Miracle-dz/UniFAR-FTUs huggingface dataset:
LincRNA-immunity landscape analysis identifies EPIC1 as a regulator of tumor immune evasion and immunotherapy resistance

EPIC1-EZH2 axis activation emerges as a targetable mechanism for tumor immune evasion and immunotherapy resistance. Through an integrative analysis of the lincRNA expression and tumor immune response in 9,626 tumor samples across 32 cancer types, we developed a lincRNA-based immune response (LIMER) score that can predict the immune cells infiltration and patient prognosis in multiple cancer types. Our analysis also identified tumor-specific lincRNAs, including EPIC1, that potentially regulate tumor immune response in multiple cancer types. Immunocompetent mouse models and in vitro co-culture assays demonstrated that EPIC1 induces tumor immune evasion and resistance to immunotherapy by suppressing tumor cell antigen presentation. Mechanistically, lincRNA EPIC1 interacts with the histone methyltransferase EZH2, leading to the epigenetic silencing of IFNGR1, TAP1/2, ERAP1/2, and MHC-I genes. Genetic and pharmacological inhibition of EZH2 abolish EPIC1’s immune-related oncogenic effect and its suppression of interferon-γ signaling. The EPIC1-EZH2 axis emerges as a potential mechanism for tumor immune evasion that can serve as therapeutic targets for immunotherapy.
Effects of Water Restriction and Water Replenishment on the Content of Body Water with Bioelectrical Impedance among Young Adults in Baoding, China: A Randomized Controlled Trial (RCT)

Insufficient water intake may affect body composition. The purpose of this research was to explore the effects of water restriction and replenishment on body composition and to evaluate the optimum amount of water that improves body composition. A total of 76 young adults aged 18–23 years old (40 males and 36 females) in Baoding, China, were recruited in this randomized controlled trial, with a 100% completion rate. After fasting overnight for 12 h, at 8:00 a.m. of day 2, a baseline test, including anthropometric indices and collection of urine and blood samples, was explored. Participants were then subjected to water restriction for 24 h, and three meals with ≤75% water content were provided. At 8:00 AM of day 3, the same indices were determined as a dehydration test. Then, participants were randomly assigned into four groups: three water replenishment groups (WR groups 1, 2, and 3 given 1000, 500, and 200 mL of purified water, respectively) and one non-replenishment group (NR group, with no water). After 90 min, the same measurements were performed as a rehydration test. Compared with the baseline test, during the dehydration test, the intracellular water to total body water ratio (ICW/TBW) increased; and extracellular water (ECW), ECW/TBW (extracellular water to total body water ratio), and TBW decreased (all p < 0.05). For males, significant differences were found in ECW, ECW/ICW (extracellular water to intracellular water ratio), ICW/TBW, and ECW/TBW (all p < 0.05); for females, significant reductions were found in ICW, ECW, TBW, ECW/ICW, ICW/TBW, and ECW/TBW (all p < 0.05). Furthermore, significant differences were found in ICW, ECW, ICW/TBW, ECW/TBW, ECW/ICW, TBW, and TBW/BW between males and females during the baseline and dehydration test (all p < 0.05). Comparing the dehydration test with the rehydration test, there were significant interactions between time × volume in ICW and TBW (F = 3.002, p = 0.036; F = 2.907, p = 0.040); in males, these were only found in ICW (F = 3.061, p = 0.040); in females, they were found in ICW and TBW (F = 3.002, p = 0.036; F = 2.907, p = 0.040). The ICW levels in WR groups 1 and 2 were all higher than in the NR group (all p < 0.05); the TBW was higher in WR group 1 than in the NR group (p < 0.05). No significant differences were found between WR groups 1 and 2, either in males or in females (all p > 0.05). In the rehydration test, significant differences in body composition were found between males and females among the four groups (all p < 0.05). Water restriction had adverse effects on body composition, and females were more susceptible to water restriction than males. Water replenishment improved the water content of body composition, alleviating the adverse effects of water restriction on ICW and TBW. After water restriction for 36 h, the optimum volume of water to improve body composition among young male adults was 1000 mL, but this was not the case for females.
Proteomics Complementation of the Rat Uterotrophic Assay for Estrogenic Endocrine Disruptors: A Roadmap of Advancing High Resolution Mass Spectrometry-Based Shotgun Survey to Targeted Biomarker Quantifications

The widely used rat uterotrophic assay to assess known and potential estrogenic compounds only considers uterine weight gain as endpoint measurement. To complement this method with an advanced technology that reveals molecular targets, we analyzed changes in protein expression using label-free quantitative proteomics by nanoflow liquid chromatography coupled with high-resolution mass spectrometry and tandem mass spectrometry from uterine protein extracts of ovariectomized rats after daily 17β-estradiol exposure for five days in comparison with those of vehicle-treated control animals. Our discovery-driven study revealed 165 uterine proteins significantly regulated by estrogen treatment and mapped by pathway analyses. Estrogen-regulated proteins represented cell death, survival and development, cellular growth and proliferation, and protein synthesis as top molecular and cellular functions, and a network found with the presence of nuclear estrogen receptor(s) as a prominent molecular node confirmed the relevance of our findings to hormone-associated events. An exploratory application of targeted proteomics to bisphenol A as a well-known example of an estrogenic endocrine disruptor is also presented. Overall, the results of this study have demonstrated the power of combining untargeted and targeted quantitative proteomic strategies to identify and verify candidate molecular markers for the evaluation of endocrine-disrupting chemicals to complement a conventional bioassay.
A risk score to predict in-hospital mortality in patients with acute coronary syndrome at early medical contact: results from the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS) Project

Background A number of models have been built to evaluate risk in patients with acute coronary syndrome (ACS). However, accurate prediction of mortality at early medical contact is difficult. This study sought to develop and validate a risk score to predict in-hospital mortality among patients with ACS using variables available at early medical contact. Methods A total of 62,546 unselected ACS patients from 150 tertiary hospitals who were admitted between 2014 and 2017 and enrolled in the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS) project, were randomly assigned (at a ratio of 7:3) to a training dataset (n=43,774) and a validation dataset (n=18,772). Based on the identified predictors which were available prior to any blood test, a new point-based risk score for in-hospital death, CCC-ACS score, was derived and validated. The CCC-ACS score was then compared with Global Registry of Acute Coronary Events (GRACE) risk score. Results The in-hospital mortality rate was 1.9% in both the training and validation datasets. The CCC-ACS score, a new point-based risk score, was developed to predict in-hospital mortality using 7 variables that were available before any blood test including age, systolic blood pressure, cardiac arrest, insulin-treated diabetes mellitus, history of heart failure, severe clinical conditions (acute heart failure or cardiogenic shock), and electrocardiographic ST-segment deviation. This new risk score had an area under the curve (AUC) of 0.84 (P=0.10 for Hosmer-Lemeshow goodness-of-fit test) in the training dataset and 0.85 (P=0.13 for Hosmer-Lemeshow goodness-of-fit test) in the validation dataset. The CCC-ACS score was comparable to the Global Registry of Acute Coronary Events (GRACE) score in the prediction of in-hospital death in the validation dataset. Conclusions The newly developed CCC-ACS score, which utilizes factors that are acquirable at early medical contact, may be able to stratify the risk of in-hospital death in patients with ACS. Clinical trial registration URL: http://www.clinicaltrials. gov. Unique identifier: NCT02306616.
Rapid synthesis of highly luminescent InP and InP/ZnS nanocrystals

We report a simple method for the fast synthesis of highly photoluminescent InP and InP/ZnS core–shell nanocrystals (NCs) covering a wide range of emissions from blue to the near infrared. Both InP and InP/ZnS NCs were prepared in one-step, in a one-pot reaction within 20 min using an InCl3 complex as a precursor and zinc carboxylate as an initiator and stabilizer. The quantum yields of the InP and InP/ZnS NCs were 30% and 60%, respectively. This new synthetic method allows fast and reproducible preparation of InP and InP/ZnS NCs with a quality comparable to that of the frequently used CdSe-based ones. It is anticipated that these particles can be used to replace CdSe for many applications.
Antioxidant role of L-carnitine in an experimental model of oxidative stress induced by increased fructose consumption.

OBJECTIVES To evaluate the role of L-carnitine (LC) on fructose-induced oxidative stress in Holtzman rats. MATERIALS AND METHODS An experimental study was carried out during 56 days, in patients assigned to 4 groups: control, control+LC, fructose and fructose+LC. Patients in the fructose group received treatment during 56 days, and those in the LC groups were treated during the last 28 days. Fructose was given on demand and LC was administered orally at a dose of 500 g/kg/24 h. Lipid peroxidation (MDA), superoxide dismutase activity, free LC and mitochondrial and post-mitochondrial proteins were measured in liver tissue. Glycemia, insulin and the homeostasis model assessment of insulin resistance (HOMA-IR) were measured in blood plasma. We measured insulin concentration and studied the histology of pancreatic tissue. RESULTS LC treatment showed a decrease (p < 0.05) of MDA when compared to the control group (21.73 ± 5.36 nmol/g tissue vs. 64.46 ± 7.87 nmol/g tissue). Mitochondrial and post-mitochondrial proteins increased (p < 0.05) in comparison to the control group; pancreatic insulin also increased when compared to the control (341.8 ± 42.3 μUI/ml vs. 70.1 ± 9.6 μUI/ml, p<0.05). The role of LC against fructose-induced oxidative stress did not show any decrease of MDA, but decreased (p < 0.05) SOD Cu/Zn activity (9.39 ± 1.5 USOD/mg protein vs. 13.52 ± 1.5 USOD/mg protein). We observed that LC improves HOMA-IR in blood plasma. Histological analysis of the pancreas showed that the presence of LC increased the number and size of the islets of Langerhans. CONCLUSIONS LC favors changes in the oxidative metabolism and it also contributes to glycemic homeostasis when fructose is consumed.
Functional rarity and evenness are key facets of biodiversity to boost multifunctionality

Significance Identifying species assemblages that boost the provision of multiple ecosystem functions simultaneously (multifunctionality) is crucial to undertake effective restoration actions aiming at simultaneously promoting biodiversity and high multifunctionality in a changing world. By disentangling the effect of multiple traits on multifunctionality in a litter decomposition experiment, we show that it is possible to identify the assemblages that boost multifunctionality across multiple species mixtures originating from six biomes. We found that higher evenness among dissimilar species and the functional attributes of rare species as key biodiversity attributes to enhance multifunctionality and to reduce the abundance of plant pathogens. Our study identifies those species assemblages needed to simultaneously maximize multifunctionality and limit plant disease risks in natural and managed ecosystems. The functional traits of organisms within multispecies assemblages regulate biodiversity effects on ecosystem functioning. Yet how traits should assemble to boost multiple ecosystem functions simultaneously (multifunctionality) remains poorly explored. In a multibiome litter experiment covering most of the global variation in leaf trait spectra, we showed that three dimensions of functional diversity (dispersion, rarity, and evenness) explained up to 66% of variations in multifunctionality, although the dominant species and their traits remained an important predictor. While high dispersion impeded multifunctionality, increasing the evenness among functionally dissimilar species was a key dimension to promote higher multifunctionality and to reduce the abundance of plant pathogens. Because too-dissimilar species could have negative effects on ecosystems, our results highlight the need for not only diverse but also functionally even assemblages to promote multifunctionality. The effect of functionally rare species strongly shifted from positive to negative depending on their trait differences with the dominant species. Simultaneously managing the dispersion, evenness, and rarity in multispecies assemblages could be used to design assemblages aimed at maximizing multifunctionality independently of the biome, the identity of dominant species, or the range of trait values considered. Functional evenness and rarity offer promise to improve the management of terrestrial ecosystems and to limit plant disease risks.
The safety and efficacy of CKD-497 in patients with acute upper respiratory tract infection and bronchitis symptoms: a multicenter, double-blind, double-dummy, randomized, controlled, phase II clinical trial

Background Acute upper respiratory tract infection (AURI) together with acute bronchitis is the most common illness worldwide. Botanical medicines used as expectorants and antitussives have proven to be effective while also having excellent safety margins. We aimed at evaluating the efficacy and safety of a new botanical drug, CKD-497, in patients with AURI and acute bronchitis. Methods In this phase 2 study, 225 patients were enrolled and randomly assigned to one of four treatment groups: placebo (n=55), Synatura® (n=49), CKD-497 200 mg (n=68), or CKD-497 300 mg (n=53). The study drugs were administered three times daily over the course of 7 days. Primary endpoint was the change in the bronchitis severity score (BSS) from baseline to day 7. Secondary endpoint was evaluated based on clinical response rates on days 4 and 7. A safety analysis was also performed. Results Between baseline and day 7, the mean BSS scores decreased significantly in each group (P<0.001): –4.04±1.85, –4.31±1.47, –4.09±1.48, and –4.28±1.69. However, neither the CKD-497 nor Synatura® group showed any significant effect on the difference in BSS change (P=0.75). The rate of clinical response was higher in the CKD-497 300 mg group as compared to the placebo only on day 4 (36% vs. 18%; P<0.05) and those having more severe bronchitis (phlegm score ≥3) showed a significant reduction of total BSS in the Synatura® and CKD-497 groups (P=0.042). No significant adverse events were observed in either of the CKD-497 groups. Conclusions CKD-497 and even the positive control drug had no significant effect on BSS change in this phase 2 clinical trial. However, CKD-497 300 mg had a mild but significant clinical improvement in early bronchitis patients with more severe phlegm. Considering both efficacy and safety, a future study using 300 mg of CKD-497 with a shorter-term endpoint is warranted in patients with more severe bronchitis symptoms.
Identification of RSV Fusion Protein Interaction Domains on the Virus Receptor, Nucleolin

Nucleolin is an essential cellular receptor to human respiratory syncytial virus (RSV). Pharmacological targeting of the nucleolin RNA binding domain RBD1,2 can inhibit RSV infections in vitro and in vivo; however, the site(s) on RBD1,2 which interact with RSV are not known. We undertook a series of experiments designed to: document RSV-nucleolin co-localization on the surface of polarized MDCK cells using immunogold electron microscopy, to identify domains on nucleolin that physically interact with RSV using biochemical methods and determine their biological effects on RSV infection in vitro, and to carry out structural analysis toward informing future RSV drug development. Results of immunogold transmission and scanning electron microscopy showed RSV-nucleolin co-localization on the cell surface, as would be expected for a viral receptor. RSV, through its fusion protein (RSV-F), physically interacts with RBD1,2 and these interactions can be competitively inhibited by treatment with Palivizumab or recombinant RBD1,2. Treatment with synthetic peptides derived from two 12-mer domains of RBD1,2 inhibited RSV infection in vitro, with structural analysis suggesting these domains are potentially feasible for targeting in drug development. In conclusion, the identification and characterization of domains of nucleolin that interact with RSV provide the essential groundwork toward informing design of novel nucleolin-targeting compounds in RSV drug development.
Stationary phases for silver ion chromatography of lipids: Preparation and properties

Procedures for the preparation of stationary phases for several silver ion chromatographic techniques have been surveyed. Thin-layer chromatography (TLC), conventional (normal pressure) column chromatography, solid phase extraction (SPE), high-performance liquid chromatography (HPLC), and supercritical fluid chromatography (SFC) in silver ion mode have been considered. The utilization of these stationary phases for the analysis of fatty acids and triacylglycerols has been demonstrated.
Review of Transport Phenomena and Popular Modelling Approaches in Membrane Distillation

In this paper, the transport phenomena in four common membrane distillation (MD) configurations and three popular modelling approaches are introduced. The mechanism of heat transfer on the feed side of all configurations are the same but are distinctive from each other from the membrane interface to the bulk permeate in each configuration. Based on the features of MD configurations, the mechanisms of mass and heat transfers for four configurations are reviewed together from the bulk feed to the membrane interface on the permeate but reviewed separately from the interface to the bulk permeate. Since the temperature polarisation coefficient cannot be used to quantify the driving force polarisation in Sweeping Gas MD and Vacuum MD, the rate of driving force polarisation is proposed in this paper. The three popular modelling approaches introduced are modelling by conventional methods, computational fluid dynamics (CFD) and response surface methodology (RSM), which are based on classic transport mechanism, computer science and mathematical statistics, respectively. The default assumptions, area for applications, advantages and disadvantages of those modelling approaches are summarised. Assessment and comparison were also conducted based on the review. Since there are only a couple of full-scale plants operating worldwide, the modelling of operational cost of MD was only briefly reviewed. Gaps and future studies were also proposed based on the current research trends, such as the emergence of new membranes, which possess the characteristics of selectivity, anti-wetting, multilayer and incorporation of inorganic particles.
H7N7 Avian Influenza Virus Mutation from Low to High Pathogenicity on a Layer Chicken Farm in the UK

Avian influenza virus (AIV) subtypes H5 and H7 are capable of mutating from low to high pathogenicity strains, causing high mortality in poultry with significant economic losses globally. During 2015, two outbreaks of H7N7 low pathogenicity AIV (LPAIV) in Germany, and one each in the United Kingdom (UK) and The Netherlands occurred, as well as single outbreaks of H7N7 high pathogenicity AIV (HPAIV) in Germany and the UK. Both HPAIV outbreaks were linked to precursor H7N7 LPAIV outbreaks on the same or adjacent premises. Herein, we describe the clinical, epidemiological, and virological investigations for the H7N7 UK HPAIV outbreak on a farm with layer chickens in mixed free-range and caged units. H7N7 HPAIV was identified and isolated from clinical samples, as well as H7N7 LPAIV, which could not be isolated. Using serological and molecular evidence, we postulate how the viruses spread throughout the premises, indicating potential points of incursion and possible locations for the mutation event. Serological and mortality data suggested that the LPAIV infection preceded the HPAIV infection and afforded some clinical protection against the HPAIV. These results document the identification of a LPAIV to HPAIV mutation in nature, providing insights into factors that drive its manifestation during outbreaks.
Sobrevida de Pacientes com Insuficiência Cardíaca Aguda e Fração de Ejeção Intermediária em um País em Desenvolvimento – Estudo de Coorte no Sul do Brasil

Resumo Fundamento A insuficiência cardíaca (IC) com fração de ejeção na faixa média ou intermediária (ICFEI) (em inglês, “ mid-range ejection fraction ) foi recentemente descrita em diretrizes europeia e brasileira recentes sobre o manejo da insuficiência cardíaca (IC). A fração de ejeção (FE) é um parâmetro importante para direcionar terapia e prognóstico. Estudos têm mostrado resultados conflitantes sem dados representativos de países em desenvolvimento. Objetivo Analisar e comparar a taxa de sobrevida em pacientes com ICFEI com pacientes com IC e FE reduzida (ICFEr), e pacientes com IC e FE preservada, e avaliar as características clínicas desses pacientes. Métodos Estudo coorte que incluiu pacientes com IC aguda admitidos no departamento de emergência de um hospital terciário, referência em cardiologia, localizado no sul do Brasil, entre 2009 e 2011. A amostra foi dividida em três grupos de acordo com a FE: reduzida, intermediária e preservada. Curva de Kaplan-Meier foi analisada de acordo com a FE, e uma análise de regressão logística foi realizada. A significância estatística foi estabelecida em p<0,05. Resultados Um total de 380 pacientes foram analisados. A maioria dos pacientes apresentaram ICFEp (515), seguido de ICFEr (32%) e ICFEI (17%). Os pacientes com ICFEI apresentaram características intermediárias em relação à idade, pressão arterial, e diâmetros ventriculares, e a maioria era de etiologia isquêmica. O período mediano de acompanhamento foi de 4 anos. Não se observou diferença na sobrevida geral ou na mortalidade cardiovascular (p=0,03) entre os grupos de FE (FE reduzida: mortalidade de 40,5%; FE intermediária: 39,7%, e FE preservada 26%). A mortalidade hospitalar foi 7,6%. Conclusão Não houve diferença na taxa de sobrevida entre os grupos de FE diferentes. Os pacientes com ICFEI apresentaram maior mortalidade por doenças cardiovasculares em comparação a pacientes com ICFEp. (Arq Bras Cardiol. 2021; 116(1):14-23)
Health Care Providers’ Challenges to High-Quality HIV Care and Antiretroviral Treatment Retention in Rural South Africa

Provision of high-quality HIV care is challenging, especially in rural primary care clinics in high HIV burden settings. We aimed to better understand the main challenges to quality HIV care provision and retention in antiretroviral treatment (ART) programs in rural South Africa from the health care providers’ perspective. We conducted semi-structured qualitative interviews with 23 providers from nine rural clinics. Using thematic and framework analysis, we found that providers and patients face a set of complex and intertwined barriers at the structural, programmatic, and individual levels. More specifically, analyses revealed that their challenges are primarily structural (i.e., health system- and microeconomic context-specific) and programmatic (i.e., clinic- and provider-specific) in nature. We highlight the linkages that providers draw between the challenges they face, the motivation to do their job, the quality of the care they provide, and patients’ dissatisfaction with the care they receive, all potentially resulting in poor retention in care.