Miracle-dz/UniFAR-FTUs huggingface dataset:
METTL3-mediated m6A modification of HDGF mRNA promotes gastric cancer progression and has prognostic significance

Objective N6-methyladenosine (m6A) RNA methylation and its associated methyltransferase METTL3 are involved in tumour initiation and progression via the regulation of RNA function. This study explored the biological function and clinical significance of METTL3 in gastric cancer (GC). Design The prognostic value of METTL3 expression was evaluated using tissue microarray and immunohistochemical staining analyses in a human GC cohort. The biological role and mechanism of METTL3 in GC tumour growth and liver metastasis were determined in vitro and in vivo. Results The level of m6A RNA was significantly increased in GC, and METTL3 was the main regulator involved in the abundant m6A RNA modification. METTL3 expression was significantly elevated in GC tissues and associated with poor prognosis. Multivariate Cox regression analysis revealed that METTL3 expression was an independent prognostic factor and effective predictor in human patients with GC. Moreover, METTL3 overexpression promoted GC proliferation and liver metastasis in vitro and in vivo. Mechanistically, P300-mediated H3K27 acetylation activation in the promoter of METTL3 induced METTL3 transcription, which stimulated m6A modification of HDGF mRNA, and the m6A reader IGF2BP3 then directly recognised and bound to the m6A site on HDGF mRNA and enhanced HDGF mRNA stability. Secreted HDGF promoted tumour angiogenesis, while nuclear HDGF activated GLUT4 and ENO2 expression, followed by an increase in glycolysis in GC cells, which was correlated with subsequent tumour growth and liver metastasis. Conclusions Elevated METTL3 expression promotes tumour angiogenesis and glycolysis in GC, indicating that METTL3 expression is a potential prognostic biomarker and therapeutic target for human GC.
Skin application of glutathione and iron sulfate can inhibit elicitation of allergic contact dermatitis from hexavalent chromium

Allergic contact dermatitis (ACD) caused by hexavalent chromium, Cr(VI), is often severe and difficult to treat. The most common source of exposure to Cr(VI) in Sweden used to be cement, and more recently leather. The contact allergy can be diminished or inhibited if the exposure is decreased or ceases. Barrier creams against different kinds of allergens have been investigated for their protective properties which may offer protection against Cr(VI) exposure.
Thrombin Induces Angiotensin II-Mediated Senescence in Atrial Endothelial Cells: Impact on Pro-Remodeling Patterns

Background: Besides its well-known functions in hemostasis, thrombin plays a role in various non-hemostatic biological and pathophysiologic processes. We examined the potential of thrombin to promote premature atrial endothelial cells (ECs) senescence. Methods and Results: Primary ECs were isolated from porcine atrial tissue. Endothelial senescence was assessed by measuring beta-galactosidase (SA-β-gal) activity using flow cytometry, oxidative stress using the redox-sensitive probe dihydroethidium, protein level by Western blot, and matrix metalloproteinases (MMPs) activity using zymography. Atrial endothelial senescence was induced by thrombin at clinically relevant concentrations. Thrombin induced the up-regulation of p53, a key regulator in cellular senescence and of p21 and p16, two cyclin-dependent kinase inhibitors. Nicotinamide adenine dinucleotide phosphate NADPH oxidase, cyclooxygenases and the mitochondrial respiration complex contributed to oxidative stress and senescence. Enhanced expression levels of vascular cell adhesion molecule (VCAM)-1, tissue factor, transforming growth factor (TGF)-β and MMP-2 and 9 characterized the senescence-associated secretory phenotype of atrial ECs. In addition, the pro-senescence endothelial response to thrombin was associated with an overexpression of both angiotensin converting enzyme and AT1 receptors and was inhibited by perindoprilat and losartan. Conclusions: Thrombin promotes premature ageing and senescence of atrial ECs and may pave the way to deleterious remodeling of atrial tissue by a local up-regulation of the angiotensin system and by promoting pro-inflammatory, pro-thrombotic, pro-fibrotic and pro-remodeling responses. Hence, targeting thrombin and/or angiotensin systems may efficiently prevent atrial endothelial senescence.
Training OSCE examiners: minimal effort with far‐reaching results

clinical anatomist. The group then reconvenes, bringing to bear their refreshed anatomical knowledge on a concluding discussion of the case. We have varied the cases to maintain ongoing interest among faculty GPs, covering, for example, neck lumps, tingling painful hand, epigastric pain and abdominal masses. The chief resources are expert facilitators and anatomy staff, and the use of a dissection room. Identifying and preparing relevant specimens and developing the self-assessment exercises and cases are the key tasks for educators. What lessons were learned? Anonymous survey feedback has been very positive; GPs enjoyed the sessions, particularly returning to the dissection room, often after many years. They rated the sessions as very or extremely useful, highlighting in particular the value of the clinical cases linked to the anatomy, the hands-on time with cadavers, and the expertise of the tutors. A couple of GPs said they would prefer more emphasis on pure anatomy. Generally, the scores for enjoyment were higher than scores for usefulness, which has made us reflect on how we can ensure the educational utility of the sessions is not forgotten in the novelty of being back in the dissection room. Identifying new GP-relevant cases which lend themselves to this approach is a challenge. General practitioners have suggested a range of topics for future sessions, including musculoskeletal anatomy, the brain, and a greater focus on pathology than anatomy. Some of these topics seem better suited to our model than others; we need further experience to understand which are likely to work best. Although we already use cases, slides, drawing and hands-on teaching with cadavers, we are keen to build on this multimodal teaching approach which the literature suggests is likely to be the optimum way to support the learning of anatomy (such as by including interactive three-dimensional anatomy software).
Acute restraint stress increases blood pressure and oxidative stress in the cardiorenal system of rats: a role for AT1 receptors

Abstract We evaluate whether acute restraint stress may affect the oxidative state of the cardiorenal system and the possible contribution of angiotensin II/AT1 receptors in such response. Male Wistar rats were restrained for 60 min within wire mesh chambers. Some rats were treated with losartan (selective AT1 receptor antagonist, 10 mg/kg, p.o., gavage) 30 min before being stressed. Biochemical analyses were conducted after the 60-min period of restraint. Treatment with losartan prevented the increase in mean arterial pressure (MAP), but not heart rate (HR) induced by acute stress. Phenylephrine-induced contraction of endothelium-intact aortas was not affected by acute stress. Losartan prevented the increase in both superoxide anion (O2•−) and hydrogen peroxide (H2O2) levels induced by acute stress in the aorta and renal cortex. Similarly, the augmented activity of superoxide dismutase (SOD) induced by acute stress in the aorta and renal cortex was prevented by losartan. Enhanced levels of O2•− and thiobarbituric acid reactive species (TBARS) were detected in the left ventricle (LV) of stressed rats, but losartan did not prevent these responses. Similarly, losartan did not inhibited stress-induced decrease in the concentration of nitrate/nitrite (NOx) and H2O2 in the left ventricle. Stress increased ROS generation and affected the enzymatic antioxidant system in the cardiorenal system. In addition to its well-known cardiovascular changes during acute stress, angiotensin II also induces ROS generation in the cardiorenal system in a tissue-specific manner. The increase in oxidative stress mediated by angiotensin II/AT1 receptors could be one mechanism by which acute stress predisposes to cardiorenal dysfunctions.
The relationship between time of re-tightening and preload loss of abutment screws for two different implant designs: an in-vitro study.

The loosening of an abutment screw is one of the most frequent complications in implant-prosthetic rehabilitation, especially for single crown cemented prostheses. This complication is due to several mechanical factors, including: type of connection, abutment-screw geometry, settling effects, and cyclical load. The purpose of the present in-vitro study was to compare and associate different times of re-tightening with reductions in preload losses. We evaluated 40 internal hexagon dental implants and 40 external hexagon dental implants, with their related abutment screws. The implants were embedded in acrylic resin in cylindrical polyvinyl chloride tubes (diameter, 26 mm; height, 20 mm). The abutments were fixed to the implants with screws to an initial torque of 35 Ncm using a digital torque meter with decimal precision. The two different types of connection were randomly divided in four subgroups of 10 samples each. One subgroup was used as control. The test groups underwent re-tightening to the same initial torque at increasing times from initial torque application for tightening of the abutment screws, to their re-tightening at 2 min, 5 min, and 10 min. The re-tightening time of 2 min shows significantly reduced preload loss. Randomized clinical trials are strongly required to provide clinicians with a beneficial standardized protocol of re-tightening that can be applied in routine clinical practice.
Effect of Feeding Cold-Pressed Sunflower Cake on Ruminal Fermentation, Lipid Metabolism and Bacterial Community in Dairy Cows

Simple Summary The use of cold-pressed sunflower cake, a by-product of small-scale biodiesel manufacturing, as a substitute for prilled palm fat in dairy cows’ diet, can reduce the extent of unsaturated fatty acid biohydrogenation This favors an accumulation of vaccenic acid in the rumen concomitant with a greater daily duodenal microbial N flow and all without impairing ruminal fermentation, microbial diversity or abundance of dominant populations. In the present study, only changes in relative abundances of less-representative genera were induced. Abstract Cold-pressed sunflower cake (CPSC), by-product of oil-manufacturing, has high crude fat and linoleic acid concentrations, being a promising supplement to modulate rumen fatty acid (FA) profile. This trial studied CPSC effects on ruminal fermentation, biohydrogenation and the bacterial community in dairy cows. Ten cows were used in a crossover design with two experimental diets and fed during two 63-day periods. The cows were group fed forage ad libitum and the concentrate individually. The concentrates, control and CPSC, were isoenergetic, isoproteic and isofat. The ruminal samples collected at the end of each experimental period were analyzed for short-chain fatty acid, FA and DNA sequencing. CPSC decreased butyrate molar proportion (4%, p = 0.005). CPSC decreased C16:0 (28%, p < 0.001) and increased C18:0 (14%, p < 0.001) and total monounsaturated FA, especially C18:1 trans-11 (13%, p = 0.023). The total purine derivative excretion tended to be greater (5%, p = 0.05) with CPSC, resulting in a 6% greater daily microbial N flow. CPSC did not affect the diversity indices but increased the relative abundances of Treponema and Coprococcus, and decreased Enterococcus, Ruminococcus and Succinivibrio. In conclusion, the changes in ruminal fermentation and the FA profile were not associated with changes in microbial diversity or abundance of dominant populations, however, they might be associated with less abundant genera.
Strategic Considerations for Applying the Flipped Classroom to Neurology Education

Nowadays, the “flipped classroom” approach is taking the center stage within medical education. However, very few reports on the implementation of the flipped classroom in neurology have been published to date, and this educational model still represents a challenge for students and educators alike. In this article, neurology educators from the American Academy of Neurology's A. B. Baker Section on Neurological Education analyze reports of flipped classroom in other medical/surgical subspecialties, review the current implementation in neurology, and discuss future strategies to flip the neurology curriculum through contextualization of the benefits and the consequences. ANN NEUROL 2020;87:4–9
iTRAQ-based mitochondrial proteome analysis of the molecular mechanisms underlying postharvest senescence of Zizania latifolia.

To explore the molecular mechanisms underlying postharvest senescence of Zizania latifolia, the changes in the mitochondrial proteome of plants treated with or without (control) 1-methyleyelopropene and ethylene during storage at room temperature for 0, 3 and 6 days were investigated using isobaric tags for relative and absolute quantitation (iTRAQ) labeling combined with two-dimensional liquid chromatography-tandem mass spectrometry. A total of 1,390 proteins with two or more peptides were identified, of which 211 showed a significant (p < .05) change (at least twofold) in relative abundance. Monitoring the parallel reaction validated the reliability and accuracy of the iTRAQ results. Bioinformatics and functional analysis of these differentially expressed proteins (DEPs) revealed that postharvest senescence of Z. latifolia could be attributed to (a) strengthened pentose phosphate pathway, (b) imbalanced protein, amino acid, organic acid, and fatty acid metabolism, (c) disordered energy homeostasis, (d) exacerbated oxidative damage, (e) RNA degradation, (f) activation of the Ca2+ , mitogen-activated protein kinase, and jasmonic acid signaling pathways, (g) programed cell death, (h) excessive biosynthesis of secondary metabolites, or (i) degradation of cell structure. Our findings provide integrated insight into the molecular mechanisms of postharvest senescence during storage as well as the DEPs that show promise as targets for controlling senescence-induced quality deterioration of Z. latifolia. PRACTICAL APPLICATIONS: Postharvest senescence is the most important factor that causes fast quality deterioration of Zizania latifolia. The understanding of the processes leading to postharvest senescence of Z. latifolia is essential in enhancing the commercial value and extending the shelf life of the product. It is currently believed that the mitochondrial metabolism is closely related to postharvest senescence. For this, the changes of proteome in Z. latifolia mitochondria treated with or without (control) 1-MCP and ETH during storage at room temperature were investigated. Results showed that a variety of physiobiochemical responses occur during postharvest senescence of Z. latifolia. 1-MCP treatment significantly inhibited the changes of these physiobiochemical processes, finally, retarding the postharvest senescence of Z. latifolia. ETH treatment had opposite effects on proteome changes compared with 1-MCP treatment. Taken together, these results enrich the understanding of the molecular mechanisms of postharvest senescence of Z. latifolia.
Being ‘alone’ striving for belonging and adaption in a new reality – The experiences of spouse carers of persons with dementia

Background and aim Spouse carers of a person with dementia report feeling lonely and trapped in their role, lacking support and having no time to take care of their own health. In Sweden, the support available for family carers is not specialised to meet the needs of spouse carers of people with dementia. The aim of the study described in this paper was to explore spouse carers’ experiences of caring for a partner with dementia, their everyday life as a couple and their support needs. Methods Nine spouse carers of a partner with dementia living at home were recruited through a memory clinic and a dementia organisation. Semi-structured interviews were conducted with the participants, focusing on their experiences of providing care, their support needs in relation to their caring situation, their personal well-being and their marital relationship. The interviews were transcribed and underwent qualitative content analysis. Results The analysis resulted in one overall theme Being ‘alone’ striving for belonging and adaption in a new reality, synthesized from four sub-themes: (1) Being in an unknown country; (2) Longing for a place for me and us; (3) Being a carer first and a person second; and (4) Being alone in a relationship. Conclusions The training of care professionals regarding the unique needs of spouse carers of people with dementia needs improvement, with education, in particular, focusing on their need to be considered as a person separate from being a carer and on the significance of the couple’s relationship for their mutual well-being.
Lifestyle and occupational factors associated with participation in breast mammography screening among Western Australian women

Objectives Various lifestyle and occupational factors have been associated with an increased risk of breast cancer, but there is limited research investigating the relationship between these factors and participation in breast cancer screening. This study explores the associations between lifestyle and occupational factors and participation in breast mammography screening among women living in Western Australia. Methods This study involved 1705 women aged 40 and older who participated as controls in the Breast Cancer Environment and Employment Study conducted in Western Australia. Self-reported questionnaire data were collected on participation in mammography screening, demographic factors, and lifestyle and occupational variables (smoking, physical activity, alcohol consumption, body mass index, use of contraceptive pill and hormone replacement therapy, breastfeeding, occupation, and participation in shift work). Multivariate modified Poisson regression was used to identify variables associated with ever participation in breast mammography screening. Results Just over 88% of women reported having ever had a mammogram. Likelihood of having ever had a mammogram was higher among women who had ever used hormone replacement therapy (adjusted prevalence ratio (aPR) = 1.05, 95% CI 1.02–1.07). Women who worked in clerical occupations (aPR = 1.06, 95% CI 1.01–1.11) or home duties (aPR = 1.05, 95% CI 1.00–1.11) were also more likely to report having ever had a mammogram compared with those in professional or technical occupations. Conclusions Participation in mammography screening was found to differ by lifestyle and occupational factors. These results have important implications for public health strategies on improving screening participation.
Two new pregnane steroidal glycosides from Cynanchum taihangense

Abstract As our ongoing chemical investigation, two new pregnane steroidal glycosides, cynataihosides G (1), with a new aglycone, and H (2) were isolated from the 95% ethanol extract of Cynanchum taihangense. Their structures were elucidated on the basis of 1 D and 2 D NMR spectral data, HR-ESI-MS analysis and qualitative chemical methods. The compounds were subjected to detect the cytotoxicity against three human tumor cell lines (HL-60, THP-1 and PC-3). The compounds displayed no significant cytotoxicity. Supplemental data for this article can be accessed at https://doi.org/10.1080/14786419.2019. 1672682. Graphical Abstract Supplemental data for this article can be accessed at https://doi.org/10.1080/14786419.2019. 1672682.
Investigation of a Standardized Qualitative Behaviour Assessment and Exploration of Potential Influencing Factors on the Emotional State of Dairy Calves

Simple Summary Although welfare states of dairy calves are of public and scientific concern, no standardized protocol exists to assess the emotionality of these animals. Therefore, this study aimed at investigating and establishing a calf-specific term list for Qualitative Behavior Assessment (QBA), a technique that is already validated for assessing emotional states in many animal species. The statistically supported results showed that agreement can be reached among observers, terms showed varied results across farms, and evaluated emotional states could be linked to some explaining farm factors. Overall, results showed that calves have a neutral emotional state and profit from certain farm factors. However, we conclude that the assessment should be more widely used to gain more insight into calves’ welfare states and how their emotional state can be improved to a positive one. Abstract Assessing emotional states of dairy calves is an essential part of welfare assessment, but standardized protocols are absent. The present study aims at assessing the emotional states of dairy calves and establishing a reliable standard procedure with Qualitative Behavioral Assessment (QBA) and 20 defined terms. Video material was used to compare multiple observer results. Further, live observations were performed on 49 dairy herds in Denmark and Italy. Principal Component Analysis (PCA) identified observer agreement and QBA dimensions (PC). For achieving overall welfare judgment, PC1-scores were turned into the Welfare Quality (WQ) criterion ‘Positive Emotional State’. Finally, farm factors’ influence on the WQ criterion was evaluated by mixed linear models. PCA summarized QBA descriptors as PC1 ‘Valence’ and PC2 ‘Arousal’ (explained variation 40.3% and 13.3%). The highest positive descriptor loadings on PC1 was Happy (0.92) and Nervous (0.72) on PC2. The WQ-criterion score (WQ-C12) was on average 51.1 ± 9.0 points (0: worst to 100: excellent state) and ‘Number of calves’, ‘Farming style’, and ‘Breed’ explained 18% of the variability of it. We conclude that the 20 terms achieved a high portion of explained variation providing a differentiated view on the emotional state of calves. The defined term list proved to need good training for observer agreement.
Mining social media for prescription medication abuse monitoring: a review and proposal for a data-centric framework

Abstract Objective Prescription medication (PM) misuse and abuse is a major health problem globally, and a number of recent studies have focused on exploring social media as a resource for monitoring nonmedical PM use. Our objectives are to present a methodological review of social media–based PM abuse or misuse monitoring studies, and to propose a potential generalizable, data-centric processing pipeline for the curation of data from this resource. Materials and Methods We identified studies involving social media, PMs, and misuse or abuse (inclusion criteria) from Medline, Embase, Scopus, Web of Science, and Google Scholar. We categorized studies based on multiple characteristics including but not limited to data size; social media source(s); medications studied; and primary objectives, methods, and findings. Results A total of 39 studies met our inclusion criteria, with 31 (∼79.5%) published since 2015. Twitter has been the most popular resource, with Reddit and Instagram gaining popularity recently. Early studies focused mostly on manual, qualitative analyses, with a growing trend toward the use of data-centric methods involving natural language processing and machine learning. Discussion There is a paucity of standardized, data-centric frameworks for curating social media data for task-specific analyses and near real-time surveillance of nonmedical PM use. Many existing studies do not quantify human agreements for manual annotation tasks or take into account the presence of noise in data. Conclusion The development of reproducible and standardized data-centric frameworks that build on the current state-of-the-art methods in data and text mining may enable effective utilization of social media data for understanding and monitoring nonmedical PM use.