Miracle-dz/UniFAR-FTUs huggingface dataset:
MiR-939-5p suppresses PM2.5-induced endothelial injury via targeting HIF-1α in HAECs

Abstract Ambient air pollution is a leading cause of non-communicable disease in the world. PM2.5 has the potential to change the miRNAs profiles, which in turn causes cardiovascular effects. Hypoxia-inducible factor (HIF)-1 plays a critical role in the development of atherosclerosis. Yet, the possible role of miR-939-5p/HIF-1α in PM2.5-induced endothelial injury remains elusive. Therefore, the study aims to investigate the effects of miR-939-5p and HIF-1α on PM2.5-triggered endothelial injury. The results from immunofluorescence, qRT-PCR, LSCM, and western blot assays demonstrated that PM2.5 increased the levels of HIF-1α, inflammation and apoptosis in human aortic endothelial cells (HAECs). Yet, the inflammatory response and mitochondrial-mediated apoptosis pathway were effectively inhibited in HIF-1α knockdown HAECs lines. The expression of miR-939-5p was significantly down-regulated in HAECs after exposed to PM2.5. The luciferase reporter, qRT-PCR and western blot results demonstrated that miR-939-5p could directly targeted HIF-1α. And the miR-939-5p overexpression restricted PM2.5-triggered decreases in cell viability and increases in lactic dehydrogenase (LDH) activity, reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and inflammation. In addition, miR-939-5p overexpression remarkably suppressed PM2.5-triggered BcL-2/Bax ratio reduction and Cytochrome C, Cleaved Caspase-9 and Cleaved Caspase-3 expression increase, revealed that miR-939-5p hampered PM2.5-induced endothelial apoptosis through mitochondrial-mediated apoptosis pathway. Our results demonstrated that PM2.5 increased the expression of HIF-1α followed by a pro-inflammatory and apoptotic response in HAECs. The protective effect of miR-939-5p on PM2.5-triggered endothelial cell injury by negatively regulating HIF-1α. miR-939-5p might present a new therapeutic target for PM2.5 induced endothelial injury.
Response to evaluation of the food composition tables: Beyond the divergence and agreement of intakes

Dear Editor, Although we appreciate the author's attention to our paper (Ali & Amin, 2020), in our study, we did not evaluate the food composition tables (FCTs) and their methodological development as they imply. Instead, we examined the comparability and the agreements of the estimated nutrient intakes between the two FCTs of Bangladesh. This type of research is undertaken when different FCTs are used simultaneously for the same population (Deharveng et al., 1999; Garcia et al., 2004; Hakala et al., 2003). We have found that studies by Rahman et al. (2016) and Rahman et al. (2017) used FCTB-2012, though FCTB-2013 was available at that time and was concomitantly used by the other researchers (Al Hasan et al., 2016; Campbell et al., 2018). Thus, the estimated nutrient intakes in these studies have been threatened by concerns about reliability. The authors are correct that de-attenuated correlation may improve the energy-adjusted agreement, but this was beyond our study methodology. However, the authors misinterpreted our study findings. The authors selectively picked up the weighted kappa value of ‘poor’ for four nutrients but ignored the ‘slight’ and ‘fair’ categories of agreements for other micronutrients (Landis & Koch, 1977). We included 15 micronutrients that are matched between the two FCTs, which have significant public health and clinical implications as FCTs are widely used for the development of dietary guidelines and modification of diets for the treatment of
Frequency-Dependent Cortical Interactions during Semantic Processing: An Electrocorticogram Cross-spectrum Analysis Using a Semantic Space Model.

Convergent evidence has demonstrated that semantics are represented by the interaction between a multimodal semantic hub at the anterior temporal lobe (ATL) and other modality-specific association cortical areas. Electrocorticogram (ECoG) recording with high spatiotemporal resolutions is efficient in evaluating such cortical interactions; however, this has not been a focus of preceding studies. The present study evaluated cortical interactions during picture naming using a novel ECoG cross-spectrum analysis, which was formulated from a computational simulation of neuronal networks and combined with a vector space model of semantics. The results clarified three types of frequency-dependent cortical networks: 1) an earlier-period (0.2-0.8 s from stimulus onset) high-gamma-band (90-150 Hz) network with a hub at the posterior fusiform gyrus, 2) a later-period (0.4-1.0 s) beta-band (15-40 Hz) network with multiple hubs at the ventral ATL and posterior middle temporal gyrus, and 3) a pre-articulation theta-band (4-7 Hz) network distributed over widely located cortical regions. These results suggest that frequency-dependent cortical interactions can characterize the underlying processes of semantic cognition, and the beta-band network with a hub at the ventral ATL is especially associated with the formation of semantic representation.
Manipulating placebo analgesia and nocebo hyperalgesia by changing brain excitability

Significance Although previous studies have extensively studied the neurobiological mechanisms of placebo and nocebo effects, ways to manipulate these effects to yield further benefits remain relatively unknown. We combined simultaneous repeated transcranial direct current stimulation (tDCS)-fMRI, an expectancy manipulation model, and task-based fMRI to investigate the modulatory effects of anodal and cathodal tDCS at the right dorsolateral prefrontal cortex on placebo analgesia and nocebo hyperalgesia. Our results suggest that active tDCS has the potential to boost placebo and blunt nocebo effects and modulate brain activity and connectivity associated with placebo analgesia and nocebo hyperalgesia. These findings provide deeper understanding of mechanistic manipulation of placebo and nocebo effects and may lead to improved clinical outcomes in medical practice. Harnessing placebo and nocebo effects has significant implications for research and medical practice. Placebo analgesia and nocebo hyperalgesia, the most well-studied placebo and nocebo effects, are thought to initiate from the dorsal lateral prefrontal cortex (DLPFC) and then trigger the brain’s descending pain modulatory system and other pain regulation pathways. Combining repeated transcranial direct current stimulation (tDCS), an expectancy manipulation model, and functional MRI, we investigated the modulatory effects of anodal and cathodal tDCS at the right DLPFC on placebo analgesia and nocebo hyperalgesia using a randomized, double-blind and sham-controlled design. We found that compared with sham tDCS, active tDCS could 1) boost placebo and blunt nocebo effects and 2) modulate brain activity and connectivity associated with placebo analgesia and nocebo hyperalgesia. These results provide a basis for mechanistic manipulation of placebo and nocebo effects and may lead to improved clinical outcomes in medical practice.
What Constitutes a “Good Death”?—A Representative Cross-Sectional Survey Among the General Public in Croatia

Understanding the attitudes of a particular society on a “good death” is important when it comes to end-of-life decision-making and palliative care. In the Republic of Croatia no systematic research has been done on the attitudes of the general population about the concept of a “good death”. This cross sectional survey was conducted on a three-stage random sample, stratified by regions, counties and locations within those counties (N = 1203) during November and December, 2019. ANOVA, to determine differences, factor analysis and multiple regression analysis were used. The most important characteristics of a good death outlined by the respondents were: the absence of pain, the presence and unencumberedness of family and loved ones, the importance of a sense of fulfilment and meaning in life in this regard, reconciliation with God, the presence of awareness and sobriety, and the possibility of treatment.
Mineralocorticoid receptor antagonist effect on aldosterone to renin ratio in patients with primary aldosteronism.

PURPOSE We aimed to evaluate the effect of mineralocorticoid receptor antagonists on aldosterone-to-renin ratio in patients with primary aldosteronism. METHODS We prospectively enrolled 121 patients with confirmed primary aldosteronism who started a mineralocorticoid receptor antagonist (canrenone) treatment. Eighteen patients (11 with unilateral and 7 with bilateral primary aldosteronism) composed the short-term study cohort and underwent aldosterone, renin and potassium measurement after 2 and 8 weeks of canrenone therapy. The long-term cohort comprised 102 patients (16 with unilateral and 67 with bilateral primary aldosteronism, and 19 with undetermined subtype) who underwent hormonal and biochemical re-assessment after 2 to 12 months of canrenone therapy. RESULTS Renin and potassium levels showed a significant increase, and aldosterone-to-renin ratio displayed a significant reduction compared with baseline after both a short and long-term treatment. These effects were progressively more evident with higher doses of canrenone and after longer periods of treatment. We demonstrated that canrenone exerted a deep impact on the diagnostic accuracy of the screening test for primary aldosteronism: the rate of false negative tests raised to 16.7%, 38.9%, 54.5% and 72.5% after 2 weeks, 8 weeks, 2-6 months and 7-12 months of mineralocorticoid receptor antagonist treatment, respectively. CONCLUSIONS Mineralocorticoid receptor antagonists should be avoided in patients with hypertension before measurement of renin and aldosterone for screening of primary aldosteronism.
Development and Preclinical Evaluation of New Inhaled Lipoglycopeptides for the Treatment of Persistent Pulmonary Methicillin-Resistant Staphylococcus aureus Infections

Chronic pulmonary methicillin-resistant Staphylococcus aureus (MRSA) disease in cystic fibrosis (CF) has a high probability of recurrence following treatment with standard-of-care antibiotics and represents an area of unmet need associated with reduced life expectancy. We developed a lipoglycopeptide therapy customized for pulmonary delivery that not only demonstrates potent activity against planktonic MRSA, but also against protected colonies of MRSA both in biofilms and within cells, the latter of which have been linked to clinical antibiotic failure. ABSTRACT Chronic pulmonary methicillin-resistant Staphylococcus aureus (MRSA) disease in cystic fibrosis (CF) has a high probability of recurrence following treatment with standard-of-care antibiotics and represents an area of unmet need associated with reduced life expectancy. We developed a lipoglycopeptide therapy customized for pulmonary delivery that not only demonstrates potent activity against planktonic MRSA, but also against protected colonies of MRSA in biofilms and within cells, the latter of which have been linked to clinical antibiotic failure. A library of next-generation potent lipoglycopeptides was synthesized with an emphasis on attaining superior pharmacokinetics (PK) and pharmacodynamics to similar compounds of their class. Our strategy focused on hydrophobic modification of vancomycin, where ester and amide functionality were included with carbonyl configuration and alkyl length as key variables. Candidates representative of each carbonyl attachment chemistry demonstrated potent activity in vitro, with several compounds being 30 to 60 times more potent than vancomycin. Selected compounds were advanced into in vivo nose-only inhalation PK evaluations in rats, where RV94, a potent lipoglycopeptide that utilizes an inverted amide linker to attach a 10-carbon chain to vancomycin, demonstrated the most favorable lung residence time after inhalation. Further in vitro evaluation of RV94 showed superior activity to vancomycin against an expanded panel of Gram-positive organisms, cellular accumulation and efficacy against intracellular MRSA, and MRSA biofilm killing. Moreover, in vivo efficacy of inhaled nebulized RV94 in a 48 h acute model of pulmonary MRSA (USA300) infection in neutropenic rats demonstrated statistically significant antibacterial activity that was superior to inhaled vancomycin.
A Variant of IL1B Is Associated with the Risk and Blood Lipid Levels of Myocardial Infarction in Eastern Chinese Individuals

ABSTRACT In this study, we determined to interpret the effects of the interleukin (IL)1B gene rs1143634 C/T polymorphism on myocardial infarction (MI) risk. This study, conducted in a Chinese Han population, recruited 369 MI patients and 465 controls. The variant of IL1B gene (rs1143634 C/T polymorphism) was genotyped by PCR-RFLP method. In this study, a significant link was shown between the IL1B rs1143634 C/T polymorphism and MI risk. We found that the IL1B rs1143634 C/T polymorphism enhanced the risk of MI in this population. Subgroup analysis detected that the IL1B rs1143634 C/T polymorphism associated with MI susceptibility in males, smokers, and individuals with diabetes mellitus. In addition, the IL1B rs1143634 C/T polymorphism was related with the levels of blood lipids including low-density lipoprotein (LDL), and total cholesterol (TC). This study uncovers that the IL1B rs1143634 C/T polymorphism may associate with the risk and blood lipid levels of MI in an Eastern Chinese Han population. Abbreviations: MI: myocardial infarction; IL-1: Interleukin-1; SNP: single nucleotide polymorphism; BMI: Body Mass Index; HDL: high-density lipoprotein; TC: total cholesterol; TG: triglyceride; LDL: low-density lipoprotein; PCR: polymerase chain reaction; 95% CI: 95% confidence interval; OR: odds ratio
Knockout of a highly GC‐rich gene in Burkholderia pyrrocinia by recombineering with freeze‐thawing transformation

Abstract Genetic transformation is a valuable and essential method that provides powerful insights into the gene function of microorganisms and contributes to the construction of engineered bacteria. Here, we developed a novel genetic transformation system to easily knock out a highly GC‐rich gene (74.71% GC) from Burkholderia pyrrocinia JK‐SH007, a biocontrol strain of poplar canker disease. This system revealed a reliable selectable marker (trimethoprim resistance gene, Tmp) and a simplified, efficient transformation method (6,363.64 CFU/μg, pHKT2) that was developed via freeze‐thawing. The knockout recombineering of B. pyrrocinia JK‐SH007 was achieved through a suicide plasmid with a three‐fragment mutagenesis construct. The three‐fragment cassette for mutagenesis was generated by overlap extension and touchdown PCRs and composed of Tmp flanked by GC‐rich upstream and downstream fragments from B. pyrrocinia JK‐SH007. The mutant strain (ΔBpEG), which was verified by PCR, lost 93.3% of its ability to degrade carboxymethyl cellulose over 40 days. Overall, this system may contribute to future research on B. pyrrocinia traits.
The senior anesthesiologists and their medical profession in Korea: based on a survey

Background The number of aging physicians is increasing as the global population ages. With aging, anesthesiologists would be expected to experience changes in their professional position. Therefore, we aimed to investigate the current professional status of Korean anesthesiologists aged over 60 years. Methods Registered anesthesiologists aged over 60 years in Korea were invited for a survey. The questionnaire addressed 10 subjects with 40 questions that focused on demographics, practical activities, work conditions, difficulties experienced due to physical changes caused by aging, and economic status. Results In total, 122 anesthesiologists responded to the survey (response rate: 15.7%). Of them, 30.3% were working in honorary and advisory positions at tertiary hospitals, while 19.7% were working as pain physicians. Majority of the respondents were working for 5 days a week (41.8%) and 6–8 hours/day (48.4%). Majority of them (79.5%) were generally satisfied with their present life. Conclusions Majority of the senior anesthesiologists were working at general hospitals and they reported being “satisfied” with the current status of their life. However, the clinical practice and retirement strategies of senior anesthesiologists need to be evaluated systematically to prepare for the continuing gradual increase in the number of senior anesthesiologists.
WhatsApp-propriate? A retrospective content analysis of WhatsApp use and potential breaches in confidentiality among a team of doctors at a district hospital, South Africa.

BACKGROUND There has been a steady increase in the use of electronic media and instant messaging among healthcare professionals, where it has been almost universally adopted in the workplace. The use of WhatsApp and its perceived benefits in healthcare have been extensively studied; however, there are concerns regarding the potential for ethical breaches in confidentiality through shared electronic patient information. OBJECTIVES To identify the usage characteristics and incidence of shared patient information with WhatsApp use in a team of medical doctors in an unobserved and unregulated setting. METHODS We conducted a retrospective cross-sectional content analysis of WhatsApp messages (n=3 340) among a team of 20 doctors in a South African district hospital over 6 months. All messages found within this time period were allocated unique identifiers. The text and image messages were thematically grouped into four categories, i.e. clinical care, resource allocation, social and administrative. Messages that contained patient-identifying information were included in the analysis. RESULTS Of a total of 3 340 messages sent, 220 (6.6%) contained patient-identifying information. Of these, 109 (3.3%) contained non-anonymised patient information, while in 111 (3.3%) messages, the information was anonymised. The likelihood of sharing patient identifiers was proportionally much higher in shared images (odds ratio (OR) 5.1; 95% confidence interval (CI) 3.2 - 8.2; p<0.0001) compared with text messages, and in messages that related to clinical care (OR 9.3; 95% CI 2.2 - 38.8; p=0.0023) compared with those sent for resource allocation, and social or administrative purposes. CONCLUSIONS Non-anonymised patient identifiers were found in 3.3% of messages, constituting the potential for breaching patient confidentiality. While WhatsApp groups have significant utility in co-ordinating aspects of clinical care, resource allocation, as well as social and administrative functions, the safe use of WhatsApp should be promoted to ensure that patient confidentiality is maintained.
Altruism in Parkinson's disease.

Objective: Reward-based decision-making is a growing area of research in Parkinson's disease (PD), a disorder characterized by alterations in dopamine and cortico-striatal circuits. While reward is typically operationalized as a gain, altruistic decisions also engage the reward system in fMRI studies. Although altruism comes at a cost, individuals may be motivated by the social reward associated with benefitting another. At present, it is unclear how PD affects altruism because both increased egoistic tendencies and increased generosity have been documented. Method: To address this, 32 individuals with PD and 32 age-matched healthy controls completed two tasks of implicit and explicit altruism. First, in an intertemporal choice task, participants chose between a smaller immediate or larger later outcome. Outcome types included gains, losses, and donations, and an implicit altruism measure was derived. Second, participants completed two versions of the dictator game, which assesses nonreciprocal giving and yields an explicit measure of altruism. Results: Patients and controls showed similar altruism in the intertemporal choice task and in a dictator game for a charity, but patients were more generous than controls in the dictator game in which the recipient was a stranger. Among patients, altruism measures were moderated by laterality of hemispheric burden and medication type. Conclusions: This study was the first to examine altruistic decision-making in PD patients using both implicit and explicit measures. PD patients were neither overly generous nor egoistic in their decisions, although some disease and treatment characteristics may have a modest association with altruism in PD. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
PREPARATION AND BIOLOGICAL ACTIVITY

INTRODUCTION 507 I. α-CYCLOPROPYLPHOSPHONATES 507 1. via Diazomethylphosphonate 508 2. via Carbon-transfer from Diazoalkanes to Vinylphosphonates 515 3. via Other Carbon-transfer Methods 516 4. via Intramolecular Cyclization 523 5. via Arbuzov Reactions 524 II. β-CYCLOPROPYLPHOSPHONATES 526 III. γ-CYCLOPROPYLPHOSPHONATES 530 IV. ω-CYCLOPROPYLPHOSPHONATES 533 V. CYCLOPROPANE STRUCTURES WITH OTHER PHOSPHORUS GROUPS . 536 VI. CONCLUSIONS 537 REFERENCES 538 ORGANIC PREPARATIONS AND PROCEDURES INT., 40 (6), 505-542 (2008)
Disposition of Dietary Polyphenols in Breast Cancer Patients' Tumors, and their Associated Anticancer Activity: the Particular Case of Curcumin.

SCOPE Some polyphenol-derived metabolites reach human breast cancer (BC) tissues at concentrations that induce cell senescence. However, this is unknown for isoflavones, curcuminoids, and lignans. We evaluated here their metabolic profiling in normal (NT) and malignant (MT) mammary tissues of newly-diagnosed BC patients and explored the tissue-occurring metabolites' anticancer activity. METHODS AND RESULTS Patients (n = 26) consumed 3 capsules/day (turmeric, red clover, and flaxseed extracts plus resveratrol; 296.4 mg phenolics/capsule) from biopsy-confirmed diagnosis to surgery (5±2 days) or did not consume capsules (n = 13). NT and MT, blood, and urine were analyzed by UPLC-QTOF-MS using targeted metabolomics. Anticancer activity was tested in MCF-7 and MDA-MB-231 BC cells. Mainly phase-II metabolites were detected (108, 84, 49, and 47 in urine, plasma, NT, and MT, respectively). Total metabolite concentrations reached 10.7±11.1 and 2.5±2.4 μmol L-1 in NT and MT, respectively. Free curcumin, but not its glucuronide, was detected in the tissues (1.1±1.8 and 0.2±0.2 μmol L-1 in NT and MT, respectively). Breast tissue-occurring metabolites' antiproliferation was mainly exerted in p53-wild-type MCF-7 cells by curcuminoids through cell cycle arrest, senescence, and apoptosis induction via p53/p21 induction, while isoflavone-derived metabolites exerted estrogenic-like activity. CONCLUSION Curcuminoids could be coadjuvants that might help fight BC upon regular consumption. This article is protected by copyright. All rights reserved.
Atrial cardiopathy in embolic stroke of undetermined source

Atrial cardiopathy is one of the most common potential sources of thromboembolism for embolic stroke of undetermined source (ESUS). The study aims to investigate the incidence of atrial cardiopathy (defined by severe left atrial enlargement (sLAE) or elevated serum N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) > 250 pg/ml) in patients with ESUS and compare with other stroke subtypes.
In South Africa, a 2-dose Oxford/AZ vaccine did not prevent mild to moderate COVID-19 (cases mainly B.1.351 variant)

SOURCE CITATION Madhi SA, Baillie V, Cutland CL, et al. Efficacy of the ChAdOx1 nCoV-19 Covid-19 vaccine against the B.1. 351 variant. N Engl J Med. 2021. [Epub ahead of print. ] 33725432.