Miracle-dz/UniFAR-FTUs huggingface dataset:
The Identification of Small Molecule Inhibitors That Reduce Invasion and Metastasis of Aggressive Cancers

Transformed epithelial cells can activate programs of epithelial plasticity and switch from a sessile, epithelial phenotype to a motile, mesenchymal phenotype. This process is linked to the acquisition of an invasive phenotype and the formation of distant metastases. The development of compounds that block the acquisition of an invasive phenotype or revert the invasive mesenchymal phenotype into a more differentiated epithelial phenotype represent a promising anticancer strategy. In a high-throughput assay based on E-cadherin (re)induction and the inhibition of tumor cell invasion, 44,475 low molecular weight (LMW) compounds were screened. The screening resulted in the identification of candidate compounds from the PROAM02 class. Selected LMW compounds activated E-cadherin promoter activity and inhibited cancer cell invasion in multiple metastatic human cancer cell lines. The intraperitoneal administration of selected LMW compounds reduced the tumor burden in human prostate and breast cancer in vivo mouse models. Moreover, selected LMW compounds decreased the intra-bone growth of xenografted human prostate cancer cells. This study describes the identification of the PROAM02 class of small molecules that can be exploited to reduce cancer cell invasion and metastases. Further clinical evaluation of selected candidate inhibitors is warranted to address their safety, bioavailability and antitumor efficacy in the management of patients with aggressive cancers.
Psychosocial and medical predictors of 14-year mortality and morbidity in male and female coronary artery bypass graft recipients: a prospective observational study

Abstract Background Psychosocial factors may influence mortality and morbidity after coronary bypass surgery (CABG), but it is unclear when, post-surgery, they best predict the outcome, if they interact, or whether results differ for men and women. Methods This prospective, observational study assessed depression symptoms, social support, marital status, household responsibility, functional impairment, mortality and need for further coronary procedures over 14 years of follow-up. Data were collected in-hospital post-CABG and at home 1-year later. Mortality and subsequent cardiac procedure data were extracted from a Cardiac Registry. Results Of 296 baseline participants, 78% (43% were women) completed data at 1-year post-CABG. Long-term survival was shorter with 1-year depression and lower household responsibility but that was not true for the measures taken at baseline [HR for depression = 1.27; 95% CI 1.02–1.59 v. 0.99 (0.78–1.25), and HR = 0.71; 95% CI 0.52–0.97 v. 0.97 (0.80–1.16)] for household responsibility. An interaction between depression symptoms and social support at year 1 [χ2 (11) = 111.05, p < 0.001] revealed a greater hazard of mortality d with increased depression only at mean (HR = 1.67; 95% CI 1.21–2.26) and high social support (HR = 2.23; 95% CI 1.46–3.40). Depression also accounted for increased event recurrence. There were no significant interactions of sex with medical long-term outcomes. Conclusions In a sex-balanced sample, depression and household responsibility measured at 1-year post-CABG were associated with significant variance in unadjusted and adjusted predictor models of long-term mortality whereas the same indices determined right after the procedure were not significant predictors.
Brassinosteroid-BZR1/2-WAT1 module determines the high level of auxin signalling in vascular cambium during wood formation.

The tight regulation of local auxin homeostasis and signalling maxima in xylem precursor cells specifies the organizing activity of the vascular cambium and consequently promotes xylem differentiation and wood formation. However, the molecular mechanisms underlying the local auxin signalling maxima in the vascular cambium are largely unknown. Here, we reveal that brassinosteroid (BR)-activated WALLS ARE THIN1 (WAT1) facilitates wood formation by enhancing local auxin signalling in the vascular cambium in Solanum lycopersicum. Growth defects and low auxin signalling readouts in the BR-deficient tomato cultivar, Micro-Tom, were associated with a novel recessive allele, Slwat1-copi, created by the insertion of a retrotransposon in the last exon of the SlWAT1 locus. Molecular and genetic studies by generating the gain- and loss-of-function tomato mutants revealed that SlWAT1 is a critical regulator for fine-tuning local auxin homeostasis and signalling outputs in vascular cambium to facilitate secondary growth. Finally, we discovered that BR-regulated SlBZR1/2 directly activation of downstream auxin responses by SlWAT1 upregulation in xylem precursor cells to facilitate xylem differentiation and subsequent wood formation. Our data suggest that the BR-SlBZR1/2-WAT1 signalling network contributes to the high level of auxin signalling in the vascular cambium for secondary growth.
Genetics and Molecular Biology

Genetically antimicrobial resistance in Mycobacterium tuberculosis is currently one of the most important aspects of tuberculosis, considering that there are emerging resistant strains for almost every known drug used for its treatment. There are multiple antimicrobials used for tuberculosis treatment, and the most effective ones are the first-line drugs, which include isoniazid, pyrazinamide, rifampicin, and ethambutol. In this context, understanding the mechanisms of action and resistance of these molecules is essential for proposing new therapies and strategies of treatment. Additionally, understanding how and where mutations arise conferring a resistance profile to the bacteria and their effect on bacterial metabolism is an important requisite to be taken in producing safer and less susceptible drugs to the emergence of resistance. In this review, we summarize the most recent literature regarding novel mutations reported between 2017 and 2022 and the advances in the molecular mechanisms of action and resistance against first-line drugs used in tuberculosis treatment, highlighting recent findings in pyrazinamide resistance involving PanD and, additionally, resistance-conferring mutations for novel drugs such as bedaquiline, pretomanid, delamanid and linezolid.
An mHealth Intervention for Pregnancy Prevention for LGB Teens: An RCT

Girl2Girl is the first comprehensive mobile health pregnancy prevention program developed and tested among LGB+ across the United States. In this article, we report outcomes at 5 months. BrightcoveDefaultPlayer10.1542/6217589221001PEDS-VA_2020-013607 Video Abstract BACKGROUND: Although lesbian, gay, bisexual and other sexual minority (LGB+) girls are more likely than heterosexual girls to be pregnant during adolescence, relevant pregnancy prevention programming is lacking. METHODS: A national randomized controlled trial was conducted with 948 14- to 18-year-old cisgender LGB+ girls assigned to either Girl2Girl or an attention-matched control group. Participants were recruited on social media between January 2017 and January 2018 and enrolled over the telephone. Between 5 and 10 text messages were sent daily for 7 weeks. Both experimental arms ended with a 1-week booster delivered 12 weeks subsequently. RESULTS: A total of 799 (84%) participants completed the intervention end survey. Participants were, on average, 16.1 years of age (SD: 1.2 years). Forty-three percent were minority race; 24% were Hispanic ethnicity. Fifteen percent lived in a rural area and 29% came from a low-income household. Girl2Girl was associated with significantly higher rates of condom-protected sex (adjusted odds ratio [aOR] = 1.48, P < .001), current use of birth control other than condoms (aOR = 1.60, P = .02), and intentions to use birth control among those not currently on birth control (aOR = 1.93, P = .001). Differences in pregnancy were clinically but not statistically significant (aOR = 0.43, P = .23). Abstinence (aOR = 0.82, P = .34), intentions to be abstinent (aOR = 0.95, P = .77), and intentions to use condoms (aOR = 1.09, P = .59) were similar by study arm. CONCLUSIONS: Girl2Girl appears to be associated with increases in pregnancy preventive behaviors for LGB+ girls, at least in the short-term. Comprehensive text messaging–based interventions could be used more widely to promote adolescent sexual health behaviors across the United States.
Identification and Characterization of Novel Antibody Epitopes on the N2 Neuraminidase

The influenza virus neuraminidase is an emerging target for universal influenza virus vaccines. However, in contrast to influenza virus hemagglutinin, we know little about antibody epitopes and antigenic sites on the neuraminidase. Characterizing and defining these sites is aiding vaccine development and helping to understand antigenic drift of NA. ABSTRACT The influenza virus neuraminidase (NA) is becoming a focus for novel vaccine designs. However, the epitopes of human anti-NA antibodies have been poorly defined. Using a panel of 10 anti-N2 monoclonal antibodies (MAbs) that bind the H3N2 virus A/Switzerland/9715293/2013, we generated five escape mutant viruses. These viruses contained mutations K199E/T, E258K, A272D, and S331N. We found that mutations at K199 and E258 had the largest impact on MAb binding, NA inhibition and neutralization activity. In addition, a natural isolate from the 2017-2018 season was found to contain the E258K mutation and was resistant to numerous antibodies tested. The mutation S331N, was identified in virus passaged in the presence of antibody; however, it had little impact on MAb activity and greatly decreased viral fitness. This information aids in identifying novel human MAb epitopes on the N2 and helps with the detection of antigenically drifted NAs. IMPORTANCE The influenza virus neuraminidase is an emerging target for universal influenza virus vaccines. However, in contrast to influenza virus hemagglutinin, we know little about antibody epitopes and antigenic sites on the neuraminidase. Characterizing and defining these sites is aiding vaccine development and helping to understand antigenic drift of NA.
Surgical Management of Pediatric Inguinal Hernia: A Systematic Review and Guideline from the European Pediatric Surgeons' Association Evidence and Guideline Committee

Abstract Introduction Inguinal hernia repair represents the most common operation in childhood; however, consensus about the optimal management is lacking. Hence, recommendations for clinical practice are needed. This study assesses the available evidence and compiles recommendations on pediatric inguinal hernia. Materials and Methods The European Pediatric Surgeons' Association Evidence and Guideline Committee addressed six questions on pediatric inguinal hernia repair with the following topics: (1) open versus laparoscopic repair, (2) extraperitoneal versus transperitoneal repair, (3) contralateral exploration, (4) surgical timing, (5) anesthesia technique in preterm infants, and (6) operation urgency in girls with irreducible ovarian hernia. Systematic literature searches were performed using PubMed, MEDLINE, Embase (Ovid), and The Cochrane Library. Reviews and meta-analyses were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. Results Seventy-two out of 5,173 articles were included, 27 in the meta-analyses. Laparoscopic repair shortens bilateral operation time compared with open repair. In preterm infants, hernia repair after neonatal intensive care unit (NICU)/hospital discharge is associated with less respiratory difficulties and recurrences, regional anesthesia is associated with a decrease of postoperative apnea and pain. The review regarding operation urgency for irreducible ovarian hernia gained insufficient evidence of low quality. Conclusion Laparoscopic repair may be beneficial for children with bilateral hernia and preterm infants may benefit using regional anesthesia and postponing surgery. However, no definite superiority was found and available evidence was of moderate-to-low quality. Evidence for other topics was less conclusive. For the optimal management of inguinal hernia repair, a tailored approach is recommended taking into account the local facilities, resources, and expertise of the medical team involved.
Automated Bone Age Assessment Using Artificial Intelligence: The Future of Bone Age Assessment

Bone age assessments are a complicated and lengthy process, which are prone to inter- and intra-observer variabilities. Despite the great demand for fully automated systems, developing an accurate and robust bone age assessment solution has remained challenging. The rapidly evolving deep learning technology has shown promising results in automated bone age assessment. In this review article, we will provide information regarding the history of automated bone age assessments, discuss the current status, and present a literature review, as well as the future directions of artificial intelligence-based bone age assessments.
Kaposi's Sarcoma-Associated Herpesvirus MicroRNA Mutants Modulate Cancer Hallmark Phenotypic Differences in Human Endothelial Cells

Kaposi’s sarcoma-associated herpesvirus (KSHV) causes Kaposi’s sarcoma (KS). The contribution of KSHV microRNAs (miRNAs) to oncogenesis is not fully understood. ABSTRACT Kaposi’s sarcoma (KS) results from the transformation of Kaposi's sarcoma-associated herpesvirus (KSHV)-infected endothelial cells. The contribution of the KSHV microRNAs (miRNAs) to the process of oncogenesis in endothelial cells has not been fully elucidated. To better understand the contributions of individual miRNAs to oncogenesis-related cellular phenotypes, we used KSHV miRNA knockout mutants, each lacking one of the 12 miRNA genes. An additional mutant lacked all miRNAs. Since KSHV infection causes a variety of phenotypic changes in endothelial cells, we tested the mutants for their ability to effect such changes in telomerase-immortalized vein endothelial (TIVE) cells infected with each of the mutant viruses. Wild type- and mutant-infected as well as uninfected cells were evaluated for perturbations to proliferation, migration, tubule formation, and glycolysis. We found broad variation between the different viruses in these aspects. With respect to proliferation rate, ΔmiR-K12-3, ΔmiR-K12-8, and ΔmiR-K12-11 showed significant impairment. Cells infected with ΔmiR-K12-11 had reduced migration. In tubule formation, the ΔmiR-K12-5, -6, and -7 viruses were deficient. At the same time, cells infected with the ΔmiR-K12-10 virus showed dysregulated glycolysis. By combining these observations with previously published KSHV miRNA targetome lists from ribonomics data, we were able to functionally validate a number of new miRNA targets in specific pathways. As proof of concept, miR-K12-3 was shown to target cathepsin D, a strong promoter of apoptosis. Taken together, the results demonstrate that KSHV miRNAs play different roles in inducing the phenotypic changes that are characteristic of transformed cells. IMPORTANCE Kaposi’s sarcoma-associated herpesvirus (KSHV) causes Kaposi’s sarcoma (KS). The contribution of KSHV microRNAs (miRNAs) to oncogenesis is not fully understood. This is particularly true for human endothelial cells, the cell type from which KS tumors are derived. Here, we used a panel of KSHV miRNA knockout viruses to shed light on the roles of individual miRNAs in the process of transformation. Latently infected endothelial cells were studied for phenotypic changes related to cancer, including proliferation, migration, angiogenesis, glycolysis, and apoptosis. The mutant-infected cell lines displayed a wide range of phenotypes in these selected measures of oncogenesis, which differed from those of wild-type-infected cells and from each other. These results indicate that KSHV miRNAs contribute to different aspects of oncogenesis and that each one has a unique role to play.
Quantitative imaging decision support (QIDSTM) tool consistency evaluation and radiomic analysis by means of 594 metrics in lung carcinoma on chest CT scan

Objective: To evaluate the consistency of the quantitative imaging decision support (QIDSTM) tool and radiomic analysis using 594 metrics in lung carcinoma on chest CT scan. Materials and Methods: We included, retrospectively, 150 patients with histologically confirmed lung cancer who underwent chemotherapy and baseline and follow-ups CT scans. Using the QIDSTM platform, 3 radiologists segmented each lesion and automatically collected the longest diameter and the density mean value. Inter-observer variability, Bland Altman analysis and Spearman’s correlation coefficient were performed. QIDSTM tool consistency was assessed in terms of agreement rate in the treatment response classification. Kruskal Wallis test and the least absolute shrinkage and selection operator (LASSO) method with 10-fold cross validation were used to identify radiomic metrics correlated with lesion size change. Results: Good and significant correlation was obtained between the measurements of largest diameter and of density among the QIDSTM tool and the radiologists measurements. Inter-observer variability values were over 0.85. HealthMyne QIDSTM tool quantitative volumetric delineation was consistent and matched with each radiologist measurement considering the RECIST classification (80-84%) while a lower concordance among QIDSTM and the radiologists CHOI classification was observed (58-63%). Among 594 extracted metrics, significant and robust predictors of RECIST response were energy, histogram entropy and uniformity, Kurtosis, coronal long axis, longest planar diameter, surface, Neighborhood Grey-Level Different Matrix (NGLDM) dependence nonuniformity and low dependence emphasis as Volume, entropy of Log(2.5 mm), wavelet energy, deviation and root man squared. Conclusion: In conclusion, we demonstrated that HealthMyne quantitative volumetric delineation was consistent and that several radiomic metrics extracted by QIDSTM were significant and robust predictors of RECIST response.
Fractional heat shock protein 27 urine excretion as a short-term predictor in acute exacerbation of chronic obstructive pulmonary disease

Background Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality and is characterized by episodes of acute exacerbations. Finding a systemic biomarker that reliably predicts outcome after an acute exacerbation remains a major challenge. Heat shock protein 27 (HSP27) has been previously studied in COPD, however, urine excretion trajectory and prognostic value after an exacerbation is unknown. Methods In this retrospective post hoc analysis of a prospective study that included 253 COPD patients who were hospitalized for acute exacerbation, 207 patients were analyzed. Urine and serum were sampled at admission, discharge, and 180 days after discharge; urine excretion trajectory was analyzed and correlated with clinicopathological and survival data. Results HSP27 urine excretion increased after an exacerbation episode [1.8% admission, 1.8% discharge, 2.3% 180 days after discharge (P=0.091)]. In severely ill patients (GOLD IV) this course was even more distinct [1.6% admission, 2.1% discharge, 2.8% 180 days after discharge (P=0.007)]. Furthermore, fractional HSP27 urine excretion at discharge was increased in GOLD IV patients (P=0.031). In Kaplan-Meier and univariable Cox proportional hazard models patients with HSP27 urine excretion below 0.845% showed significantly worse survival at 30, 90 and 180 days after discharge. In a multivariable Cox proportional hazard model including established COPD outcome parameters fractional HSP27 urine excretion remained a significant predictor of survival at 30 and 90 days after discharge. Comparing this model to our already published model that includes HSP27 serum concentration we could show that fractional HSP27 urine excretion performs better in short-term survival. Conclusions Our findings provide novel information about fractional HSP27 urine excretion trajectory in acute exacerbation of COPD. Fractional HSP27 urine excretion may be significantly reduced during an episode of acute exacerbation in COPD patients and may be used as a predictor of short-term all-cause mortality.
Aphasia and Math: Deficits with Basic Number Comprehension and in Numerical Activities of Daily Living

Abstract Objective: In the present study, we explored numerical problems in individuals with aphasia. We investigate whether numerical deficits, usually accompanying aphasia, can be observed on number comprehension tasks that do not necessarily require an oral response. Method: Individuals with aphasia were classified into anterior, posterior, and global subgroups according to the lesion type. To investigate numerical cognition, we used a relatively recent tool, the Numerical Activities of Daily Living (NADL). Results: The results showed that individuals with aphasia have problems with tasks of basic number comprehension as well as in most NADL. In the formal part of the NADL, anterior aphasic patients made comparatively more errors than the posterior aphasic patients. Global aphasic patients presented an invariably poor performance on almost all tasks. Conclusion: The results provide insight into how numerical deficits may impair an individual with aphasia in activities of daily living. This study is a preliminary attempt to start the validation process of the NADL for the Greek population.
Co-existence of myopia and amblyopia in a guinea pig model with monocular form deprivation

Background Form deprivation myopia is a type of ametropia, with identifiable causes in humans, that has been induced in many animals. The age of onset of myopia induced by monocular form deprivation coincides with the period of visual development in guinea pigs. However, visual acuity of form-deprived eyes in guinea pigs is not understood yet. In this study, we investigated whether monocular form deprivation would affect visual acuity in infant guinea pigs by evaluating the development of myopia and amblyopia after monocular form deprivation, and whether form deprivation myopia and amblyopia occurred simultaneously or successively. Methods Twenty pigmented guinea pigs (2 weeks old) were randomly assigned to two groups: monocularly form-deprived (n=10), in which facemasks modified from latex balloons covered the right eye, and normal controls (n=10). Refraction, axial length, and visual acuity were measured at 4 intervals (after 0, 1, 4, and 8 weeks of form deprivation), using cycloplegic streak retinoscopy, A-scan ultrasonography (with an oscillation frequency of 10 MHz), and sweep visual evoked potentials (sweep VEPs), respectively. Sweep VEPs were performed with correction of the induced myopic refractive error. Results Longer deprivation periods resulted in significant refractive errors in form-deprived eyes compared with those in contralateral and normal control eyes; the axial lengths of form-deprived eyes increased significantly after 4 and 8 weeks of form deprivation. These results revealed that myopia was established at 4 weeks. The acuity of form-deprived eyes was unchanged compared to that at the pretreatment time point, while that of contralateral eyes and eyes in normal control guinea pigs improved; there were significant differences between the deprived eyes and the other two open eyes from 1 to 8 weeks of form deprivation, showing that amblyopia was possibly established during 1 week of form deprivation. Conclusions This study demonstrated the feasibility of using sweep VEPs to estimate the visual acuity of guinea pigs. Further, our results revealed that amblyopia likely occurred earlier than myopia; amblyopia and myopia coexisted after a long duration of monocular form deprivation in guinea pigs. Understanding this relationship may help provide insights into failures of treatment of amblyopia associated with myopic anisometropia.