Miracle-dz/UniFAR-FTUs huggingface dataset:
Controversial Roles of the Renin Angiotensin System and Its Modulators During the COVID-19 Pandemic

Since December 2019, the coronavirus 2019 (COVID-19) pandemic has rapidly spread and overwhelmed healthcare systems worldwide, urging physicians to understand how to manage this novel infection. Early in the pandemic, more severe forms of COVID-19 have been observed in patients with cardiovascular comorbidities, who are often treated with renin-angiotensin aldosterone system (RAAS)-blockers, such as angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), but whether these are indeed independent risk factors is unknown. The cellular receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the membrane-bound angiotensin converting enzyme 2 (ACE2), as for SARS-CoV(-1). Experimental data suggest that expression of ACE2 may be increased by RAAS-blockers, raising concerns that these drugs may facilitate viral cell entry. On the other hand, ACE2 is a key counter-regulator of the RAAS, by degrading angiotensin II into angiotensin (1-7), and may thereby mediate beneficial effects in COVID-19. These considerations have raised concerns about the management of these drugs, and early comments shed vivid controversy among physicians. This review will describe the homeostatic balance between ACE-angiotensin II and ACE2-angiotensin (1-7) and summarize the pathophysiological rationale underlying the debated role of the RAAS and its modulators in the context of the pandemic. In addition, we will review available evidence investigating the impact of RAAS blockers on the course and prognosis of COVID-19 and discuss why retrospective observational studies should be interpreted with caution. These considerations highlight the importance of solid evidence-based data in order to guide physicians in the management of RAAS-interfering drugs in the general population as well as in patients with more or less severe forms of SARS-CoV-2 infection.
Biological convolutions improve DNN robustness to noise and generalisation

Deep Convolutional Neural Networks (DNNs) have achieved superhuman accuracy on standard image classification benchmarks. Their success has reignited significant interest in their use as models of the primate visual system, bolstered by claims of their architectural and representational similarities. However, closer scrutiny of these models suggests that they rely on various forms of shortcut learning to achieve their impressive performance, such as using texture rather than shape information. Such superficial solutions to image recognition have been shown to make DNNs brittle in the face of more challenging tests such as noise-perturbed or out-of-domain images, casting doubt on their similarity to their biological counterparts. In the present work, we demonstrate that adding fixed biological filter banks, in particular banks of Gabor filters, helps to constrain the networks to avoid reliance on shortcuts, making them develop more structured internal representations and more tolerant to noise. Importantly, they also gained around 20 35% improved accuracy when generalising to our novel out-of-domain test image sets over standard end-to-end trained architectures. We take these findings to suggest that these properties of the primate visual system should be incorporated into DNNs to make them more able to cope with real-world vision and better capture some of the more impressive aspects of human visual perception such as generalisation.
Clinical Implications of Inflammation in Acute Myeloid Leukemia

Recent advances in the description of the tumor microenvironment of acute myeloid leukemia, including the comprehensive analysis of the leukemic stem cell niche and clonal evolution, indicate that inflammation may play a major role in many aspects of acute myeloid leukemia (AML) such as disease progression, chemoresistance, and myelosuppression. Studies on the mechanisms of resistance to chemotherapy or tyrosine kinase inhibitors along with high-throughput drug screening have underpinned the potential role of glucocorticoids in this disease classically described as steroid-resistant in contrast to acute lymphoblastic leukemia. Moreover, some mutated oncogenes such as RUNX1, NPM1, or SRSF2 transcriptionally modulate cell state in a manner that primes leukemic cells for glucocorticoid sensitivity. In clinical practice, inflammatory markers such as serum ferritin or IL-6 have a strong prognostic impact and may directly affect disease progression, whereas interesting preliminary data suggested that dexamethasone may improve the outcome for AML patients with a high white blood cell count, which paves the way to develop prospective clinical trials that evaluate the role of glucocorticoids in AML.
Manipulating Levels of Socially Evaluative Threat and the Impact on Anticipatory Stress Reactivity

Previous work suggests that relative increases in socially evaluative threat modulate the psychobiological stress response. However, few studies have compared stressors which manipulate the level of socially evaluative threat to which the participant is exposed. Here we present two studies. In the first, we assessed the integrity of an ecologically valid, laboratory stressor (direct socially evaluated multitasking) and its effects on acute psychobiological reactivity and ability to evoke an anticipatory response prior to participation. Specifically, we assessed whether the expectation and experience of direct social evaluation (multitasking while standing and facing an evaluator) evokes greater reactivity than indirect evaluation (over-the-shoulder evaluation). In the second study, we sought to replicate the findings regarding acute stress reactivity whilst extending the assessment window to assess the extent to which the stressor evokes anticipatory responses. As hypothesized, greater reactivity was observed following direct social evaluation compared with indirect observation. Increases in anxiety, heart rate and blood pressure were demonstrated across both studies and the paradigm therefore provides an ecologically valid technique for the activation of psychological and cardiovascular stress responding. Additionally, anticipation of experiencing socially evaluated multitasking led to increases in anxiety, tension, and worry prior to the event itself, supporting previous suggestions that threat anticipation may prolong the activation of stress mechanisms. In the present studies we assessed whether the expectation and experience of direct social evaluation evokes greater reactivity than indirect evaluation. The findings have demonstrated that direct social evaluation of multitasking is a more potent stressor than multitasking with indirect evaluation. Furthermore, our findings indicate that the period of anticipation of stressful events may be critical to understanding the process of stress regulation, and as such we recommend extending the sampling window to allow for the investigation of these processes.
Small Molecule Treatments Improve Differentiation Potential of Human Amniotic Fluid Stem Cells

Human amniotic fluid stem cells (AFSC) are an exciting and very promising source of stem cells for therapeutic applications. In this study we investigated the effects of short-term treatments of small molecules to improve stem cell properties and differentiation capability. For this purpose, we used epigenetically active compounds, such as histone deacetylase inhibitors Trichostatin A (TSA) and sodium butyrate (NaBut), as well as multifunctional molecules of natural origin, such as retinoic acid (RA) and vitamin C (vitC). We observed that combinations of these compounds triggered upregulation of genes involved in pluripotency (KLF4, OCT4, NOTCH1, SOX2, NANOG, LIN28a, CMYC), but expression changes of these proteins were mild with only significant downregulation of Notch1. Also, some alterations in cell surface marker expression was established by flow cytometry with the most explicit changes in the expression of CD105 and CD117. Analysis of cellular energetics performed using Seahorse analyzer and assessment of gene expression related to cell metabolism and respiration (NRF1, HIF1α, PPARGC1A, ERRα, PKM, PDK1, LDHA, NFKB1, NFKB2, RELA, RELB, REL) revealed that small molecule treatments stimulate AFSCs toward a more energetically active phenotype. To induce cells to differentiate toward neurogenic lineage several different protocols including commercial supplements N2 and B27 together with RA were used and compared to the same differentiation protocols with the addition of a pre-induction step consisting of a combination of small molecules (vitC, TSA and RA). During differentiation the expression of several neural marker genes was analyzed (Nestin, MAP2, TUBB3, ALDH1L1, GFAP, CACNA1D, KCNJ12, KCNJ2, KCNH2) and the beneficial effect of small molecule treatment on differentiation potential was observed with upregulated gene expression. Differentiation was also confirmed by staining TUBB3, NCAM1, and Vimentin and assessed by secretion of BDNF. The results of this study provide valuable insights for the potential use of short-term small molecule treatments to improve stem cell characteristics and boost differentiation potential of AFSCs.
Retrograde Control of Cytosolic Translation Targets Synthesis of Plastid Proteins and Nuclear Responses for High-Light Acclimation

Canonical retrograde signalling comprises information transmission from organelles to the nucleus and in particular controls gene expression for organellar proteins. The need to re-assess this paradigm was suggested by discrepancies between de novo protein synthesis and transcript abundance in response to excess light. Here we uncover major components of a translation-dependent retrograde signalling pathway that first impacts translation and then transcription. The response realization depends on the kinases Mitogen-activated protein kinase 6 (MPK6) and Sucrose non-fermenting 1-related kinase (SnRK1) subunit, AKIN10. Global ribosome foot-printing revealed differential ribosome association of 951 transcripts within 10 min after transfer from low to high light. Despite predominant translational repression, 15 % of transcripts were increased in translation and enriched for chloroplast-localized photosynthetic proteins. About one third of these transcripts, including Stress associated proteins (SAP) 2 and 3, share regulatory motifs in their 5′-UTR that act as binding sites for glyceraldehyde-3-phosphate dehydrogenase (GAPC) and light responsive RNA binding proteins (RBPs). SAP2 and 3 are both translationally regulated and interact with the calcium sensor Calmodulin-like 49 (CML49), which promotes relocation to the nucleus inducing a translation-dependent nuclear stress response. Thus, translation-dependent retrograde signalling bifurcates to directly regulate a translational circuit of chloroplast proteins and simultaneously initiate a nuclear circuit synchronizing retrograde and anterograde response pathways, serving as a rapid mechanism for functional acclimation of the chloroplast.
Spouse-Appraised Memory Functioning Predicts Memory Decline Better Than Subjective Memory Complaints in Community Dwelling Older Adults at Genetic Risk for Alzheimer's Disease

Objective: Alzheimer's disease (AD) begins with subtle memory decline, years before dementia onset. The presence of subjective memory complaints (SMC) has been proposed as a marker of preclinical AD. However, recent evidence has demonstrated early and progressive loss of awareness of memory difficulties in non-demented older adults harboring AD pathology. We investigated the respective contributions of SMC and spouse-appraised memory functioning (SAM) to predict memory decline in a large cohort of community dwelling older adults. Methods: The Wisconsin Longitudinal Study collected cognitive data from a community-based cohort of 3,583 participants in both 2005 and 2011. The participant and the participant's spouse were each asked to rate the participant's memory functioning using a Likert scale. We predicted change in objective episodic memory with models including baseline SMC, baseline SAM, or both SMC and SAM. We also evaluated an awareness index (SMC minus SAM). We then tested the interaction between Apolipoprotein E (APOE ε4) carrier status and SMC/SAM to evaluate whether the effects were driven by individuals at-risk for AD pathology. Results: In separate models, SMC (−0.081 ± 0.036, p = 0.025) and SAM (−0.084 ± 0.278, p = 0.003) were both associated with memory decline over ~6 years. However, the AI was not significantly associated with memory decline (0.031 ± 0.024, p = 0.19). When both predictors were included in the same model, SAM (−0.074 ± 0.03, p = 0.0092) was associated with memory decline, while SMC was not significant (−0.061 ± 0.04, p = 0.99). The association between SAM and memory decline was stronger in the APOE ε4 carriers than in the non-carriers (APOE-by-SAM interaction: F = 6.07; p = 0.002), and follow up analyses revealed that SAM was particularly predictive of decline only for APOE ε4 carriers. The association between SMC and memory decline was independent of APOE ε4 carrier status (APOE-by-SMC interaction: F = 2.29; p = 0.13). Conclusions: Spouse-appraised memory functioning was more predictive of memory decline than SMC or an awareness index, particularly in APOE ε4 carriers, who are at increased risk for AD pathology.
Drug Checking as Strategy for Harm Reduction in Recreational Contests: Evaluation of Two Different Drug Analysis Methodologies

Introduction: Drug checking as a part of drug harm-reduction strategies represents an essential aspect of public health policies. It focuses on rapid identification of drugs that individuals intend to use during night events, in order to implement health-protective behaviors. Chemical drug analysis techniques vary considerably, from simple colorimetric reagents to advanced forensic methods such as gas chromatography/mass spectrometry (GC/MS). Materials and Methods: In 2019, drug-check services were offered at some night events in Umbria (Central Italy). One hundred and twenty attendees directly delivered unidentified substances to a harm-reduction worker, who collected a few milligrams of the substances on ceramic plates and added a drop of colorimetric reagent. Multiple reagents were used to increase the diagnostic capacity of a substance, which may react with a specific drug or a few drugs. Later, a fraction of the samples was analyzed by GC/MS. The concordance of the results obtained using these two methodologies and the intended behaviors of consumers after being informed of the test result was evaluated. Results: We analyzed 120 samples by colorimetric test: 32 MDMA, 25 ketamine, 10 amphetamine, 11 cocaine, 8 heroin, and 4 LSD samples. The results were inconclusive for 29 samples. The GS/MS analysis confirmed MDMA in 84%, ketamine in 78%, amphetamine in 91%, cocaine in 92%, heroin in 88%, and LSD in 100% of the samples. The results of samples with inconclusive results were as follows: 2, MDMA; 7, ketamine; 2, amphetamine; 2, cocaine; 2, heroin; 2, mephedrone; 6, mixes; 1, debris; and 5, adulterants as the main component. Twenty-one of 29 participants reported that they had no intention of consuming the unidentified substance. Discussion: The high percentage of individuals who claimed no intention of consuming the unidentified drugs indicates that drug checking is viable as a part of drug harm-reduction strategies. Overall, colorimetric reagents showed a good performance with regard to samples being unadulterated (LSD) or minimal in quantity, but failed to identify mixtures of substances and the adulterants present in them. Therefore, the use of more discriminatory on-site methods such as Raman or infrared spectrometry is strongly recommended.
Effects of High Intensity Interval vs. Endurance Training on Cardiac Parameters in Ischemia/Reperfusion of Male Rats: Focus on Oxidative Stress

Citation: Rankovic M, Jakovljevic V, Bradic J, Jakovljevic B, Zivkovic V, Srejovic I, Bolevich S, Milosavljevic I, Jeremic J, Ravic M, Mijanovic O, Turnic TN and Jeremic N (2021) Effects of High Intensity Interval vs. Endurance Training on Cardiac Parameters in Ischemia/Reperfusion of Male Rats: Focus on Oxidative Stress. Front. Physiol. 12:534127. doi: 10.3389/fphys.2021. 534127 Effects of High Intensity Interval vs. Endurance Training on Cardiac Parameters in Ischemia/Reperfusion of Male Rats: Focus on Oxidative Stress
Application of Fractions of Crop Evapotranspiration Affects Carbon Partitioning of Grapevine Differentially in a Hot Climate

Majority of viticulture regions are located in mid-latitudes characterized by weather variability and stressful environments relying on irrigation for mitigating environmental stress during the growing season and to ensure a profitable yield. The aim of this study was to characterize the response of grapevine (Vitis vinifera L. cv. Cabernet Sauvignon) to different applied water amounts based on the replacement of fractions of crop evapotranspiration (ETc) during two growing seasons with contrasting precipitation patterns. The experiment consisted of three irrigation treatments based on the weekly replacement of 25, 50, and 100% of ETc. Grapevine stem water potential decreased during the growing season reaching its lowest value (-1.5 and -1.2 MPa, respectively) at harvest in the more stressed vines (25 and 50% ETc). Leaf gas exchange variables were measured during the two seasons and 100% ETc had the highest rates of photosynthesis and stomatal conductance and better instantaneous water use efficiency, also resulting in higher leaf chlorophyll and carotenoid content. Mineral nutrient content for nitrogen and potassium increased linearly with the increase in applied water. At harvest, no differences were observed in the number of clusters per vine; however, the 25% ETc had the lowest berry size and yield per vine with no difference in sugar content of berry. Conversely, sugar allocation to reserve organs was highly affected by applied water leading to different shoot to root biomass partitioning, where shoot:root ratio, leaf non-structural carbohydrates, and photosynthetic pigments increased with greater applied water. Likewise sucrose:N ratio and root non-structural carbohydrates decreased with the lower applied water. Altogether, carbon allocation between the source and sink organs likely controlled the response of grapevines to water deficits in a hot climate, and replacing 50% ETc was sufficient to sustain the grapevine performance given the enhancement of sugar transport, which could slow down the detrimental effect of water deficits on yield.
The Relationship Between Fears of Cancer Recurrence and Patient Gender: A Systematic Review and Meta-Analysis

Background: A significant concern for patients treated for cancer is fear of cancer recurrence (FCR). Although a common experience, some patients report high levels of FCR that are difficult to manage and result in over vigilant checking and high use of health services. There has been speculation about the relationship of FCR with gender with mixed reports from several systematic reviews. Aims: To determine the association of FCR with gender in previous reported studies and investigate the strength of this relationship with various moderators including year of publication, type of cancer and measurement attributes of self-reported FCR instruments. Methods: A systematic review was conducted with searches of the literature from the MEDLINE, PubMed, Embase, and PsycINFO databases following PRISMA guidelines. All the included papers were divided into two groups, namely: “pure” that comprise only of patients with cancer types that both men and women can contract and “mixed” that report on patients with a variety of cancer types. The association between gender and FCR level was assessed by meta-analysis. A meta-regression was performed to investigate the moderating effects of factors including: the year of publication, cancer type, mean age of the sample and the length of the FCR scale measurement. This review was registered with PROSPERO, ID: CRD42020184812. Results: Finally, 29 studies were included. The N size of pooled participants was 33,339. The meta-analysis showed females to have an overall higher level of FCR than males (ES = 0.30; 95% CI, 0.23, 0.36). The meta-regression of moderating or control variables found little, if any, systematic variation in effect-sizes. Conclusion: This systematic review has clarified a potentially confused pattern of previous results in understanding the relationship between gender and FCR. Women report higher levels of FCR than men and this feature is one that clinicians and researchers can factor into their practice and future studies. The effect size is moderate, hence there is ample variation in FCR level, independent of gender, that requires further investigation.
Structure of Organic/Inorganic Interface in Assembled Materials Comprising Molecular Components. Crystal Structure of the Sensitizer Bis[(4,4‘-carboxy-2,2‘-bipyridine)(thiocyanato)]ruthenium(II)

Structural data have been obtained for the photosensitizer bis[(4,4‘-carboxy-2,2‘-bipyridine)(thiocyanato)]ruthenium(II) (1) via X-ray diffraction analysis. Crystals of 1 are triclinic, a = 11.4663(4) A, b = 12.5897(5) A, c = 18.9329(7) A, α = 75.238(2)°, β = 89.611(2)°, γ = 66.446(2)°, space group P1, Z = 2, refinement to R = 0.0809, Rw = 0.0950 for 4045 observed reflections. Structural models of sensitizer molecules anchoring to the TiO2 anatase surface and models of close-packed sensitizer monolayers with different anchoring types have been built by using experimental geometry of known organic Ti complexes and the X-ray structure of sensitizer 1. On the basis of a simple one-dimensional tight-binding model, it was suggested that possible modifications of TiO2/sensitizer interface could enhance interfacial transparency for injected electrons.
Preliminary results of a screening programme for Chlamydia in an asymptomatic young population

Introduction Chlamydia trachomatis infection has increased in recent years, reaching 127 million cases in 2016. Possible complications, especially among women, require intervention for early detection. The objective of our study was to determine the prevalence of Chlamydia infection in a young, sexually active, asymptomatic population.Methods A cross-sectional study was conducted among young patients aged 18 to 25 years attending the emergency room for any reason. The presence of Chlamydia trachomatis and other STIs in urine was determined.Results Twenty-two patients enrolled in the screening (7.4%) were diagnosed with Chlamydia. A further nine patients among the partners of those affected were detected. Young people with two or more sexual partners in the last month and those suffering from infection by ureaplasma were at greater risk of infection by Chlamydia. Up to 50% of participants do not use barrier methodsConclusion The prevalence of infection by Chlamydia in the asymptomatic young population is higher than expected. The scarce use of barrier methods among this population may be one of the causes of this increase and one of the targets to work on in order to reduce the prevalence of the infection.