Miracle-dz/UniFAR-FTUs huggingface dataset:
An integrated approach to determine interactive genotoxic and global gene expression effects of multiwalled carbon nanotubes (MWCNTs) and benzo[a]pyrene (BaP) on marine mussels: evidence of reverse ‘Trojan Horse’ effects

Abstract The interactions between carbon-based engineered nanoparticles (ENPs) and organic pollutants might enhance the uptake of contaminants into biota. The present integrated study aimed to assess this potential ‘Trojan Horse’, probing the interactive effects of purpose-made multi-walled carbon nanotubes (MWCNTs), a representative ENP, and benzo[a]pyrene (BaP), a ubiquitous polycyclic aromatic hydrocarbon (PAH) pollutant, on the marine mussel Mytilus galloprovincialis. Mussels were exposed to MWCNTs and BaP either alone or in various combinations. The co-exposure of BaP with MWCNTs revealed that the presence of MWCNTs enhanced the aqueous concentrations of BaP, thereby reducing the uptake of this pollutant by mussels as evidenced by lowering BaP concentrations in the tissues. Determination of DNA damage (comet assay) showed a concentration-dependent response for BaP alone which was absent when MWCNTs were present. Global gene expression using microarray analyses indicated that BaP and MWCNTs, in combination, differentially activated those genes which are involved in DNA metabolism compared to the exposures of BaP or MWCNTs alone, and the gene expression response was tissue-specific. Mechanisms to explain these results are discussed and relate primarily to the adsorption of BaP on MWCNTs, mediated potentially by van der Waals interactions. The use of a novel approach based on gold-labeled MWCNTs to track their uptake in tissues improved the traceability of nanotubes in biological samples. Overall, our results did not indicate the ‘Trojan Horse’ effects following co-exposure to the contaminants and clearly showed that the adsorption of BaP to MWCNTs modified the uptake of the pollutant in marine mussels.
Awareness of Ocular Manifestations, Complications, and Treatment of Sickle Cell Disease in the Eastern Province of Saudi Arabia: A Cross-Sectional Study

AIM: This study aims to assess the level of awareness about the effect of sickle cell disease (SCD) on the eye and vision and factors influencing SCD awareness. SUBJECTS AND METHODS: The study design was cross-sectional and was carried out in 2018 among the general population in the Eastern province of Saudi Arabia. It was conducted using an online, validated questionnaire, after obtaining consent from the participants. The outcome variable was 557. The level of awareness was correlated to demographic information. RESULTS: The study population was 557 Saudi adults. 84 were male and 473 female. Their mean age was 22 ± 23 years. Majority of the participants (57.3%) were not aware that SCD could affect the eye and vision. There was no difference in the knowledge regarding ocular complications of SCD among different ages and sexes. CONCLUSIONS: The result of this study indicates the need for raising the knowledge regarding the disease, its ocular complications, screening methods, and management. Health educations campaigns would be an effective tool in increasing SCD awareness.
Characterization of new races of Xanthomonas oryzae pv. oryzae in Mali informs Resistance gene deployment.

Bacterial leaf Blight caused by Xanthomonas oryzae pv. oryzae represents a severe threat to rice cultivation in Mali. Characterizing the pathotypic diversity of bacterial populations is key to the management of pathogen-resistant varieties. Forty-one Xanthomonas oryzae pv. oryzae isolates were collected between 2010 and 2013 in the major rice growing regions in Mali. All of them were virulent on the susceptible rice variety Azucena, and their evaluation on twelve near-isogenic rice lines, each carrying a single resistance gene, identified six new races (A4 to A9) and confirmed race A3 that was previously reported in Mali. Races A5 and A6, isolated in Office du Niger and Selingue are the most prevalent ones in Mali. Race A9 is the most virulent, circumventing all the resistance genes tested. Xa3 controlled six out of seven races, i.e. 89% of the isolates tested. The expansion of race A9 represents a major risk to rice cultivation and the urgent need to identify local source of resistance. We selected fourteen isolates of Xanthomonas oryzae pv. oryzae representative of the most prevalent races to evaluate twenty-nine rice varieties grown by farmers in Mali. Six of them showed a high level of resistance to Xanthomonas oryzae pv. oryzae and were then screened with a larger collection of isolates. Based on the interactions among the six varieties and the Xanthomonas oryzae pv. oryzae isolates we characterized eight different pathotypes (P1 to P8). Two rice varieties, SK20-28 and Gigante effectively control all the isolates tested. The low association observed among races and pathotypes of Xanthomonas oryzae pv. oryzae suggests that the resistance observed in the local rice varieties does not simply rely on single known Xa genes. Xanthomonas oryzae pv. oryzae is pathogenically and geographically diverse. Both the races of Xanthomonas oryzae pv. oryzae characterized in this study and the identification of sources of resistance in local rice varieties provide useful information to inform the design of effective breeding programs for resistance to bacterial leaf blight in Mali.
Derivation and Validation of a Novel Cardiac Intensive Care Unit Admission Risk Score for Mortality

Background There are no risk scores designed specifically for mortality risk prediction in unselected cardiac intensive care unit (CICU) patients. We sought to develop a novel CICU‐specific risk score for prediction of hospital mortality using variables available at the time of CICU admission. Methods and Results A database of CICU patients admitted from January 1, 2007 to April 30, 2018 was divided into derivation and validation cohorts. The top 7 predictors of hospital mortality were identified using stepwise backward regression, then used to develop the Mayo CICU Admission Risk Score (M‐CARS), with integer scores ranging from 0 to 10. Discrimination was assessed using area under the receiver‐operator curve analysis. Calibration was assessed using the Hosmer–Lemeshow statistic. The derivation cohort included 10 004 patients and the validation cohort included 2634 patients (mean age 67.6 years, 37.7% females). Hospital mortality was 9.2%. Predictor variables included in the M‐CARS were cardiac arrest, shock, respiratory failure, Braden skin score, blood urea nitrogen, anion gap and red blood cell distribution width at the time of CICU admission. The M‐CARS showed a graded relationship with hospital mortality (odds ratio 1.84 for each 1‐point increase in M‐CARS, 95% CI 1.78–1.89). In the validation cohort, the M‐CARS had an area under the receiver‐operator curve of 0.86 for hospital mortality, with good calibration (P=0.21). The 47.1% of patients with M‐CARS <2 had hospital mortality of 0.8%, and the 5.2% of patients with M‐CARS >6 had hospital mortality of 51.6%. Conclusions Using 7 variables available at the time of CICU admission, the M‐CARS can predict hospital mortality in unselected CICU patients with excellent discrimination.
Current Treatment Options in Acute Limb Ischemia

Abstract Background Acute limb ischemia represents a clinical emergency with eventual limb loss and life-threatening consequences. It is characterized by a sudden decrease in limb perfusion. Acute ischemia is defined as a duration of symptoms for less than 14 days. Aging of the population increases the prevalence of acute limb ischemia. The two principal etiologies are arterial embolism and in situ thrombosis of an atherosclerotic artery. Immediate diagnosis, accurate assessment and urgent intervention when needed are crucial to save the limb and to prevent a major amputation. Delay in diagnosis and therapy may lead to irreversible ischemic damage. Method To assess the current treatment options in acute limb ischemia, this review is based on a selective literature search in PubMed representing the current state of research. Results and Conclusion Patients with acute limb ischemia should receive immediate anticoagulation. Treatment depends on the classification based on the degree of ischemia and limb viability. Especially acute (< 14 days symptom duration) Rutherford Categories IIa and IIb with marginally and immediately threatened limbs require definitive therapeutic intervention and are salvageable, if promptly revascularized. The current literature suggests that open surgical revascularization is more time effective then catheter-directed thrombolysis. However, with the advent of thrombolytic delivery systems and mechanical thrombectomy devices, treatment time can be minimized and successful utilization in patients with Category IIb (Rutherford Classification for Acute Limb Ischemia) has been reported with promising limb-salvage and survival rates. Large randomized studies are still missing, and guidelines suggest choosing the method of revascularization depending on anatomic location, etiology, and local practice patterns, with the time to restore the blood flow being an important factor to consider. Key points: Acute limb ischemia is an interdisciplinary emergency. It can lead to limb loss with life-threatening consequences. Immediate diagnosis and treatment are crucial to prevent irreversible damage. An endovascular approach should be considered in acute limb ischemia Category IIa and IIb of the Rutherford Classification for Acute Limb Ischemia (< 14 days), on a case-based decision and local capabilities. Especially elderly, multimorbid patients with high perioperative risk (may probably) benefit from these minimally invasive procedures. Citation Format Fluck F, Augustin A, Bley T et al. Current Treatment Options in Acute Limb Ischemia. Fortschr Röntgenstr 2020; 192: 319 – 326
The Exacerbating Impact of Moral Disapproval on the Relationship Between Pornography Use and Depression, Anxiety, and Relationship Satisfaction

Abstract Using an online sample of participants in committed relationships, support was found for a moderated mediation model in which depression mediated the relationship between pornography use and relationship satisfaction, and this indirect effect was moderated by level of moral disapproval. Results indicate that, among consumers of pornography, their level of moral disapproval exacerbates adverse intra- and interpersonal outcomes such as distress and decreased relationship satisfaction. These results extend the empirical literature that examines the conditional effects of moral disapproval of pornography use to relational outcomes.
Hydrogen Sulfide Prevents Elastin Loss and Attenuates Calcification Induced by High Glucose in Smooth Muscle Cells through Suppression of Stat3/Cathepsin S Signaling Pathway

Vascular calcification can be enhanced by hyperglycemia. Elastin loss in tunica media promotes the osteogenic transformation of smooth muscle cells (SMCs) and involves arterial medial calcification (AMC) that is associated with a high incidence of cardiovascular risk in patients with type 2 diabetes. Here, we tested whether hydrogen sulfide (H2S), an endogenous gaseous mediator, can prevent elastin loss and attenuate calcification induced by high glucose in SMCs. Calcification was induced by high glucose (4500 mg/L) in human aortic SMCs (HASMCs) under the condition of calcifying medium containing 10 mM β-glycerophosphate (β-GP). The experiments showed that NaHS (an H2S donor, 100 μM) mitigated the calcification of HASMCs treated with high glucose by decreasing calcium and phosphorus levels, calcium deposition and ALP activity and inhibited osteogenic transformation by increasing SMα-actin and SM22α, two phenotypic markers of smooth muscle cells, and decreasing core binding factor α-1 (Cbfα-1), a key factor in bone formation, protein expressions in HASMCs. Moreover, NaHS administration inhibited the activation of Stat3, cathepsin S (CAS) activity and its expression, but increased the level of elastin protein. Pharmacological inhibition or gene silencing Stat3 not only reversed elastin loss, but also attenuated CAS expression. Inhibition of CAS alleviated, while CAS overexpression exacerbated, elastin loss. Interestingly, overexpression of wild type (WT)-Stat3, but not its mutant C259S, elevated CAS protein expression and reduced elastin level. Moreover, NaHS induced S-sulfhydration in WT, but not in the C259S Stat3. These data suggest that H2S may directly regulate Cys259 residue in Stat3 and then impair its signaling function. Our data indicate that H2S may attenuate vascular calcification by upregulating elastin level through the inhibition of Stat3/CAS signaling.
Physiologically Relevant Oxygen Concentration (6% O2) as an Important Component of the Microenvironment Impacting Melanoma Phenotype and Melanoma Response to Targeted Therapeutics In Vitro

Cancer cell phenotype largely depends on oxygen availability. The atmospheric oxygen concentration (21%) used in in vitro studies is much higher than in any human tissue. Using well-characterized patient-derived melanoma cell lines, we compared: (i) activities of several signaling pathways, and (ii) the effects of vemurafenib and trametinib in hyperoxia (21% O2), normoxia (6% O2) and hypoxia (1% O2). A high plasticity of melanoma cells in response to changes in oxygen supplementation and drug treatment was observed, and the transcriptional reprograming and phenotypic changes varied between cell lines. Normoxia enhanced the expression of vascular endothelial growth factor (VEGF), glucose metabolism/transport-related genes, and changed percentages of NGFR- and MITF-positive cells in cell line-dependent manner. Increased protein stability might be responsible for high PGC1α level in MITFlow melanoma cells. Vemurafenib and trametinib while targeting the activity of MAPK/ERK pathway irrespective of oxygen concentration, were less effective in normoxia than hyperoxia in reducing levels of VEGF, PGC1α, SLC7A11 and Ki-67-positive cells in cell line-dependent manner. In conclusion, in vitro studies performed in atmospheric oxygen concentration provide different information on melanoma cell phenotype and response to drugs than performed in normoxia, which might partially explain the discrepancies between results obtained in vitro and in clinical settings.
A Proposal for New Software Testing Technique for Component Based Software System

A Component-Based Software (CBS) system consists of integrated components that work together to perform specific tasks. Different components are selected and integrated to form a new software system. The components may have been developed by other third party, thus it is expected that the development time and effort can be reduced significantly. However just like any traditional development, the testing activities requires a specific evaluation to assess the software. Most of the components do not come with the source code, but only some information of the components. Thus, a specific testing technique is required. In this paper, we propose a new testing technique for Component-Based Software system. Older techniques had been developed based on traditional metrics, while other CBS system had different strategy from what we propose in this research. The technique help determining test adequacy criteria based on a set of complexity and criticality metrics of a CBS system. Based on this test adequacy criteria, our experimental studies have shown that it has assisted in reducing the number of test suite and test cases. For software testers, this technique would significantly reduce the testing time and effort in CBS development. Keyword: Component Based Software (CBS), Component Based Metrics, Component Integration Metrics, Software Testing, Component Based Software Engineering
Predictors of treatment resistant schizophrenia: a systematic review of prospective observational studies

Abstract Treatment-resistant schizophrenia, affecting approximately 20–30% of patients with schizophrenia, has a high burden both for patients and healthcare services. There is a need to identify treatment resistance earlier in the course of the illness, in order that effective treatment, such as clozapine, can be offered promptly. We conducted a systemic literature review of prospective longitudinal studies with the aim of identifying predictors of treatment-resistant schizophrenia from the first episode. From the 545 results screened, we identified 12 published studies where data at the first episode was used to predict treatment resistance. Younger age of onset was the most consistent predictor of treatment resistance. We discuss the gaps in the literature and how future prediction models can identify predictors of treatment response more robustly.
Impact of hormonal replacement therapy on macula and retinal nerve fiber layer in postmenopausal women

Objective: The objective of this study was to investigate the effect of hormonal replacement therapy (HRT) in postmenopausal women on peripapillary retinal nerve fiber layer (RNFL) and macular thickness and macular volume and to compare them with postmenopausal women who are not on hormonal replacement therapy. Materials and Methods: The study population included postmenopausal women who are taking HRT (n = 50) and postmenopausal women who are not taking HRT (n = 50). Peripapillary retinal nerve fiber layer and macular thickness and macular volume were evaluated using spectral domain-optical coherence tomography. Results: There was no statistically significant difference in all peripapillary RNFL thickness and macular thickness and volume parameters between the two groups, HRT and non-HRT groups, except for superior outer macular thickness and volume were significantly thicker in postmenopausal women who are taking hormonal replacement therapy, P = 0.036 and P = 0.037, respectively. There was a positive correlation between duration on HRT with most of peripapillary RNFL and macular thickness and macular volume, but the correlation was only significant at superotemporal peripapillary RNFL. Conclusion: Our result does not provide strong evidence for a protective effect of postmenopausal HRT usage against ocular diseases. However, the increased macular thickness in superior outer macula and positively correlated peripapillary retinal nerve fiber layer at superotemporal encouraged us to think of promising positive effect of HRT on ocular structure.
Effect of Aflibercept Plus Modified FOLFOX6 Induction Chemotherapy Before Standard Chemoradiotherapy and Surgery in Patients With High-Risk Rectal Adenocarcinoma: The GEMCAD 1402 Randomized Clinical Trial.

Importance Preclinical studies suggest that a vascular endothelial growth factor (VEGF) blockade may play a role in the preoperative treatment of rectal adenocarcinoma; however, how to combine anti-VEGF drugs with neoadjuvant chemotherapy (CT) and/or chemoradiotherapy (CRT) remains controversial. Objective To study the effect of aflibercept plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) induction CT prior to standard CRT and total mesorectal excision (TME) surgery in patients with high-risk rectal adenocarcinoma. Design, Setting, and Participants In the Grupo Español Multidisciplinar En Cancer Digestivo (GEMCAD) 1402 phase 2 randomized clinical trial, 180 patients aged 18 to 75 years, identified by centrally reviewed magnetic resonance imaging to have mrT3c-d/T4/N2 rectal adenocarcinoma, were enrolled from 20 treatment centers in Spain between January 2015 and March 2017. Patients were randomized in a 2:1 treatment to control arm ratio. The primary end point was evaluated at 2 interim and 1 final analyses. The study was designed to perform hypothesis testing at α = . 2 and β = . 2. A 2-sided P value of <. 1984 in the final analysis of the intention-to-treat population was the threshold for considering the experimental treatment to be more effective than the control. Interventions Patients received neoadjuvant mFOLFOX6 with (arm A; n = 115) or without (arm B; n = 65) aflibercept, 4 mg/kg (every 2 weeks, 6 cycles, and 3 months) prior to standard CRT and TME surgery. Main Outcomes and Measures The primary end point was a pathologic complete response (pCR) (ypT0N0). Secondary end points included toxic effects, surgical morbidity, R0 resections, compliance, and 3-year disease-free survival. Results For the 115 patients who received treatment with mFOLFOX6 plus aflibercept, the median (range) age was 60 (32-75) years, 77 men (66.9%) and 38 women (33.0%). For the 65 patients who received induction CT treatment with only mFOLFOX6, the median (range) age was 65 (39-75) years, 39 men (60.0%) and 26 women (40.0%). The pCR rate in the intention-to-treat population was 22.6% (95% CI, 15.3%-31.3%) in arm A and 13.8% (95% CI, 6.5%-24.6%) in arm B (P = .15). The main differential toxic effect was grade 3/4 hypertension during the induction phase. Postoperative complications were similar in both arms (15.5% in arm A and 12.9% in arm B). A total of 106 patients (92.1%) in arm A and 63 (96.9%) in arm B received all treatment cycles. Conclusions and Relevance The study met its primary end point. The findings suggest that adding aflibercept to an induction regimen using mFOLFOX6 plays a role in increasing the pCR rate in patients with high-risk rectal adenocarcinoma, without substantially increasing surgical complications. The GEMCAD 1402 trial provides a rationale for phase 3 trials. Trial Registration ClinicalTrials.gov identifier: NCT02340949.
Comparison of the Effects of Coaching and Receipt of App Recommendations on Depression, Anxiety, and Engagement in the IntelliCare Platform: Factorial Randomized Controlled Trial

Background IntelliCare is a modular platform that includes 12 simple apps targeting specific psychological strategies for common mental health problems. Objective This study aimed to examine the effect of 2 methods of maintaining engagement with the IntelliCare platform, coaching, and receipt of weekly recommendations to try different apps on depression, anxiety, and app use. Methods A total of 301 participants with depression or anxiety were randomized to 1 of 4 treatments lasting 8 weeks and were followed for 6 months posttreatment. The trial used a 2X2 factorial design (coached vs self-guided treatment and weekly app recommendations vs no recommendations) to compare engagement metrics. Results The median time to last use of any app during treatment was 56 days (interquartile range 54-57), with 253 participants (84.0%, 253/301) continuing to use the apps over a median of 92 days posttreatment. Receipt of weekly recommendations resulted in a significantly higher number of app use sessions during treatment (overall median=216; P=.04) but only marginal effects for time to last use (P=.06) and number of app downloads (P=.08). Coaching resulted in significantly more app downloads (P<.001), but there were no significant effects for time to last download or number of app sessions (P=.36) or time to last download (P=.08). Participants showed significant reductions in the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) across all treatment arms (P s<.001). Coached treatment led to larger GAD-7 reductions than those observed for self-guided treatment (P=.03), but the effects for the PHQ-9 did not reach significance (P=.06). Significant interaction was observed between receiving recommendations and time for the PHQ-9 (P=.04), but there were no significant effects for GAD-7 (P=.58). Conclusions IntelliCare produced strong engagement with apps across all treatment arms. Coaching was associated with stronger anxiety outcomes, and receipt of recommendations enhanced depression outcomes. Trial Registration ClinicalTrials.gov NCT02801877; https://clinicaltrials.gov/ct2/show/NCT02801877