Miracle-dz/UniFAR-FTUs huggingface dataset:
From Interconnection between Genes and Microenvironment to Novel Immunotherapeutic Approaches in Upper Gastro-Intestinal Cancers—A Multidisciplinary Perspective

Despite the progress during the last decade, patients with advanced gastric and esophageal cancers still have poor prognosis. Finding optimal therapeutic strategies represents an unmet need in this field. Several prognostic and predictive factors have been evaluated and may guide clinicians in choosing a tailored treatment. Data from large studies investigating the role of immunotherapy in gastrointestinal cancers are promising but further investigations are necessary to better select those patients who can mostly benefit from these novel therapies. This review will focus on the treatment of metastatic esophageal and gastric cancer. We will review the standard of care and the role of novel therapies such as immunotherapies and CAR-T. Moreover, we will focus on the analysis of potential predictive biomarkers such as Modify as: Microsatellite Instability (MSI) and PD-L1, which may lead to treatment personalization and improved treatment outcomes. A multidisciplinary point of view is mandatory to generate an integrated approach to properly exploit these novel antiproliferative agents.
The Risk of Osteoporotic Forearm Fractures in Postmenopausal Women in a Siberian Population Sample

The reduction in bone and muscle mass increases in menopausal women and poses a threat to the loss of self-dependence in the elderly. The aim of the study was to assess the frequency of osteoporotic forearm fractures (OFF) in postmenopausal women and to study their association with risk factors for chronic non-communicable diseases (NCD). The study was based on the Russian arm of the Health, Alcohol and Psychosocial Factors In Eastern Europe (HAPIEE) project (Novosibirsk). In a subsample of postmenopausal women aged 55–84 years old (n = 2005), we assessed the history of OFF during the last 3 years and risk factors for fracture and common NCD/. Cross-sectional associations between OFF history and potential determinants were analyzed using multivariable-adjusted logistic regression. A history of OFF in the last 3 years was found in 3.9% women. In a multivariable-adjusted model, the risk of OFF was directly associated with smoking in the past (OR = 2.23; 95% Cl 1.10–4.55), total cholesterol level higher than 200 mg/dL (OR = 1.98; 95% Cl 1.19–3.29), and it was inversely associated with body mass index (OR = 0.91; 95% Cl 0.86–0.96). In studied population sample of postmenopausal women the cross-sectional determinants of osteoporotic forearm fractures were smoking in the past and high total cholesterol value; body mass index protectively related to the risk of osteoporotic fractures. These findings might have implications for fracture prevention in postmenopausal women.
Choroidal Vascularity in Non-arteritic Anterior Ischaemic Optic Neuropathy

ABSTRACT This study evaluates the peripapillary choroidal vascularity in eyes with non-arteritic anterior ischaemic optic neuropathy (NAION) and compares it with the vascularity of healthy fellow eyes and age-matched subjects. The peripapillary choroidal vascularity index (CVI), a new tool of measurement, was calculated using horizontal swept-source optical coherence tomography scans. CVI was calculated using a previously validated automated algorithm. CVI in NAION and fellow eyes of NAION patients were compared with age-matched eyes of healthy individuals using Kruskal–Wallis test. A total of 20 eyes of 20 patients with acute unilateral NAION with healthy fellow eyes (20 eyes) and 40 eyes of 40 healthy patients were included in the study. The average age of patients with NAION was 56 ± 8 and 55 ± 7 years in age-matched healthy controls. NAION eyes had a significantly lower CVI than age-matched controls in both nasal and temporal areas. NAION nasal CVI was 0.47 ± 0.47 compared to 0.62 ± 0.04 in controls (p < 0.001). NAION temporal CVI was 0.45 ± 0.48 compared to 0.58 ± 0.04 in controls (p < 0.001). Temporal CVI was 0.45 ± 0.48 in NAION eyes and was significantly lower than counterpart healthy fellow eyes 0.48 ± 0.02 (p = 0.007). In conclusion, NAION eyes have significantly reduced vascularity in the peripapillary area. CVI is lower in the nasal and temporal of the optic disc compared to healthy individuals. This may suggest those with smaller CVI are more prone to ischaemia from reduced vascularity resulting in NAION.
Drug Use among Nursing Home Residents in Denmark for Drugs Having Pharmacogenomics Based (PGx) Dosing Guidelines: Potential for Preemptive PGx Testing

Background: Polypharmacy is most prevalent among the elderly population and in particular among nursing home residents. The frequency of the use of drugs with pharmacogenomics (PGx)-based dosing guidelines for CYP2D6, CYP2C9, CYP2C19 and SLCO1B1 were measured among nursing home residents in the Capital Region of Denmark as well as drug–drug interactions. The aim was to evaluate the potential of applying PGx-test as a supportive tool in medication reviews. Methods: Drug use among nursing home residents during 2017–2018 in the Capital Region of Copenhagen, for drugs with PGx-based dosing guidelines available through the PharmGKB website, were measured. Drug–drug interactions were scored in severity by using drug interaction checkers. Results: The number of residents using drugs with PGx-based actionable dosing guidelines (AG) were 119 out of 141 residents (84.3%). Of these 119 residents, 87 residents used drugs with AG for CYP2C19, 47 residents for CYP2D6, and 42 residents for SLCO1B1. In addition, 30 residents used two drugs with an AG for CYP2C19, and for CYP2D6, it was only seven residents. The most used drugs with AG were clopidogrel (42), pantoprazole (32), simvastatin (30), metoprolol (25), and citalopram (24). The most frequent drug interactions found with warnings were combinations of proton pump inhibitors and clopidogrel underscoring the potential for phenoconversion. Conclusion: this study clearly showed that the majority of the nursing home residents were exposed to drugs or drug combinations for which there exist PGx-based AG. This indeed supports the notion of accessing and accounting for not only drug–gene but also drug–drug–gene interactions as a supplement to medication review.
The Employability Process of Spanish Retired Elite Athletes: Gender and Sport Success Comparison

The aims of the study were: (i) to describe the work integration after retirement in elite athletes, (ii) to compare the working integration of women and men, and Olympic and non-Olympic athletes, and (iii) to specify the factors that affect their employment status and current monthly income. A total of 476 former elite athletes were surveyed. Non-parametric statistics were applied to compare the differences between groups and a classification tree analysis was performed for the dependent variables. The former elite athlete’s unemployment rate was better than the general population. At the gender comparison, a wage gap appeared between women and men. At the comparison between Olympic and non-Olympic athletes, the link to first employment differed in both groups. In the prediction models, finishing higher education arose as a key factor of the working status and the monthly salary. Among those without higher education studies, planning arose as a factor determining their salary, while among those with high qualifications, gender was the key factor. This study supports the importance of a holistic view of athletic career development and it offers practical insights into the process of reaching first employment after retirement.
Neonatal RDS and LUS, is the debate still open?

We read the letter to the editor “B-lines score: artifacts as a sign of neonatal specific disease? ” by Quarato et al. and we are pleased by the interest aroused by our article “Neonatal lung ultrasonography score after surfactant in preterm infants: A prospective observational study” published on your journal. This study included preterm neonates with respiratory distress syndrome (RDS), requiring non-invasive ventilation and surfactant. The aim of our citated study was to asses changes of a validated neonatal lung ultrasonography score (nLUS) after surfactant treatment. Our data demonstrate a lowering of the nLUS 2h and 12h after surfactant treatment. In their letter to the editor Quarato et al. expressed criticism about the nLUS score validation and about the utility of the Lung Ultrasound (LUS) as a diagnostic tool. They conclude that “LUS can be used only for diagnosing minimal pleural effusion and, at least, as complementary imaging, in addiction to chest radiographs (CR), for monitoring the reduction of subpleural pneumonitic consolidations under therapy”. Our citated study hasn’t focused on validation of the nLUS score or on LUS as a diagnostic tool for neonatal RDS, so we don’t get how Quarato’s concerns can be addressed to our paper. Nevertheless, finding the debate about nLUS or LUS in the neonatal field an occasion to promote an improving in the care of the preterm babies, we will discuss objections raised in Quadrato’s work, point by point.
Flavonoids isolated from Medicago littoralis Rhode (Fabaceae): their ecological and chemosystematic significance

Abstract Three ﬂavonoids, laricitrin 3,5’-di-O-β-glucopyranoside (1), genistein 7-O-β-glucopyranoside (2), and biochanin A 7-O-β-glucopyranoside (= sissotrin) (3), were isolated for the ﬁrst time from the aerial parts of Medicago littoralis Rhode. The structures of the isolated compounds were established by NMR and LCDAD-ESI-MS analyses. The chemosystematic of ﬂ avones and isoﬂ avones identiﬁ ed was useful for discriminating different taxa inside the section Spirocarpos. In addition, the phytochemical proﬁ le of M. littoralis showed a behaviour due to the ecological conditions of sandy dunes, where this plant normally grows.
Performance characteristics of effluent toxicity tests: Variability and its implications for regulatory policy

An essential consideration when imposing a requirement for, or evaluating the results generated by, effluent toxicity tests in the National Pollutant Discharge Elimination System (NPDES) permit program is the amount of uncertainty in the measured test end point Variability in effluent toxicity test results is explored by examining round-robin test data with Daphnia magna, fathead minnows, and Certodaphnia dubia as test organisms Inter and intralaboratory percentages of survival of the test organisms are examined by using plots, descriptive statistics, and logistic regression models The results of the analyses demonstrate that the variation in survival is large (0-100% for some test solutions) In addition, the amount of variability is shown to be a function of the toxicity of the test solution The variability in survival is shown to be larger than the variability associated with the LC50 (a model-based end point) The large variability in effluent toxicity tests can have significant implications for the interpretation of toxicity test results used to measure compliance with effluent toxicity limits
MCF7 Spheroid Development: New Insight about Spatio/Temporal Arrangements of TNTs, Amyloid Fibrils, Cell Connections, and Cellular Bridges

Human breast adenocarcinoma cells (MCF7) grow in three-dimensional culture as spheroids that represent the structural complexity of avascular tumors. Therefore, spheroids offer a powerful tool for studying cancer development, aggressiveness, and drug resistance. Notwithstanding the large amount of data regarding the formation of MCF7 spheroids, a detailed description of the morpho-functional changes during their aggregation and maturation is still lacking. In this study, in addition to the already established role of gap junctions, we show evidence of tunneling nanotube (TNT) formation, amyloid fibril production, and opening of large stable cellular bridges, thus reporting the sequential events leading to MCF7 spheroid formation. The variation in cell phenotypes, sustained by dynamic expression of multiple proteins, leads to complex networking among cells similar to the sequence of morphogenetic steps occurring in embryogenesis/organogenesis. On the basis of the observation that early events in spheroid formation are strictly linked to the redox homeostasis, which in turn regulate amyloidogenesis, we show that the administration of N-acetyl-l-cysteine (NAC), a reactive oxygen species (ROS) scavenger that reduces the capability of cells to produce amyloid fibrils, significantly affects their ability to aggregate. Moreover, cells aggregation events, which exploit the intrinsic adhesiveness of amyloid fibrils, significantly decrease following the administration during the early aggregation phase of neutral endopeptidase (NEP), an amyloid degrading enzyme.
Thermal Effects on the Population Parameters and Growth of Acyrthosiphon pisum (Harris) (Hemiptera: Aphididae)

The pea aphid Acyrthosiphon pisum (Harris) (Hemiptera: Aphididae) is a cosmopolitan and polyphagous species. An evaluation of A. pisum’s demographic parameters and growth was carried out after rearing aphids on faba bean plants (Vicia faba) under five different temperature conditions (10 °C, 15 °C, 20 °C, 25 °C and 30 °C). We analyzed the raw life history data, including developmental time, survival, longevity and reproduction, using an age-stage, two-sex life table to consider variable developmental rates among individuals. The population fluctuation of A. pisum determined the stage-specific population structure and potential population growth under different temperature conditions. A. pisum individuals developed successfully from nymphs to adults at all temperatures in this study. The developmental rate of A. pisum increased as the temperature increased. Our results indicated that A. pisum showed a higher pre-adult mortality, lower total fecundity and a negative intrinsic rate of increase at 30 °C. The highest intrinsic rate of increase (0.30) and finite rate of increase (1.35) were observed at 25 °C. Comparisons of population parameters and their analytical methods between different A. pisum populations from other geographic areas are also discussed.
Correspondence on ‘2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus’ by Aringer et al

The 2019 European League against rheumatism/American College of Rheumatology classification criteria (EULAR/ACR 2019 criteria) for systemic lupus erythematosus (SLE) has introduced a new scoring system to classify SLE.1 The EULAR/ACR 2019 criteria include positive antinuclear antibody at least once as obligatory entry criterion; followed by additive weighted criteria grouped in seven clinical and three immunological domains and weighted from 2 to 10. Patients fulfilling at least one clinical criterion and accumulating ≥10 points are classified. In validation cohort, a classification threshold score of ≥10 yielded a sensitivity similar to that of the Systemic Lupus International Collaborating Clinics (SLICC) 2012 criteria (96.1% vs 96.7%) and a specificity similar to that of the ACR 1997 criteria (93.4% vs 93.4%), demonstrating both excellent sensitivity and specificity. However, we have two concerns about its additive criteria and methodology. First, some gastrointestinal injuries related to SLE, especially lupus enteritis, may be underestimated. Gastrointestinal symptoms are reported to occur in more than 50% of patients with SLE at some point in the course of their disease; …
Influence of murine maternal diabetes on placental morphology, gene expression, and function

Abstract Maternal diabetes causes placental and foetal abnormalities in both rat and humans; however, its effect is less well documented in the mouse. We used a standard approach to induce manifest diabetes in pregnant mice and assessed morphology, function and gene expression in the placentas isolated from these females. We found that diabetic placentas exhibit a consistent abnormal phenotype characterized by increased junctional zone cross sectional area. Lipid profiling of diabetic foetuses and placentas showed that the placental phenotypes do not compromise the lipid transport function of this organ. In a genome-wide survey of mRNA expression by using cDNA micro-arrays, we identified 118 ESTs, corresponding to 59 annotated genes, with differential expression in the diabetic placentas. A significant proportion of these known is involved in metabolism, immunity and defence, and signal transduction. In addition, we found two imprinted genes, Igf2 and Gatm, which exhibited altered expression. The expression of other imprinted genes, Peg1, Gtl2, Peg3, Igf2r and Grb10, was determined by quantitative RT-PCR. For all of these genes, slight changes in gene expression were observed between diabetic placentas and control placentas. Our study thus provides the basis for future work that will address gene action in the diabetic mouse placenta.
A Novel Culinary Medicine Course for Undergraduate Medical Education

Traditional nutrition education in medical school has been inadequate to prepare future physicians to counsel patients on practical dietary changes that can prevent and treat food-related disease. Culinary medicine is being used to address this in a variety of settings, including medical education. The Teaching Kitchen Elective for Medical Students at Stanford University School of Medicine spans 1 academic quarter and combines hands-on cooking of food that is delicious and healthy, correlations with multiple clinical specialties, and role-playing real-life examples of brief dietary counseling with patients to make nutrition education practical and approachable. The course has been run as a quasi-randomized controlled study comparing 3 cohorts of students versus wait-listed controls via precourse and postcourse surveys. Preliminary analysis of the first cohort of students shows significant improvements in attitudes, knowledge, and behaviors around healthy cooking and meal planning for the students compared with controls. Despite these promising preliminary results, more resources are needed to be able to hold the course frequently enough to meet student demand.
Garcinia kola (Heckel) and Alchornea cordifolia (Schumach. & Thonn.) Müll. Arg. from Cameroon possess potential antisalmonellal and antioxidant properties

Drug resistant Salmonella species and shortcomings related to current drugs stress the urgent need to search for new antimicrobial agents to control salmonellosis. This study investigated the antisalmonellal and antioxidant potentials of methanolic and hydro-ethanolic extracts of Garcinia kola and Alchornea cordifolia as potential sources of drugs to control Salmonella species and to reduce related oxidative stress. The antisalmonellal activity was assessed using the broth microdilution, membrane destabilization and time-kill kinetic assays. While, the DPPH, ABTS and FRAP assays were used for the determination of the antioxidant activities. The minimum inhibitory concentrations ranged from 125 to 1000 μg/mL, with the methanolic root extract of G. kola being the most active. The time kill kinetic assay revealed a concentration-dependent bacteriostatic activity for promising extracts. Potent extracts from G. kola showed the ability to destabilize S. typhi outer membrane, with the methanolic root extract presenting the highest activity; two-fold higher than those of polymyxin B tested as reference. In addition, this methanolic root extract of G. kola also provoked nucleotide leakage in a concentration-dependent manner. From the antioxidant assays, the hydro-ethanolic extract from the stem bark of A. cordifolia presented significant activities comparable to that of Vitamin C. The methanolic root extract of G. kola also presented appreciable antioxidant activities, though less than that of A. cordifolia. Overall, the phytochemical screening of active extracts revealed the presence of anthocyanins, flavonoids, glycosides, phenols, tannins, triterpenoids and steroids. These results provide evidence of the antibacterial potential of G. kola and offer great perspectives in a possible standardisation of an antisalmonellal phytomedicine.
Limbic-predominant age-related TDP-43 encephalopathy, ADNC pathology, and cognitive decline in aging

Objective To examine the impact of 3 pathologic groups, pure limbic-predominant age-related transactive response DNA-binding protein 43 encephalopathy (LATE) neuropathologic changes (NC), pure Alzheimer disease neuropathologic change (ADNC), and mixed ADNC with LATE-NC, on late-life cognitive decline. Methods Data came from 1,356 community-based older persons who completed detailed annual cognitive testing and systematic neuropathologic examination at autopsy to identify LATE-NC, ADNC, and other age-related pathologies. Persons were categorized into (0) a group without a pathologic diagnosis of LATE or ADNC (n = 378), (1) LATE-NC without ADNC (n = 91), (2) ADNC without LATE-NC (n = 535), and (3) mixed ADNC with LATE-NC (n = 352). We used mixed-effect models to examine the group associations with rate of decline in global cognition and 5 cognitive domains and then examined whether age modified associations. Results Compared to those without LATE-NC or ADNC, those with pure LATE-NC had a faster decline in global cognition (p = 0.025) and episodic memory (p = 0.002); however, compared to persons with pure ADNC, those with pure LATE-NC showed a slower decline. Those with mixed ADNC with LATE-NC showed the fastest decline compared to those with either pathology alone. Persons ≥90 years of age with mixed ADNC with LATE-NC had slower cognitive decline compared to those ≤89 years of age. Conclusion Persons with pure LATE-NC follow a slower trajectory compared to those with pure ADNC. Those with mixed LATE/ADNC have a steeper decline than individuals with either pathology alone. In addition, age may modify the effect of pathology on cognitive decline. These findings have important implications for the development of biomarkers and prognosis for late-life cognitive decline. Classification of evidence This study provides Class I evidence that LATE-NC and Alzheimer disease pathologic changes are associated with different trajectories of late-life cognitive decline.
Tiwouh: An enriched technology-based solution for communication interventions

Democratizing mobile technological devices lead to the development and spreading of tools supporting communication of individuals with Intellectual Disabilities (ID). Although promising, these tools exhibit limited impacts in daily life given their limited features and the lack of health professional support. This article presents Tiwouh, an enriched technological solution to support communication interventions. After documenting the needs, this solution has been deployed and used in real life situations within a daycare facility for adults with ID.
Comment on López-Yerena et al. “Absorption and Intestinal Metabolic Profile of Oleocanthal in Rats” Pharmaceutics 2020, 12, 134

This comment is intended to discuss errors observed in the title paper, doi:10.3390/pharmaceutics12020134. When this paper was published, the authors of this commentary were excited to read it. However, the more we read, the more pitfalls were observed, which necessitated a response to revise the many errors and misleading information included in this publication.