Miracle-dz/UniFAR-FTUs huggingface dataset:
Triple‐negative breast cancer—Role of immunology: A systemic review

Recently, the complex role of immune therapy has been the target of increased attention in breast cancer, particularly in triple‐negative breast cancer (TNBC). Although TNBC is sensitive to chemotherapy, the recurrence and mortality rates are worse compared with the other breast cancer types. In addition, TNBC still lacks targeted treatment options. With the improved understanding of the immune system in TNBC, it is expected that new predictive and prognostic markers will be identified, and innovative treatment modalities will be developed. The aim of this review was to provide an overview of the effector cells in the TNBC's microenvironment and to highlight a novel approach to treat this kind of cancer. A computer‐based literature research was carried out using PubMed, American Society of Clinical Oncology Annual Meeting (ASCO) and San Antonio Breast Cancer Symposium (SABCS). To date, studies have shown that tumor‐infiltrating lymphocytes (TILs) and tumor‐associated macrophages (TAMs) play a very important role in the TNBC's microenvironment. Tumor‐infiltrating lymphocytes can even be considered as biomarkers to predict chemotherapy response in TNBC. Furthermore, TNBC was shown to have immune active subtypes, and therefore, the use of immunotherapy may be an attractive treatment approach. In this respect, several randomized studies have been designed or are currently ongoing to explore the combination of chemotherapy with immunotherapy in TNBC. Combination of chemo‐ and immunotherapy is likely to be beneficial in a subgroup of patients with TNBC.
Immunosuppressive Compounds Affect the Fungal Growth and Viability of Defined Aspergillus Species

Immunosuppressive drugs are administered to a number of patients; e.g., to allogeneic hematopoietic stem cell transplant recipients. Immunosuppressive drugs impair the immune system and thus increase the risk of invasive fungal disease, but may exhibit antifungal activity at the same time. We investigated the impact of various concentrations of three commonly used immunosuppressive compounds—cyclosporin A (CsA), methylprednisolone (mPRED), and mycophenolic acid (MPA)—on the growth and viability of five clinically important Aspergillus species. Methods included disc diffusion, optical density of mycelium, and viability assays such as XTT. MPA and CsA had a species-specific and dose-dependent inhibitory effect on the growth of all Aspergillus spp. tested, although growth inhibition by MPA was highest in A. niger, A. flavus and A. brasiliensis. Both agents exhibited species-specific hyphal damage, which was higher when the immunosuppressants were added to growing conidia than to mycelium. In contrast, mPRED increased the growth of A. niger, but had no major impact on the growth and viability of any of the other Aspergillus species tested. Our findings may help to better understand the interaction of drugs with Aspergillus species and ultimately may have an impact on individualizing immunosuppressive therapy.
IgA Nephropathy in North West Frontier Province of Pakistan

Background: IgA nephropathy is the most common form of glomerulonephritis in the world. The extent to which IgA nephropathy is diagnosed depends upon the local attitude towards urine testing and renal biopsy. This study was conducted to know the frequency and behavior of IgA nephropathy in our setup. Material and Methods: This study was conducted at Khyber Teaching Hospital Peshawar, from July 2005 to December 2006. Kidney biopsy was performed in 120 patients having glomerulonephritis. Those with IgA nephropathy were further studied. Results: Out of 120 patients with glomerulonephritis, 25 (20.83%) were having IgA nephropathy. Among these 21 (84%) were males and 4 (16%) females. Majority of patients were 20-39 years old and had microscopic haematuria with non-nephrotic range proteinuria. Six (24%) patient had impaired renal function and they were also hypertensive. Only one (4%) patient had nephrotic range proteinuria and none had gross hematuria. Conclusion: IgA nephropathy is not uncommon in our setup. Majority of patients have microscopic hematuria with non-nephrotic range proteinuria. Hypertension and renal insufficiency occurs in 24% of these patients.
Association between cigarette smoking and the susceptibility of acute myeloid leukemia: a systematic review and meta-analysis.

OBJECTIVE To elucidate the association between cigarette smoking and the susceptibility of acute myeloid leukemia (AML). MATERIALS AND METHODS We searched relevant articles from PubMed, Embase, and Cochrane by 1st December, 2018. This meta-analysis included 20 case-control studies, involving 7,538 AML patients and 137,924 healthy controls. Studies reported OR and 95%CI of the correlation between cigarette smoking and AML susceptibility were eligible. Subsequently, the included data were weighted by an inverse variance and analyzed using fixed-effects or random-effects model. Subgroup analysis was conducted based on ethnicities and sources of controls. Heterogeneity test was applied for the included articles. Data analyses were conducted using STATA 12.0. RESULTS Current smokers (OR=1.42, 95%CI= 1.28-1.57; p=0.392) and ever-smokers (OR=1.16, 95%CI=1.05-1.28; p=0.036) were associated with AML susceptibility. In the subgroup analysis by ethnicity, only current smokers (OR=1.45, 95%CI=1.29-1.63; p=0.371) and ever-smokers (OR=1.16, 95%CI=1.03-1.30; p=0.034) of the Caucasian population were associated with AML susceptibility. Stratified analysis based on SOC (source of controls) indicated increased susceptibility of AML in current smokers (OR=1.43, 95%CI=1.26-1.63; p=0.283) and ever-smokers (OR=1.20, 95%CI=1.07-1.35; p=0.078) of the population-based group. Nevertheless, only current smokers in the hospital-based group had increased susceptibility of AML (OR=1.45, 95%CI=1.19-1.76; p=0.198). The risks of AML in ever-smokers (OR=1.04, 95%CI = 0.81-1.35; p=0.054) of the hospital-based group did not remarkably changed. CONCLUSIONS In this meta-analysis, we confirmed the association between cigarette smoking and onset risk of AML, especially in the Caucasian population. High-quality, large-scale researches are required to be conducted in multi-center hospitals for verification.
Discovery of a Potent PLK1-PBD Small-Molecule Inhibitor as an Anticancer Drug Candidate through Structure-Based Design

Polo-box domain of polo-like kinase 1 (PLK1-PBD) has a pivotal role in cell proliferation and could be implicated as a potential anticancer target. Although some small-molecule inhibitors have been developed, their clinical application has been restricted by the poor selectivity. Therefore, there is an urgent need to develop effective PLK1-PBD inhibitors. Herein, we have developed a virtual screening protocol to find PLK1-PBD inhibitors by using combination of structure-based pharmacophore modeling and molecular docking. This protocol was successfully applied to screen PLK1-PBD inhibitors from specs database. MTT assay indicated that five screened hits suppressed the growth of HeLa cells. Particularly, hit-5, as a selective PLK1 inhibitor targeting PLK1-PBD, significantly inhibited the progression of HeLa cells-derived xenograft, with no obvious side effects. This work demonstrates that hit-5 may be a potential anticancer agent.
Biomedical Processing of Polyhydroxyalkanoates

The rapidly growing interest on polyhydroxyalkanoates (PHA) processing for biomedical purposes is justified by the unique combinations of characteristics of this class of polymers in terms of biocompatibility, biodegradability, processing properties, and mechanical behavior, as well as by their great potential for sustainable production. This article aims at overviewing the most exploited processing approaches employed in the biomedical area to fabricate devices and other medical products based on PHA for experimental and commercial applications. For this purpose, physical and processing properties of PHA are discussed in relationship to the requirements of conventionally-employed processing techniques (e.g., solvent casting and melt-spinning), as well as more advanced fabrication approaches (i.e., electrospinning and additive manufacturing). Key scientific investigations published in literature regarding different aspects involved in the processing of PHA homo- and copolymers, such as poly(3-hydroxybutyrate), poly(3-hydroxybutyrate-co-3-hydroxyvalerate), and poly(3-hydroxybutyrate-co-3-hydroxyhexanoate), are critically reviewed.
Cross-talk between iNKT cells and CD8 T cells in the spleen requires the IL-4/CCL17 axis for the generation of short-lived effector cells

Significance Efficient iNKT help require antigen presentation to both the CD8+ T cell and the helper cell interacting with the same DCs. However, it remains unclear where and when iNKT cells, DCs, and CD8+ T cells meet, but it is rather accepted that these interactions should occur sequentially. Here, we show that iNKT cell help occurs in 2 spatiotemporal distinct phases and involves rather concomitant interactions. Indeed, at 24 h, iNKT cells are massively recruited in the white pulp, and the majority of activated CD8+ T cells are forming concomitant long-lasting interactions with iNKT cells and DCs. This study illustrates the importance of simultaneous delivery of antigen and adjuvant and should be considered in the design of new vaccines or immunotherapies. Mounting an effective immune response relies critically on the coordinated interactions between adaptive and innate compartments. How and where immune cells from these different compartments interact is still poorly understood. Here, we demonstrate that the cross-talk between invariant natural killer T cells (iNKT) and CD8+ T cells in the spleen, essential for initiating productive immune responses, is biphasic and occurs at 2 distinct sites. Codelivery of antigen and adjuvant to antigen-presenting cells results in: 1) initial short-lived interactions (0 to 6 h), between CD8+ T cells, dendritic cells (DCs), and iNKT cells recruited outside the white pulp; 2) followed by long-lasting contacts (12 to 24 h) between iNKT cells, DCs, and CD8+ T cells occurring in a 3-way interaction profile within the white pulp. Both CXCR3 and CCR4 are essential to orchestrate this highly dynamic process and play nonredundant in T cell memory generation. While CXCR3 promotes memory T cells, CCR4 supports short-lived effector cell generation. We believe our work provides insights into the initiation of T cell responses in the spleen and their consequences for T cell differentiation.
A conceptual framework for infusing social justice in school psychology training

This paper presents a framework for how a school psychology program that desires to embrace a philosophy of social justice can implement this philosophy throughout training. Five key areas will be shared that contribute to social justice being infused throughout the entire program. These areas include: a) the program mission statement; b) the student body, admittance criteria and interview techniques; c) specific courses, course content, and assignments focused on social justice issues; d) community partnering; and e) student and faculty involved community-based projects. It is believed that this framework will assist trainers in providing a practical application of social justice to school psychology training which will ultimately be carried over into practice.
Targeting chronic NFAT activation with calcineurin inhibitors in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) represents the most common adult lymphoma that is divided into two major molecular subtypes, the germinal center B-cell-like (GCB) and the aggressive activated B-cell-like (ABC) DLBCL. Previous studies suggested that chronic BCR signaling and increased NF-κB activation contribute to ABC DLBCL. Here we show that the activity of the transcription factor NFAT is chronically elevated in both DLBCL subtypes. Surprisingly, NFAT activation was independent of BCR signaling, but mediated by an increased calcium flux and calcineurin-mediated dephosphorylation of NFAT. Intriguingly, although NFAT was activated in both DLBCL subtypes, long-term calcineurin inhibition by cyclosporin A or FK506, both clinically approved drugs, triggered potent cytotoxicity specifically in ABC DLBCL cells. The antitumor effects of calcineurin inhibitors were associated with the downregulation of c-Jun, IL-6 and IL-10, which were identified as NFAT target genes particularly important for survival of ABC DLBCL. Furthermore, calcineurin blockade synergized with BCL-2 and MCL-1 inhibitors in killing ABC DLBCL cells. Collectively, these findings identify constitutive NFAT signaling as a crucial functional driver of ABC DLBCL and highlight calcineurin inhibition as a novel strategy for the treatment of ABC DLBCL.
EFFECT OF YOGA ON DEPRESSION AND QUALITY OF LIFE IN DRUG ABUSERS

Background: Drug abuse including alcohol may lead to health problems, social problems, morbidity, injuries, unprotected sex, violence, deaths, motor vehicle accidents, homicides, suicides, physical dependence or psychological addiction. Objectives: To study the efficacy of yoga on Quality of life of drug abusers and to study the efficacy of Yoga on measures of depression of drug abusers. Methods and Materials: 66 drug abused males with the mean age of 32. 50Â±9.86 years participated in the randomized control trial pre and post study. BDI-II and WHOQOL-BREF were used to assess depression score and quality of life before and after. Statistical analysis : Shapiro - Wilk, Wilcoxon signed rank test and Mann Whitney test were used for analyzing the data with the help of SPSS 16. Results: There was significant reduction after yoga intervention in depression scores (BDI-II) (p=0.000) and significant increase in Quality of life Domain 1, 2 and 3 (p=0.000, p=0.043, p=0.015). There was no significant increase in QOL Domain 4 (p=0.089). Regarding wait list control group, after the intervention programme, there was significant reduction in depression score, (p=0.040) and no significant increase in QOLBREF score in all four domains. Conclusion: Thus this study has shown that Yoga practice can help in reducing depression symptoms and increased quality of life in drug abuser.
Bilayer MoSe2/HfS2 Nanocomposite as a Potential Visible-Light-Driven Z-Scheme Photocatalyst

Visible-light-driven photocatalytic overall water splitting is deemed to be an ideal way to generate clean and renewable energy. The direct Z-scheme photocatalytic systems, which can realize the effective separation of photoinduced carriers and possess outstanding redox ability, have attracted a huge amount of interest. In this work, we have studied the photocatalytic performance of the bilayer MoSe2/HfS2 van der Waals (vdW) heterojunction following the direct Z-scheme mechanism by employing the hybrid density functional theory. Our calculated results show that the HfS2 and MoSe2 single layers in this heterojunction are used for the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER), respectively. The charge transfer between the two layers brought about an internal electric field pointing from the MoSe2 layer to the HfS2 slab, which can accelerate the separation of the photoinduced electron–hole pairs and support the Z-scheme electron migration near the interface. Excitingly, the optical absorption intensity of the MoSe2/HfS2 heterojunction is enhanced in the visible and infrared region. As a result, these results reveal that the MoSe2/HfS2 heterojunction is a promising direct Z-scheme photocatalyst for photocatalytic overall water splitting.
Evaluation of the Cytotoxicity and Oxidative Stress Response of CeO2-RGO Nanocomposites in Human Lung Epithelial A549 Cells

Graphene-based nanocomposites have attracted enormous interest in nanomedicine and environmental remediation, owing to their unique characteristics. The increased production and widespread application of these nanocomposites might raise concern about their adverse health effects. In this study, for the first time, we examine the cytotoxicity and oxidative stress response of a relatively new nanocomposite of cerium oxide-reduced graphene oxide (CeO2-RGO) in human lung epithelial (A549) cells. CeO2-RGO nanocomposites and RGO were prepared by a simple hydrothermal method and characterized by relevant analytical techniques. Cytotoxicity data have shown that RGO significantly induces toxicity in A549 cells, evident by cell viability reduction, membrane damage, cell cycle arrest, and mitochondrial membrane potential loss. However, CeO2-RGO nanocomposites did not cause statistically significant toxicity as compared to a control. We further observed that RGO significantly induces reactive oxygen species generation and reduces glutathione levels. However, CeO2-RGO nanocomposites did not induce oxidative stress in A549 cells. Interestingly, we observed that CeO2 nanoparticles (NPs) alone significantly increase glutathione (GSH) levels in A549 cells as compared to a control. The GSH replenishing potential of CeO2 nanoparticles could be one of the possible reasons for the biocompatible nature of CeO2-RGO nanocomposites. Our data warrant further and more advanced research to explore the biocompatibility/safety mechanisms of CeO2-RGO nanocomposites in different cell lines and animal models.
Multiple Functions of B Cells in the Pathogenesis of Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by excessive autoantibody production and multi-organ involvement. Although the etiology of SLE still remains unclear, recent studies have characterized several pathogenic B cell subsets and regulatory B cell subsets involved in the pathogenesis of SLE. Among pathogenic B cell subsets, age-associated B cells (ABCs) are a newly identified subset of autoreactive B cells with T-bet-dependent transcriptional programs and unique functional features in SLE. Accumulation of T-bet+ CD11c+ ABCs has been observed in SLE patients and lupus mouse models. In addition, innate-like B cells with the autoreactive B cell receptor (BCR) expression and long-lived plasma cells with persistent autoantibody production contribute to the development of SLE. Moreover, several regulatory B cell subsets with immune suppressive functions have been identified, while the impaired inhibitory effects of regulatory B cells have been indicated in SLE. Thus, further elucidation on the functional features of B cell subsets will provide new insights in understanding lupus pathogenesis and lead to novel therapeutic interventions in the treatment of SLE.
Risk factors of insomnia in the elderly with special reference to depression and hypertension

Dear Editor, Zou et al. conducted a cross-sectional study to investigate clinical risk factors of insomnia in the elderly. In a logistic regression model, insomnia was significantly associated with coronary heart disease, dizziness, chronic pain, anorexia, malnutrition, depression, and cognitive decline. In contrast, hypertension, diabetes, hyperlipidaemia, headache, age, and education level were not significantly associated with insomnia. I have some comments on this report. First, Gulia and Kumar summarized sleep disorders in the elderly. They presented evidence that obstructive sleep apnoea leads to a higher risk of cardiovascular diseases, headaches, memory loss, and depression. In addition, metabolic disorders such as hypertension, diabetes mellitus, and renal failure were closely associated with sleep disturbances, which is inconsistent with results by Zou et al. Causal association should be verified by prospective and/or interventional studies. Second, Jarrin et al. conducted a systematic review on the association between insomnia and hypertension by considering causal direction. Hypertension did not significantly predict future insomnia in middleaged adults, but it did in older adults. Additionally, there was no evidence of the impact of insomnia therapy on blood pressure control. I speculate that a significant association between hypertension and insomnia in the elderly would be caused by another factor such as obstructive sleep apnoea, and risk assessment should be comprehensively made. Finally, Dong and Yang conducted a prospective study to evaluate the effect of insomnia on subsequent incident hypertension and depression in older populations. Adjusted hazard ratios (95% confidence intervals) of insomnia for hypertension and depression were 1.11 (1.01–1.21) and 9.91 (6.37– 15.41), respectively. The association between insomnia and physical-mental disorders might be complicated, and insomnia may present as concurrent or subsequent disorders in the elderly.
Indoor Pollutants Detection in Buildings Based on Numerical Simulation

According to statistics, the proportion of indoor activities in today’s society has reached more than 70%. Indoor air quality has become a major factor affecting the people’s quality of life and health. In order to realize the detection and monitoring of diversified indoor air pollutants, this paper proposes one research idea of detecting indoor pollutants based on numerical simulation method. The visualization program ITES2.0 was used as the numerical simulation software to simulate and evaluate the indoor indexes such as formaldehyde, carbon dioxide, temperature and airflow velocity etc. in the building. Besides, the two schemes of the actual instrumental measurement and the subjective evaluation questionnaire were set up respectively for comparison. By taking one indoor office in Changsha city as the example, the numerical simulation was conducted to make comparation and validation of pollutant concentrations between instrument measurement and subjective evaluation. The experimental comparison results show that the relative error of the average index values between the numerical simulation results and the actual measured values at each detection point is 10%, which is consistent with the subjective evaluation of the indoor air quality grade.
Inhibitors of Brassinosteroid Biosynthesis and Signal Transduction

Chemical inhibitors are invaluable tools for investigating protein function in reverse genetic approaches. Their application bears many advantages over mutant generation and characterization. Inhibitors can overcome functional redundancy, their application is not limited to species for which tools of molecular genetics are available and they can be applied to specific tissues or developmental stages, making them highly convenient for addressing biological questions. The use of inhibitors has helped to elucidate hormone biosynthesis and signaling pathways and here we review compounds that were developed for the plant hormones brassinosteroids (BRs). BRs are steroids that have strong growth-promoting capacities, are crucial for all stages of plant development and participate in adaptive growth processes and stress response reactions. In the last two decades, impressive progress has been made in BR inhibitor development and application, which has been instrumental for studying BR modes of activity and identifying and characterizing key players. Both, inhibitors that target biosynthesis, such as brassinazole, and inhibitors that target signaling, such as bikinin, exist and in a comprehensive overview we summarize knowledge and methodology that enabled their design and key findings of their use. In addition, the potential of BR inhibitors for commercial application in plant production is discussed.