

Understanding brain structures and circuits impacted by alcohol use disorder is critical for improving our future prevention techniques and treatment options. A brain region that has recently gained traction for its involvement in substance use disorder is the insular cortex. This brain region is multi‐functional and spatially complex, resulting in a relative lack of understanding of the involvement of the insular cortex in alcohol use disorder. Here we discuss the role of the insular cortex in alcohol use disorder, particularly during periods of abstinence and in response to alcohol and alcohol‐related cues and contexts. We also discuss a broader role of the insular in alcohol‐associated risky decision making and impulse control. Finally, we canvas potential challenges associated with targeting the insular cortex to treat individuals with alcohol use disorder.
Assessment of a Pharmacist-Led Direct Oral Anticoagulant Monitoring Clinic.

Background Direct oral anticoagulants (DOACs) are recommended as first-line therapy for treatment and prevention of venous thromboembolism (VTE) and prevention of stroke related to nonvalvular atrial fibrillation. Recent publications have suggested incorporating DOAC monitoring into anticoagulant management clinics. The Eastern Health Adult Outpatient Thrombosis Service (Newfoundland and Labrador) includes a pharmacist-led DOAC monitoring clinic that uses standardized evidence-based care processes. Objectives To describe a new pharmacist-led DOAC monitoring clinic and to assess patients' adherence to medication therapy, adherence to guideline-recommended frequencies for blood work, and adverse and non-adverse events. Methods This retrospective chart review involved patients who attended their first visit to the DOAC clinic between October 10, 2017, and May 31, 2018. Patients were followed until November 30, 2018. Data were abstracted from electronic hospital records and the provincial pharmacy network. Descriptive statistics were used to analyze the data: categorical variables were presented as frequencies and percentages; continuous variables were analyzed and presented as means with standard deviations and, where applicable, as medians with interquartile ranges. Results Forty-seven patients, who attended a total of 74 clinic visits, were included. Twenty-eight patients (60%) were adherent to their DOAC therapy. All patients had blood work completed before each clinic appointment. The mean time between the first and second sets of blood tests was 6.2 (standard deviation [SD] 1.4) months and between the second and third sets of blood tests was 5.1 (SD 1.0) months. There were no episodes of VTE or major bleeding. There was 1 cerebrovascular accident (3.2 events per 100 person-years, 95% confidence interval [CI] 0.2-15.7) and 5 episodes of clinically relevant non-major bleeding (12.8 events per 100 person-years, 95% CI 4.1-30.1). Pharmacists identified 51 issues at the clinic appointments, of which 48 were medication-related. Referral to the Thrombosis Service physician was required to resolve 8 (16%) of the issues identified. A brief discussion between the Thrombosis Service physician and pharmacist was required to resolve 30 (59%) of the issues, with 13 (25%) resolved by the pharmacist alone. Conclusions This study described the implementation and outcomes of a novel pharmacist-led DOAC clinic. Clinic patients underwent blood work at recommended intervals and received guidance on adherence and adverse events; as such, patients had follow-up that aligned with guideline recommendations.
In silico screening and molecular dynamics simulation of deleterious PAH mutations responsible for phenylketonuria genetic disorder

Phenylketonuria (PKU) is a genetic disorder that if left untreated can lead to behavioral problems, epilepsy, and even mental retardation. PKU results from mutations within the phenylalanine‐4‐hydroxylase (PAH) gene that encodes for the PAH protein. The study of all PAH causing mutations is improbable using experimental techniques. In this study, a collection of in silico resources, sorting intolerant from tolerant, Polyphen‐2, PhD‐SNP, and MutPred were used to identify possible pathogenetic and deleterious PAH non‐synonymous single nucleotide polymorphisms (nsSNPs). We identified two variants of PAH, I65N and L311P, to be the most deleterious and disease causing nsSNPs. Molecular dynamics (MD) simulations were carried out to characterize these point mutations on the atomic level. MD simulations revealed increased flexibility and a decrease in the hydrogen bond network for both mutants compared to the native protein. Free energy calculations using the MM/GBSA approach found that BH4, a drug‐based therapy for PKU patients, had a higher binding affinity for I65N and L311P mutants compared to the wildtype protein. We also identify important residues in the BH4 binding pocket that may be of interest for the rational drug design of other PAH drug‐based therapies. Lastly, free energy calculations also determined that the I65N mutation may impair the dimerization of the N‐terminal regulatory domain of PAH.
The response of adipose tissues to Mycoplasma pulmonis and Sendai virus infection in C57BL/6 and DBA/2 mice

Adipose tissues in mammals are categorized into white and brown adipose tissues in which cellular morphology, cell functions, and tissue distribution are different. White adipose tissue (WAT) plays a major role in energy reservation, while brown adipose tissue (BAT) mainly relates to the thermoregulation of the body. One interesting function of adipose tissue is the response to the infection, especially the pathogens that cause pneumonia. We have previously reported that DBA/2 (D2) mice are susceptible to pathogens causing pneumonia, Mycoplasma (M.) pulmonis and Sendai virus (SeV), whereas C57BL/6 (B6) mice are resistant to them. Furthermore, morphological alteration of mediastinal fat tissue (MFT) was seen after infection of M. pulmonis in D2 mice but not in B6 mice. In this study, we aimed to exhibit the difference in adipose tissue response in other areas, including interscapular brown adipose tissue (iBAT), inguinal white adipose tissue (ingWAT), and perigonadal WAT (perigoWAT) between resistant strain, B6 and susceptible strain, D2 after challenging them with M. pulmonis and SeV. Compared with B6 mice, D2 mice showed an increase in fat-associated lymphoid cluster in MFT, an increase in BAT in both iBAT and ingWAT after M. pulmonis and SeV infection. The results of this study indicate that pneumonia caused by M. pulmonis and SeV infection induces browning of adipocyte, suggesting that BAT plays a role in pathogen infection and inflammation.
EVALUATION OF MEDHOVIKAS, A HERBAL FORMULATION FOR ANTIDEPRESSANT ACTIVITY

Objective: The present study was conducted to evaluate the antidepressant activity of Medhovikas and its activity is compared with that of Imipramine and Mentat. The MAO-A and MAO-B levels were estimated by the Biochemical Method. Methods: There are several methods available to evaluate the antidepressant activity. In the present study the antidepressant activity is assessed using behavioural despair method such as Forced swim test (FST) in mice. Imipramine is used as a positive control in doses of 10mg/kg and 20mg/kg, Similar activity was also observed with Medhovikas in doses of 200 and 400mg/kg. Biochemical method in rats to estimate the levels of MAO-A and MAO-B, the biogenic amine 5-HT is oxidized by MAO to 5-hydrixy indole acetic acid (5-HIAA) as a major metabolite and is excreted in urine. Hence the reduction in the urinary 5-HIAA level from normal after treatment with the test compound was taken as a measure of it’s MAO inhibitory action. Results : The antidepressant activity of 200 and 400mg/kg of Medhovikas was equivalent to that of 10 and 20mg/kg of imipramine respectively. It significantly reduced the duration of immobility indicating antidepressant activity. Significant decrease in brain MAO-A and MAO-B levels were observed which was determined by the Biochemical method. Conclusion: Antidepressant activity was probably shown by inhibiting MAO-A and MAO-B, There are several methods to detect the monoamine oxidaise inhibitor activity of substances. These methods are based on biochemical estimation of biogenic amines and /or their pharmacological responses. This shows that Medhovikas is a potential antidepressant and the probable mechanism of action is in interest for further investigation. Keywords: Antidepressant, Forced swim test, Imipramine,MAO-A & B, Medhovika and Mentat
Supervised mutational signatures for obesity and other tissue-specific etiological factors in cancer

Determining the etiologic basis of the mutations that are responsible for cancer is one of the fundamental challenges in modern cancer research. Different mutational processes induce different types of DNA mutations, providing ‘mutational signatures’ that have led to key insights into cancer etiology. The most widely used signatures for assessing genomic data are based on unsupervised patterns that are then retrospectively correlated with certain features of cancer. We show here that supervised machine-learning techniques can identify signatures, called SuperSigs, that are more predictive than those currently available. Surprisingly, we found that aging yields different SuperSigs in different tissues, and the same is true for environmental exposures. We were able to discover SuperSigs associated with obesity, the most important lifestyle factor contributing to cancer in Western populations.
Density functional theory study of the vertical ionization energies of the valence and core electrons of cyclopentadiene, pyrrole, furan, and thiophene

The procedure abbreviated as ΔPBE0(SAOP)/et-pVQZ, based on density functional theory, was developed recently for the calculation of vertical ionization energies of the valence electrons of organic and other small molecules and succeeded in giving results with an average absolute deviation of 0.21 eV from experiment for a collection of 115 reliable test cases of nonperhalo molecules. The objective of this work is to add a number of test cases to the benchmark database. We chose the set of molecules cyclo-C4H4X, with X = CH2, NH, O, and S, previously studied by many workers both experimentally and theoretically. The results show that the ΔPBE0(SAOP)/et-pVQZ procedure is not only as good as ab initio methods such as SAC-CI, OVGF, and ADC(3) in performance, but also handles inner valence ionized cations more efficiently. Although the core-electron binding energies of the titled molecules have not been as well investigated theoretically, we apply the methods we developed in recent years to calculate the bindin.
Pharmaceutical Nanotechnology Encapsulation of amphotericin B in poly(ethylene glycol)-block-poly(-caprolactone-co-trimethylenecarbonate) polymeric micelles

The aim of this work was to evaluate the potential of self-assembling poly(ethyleneglycol) 750-block-poly(-caprolactone-co-trimethylenecarbonate)4500 50/50 copolymers (PEG-p(CL-co-TMC)) to solubilize amphotericin B in polymeric micelles and to disaggregate the drug to the less toxic monomeric form. Amphotericin B was encapsulated in the micelles upon dilution of a mixture of the liquid polymer and the drug in water. Its solubility was increased by two orders of magnitude depending on polymer concentration. The aggregation state of amphotericin B was decreased by PEG-p(CL-co-TMC). The preparation method and the loading of the polymeric micelles influenced it. The antifungal activity of the drug was reduced by encapsulation in the polymeric micelles whereas the onset of amphotericin B-induced hemolysis was delayed. PEG-p(CL-co-TMC) micelles could be an easy method for amphotericin B encapsulation. © 2005 Published by Elsevier B.V.