Miracle-dz/UniFAR-FTUs huggingface dataset:
FACTORS ASSOCIATED WITH INADEQUATE MILK CONSUMPTION AMONG ADOLESCENTS: NATIONAL SCHOOL HEALTH SURVEY - PENSE 2012

ABSTRACT Objective: To identify the prevalence and factors associated with inadequate milk consumption among adolescents. Methods: This was a cross-sectional study based on secondary data from the National School Health Survey (2012), a Brazilian survey carried out using a self-administered questionnaire in a representative sample of 9th-grade students from public and private schools. The frequency of milk intake and its association with socio-demographic characteristics, food consumption and physical activity were estimated. A descriptive and inferential analysis of factors associated with inadequate milk consumption (no consumption at least one of the seven days of the week) was performed. A multiple logistic model was adjusted to control confounders. Results: The sample included 108,828 adolescents and inadequate milk consumption ocurred in 58.9%. The final model included nine variables independently associated with inadequate milk intake: breakfast frequency less than 4 days per week (odds ratio [OR]=2.40; p<0.001), unprocessed or minimally processed foods intake less than 5 days per week (OR=1.93; p<0.001), living in the northeast region (OR=1.39; p<0.001), less maternal schooling (OR=1.35; p<0.001), physical inactivity (OR=1.33; p<0.001), attending public school (OR=1.26; p<0.001), not being white (OR=1.14; p<0.001), being older than 14 years old (OR=1.13; p<0.001) and having a habit of eating meals while watching TV or studying (OR=1.04; p=0.036). Conclusions: Inadequate milk consumption is prevalent among Brazilian adolescents. The identification of associated factors suggests the need to develop nutritional guidance strategies for the prevention of diseases that result from low calcium intake.
Modulation of nanoparticle uptake, intracellular distribution, and retention with docetaxel to enhance radiotherapy.

OBJECTIVE One of the major issues in current radiotherapy (RT) is the normal tissue toxicity. A smart combination of agents within the tumor would allow lowering the RT dose required while minimizing the damage to healthy tissue surrounding the tumor. We chose gold nanoparticles (GNPs) and docetaxel (DTX) as our choice of two radiosensitizing agents. They have a different mechanism of action which could lead to a synergistic effect. Our first goal was to assess the variation in GNP uptake, distribution, and retention in the presence of DTX. Our second goal was to assess the therapeutic results of the triple combination, RT/GNPs/DTX. METHODS We used HeLa and MDA-MB-231 cells for our study. Cells were incubated with GNPs (0.2 nM) in the absence and presence of DTX (50 nM) for 24 h to determine uptake, distribution, and retention of NPs. For RT experiments, treated cells were given a 2 Gy dose of 6 MV photons using a linear accelerator. RESULTS Concurrent treatment of DTX and GNPs resulted in over 85% retention of GNPs in tumor cells. DTX treatment also forced GNPs to be closer to the most important target, the nucleus, resulting in a decrease in cell survival and increase in DNA damage with the triple combination of RT/ GNPs/DTX vs RT/DTX. Our experimental therapeutics results were supported by Monte Carlo simulations. CONCLUSION The ability to not only trap GNPs at clinically feasible doses but also to retain them within the cells could lead to meaningful fractionated treatments in future combined cancer therapy. Furthermore, the suggested triple combination of RT/GNPs/DTX may allow lowering the RT dose to spare surrounding healthy tissue. ADVANCES IN KNOWLEDGE This is the first study to show intracellular GNP transport disruption by DTX, and its advantage in radiosensitization.
Age at First Alcohol Use as a Possible Risk Factor for Adolescent Acute Alcohol Intoxication Hospital Admission in the Netherlands

Background The primary objective of this study is to determine whether age at first alcohol use is a determinant for adolescent acute alcohol intoxication characteristics, such as age at first acute alcohol intoxication and blood alcohol concentration (BAC) at hospital admission. Around the world, as in the Netherlands, a key aim of alcohol policy is to postpone the age at first alcohol use. This is based on cohort studies that indicate a relationship between a younger age at first alcohol use and subsequent adult alcohol use disorders. Methods This study was conducted using a cohort of data comprising individuals under 18 years of age. Data were collected between 2007 and 2017 by the Dutch Pediatric Surveillance System (NSCK) in order to monitor trends in admissions for acute alcohol intoxication. Multivariate linear regression analyses were used to determine the association between age at first alcohol use and acute alcohol intoxication characteristics, such as age at first acute alcohol intoxication and BAC at admission. Results This study indicates that among adolescents admitted for acute alcohol intoxication, adolescents who started drinking at ≤ 14 years of age are significantly more often female, lower educated, and raised in nontraditional family structures than adolescents who started drinking between 15 and 18 years of age. Multiple linear regression analyses indicated that age at first alcohol use, corrected for covariates, significantly predicted the age at acute alcohol intoxication and BAC at admission. The association between age at first alcohol use and age at intoxication was also found to be clinically relevant. Conclusions Although causation cannot be implied based on the results of these analyses, the results of this study suggest that interventions delaying the age at first alcohol use could be successful in increasing the average age that adolescents are admitted to the hospital for acute alcohol intoxication.
The chaperone MeHSP90 recruits MeWRKY20 and MeCatalase1 to regulate drought stress resistance in cassava.

The 90-kDa heat shock protein (HSP90) is widely involved in various developmental processes and stress responses in plants. However, the molecular chaperone HSP90-constructed protein complex and its function in cassava remain elusive. In this study, we report that HSP90 is essential for drought stress resistance in cassava by regulating abscisic acid (ABA) and hydrogen peroxide (H2 O2 ) using two specific protein inhibitors of HSP90 (geldanamycin (GDA) and radicicol (RAD)). Among 10 MeHSP90s, the transcript of MeHSP90.9 is largely induced during drought stress. Further investigation identifies MeWRKY20 and MeCatalase1 as MeHSP90.9-interacting proteins. MeHSP90.9-, MeWRKY20-, or MeCatalase1-silenced plants through virus-induced gene silencing (VIGS) display drought sensitivity in cassava, indicating that they are important to drought stress response. MeHSP90.9 can promote the direct transcriptional activation of MeWRKY20 on the W-box element of MeNCED5 promoter, encoding a key enzyme in ABA biosynthesis. Moreover, MeHSP90.9 positively regulates the activity of MeCatalase1, and MeHSP90.9-silenced cassava leaves accumulate more H2 O2 under drought stress. Taken together, we demonstrate that the MeHSP90.9 chaperone complex is a regulator of drought stress resistance in cassava.
A study on depression in elderly inmates living in old age homes in Gujarat

Background: Conclusion: Active ageing aims to extend healthy life expectancy and quality of life for all people as they age, including those who are frail, disabled and in need of care. Globally, and developing countries in particular; measures to help older people remain healthy and active are a necessity, not a luxury. The study was aimed to assess depression among elderly inmates in old age homes (OAH). A cross sectional study was conducted on 314 elderly residing in 11 OAH of central Gujarat. Socio-demographic factors, physical examination and mental health data was collected and analyzed with SPSS software. Chi-square test was applied to find out association between variables. Maximum number of inmates (31.9%) was in the age group of 65-69 years. Depression was observed more in not working inmates (65.8%), as well as in those who stayed for shorter duration (64.1%). Also, it was noticeably present in those having visual problem (66.7%), hearing problem (83.3%) and sleeping problem (66.7%). Incidence of depression was less in inmates who were living with spouse (57.7%). Urbanization and industrialization leads to outward migration of younger peoples away from parents. Prevalence of depression was significantly more with increased age, in females and with hearing and sleeping problem. The prevalence was significantly higher in inmates who stayed for shorter duration in old age homes.
Osteoarthritis in the Middle-Aged and Elderly in China: Prevalence and Influencing Factors

Background: Osteoarthritis is a common joint disease, with the acceleration of the aging process in China, it has troubled the middle-aged and elderly. There have been some epidemiological studies of osteoarthritis conducted in one single site, and most of them were on knee osteoarthritis. The results varied greatly between different surveys. There was still a lack of large-scale and multicenter epidemiological studies of osteoarthritis. This paper aimed to estimate the overall prevalence of lumbar osteoarthritis, cervical osteoarthritis, hand osteoarthritis, knee osteoarthritis, and hip osteoarthritis in the middle-aged and elderly in China by summarizing the existing publications. Methods: We comprehensively searched publications on 1 January 2019 in PubMed, Web of Science, Embase, Cochrane Library, CBM, CNNI, VIP, and Wan Fang. Epidemiological publications on osteoarthritis in the middle-aged and elderly Chinese published from 2000 to 2018 were summarized and analyzed by means of systematic review and meta-analysis. Data of prevalence of osteoarthritis in five joints were extracted from the included publications. The Hoy 2012 tool was used to assess the risk of bias of included studies. Results: After performing a systematic search in eight databases and manually searching, 3058 articles were obtained, and 21 articles were included in the meta-analysis. Lumbar osteoarthritis was the most prevalent with a prevalence of 25.03% (95% CI: 0.1444–0.3562). The prevalence of knee osteoarthritis followed, which was 21.51% (95% CI: 0.1873–0.2429). The prevalence of cervical osteoarthritis was 20.46% (95% CI: 0.1244–0.2849). The prevalence of hand osteoarthritis was 8.99% (95% CI: 0.0435–0.1364). The prevalence of hip osteoarthritis was not pooled due to its lack of data. Higher prevalence of knee, hand, lumbar, and cervical osteoarthritis was seen in the female group and southern regions. The prevalence of knee and hand osteoarthritis increased with age. The prevalence of lumbar and cervical osteoarthritis increased with age. There was also a trend that the prevalence increased with age before 70 years old and slightly decreased in the oldest ages. Conclusions: The lumbar joint was the joint most prevalently affected by osteoarthritis, followed by the prevalence of knee, cervical, hand, and hip joint osteoarthritis. Women, the southern population, and the older population are more susceptible to osteoarthritis. The paucity of epidemiology data of osteoarthritis in China appeals for more population-based surveys being conducted in the future. Based on the relatively high prevalence of osteoarthritis obtained from this review, self-management and community-based management should be considered, which can provide experience from the management of hypertensions and diabetes.
Micellar Aggregation Behavior of Alkylaryl Sulfonate Surfactants for Enhanced Oil Recovery

Alkylaryl sulfonate is a typical family of surfactants used for chemically enhanced oil recovery (EOR). While it has been widely used in surfactant–polymer flooding at Karamay Oilfield (40 °C, salinity 14,000 mg/L), its aggregation behavior in aqueous solutions and the contribution of aggregation to EOR have not been investigated so far. In this study, raw naphthenic arylsulfonate (NAS) and its purified derivatives, alkylaryl monosulfonate (AMS) and alkylaryl disulfonate (ADS), were examined under simulated temperature and salinity environment of Karamay reservoirs for their micellar aggregation behavior through measuring surface tension, micellar size, and micellar aggregation number. It was found that all three alkylaryl sulfonate surfactants could significantly lower the surface tension of their aqueous solutions. Also, it has been noted that an elevation both in temperature and salinity reduced the surface tension and critical micellar concentration. The results promote understanding of the performance of NAS and screening surfactants in EOR.
Endoplasmic Reticulum Protein Disulfide Isomerase Shapes T Cell Efficacy for Adoptive Cellular Therapy of Tumors

Effective cancer therapies simultaneously restrict tumor cell growth and improve anti-tumor immune responses. Targeting redox-dependent protein folding enzymes within the endoplasmic reticulum (ER) is an alternative approach to activation of the unfolded protein response (UPR) and a novel therapeutic platform to induce malignant cell death. E64FC26 is a recently identified protein disulfide isomerase (PDI) inhibitor that activates the UPR, oxidative stress, and apoptosis in tumor cells, but not normal cell types. Given that targeting cellular redox homeostasis is a strategy to augment T cell tumor control, we tested the effect of E64FC26 on healthy and oncogenic T cells. In stark contrast to the pro-UPR and pro-death effects we observed in malignant T cells, we found that E64FC26 improved viability and limited the UPR in healthy T cells. E64FC26 treatment also diminished oxidative stress and decreased global PDI expression in normal T cells. Oxidative stress and cell death are limited in memory T cells and we found that PDI inhibition promoted memory traits and reshaped T cell metabolism. Using adoptive transfer of tumor antigen-specific CD8 T cells, we demonstrate that T cells activated and expanded in the presence of E64FC26 control tumor growth better than vehicle-matched controls. Our data indicate that PDI inhibitors are a new class of drug that may dually inhibit tumor cell growth and improve T cell tumor control.
TAK1 inhibition in mouse astrocyte cultures ameliorates cytokine‐induced chemokine production and neutrophil migration

Systemic inflammation can exacerbate symptoms of many neurological diseases. This effect may be facilitated by glial cells of the central nervous system (CNS) that alter their transcriptional responses and up‐regulate cytokine and chemokine expression which can, in turn trigger immune surveillance. In this study, we sought to determine the effects of pro‐inflammatory cytokine stimulation (TNF, IL‐1α, IL‐1β) on astrocyte and microglia chemokine secretion. Primary cultures of astrocytes or microglia were stimulated with the recombinant cytokines and the levels of secreted chemokines were semi‐quantitatively determined using a chemokine‐specific proteome profiler array and densitometry. Pharmacological inhibitors were used to determine the effects of p38 MAPK, JNK, ERK1/2, NFkB, and transforming growth factor beta‐associated kinase 1 (TAK1) in controlling chemokine production. Finally, neutrophil migration assays were performed to demonstrate functionality. Our data show that stimulated astrocytes secrete at least eight chemokines as a response to cytokine stimulation. These include those involved in neutrophil chemo‐attraction and proved capable of promoting neutrophil migration in vitro. In contrast, microglia up‐regulated few chemokines in response to cytokine stimulation and did not promote neutrophil migration. However, microglia readily secreted chemokines following stimulation with the toll‐like receptor agonists. Finally, we show that both the production of chemokines and neutrophil migration resulting from cytokine stimulation of astrocytes was dependent on TAK1 signaling. Collectively, this study adds to the understanding of how astrocytes and microglia respond to stimuli and their role in promoting neutrophil migration to the CNS during inflammatory conditions.
Economic evaluation of olmesartan/amlodipine fixed-dose combination for hypertension treatment in China

Abstract Objectives: To evaluate the cost-effectiveness of olmesartan/amlodipine fixed-dose combination vs olmesartan and amlodipine free combination, amlodipine single drug, and valsartan/amlodipine fixed-dose combination in the treatment of hypertensive patients from payer perspective in China. Methods: A Markov model was constructed, which included five health states of hypertensive patients who are aged 35–84 years at baseline and free of cardiovascular disease. Clinical data were obtained from a network meta-analysis. Epidemiology data, adverse events (AEs), cost, and utility data were obtained from the literature. The cost associated with AEs was estimated based on the cost of same symptoms of hypertensive patients in an electric medical record database. The model projected quality-adjusted life years (QALYs) gained, total costs per patient in a 20-year time horizon, and incremental cost-effectiveness ratios. Probability sensitivity analyses (PSA) and one-way sensitivity analyses were conducted for the main parameters to test the robustness of the model. Results: Compared to olmesartan and amlodipine free combination, amlodipine, and valsartan/amlodipine fixed-dose combination, treatment with olmesartan/amlodipine fixed-dose combination led to fewer CVD events and deaths; resulted in an incremental cost of ¥−5,439 ($−791.36), ¥6,530 ($950.09), and ¥−1,019 ($−148.26) and gained additional QALYs of 0.052, 0.094, and 0.037 per patient, respectively. Compared with olmesartan and amlodipine free combination and valsartan/amlodipine fixed-dose combination, olmesartan/amlodipine fixed-dose combination was dominant. Compared with amlodipine alone, the incremental cost-effectiveness ratios were below the WHO recommended cost-effectiveness threshold, indicating the olmesartan/amlodipine fixed-dose combination was a cost-effective option for hypertensive patients in China. The 10-years’ time horizon scenario analysis showed similar results to the 20-years’ time horizon. Probabilistic sensitivity analysis and one-way sensitivity analyses showed the robustness of the model results. Conclusions: Olmesartan/amlodipine fixed-dose combination confers better health outcomes and costs less compared with olmesartan and amlodipine free combination and valsartan/amlodipine fixed-dose combination, and is cost-effective compared to amlodipine for hypertension treatment in China.
Rapid affinity purification of intracellular organelles using a twin strep tag

ABSTRACT Cells are internally organized into compartmentalized organelles that execute specialized functions. To understand the functions of individual organelles and their regulations, it is critical to resolve the compositions of individual organelles, which relies on a rapid and efficient isolation method for specific organellar populations. Here, we introduce a robust affinity purification method for rapid isolation of intracellular organelles (e.g. lysosomes, mitochondria and peroxisomes) by taking advantage of the extraordinarily high affinity between the twin strep tag and streptavidin variants. With this method, we can isolate desired organelles with high purity and yield in 3 min from the post-nuclear supernatant of mammalian cells or less than 8 min for the whole purification process. Using lysosomes as an example, we show that the rapid procedure is especially useful for studying transient and fast cellular activities, such as organelle-initiated signaling and organellar contents of small-molecular metabolites. Therefore, our method offers a powerful tool to dissect spatiotemporal regulation and functions of intracellular organelles. Highlighted Article: A method for rapid, high purity, isolation of lysosomes, mitochondria and peroxisomes from cell lysate was developed based on twin strep tag binding to Strep-Tactin XT magnetic beads.
8-chloroadenosine alters the metabolic profile and downregulates antioxidant and DNA damage repair pathways in macrophages.

The exposure of RNA and DNA nucleobases to the oxidant hypochlorous acid (HOCl) results in the generation of different stable chlorinated products. These chlorinated nucleobases are formed in vivo, particularly in chronic inflammatory pathologies, which are characterised by the over-production of HOCl by myeloperoxidase. As such, chlorinated nucleosides are used as biomarkers of inflammation. However, these compounds have also attracted attention as potential chemotherapeutic agents with 8-chloro-adenosine (8ClA), for example, currently in clinical trials for the treatment of haematological cancers, including chronic lymphocytic leukemia. 8ClA has mainly RNA-directed effects in malignant cells, with exposure resulting in ATP depletion and apoptotic cell death. Whether 8ClA has significant reactivity with non-malignant cells has not been widely studied. Here we show that prolonged incubation of J774A.1 macrophage-like cells with 8ClA results in the perturbation of cellular metabolism and apoptotic cell death. These effects are associated with an accumulation of 8-chloro-adenosine triphosphate (8Cl-ATP), an effect not seen in experiments utilising other chlorinated nucleosides. Exposure of the macrophages to 8ClA did not significantly change basal mitochondrial respiration or glycolysis, but resulted in an increase in maximal mitochondrial respiration as well as spare respiratory capacity within these cells. Additionally, 8ClA exposure also altered the mRNA expression of a range of antioxidant and DNA damage repair genes in the macrophages, in a manner consistent with a reduction in the capacity of the cells to cope with oxidative stress and repair DNA damage. Taken together, these results provide new insight into pathways by which the production of HOCl during chronic inflammation could perturb immune cell function, and may also have implications for the use of 8ClA as a chemotherapeutic drug.
Dietary protein insufficiency: an important consideration in fatty liver disease?

Abstract Dietary protein insufficiency has been linked to excessive TAG storage and non-alcoholic fatty liver disease (NAFLD) in developing countries. Hepatic TAG accumulation following a low-protein diet may be due to altered peroxisomal, mitochondrial and gut microbiota function. Hepatic peroxisomes and mitochondria normally mediate metabolism of nutrients to provide energy and substrates for lipogenesis. Peroxisome biogenesis and activities can be modulated by odd-chain fatty acids (OCFA) and SCFA that are derived from gut bacteria, for example, propionate and butyrate. Also produced during amino acid metabolism by peroxisomes and mitochondria, propionate and butyrate concentrations correlate inversely with risk of obesity, insulin resistance and NAFLD. In this horizon-scanning review, we have compiled available evidence on the effects of protein malnutrition on OCFA production, arising from loss in mitochondrial, peroxisomal and gut microbiota function, and its association with lipid accumulation in the liver. The methyl donor amino acid composition of dietary protein is an important contributor to liver function and lipid storage; the presence and abundance of dietary branched-chain amino acids can modulate the composition and metabolic activity of the gut microbiome and, on the other hand, can affect protective OCFA and SCFA production in the liver. In preclinical animal models fed with low-protein diets, specific amino acid supplementation can ameliorate fatty liver disease. The association between low dietary protein intake and fatty liver disease is underexplored and merits further investigation, particularly in vulnerable groups with dietary protein restriction in developing countries.