Miracle-dz/UniFAR-FTUs huggingface dataset:
The HIV epidemic in Latin America: a time to reflect on the history of success and the challenges ahead

The HIV epidemic in Latin America: a time to reflect on the history of success and the challenges ahead Brenda Crabtree-Ram ırez* , Pablo F Belaunzar an-Zamudio* , Claudia P Cortes, Miguel Morales, Omar Sued, Juan Sierra-Madero, Pedro Cahn, Anton Pozniak and Beatriz Grinsztejn Corresponding author: Brenda Crabtree Ram ırez, Departamento de Infectolog ıa, Instituto Nacional de Ciencias M edicas y Nutrici on, Salvador Zubir an, Vasco de Quiroga 15, Tlalpan, C.P. 14080, Mexico. Tel: +52 5554870900, ext. 5504, 5508 (brenda.crabtree@infecto.mx) *These authors have contributed equally to this work.
Apoptotic effects of thymol, a novel monoterpene phenol, on different types of cancer.

BACKGROUND Cancer is a major public health problem in many areas of the world. Many anticancer drugs in current clinical use have been isolated from plant species or are based on such substances. Thymol (5-methyl-2-isopropylphenol) is an oxygenated aromatic compound from monoterpene group. It is the main constituent of thyme essential oil and shows antioxidant, antiseptic and antiproliferative properties. The aim of this study is to determine the antiproliferative activity and apoptotic effect of thymol on prostate cancer (PC-3, DU145), breast cancer (MDA-MB-231), and lung cancer (KLN205) cell lines. METHODS The cancer cells were treated with different concentrations of thymol (100, 200, 400, 600, 800 µM) at 24 h, 48 h and 72 h. The cell viability was investigated by MTT assay and analysis of apoptosis was determined with annexin V assay. RESULTS The study showed the dose and time-dependent cytotoxic effect of thymol in PC-3, DU145, MDA-MB-231, and KLN205 cancer cell lines. Thymol significantly induced apoptosis in all groups in a dose-dependent manner. Statistical analysis showed a significant difference between thymol‑treated cell lines compared to the control (p < 0.001). CONCLUSION The data in the present study demonstrated that thymol has apoptotic and antiproliferative properties in lung, breast and prostate cancer cell lines. Thymol could serve as a potential therapeutic agent in the future (Fig. 5, Ref. 26).
Unpredictable maternal behavior is associated with a blunted infant cortisol response.

BACKGROUND Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is associated with poor physical and mental health. Early-life adversity may dysregulate cortisol response to subsequent stress. This study examines the association between patterns of maternal behavior and infant stress response to a challenge. Specifically, we test whether infant exposure to unpredictable maternal sensory signals is related to the cortisol response to a painful stressor. METHOD Participants were 102 mothers and their children enrolled in a longitudinal study. Patterns of maternal sensory signals were evaluated at 6 and 12 months during a 10-min mother-infant play episode. Entropy rate was calculated as a quantitative measure of the degree of unpredictability of maternal sensory signals (visual, auditory, and tactile) exhibited during the play episode. Infant saliva samples were collected for cortisol analysis before and after inoculation at 12 months. RESULTS Unpredictable patterns of maternal sensory signals were associated with a blunted infant cortisol response to a painful stressor. This relation persisted after evaluation of covariates including maternal sensitivity and maternal psychological distress. CONCLUSIONS This study provides evidence that unpredictable patterns of maternal sensory signals are one process through which caregiving affects the function of infant stress response systems.
Some non-bacteriological determinants and implications of antibiotic use in upper respiratory tract illness.

: Antibiotics are widely but inconsistently used by general practitioners in the UK for treatment of respiratory infections. Although it might be expected that antibiotic use would be governed by biomedical factors this is often not the case. Four non-bacteriological determinants of antibiotic use are identified and discussed; these are (i) the doctor's anxiety about his workload, (ii) the response of doctors to social pressures, (iii) misinterpretation of underlying reasons for a consultation and (iv) fear of the possible development of sequels to streptococcal illness. The implications of the variable response of doctors to these influences are discussed. These apply, not only to doctors and patients, but also to relationships between them. In addition there are important implications for the credibility of general practice as a critical and academically respectable discipline.
Transient enhanced cell division by blocking DNA synthesis in Escherichia coli

Duplication of the bacterial nucleoid is necessary for cell division hence specific arrest of DNA replication inhibits divisions culminating in filamentation, nucleoid dispersion and appearance of a-nucleated cells. It is demonstrated here that during the first 10 min however, Escherichia coli enhanced residual divisions: the proportion of constricted cells doubled (to 40%), nucleoids contracted and cells remodelled dimensions: length decreased and width increased. The preliminary data provides further support to the existence of temporal and spatial couplings between the nucleoid/replisome and the sacculus/divisome, and is consistent with the idea that bacillary bacteria modulate width during the division process exclusively.
Whether statin use improves the survival of patients with glioblastoma?

Abstract Background: Glioblastomas are malignant brain tumors associated with high mortality and poor prognosis. Evidence from preclinical studies suggests that statins have an antitumor role, but their effects on the survival of patients with glioblastoma remain controversial. This meta-analysis attempts to assess the association between statins and glioblastoma. Methods: We searched 4 databases (PubMed, Web of Science, Embase, and Cochrane Library) for articles that evaluate the effect of statins on the survival of patients with glioblastoma. Two reviewers were asked to assess the quality of the studies and extract the data regarding progression-free survival (PFS) and overall survival (OS). Result: A total of 5 studies met the inclusion criteria with 430 statin users and 2089 nonstatin users. All 5 studies were retrospectively analyzed. The pooled hazard ratio (HR) and 95% confidence intervals (CIs) were calculated. There was no benefit of statins found pertaining to the survival of glioblastoma patients in both PFS (HR, 0.97; CI, 0.84–1.13) and OS (HR, 0.98; CI, 0.87–1.11). In a subgroup defined by the patterns of statin use, it was determined that usage before glioblastoma diagnosis favored the OS of patients (HR, 0.85). The result, however, failed to demonstrate a statistically significant difference. Conclusion: Use of statins was not associated with prolonged survival of patients with glioblastoma. Further well-designed randomized controlled trials are needed to confirm.
The effect of maternal sleep deprivation on differentiation of mesenchymal stem cells in the presence of neonates brain cerebrospinal fluid of Wistar rats.

OBJECTIVE Cerebrospinal fluid (CSF) contains proliferation, differentiation and maturation signals that are essential factors for brain development. Due to presence of such factors this fluid has proliferative and differentiation potential. A previous study showed that maternal sleep deprivation (MSD) decrease the number of newborn neurons in development of hippocampus. Also, it impairs hippocampus-dependent spatial learning and memory in the young offspring rat. MSD can change CSF factors. In the present study, the effect of MSD-CSF on differentiation of mesenchymal stem cells to neural cells was examined, and expression of Nestin, Neun, and NeurD1 that are neurogenic markers was investigated. MATERIAL AND METHODS In this study, bone marrow mesenchymal stem cells were aspirated from the femur and tibia of young male Wistar rats. Then cell suspension was cultured in DMEM medium supplemented with 10 % FBS and 1 % antibiotics. Pregnant rats were subjected to sleep deprivation for 6 h by gentle handling during 4th, 7th, and 18th day of pregnancy. CSF was collected from cisterna magna of neonate rats. CSF was added to culture media with a 5 % ratio (v/v). Then cell viability was determined with MTT assay. Total cellular RNA was extracted, cDNA was synthesized and NeuN, Nestin, NeuroD1 and IL-6 genes were analyzed by Real-time PCR. RESULTS Real time-PCR analysis showed that expression of Neun and NeurD1gene decreased compared with culture in normal CSF (N-CSF), and also showed that expression of Nestin did not decrease, inflammatory gene (IL-6) showed high expression compared to culture with N-CSF. CONCLUSION Based on our results, MSD-CSF could inhibit neurogenesis process in mesenchymal stem cells and also, this result suggests that MSD can suppress neural differentiation and decrease of neurogenesis gene expression. Overall these findings suggest that insomnia and sleep loss may active inflammatory responses in the brain and change CSF-markers (Fig. 3, Ref. 34).
Evidence supporting the enhanced efficacy of pentavalent antimonials with adjuvant therapy for cutaneous leishmaniasis: a systematic review and meta‐analysis

Cutaneous leishmaniasis (CL) is one of the major neglected disease worldwide. Although many drugs have been used, the pentavalent antimonials (PA) remain as the first‐line choice despite their toxicity and limited efficacy. The combination of two drugs has risen as a potential alternative to increase the cure rate while lowering the side‐effects caused by pentavalent antimonials (PA). The objective of this study was to critically review and appraise the potential synergism of the adjuvant therapies of PA with other drugs/interventions previously used in the literature. We carried out a search of literature from PubMed, MEDLINE, Embase, Cochrane and clinicaltrials.gov. Articles that described a two‐arm or three‐arm design in which one of the arms consisted in a combination of a drug/intervention with intralesional or systemic PA were selected. The primary outcome was proportion of complete clearance of the lesions defined as complete re‐epithelization and/or negative direct smear. Our literature search identified 554 references. Thirty‐one records with a total sample size of 2668 participants met the eligibility criteria. The studies investigated the association of PA with the following: cryotherapy (five studies), allopurinol, imiquimod, pentoxifylline (four studies each), trichloroacetic acid 50% (three studies) and other additional interventions (eleven studies). Overall, the combined therapy of PA with a supplementary intervention was superior to PA monotherapy (RR: 1.23 95% CI: 1.11–1.35, I2 = 64%). In association with PA, the comparator‐specific stratified analysis showed that cryotherapy (RR: 1.50 95% CI: 1.25–1.81, I2 = 57%) and allopurinol (RR: 1.70 95% CI: 1.37–2.12, I2 = 28%) were superior to PA in monotherapy. On the contrary, the combined therapy with imiquimod (RR: 1.08 95% CI: 0.88–1.32, I2 = 40%) and pentoxifylline (RR: 1.14 95% CI: 0.94–1.40, I2 = 41%) revealed a non‐significant result. The application of TCA along with PA did not show significant differences in the clearance rate, although it was close to it (RR: 1.31 95% CI: 0.99–1.73, I2 = 84%). The present work represents an attempt to find new and reliable treatment modalities to enhance the efficacy based on the adjuvant therapy of pre‐existing drugs/interventions with PA. According to our results, the combination of allopurinol‐PA is the most effective adjuvant therapy. The application of cryotherapy and TCA stand as useful and encouraging supplementary interventions. The combination of imiquimod‐PA and pentoxifylline adds no additional benefit. The results of this work may be helpful in devising and modifying the current guidelines for CL which face major remaining evidence gaps. Triple therapies consisting in cryotherapy‐PA‐TCA or allopurinol‐PA‐cryotherapy or allopurinol‐PA‐TCA can represent promising treatments yet to be confirmed in future trials.
Systems and in vitro pharmacology profiling of diosgenin against breast cancer

Aim: The purpose of this study was to establish a mode of action for diosgenin against breast cancer employing a range of system biology tools and to corroborate its results with experimental facts. Methodology: The diosgenin-regulated domains implicated in breast cancer were enriched in the Kyoto Encyclopedia of Genes and Genomes database to establish diosgenin-protein(s)-pathway(s) associations. Later, molecular docking and the lead complexes were considered for molecular dynamics simulations, MMPBSA, principal component, and dynamics cross-correlation matrix analysis using GROMACS v2021. Furthermore, survival analysis was carried out for the diosgenin-regulated proteins that were anticipated to be involved in breast cancer. For gene expression analyses, the top three targets with the highest binding affinity for diosgenin and tumor expression were examined. Furthermore, the effect of diosgenin on cell proliferation, cytotoxicity, and the partial Warburg effect was tested to validate the computational findings using functional outputs of the lead targets. Results: The protein-protein interaction had 57 edges, an average node degree of 5.43, and a p-value of 3.83e-14. Furthermore, enrichment analysis showed 36 KEGG pathways, 12 cellular components, 27 molecular functions, and 307 biological processes. In network analysis, three hub proteins were notably modulated: IGF1R, MDM2, and SRC, diosgenin with the highest binding affinity with IGF1R (binding energy −8.6 kcal/mol). Furthermore, during the 150 ns molecular dynamics (MD) projection run, diosgenin exhibited robust intermolecular interactions and had the least free binding energy with IGF1R (−35.143 kcal/mol) compared to MDM2 (−34.619 kcal/mol), and SRC (-17.944 kcal/mol). Diosgenin exhibited the highest cytotoxicity against MCF7 cell lines (IC50 12.05 ± 1.33) µg/ml. Furthermore, in H2O2-induced oxidative stress, the inhibitory constant (IC50 7.68 ± 0.51) µg/ml of diosgenin was lowest in MCF7 cell lines. However, the reversal of the Warburg effect by diosgenin seemed to be maximum in non-cancer Vero cell lines (EC50 15.27 ± 0.95) µg/ml compared to the rest. Furthermore, diosgenin inhibited cell proliferation in SKBR3 cell lines more though. Conclusion: The current study demonstrated that diosgenin impacts a series of signaling pathways, involved in the advancement of breast cancer, including FoxO, PI3K-Akt, p53, Ras, and MAPK signaling. Additionally, diosgenin established a persistent diosgenin-protein complex and had a significant binding affinity towards IGF1R, MDM2, and SRC. It is possible that this slowed down cell growth, countered the Warburg phenomenon, and showed the cytotoxicity towards breast cancer cells.
Attitudes to disclosure of HIV-serostatus to new sexual partners and sexual behaviours among HIV-diagnosed gay, bisexual and other men who have sex with men in the UK

ABSTRACT We assessed attitudes to disclosure to new sexual partners and association with sexual behaviours among HIV-diagnosed gay, bisexual, and other men who have sex with men (GBMSM) in the UK Antiretrovirals, Sexual Transmission Risk and Attitudes (ASTRA) study in 2011-12. Among 1373 GBMSM diagnosed with HIV for ≥3 months and reporting sex in the past three months (84% on antiretroviral therapy (ART), 75% viral load (VL) ≤50c/mL), 56.3% reported higher sexual disclosure (“agree” or “tend to agree” with “I’d expect to tell a new partner I’m HIV-positive before we have sex”). GBMSM on ART with self-reported undetectable VL had lower disclosure than those on ART without self-reported undetectable VL and those not on ART. Higher sexual disclosure was associated with higher prevalence of CLS in the past three months; this was due to its association with CLS with other HIV-positive partners. Higher sexual disclosure was more common among GBMSM who had CLS with other HIV-positive partners only (72.1%) compared to those who had higher-risk CLS with HIV-serodifferent partners (55.6%), other CLS with HIV-serodifferent partners (45.9%), or condom-protected sex only (47.6%). Findings suggest mutual HIV-disclosure and HIV-serosorting were occurring in this population. Knowledge of VL status may have impacted on disclosure to sexual partners.
Location Con(cid:29)ict Resolution with an Ontology

Location modelling is central for many pervasive applications and is a key challenge in this area. One major di(cid:30)culty in location modelling is due to the nature of evidence about a person’s location; the evidence is commonly noisy, uncertain and con(cid:29)icting. Ontological reasoning is intuitively appealing to help address this problem, as re(cid:29)ected in several previous proposals for its use. This paper makes several important contributions to the exploration of the potential power of ontologies for improving reasoning about people’s location from the available evidence. We describe ONCOR, our lightweight ontology framework: it has the notable and important property that it can be semi-automatically constructed, making new uses of it practical. This paper provides a comprehensive evaluation on how on-tological reasoning can support location modelling: we introduce three algorithms for such reasoning and their evaluation based on a study of 8 people over 10(cid:21)13 days. The results indicate the power of the approach, with mean error rates dropping from 55% with a naive algorithm to 16% with the best of the ontologically based algorithms. This work provides the (cid:28)rst implementation of such an approach with a range of ontological reasoning approaches explored and evaluated.
A Human-Centered Approach to Designing Teachable Systems

Machine Learning technologies will eventually enable an unprecedented level of empowerment for end users–letting them adapt and personalize the behavior of AI systems to their own unique situations, needs, and desires through naturalistic interactions. Similar to how people can improve and extend one another through teaching, machine learning technologies promise to let users modify the behavior of systems by teaching rather than programming. However, there are many challenges faced when designing such teachable systems that have heretofore impeded their development. This paper aims to highlight two of these challenges. First, the development of learning systems has largely been restricted to technical fields, such as machine learning or cybernetics, due to the complexity of making such systems even work. Thus, there has been a lack of opportunities to provide an HCI perspective on how interactions with such systems should be designed. To address this challenge, we introduce a framework for conceptualizing teachable systems that distinguishes the interactive component from the learning component of these systems, to better enable the application of the HCI perspective on the design of the interaction between the user and system. Second, there is also a general lack of HCI methods for prototyping teachable systems, specifically when it comes to designing systems with learning capabilities that do not currently exist. To overcome this challenge, we presents a
Identification of extremely GC-rich micro RNAs for RT-qPCR data normalization in human plasma

We aimed at extending the repertoire of high-quality miRNA normalizers for reverse transcription-quantitative PCR (RT-qPCR) of human plasma with special emphasis on the extremely guanine-cytosine-rich portion of the miRNome. For high-throughput selection of stable candidates, microarray technology was preferred over small-RNA sequencing (sRNA-seq) since the latter underrepresented miRNAs with a guanine-cytosine (GC) content of at least 75% (p = 0.0002, n = 2). miRNA abundances measured on the microarray were ranked for consistency and uniformity using nine normalization approaches. The eleven most stable sequences included miRNAs of moderate, but also extreme GC content (45%–65%: miR-320d, miR-425-5p, miR-185-5p, miR-486-5p; 80%–95%: miR-1915-3p, miR-3656-5p, miR-3665-5p, miR-3960-5p, miR-4488-5p, miR-4497 and miR-4787-5p). In contrast, the seven extremely GC-rich miRNAs were not found in the two plasma miRNomes screened by sRNA-seq. Stem-loop RT-qPCR was employed for stability verification in 32 plasma samples of healthy male Caucasians (age range: 18–55 years). In general, inter-individual variance of miRNA abundance was low or very low as indicated by coefficient of variation (CV) values of 0.6%–8.2%. miR-3665 and miR-1915-3p outperformed in this analysis (CVs: 0.6 and 2.4%, respectively). The eight most stable sequences included four extremely GC-rich miRNAs (miR-1915-3p, miR-3665, miR-4787-5p and miR-4497). The best-performing duo normalization factor (NF) for the condition of human plasma, miR-320d and miR-4787-5p, also included a GC-extreme miRNA. In summary, the identification of extremely guanine-cytosine-rich plasma normalizers will help to increase accuracy of PCR-based miRNA quantification, thus raise the potential that miRNAs become markers for psychological stress reactions or early and precise diagnosis of clinical phenotypes. The novel miRNAs might also be useful for orthologous contexts considering their conservation in related animal genomes.
Synthesis of Naphtho-Quinoxaline-7, 12-Dione, Anthra-Ptereidine-7, 12-Dione and Anthra-Pyridine Derivatives

In present investigation, addition of nitroso group at position 1 of 2-aminoanthraquinone (1) yielded 2-amino-1-nitroanthraquinone (2) was carried out by the reaction of compound (1) with sodium nitrite in water. Compound (2) was used as an initial intermediate to produce 3-amino-2-cyano-naphtho[2,3- f]quinoxaline-7, 12-dione (4) by reaction of compound (2) with cyanoacetamide in dimethylformamide in presence of piperidine gave intermediate (3), then cyclization may be carried out by releasing of water molecule. Compound (4) consider good and available starting key to synthesis many new of quinoxaline-dione, naphthoquinoxaline-dione, anthrapetridine-dione, anthrapyredine-dione, triazolepyredine-dione derivatives. The structures of the resulting products were determined by elemental analysis, mass, IR and 1H NMR spectral data.