Miracle-dz/UniFAR-FTUs huggingface dataset:
The Potential Mechanism of Bufadienolide-Like Chemicals on Breast Cancer via Bioinformatics Analysis

Bufadienolide-like chemicals are mostly composed of the active ingredient of Chansu and they have anti-inflammatory, tumor-suppressing, and anti-pain activities; however, their mechanism is unclear. This work used bioinformatics analysis to study this mechanism via gene expression profiles of bufadienolide-like chemicals: (1) Differentially expressed gene identification combined with gene set variation analysis, (2) similar small -molecule detection, (3) tissue-specific co-expression network construction, (4) differentially regulated sub-networks related to breast cancer phenome, (5) differentially regulated sub-networks with potential cardiotoxicity, and (6) hub gene selection and their relation to survival probability. The results indicated that bufadienolide-like chemicals usually had the same target as valproic acid and estradiol, etc. They could disturb the pathways in RNA splicing, the apoptotic process, cell migration, extracellular matrix organization, adherens junction organization, synaptic transmission, Wnt signaling, AK-STAT signaling, BMP signaling pathway, and protein folding. We also investigated the potential cardiotoxicity and found a dysregulated subnetwork related to membrane depolarization during action potential, retinoic acid receptor binding, GABA receptor binding, positive regulation of nuclear division, negative regulation of viral genome replication, and negative regulation of the viral life cycle. These may play important roles in the cardiotoxicity of bufadienolide-like chemicals. The results may highlight the potential anticancer mechanism and cardiotoxicity of Chansu, and could also explain the ability of bufadienolide-like chemicals to be used as hormones and anticancer and vasoprotectives agents.
Adenosine Deaminase Two and Immunoglobulin M Accurately Differentiate Adult Sneddon’s Syndrome of Unknown Cause

Background: The association that exists between livedo reticularis (LR) and stroke is known as Sneddon’s syndrome (SnS). The disorder is classified as primary SnS (PSnS), if the cause remains unknown and secondary SnS. The condition is rare and it occurs mainly sporadically. In 2014, 2 independent teams described a new genetic disorder with childhood-onset, which was called deficiency of adenosine deaminase 2 (DADA2), characterized by recurrent fevers and vascular pathologic features that included LR and stroke. All the patients carried recessively inherited mutations in cat eye syndrome chromosome region candidate 1 gene (CECR1), encoding the adenosine deaminase 2 (ADA2) protein. Genetic testing is the standard for the diagnosis of DADA2. However, the diagnostic accuracy of more affordable laboratorial analysis in CECR1-mutated individuals remains to be established. We aim to determine whether plasma ADA2 activity and serum immunoglobulin M (IgM) levels can distinguish (1) DADA2 from other adult patients within the SnS spectrum, and (2) healthy CECR1 heterozygous (HHZ) from healthy controls (HC). Methods: ADA2 activity in plasma and serum IgM concentrations was measured in adult patients within the SnS spectrum, healthy first-degree relatives and HC. Genetic results were used as the reference standard. The primary outcome measures were sensitivity and specificity derived from receiver operating curve analysis. Results: A total of 73 participants were included in the study: 26 patients with PSnS with no CECR1 mutation (PSnS), 6 bi-allelic (DADA2 patients) and 7 HHZ CECR1 mutations and 34 HC. Plasma ADA2 activity and serum IgM levels were significantly lower in DADA2 patients than in PSnS. With the use of the best indexes, plasma ADA2 activity differentiated PSnS from DADA2 with a sensitivity and specificity of 100.0% and HHZ from HC with a sensitivity of 97.1% and specificity of 85.7%. Serum IgM levels also differentiated PSnS from DADA2 with a sensitivity of 85.2% and specificity of 83.3%. Conclusion: Serum IgM levels might be used as a triage tool and plasma ADA2 activity performs perfectly as a diagnostic test for DADA2 in adult patients within the SnS spectrum. ADA2 activity in plasma also reliably distinguishes HHZ from HC.
Millennials and the Future of Magazines: How the Generation of Digital Natives Will Determine Whether Print Magazines Survive

Abstract:Through a mixed-methods study using a survey and focus groups, this exploratory work investigates how Millennials feel about print magazines in the Internet age. Participants reported reading magazines for reasons pertaining to content, aesthetics, entertainment, escape, habit, and ease of use. Findings revealed instrumental themes, reported as recommendations to the magazine industry, as these digital natives will inevitably dictate the fate of print media.
Whole-Genome Association Mapping and Genomic Prediction for Iron Concentration in Wheat Grains

Malnutrition of iron (Fe) affects two billion people worldwide. Therefore, enhancing grain Fe concentration (GFeC) in wheat (Triticum aestivum L.) is an important goal for breeding. Here we study the genetic factors underlying GFeC trait by genome-wide association studies (GWAS) and the prediction abilities using genomic prediction (GP) in a panel of 369 European elite wheat varieties which was genotyped with 15,523 mapped single-nucleotide polymorphism markers (SNP) and a subpanel of 183 genotypes with 44,233 SNP markers. The resulting means of GFeC from three field experiments ranged from 24.42 to 52.42 μg·g−1 with a broad-sense heritability (H2) equaling 0.59 over the years. GWAS revealed 41 and 137 significant SNPs in the whole and subpanel, respectively, including significant marker-trait associations (MTAs) for best linear unbiased estimates (BLUEs) of GFeC on chromosomes 2A, 3B and 5A. Putative candidate genes such as NAC transcription factors and transmembrane proteins were present on chromosome 2A (763,689,738–765,710,113 bp). The GP for a GFeC trait ranged from low to moderate values. The current study reported GWAS of GFeC for the first time in hexaploid wheat varieties. These findings confirm the utility of GWAS and GP to explore the genetic architecture of GFeC for breeding programs aiming at the improvement of wheat grain quality.
Quasi-Monte Carlo Methods in Computer Graphics, Part I: The QMC-Buffer

Monte Carlo integration is often used for antialiasing in rendering processes. Due to low sampling rates only expected error estimates can be stated, and the variance can be high. In this article quasi-Monte Carlo methods are presented, achieving a guaranteed upper error bound and a convergence rate essentially as fast as usual Monte Carlo.
Mission‐oriented translational cancer research – health economics

Health economics is an integrated aspect of all phases of mission‐oriented translational cancer research and should be considered an intrinsic component of any study aimed at improving outcomes for patients and intervention costs. Information about value and value for money of new options for prevention and treatment is needed for decisions about their adoption and use by healthcare systems.
Therapeutic alliance—not therapist competence or group cohesion—contributes to reduction of psychological distress in group‐based mindfulness‐based cognitive therapy for cancer patients

Mindfulness‐based cognitive therapy (MBCT) is an innovative evidence‐based intervention in mental and somatic health care. Gaining knowledge of therapeutic factors associated with treatment outcome can improve MBCT. This study focused on predictors of treatment outcome of MBCT for cancer patients and examined whether group cohesion, therapeutic alliance, and therapist competence predicted reduction of psychological distress after MBCT for cancer patients. Moreover, it was examined whether therapist competence facilitated therapeutic alliance or group cohesion. Multilevel analyses were conducted on a subsample of patients collected in a larger randomized controlled trial on individual internet‐based versus group‐based MBCT versus treatment as usual in distressed cancer patients. The current analyses included the 84 patients who completed group‐based MBCT out of 120 patients who were randomized to group‐based MBCT. Group cohesion and therapist competence did not predict reduction in psychological distress, whereas therapeutic alliance did. In addition, therapist competence did not predict therapeutic alliance but was associated with reduced group cohesion. Our findings revealed that therapeutic alliance significantly contributed to reduction of psychological distress in MBCT for cancer patients. Elaborating the clinical implications of the predictive significance of therapeutic alliance might be of added value to enhance the potential effect of MBCT.
Purification and Glutaraldehyde Activation Study on HCl-Doped PVA–PANI Copolymers with Different Aniline Concentrations

In this work, we report the synthesis and purification of polyvinyl alcohol-polyaniline (PVA⁻PANI) copolymers at different aniline concentrations, and their molecular (¹H-NMR and FTIR), thermal (TGA/DTG/DSC), optical (UV⁻Vis-NIR), and microstructural (XRD and SEM) properties before and after activation with glutaraldehyde (GA) in order to obtain an active membrane. The PVA⁻PANI copolymers were synthesized by chemical oxidation of aniline using ammonium persulfate (APS) in an acidified (HCl) polyvinyl alcohol matrix. The obtained copolymers were purified by dialysis and the precipitation⁻redispersion method in order to eliminate undesired products and compare changes due to purification. PVA⁻PANI products were analyzed as gels, colloidal dispersions, and thin films. ¹H-NMR confirmed the molecular structure of PVA⁻PANI as the proposed skeletal formula, and FTIR of the obtained purified gels showed the characteristic functional groups of PVA gels with PANI nanoparticles. After exposing the material to a GA solution, the presence of the FTIR absorption bands at 1595 cm-1, 1650 cm-1, and 1717 cm-1 confirmed the activation of the material. FTIR and UV⁻Vis-NIR characterization showed an increase of the benzenoid section of PANI with GA exposure, which can be interpreted as a reduction of the polymer with the time of activation and concentration of the solution.
Heterozygous Tbk1 loss has opposing effects in early and late stages of ALS in mice

Heterozygous loss-of-function mutations of TANK-binding kinase 1 (TBK1) cause familial ALS, yet downstream mechanisms of TBK1 mutations remained elusive. TBK1 is a pleiotropic kinase involved in the regulation of selective autophagy and inflammation. We show that heterozygous Tbk1 deletion alone does not lead to signs of motoneuron degeneration or disturbed autophagy in mice during a 200-d observation period. Surprisingly, however, hemizygous deletion of Tbk1 inversely modulates early and late disease phases in mice additionally overexpressing ALS-linked SOD1G93A, which represents a “second hit” that induces both neuroinflammation and proteostatic dysregulation. At the early stage, heterozygous Tbk1 deletion impairs autophagy in motoneurons and prepones both the clinical onset and muscular denervation in SOD1G93A/Tbk1+/− mice. At the late disease stage, however, it significantly alleviates microglial neuroinflammation, decelerates disease progression, and extends survival. Our results indicate a profound effect of TBK1 on brain inflammatory cells under pro-inflammatory conditions and point to a complex, two-edged role of TBK1 in SOD1-linked ALS.
Adherence to Treatment in Stroke Patients

Background: Compliance with medication in patients who have suffered stroke is usually not-optimal. This study aims to measure the level of compliance with the treatment and to identify socio-demographic, clinical, and subjective factors related to the long-term compliance of stroke patients with their treatment. Methods: 140 patients (66.4% males) suffered an ischemic stroke at least six months old, participated in the survey. Compliance was measured using the Medication Adherence Report Scale and the quality of life by the Stroke Specific Quality of Life questionnaire. Furthermore, the Beliefs about Medicines Questionnaire and the Brief Illness Perception Questionnaire on perceptions about the disease were assessed. The doctor–patient relationship was assessed by the Common-Sense Model of Self-Regulation questionnaire and the family support was assessed by the FSS scale. Univariate and multivariate analysis was employed to identify the significant factors affecting compliance in these stroke patients. Results: In 68.6% of patients the compliance was classified as optimal, in 25.7% as partial and as poor in 5.7%; the last two categories were treated as sub-optimal compliance in multivariate analysis. The high compliance was related to patient’s mental state (OR:3.94 95% CI: 1.84–4.46), the perception medication necessity (OR:1.26 95% CI: 1.01–1.56), and the doctor–patient communication (OR:1.76 95% CI: 1.15–2.70). Men showed a lower compliance than women, as well as increased concerns about taking medication (OR: 0.83, 95% CI: 0.69–0.99). Paradoxically, the work /productivity related quality of life was inversely associated with compliance (OR (95% CI): 0.44 (0.23 to 0.82)). Conclusions: The perception of medication necessity and the doctor–patient communication are manageable factors associated with compliance in treating patients who have suffered stroke. In addition, rehabilitation and return to work programs should consider these factors when providing support to those persons.
Multiple pulmonary ground glass opacities: is it time for new guidelines?

The National Lung Screening Trial (NLST) enrolled 53,454 current or former heavy smokers aged 55 to 74 years, and showed a relative reduction in mortality from lung cancer with low-dose computed tomography (CT) screening of 20.0% [95% confidence interval (CI), 6.8 to 26.7; P=0.004] (1).
Bi‐directional modulation of food habit expression by the endocannabinoid system

The compulsive, habitual behaviors that have been observed in individuals diagnosed with substance use disorders may be due to disruptions in the neural circuits that mediate goal‐directed actions. The endocannabinoid system has been shown to play a critical role in habit learning, but the role of this neuromodulatory system in habit expression is unclear. Here, we investigated the role of the endocannabinoid system in established habitual actions using contingency degradation in male C57BL/6 mice. We found that administration of the endocannabinoid transport inhibitor AM404 reduced habitual responding for food and that antagonism of cannabinoid receptor type 1 (CB1), but not transient receptor potential cation subfamily V (TRPV1), receptors produced a similar reduction in habitual responding. Moreover, pharmacological stimulation of CB1 receptors increased habitual responding for food. Co‐administration of an enzyme inhibitor that selectively increases the endocannabinoid 2‐arachidonoyl glycerol (2‐AG) with AM404 partially restored habitual responding for food. Together, these findings demonstrate an important role for the endocannabinoid system in the expression of habits and provide novel insights into potential pharmacological strategies for reducing habitual behaviors in mental disorders.
Revisiting human cerebral blood flow responses to augmented blood pressure oscillations

Cerebral autoregulation is most effective in buffering against pressure fluctuations slower than 0.03 Hz (∼30 s). This suggests that frequency bands for characterizing cerebral autoregulation should be redefined Low cross‐spectral coherence below 0.03 Hz highlights the limitations of transfer function approaches Haemodynamic changes induced by lower body pressure could not fully explain the differences in autoregulation estimated from spontaneous vs. augmented fluctuations, and thus, observations of spontaneous fluctuations should not be relied on whenever possible.
Empagliflozin Reduced Mortality and Hospitalization for Heart Failure Across the Spectrum of Cardiovascular Risk in the EMPA-REG OUTCOME Trial

Background: In the EMPA-REG OUTCOME trial (BI 10773 [Empagliflozin] Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) in patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease, in comparison with placebo, empagliflozin reduced the risks of 3-point major adverse cardiovascular events (3-point MACE), cardiovascular and all-cause death, and hospitalization for heart failure. We investigated whether these effects varied across the spectrum of baseline cardiovascular risk. Methods: Cardiovascular death, all-cause mortality, 3-point MACE, and hospitalization for heart failure in the pooled empagliflozin and placebo groups were analyzed in subgroups by prior myocardial infarction and stroke at baseline, and by estimated baseline cardiovascular risk based on the 10-point TIMI (Thrombolysis In Myocardial Infarction) Risk Score for Secondary Prevention. Results: Of 7020 patients who received the study drug, 65% had a prior myocardial infarction or stroke, and 12%, 40%, 30%, and 18% were at low, intermediate, high, and highest estimated cardiovascular risk according to TIMI Risk Score for Secondary Prevention (⩽2, 3, 4, and ≥5 points, respectively). In the placebo group, 3-point MACE occurred during the trial in 7.3%, 9.4%, 12.6%, and 20.6% of patients at low, intermediate, high, and highest estimated baseline risk, respectively. Relative reductions in risk of cardiovascular death, all-cause mortality, 3-point MACE and hospitalization for heart failure with empagliflozin versus placebo were consistent in patients with and without prior myocardial infarction and/or stroke and across subgroups by TIMI Risk Score for Secondary Prevention at baseline (P>0.05 for randomized group-by-subgroup interactions). Conclusions: Despite all patients having atherosclerotic cardiovascular disease, patients in EMPA-REG OUTCOME demonstrated a broad risk spectrum for cardiovascular events. Reductions in key cardiovascular outcomes and mortality with empagliflozin versus placebo were consistent across the range of cardiovascular risk. Clinical Trial Registration: URL: https://www.clinicaltrials. gov. Unique identifier: NCT01131676.
Novel tretinoin 0.05% lotion for the once‐daily treatment of moderate‐to‐severe acne vulgaris in a preadolescent population

Acne vulgaris (acne) is a common skin condition in children and adolescents. Efficacy of tretinoin is well documented in studies that included pediatric patients (12‐18 years of age). With acne routinely presenting in younger patients, data are needed in this important group. Lotion formulations are commonly used across dermatology and are well liked by patients.
Sharing and valuing older Aboriginal people’s voices about social and emotional wellbeing services: a strength-based approach for service providers

Abstract Objective: Over the last decade, the literature relating to older Aboriginal and Torres Strait Islander people’s preferences for social and emotional wellbeing services has grown. However, little evidence exists in relation to older Aboriginal and Torres Strait Islander people’s experiences of services relating to social and emotional wellbeing. This paper highlights older Aboriginal and Torres Strait Islander people’s experiences of social and emotional wellbeing services in Australia and then uses these key findings of the research, along with the literature, to develop a strength-based approach for service providers. Methods: Yarning was the preferred research method for the older Aboriginal community. In total, 16 older Aboriginal people, including eight women and eight men participated in the research yarning sessions. A modified version of an existing thematic analysis process supported yarning members to participate in each stage of the research, including data analysis. Results: The themes emerging from the voices of the yarning members are they couldn’t give a damn about them, You’ve got to get the right one and ticking the box. The themes focus on negative, positive and preferred experiences of social and emotional wellbeing service provision. Conclusion: The key findings and related literature contribute to the development of a strength-based approach, which supports the implementation of responsive and effective services that address Elders, older peoples and their communities’ social and emotional wellbeing issues and aspirations.
Mortality Due to Cystic Fibrosis over a 36-Year Period in Spain: Time Trends and Geographic Variations

The aim of this study is to analyze population-based mortality attributed to cystic fibrosis (CF) over 36 years in Spain. CF deaths were obtained from the National Statistics Institute, using codes 277.0 from the International Classification of Diseases (ICD) ninth revision (ICD9-CM) and E84 from the tenth revision (ICD10) to determine the underlying cause of death. We calculated age-specific and age-adjusted mortality rates, and time trends were assessed using joinpoint regression. The geographic analysis by district was performed by standardized mortality ratios (SMRs) and smoothed-SMRs. A total of 1002 deaths due to CF were identified (50.5% women). Age-adjusted mortality rates fell by −0.95% per year between 1981 and 2016. The average age of death from CF increased due to the annual fall in the mortality of under-25s (−3.77% males, −2.37% females) and an increase in over-75s (3.49%). We identified districts with higher than expected death risks in the south (Andalusia), the Mediterranean coast (Murcia, Valencia, Catalonia), the West (Extremadura), and the Canary Islands. In conclusion, in this study we monitored the population-based mortality attributed to CF over a long period and found geographic differences in the risk of dying from this disease. These findings complement the information provided in other studies and registries and will be useful for health planning.
Comparative Behavioral Phenotypes of Fmr1 KO, Fxr2 Het, and Fmr1 KO/Fxr2 Het Mice

Fragile X syndrome (FXS) is caused by silencing of the FMR1 gene leading to loss of the protein product fragile X mental retardation protein (FMRP). FXS is the most common monogenic cause of intellectual disability. There are two known mammalian paralogs of FMRP, FXR1P, and FXR2P. The functions of FXR1P and FXR2P and their possible roles in producing or modulating the phenotype observed in FXS are yet to be identified. Previous studies have revealed that mice lacking Fxr2 display similar behavioral abnormalities as Fmr1 knockout (KO) mice. In this study, we expand upon the behavioral phenotypes of Fmr1 KO and Fxr2+/− (Het) mice and compare them with Fmr1 KO/Fxr2 Het mice. We find that Fmr1 KO and Fmr1 KO/Fxr2 Het mice are similarly hyperactive compared to WT and Fxr2 Het mice. Fmr1 KO/Fxr2 Het mice have more severe learning and memory impairments than Fmr1 KO mice. Fmr1 KO mice display significantly impaired social behaviors compared to WT mice, which are paradoxically reversed in Fmr1 KO/Fxr2 Het mice. These results highlight the important functional consequences of loss or reduction of FMRP and FXR2P.
Measuring and Predicting Individual Differences in Executive Functions at 14 Months: A Longitudinal Study

This study of 195 (108 boys) children seen twice during infancy (Time 1: 4.12 months; Time 2: 14.42 months) aimed to investigate the associations between and infant predictors of executive function (EF) at 14 months. Infants showed high levels of compliance with the EF tasks at 14 months. There was little evidence of cohesion among EF tasks but simple response inhibition was related to performance on two other EF tasks. Infant attention (but not parent‐rated temperament) at 4 months predicted performance on two of the four EF tasks at 14 months. Results suggest that EF skills build on simpler component skills such as attention and response inhibition.