Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of the COVID-19 Epidemic on Hospital Admissions for Non-Communicable Diseases in a Large Italian University-Hospital: A Descriptive Case-Series Study

Background: Concern is growing about the negative consequences that response measures to the COVID-19 epidemic may have on the management of other medical conditions. Methods: A retrospective descriptive case-series study conducted at a large University-hospital in northern Italy, an area severely hit by the epidemic. Results: Between 23 February and 14 May 2020, 4160 (52%) COVID-19 and 3778 (48%) non-COVID-19 patients were hospitalized. COVID-19 admissions peaked in the second half of March, a period characterized by an extremely high mortality rate (27.4%). The number of admissions in 2020 was similar to 2019, but COVID-19 patients gradually occupied all available beds. Comparison between COVID-19 and non-COVID-19 admissions in 2020 revealed significant differences concerning all age classes and gender. Specifically, COVID-19 patients were older, predominantly male, and exhibited more comorbidities. Overall, admissions for non-communicable diseases (NCDs) in 2020 vs. 2019 dropped by approximately one third. Statistically significant reductions were observed for acute myocardial infarction (−78, −33.9%), cerebrovascular disease (−235, −41.5%), and cancer (−368, −31.9%). While the first two appeared equally distributed between COVID-19 and non-COVID-19 patients, chronic NCDs were statistically significantly more frequent in the former, except cancer, which was less frequent in COVID-19 patients. Conclusions: Prevention of collateral damage to patients with other diseases should be an integral part of epidemic response plans. Prospective cohort studies are needed to understand the long-term impact.
Development of BCR-ABL1 Transgenic Zebrafish Model Reproducing Chronic Myeloid Leukemia (CML) Like-Disease and Providing a New Insight into CML Mechanisms

Zebrafish has proven to be a versatile and reliable experimental in vivo tool to study human hematopoiesis and model hematological malignancies. Transgenic technologies enable the generation of specific leukemia types by the expression of human oncogenes under specific promoters. Using this technology, a variety of myeloid and lymphoid malignancies zebrafish models have been described. Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasia characterized by the BCR-ABL1 fusion gene, derived from the t (9;22) translocation causing the Philadelphia Chromosome (Ph). The BCR-ABL1 protein is a constitutively activated tyrosine kinas inducing the leukemogenesis and resulting in an accumulation of immature leukemic cells into bone marrow and peripheral blood. To model Ph+ CML, a transgenic zebrafish line expressing the human BCR-ABL1 was generated by the Gal4/UAS system, and then crossed with the hsp70-Gal4 transgenic line. The new line named (BCR-ABL1pUAS:CFP/hsp70-Gal4), presented altered expression of hematopoietic markers during embryonic development compared to controls and transgenic larvae showed proliferating hematopoietic cells in the caudal hematopoietic tissue (CHT). The present transgenic zebrafish would be a robust CML model and a high-throughput drug screening tool.
Refractive Precision of Ray Tracing IOL Calculations Based on OCT Data versus Traditional IOL Calculation Formulas Based on Reflectometry in Patients with a History of Laser Vision Correction for Myopia

Purpose To compare the refractive predictability of ray tracing IOL calculations based on OCT data versus traditional IOL calculation formulas based on reflectometry in patients with a history of previous myopic laser vision correction (LVC). Patients and Methods This was a prospective interventional single-arm study of IOL calculations for cataract and refractive lens exchange (RLE) patients with a history of myopic LVC. Preoperative biometric data were collected using an optical low coherence reflectometry (OLCR) device (Haag-Streit Lenstar 900) and two optical coherence tomography (OCT) devices (Tomey Casia SS-1000 and Heidelberg Engineering Anterion). Traditional post LVC formulas (Barret True-K no-history and Haigis-L) with reflectometry data, and ray tracing IOL calculation software (OKULIX, Panopsis GmbH, Mainz, Germany) with OCT data were used to calculate IOL power. Follow-up examination was 2 to 3 months after surgery. The main outcome measure, refractive prediction error (RPE), was calculated as the achieved postoperative refraction minus the predicted refraction. Results We found that the best ray tracing combination (Anterion-OKULIX) resulted in an arithmetic prediction error statistically significantly lower than that achieved with the best formula calculation (Barret True-K no-history) (−0.13 D and −0.32 D, respectively, adjusted p = 0.01), while the Barret TK NH had the lowest SD. The absolute prediction error was 0.26 D and 0.35 D for Anterion-OKULIX and Barret TK NH, respectively, but this was not statistically significantly different. The Anterion-OKULIX calculation also had the highest percentage of eyes within ± 0.25, compared to both formulas and within ±0.50 and ±0.75 compared to the Haigis-L (p = 0.03). Conclusion Ray tracing calculation based on OCT data from the Anterion device can yield similar or better results than traditional post LVC formulas. Ray tracing calculations are based on individual measurements and do not rely on the ocular history of the patient and are therefore applicable for any patient, also without previous refractive surgery.
Exposure to Quaternary Ammonium Compounds Selects Resistance to Ciprofloxacin in Listeria monocytogenes

In this contribution, the antimicrobial susceptibility toward 11 antibiotics and four biocides of a panel of 205 Listeria monocytogenes (Lm) strains isolated from different ecological niches (i.e., food, animals and natural environment) was evaluated. The impact of exposure to biocides on the antibiotic susceptibilities of Lm was also investigated. Lm strains isolated from food exhibited overall a lower susceptibility (higher minimal inhibitory concentrations, MIC) for ammonium quaternary compounds (QACs) and peracetic acid (PAC) than strains isolated from animals and natural environments. Conversely, the ecological origins of Lm strains did not significantly affect their susceptibilities towards antibiotics. Interestingly, repeated exposure to QACs recurrently led to a decrease in susceptibility toward ciprofloxacin (CIP), a fluoroquinolone antibiotic, largely used in human medicine. Moreover, these lower levels of susceptibility to CIP remained stable in most Lm strains even after subcultures without biocide selection pressure, suggesting an adaptation involving modifications at the genetic level. Results underlined the ability of Lm to adapt to biocides, especially QACs, and the potential link between this adaptation and the selection of resistance toward critical antibiotics such as ciprofloxacin. These data support a potential role of the extensive use of QACs from “farm to fork” in the selection of biocide and antibiotic resistance in pathogenic bacteria such as Lm.
Therapeutic Targeting of the Tumour Microenvironment in Metastatic Colorectal Cancer

Liver metastasis is the primary contributor to the death of patients with colorectal cancer. Despite the overall success of current treatments including targeted therapy, chemotherapy, and immunotherapy combinations in colorectal cancer patients, the prognosis of patients with liver metastasis remains poor. Recent studies have highlighted the importance of the tumour microenvironment and the crosstalk within that determines the fate of circulating tumour cells in distant organs. Understanding the interactions between liver resident cells and tumour cells colonising the liver opens new therapeutic windows for the successful treatment of metastatic colorectal cancer. Here we discuss critical cellular interactions within the tumour microenvironment in primary tumours and in liver metastases that highlight potential therapeutic targets. We also discuss recent therapeutic advances for the treatment of metastatic colorectal cancer.
Community Garden Initiatives Addressing Health and Well-Being Outcomes: A Systematic Review of Infodemiology Aspects, Outcomes, and Target Populations

Previous research has suggested that activities such as community gardens could offer a wide range of health benefits. The aim of the article is to systematically review the available literature to analyse the magnitude of the phenomenon, the geographical distribution, and the main characteristics in terms of health outcomes and target populations. The search addresses the question whether the activity in community gardens improves health and well-being outcomes of individuals. From the total amount of 7226, 84 selected articles showed that:(1) up to 50% are published by U.S. universities or institutions; (2) up to 44% of the studies considered “community gardens” as the main activity of the research focus; (3) one-third of the studies included adults; (4) almost 25% of the studies used “general health” as the main outcome when investigating the benefits of community gardens; (5) the percentage of studies that achieved their outcomes was heterogeneous among the different health dimensions. In conclusion, while a certain degree of heterogeneity in the used definition and outcome still exist, community gardens may be a viable strategy for well-being promotion in terms of psychological, social, and physical health and may be considered as an innovative urban strategy to promote urban public health.
Arginine Alters miRNA Expression Involved in Development and Proliferation of Rat Mammary Tissue

Simple Summary MiRNAs are small noncoding RNAs that regulate a variety of developmental and physiological processes, with many having well-defined developmental and cell-type specific expression patterns. Aspects of the cell cycle such as cell differentiation, proliferation and apoptosis can be regulated by miRNA, underscoring an unexplored link between arginine supply and mammary tissue function during lactation. The specific objective of the present study was to determine miRNA profiles in mammary tissue at the end of lactation in response to enhanced dietary supply of arginine. Our results indicate that arginine may potentially be involved in the development of rat mammary glands through miRNA. Abstract This study was designed to determine the effects of dietary arginine on development and proliferation in rat mammary tissue through changes in miRNA profiles. Twelve pregnant Wistar rats were allocated randomly to two groups. A basal diet containing arginine or the control diet containing glutamate on an equal nitrogen basis as the arginine supplemented diet were used. The experiment included a pre-experimental period of four days before parturition and an experimental period of 17 days after parturition. Mammary tissue was collected for histology, RNA extraction and high-throughput sequencing analysis. The greater mammary acinar area indicated that arginine supplementation enhanced mammary tissue development (p < 0.01). MicroRNA profiling indicated that seven miRNA (miR-206-3p, miR-133a-5p, miR-133b-3p, miR-1-3p, miR-133a-3p, miR-1b and miR-486) were differentially expressed in response to Arginine when compared with the glutamate-based control group. In silico gene ontology enrichment and KEGG pathway analysis revealed between 240 and 535 putative target genes among the miRNA. Further verification by qPCR revealed concordance with the differential expression from the sequencing results: 17 of 28 target genes were differentially expressed (15 were highly expressed in arginine and 2 in control) and 11 target genes did not have significant difference in expression. In conclusion, our study suggests that arginine may potentially regulate the development of rat mammary glands through regulating miRNAs.
Association of Multiple Glycemic Parameters at Hospital Admission with Mortality and Short-Term Outcomes in Acutely Poisoned Patients

The prognostic value of multiple glycemic parameters in poisoned patients was never assessed. We aim to explore the effects of glucose variability on short-term outcomes in nondiabetic and diabetic patients acutely poisoned with undifferentiated xenobiotics. We performed a prospective observational study in a tertiary center for toxicology in northeastern Romania. Over the course of 3 years, we included 1076 adults, older than 18 years, admitted for acute poisoning with a xenobiotic. The mortality rate was 4.1%. The admission blood glucose level (BGL) predicted mortality (OR 1.015, 95% CI 1.011–1.019, p < 0.001) and complications (OR 1.005, 95% CI 1.001–1.009, p 0.02). The mean glucose level (MGL) after admission (OR 1.007, 95% CI 1.000–1.013, p 0.034) and coefficient of glucose variability (CV) were predictive for complications (OR 40.58, 95% CI 1.35–1220.52, p 0.033), using the same multivariable model. The receiver operating characteristic curve (ROC) analysis revealed that BGL had good predictive value for in-hospital mortality (area under the curve (AUC) = 0.744, 95% CI = 0.648–0.841, p < 0.001), and complications (AUC = 0.618, 95% CI = 0.584–0.653, p < 0.001). In patients acutely poisoned with xenobiotics, the BGL, MGL and CV can be useful as mortality and short-outcome predictors.
Monitoring Contractile Cardiomyocytes via Impedance Using Multipurpose Thin Film Ruthenium Oxide Electrodes

A ruthenium oxide (RuOx) electrode was used to monitor contractile events of human pluripotent stem cells-derived cardiomyocytes (hPSC-CMs) through electrical impedance spectroscopy (EIS). Using RuOx electrodes presents an advantage over standard thin film Pt electrodes because the RuOx electrodes can also be used as electrochemical sensor for pH, O2, and nitric oxide, providing multisensory functionality with the same electrode. First, the EIS signal was validated in an optically transparent well-plate setup using Pt wire electrodes. This way, visual data could be recorded simultaneously. Frequency analyses of both EIS and the visual data revealed almost identical frequency components. This suggests both the EIS and visual data captured the similar events of the beating of (an area of) hPSC-CMs. Similar EIS measurement was then performed using the RuOx electrode, which yielded comparable signal and periodicity. This mode of operation adds to the versatility of the RuOx electrode’s use in in vitro studies.
Potassium Channels Kv1.3 and Kir2.1 But Not Kv1.5 Contribute to BV2 Cell Line and Primary Microglial Migration

(1) Background: As membrane channels contribute to different cell functions, understanding the underlying mechanisms becomes extremely important. A large number of neuronal channels have been investigated, however, less studied are the channels expressed in the glia population, particularly in microglia. In the present study, we focused on the function of the Kv1.3, Kv1.5 and Kir2.1 potassium channels expressed in both BV2 cells and primary microglia cultures, which may impact the cellular migration process. (2) Methods: Using an immunocytochemical approach, we were able to show the presence of the investigated channels in BV2 microglial cells, record their currents using a patch clamp and their role in cell migration using the scratch assay. The migration of the primary microglial cells in culture was assessed using cell culture inserts. (3) Results: By blocking each potassium channel, we showed that Kv1.3 and Kir2.1 but not Kv1.5 are essential for BV2 cell migration. Further, primary microglial cultures were obtained from a line of transgenic CX3CR1-eGFP mice that express fluorescent labeled microglia. The mice were subjected to a spared nerve injury model of pain and we found that microglia motility in an 8 µm insert was reduced 2 days after spared nerve injury (SNI) compared with sham conditions. Additional investigations showed a further impact on cell motility by specifically blocking Kv1.3 and Kir2.1 but not Kv1.5; (4) Conclusions: Our study highlights the importance of the Kv1.3 and Kir2.1 but not Kv1.5 potassium channels on microglia migration both in BV2 and primary cell cultures.
Transcranial Magnetic Stimulation of the Right Superior Parietal Lobule Modulates the Retro-Cue Benefit in Visual Short-Term Memory

Several studies have shown enhanced performance in change detection tasks when spatial cues indicating the probe’s location are presented after the memory array has disappeared (i.e., retro-cues) compared with spatial cues that are presented simultaneously with the test array (i.e., post-cues). This retro-cue benefit led some authors to propose the existence of two different stores of visual short-term memory: a weak but high-capacity store (fragile memory (FM)) linked to the effect of retro-cues and a robust but low-capacity store (working memory (WM)) linked to the effect of post-cues. The former is thought to be an attention-free system, whereas the latter would strictly depend on selective attention. Nonetheless, this dissociation is under debate, and several authors do not consider retro-cues as a proxy to measure the existence of an independent memory system (e.g., FM). We approached this controversial issue by altering the attention-related functions in the right superior parietal lobule (SPL) by transcranial magnetic stimulation (TMS), whose effects were mediated by the integrity of the right superior longitudinal fasciculus (SLF). Specifically, we asked whether TMS on the SPL affected the performance of retro cues vs. post-cues to a similar extent. The results showed that TMS on the SPL, mediated by right SLF-III integrity, produced a modulation of the retro-cue benefit, namely a memory capacity decrease in the post-cues but not in the retro-cues. These findings have strong implications for the debate on the existence of independent stages of visual short-term memory and for the growing literature showing a key role of the SLF for explaining the variability of TMS effects across participants.
In Silico Strategy for Targeting the mTOR Kinase at Rapamycin Binding Site by Small Molecules

Computer aided drug-design methods proved to be powerful tools for the identification of new therapeutic agents. We employed a structure-based workflow to identify new inhibitors targeting mTOR kinase at rapamycin binding site. By combining molecular dynamics (MD) simulation and pharmacophore modelling, a simplified structure-based pharmacophore hypothesis was built starting from the FKBP12-rapamycin-FRB ternary complex retrieved from RCSB Protein Data Bank (PDB code 1FAP). Then, the obtained model was used as filter to screen the ZINC biogenic compounds library, containing molecules derived from natural sources or natural-inspired compounds. The resulting hits were clustered according to their similarity; moreover, compounds showing the highest pharmacophore fit-score were chosen from each cluster. The selected molecules were subjected to docking studies to clarify their putative binding mode. The binding free energy of the obtained complexes was calculated by MM/GBSA method and the hits characterized by the lowest ΔGbind values were identified as potential mTOR inhibitors. Furthermore, the stability of the resulting complexes was studied by means of MD simulation which revealed that the selected compounds were able to form a stable ternary complex with FKBP12 and FRB domain, thus underlining their potential ability to inhibit mTOR with a rapamycin-like mechanism.
Inspiratory Off-Switch Mediated by Optogenetic Activation of Inhibitory Neurons in the preBötzinger Complex In Vivo

The role of inhibitory neurons in the respiratory network is a matter of ongoing debate. Conflicting and contradicting results are manifold and the question whether inhibitory neurons are essential for the generation of the respiratory rhythm as such is controversial. Inhibitory neurons are required in pulmonary reflexes for adapting the activity of the central respiratory network to the status of the lung and it is hypothesized that glycinergic neurons mediate the inspiratory off-switch. Over the years, optogenetic tools have been developed that allow for cell-specific activation of subsets of neurons in vitro and in vivo. In this study, we aimed to identify the effect of activation of inhibitory neurons in vivo. Here, we used a conditional transgenic mouse line that expresses Channelrhodopsin 2 in inhibitory neurons. A 200 µm multimode optical fiber ferrule was implanted in adult mice using stereotaxic surgery, allowing us to stimulate inhibitory, respiratory neurons within the core excitatory network in the preBötzinger complex of the ventrolateral medulla. We show that, in anesthetized mice, activation of inhibitory neurons by blue light (470 nm) continuously or with stimulation frequencies above 10 Hz results in a significant reduction of the respiratory rate, in some cases leading to complete cessation of breathing. However, a lower stimulation frequency (4–5 Hz) could induce a significant increase in the respiratory rate. This phenomenon can be explained by the resetting of the respiratory cycle, since stimulation during inspiration shortened the associated breath and thereby increased the respiratory rate, while stimulation during the expiratory interval reduced the respiratory rate. Taken together, these results support the concept that activation of inhibitory neurons mediates phase-switching by inhibiting excitatory rhythmogenic neurons in the preBötzinger complex.
Wpływ wyciągu z alg morskich Ecklonia maxima (Kelpak SL) na rośliny rzepaku ozimego

W latach 2008–2010 w Instytucie Ochrony Roślin w Poznaniu wykonano ścisłe doświadczenia polowe, których celem była ocena wpływu wyciągu z alg morskich Ecklonia maxima (Kelpak SL) na rośliny rzepaku ozimego odmiany Galileo. W badaniach porównywano działanie preparatu w zależności od terminu aplikacji. Kelpak SL stosowano w dawce 2 dm∙ha jednorazowo w fazach rozwojowych BBCH 13–14 i BBCH 28–30 oraz sekwencyjnie w obu podanych fazach rozwojowych. Dodatkową kombinację doświadczalną stanowił preparat Asahi SL. W doświadczeniach stosowano standardową ochronę fungicydową, herbicydową i insektycydową. Określono wysokość roślin, zawartość chlorofilu w liściach oraz parametry ilościowe i jakościowe plonu. Lata badań różniły się warunkami pogodowymi w okresie wegetacji rzepaku, co znacznie wpłynęło na działanie preparatu Kelpak SL. Udowodniono także wpływ terminu zabiegu na badane cechy roślin. Korzystniejsze działanie odnotowano po aplikacji preparatu w fazie BBCH 28–30 w porównaniu do aplikacji wcześniejszej (BBCH 13–14). Kelpak SL wykazał działanie stymulujące plonowanie rzepaku, korzystnie wpływał na masę 1000 nasion, liczbę nasion w łuszczynach, wysokość roślin i zwartość chlorofilu w liściach. Kelpak SL nie zmieniał parametrów jakościowych nasion rzepaku.