Miracle-dz/UniFAR-FTUs huggingface dataset:
Optimization of the Cytotoxic Activity of Three Streptomyces Strains Isolated from Guaviare River Sediments (Colombia, South America)

Three Streptomyces strains isolated from Guaviare sediments (Colombia, South America) with cytotoxic activity against prostate cancer (PC3), breast cancer (MDA-MB-231), and lung cancer (A549) line cells were studied. The present investigation reveals the enhancement of the cytotoxic activity evaluating different values of pH, carbon sources (sucrose, glucose, xylose, maltose, and starch), and nitrogen sources (malt extract, yeast extract, meat extract, peptone, and potassium nitrate). Based on the response surface methodology, the isolates Streptomyces aburaviensis (73) had the maximum activity for lung cancer (IC50= 25.00 ± 1.86 ppm) with 4% of yeast extract, 3% of starch, and a pH value of 7. Streptomyces gramineus (386) had the maximum activity against prostate cancer (IC50= 6.14 ± 2.07 ppm) with 5% of malt extract, 3% of glucose, and a pH value of 6. Finally, Streptomyces psammoticus (519) had the maximum activity against breast cancer (IC50= 35.53 ± 2.71 ppm) with 1% of yeast extract, 4% of starch, and a pH 8. The results suggest that the ethyl acetate extracts from isolates Streptomyces aburaviensis (73), Streptomyces gramineus (386), and Streptomyces psammoticus (519) have a potential for use in pharmaceuticals as cytotoxic agents.
Biochemical and Epigenetic Insights into L-2-Hydroxyglutarate, a Potential Therapeutic Target in Renal Cancer

Purpose: Elevation of L-2-hydroxylgutarate (L-2-HG) in renal cell carcinoma (RCC) is due in part to reduced expression of L-2-HG dehydrogenase (L2HGDH). However, the contribution of L-2-HG to renal carcinogenesis and insight into the biochemistry and targets of this small molecule remains to be elucidated. Experimental Design: Genetic and pharmacologic approaches to modulate L-2-HG levels were assessed for effects on in vitro and in vivo phenotypes. Metabolomics was used to dissect the biochemical mechanisms that promote L-2-HG accumulation in RCC cells. Transcriptomic analysis was utilized to identify relevant targets of L-2-HG. Finally, bioinformatic and metabolomic analyses were used to assess the L-2-HG/L2HGDH axis as a function of patient outcome and cancer progression. Results: L2HGDH suppresses both in vitro cell migration and in vivo tumor growth and these effects are mediated by L2HGDH's catalytic activity. Biochemical studies indicate that glutamine is the predominant carbon source for L-2-HG via the activity of malate dehydrogenase 2 (MDH2). Inhibition of the glutamine-MDH2 axis suppresses in vitro phenotypes in an L-2-HG–dependent manner. Moreover, in vivo growth of RCC cells with basal elevation of L-2-HG is suppressed by glutaminase inhibition. Transcriptomic and functional analyses demonstrate that the histone demethylase KDM6A is a target of L-2-HG in RCC. Finally, increased L-2-HG levels, L2HGDH copy loss, and lower L2HGDH expression are associated with tumor progression and/or worsened prognosis in patients with RCC. Conclusions: Collectively, our studies provide biochemical and mechanistic insight into the biology of this small molecule and provide new opportunities for treating L-2-HG–driven kidney cancers.
Use and Opinions of Prescription Opioids Among Older American Adults: Sociodemographic Predictors.

Objectives This study identifies sociodemographic predictors of prescription opioid use among older adults (age 65+) during the peak decade of U.S. opioid prescription, and tests whether pain level and Medicaid coverage mediate the association between low wealth and opioid use. Predictors of prescription nonsteroidal anti-inflammatory drug (NSAID) use, and of opinions of both drug classes, are also examined. Method Regressions of opioid and NSAID use on sociodemographic characteristics, pain level, and insurance type were conducted using Health and Retirement Study 2004 core and 2005 Prescription Drug Study data (n=3,721). Mediation analyses were conducted, and user opinions of drug importance, quality, and side effects were assessed. Results Low wealth was a strong, consistent predictor of opioid use. Both pain level and Medicaid coverage significantly, but only partially, mediated this association. Net of wealth, there were no significant associations between education and use of, or opinions of, either class of drugs. Discussion Among older American adults, the poorest are disproportionately likely to have been exposed to prescription opioid analgesics. Wealth, rather than education, drove social class differences in mid-2000s opioid use. Opioid-related policies should take into account socioeconomic contributors to opioid use, and the needs and treatment histories of chronic pain patients.
Information and Communication Technologies Interest, Access, and Use: Cross-Sectional Survey of a Community Sample of Urban, Predominantly Black Women

Background Information and communication technologies (ICT) offer the potential for delivering health care interventions to low socioeconomic populations who often face barriers in accessing health care. However, most studies on ICT for health education and interventions have been conducted in clinical settings. Objective The aim of this study was to examine access to and use of mobile phones and computers, as well as interest in, using ICT for receipt of behavioral health information among a community sample of urban, predominately black, women with low socioeconomic status. Methods Participants (N=220) were recruited from hair salons and social service centers and completed audio-computer assisted self-interviews. Results The majority of the participants (212/220, 96.3%) reported use of a cell phone at least weekly, of which 89.1% (189/212) used smartphones and 62.3% (137/220) reported computer use at least weekly. Of the women included in the study, 51.9% (107/206) reported using a cell phone and 39.4% (74/188) reported using a computer to access health and/or safety information at least weekly. Approximately half of the women expressed an interest in receiving information about stress management (51%-56%) or alcohol and health (45%-46%) via ICT. Smartphone ownership was associated with younger age (odds ratio [OR] 0.92, 95% CI 0.87-0.97) and employment (OR 5.12, 95% CI 1.05-24.95). Accessing health and safety information weekly by phone was associated with younger age (OR 0.96, 95% CI 0.94-0.99) and inversely associated with higher income (OR 0.42, 95% CI 0.20-0.92). Conclusions Our findings suggest that ICT use, particularly smartphone use, is pervasive among predominantly black women with low socioeconomic status in urban, nonclinical settings. These results show that ICT is a promising modality for delivering health information to this population. Further exploration of the acceptability, feasibility, and effectiveness of using ICT to disseminate behavioral health education and intervention is warranted.
New Properties of a Bioinspired Pyridine Benzimidazole Compound as a Novel Differential Staining Agent for Endoplasmic Reticulum and Golgi Apparatus in Fluorescence Live Cell Imaging

In this study, we explored new properties of the bioinspired pyridine benzimidazole compound B2 (2,4-di-tert-butyl-6-(3H-imidazo[4,5-c]pyridine-2-yl)phenol) regarding its potential use as a differential biomarker. For that, we performed 1D 1HNMR (TOCSY), UV-Vis absorption spectra in different organic solvents, voltammetry profile (including a scan-rate study), and TD-DFT calculations that including NBO analyses, to provide valuable information about B2 structure and luminescence. In our study, we found that the B2 structure is highly stable, where the presence of an intramolecular hydrogen bond (IHB) seems to have a crucial role in the stability of luminescence, and its emission can be assigned as fluorescence. In fact, we found that the relatively large Stokes Shift observed for B2 (around 175 nm) may be attributed to the stability of the B2 geometry and the strength of its IHB. On the other hand, we determined that B2 is biocompatible by cytotoxicity experiments in HeLa cells, an epithelial cell line. Furthermore, in cellular assays we found that B2 could be internalized by passive diffusion in absence of artificial permeabilization at short incubation times (15 min to 30 min). Fluorescence microscopy studies confirmed that B2 accumulates in the endoplasmic reticulum (ER) and Golgi apparatus, two organelles involved in the secretory pathway. Finally, we determined that B2 exhibited no noticeable blinking or bleaching after 1 h of continuous exposure. Thus, B2 provides a biocompatible, rapid, simple, and efficient way to fluorescently label particular organelles, producing similar results to that obtained with other well-established but more complex methods.
Cardiac branched-chain amino acid oxidation is reduced during insulin resistance in the heart.

Recent studies have proposed that elevated branched-chain amino acids (BCAAs) may induce insulin resistance (IR) in muscle secondary to increased BCAA oxidation inhibiting glucose oxidation (GO) and fatty acid oxidation (FAO). However, BCAA oxidation rates have not been assessed in muscle IR, and cardiac FAO rates are actually already elevated in obesity-associated IR. We therefore directly examined cardiac BCAA oxidation in mice fed a high-fat diet (HFD) to induce insulin resistance to better understand the role of cardiac BCAA oxidation in cardiac IR. BCAA oxidation, GO, FAO, and glycolysis were measured in isolated working hearts from mice fed either a low-fat diet (LFD) or HFD for 10 wk. Insulin stimulation of cardiac GO and inhibition of FAO were blunted in HFD mice, resulting in a marked increase in FAO contribution to ATP production compared with LFD mice hearts (71.2% vs. 37.1%, respectively). Surprisingly, cardiac BCAA oxidation rate was reduced in HFD compared with LFD mice (33.5 ± 3.4 vs. 56.7 ± 7.1 nmol·min-1·g dry wt-1, respectively, P < 0.05, n = 9/group). In addition, BCAA oxidation contributed ~1% of the ATP production of the heart, and, as a result, alterations in BCAA oxidation could not significantly impact either GO or FAO rates. However, the decrease in BCAA oxidation was accompanied by an increase in BCAA concentration and impaired insulin signaling. These results suggest that cardiac IR is not due to an increase in BCAA oxidation and subsequent inhibition of GO and FAO. Rather, we propose that an inhibition of BCAA oxidation rate contributes to IR by leading to increased BCAA concentration, which negatively impacts insulin signaling.
Intravenous iron does not effectively correct preoperative anaemia in cardiac surgery: a pilot randomized controlled trial.

OBJECTIVES Preoperative anaemia is a strong predictor of blood transfusion requirements and must be assessed for appropriate optimization before elective surgery. Iron therapy is a transfusion-sparing approach effective for increasing haemoglobin concentrations. However, its role in elective cardiac surgery and the optimal route of administration remain unknown. This single-centre, non-blinded, randomized, controlled trial compared the effectiveness of intravenous ferric carboxymaltose therapy with oral iron for anaemic patients undergoing elective cardiac surgery. METHODS Fifty anaemic patients scheduled for elective cardiac surgery were randomized to receive either oral or intravenous iron therapy 3-8 weeks preoperatively. Changes in haemoglobin concentration were measured. Blood transfusion and postoperative outcome data were collected. RESULTS Preoperative median increases in haemoglobin were 1.0 g/l (interquartile range -3.25 to 7.25 g/l) and 3.0 g/l (interquartile range -1.25 to 6.25 g/l) for patients receiving intravenous and oral iron, respectively (P = 0.42). The median first 12-h blood loss was significantly higher in the intravenous group (655 ml; interquartile range 162-1540 ml) compared to the oral group (313 ml; interquartile range 150-1750 ml; P < 0.007). Median increments in serum ferritin were superior for the intravenous group (median difference 313 µg/l; interquartile range 228-496) compared to the oral group (median difference 5.5 µg/l; interquartile range -1.4 to 19.4; P < 0.001). CONCLUSIONS Increases in ferritin after intravenous iron administration were significantly greater than those after oral iron administration. There was no significant difference in haemoglobin increments between groups. Despite significantly higher intraoperative blood loss in the group receiving intravenous iron, blood transfusion requirements for both groups were not statistically different. CLINICAL TRIAL REGISTRATION ISRCTN22158788.
Optimizing a Parameterized Plug-and-Play ADMM for Iterative Low-Dose CT Reconstruction

Reducing the exposure to X-ray radiation while maintaining a clinically acceptable image quality is desirable in various CT applications. To realize low-dose CT (LdCT) imaging, model-based iterative reconstruction (MBIR) algorithms are widely adopted, but they require proper prior knowledge assumptions in the sinogram and/or image domains and involve tedious manual optimization of multiple parameters. In this paper, we propose a deep learning (DL)-based strategy for MBIR to simultaneously address prior knowledge design and MBIR parameter selection in one optimization framework. Specifically, a parameterized plug-and-play alternating direction method of multipliers (3pADMM) is proposed for the general penalized weighted least-squares model, and then, by adopting the basic idea of DL, the parameterized plug-and-play (3p) prior and the related parameters are optimized simultaneously in a single framework using a large number of training data. The main contribution of this paper is that the 3p prior and the related parameters in the proposed 3pADMM framework can be supervised and optimized simultaneously to achieve robust LdCT reconstruction performance. Experimental results obtained on clinical patient datasets demonstrate that the proposed method can achieve promising gains over existing algorithms for LdCT image reconstruction in terms of noise-induced artifact suppression and edge detail preservation.
A Meta-Analysis of the Influencing Factors for Tracheostomy after Cervical Spinal Cord Injury

Background Traumatic cervical spinal cord injury (CSCI) is a common disease that has high complication, disability, and mortality rates and a poor prognosis. Tracheostomy is an important supportive therapy for patients with CSCI. However, a consensus on the predictive factors for tracheostomy after CSCI has not been reached. Objective This meta-analysis study assessed the influencing factors for tracheostomy after CSCI. Methods We searched for relevant studies on the influencing factors for tracheostomy after CSCI. The extracted data were analyzed using RevMan 5.3 software. We calculated the odds ratio (OR) or mean difference (MD) and 95% confidence intervals (CIs). Results Sixteen eligible studies containing 9697 patients with CSCI were selected. The pooled OR (MD) and 95% CI of the influencing factors were as follows: age (mean ± SD): -0.98 (-4.00 to 2.03), advanced age: 1.93 (0.80 to 4.63), sex (male): 1.29 (1.12 to 1.49), American Spinal Injury Association Impairment Scale (AIS) A grade: 7.79 (5.28 to 11.50), AIS B grade: 1.15 (1.13 to 2.02), AIS C grade: 0.28 (0.20 to 0.41), AIS D grade: 0.04 (0.02 to 0.09), neurological level of injury (upper CSCI): 2.36 (1.51 to 3.68), injury severity score (ISS): 8.97 (8.11 to 9.82), Glasgow Coma Scale (GCS) score ≤8: 6.03 (2.19 to 16.61), thoracic injury: 1.78 (1.55 to 2.04), brain injury: 0.96 (0.55 to 1.69), respiratory complications: 5.97 (4.03 to 8.86), smoking history: 1.45 (0.99 to 2.13), traffic accident injury: 1.27 (0.92 to 1.74), and fall injury: 0.72 (0.52 to 1.01). Conclusions The current evidence shows that male sex, AIS A grade, AIS B grade, neurological level of injury (upper CSCI), high ISS, GCS≤8, thoracic injury, and respiratory complications are risk factors for tracheostomy after CSCI, and AIS C grade and AIS D grade are protective factors. This study will allow us to use these factors for tracheostomy decisions and ultimately optimize airway management in patients with CSCI.
[Effects of aroma therapy and music intervention on pain and anxious for breast cancer patients in the perioperative period].

OBJECTIVE To investigate the effect of the aroma therapy and music intervention on anxious and pain for the breast cancer patients in the perioperative period and the potential mechanisms. Methods: A total of 100 breast cancer patients who received surgical treatment in the comprehensive hospitals of Hunan province were recruited for this study. Patients were assigned randomly into a control group, an aroma therapy group, a music intervention group, and a joint-therapy group (n=25 per group). The patients in the control group received regular post-surgical nursery, while the patients from other groups received aroma therapy, music intervention, or both in addition to the regular nursery. The scale of anxiety and pain were measured. The measurements were carried at three time points, namely 30 min before the surgery (T1), 30 min after the recovery period of anesthesia (T2), and 4 hours after the removal of anesthesia tubing (T3). Repeated ANOVA was used to perform statistic analysis. Results: The scale of pain was significantly increased at the post-operation (T2, T3) compared to pre-surgery (T1). The therapeutic group showed significant decrease in pain at post-operation (T3) comparing with the control group (P<0.05). The scale of anxiety was the highest at pre-surgery (T1). During anaesthesia recovery, the anxiety of patients at post-operation T2 and T3 in the therapeutic groups significantly decreased compared with the control group (P<0.05). Conclusion: Both the aroma therapy and the music therapy can decrease the stress-responsive anxiety and pain for the breast cancer patients in the perioperative period.
Online Academic Networks as Knowledge Brokers: The Mediating Role of Organizational Support

Placing online academic networks in the framework of social, cultural and institutional “deterritorialization,” the current paper aims at investigating the functionality of these new forms of transnational and trans-organizational aggregations as knowledge brokers. The emphasis is laid on the influence of human collective intelligence and consistent knowledge flows on research innovation, considering the role of organizational support within higher education systems. In this respect, the research relied on a questionnaire-based survey with 140 academics from European emerging countries, the data collected being processed via a partial least squares structural equation modelling technique. Evidence was brought that, as knowledge brokers, online academic networks are systems aimed to support the access to human collective intelligence and consistent knowledge flows which exert a positive influence on research innovation, both directly and indirectly, by means of formal and informal organizational support. As facilitators of collaborative environments for individuals with specialized knowledge, competence, expertise and experience, online academic networks have set themselves up as an agora for academics worldwide and as an outlet for their acumen and literacy.
CEP55 is a determinant of cell fate during perturbed mitosis in breast cancer

The centrosomal protein, CEP55, is a key regulator of cytokinesis, and its overexpression is linked to genomic instability, a hallmark of cancer. However, the mechanism by which it mediates genomic instability remains elusive. Here, we showed that CEP55 overexpression/knockdown impacts survival of aneuploid cells. Loss of CEP55 sensitizes breast cancer cells to anti‐mitotic agents through premature CDK1/cyclin B activation and CDK1 caspase‐dependent mitotic cell death. Further, we showed that CEP55 is a downstream effector of the MEK1/2‐MYC axis. Blocking MEK1/2‐PLK1 signaling therefore reduced outgrowth of basal‐like syngeneic and human breast tumors in in vivo models. In conclusion, high CEP55 levels dictate cell fate during perturbed mitosis. Forced mitotic cell death by blocking MEK1/2‐PLK1 represents a potential therapeutic strategy for MYC‐CEP55‐dependent basal‐like, triple‐negative breast cancers.
Characterization of a Novel blaKLUC Variant With Reduced β-Lactam Resistance From an IncA/C Group Plasmid in a Clinical Klebsiella pneumoniae Isolate

Similar to other CTX-M family enzymes, KLUC is a recently identified and emerging determinant of cefotaxime resistance that has been recovered from at least three Enterobacteriaceae species, including Kluyvera cryocrescens, Escherichia coli, and Enterobacter cloacae. Whether this extended-spectrum β-lactamase (ESBL) has been disseminated among commonly isolated Enterobacteriaceae is worthy of further investigation. In this study, we screened 739 nosocomial Enterobacteriaceae isolates (240 Klebsiella pneumoniae and 499 E. coli strains) and found that one K. pneumoniae and four E. coli isolates harbored the blaKLUC gene. Three blaKLUC determinants isolated from E. coli were entirely identical to a blaKLUC-3 gene previously recovered in the same hospital. PFGE of four blaKLUC-harboring E. coli strains showed that prevalence of these determinants was most likely mediated by horizontal gene transfer but not clonal dissemination. However, the variant isolated from K. pneumoniae belonged to a novel member of the KLUC enzyme group. This newly identified enzyme (KLUC-5) has an amino acid substitution compared with previously identified KLUC-1 (G18S) and KLUC-3 (G240D). Antimicrobial susceptibility tests showed that KLUC-5 significantly reduced resistance activity to almost all the selected antimicrobials compared to previously identified KLUC-3. Site-directed mutagenesis showed that blaKLUC-5-D240G and blaKLUC-5-S18G significantly enhanced the MIC against its best substrate. Conjugation and S1-PFGE indicated that blaKLUC-5 was located on a transferable plasmid, which was further decoded by single-molecule, real-time sequencing. Comparative genome analysis showed that its backbone exhibited genetic homology to the IncA/C incompatibility group plasmids. A transposable element, ISEcp1, was detected 256-bp upstream of the blaKLUC-5 gene; this location was inconsistent with the previously identified blaKLUC-1 but congruent with the variants recovered from E. coli in the same hospital. These data provide evidence of the increasingly emerging KLUC group of ESBLs in China.
Critical path of women in situations of intimate partner violence 1

ABSTRACT Objective: To know and analyze the critical path followed by women subjected to intimate partner violence until reaching a Reference Center of a Brazilian city, from the perspective of these women. Method: Qualitative research, based on the concept of critical path. Participant observations of the support group of the Reference Center and interviews with ten women in situations of violence who were followed up in this service. Results: the motivating factors for women to seek help were the increase in the severity of the aggressions, the impact of the violence on their children and support from their family. They go to several sectors and services before reaching the Reference Center, such as the police and legal counsel, health and social services. They find little effective responses from the services, and care is indicated as the most relevant response factor to face the situation. Conclusion: the assistance is fragmented and dependent on the posture of the professional. The Reference Center is recognized as an important place of support for women. In addition to governmental efforts to maintain the network structured, the permanent education of the working professionals is also fundamental.