Miracle-dz/UniFAR-FTUs huggingface dataset:
LSD1 Inhibition Attenuates Tumor Growth by Disrupting PLK1 Mitotic Pathway

Lysine-specific demethylase 1 (LSD1) is a histone modifier that is highly overexpressed in lung adenocarcinoma, which results in aggressive tumor biology. Tumor cell proliferation and migration analysis after LSD1 inhibition in the lung adenocarcinoma cell line PC9, using the LSD1 inhibitor HCI-2509 and siRNA, demonstrated that LSD1 activity was essential for proliferation and migration capacities of tumor cells. Moreover, reduced proliferation rates after LSD1 inhibition were shown to be associated with a cell-cycle arrest of the tumor cells in the G2–M-phase. Expression profiling followed by functional classification and pathway analysis indicated prominent repression of the polo-like kinase 1 (PLK1) pathway upon LSD1 inhibition. In contrast, transient overexpression of exogenous PLK1 plasmid rescued the LSD1 inhibition–mediated downregulation of PLK1 pathway genes. Mechanistically, LSD1 directly regulates expression of PLK1 by binding to its promoter region that subsequently affects expression of its downstream target genes. Notably, using lung adenocarcinoma TCGA datasets a significant correlation between LSD1 and PLK1 along with its downstream targets was observed. Furthermore, the LSD1/PLK1 linkage was confirmed by IHC analysis in a clinical lung adenocarcinoma cohort (n = 43). Conclusively, this is the first study showing a direct transcriptional link between LSD1 and PLK1. Implications: These findings point to a role of LSD1 in regulating PLK1 and thus efficient G2–M-transition–mediating proliferation of tumor cells and suggest targeting the LSD1/PLK1 axis as a novel therapeutic approach for lung adenocarcinoma treatment.
Different penalty methods for assessing interval from first to successful insemination in Japanese Black heifers

Objective The objective of this study was to determine the best approach for handling missing records of first to successful insemination (FS) in Japanese Black heifers. Methods Of a total of 2,367 records of heifers born between 2003 and 2015 used, 206 (8.7%) of open heifers were missing. Four penalty methods based on the number of inseminations were set as follows: C1, FS average according to the number of inseminations; C2, constant number of days, 359; C3, maximum number of FS days to each insemination; and C4, average of FS at the last insemination and FS of C2. C5 was generated by adding a constant number (21 d) to the highest number of FS days in each contemporary group. The bootstrap method was used to compare among the 5 methods in terms of bias, mean squared error (MSE) and coefficient of correlation between estimated breeding value (EBV) of non-censored data and censored data. Three percentages (5%, 10%, and 15%) were investigated using the random censoring scheme. The univariate animal model was used to conduct genetic analysis. Results Heritability of FS in non-censored data was 0.012±0.016, slightly lower than the average estimate from the five penalty methods. C1, C2, and C3 showed lower standard errors of estimated heritability but demonstrated inconsistent results for different percentages of missing records. C4 showed moderate standard errors but more stable ones for all percentages of the missing records, whereas C5 showed the highest standard errors compared with non-censored data. The MSE in C4 heritability was 0.633×10−4, 0.879×10−4, 0.876×10−4 and 0.866 ×10−4 for 5%, 8.7%, 10%, and 15%, respectively, of the missing records. Thus, C4 showed the lowest and the most stable MSE of heritability; the coefficient of correlation for EBV was 0.88; 0.93 and 0.90 for heifer, sire and dam, respectively. Conclusion C4 demonstrated the highest positive correlation with the non-censored data set and was consistent within different percentages of the missing records. We concluded that C4 was the best penalty method for missing records due to the stable value of estimated parameters and the highest coefficient of correlation.
Mimicry, deception and competition: The life of competing endogenous RNAs

Since their discovery, small regulatory RNAs (sRNAs) were thought to be regulated exclusively at the transcriptional level. However, accumulating data from recent reports indicate that posttranscriptional signals can also modulate the function and stability of sRNAs. One of these posttranscriptional signals are competing endogenous RNAs (ceRNAs). Commonly called RNA sponges, ceRNAs can effectively sequester sRNAs and prevent them from binding their cognate target messenger RNAs (mRNAs). Subsequently, they prevent sRNA‐dependent regulation of translation and stability of mRNA targets. While some ceRNAs seem to be expressed constitutively, others are intricately regulated according to environmental conditions. The outcome of ceRNA binding to a sRNA reaches beyond simple sequestration. Various effects observed on sRNA functions extend from reducing transcriptional noise to promote RNA turnover. Here, we present a historical perspective of the discovery of ceRNAs in eukaryotic organisms and mainly focus on the synthesis and function of select, well‐described, ceRNAs in bacterial cells.
Ovarian Reserve Reduction With Surgery Is Not Correlated With the Amount of Ovarian Tissue Inadvertently Excised at Laparoscopic Surgery for Endometriomas

The aim of the present study was to evaluate the effect of laparoscopic cystectomy on ovarian reserve by means of anti-Müllerian hormone (AMH) serial measurements and to compare AMH values with the number of inadvertently removed follicles in histological specimens. Fifty-two women were enrolled: 34 patients with endometriomas (group 1) and 18 patients with other benign ovarian cysts (group 2). All patients underwent laparoscopic cystectomy performed by a single experienced surgeon. The AMH was measured before, and 1, 3, and 6 months after cystectomy in group 1, and before and 6 months after surgery in group 2. Preoperative AMH levels (mean [standard deviation, SD]) in group 1 (3.39 [2.43] ng/mL) were not significantly different from group 2 (3.74 [2.57] ng/mL; P = .68). In group 1, a significant decrease in AMH levels of 43.4% was observed at 1 month (1.93 [1.36]; P = .003), and of 63.1% at 3 months (1.25 [1.00]; P = .007) postoperatively. The AMH increased not significantly between the third and sixth months in group 1 (+9.4%). Six months after surgery, AMH was reduced by 59.3% compared to baseline values in group 1 (P = .012), and by 29.5% in group 2 (P = .200). A significant difference in the AMH decrease was present between bilateral and monolateral endometriomas (P = .006). There was no correlation between the reduction rate of AMH and the number of follicles inadvertently removed in patients with endometriomas (P = .669). In conclusion, AMH decreases significantly after surgical excision of ovarian endometriomas. The postoperative decrease does not appear to correlate with the amount of ovarian tissue inadvertently excised with the endometrioma wall.
Life Course Socioeconomic Conditions and Frailty at Older Ages

Abstract Objectives This article aimed to assess associations of childhood socioeconomic conditions (CSC) with the risk of frailty in old age and whether adulthood socioeconomic conditions (ASC) influence this association. Methods Data from 21,185 individuals aged 50 years and older included in the longitudinal Survey of Health, Ageing, and Retirement in Europe were used. Frailty was operationalized as a sum of presenting weakness, shrinking, exhaustion, slowness, or low activity. Confounder-adjusted multilevel logistic regression models were used to analyze associations of CSC and ASC with frailty. Results While disadvantaged CSC was associated with higher odds of (pre-)frailty in women and men (odds ratio [OR] = 1.73, 95% confidence interval [CI] 1.34, 2.24; OR = 1.84, 95% CI 1.27, 2.66, respectively), this association was mediated by ASC. Personal factors and demographics, such as birth cohort, chronic conditions, and difficulties with activities of daily living, increased the odds of being (pre-)frail. Discussion Findings suggest that CSC are associated with frailty at old age. However, when taking into account ASC, this association no longer persists. The results show the importance of improving socioeconomic conditions over the whole life course in order to reduce health inequalities in old age.
Sickly Sweet: Insecticidal Polyols Induce Lethal Regurgitation in Dipteran Pests

Polyols are commonly used in food and medicines as sweeteners and preservatives but may also have insecticidal properties against some species of Diptera. Here we compared the insecticidal activity and feeding response of glycerol and propylene glycol (PG) on two tephritids: Anastrepha ludens and Anastrepha obliqua, and the drosophilid Drosophila suzukii. First, flies were exposed to solutions of 50% sucrose and the two polyols at concentrations of 1.67 M, 2.78 M and 4.18 M for 24 h and then observed at 24 h intervals for a period of three days. Both polyols elicited strong regurgitation behavior in the three flies and killed them. Regurgitation apparently also reduced flies’ body weight, and this was particularly apparent in insects that fed on 4.18 M PG solutions. A high percentage of individuals exposed to PG solutions perished after 72 h. The number of proboscis extensions, which is associated with feeding preference, was lower in the 4.18 M polyols + sucrose mixtures than in the 50% sucrose solution. Glycerol had a lower insecticidal effect in Anastrepha spp. and very little insecticidal effect in D. suzukii. Finally, elevated regurgitation and mortality was confirmed in A. ludens treated with 1.0–2.78 M of erythritol plus sucrose. Our results demonstrate that PG, and to a lower extent glycerol, have the potential for being used as a safer method of insect pest control. The hyper-regurgitation response may contribute to the insecticidal properties of these polyols in Diptera.
Increased risk of neurodegenerative dementia in women with migraines

Abstract The present study aimed to evaluate the association between migraines and dementia. Data were collected from 11,438 dementia participants who were 1:4 matched by age, sex, income, region of residence, hypertension, diabetes, and dyslipidemia with 45,752 controls from the Korean National Health Insurance Service-National Sample Cohort from 2002 to 2013. Dementia was diagnosed using the International Classification of Disease-10 (ICD-10) codes (G30 or F00). For the integrity of diagnoses, we included only participants ≥60 years old who had been diagnosed with an ICD-10 code twice or more during ambulatory visits for the same episode. For migraine (ICD-10 code, G43), we included participants who had visited outpatient clinics twice or more for the same episode. In both dementia and control groups, a previous history of migraine was investigated. Approximately 7.7% (881/11,438) of patients in the dementia group and 6.3% (2888/45,752) of those in the control group had a history of migraine (P < .001). The crude and adjusted odds ratios (ORs) for migraine with dementia was 1.22 (95% confidence interval [CI] = 1.13–1.32, P < .001) and 1.13 (95% CI = 1.05–1.23, P = .002), respectively. In the subgroup analyses according to age and sex, women demonstrated a significantly higher adjusted OR for migraine with dementia, whereas men did not exhibit an association between migraine and dementia. In a nested case–control study using a national sample cohort, migraine increased the risk of dementia in women.
Test–retest reliability of the special interest group on amputation medicine/Dutch working group on amputations and prosthetics mobility scale, in persons wearing a prosthesis after a lower-limb amputation

Abstract Purpose: To assess the test–retest reliability of the Special Interest Group on Amputation Medicine Mobility Scale/Dutch Working Group on Amputations and Prosthetics, better known as SIGAM/WAP mobility scale, in persons with a lower-limb amputation. Method: Longitudinal study at the outpatient departments of a rehabilitation center and a university medical center. Persons with a lower-limb amputation, wearing a prosthesis, were assessed at the end of their multidisciplinary rehabilitation treatment twice, with a 3-week interval, by the same practitioner. Test–retest reliability was quantified using the intraclass correlation coefficient for agreement. Results: Eighty persons participated (mean age ± SD, 61 ± 15 years; 61% men; 76% vascular cause of amputation; 70% able to walk >50m). Fifty-one of them rated themselves to be stable with respect to their mobility and their intraclass correlation coefficient was 0.90 (95% confidence intervals 0.84–0.94). Conclusions: The Special Interest Group on Amputation Medicine Mobility Scale/Dutch Working Group on Amputations and Prosthetics had, at the outpatient departments of a rehabilitation center and a university medical center, excellent test-retest reliability in persons wearing a prosthesis after a lower-limb amputation. Implications for rehabilitation The Special Interest Group on Amputation Medicine/Dutch Working Group on Amputations and Prosthetics Mobility Scale was developed to classify mobility after a lower-limb amputation and wearing a prosthesis. The Dutch translation of this mobility scale has excellent test–retest reliability.
Parts‐based representations of perceived face movements in the superior temporal sulcus

Facial motion is a primary source of social information about other humans. Prior fMRI studies have identified regions of the superior temporal sulcus (STS) that respond specifically to perceived face movements (termed fSTS), but little is known about the nature of motion representations in these regions. Here we use fMRI and multivoxel pattern analysis to characterize the representational content of the fSTS. Participants viewed a set of specific eye and mouth movements, as well as combined eye and mouth movements. Our results demonstrate that fSTS response patterns contain information about face movements, including subtle distinctions between types of eye and mouth movements. These representations generalize across the actor performing the movement, and across small differences in visual position. Critically, patterns of response to combined movements could be well predicted by linear combinations of responses to individual eye and mouth movements, pointing to a parts‐based representation of complex face movements. These results indicate that the fSTS plays an intermediate role in the process of inferring social content from visually perceived face movements, containing a representation that is sufficiently abstract to generalize across low‐level visual details, but still tied to the kinematics of face part movements.
Possible adverse effect of high δ-alpha-tocopherol intake on hepatic iron overload: Enhanced production of vitamin C and the genotoxin, 8-hydroxy-2′- deoxyguanosine

Excess hepatic iron generates reactive oxygen species that result in oxidative stress and oxidative damage to the liver. Vitamins have hitherto been considered to be a possible remedy. The aim of this study was to determine if high doses of δ-α-tocopherol supplementation in iron overload would ameliorate the oxidative stress. Four groups of 20 male Wistar albino rats were studied: group 1 (control) was fed normal diet, group 2 (Fe) 0.75% Ferrocene iron, group 3 (FV gp) 0.75% Ferrocene/δ-α-tocopherol (10× RDA), group 4 (V gp) normal diet/δ-α-tocopherol. After 12 months, serum iron, reduced glutathione, catalase, vitamin C, Oxygen Radical Absorbance Capacity, lipid peroxidation, 8-hydroxy-2′-deoxyguanosine (8-OHdG), aspartate transaminase (AST), and alanine transaminase (ALT) were measured. Vitamin C levels were: F gp = 5.04 ± 0.09; FV gp = 5.85 ± 0.13 (μmol/l) (p < 0.05). 8-hydroxy-2′-deoxyguanosine levels were: F gp = 143.6 ± 6.4; FV gp = 179.2 ± 18.2 (ng/ml) (p < 0.05). Oxidative liver damage, as determined by serum AST and ALT levels, was not attenuated by α-tocopherol. A positive correlation existed between vitamin C and 8-OHdG, suggesting possible δ-α-tocopherol toxicity.
Attacks on healthcare in conflict: generating attention in the modern information landscape

ABSTRACT Attacks on healthcare in conflict (AHCC) is receiving increased attention as a pressing global concern from humanitarian organisations, the media, policymakers, academics, and the public. This study examines the extent to which this increased attention leads to mainstream reporting and understanding of AHCC that is representative of reality by investigating the ways that information and knowledge about the issue is produced. Based on a rapid review of documentation on AHCC since 2011, this is one of the first studies to assess the rigour, validity, and representativeness of mainstream data on AHCC. Findings indicate that information and knowledge about AHCC is molded by a particular representation of the issue created by international media and humanitarian organisations seeking to capture public and political attention. This dominant understanding is not representative of the complex reality of AHCC, but is instead driven by organisational objectives and advocacy agendas. These findings hold important implications for the above-mentioned stakeholders by exploring the complexity and impacts of documenting AHCC. Most notably, the research investigates the relationship between information and understanding about the issue and the action that it encourages.
Clinical assessment and management of multimorbidity: NICE guideline.

The National Institute for Health and Care Excellence (NICE) has published a guideline on the assessment and management of patients with multimorbidity.1 Multimorbidity is defined as the presence of two or more long-term conditions and is increasingly common as people age. Two-thirds of people aged >65 years will have multimorbidity, which is associated with reduced quality of life and higher mortality.2 In older people this is associated with higher rates of physical health conditions, polypharmacy, adverse drug events, high treatment burden, and greater use of health services. In younger people and people from less affluent areas, multimorbidity is often due to a combination of physical and mental health conditions. The guideline emphasises that multimorbidity includes conditions such as sensory problems and pain as well as defined physical and mental health conditions such as diabetes or schizophrenia; ongoing conditions such as learning disability; symptom complexes such as frailty or chronic pain; sensory impairment such as sight or hearing loss; and alcohol and substance misuse. The aim of this guideline is to support patients and clinicians in optimising care for people with multimorbidity, in particular where there is potential for care to become burdensome or uncoordinated. ### Impact of multimorbidity Some patients with two or more conditions can manage those conditions and associated treatments in line with single disease guidelines. This guideline suggests that healthcare professionals should consider an approach to care that takes account of multimorbidity, for patients such as those who: find it difficult to manage their treatments for day-to-day activities; are prescribed multiple regular medications; frequently seek unplanned or emergency care; and have frailty (that is, reduction in resilience or biological/physiological reserve). The guideline suggests that such people might be identified proactively using …
8-Hydroxy-2’-deoxyguanosine as a biomarker of oxidative stress in acute exacerbation of chronic obstructive pulmonary disease

Background/aim 8-Hydroxy-2’-deoxyguanosine (8-OHdG) is a biomarker of oxidative stress and has been implicated in many diseases. The aim of this study was to investigate the clinical value of plasma 8-OHdG level in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Materials and methods A total of 154 subjects were enrolled in this study, including 20 healthy volunteers, 24 COPD patients in the stable phase, and 110 AECOPD patients. Peripheral blood samples, demographic information, and clinical characteristics were collected from all subjects at the time of being recruited into the study. Plasma 8-OHdG level was detected by enzyme-linked immunosorbent a ss ay. Results 8-OHdG was increased in patients with AECOPD compared to healthy subjects and patients with stable COPD, especially in smokers. It also increased with the GOLD stage, mMRC grade, CAT score, and group level of combined COPD assessment. Additionally, further analysis revealed that 8-OHdG was negatively correlated with FEV1, FEV1% predicted, and FEV1/FVC and positively correlated with C-reactive protein, procalcitonin, and neutrophil CD64. Conclusion 8-OHdG is associated with spirometric severity, symptomatic severity, exacerbation risk, and inflammatory biomarkers in AECOPD patients, suggesting it as a promising biomarker for reflecting disease severity and guiding the choice of optimal therapeutic decision.
Specific Disruption of Abca1 Targeting Largely Mimics the Effects of miR-33 Knockout on Macrophage Cholesterol Efflux and Atherosclerotic Plaque Development

Rationale: Inhibition of miR-33 reduces atherosclerotic plaque burden, but miR-33 deficient mice are predisposed to the development of obesity and metabolic dysfunction. The proatherogenic effects of miR-33 are thought to be in large part because of its repression of macrophage cholesterol efflux, through targeting of Abca1 (ATP-binding cassette subfamily A member 1). However, targeting of other factors may also be required for the beneficial effects of miR-33, and currently available approaches have not allowed researchers to determine the specific impact of individual miRNA target interactions in vivo. Objective: In this work, we sought to determine how specific disruption of Abca1 targeting by miR-33 impacts macrophage cholesterol efflux and atherosclerotic plaque formation in vivo. Methods and Results: We have generated a novel mouse model with specific point mutations in the miR-33 binding sites of the Abca1 3’untranslated region, which prevents targeting by miR-33. Abca1 binding site mutant (Abca1BSM) mice had increased hepatic ABCA1 expression but did not show any differences in body weight or metabolic function after high fat diet feeding. Macrophages from Abca1BSM mice also had increased ABCA1 expression, as well as enhanced cholesterol efflux and reduced foam cell formation. Moreover, LDLR (low-density lipoprotein receptor) deficient animals transplanted with bone marrow from Abca1BSM mice had reduced atherosclerotic plaque formation, similar to mice transplanted with bone marrow from miR-33 knockout mice. Conclusion: Although the more pronounced phenotype of miR-33 deficient animals suggests that other targets may also play an important role, our data clearly demonstrate that repression of ABCA1 is primarily responsible for the proatherogenic effects of miR-33. This work shows for the first time that disruption of a single miRNA/target interaction can be sufficient to mimic the effects of miRNA deficiency on complex physiological phenotypes in vivo and provides an approach by which to assess the impact of individual miRNA targets.