Miracle-dz/UniFAR-FTUs huggingface dataset:
IL‐11 in cardiac and renal fibrosis: Late to the party but a central player

Fibrosis is a pathophysiological hallmark of cardiorenal disease. In the heart, fibrosis leads to contractile dysfunction and arrhythmias; in the kidney, it is the final common pathway for many diseases and predicts end‐stage renal failure. Despite this, there are currently no specific anti‐fibrotic treatments available for cardiac or renal disease. Recently and unexpectedly, IL‐11 was found to be of major importance for cardiorenal fibroblast activation and fibrosis. In mouse models, IL‐11 overexpression caused fibrosis of the heart and kidney while genetic deletion of Il11ra1 protected against fibrosis and preserved organ function. Neutralizing antibodies against IL‐11 or IL‐11RA have been developed that have anti‐fibrotic activity in human fibroblasts and protect against fibrosis in murine models of disease. While IL‐11 biology has been little studied and, we suggest, largely misunderstood, its autocrine activity in myofibroblasts appears non‐redundant for fibrosis, which offers new opportunities to better understand and potentially target cardiorenal fibrosis.
Younger and older adults’ prospective memory: the role of delay task difficulty

ABSTRACT There is mixed evidence on the impact of delay task difficulty on prospective memory (PM) performance and little research has examined this among older adults. The present study examined younger (N = 60) and older (N = 57) adults’ prospective memory (PM) performance after completing an easy or difficult Raven’s matrices task. To assess whether delay difficulty impacted how often participants thought about their PM intention, participants were asked to report on what they thought about during the delay task itself and retrospectively after all tasks were completed. Younger adults outperformed older adults on the PM task; however, delay task difficulty had no impact PM for either age group. Reports of thinking about the intention during the delay task differed by age group depending whether they were online or retrospective, however, overall greater reports of thinking about the intention was positively associated with PM performance.
Experiences of BRCA1/2 Gene Mutation-Positive Women With Cancer in Communicating Genetic Risk to Their Relatives.

BACKGROUND When a woman is diagnosed with hereditary breast or ovarian cancer, family members may be at high risk of cancers associated with BRCA1/2 gene mutation and benefit from disclosure of the genetic test result. This duty of informing relatives may be distressing, or relatives may not be properly informed. OBJECTIVE To qualitatively describe breast cancer patients' experiences communicating genetic risk of cancer to their relatives. METHODS Probands with BRCA1/2 gene mutations were recruited from an oncology institute in Istanbul, Turkey, and interviewed by telephone. Qualitative content analysis was conducted to derive central elements of the 30 women's experiences communicating genetic risk to their relatives. RESULTS Six themes were identified: response to genetic test results, reason for communication, feelings about communication, reflection after communication, results of communication, and needs. CONCLUSION Women with cancer found to have BRCA1/2 gene mutations tended to share their genetic test results within the family. The main motives for sharing test results were the desire to encourage relatives to get tested and moral and ethical convictions. Women needed explicit information regarding cancer risk and risk-reducing strategies to act upon. IMPLICATIONS FOR PRACTICE The women's feelings and reflections about the communication process were varied and suggest that personalized genetic risk communication interventions may better support women with BRCA1/2 gene mutations during and after communication with relatives. Long-term follow-up of those women is essential because of the need for informed decision on risk-reducing strategies.
Vaccine dose usage and wastage in the Metropolitan Region of Porto Alegre, Rio Grande do Sul, Brazil: a descriptive study, 2015-2017*

Correspondence: Scheila Mai – Rua Professor Cristiano Fischer, No 2062, Apto. 1209, Bairro Petrópolis, Porto Alegre, RS, Brazil. Postcode: 91410-000 E-mail: scheilamaienf@gmail.com Abstract Objective: to estimate usage and wastage of multi-dose and single-dose vaccine vials in the Metropolitan Region of Porto Alegre, Rio Grande do Sul, Brazil, from 2015 to 2017. Methods: a descriptive study was carried out based on secondary data from the National Immunization Program Information System (SIPNI) and the Strategic Health Supplies Information System (SIES). Results: a total of 12,342 records were examined; mean wastage rate was 45.8% (95%CI 39.5;51.7), while usage rate was 54.2% (95%CI 48.3;60.5); vaccines with the highest mean annual wastage rate were MMR (68.8% – 95%CI 66.5;71.1), BCG (68.1% – 95%CI 65.4;70.7), Hepatitis B (56.4% – 95%CI 53.0-59.7) and Yellow Fever (55.9% – 95%CI 51.4;60.4). Conclusion: the highest rates of vaccine wastage were for multi-dose vials; although single-dose vaccines also exceeded the acceptable limit defined by the World Health Organization.
Air Trapping Correlates With Increased Frequency of Albuterol Use and Severity of Wheeze in Persistent Asthma

BACKGROUND: Symptoms of asthma have been shown to correlate poorly with spirometric variables of obstruction. We hypothesized that lung volume measurements might correlate with symptoms and frequency of rescue inhaler use in asthma. METHODS: Patients with persistent asthma on treatment for ≥12 months were enrolled from university-based clinics. The association between lung volumes, spirometry, asthma symptoms, and rescue inhaler use were explored by using linear modeling. RESULTS: Among the 120 subjects, 76% were women. The mean age ± SD was 52 ± 15 y. With regard to ethnicity, 64% of the subjects were caucasian, 23% were Hispanic, and 13% were African-American. Twenty-one percent of the subjects reported chest pain. There was no significant correlation between asthma symptoms or rescue inhaler use to spirometry indices of obstruction. The residual volume percent of predicted showed a significant association with the wheeze score (r = 0.32, P = .001) and frequency of rescue inhaler use (r = 0.35, P ≤ .001). Linear contrast analysis showed that the mean wheeze score (P = .003) and frequency of rescue inhaler (P = .007) use increased linearly from the lowest to the highest quartiles of residual volume. Furthermore, multiple regression analysis showed an association only to the residual volume percent predicted value to the pressurized metered-dose inhaler score and the wheeze score. CONCLUSIONS: Frequent albuterol use and wheezing may be a sign of unrelieved air trapping. Chest pain is a unique symptom in persistent asthma, and the pathogenesis requires further studies. Lung volume measurement added to routine spirometry can help identify patients with asthma and with air trapping.
Moderate prenatal ethanol exposure stimulates CXCL12/CXCR4 chemokine system in radial glia progenitor cells in hypothalamic neuroepithelium and peptide neurons in lateral hypothalamus of the embryo and postnatal offspring.

BACKGROUND Prenatal exposure to ethanol has lasting effects on neuropeptide and neuroimmune systems in the brain alongside detrimental alcohol-related behaviors. At low-to-moderate doses, prenatal ethanol stimulates neurogenesis in lateral hypothalamus (LH) and increases neurons that express the orexigenic peptides, hypocretin/orexin (Hcrt/OX) and melanin-concentrating hormone (MCH), and the proinflammatory chemokine CCL2 which through its receptor CCR2 stimulates cell differentiation and movement. Our recent studies demonstrated that CCL2 and CCR2 colocalize with MCH neurons and are involved in ethanol's stimulatory effect on their development but show no relation to Hcrt/OX. Here we investigated another chemokine CXCL12 and its receptor CXCR4 which promote neurogenesis and neuroprogenitor cell proliferation, to determine if they also exhibit peptide specificity in their response to ethanol exposure. METHODS Pregnant rats were intraorally administered a moderate dose of ethanol (2 g/kg/d) from embryonic day 10 (E10) to E15. Their embryos and postnatal offspring were examined using real-time quantitative PCR and immunofluorescence histochemistry, to determine if ethanol affects CXCL12 and CXCR4 and the colocalization of CXCR4 with Hcrt/OX and MCH neurons in the LH and with radial glia neuroprogenitor cells in the hypothalamic neuroepithelium (NEP). RESULTS Prenatal ethanol strongly stimulated CXCL12 and CXCR4 in LH neurons of embryos and postnatal offspring. This stimulation was significantly stronger in Hcrt/OX than MCH neurons in LH and also occurred in radial glia neuroprogenitor cells dense in the NEP. These effects were sexually dimorphic, consistently stronger in females than males. CONCLUSIONS While showing prenatal ethanol exposure to have a sexually dimorphic, stimulatory effect on CXCL12 and CXCR4 in LH similar to CCL2 and its receptor, these results reveal their distinct relationship to the peptide neurons, with the former closely related to Hcrt/OX and the latter to MCH, and they link ethanol's actions in LH to a stimulatory effect on neuroprogenitor cells in the NEP.
Improving genomic prediction accuracy for meat tenderness in Nellore cattle using artificial neural networks.

The goal of this study was to compare the predictive performance of artificial neural networks (ANNs) with Bayesian ridge regression, Bayesian Lasso, Bayes A, Bayes B and Bayes Cπ in estimating genomic breeding values for meat tenderness in Nellore cattle. The animals were genotyped with the Illumina Bovine HD Bead Chip (HD, 777K from 90 samples) and the GeneSeek Genomic Profiler (GGP Indicus HD, 77K from 485 samples). The quality control for the genotypes was applied on each Chip and comprised removal of SNPs located on non-autosomal chromosomes, with minor allele frequency <5%, deviation from HWE (p < 10-6 ), and with linkage disequilibrium >0.8. The FImpute program was used for genotype imputation. Pedigree-based analyses indicated that meat tenderness is moderately heritable (0.35), indicating that it can be improved by direct selection. Prediction accuracies were very similar across the Bayesian regression models, ranging from 0.20 (Bayes A) to 0.22 (Bayes B) and 0.14 (Bayes Cπ) to 0.19 (Bayes A) for the additive and dominance effects, respectively. ANN achieved the highest accuracy (0.33) of genomic prediction of genetic merit. Even though deep neural networks are recognized to deliver more accurate predictions, in our study ANN with one single hidden layer, 105 neurons and rectified linear unit (ReLU) activation function was sufficient to increase the prediction of genetic merit for meat tenderness. These results indicate that an ANN with relatively simple architecture can provide superior genomic predictions for meat tenderness in Nellore cattle.
Probing the mutational landscape of regulators of G protein signaling proteins in cancer

Cancer-associated mutations in RGS proteins impair their ability to inhibit G protein signaling. Impairing RGS protein function Mutations in the genes encoding the α subunits of heterotrimeric G proteins are associated with cancer. In particular, mutations that prevent the Gα subunits from hydrolyzing GTP, thus rendering them constitutively active, are pro-oncogenic. DiGiacomo et al. surveyed cancer-associated mutations in regulator of G protein signaling (RGS) proteins, which are physiological inhibitors of G proteins. Through bioinformatics analysis, genetic interaction studies in yeast, and functional assays in mammalian cells, the authors showed that many cancer-associated RGS mutants fail to inhibit G protein signaling because of reduced protein stability or impaired interactions with their targets. With these tools, further cancer-associated mutations in RGS proteins can be characterized. The advent of deep-sequencing techniques has revealed that mutations in G protein–coupled receptor (GPCR) signaling pathways in cancer are more prominent than was previously appreciated. An emergent theme is that cancer-associated mutations tend to cause enhanced GPCR pathway activation to favor oncogenicity. Regulators of G protein signaling (RGS) proteins are critical modulators of GPCR signaling that dampen the activity of heterotrimeric G proteins through their GTPase-accelerating protein (GAP) activity, which is conferred by a conserved domain dubbed the “RGS-box. ” Here, we developed an experimental pipeline to systematically assess the mutational landscape of RGS GAPs in cancer. A pan-cancer bioinformatics analysis of the 20 RGS domains with GAP activity revealed hundreds of low-frequency mutations spread throughout the conserved RGS domain structure with a slight enrichment at positions that interface with G proteins. We empirically tested multiple mutations representing all RGS GAP subfamilies and sampling both G protein interface and noninterface positions with a scalable, yeast-based assay. Last, a subset of mutants was validated using G protein activity biosensors in mammalian cells. Our findings reveal that a sizable fraction of RGS protein mutations leads to a loss of function through various mechanisms, including disruption of the G protein–binding interface, loss of protein stability, or allosteric effects on G protein coupling. Moreover, our results also validate a scalable pipeline for the rapid characterization of cancer-associated mutations in RGS proteins.
ADAM12 is A Potential Therapeutic Target Regulated by Hypomethylation in Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and currently lacks any effective targeted therapy. Since epigenetic alterations are a common event in TNBC, DNA methylation profiling can be useful for identifying potential biomarkers and therapeutic targets. Here, genome-wide DNA methylation from eight TNBC and six non-neoplastic tissues was analysed using Illumina Human Methylation 450K BeadChip. Results were validated by pyrosequencing in an independent cohort of 50 TNBC and 24 non-neoplastic samples, where protein expression was also assessed by immunohistochemistry. The functional role of disintegrin and metalloproteinase domain-containing protein 12(ADAM12) in TNBC cell proliferation, migration and drug response was analysed by gene expression silencing with short hairpin RNA. Three genes (Von Willenbrand factor C and Epidermal Growth Factor domain-containing protein (VWCE), tetraspanin-9 (TSPAN9) and ADAM12) were found to be exclusively hypomethylated in TNBC. Furthermore, ADAM12 hypomethylation was associated with a worse outcome in TNBC tissues and was also found in adjacent-to-tumour tissue and, preliminarily, in plasma from TNBC patients. In addition, ADAM12 silencing decreased TNBC cell proliferation and migration and improved doxorubicin sensitivity in TNBC cells. Our results indicate that ADAM12 is a potential therapeutic target and its hypomethylation could be a poor outcome biomarker in TNBC.
Psychopathological Symptoms and Loneliness in Adult Internet Users: A Contemporary Public Health Concern

There are different concepts that translate abusive Internet use. Almost all these concepts converge on excessive time spent online, which can trigger the emergence of problematic situations. Most of the studies reported in the literature, both nationally and internationally, focused on a young population and found negative consequences of this Internet misuse. The objective of this study consists of associating the time spent using the Internet—in years, times per week, and hours per day—with psychopathological symptoms, as well as assessing the perception of loneliness, in an adult Portuguese population. A quantitative approach, based on a survey application, was conducted in a convenience sample composed by 418 participants (64.4% female), with a mean age of 29.9 years old (SD = 9.26), ranging from 18 to 73 years. The results suggest that maladaptive patterns of Internet use found in young people seem to be replicated in the adult population. A relationship between time spent on the Internet and psychopathological symptoms, and an association between loneliness and the number of hours spent on the Internet, were also identified. In an individualized and disconnected offline world, Internet impact in individuals’ well-being results must be highlighted, since it should be understood as a public health issue. The novelty of this study lies in the target population: Portuguese Internet users over 18 years of age, for which there is no specific study on the subject, thus emphasizing the transverse nature of the problem.
The Association of Stalking Victimization With Adolescents’ Depressed Mood and School Mattering

Stalking victimization may have a significant impact on adolescents’ well-being, above and beyond the effects of other types of interpersonal violence victimization. This article explored the association of stalking victimization (unwanted harassing or threats) with adolescents’ depressed mood and perception of mattering to other people. Adolescents (age M = 15.8 at baseline, 50.3% girls, 88.9% non-Hispanic White, 85.9% heterosexual) took surveys at two time points and reported on stalking victimization, depressed mood, and perception of mattering. Results indicate that, even when controlling for previous depressed mood and mattering, the odds of depressed mood and mattering among stalking victims was, respectively, 3.31 times higher and 0.49 times lower than the odds of depressed mood and mattering in non-victims. When controlling for other victimization experiences (i.e., dating violence, sexual assault, sexual harassment), the odds of depressed mood among stalking victims was 2.31 times higher than the odds of depressed mood among non-victims, but stalking victims were not less likely to report mattering. Although more research is needed, these results suggest that assessment and intervention efforts should target depressed mood in stalking victims in addition to underscoring the need for primary prevention of stalking in adolescence.
Sex- and Gender-Based Analysis in Cannabis Treatment Outcomes: A Systematic Review

There is evidence that sex- and gender-related factors are involved in cannabis patterns of use, health effects and biological mechanisms. Women and men report different cannabis use disorder (CUD) symptoms, with women reporting worse withdrawal symptoms than men. The objective of this systematic review was to examine the effectiveness of cannabis pharmacological interventions for women and men and the uptake of sex- and gender-based analysis in the included studies. Two reviewers performed the full-paper screening, and data was extracted by one researcher. The search yielded 6098 unique records—of which, 68 were full-paper screened. Four articles met the eligibility criteria for inclusion. From the randomized clinical studies of pharmacological interventions, few studies report sex-disaggregated outcomes for women and men. Despite emergent evidence showing the influence of sex and gender factors in cannabis research, sex-disaggregated outcomes in pharmacological interventions is lacking. Sex- and gender-based analysis is incipient in the included articles. Future research should explore more comprehensive inclusion of sex- and gender-related aspects in pharmacological treatments for CUD.
Impact and Intricacies of Bone Marrow Microenvironment in B-cell Lymphomas: From Biology to Therapy

Lymphoma, a group of widely prevalent hematological malignancies of lymphocyte origin, has become the focus of significant clinical research due to their high propensity for refractory/relapsed (R/R) disease, leading to poor prognostic outcomes. The complex molecular circuitry in lymphomas, especially in the aggressive phenotypes, has made it difficult to find a therapeutic option that can salvage R/R disease. Furthermore, the association of lymphomas with the Bone Marrow (BM) microenvironment has been found to portend worse outcomes in terms of heightened chances of relapse and acquired resistance to chemotherapy. This review assesses the current therapy options in three distinct types of lymphomas: diffuse large B-cell lymphoma, follicular lymphoma and mantle cell lymphoma. It also explores the role of the BM tumor microenvironment as a secure ‘niche’ for lymphoma cells to grow, proliferate and survive. It further evaluates potential mechanisms through which the tumor cells can establish molecular connections with the BM cells to provide pro-tumor benefits, and discusses putative therapeutic strategies for disrupting the BM-lymphoma cell communication.
Immunoinformatics‐aided identification of T cell and B cell epitopes in the surface glycoprotein of 2019‐nCoV

The 2019 novel coronavirus (2019‐nCoV) outbreak has caused a large number of deaths with thousands of confirmed cases worldwide, especially in East Asia. This study took an immunoinformatics approach to identify significant cytotoxic T lymphocyte (CTL) and B cell epitopes in the 2019‐nCoV surface glycoprotein. Also, interactions between identified CTL epitopes and their corresponding major histocompatibility complex (MHC) class I supertype representatives prevalent in China were studied by molecular dynamics simulations. We identified five CTL epitopes, three sequential B cell epitopes and five discontinuous B cell epitopes in the viral surface glycoprotein. Also, during simulations, the CTL epitopes were observed to be binding MHC class I peptide‐binding grooves via multiple contacts, with continuous hydrogen bonds and salt bridge anchors, indicating their potential in generating immune responses. Some of these identified epitopes can be potential candidates for the development of 2019‐nCoV vaccines.
Influence of SLCO1B1 polymorphisms on lopinavir Ctrough in Serbian HIV/AIDS patients

Lopinavir (LPV) is not a first‐line regimen. According to recent WHO data, LPV usage in low‐ and middle‐income countries accounted for approximately 52% of the adult and 23% of the paediatric protease inhibitor market in 2017. Since LPV is a substrate for the SLCO1B1 (OATP1B1) transporter, the aim of this study was to assess the impact of SLCO1B1 polymorphisms (rs11045819, rs4149032 and rs4149056) on LPV trough plasma concentrations (Ctrough) in Serbian patients.