Miracle-dz/UniFAR-FTUs huggingface dataset:
Circular RNA expression in ovarian endometriosis.

AIM Circular RNAs (circRNAs) with miRNA response elements (MREs) could function as competing endogenous RNA (ceRNA) in regulating gene expression. This study was carried out to identify the expression profile and role of circRNAs in endometriosis. MATERIALS & METHODS Microarray assay was performed in four paired ovarian endometriomas and eutopic endometrium, followed by quantitative real-time RT-PCR in 24 paired samples. Bioinformatical algorithms were used to predict MREs, as well as ceRNA and KEGG pathway analysis. RESULTS We identified 262 upregulated and 291 downregulated circRNAs, binding with 1225 MREs. The ceRNA network included 122 miRNAs and 137 mRNAs, which are involed in nine pathways. CONCLUSION CircRNAs are differentially expressed in endometriosis, which might be related with pathogenesis of endometriosis.
Flow Cytometric Analysis of Porcine Peripheral Blood Leukocytes Infected With Pseudorabies Virus

The susceptibility of fractionated porcine peripheral blood leukocytes (PBL) to pseudorabies virus (PRV) was studied by flow cytometry and defined by viral antigen expression. Viral antigens on the surface of infected cells and cell viability were evaluated by forward angle light scatter (FALS), 90‐degree light scatter (90LS), green fluorescence (FITC‐anti‐PRV), and red fluorescence (propidium iodide). Approximately 10% of infected mononuclear cells from healthy pigs expressed cell‐surface PRV antigen. Cell‐surface fluorescence and cell type were confirmed by sorting live positive cells for microscopy. In sorted positive samples, the lymphocyte versus monocyte ratio was approximately 50%:50%, defined by morphology. Positive lymphocytes represent 5.75% of total mononuclear cells. When cells were stimulated with phytohemagglutinin (PHA) and lipopolysaccharide (LPS) before infection, mitogen‐stimulated T‐lymphoblasts showed increased susceptibility to PRV (40.7% positive) and died of infection. Monocytes, particularly adherent monocytes, were highly susceptible (40% to 71.4% positive). Granulocytes appeared to be refractory. The relative susceptibility of various PBL populations was compared by normalizing lymphocyte susceptibility to 1 as follows: resting total lymphocytes (1); B‐lymphocytes (0.67); T‐lymphoblasts (7.08); total monocytes (4.27); adherent cells (4.03 to 10.88); adherent monocytes (6.95 to 12.42); granulocytes (0.24). These findings suggest a possible mechanism by which PRV could have an immunosuppressive effect as well as a pathway for dissemination of PRV.
Role of Angiotensin II in Cardiovascular Disease — Therapeutic Implications of More Than a Century of Research

More than a century of research on the renin-angiotensin system (RAS) has uncovered the widespread involvement of angiotensin II (Ang II) in the pathophysiology of cardiovascular diseases. A number of outcomes-based mega trials utilising hard clinical endpoints have revealed beneficial effects of angiotensin receptor antagonists (AIIAs/ARBs) in patients with hypertension, heart failure, diabetic nephropathy, and post-myocardial infarction (MI). The results of these studies not only emphasise the importance of Ang II in the pathophysiology of these diseases but have provided the basis for an evidence-based approach for the use of AIIAs in clinical practice. It is hoped that the next 100 years of research into the RAS will uncover hitherto unimaginable therapeutic opportunities.
LGR5 is a promising biomarker for patients with stage I and II gastric cancer.

OBJECTIVE To investigate Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) expressions in gastric cancer and to evaluate its clinical significance. METHODS LGR5 expression was assessed by immunohistochemistry in 257 gastric cancer patients after surgery. The relationships between LGR5 expression and clinicopathological features and patients prognosis were statistically analyzed. RESULTS The expression of LGR5 was significantly higher in gastric cancers as a cancer stem cell marker than in adjacent normal tissues (P<0.001), and more frequently in patients with intestinal type, well-moderate differentiation and stage I and II (P<0.05). Although we found gastric cancer patients with LGR5 positive expression had a poorer prognosis, it didn't meet statistical signiﬁcance (P>0.05). LGR5 negative expression was significantly related to the favorable overall survival in stage I and II gastric cancer patients (P<0.05). Furthermore, patients with high LGR5 expression tended to be more likely to get progression and have poorer progress-free survival (P<0.05). Multivariate Cox regression analysis revealed that LGR5 expression was an independent factor of overall survival for the patients with stage I and II gastric cancer (P<0.05). CONCLUSIONS Our results show that LGR5 may play an important role in tumorigenesis and progression and would be a powerful marker to predict the prognosis of patients with stage I and II gastric cancer.
Loss of Fhit expression in non-small-cell lung cancer: correlation with molecular genetic abnormalities and clinicopathological features

The FHIT gene is located at a chromosomal site (3p14.2) which is commonly affected by translocations and deletions in human neoplasia. Although FHIT alterations at the DNA and RNA level are frequent in many types of tumours, the biological and clinical significance of these changes is not clear. In this study we aimed at correlating loss of Fhit protein expression with a large number of molecular genetic and clinical parameters in a well-characterized cohort of non-small-cell lung cancers (NSCLCs). Paraffin sections of 99 non-small-cell carcinomas were reacted with an anti-Fhit polyclonal antibody in a standard immunohistochemical reaction. Abnormal cases were characterized by complete loss of cytoplasmic Fhit staining. The Fhit staining results were then correlated with previously obtained clinical and molecular data. Fifty-two of 99 tumours lacked cytoplasmic Fhit staining, with preserved reactivity in adjacent normal cells. Lack of Fhit staining correlated with: loss of heterozygosity (LOH) at the FHIT 3p14.2 locus, but not at other loci on 3p; squamous histology; LOH at 17p13 and 5q but not with LOH at multiple other suspected tumour suppressor gene loci; and was inversely correlated with codon 12 mutations in K- ras. Fhit expression was not correlated overall with a variety of clinical parameters including survival and was not associated with abnormalities of immunohistochemical expression of p53, RB, and p16. All of these findings are consistent with loss of Fhit protein expression being as frequent an abnormality in lung cancer pathogenesis as are p53 and p16 protein abnormalities and that such loss occurs independently of the commitment to the metastatic state and of most other molecular abnormalities. © 2000 Cancer Research Campaign
Safety and Immunogenicity of Heterologous Prime-Boost Immunisation with Plasmodium falciparum Malaria Candidate Vaccines, ChAd63 ME-TRAP and MVA ME-TRAP, in Healthy Gambian and Kenyan Adults

Background Heterologous prime boost immunization with chimpanzee adenovirus 63 (ChAd63) and Modified vaccinia Virus Ankara (MVA) vectored vaccines is a strategy recently shown to be capable of inducing strong cell mediated responses against several antigens from the malaria parasite. ChAd63-MVA expressing the Plasmodium falciparum pre-erythrocytic antigen ME-TRAP (multiple epitope string with thrombospondin-related adhesion protein) is a leading malaria vaccine candidate, capable of inducing sterile protection in malaria naïve adults following controlled human malaria infection (CHMI). Methodology We conducted two Phase Ib dose escalation clinical trials assessing the safety and immunogenicity of ChAd63-MVA ME-TRAP in 46 healthy malaria exposed adults in two African countries with similar malaria transmission patterns. Results ChAd63-MVA ME-TRAP was shown to be safe and immunogenic, inducing high-level T cell responses (median >1300 SFU/million PBMC). Conclusions ChAd63-MVA ME-TRAP is a safe and highly immunogenic vaccine regimen in adults with prior exposure to malaria. Further clinical trials to assess safety and immunogenicity in children and infants and protective efficacy in the field are now warranted. Trial Registration Pactr.org PACTR2010020001771828 Pactr.org PACTR201008000221638 ClinicalTrials.gov NCT01373879 NCT01373879 ClinicalTrials.gov NCT01379430 NCT01379430
Functional effect of polymorphisms in 15q25 locus on CHRNA5 mRNA, bulky DNA adducts and TP53 mutations

Genome‐wide association studies have demonstrated that genetic polymorphisms influence the risk of developing lung cancer. Nicotinic acetylcholine receptor alpha3, alpha5 and beta4 genes (CHRNA3, CHRNA5 and CHRNB4) cluster at the 15q25.1 lung cancer susceptibility locus. We genotyped 310 patients with non‐small cell lung cancer and a control group of 348 cancer‐free individuals for seven sequence variants located in CHRNA3 and CHRNA5 genes. Two of the polymorphisms (rs3829787 and rs3841324) statistically influenced the risk of developing lung cancer. We found that four of the variants (rs3829787, rs3841324, rs588765 and rs3743073) were associated with differential levels of genetic alterations measured as the levels of hydrophobic DNA adducts in the adjacent histologically normal tissue of the lung cancer patients and as TP53 mutations in their lung tumors. The seven sequence variants formed three haplotypes with a frequency above 5%. The two most frequent haplotypes were associated with the risk of developing lung cancer and with smoking‐related DNA alterations. We also found an association between CHRNA5 mRNA levels and the sequence variants or haplotypes. In conclusion, our results showed that several of the polymorphisms and their haplotypes in CHRNA5/CHRNA3 genes may have functional effects on (i) CHRNA5 mRNA levels, (ii) polycyclic aromatic hydrocarbon–DNA adduct levels, (iii) TP53 mutations and (iv) susceptibility to lung cancer.
Limited Feedback Hybrid Precoding for Multi-User Millimeter Wave Systems

Antenna arrays will be an important ingredient in millimeter-wave (mmWave) cellular systems. A natural application of antenna arrays is simultaneous transmission to multiple users. Unfortunately, the hardware constraints in mmWave systems make it difficult to apply conventional lower frequency multiuser MIMO precoding techniques at mmWave. This paper develops low-complexity hybrid analog/digital precoding for downlink multiuser mmWave systems. Hybrid precoding involves a combination of analog and digital processing that is inspired by the power consumption of complete radio frequency and mixed signal hardware. The proposed algorithm configures hybrid precoders at the transmitter and analog combiners at multiple receivers with a small training and feedback overhead. The performance of the proposed algorithm is analyzed in the large dimensional regime and in single-path channels. When the analog and digital precoding vectors are selected from quantized codebooks, the rate loss due to the joint quantization is characterized, and insights are given into the performance of hybrid precoding compared with analog-only beamforming solutions. Analytical and simulation results show that the proposed techniques offer higher sum rates compared with analog-only beamforming solutions, and approach the performance of the unconstrained digital beamforming with relatively small codebooks.
Localization of salivary proteins in granules of human parotid and submandibular acinar cells.

Electron microscopic immunocytochemistry was used to investigate the distribution of four secretory proteins within the granules of human parotid and submandibular gland acinar cells. The results demonstrate that the distribution of the individual proteins differs significantly. Amylase is concentrated within the electron-dense regions of the granules, whereas agglutinin is present mainly in the regions of lower density. In contrast, the proline-rich proteins and histatins are distributed throughout the content of the granules and do not appear to be concentrated in either the high- or low-density regions. The results also suggest that different mechanisms, such as self-aggregation or ionic complexes with metal ions and charged macromolecules, may be involved in the packaging of individual proteins within the same granule. Further, they also show that among the salivary glands of various species, the intragranular distribution of similar proteins (e.g., amylase and proline-rich proteins) may differ.
Serial Section Scanning Electron Microscopy (S3EM) on Silicon Wafers for Ultra-Structural Volume Imaging of Cells and Tissues

High resolution, three-dimensional (3D) representations of cellular ultrastructure are essential for structure function studies in all areas of cell biology. While limited subcellular volumes have been routinely examined using serial section transmission electron microscopy (ssTEM), complete ultrastructural reconstructions of large volumes, entire cells or even tissue are difficult to achieve using ssTEM. Here, we introduce a novel approach combining serial sectioning of tissue with scanning electron microscopy (SEM) using a conductive silicon wafer as a support. Ribbons containing hundreds of 35 nm thick sections can be generated and imaged on the wafer at a lateral pixel resolution of 3.7 nm by recording the backscattered electrons with the in-lens detector of the SEM. The resulting electron micrographs are qualitatively comparable to those obtained by conventional TEM. S3EM images of the same region of interest in consecutive sections can be used for 3D reconstructions of large structures. We demonstrate the potential of this approach by reconstructing a 31.7 µm3 volume of a calyx of Held presynaptic terminal. The approach introduced here, Serial Section SEM (S3EM), for the first time provides the possibility to obtain 3D ultrastructure of large volumes with high resolution and to selectively and repetitively home in on structures of interest. S3EM accelerates process duration, is amenable to full automation and can be implemented with standard instrumentation.
Proteinuria Independently Predicts Unfavorable Outcome of Ischemic Stroke Patients Receiving Intravenous Thrombolysis

Background and Purpose Patients with low estimated glomerular filtration rate (eGFR) and proteinuria may be at increased risk for stroke. This study investigated whether low eGFR and proteinuria are outcome predictors in stroke patients treated with intravenous thrombolysis. Methods We studied 432 consecutive stroke patients who received thrombolysis from January 2006 to December 2012, in Taiwan. Unfavorable outcome was defined as modified Rankin scale ≥2 at 3 months after stroke. Proteinuria was classified as negative or trace, mild, and moderate to severe. Using logistic regression analysis, we identified independent factors for unfavorable outcome after thrombolysis. Results Of all patients, 32.7% had proteinuria. Patients with proteinuria were older, had higher frequencies of diabetes mellitus, hyperlipidemia, atrial fibrillation, lower eGFR, and greater severity of stroke upon admission than those without proteinuria. Proteinuria, not low eGFR, was an independent predictor for unfavorable outcome for stroke (OR = 2.00 for mild proteinuria, p = 0.035; OR = 2.54 for moderate to severe proteinuria, p = 0.035). However, no clear relationship was found between proteinuria and symptomatic hemorrhage after thrombolysis. Conclusions Proteinuria is an independent predictor of unfavorable outcome for acute ischemic stroke in patients treated with intravenous thrombolysis, indicating the crucial role of chronic kidney disease on the effectiveness of thrombolysis.
A Proteomic Analysis Reveals the Interaction of GluK1 Ionotropic Kainate Receptor Subunits with Go Proteins

Kainate receptors (KARs) are found ubiquitously in the CNS and are present presynaptically and postsynaptically regulating synaptic transmission and excitability. Functional studies have proven that KARs act as ion channels as well as potentially activating G-proteins, thus indicating the existance of a dual signaling system for KARs. Nevertheless, it is not clear how these ion channels activate G-proteins and which of the KAR subunits is involved. Here we performed a proteomic analysis to define proteins that interact with the C-terminal domain of GluK1 and we identified a variety of proteins with many different functions, including a Go α subunit. These interactions were verified through distinct in vitro and in vivo assays, and the activation of the Go protein by GluK1 was validated in bioluminescence resonance energy transfer experiments, while the specificity of this association was confirmed in GluK1-deficient mice. These data reveal components of the KAR interactome, and they show that GluK1 and Go proteins are natural partners, accounting for the metabotropic effects of KARs.
Chronic Cough Due to Chronic Bronchitis

Background: Chronic bronchitis is a disease of the bronchi that is manifested by cough and sputum expectoration occurring on most days for at least 3 months of the year and for at least 2 consecutive years when other respiratory or cardiac causes for the chronic productive cough are excluded. The disease is caused by an interaction between noxious inhaled agents (eg, cigarette smoke, industrial pollutants, and other environmental pollutants) and host factors (eg, genetic and respiratory infections) that results in chronic inflammation in the walls and lumen of the airways. As the disease advances, progressive airflow limitation occurs, usually in association with pathologic changes of emphysema. This condition is called COPD. When a stable patient experiences a sudden clinical deterioration with increased sputum volume, sputum purulence, and/or worsening of shortness of breath, this is referred to as an acute exacerbation of chronic bronchitis as long as conditions other than acute tracheobronchitis are ruled out. The purpose of this review is to present the evidence for the diagnosis and treatment of cough due to chronic bronchitis, and to make recommendations that will be useful for clinical practice. Methods: Recommendations for this section of the review were obtained from data using a National Library of Medicine (PubMed) search dating back to 1950, performed in August 2004, of the literature published in the English language. The search was limited to human studies, using the search terms “cough,” “chronic bronchitis,” and “COPD. ” Results: The most effective way to reduce or eliminate cough in patients with chronic bronchitis and persistent exposure to respiratory irritants, such as personal tobacco use, passive smoke exposure, and workplace hazards is avoidance. Therapy with a short-acting inhaled β-agonist, inhaled ipratropium bromide, and oral theophylline, and a combined regimen of inhaled long-acting β-agonist and an inhaled corticosteroid may improve cough in patients with chronic bronchitis, but there is no proven benefit for the use of prophylactic antibiotics, oral corticosteroids, expectorants, postural drainage, or chest physiotherapy. For the treatment of an acute exacerbation of chronic bronchitis, there is evidence that inhaled bronchodilators, oral antibiotics, and oral corticosteroids (or in severe cases IV corticosteroids) are useful, but their effects on cough have not been systematically evaluated. Therapy with expectorants, postural drainage, chest physiotherapy, and theophylline is not recommended. Central cough suppressants such as codeine and dextromethorphan are recommended for short-term symptomatic relief of coughing. Conclusions: Chronic bronchitis due to cigarette smoking or other exposures to inhaled noxious agents is one of the most common causes of chronic cough in the general population. The most effective way to eliminate cough is the avoidance of all respiratory irritants. When cough persists despite the removal of these inciting agents, there are effective agents to reduce or eliminate cough.
The incidence and nature of drug-related hospital admission: A 6-month observational study in a tertiary health care hospital

Objective: To assess and evaluate the frequency, severity and classification of drug-related problems (DRP) resulting in hospitalization in an internal medicine department of a large tertiary care hospital and to identify any patient, prescriber, drug, and system factors associated with these events. Materials and Methods: A prospective and descriptive study carried out in Department of Medicine, Government Medical College, Jagdalpur. The DRP and relevant data were recorded on the personal record of every individual patient, filled during the course of treatment. Result: A total of 3560 patient’s records were analyzed. Among them118 admissions were due to DRP. The most common DRP noted was noncompliance in part of patient’s i.e 55 (46.6%). Statistically significant correlations were found in the number of prescribed drugs and over the counter drugs (OTC) used by patients. Conclusion: The DRP that attributed to hospital admission are mostly avoidable through proper patient education and strengthening the need of pharmacovigilance with little more vigilance in patient care.
Dynamic condensation of linker histone C-terminal domain regulates chromatin structure

The basic and intrinsically disordered C-terminal domain (CTD) of the linker histone (LH) is essential for chromatin compaction. However, its conformation upon nucleosome binding and its impact on chromatin organization remain unknown. Our mesoscale chromatin model with a flexible LH CTD captures a dynamic, salt-dependent condensation mechanism driven by charge neutralization between the LH and linker DNA. Namely, at low salt concentration, CTD condenses, but LH only interacts with the nucleosome and one linker DNA, resulting in a semi-open nucleosome configuration; at higher salt, LH interacts with the nucleosome and two linker DNAs, promoting stem formation and chromatin compaction. CTD charge reduction unfolds the domain and decondenses chromatin, a mechanism in consonance with reduced counterion screening in vitro and phosphorylated LH in vivo. Divalent ions counteract this decondensation effect by maintaining nucleosome stems and expelling the CTDs to the fiber exterior. Additionally, we explain that the CTD folding depends on the chromatin fiber size, and we show that the asymmetric structure of the LH globular head is responsible for the uneven interaction observed between the LH and the linker DNAs. All these mechanisms may impact epigenetic regulation and higher levels of chromatin folding.