Miracle-dz/UniFAR-FTUs huggingface dataset:
Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Protect Cardiomyocytes from Doxorubicin-Induced Cardiomyopathy by Upregulating Survivin Expression via the miR-199a-3p-Akt-Sp1/p53 Signaling Pathway

Cardiotoxicity is associated with the long-term clinical application of doxorubicin (DOX) in cancer patients. Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) including exosomes have been suggested for the treatment of various diseases, including ischemic diseases. However, the effects and functional mechanism of MSC-sEVs in DOX-induced cardiomyopathy have not been clarified. Here, MSC-sEVs were isolated from murine embryonic mesenchymal progenitor cell (C3H/10T1/2) culture media, using ultrafiltration. H9c2 cardiac myoblast cells were pretreated with MSC-sEVs and then exposed to DOX. For in vivo studies, male C57BL/6 mice were administered MSC-sEVs intravenously, prior to a single dose of DOX (15 mg/kg, intraperitoneal). The mice were sacrificed 14 days after DOX treatment. The results showed that MSC-sEVs protected cardiomyocytes from DOX-induced cell death. H9c2 cells treated with DOX showed downregulation of both phosphorylated Akt and survivin, whereas the treatment of MSC-sEVs recovered expression, indicating their anti-apoptotic effects. Three microRNAs (miRNAs) (miR 199a-3p, miR 424-5p, and miR 21-5p) in MSC-sEVs regulated the Akt-Sp1/p53 signaling pathway in cardiomyocytes. Among them, miR 199a-3p was involved in regulating survivin expression, which correlated with the anti-apoptotic effects of MSC-sEVs. In in vivo studies, the echocardiographic results showed that the group treated with MSC-sEVs recovered from DOX-induced cardiomyopathy, showing improvement of both the left ventricle fraction and ejection fraction. MSC-sEVs treatment also increased both survivin and B-cell lymphoma 2 expression in heart tissue compared to the DOX group. Our results demonstrate that MSC-sEVs have protective effects against DOX-induced cardiomyopathy by upregulating survivin expression, which is mediated by the regulation of Akt activation by miRNAs in MSC-sEVs. Thus, MSC-sEVs may be a novel therapy for the prevention of DOX-induced cardiomyopathy.
Decreased Glucocorticoid Signaling Potentiates Lipid-Induced Inflammation and Contributes to Insulin Resistance in the Skeletal Muscle of Fructose-Fed Male Rats Exposed to Stress

The modern lifestyle brings both excessive fructose consumption and daily exposure to stress which could lead to metabolic disturbances and type 2 diabetes. Muscles are important points of glucose and lipid metabolism, with a crucial role in the maintenance of systemic energy homeostasis. We investigated whether 9-week fructose-enriched diet, with and without exposure to 4-week unpredictable stress, disturbs insulin signaling in the skeletal muscle of male rats and evaluated potential contributory roles of muscle lipid metabolism, glucocorticoid signaling and inflammation. The combination of fructose-enriched diet and stress increased peroxisome proliferator-activated receptors-α and -δ and stimulated lipid uptake, lipolysis and β-oxidation in the muscle of fructose-fed stressed rats. Combination of treatment also decreased systemic insulin sensitivity judged by lower R-QUICKI, and lowered muscle protein content and stimulatory phosphorylations of insulin receptor supstrate-1 and Akt, as well as the level of 11β-hydroxysteroid dehydrogenase type 1 and glucocorticoid receptor. At the same time, increased levels of protein tyrosine phosphatase-1B, nuclear factor-κB, tumor necrosis factor-α, were observed in the muscle of fructose-fed stressed rats. Based on these results, we propose that decreased glucocorticoid signaling in the skeletal muscle can make a setting for lipid-induced inflammation and the development of insulin resistance in fructose-fed stressed rats.
Combination of the G-8 Screening Tool and Hand-Grip Strength to Predict Long-Term Overall Survival in Non-Small Cell Lung Cancer Patients Undergoing Stereotactic Body Radiotherapy

Simple Summary As the world’s population ages, the number of older patients diagnosed with non-small cell lung cancer will increase, and more patients are expected to suffer from comorbidities. Stereotactic body radiation therapy presents a curative modality and is the treatment of choice for patients with localized non-small cell lung cancer that is considered medically inoperable (often due to multimorbidity). However, in these patients, age-related comorbidities—rather than lung cancer—are the leading cause of mortality. To address age-related comorbidities and optimize the general health status of older patients with cancer, the Geriatric 8 screening tool was developed. However, the Geriatric 8 is mainly based on nutritional assessment; therefore, we aimed to evaluate if a combination of the Geriatric 8 and a test of physical functioning, such as hand-grip strength, can lead to more accurate identification of patients who are in need of geriatric care than the Geriatric 8 alone. Abstract The Geriatric 8 (G-8) is a known predictor of overall survival (OS) in older cancer patients, but is mainly based on nutritional aspects. This study aimed to assess if the G-8 combined with a hand-grip strength test (HGST) in patients with NSCLC treated with stereotactic body radiotherapy can predict long-term OS better than the G-8 alone. A total of 46 SBRT-treated patients with NSCLC of stage T1-T2N0M0 were included. Patients were divided into three groups: fit (normal G-8 and HGST), vulnerable (abnormal G-8 or HGST), or frail (abnormal G-8 and HGST). Statistically significant differences were found in 4-year OS between the fit, vulnerable, and frail groups (70% vs. 46% vs. 25%, p = 0.04), as well as between the normal and abnormal G-8 groups (69% vs. 39%, p = 0.02). In a multivariable analysis of OS, being vulnerable with a hazard ratio (HR) of 2.03 or frail with an HR of 3.80 indicated poorer OS, but this did not reach statistical significance. This study suggests that there might be a benefit of adding a physical test to the G-8 for more precisely predicting overall survival in SBRT-treated patients with localized NSCLC. However, this should be confirmed in a larger study population.
Large Deformation and Energy Absorption Behaviour of Perforated Hollow Sphere Structures under Quasi-Static Compression

Hollow sphere structures with perforations (PHSSs) in three different arrangements (simple cubic (SC), body-centred cubic (BCC), and face-centred cubic (FCC)) were fabricated through three-dimensional (3D) printing, and the mechanical behaviours of these PHSSs under quasi-static compression were investigated experimentally and numerically. The results indicated that under uniaxial compression, the PHSSs mainly undergo three stages, i.e., a linear elastic stage, a large deformation or plateau stage, and a densification stage. During the stage of large deformation, the SC and BCC PHSSs experience a preliminary compaction sub-stage after layer-by-layer buckling, while for the FCC PHSS, layer-by-layer collapse and compaction are the dominant deformation behaviours. A numerical simulation was employed to study the mechanical properties of PHSSs with different geometric parameters under quasi-static compression and to explore the effect of the wall thickness, hole diameter, and sphere arrangement on the first peak stress, plateau stress, and specific energy absorption (SEA) of the PHSSs. The results reveal that the geometric parameters have a significant impact on the large deformation behaviour and energy absorption capacity of PHSSs. The presented PHSS is also proven to be much lighter than traditional metallic hollow sphere structure (MHSS) and has higher specific strength and SEA.
Best Practices and Progress in Precision-Cut Liver Slice Cultures

Thirty-five years ago, precision-cut liver slices (PCLS) were described as a promising tool and were expected to become the standard in vitro model to study liver disease as they tick off all characteristics of a good in vitro model. In contrast to most in vitro models, PCLS retain the complex 3D liver structures found in vivo, including cell–cell and cell–matrix interactions, and therefore should constitute the most reliable tool to model and to investigate pathways underlying chronic liver disease in vitro. Nevertheless, the biggest disadvantage of the model is the initiation of a procedure-induced fibrotic response. In this review, we describe the parameters and potential of PCLS cultures and discuss whether the initially described limitations and pitfalls have been overcome. We summarize the latest advances in PCLS research and critically evaluate PCLS use and progress since its invention in 1985.
Epstein–Barr Virus-Associated T- and NK-Cell Lymphoproliferative Diseases: A Review of Clinical and Pathological Features

Simple Summary In most Epstein–Barr virus (EBV)-infected individuals, the virus establishes a lifelong latent infection with no specific clinical manifestation. However, EBV primary infection and secondary reactivation may cause various EBV-associated lymphoproliferative disorders (LPD), including hematologic malignancies. Among them, EBV-positive T/NK LPD are uncommon diseases defined by the proliferation of T- or NK-cells infected by EBV, more commonly encountered in Asians and Latin Americans. They encompass a spectrum of disorders ranging from indolent reactive lesions to malignant and aggressive diseases. Despite novel insights from high-throughput molecular studies, the pathogenesis of these disorders is not well understood, and EBV-positive T/NK LPD diagnoses remain challenging due to their rarity and considerable overlap. Indeed, this article discusses new insights into EBV-positive T/NK LPD and focuses on diagnosis challenges, describing the difficulties to clarify the borders between overlapping LPD subtypes. Abstract Epstein–Barr virus (EBV) is a ubiquitous virus detected in up to 95% of the general population. Most people are asymptomatic, while some may develop a wide range of EBV-associated lymphoproliferative disorders (LPD). Among them, EBV-positive T/NK LPD are uncommon diseases defined by the proliferation of T- or NK-cells infected by EBV. The 2017 World Health Organization (WHO) classification recognizes the following entities characterized by different outcomes: chronic active EBV infection of T- or NK-cell types (cutaneous and systemic forms), systemic EBV-positive T-cell lymphoma of childhood, EBV-positive aggressive NK-cell leukemia, extra nodal NK/T-cell lymphoma nasal type, and the new provisional entity known as primary EBV-positive nodal T/NK-cell lymphoma. In addition, EBV associated-hemophagocytic lymphohistiocytosis is part of EBV-positive T/NK LPD, but has not been included in the WHO classification due to its reactive nature. Despite novel insights from high-throughput molecular studies, EBV-positive NK/T-cell LPD diagnoses remain challenging, especially because of their rarity and overlap. Until now, an accurate EBV-positive NK/T LPD diagnosis has been based on its clinical presentation and course correlated with its histological features. This review aims to summarize clinical, pathological and molecular features of EBV-positive T/NK LPD subtypes and to provide an overview of new understandings regarding these rare disorders.
How to Write a Systematic Review: A Narrative Review

In recent years, published systematic reviews in the world and in Iran have been increasing. These studies are an important resource to answer evidence-based clinical questions and assist health policy-makers and students who want to identify evidence gaps in published research. Systematic review studies, with or without meta-analysis, synthesize all available evidence from studies focused on the same research question. In this study, the steps for a systematic review such as research question design and identification, the search for qualified published studies, the extraction and synthesis of information that pertain to the research question, and interpretation of the results are presented in details. This will be helpful to all interested researchers.
Adiponectin Modulation by Genotype and Maternal Choline Supplementation in a Mouse Model of Down Syndrome and Alzheimer’s Disease

Down syndrome (DS) is a genetic disorder caused by the triplication of human chromosome 21, which results in neurological and physiological pathologies. These deficits increase during aging and are exacerbated by cognitive decline and increase of Alzheimer’s disease (AD) neuropathology. A nontoxic, noninvasive treatment, maternal choline supplementation (MCS) attenuates cognitive decline in mouse models of DS and AD. To evaluate potential underlying mechanisms, laser capture microdissection of individual neuronal populations of MCS offspring was performed, followed by RNA sequencing and bioinformatic inquiry. Results at ~6 months of age (MO) revealed DS mice (the well-established Ts65Dn model) have significant dysregulation of select genes within the Type 2 Diabetes Mellitus (T2DM) signaling pathway relative to normal disomic (2N) littermates. Accordingly, we interrogated key T2DM protein hormones by ELISA assay in addition to gene and encoded protein levels in the brain. We found dysregulation of adiponectin (APN) protein levels in the frontal cortex of ~6 MO trisomic mice, which was attenuated by MCS. APN receptors also displayed expression level changes in response to MCS. APN is a potential biomarker for AD pathology and may be relevant in DS. We posit that changes in APN signaling may be an early marker of cognitive decline and neurodegeneration.
The complete chloroplast genome sequence of Pennisetum centrasiaticum, a widespread grass in Tibet, China

Abstract The complete chloroplast genome of Pennisetum centrasiaticum was sequenced and reported here. The total genome size was 138,294 bp in length, containing a large single-copy region of 81,229 bp, a small single-copy region of 12,419 bp, and a pair of inverted repeat regions of 22,288 bp. The GC content of P. centrasiaticum chloroplast genome was 38.6%. It encodes a total of 119 unique genes, including 81 protein-coding genes, 34 tRNA genes, and four rRNA genes. Phylogenetic analysis showed a strong sister relationship with Cenchrus ciliaris and Cenchrus purpureus. Our findings provide fundamental information for further evolutionary and phylogenetic researches of P. centrasiaticum.
Determination of Ceftazidime in Plasma by HPLC

Aim To establish a method for the determination of ceftazidime concentration in plasma. Method The HPLC separation was performed on Kromasil C18 column (250mm×4.6mm, 5μm). The mobile phase was methanol-potassium dihydrogen phosphate (15∶85) at a rate of 1.0ml/min. The detection wavelength was 254nm. Results The linear range was 0.5～200.0mg·L-1(r=0.999 9). The method recovery of ceftazidime was 94.91%～105.95% (RSDs lower than 12%) and the extraction recovery of ceftazidime was 89.50%～92.94% (RSDs lower than 5%). Conclusion The method appeared to be simple,accurate and precise. It is suitable for clinical pharmacokinetic study.
Chronic Neutrophilic Leukemia: A Literature Review of the Rare Myeloproliferative Pathology

Hematological malignancies often develop due to a vast spectrum of environmental and genetic etiologies. Chronic neutrophilic leukemia (CNL) can be described as a BCR-ABL1 (Philadelphia chromosome)-negative myeloproliferative neoplastic disease with various genetic mutations that may directly or indirectly play a role in its pathogenesis. A well-established mutation in CNL is the CSF3R (a cytokine receptor) which has been incorporated into the diagnostic criteria for the disease. However, evidence of other mutations such as SETBP1, ASXL1, and TET2 has also shed more light on the pathogenesis of this condition. Due to the unknown incidence and heterogeneous presentation of the disease, the diagnosis and management are often difficult and lack satisfactory data. The purpose of this review is to yield further insight into a disease that lacks awareness in the medical community. Using PubMed as a database, relevant studies and case reports were reviewed. The data compiled were used to acknowledge the disease in terms of etiology, clinical manifestation, molecular pathogenesis, and available treatment modalities. Though existing treatment modalities have been shown to induce clinical improvement, the outcomes are not reliable, and further research is required to reach a comprehensive “standard of care” for the disease.
Prognostic value of the PrPC-ILK-IDO1 axis in the mesenchymal colorectal cancer subtype

ABSTRACT The CMS4 mesenchymal subtype of colorectal cancer (CRC) is associated with poor prognosis and resistance to treatment. The cellular prion protein PrPC is overexpressed in CMS4 tumors and controls the expression of a panel of CMS4-specific genes in CRC cell lines. Here, we sought to investigate PrPC downstream pathways that may underlie its role in CMS4 CRC. By combining gene set enrichment analyses and gain and loss of function approaches in CRC cell lines, we identify the integrin-linked kinase ILK as a proximal effector of PrPC that mediates its control on the CMS4 phenotype. We further leveraged three independent large CRC cohorts to assess correlations in gene expression pattern with patient outcomes and found that ILK is overexpressed in CMS4 mesenchymal tumors and confers a poor prognosis, especially when combined with high expression of the PrPC encoding gene PRNP. Of note, we discovered that the PrPC-ILK signaling axis controls the expression and activity of the tryptophan metabolizing enzyme indoleamine 2,3 dioxygenase IDO1, a key player in immune tolerance. In addition, we monitored alterations in the levels of tryptophan and its metabolites of the kynurenine pathway in the plasma of metastatic CRC patients (n = 325) and we highlight their prognostic value in combination with plasma PrPC levels. Thus, the PrPC-ILK-IDO1 axis plays a key role in the mesenchymal subtype of CRC. PrPC and IDO1-targeted strategies may represent new avenues for patient stratification and treatment in CRC.
Lowering the density: ants associated with the myrmecophyte Tillandsia caput-medusae diminish the establishment of epiphytes

Abstract Ants benefit myrmecophytic plants by two main activities defending them from herbivores and offering nutrients. Ants’ territorial defence behaviour also benefits their myrmecophytic plants; in the case of trees, this behaviour includes eliminating structural parasites (epiphytes and lianas). These benefits could also occur with myrmecophytic epiphytes by decreasing the abundance of competing epiphytes. In two subunits of a tropical dry forest in the centre of Mexico, we (i) recorded the diversity of ants associated with the myrmecophyte Tillandsia caput-medusae, and experimentally tested: (ii) the effect of the ants associated with the myrmecophyte in the removal of its seeds and the seeds of other sympatric non-myrmecophyte species of Tillandsia; and (iii) if seed remotion by ants corresponds with epiphyte load in the preferred (Bursera copallifera) and limiting phorophyte species (B. fagaroides, Ipomoea pauciflora and Sapium macrocarpum). In five trees per species, we tied seed batches of T. caput-medusae, T. hubertiana, T. schiedeana and T. recurvata. One seed batch was close, and the other far away from a T. caput-medusae with active ants. Between forest subunits, ant richness was similar, but diversity and evenness differed. Ants diminish seed establishment of all the Tillandsia species; this effect is stronger in the forest subunit with a large ant diversity, maybe because of ant competition. Seed remotion by ants is independent of phorophyte species identity. Although ants can provide benefits to T. caput-medusae, they also could be lowering their abundance.
Use of medicines in São Paulo, Brazil, and State Health Care Coverage, 2003 and 2015

OBJECTIVES: To analyze the use and acquisition of medicines in São Paulo, Brazil, in 2003 and 2015, according to sociodemographic factors, socioeconomic status, and health conditions of the population. METHODS: Data were obtained from population health surveys “ISA-Capital”. Descriptive analysis, bivariate analysis, and logistic regression models were used to evaluate the use of medicines and coverage by the Brazilian Unified Health System (SUS) according to socioeconomic status and health conditions in two periods: 2003 and 2015. RESULTS: From 2003 to 2015, the surveys showed an increase in the income and education level of the study population. There was no increase in the prevalence of chronic diseases and use of medicines from 2003 to 2015. The provision of medicines by SUS was higher in 2015 than in 2003, and the coverage by SUS was higher in the population with lower education level and income in both 2003 and 2015. CONCLUSIONS: The use of medicines, mainly for chronic disease control, did not change over the years, and there was an increase in SUS coverage for medicines during 2003-2015 in all population groups, with a greater impact on the lower socioeconomic status population. The programs of the provision of medicines implanted since 2003 had influenced the greater SUS coverage for medicines and in the reduction of inequalities in access to medicines.
Comparison of the effect of training academic honesty using two workshop and virtual training methods on the knowledge and attitude of M. S. students

BACKGROUND: Nowadays, one of the most important challenges of the universities and higher education centers is academic dishonesty among students. Academic dishonesty is done through cheating, deception, and plagiarism, which creates serious educational, studious, and social problems for the students and society. The purpose of this study was to compare the effect of virtual and workshop training on the knowledge and attitude of M. S. students in terms of plagiarism. MATERIALS AND METHODS: This research was an applied interventional study of quasi-experimental type having pretest and posttest and the participants of this study included 90 M. S. nursing students of Medical Science University of Shiraz in the southwestern part of Iran. RESULTS: The comparison of the three groups indicated that virtual and workshop training, both, developed the knowledge and attitude of students regarding plagiarism; however, the comparison between two methods did not indicate a statistically significant difference. CONCLUSION: Both virtual and workshop training methods had an effect on increasing students’ knowledge and attitude. Regarding the positive effect of training academic dishonesty using two workshop and virtual training methods, both can be used as efficient and effective methods in training dimensions depending on the condition and facilities to prevent and reduce plagiarism in students.