Miracle-dz/UniFAR-FTUs huggingface dataset:
Flower colour and cytochromes P450†

Cytochromes P450 play important roles in biosynthesis of flavonoids and their coloured class of compounds, anthocyanins, both of which are major floral pigments. The number of hydroxyl groups on the B-ring of anthocyanidins (the chromophores and precursors of anthocyanins) impact the anthocyanin colour, the more the bluer. The hydroxylation pattern is determined by two cytochromes P450, flavonoid 3′-hydroxylase (F3′H) and flavonoid 3′,5′-hydroxylase (F3′5′H) and thus they play a crucial role in the determination of flower colour. F3′H and F3′5′H mostly belong to CYP75B and CYP75A, respectively, except for the F3′5′Hs in Compositae that were derived from gene duplication of CYP75B and neofunctionalization. Roses and carnations lack blue/violet flower colours owing to the deficiency of F3′5′H and therefore lack the B-ring-trihydroxylated anthocyanins based upon delphinidin. Successful redirection of the anthocyanin biosynthesis pathway to delphinidin was achieved by expressing F3′5′H coding regions resulting in carnations and roses with novel blue hues that have been commercialized. Suppression of F3′5′H and F3′H in delphinidin-producing plants reduced the number of hydroxyl groups on the anthocyanidin B-ring resulting in the production of monohydroxylated anthocyanins based on pelargonidin with a shift in flower colour to orange/red. Pelargonidin biosynthesis is enhanced by additional expression of a dihydroflavonol 4-reductase that can use the monohydroxylated dihydrokaempferol (the pelargonidin precursor). Flavone synthase II (FNSII)-catalysing flavone biosynthesis from flavanones is also a P450 (CYP93B) and contributes to flower colour, because flavones act as co-pigments to anthocyanins and can cause blueing and darkening of colour. However, transgenic plants expression of a FNSII gene yielded paler flowers owing to a reduction of anthocyanins because flavanones are precursors of anthocyanins and flavones.
Pemetrexed-induced severe rhabdomyolysis in lung cancer: A case report

Pemetrexed is an antifolate metabolite used to treat non-small cell lung cancer in the adjuvant and advanced setting. It is commonly known to cause rash, diarrhea, fatigue, mucositis, and myelosuppression. We report a case of a patient receiving adjuvant cisplatin and pemetrexed for non-small cell lung adenocarcinoma and experienced severe rhabdomyolysis.
The effect of probiotic yoghurt consumption on oxidative stress and inflammatory factors in young females after exhaustive exercise.

OBJECTIVE To evaluate the effect of probiotic yoghurt consumption on oxidative stress and inflammatory factors in young females after exhaustive exercise. METHODS TThis study included 27 healthy participants with an age range of 18-25. For two weeks, 450 grams of probiotic yoghurt and 450 grams of ordinary yoghurt were given to the supplement and control groups, respectively. Fasting blood samples were taken at baseline and at the end of study. At the end of the intervention, the participants were given one exhaustive exercise and then fasting blood samples were taken to test for blood antioxidant enzymes, inflammatory markers, and oxidative markers. Data were analyzed using descriptive statistics as well as paired and independent samples t-test. RESULTS In supplement group, the glutathione peroxidise (GPX) blood levels and serum levels of total antioxidant capacity (TAC) significantly increased at the end of two weeks of intervention (p<0.05). After intense physical activity, the blood levels of superoxide dismutase (SOD), GPX and serum levels of TAC significantly increased, whereas the serum level of tumour necrosis factor alpha (TNF-? ), matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9), and malondialdehyde (MDA) significantly decreased in the supplement group compared to the control group (p<0.05). Besides, there were no significant changes in other biochemical factors. CONCLUSIONS Regular probiotic yoghurt consumption significantly modulated MMP2, MMP9 and some inflammatory factors, and thus guarded against exhaustive exercise-inducing oxidative injury in young healthy females.
Configuration and Change Maturity Optimization - The Case of Complex Engineering Environments

In the current global competitive market, where businesses thrive to reach higher market share by providing sophisticated yet customer-oriented solutions, management and protection of product information along different stages of its lifecycle (from collection of customer requirements to prototyping and launch), is of significant importance. The discipline that provides assurance for product information management is Configuration Management and depending on the scope and complexity of the application environment, requires several activities and measures to be implemented in a proper manner. This thesis aims at providing an optimization framework for industries to evaluate their level of competence in this discipline and move towards empowering their processes and consequently gain a competitive advantage among their competitors. This goal was achieved by first identifying the critical success factors of Configuration Management and developing a maturity assessment model that evaluates the baseline maturity of organizations with respect to their configuration management efforts and provides a roadmap for further improvements in them. The developed maturity model was then validated through a cross industry assessment and the results laid the foundation for identifying the current state of maturity in several industries, possibilities for enhancing the usability of the maturity model for evaluation purposes as well as the potential research opportunities for solutions that provide enhancements in process capabilities of the discipline. The primary potential for further development of the model was identified as the lack of quantitative key performance indicators and it was addressed by identification of relevant KPIs that enable quantitative measurement of organizations’ maturity. At the same time, an opportunity was identified for conceptualization of a Decision Support System for the Engineering Change Management process that can utilize historical knowledge of past configuration changes to assist decision makers in their change impact analysis by incorporating several variables.
Changes to mineral levels in the yolk of meat chicken embryos during incubation

ABSTRACT A total of 864 settable Cobb 500 eggs were used to explore changes in yolk mineral content during incubation. Eggs were individually weighed and then placed in a commercial incubator. On embryonic day (ED) 0, 6.5, 13.5, and 17.5, 36 eggs were sampled and yolk weight and mineral content were determined. The concentration of iron (Fe), phosphorus (P), and zinc (Zn) declined (P < 0.05) from ED0 to ED17.5. The concentration of calcium (Ca), magnesium (Mg), and strontium (Sr) increased (P < 0.05) from ED0 to ED17.5. The concentration of copper (Cu), potassium (K), and sodium (Na) increased initially (ED0 to ED6.5) but declined thereafter. There was no change (P > 0.05) in the concentration of yolk manganese (Mn) from ED0 to ED17.5. Substantial changes in yolk mineral concentration occur during incubation and are presumably associated with mobilization of shell reserves and flux between albumen and yolk. These data may be useful in designing in ovo interventions, optimizing meat chicken breeder premix formulation or assembly of suitable neonatal or pre‐starter diets for meat chicken chicks.
Methyl-mercury induces apoptosis through ROS-mediated endoplasmic reticulum stress and mitochondrial apoptosis pathways activation in rat cortical neurons

Abstract Methyl-mercury (MeHg) is a dangerous environmental contamination biotransformed from mercury or inorganic mercury compounds in waterways, which induces severe toxic effects in central nervous system. Oxidative stress is involved in various ways of intracellular physiological or pathological processes including neuronal apoptosis. For understanding the ways that oxidative stress participating in MeHg-induced apoptosis, the current study attempted to explore the effects of oxidative stress on endoplasmic reticulum (ER) and mitochondria function, especially focussing on ER stress followed by unfold protein response (UPR), as well as mitochondrial apoptosis pathways activation in primary cultured cortical neurons. Cells were exposed to 0, 0.25, 0.5, or 1 µM MeHg for 1–6 h, respectively, followed by cell viability quantification. For further experiments, 100 µM of 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (trolox) pre-treatment for 3 h followed by 1 µM MeHg for 6 h were performed for evaluation of oxidative stress, neuronal apoptosis, ER stress, UPR activation, and mitochondrial dysfunction. Results showed that MeHg induced neuronal oxidative stress, apoptosis, up-regulating glucose-regulated protein (GRP78, GRP94), spliced Xbp1, activating transcription factor 4 (ATF4) mRNA, with activation of UPR including PKR-like ER kinase-eIF2α, inositol-requiring enzyme 1, and ATF6 pathways, as well as C/EBP homologous transcription factor protein and cleaved caspase-12 up-regulation. In addition, mitochondrial function was disrupted by MeHg, which was supported by caspase-3 and caspase-9 activation, and high levels of cytoplasm cytochrome C and apoptosis induce factor. Trolox pre-treatment significantly blocked neuronal apoptosis, ER stress, UPR activation, as well as mitochondrial dysfunction, in addition to the direct anti-oxidation. In conclusion, MeHg induces neuronal apoptosis through ER and mitochondria pathway, oxidative stress plays important roles in mediating apoptosis pathways activation.
Strategies to decrease social jetlag: Reducing evening blue light advances sleep and melatonin

The timing of sleep is under the control of the circadian clock, which uses light to entrain to the external light‐dark cycle. A combination of genetic, physiological and environmental factors produces individual differences in chronotype (entrained phase as manifest in sleep timing). A mismatch between circadian and societal (e.g., work) clocks leads to a condition called social jetlag, which is characterized by changing sleep times over work and free days and accumulation of sleep debt. Social jetlag, which is prevalent in late chronotypes, has been related to several health issues. One way to reduce social jetlag would be to advance the circadian clock via modifications of the light environment. We thus performed two intervention field studies to describe methods for decreasing social jetlag. One study decreased evening light exposure (via blue‐light‐blocking glasses) and the other used increased morning light (via the use of curtains). We measured behaviour as well as melatonin; the latter in order to validate that behaviour was consistent with this neuroendocrinological phase marker of the circadian clock. We found that a decrease in evening blue light exposure led to an advance in melatonin and sleep onset on workdays. Increased morning light exposure advanced neither melatonin secretion nor sleep timing. Neither protocol led to a significant change in social jetlag. Despite this, our findings show that controlling light exposure at home can be effective in advancing melatonin secretion and sleep, thereby helping late chronotypes to better cope with early social schedules.
The Intergenerational Effects of Intimate Partner Violence in Pregnancy: Mediating Pathways and Implications for Prevention

Prenatal intimate partner violence (P-IPV) can have significant adverse impacts on both mother and fetus. Existing P-IPV interventions focus on the safety of the mother and on reducing revictimization; yet expanding these to address the adverse impact on the fetus has considerable potential for preventing long-term negative developmental outcomes. In this review, we draw together evidence on major pathways linking exposure to P-IPV and child outcomes, arguing that these pathways represent potential targets to improve P-IPV intervention efforts. Using a narrative review of 112 articles, we discuss candidate pathways linking P-IPV to child outcomes, as well as their implications for intervention. Articles were identified via key word searches of social science and medical databases and by inspection of reference lists of the most relevant articles, including recent reviews and meta-analyses. Articles were included if they addressed issues relevant to understanding the effects of P-IPV on child outcomes via six core pathways: maternal stress and mental illness, maternal–fetal attachment, maternal substance use, maternal nutritional intake, maternal antenatal health-care utilization, and infection. We also included articles relevant for linking these pathways to P-IPV interventions. We conclude that developing comprehensive P-IPV interventions that target immediate risk to the mother as well as long-term child outcomes via the candidate mediating pathways identified have significant potential to help reduce the global burden of P-IPV.
Vitamin E Improves Transplant‐Free Survival and Hepatic Decompensation Among Patients With Nonalcoholic Steatohepatitis and Advanced Fibrosis

Vitamin E improves liver histology in adults with nonalcoholic steatohepatitis (NASH) but not diabetes, but its impact on long‐term patient outcomes is unknown. We evaluated whether vitamin E treatment improves clinical outcomes of NASH patients with bridging fibrosis or cirrhosis. Two hundred and thirty‐six patients with biopsy‐proven NASH and bridging fibrosis or cirrhosis seen at Indiana University Medical Center between October 2004 and January 2016 were included. Ninety of them took 800 international units/day of vitamin E for ≥2 years (vitamin E users) and were propensity‐matched to 90 adults who did not take vitamin E (controls) after adjusting for fibrosis severity, age, gender, body mass index, comorbidities and their treatment, low‐density lipoprotein cholesterol, liver biochemistries, and length of follow‐up on vitamin E. Covariate‐adjusted Cox and competing risk regression models were assessed to evaluate the association between vitamin E treatment and patient outcomes. The median follow‐up was 5.62 (interquartile range [IQR], 4.3‐7.5) and 5.6 (IQR, 4‐6.9) years for vitamin E users and controls, respectively. Vitamin E users had higher adjusted transplant‐free survival (78% versus 49%, P < 0.01) and lower rates of hepatic decompensation (37% versus 62%, P = 0.04) than controls. After controlling for severity of fibrosis, calendar year of patient enrollment, and other potential confounders, vitamin E treatment decreased the risk of death or transplant (adjusted hazard ratio, 0.30; 95% confidence interval [CI], 0.12‐0.74; P < 0.01) and hepatic decompensation (adjusted sub‐HR, 0.52; 95% CI, 0.28‐0.96; P = 0.036). These benefits were evident in both those with diabetes and those without diabetes. Adjusted 10‐year cumulative probabilities of hepatocellular carcinoma, vascular events, and nonhepatic cancers were not different between vitamin E–exposed patients and controls. Conclusion: Vitamin E use was associated with improved clinical outcomes in patients with NASH and bridging fibrosis or cirrhosis.
Drug-eluting or bare-metal stents in large coronary arteries.

To the Editor: In their article on the use of oral rivaroxaban for the treatment of acute deep-vein thrombosis (DVT), the EINSTEIN investigators (Dec. 23 issue)1 report that rivaroxaban had noninferior efficacy, as compared with subcutaneous enoxaparin followed by a vitamin K antagonist. In a separate double-blind, randomized superiority study comparing extended rivaroxaban therapy with placebo, rivaroxaban was claimed to be superior. However, the net clinical benefit was not predefined as a separate secondary end point in the protocol and at ClinicalTrials.gov. The combination of major and clinically relevant nonmajor bleeding was defined as the principal safety outcome. Although the post hoc definition of net clinical benefit is questionable, it is nevertheless clinically relevant. The greatest threats of DVT and its treatment are pulmonary embolism and major bleeding, whereas recurrent DVT and clinically relevant bleeding are primarily important from the perspective of quality of life and cost.2,3 Therefore, we would like to know the clinical benefit of rivaroxaban when it is defined as the rate of recurrent venous thromboembolism combined with the principal safety outcome, as well as when it is defined as the rate of recurrent pulmonary embolism and major bleeding. Gijs W. Landman, M.D.
Structural and effective brain connectivity underlying biological motion detection

Significance Visual perception of body motion is of substantial value for social cognition and everyday life. By using an integrative approach to brain connectivity, the study sheds light on architecture and functional principles of the underlying cerebro-cerebellar network. This circuity is organized in a parallel rather than hierarchical fashion. This may explain why body-language reading is rather resilient to focal brain damage but severely affected in neuropsychiatric conditions with distributed network alterations. Furthermore, visual sensitivity to body motion is best predicted by specific top-down feedback to the early visual cortex, as well as functional communication (effective connectivity) and presence of white-matter pathways between the right fusiform gyrus and superior temporal sulcus. The findings allow better understanding of the social brain. The perception of actions underwrites a wide range of socio-cognitive functions. Previous neuroimaging and lesion studies identified several components of the brain network for visual biological motion (BM) processing, but interactions among these components and their relationship to behavior remain little understood. Here, using a recently developed integrative analysis of structural and effective connectivity derived from high angular resolution diffusion imaging (HARDI) and functional magnetic resonance imaging (fMRI), we assess the cerebro-cerebellar network for processing of camouflaged point-light BM. Dynamic causal modeling (DCM) informed by probabilistic tractography indicates that the right superior temporal sulcus (STS) serves as an integrator within the temporal module. However, the STS does not appear to be a “gatekeeper” in the functional integration of the occipito-temporal and frontal regions: The fusiform gyrus (FFG) and middle temporal cortex (MTC) are also connected to the right inferior frontal gyrus (IFG) and insula, indicating multiple parallel pathways. BM-specific loops of effective connectivity are seen between the left lateral cerebellar lobule Crus I and right STS, as well as between the left Crus I and right insula. The prevalence of a structural pathway between the FFG and STS is associated with better BM detection. Moreover, a canonical variate analysis shows that the visual sensitivity to BM is best predicted by BM-specific effective connectivity from the FFG to STS and from the IFG, insula, and STS to the early visual cortex. Overall, the study characterizes the architecture of the cerebro-cerebellar network for BM processing and offers prospects for assessing the social brain.
Acetylation drives hepatocyte nuclear factor 1β stability by blocking proteasome‐mediated degradation

Hepatocyte nuclear factor 1β (HNF1β) is mostly expressed in the liver, but is also expressed in other organs, like kidney, pancreas and genitourinary tract. In fact, HNF1β, a member of the superfamily of homeodomain‐containing transcription factors, has been described as a hallmark in clear cell carcinomas. However, its role as an oncogene or as tumor suppressor gene remains controversial. Here, we disclose a mechanism of HNF1β stabilization and degradation, using human HNF1β‐expressing cell lines of ovarian clear cell carcinoma (ES2), hepatocellular carcinoma (HEPG2), and normal immortalized kidney tubular cells (HK2). We show that increased levels of HNF1β is concomitant with an increase in the acetylation load and protein stabilization by interfering with the ubiquitin‐proteasome degradation system. This study reinforces that acetylation, besides their role in regulating chromatin conformation and gene expression, could also act in the action, turnover and stability of proteins essential for the survival and progression of certain cancer types.
TLR4 interaction with LPS in glioma CD133+ cancer stem cells induces cell proliferation, resistance to chemotherapy and evasion from cytotoxic T lymphocyte-induced cytolysis

Despite advances in treatment modalities, 5-year survival among glioma patients remains poor. Glioma cancer stem cells (CSCs) exhibit high tumorigenic activity and are associated with resistance to treatment and tumor recurrence. Because overexpression of toll-like receptor 4 (TLR4) correlated with cancer development, we investigated LPS-induced TLR4 signaling in glioma CD133-positive (CD133+) CSCs. The proliferation of CD133+ CSCs isolated from CSCs derived from the U251 and SF295 glioma cell lines and from human glioma samples was upregulated on a time- and concentration-dependent basis by LPS stimulation, with increases in CD133, NANOG, and NESTIN mRNA and protein levels. Also elevated was cytokine expression, which was coupled to phosphorylation of mitogen-activated protein kinase, and activation of cyclins and cyclin-dependent kinase complexes. TLR4 knockdown reduced LPS-induced CD133+ CSC proliferation, whereas Adriamycin-induced CD133+ CSC apoptosis was moderately inhibited by treatment with LPS, implying a protective effect of LPS. The capacity of glioma CD133+ CSC-reactive cytotoxic T lymphocyte to selectively kill CD133+ CSCs was reduced by LPS, and this effect was not apparent after TLR4 knockdown in CD133+ CSCs. These data suggest TLR4 signaling is a factor in CD133+ CSC immune evasion, and thus disruption of TLR4 signaling is a potential therapeutic strategy in glioma.
Evaluation of a pilot interprofessional education programme for eating disorder training in mental health services

Objective To evaluate the effectiveness of an Interprofessional Education (IPE) programme in eating disorders for mental health practitioners using a case-based learning approach. Methods A total of 25 mental health clinicians were asked to evaluate their IPE programme as part of training for the National Clinical Programme in Eating Disorders. They completed a Readiness for Interprofessional Learning Scale (RIPLS), a learner reaction questionnaire after each session and a final open evaluation at 4 months. Non-parametric statistical analysis was employed to analyse learner attitudes and reactions, and qualitative information was coded. Results A total of 23 (92%) clinicians from five disciplines participated. Baseline attitudes towards IPE were positive on all RIPLS subscales, and those with prior IPE experience had most positive views as to its benefits for teamwork and patient care (p=0.036). Learner reactions on content, delivery, outcome and structure indicated that individual learning experience was strongly positively endorsed. Change in clinical practice behaviour was reported in terms of communication, clinical activity, outcome evaluation and confidence. Barriers included other demands on time, organisational support, not having enough patients or co-workers to practice skills, and knowledge differentials between learners. Conclusions IPE using a case based learning approach is an effective and acceptable means of developing specialist training across existing service, team and professional boundaries. It has potential for positive impact on knowledge, clinical behaviour and service delivery. Recommendations include the introduction of IPE group guidelines, wider circulation of learning points and content, and the use of self-competency ratings and reflective logs.