Miracle-dz/UniFAR-FTUs huggingface dataset:
Preferences of Italian patients for return of secondary findings from clinical genome/exome sequencing

Exome/genome sequencing (ES/GS) is increasingly becoming routine in clinical genetic diagnosis, yet issues regarding how to disclose and manage secondary findings (SFs) remain to be addressed, and limited evidence is available on patients’ preferences. We carried out semi‐structured interviews with 307 individuals undergoing clinical genetic testing to explore their preferences for return of SFs in the hypothetical scenario that their test would be performed using ES/GS. Participants were 254 females (82.7%) and 53 males (17.3%), aged 18–86 years; 73.9% (81.1% of those with lower education levels) reported no prior knowledge of ES/GS. Prior knowledge of ES/GS was more common among patients tested for Mendelian conditions (34.5%), compared to those undergoing cancer genetic testing (22.3%) or carrier screening (7.4%). Despite this reported lack of knowledge, most participants (213, 69.6%) stated they would prefer to be informed of all possible results. Reasons in favor of disclosure included wanting to be aware of any risks (168; 83.6%) and to help relatives (23; 11.4%), but also hope that preventive measures might become available in the future (10, 5%). Conversely, potential negative impact on quality of life was the commonest motivation against disclosure. Among 179 participants seen for cancer genetic counseling who were interviewed again after test disclosure, 81.9% had not heard about ES/GS in the meantime; however, the proportion of participants opting for disclosure of any variants was lower (116; 64.8%), with 36 (20.1%) changing opinion compared to the first interview. Based on these findings, we conclude that genetic counseling for ES/GS should involve enhanced education and decision‐making support to enable informed consent to SFs disclosure.
Enhanced structure and function of human pluripotent stem cell‐derived beta‐cells cultured on extracellular matrix

The differentiation of human stem cells into insulin secreting beta‐like cells holds great promise to treat diabetes. Current protocols drive stem cells through stages of directed differentiation and maturation and produce cells that secrete insulin in response to glucose. Further refinements are now needed to faithfully phenocopy the responses of normal beta cells. A critical factor in normal beta cell behavior is the islet microenvironment which plays a central role in beta cell survival, proliferation, gene expression and secretion. One important influence on native cell responses is the capillary basement membrane. In adult islets, each beta cell makes a point of contact with basement membrane protein secreted by vascular endothelial cells resulting in structural and functional polarization. Interaction with basement membrane proteins triggers local activation of focal adhesions, cell orientation, and targeting of insulin secretion. This study aims to identifying the role of basement membrane proteins on the structure and function of human embryonic stem cell and induced pluripotent stem cell‐derived beta cells. Here, we show that differentiated human stem cells‐derived spheroids do contain basement membrane proteins as a diffuse web‐like structure. However, the beta‐like cells within the spheroid do not polarize in response to this basement membrane. We demonstrate that 2D culture of the differentiated beta cells on to basement membrane proteins enforces cell polarity and favorably alters glucose dependent insulin secretion.
Enhanced Performance of Carbon Nanotube Immobilized Membrane for the Treatment of High Salinity Produced Water via Direct Contact Membrane Distillation

Membrane distillation (MD) is a promising desalination technology for the treatment of high salinity water. Here, we investigated the fouling characteristics of produced water obtained from hydraulic fracturing by implementing a carbon nanotube immobilized membrane (CNIM) via direct contact membrane distillation. The CNIM exhibited enhanced water vapor flux and antifouling characteristics compared to the pristine membrane. The normalized flux decline with the polytetrafluoroethylene (PTFE) membrane after 7 h of operation was found to be 18.2% more than the CNIM. The addition of 1-Hydroxy Ethylidene-1, 1-Diphosphonic acid (HEDP) antiscalant was found to be effective in reducing the membrane fouling. The salt deposition on the membrane surface was 77% less in the CNIM, which was further reduced with the addition of HEDP in the feed by up to 135.4% in comparison with the PTFE membrane. The presence of carbon nanotubes (CNTs) on the membrane surface also facilitated the regenerability of the membrane. The results indicated that the CNIM regained 90.9% of its initial water flux after washing, whereas the unmodified PTFE only regained 81.1% of its initial flux after five days of operation.
A Review of Nephrotoxicity of Microcystins

Cyanobacterial blooms triggered by eutrophication and climate change have become a global public health issue. The toxic metabolites microcystins (MCs) generated by cyanobacteria can accumulate in food chain and contaminate water, thus posing a potential threat to human and animals health. Studies have suggested that aside liver, the kidney may be another target organ of MCs intoxication. Therefore, this review provides various evidences on the nephrotoxicity of MCs. The review concludes that nephrotoxicity of MCs may be related to inhibition of protein phosphatases and excessive production of reactive oxygen species, cytoskeleton disruption, endoplasmic reticulum stress, DNA damage and cell apoptosis. To protect human from MCs toxic consequences, this paper also puts forward some directions for further research.
Protective Effects of Colomast®, a New Formulation of Adelmidrol and Sodium Hyaluronate, in a Mouse Model of Acute Restraint Stress

Stress is generally defined as a homeostatic disruption from actual or implied threats and alters the homeostatic balance of different body organs, such as gastrointestinal function and the hypothalamic-pituitary-adrenal axis (HPA), inducing the release of glucocorticoid hormones. Stress is also known to be a risk factor for the development of depression and anxiety. However, until today there are no suitable therapies for treating of stress. The aim of this study was to explore the protective effect of Colomast®, a new preparation containing Adelmidrol, an enhancer of physiological of palmitoylethanolamide (PEA), and sodium hyaluronate in an animal model of immobilization stress. Acute restraint stress (ARS) was induced in mice by fixation for 2 h of the four extremities with an adhesive tape and Colomast® (20 mg/kg) was administered by oral gavage 30 min before the immobilization. Colomast® pre-treatment was able to decrease histopathological changes in the gastrointestinal tract, cytokines expression, neutrophil infiltration, mast cell activation, oxidative stress, as well as modulate nuclear factor NF-kB and apoptosis pathways after ARS induction. Moreover, Colomast® was able to restore tight junction in both ileum and hippocampus and cortex. Additionally, we demonstrated that Colomast® ameliorated depression and anxiety-related behaviours, and modulate inflammatory and apoptosis pathways also in brain after ARS induction. In conclusion, our results suggest Colomast® to be a potential approach to ARS.
A concept analysis of health communication in a home environment: Perspectives of older persons and their informal caregivers.

BACKGROUND Health communication (HC) is a vast research field focusing on changing health behaviours, and rapidly evolving technology is creating different ways and possibilities to reach target groups and audiences. In the context of home care, a deeper understanding of HC is lacking, specifically for older persons with care needs and their informal caregivers. The aim of this concept analysis is to identify and construct the meaning of HC from the perspective of older persons in need of care in the home environment and their informal caregivers. MATERIALS AND METHODS This study utilised Rogers' (2000) Evolutionary Concept Analysis Method (EMCA) to create and construct a meaning of the concept of HC. The EMCA was based on a systematic literature review of scientific articles, using CINAHL, Pubmed and Inspec (2000-2017). A total of 29 articles were retrieved and analysed. RESULTS The identified attributes of the concept were as follows: resources of the recipient, influence on decisions and advantages of tailored information. HC was described as both contributing to knowledge as well as being overwhelming where habits and resources influenced the use of information. The attributes led to the following descriptive definition of HC: 'Tailored HC, based on needs and resources of the recipient influence care decisions'. The home environment influenced HC by habits and interactions between older persons and their informal caregivers. CONCLUSIONS The home environment influenced HC in terms of social aspects of interactions and habits and between the older person and the informal caregiver. Tailored information with the use of technology contributed to knowledge in care of older persons and their informal caregivers. HC was shown to contribute to improve care for older people in their home environment.
Nucleolar stress induces a senescence-like phenotype in smooth muscle cells and promotes development of vascular degeneration

Senescence of smooth muscle cells (SMCs) has a crucial role in the pathogenesis of abdominal aortic aneurysm (AAA), a disease of vascular degeneration. Perturbation of cellular ribosomal DNA (rDNA) transcription triggers nucleolar stress response. Previously we demonstrated that induction of nucleolar stress in SMCs elicited cell cycle arrest via the ataxia-telangiectasia mutated (ATM)/ATM- and Rad3-related (ATR)-p53 axis. However, the specific roles of nucleolar stress in vascular degeneration remain unexplored. In the present study, we demonstrated for the first time that in both human and animal AAA tissues, there were non-coordinated changes in the expression of RNA polymerase I machinery components, including a downregulation of transcription initiation factor-IA (TIF-IA). Genetic deletion of TIF-IA in SMCs in mice (smTIF-IA-/-) caused spontaneous aneurysm-like lesions in the aorta. In vitro, induction of nucleolar stress triggered a non-canonical DNA damage response, leading to p53 phosphorylation and a senescence-like phenotype in SMCs. In human AAA tissues, there was increased nucleolar stress in medial cells, accompanied by localized DNA damage response within the nucleolar compartment. Our data suggest that perturbed rDNA transcription and induction of nucleolar stress contribute to the pathogenesis of AAA. Moreover, smTIF-IA-/- mice may be a novel animal model for studying spontaneous AAA-like vascular degenerations.
Plaque Reduction Neutralization Test (PRNT) in the Congenital Zika Syndrome: Positivity and Associations with Laboratory, Clinical, and Imaging Characteristics

The short duration of viremia, low blood viral load, inaccessibility to timely specific diagnostic tests, and cross-reactions with other flaviviruses have hindered laboratory confirmation of Congenital Zika Syndrome (CZS). This study analyzes the positivity of the plaque reduction neutralization test (PRNT) in children with clinical or imaging characteristics of CZS and its association with laboratory, clinical, and imaging characteristics. The 94 clinical cases of CZS submitted to the ZIKV PRNT90 test were followed from 2016 to 2018. The mean age of children at PRNT90 collection was 22 ± 6 months Standard Deviation. The ZIKV PRNT90 was positive (titer ≥ 10) in 40 (42.5%) children. ZIKV PRNT90 positivity was associated with severe microcephaly in newborns (p = 0.016), lower head circumference z-score at birth (p = 0.043) and 24 months of age (p = 0.031), and severe reduction of the cerebral parenchyma volume (p = 0.021), expressing greater disease severity. Negative PRNT90 in children with characteristic signs of CZS may be due to false-negative results, indicating that the diagnosis of CZS should be primarily syndromic.
Evidence of Mitochondrial Dysfunction in Fibromyalgia: Deviating Muscle Energy Metabolism Detected Using Microdialysis and Magnetic Resonance

In fibromyalgia (FM) muscle metabolism, studies are sparse and conflicting associations have been found between muscle metabolism and pain aspects. This study compared alterations in metabolic substances and blood flow in erector spinae and trapezius of FM patients and healthy controls. FM patients (n = 33) and healthy controls (n = 31) underwent a clinical examination that included pressure pain thresholds and physical tests, completion of a health questionnaire, participation in microdialysis investigations of the etrapezius and erector spinae muscles, and also underwent phosphorus-31 magnetic resonance spectroscopy of the erector spinae muscle. At the baseline, FM had significantly higher levels of pyruvate in both muscles. Significantly lower concentrations of phosphocreatine (PCr) and nucleotide triphosphate (mainly adenosine triphosphate) in erector spinae were found in FM. Blood flow in erector spinae was significantly lower in FM. Significant associations between metabolic variables and pain aspects (pain intensity and pressure pain threshold PPT) were found in FM. Our results suggest that FM has mitochondrial dysfunction, although it is unclear whether inactivity, obesity, aging, and pain are causes of, the results of, or coincidental to the mitochondrial dysfunction. The significant regressions of pain intensity and PPT in FM agree with other studies reporting associations between peripheral biological factors and pain aspects.
Behaviour-dependent neuronal network activity in a novel Cyfip1 haploinsufficient rat model of psychiatric risk

Advances in psychiatric genetics have begun to reveal the complex biological underpinnings of psychiatric disorders. Rare but penetrant copy number variants offer particularly direct mechanistic clues. The deletion at 15q11.2(BP1-BP2) has a 13% penetrance for developmental delay, congenital malformation, autism or schizophrenia. Reduced dosage of CYFIP1, one of four genes within this deletion, has emerged as a likely contributor to cognitive dysfunction seen in 15q11.2(BP1- BP2) deletion patients. However, the route from CYFIP1 haploinsufficiency to impaired behaviour has not been fully mapped. While synaptic deficits have been identified in mice haploinsufficient for Cyfip1 (Cyfip1+/-), circuit-level phenotypes have not been investigated. Using multi-site chronic electrode implants I recorded local field potential data simultaneously from prefrontal cortex, hippocampus and nucleus accumbens in a novel Cyfip1+/- rat model during a behavioural task and during sleep. Cyfip1+/- rats show normal performance accuracy on a discrete-trial alternation T maze task, but require more trials to achieve criterion during training. Task- dependent hippocampal-prefrontal network coordination remains intact in well-trained Cyfip1+/- rats, although theta-gamma phase-amplitude coupling within dorsal hippocampus is reduced compared to WTs. While circadian patterns and sleep architecture appear normal, hippocampal non-REM ripples are diminished in Cyfip1+/- rats compared to WTs, and preliminary data from the related Fmr1 (Fragile X Mental retardation 1) knockout rat also show aberrant ripples. Disrupted interactions are seen in the cortico-hippocampal-accumbal network, most prominently during approach to sucrose reward locations. Altered N-methyl-D- aspartate receptor signalling is implicated, as Cyfip1+/- rats show an exaggerated response to acute ketamine injection in the form of an enhanced surge in high frequency oscillations in nucleus accumbens and prelimbic cortex. Overall, abnormal behaviour- and ketamine-dependent network dynamics in hippocampus, prefrontal cortex and nucleus accumbens of Cyfip1+/- rats are reminiscent of some features of neuropsychiatric disorders, and lend weight to causal roles for CYFIP1 haploinsufficiency in predisposing patients to cognitive dysfunction.
Whole egg consumption increases gene expression within the glutathione pathway in the liver of Zucker Diabetic Fatty rats

Nutrigenomic evidence supports the idea that Type 2 Diabetes Mellitus (T2DM) arises due to the interactions between the transcriptome, individual genetic profiles, lifestyle, and diet. Since eggs are a nutrient dense food containing bioactive ingredients that modify gene expression, our goal was to examine the role of whole egg consumption on the transcriptome during T2DM. We analyzed whether whole egg consumption in Zucker Diabetic Fatty (ZDF) rats alters microRNA and mRNA expression across the adipose, liver, kidney, and prefrontal cortex tissue. Male ZDF (fa/fa) rats (n = 12) and their lean controls (fa/+) (n = 12) were obtained at 6 wk of age. Rats had ad libitum access to water and were randomly assigned to a modified semi-purified AIN93G casein-based diet or a whole egg-based diet, both providing 20% protein (w/w). TotalRNA libraries were prepared using QuantSeq 3' mRNA-Seq and Lexogen smallRNA library prep kits and were further sequenced on an Illumina HighSeq3000. Differential gene expression was conducted using DESeq2 in R and Benjamini-Hochberg adjusted P-values controlling for false discovery rate at 5%. We identified 9 microRNAs and 583 genes that were differentially expressed in response to 8 wk of consuming whole egg-based diets. Kyto Encyclopedia of Genes and Genomes/Gene ontology pathway analyses demonstrated that 12 genes in the glutathione metabolism pathway were upregulated in the liver and kidney of ZDF rats fed whole egg. Whole egg consumption primarily altered glutathione pathways such as conjugation, methylation, glucuronidation, and detoxification of reactive oxygen species. These pathways are often negatively affected during T2DM, therefore this data provides unique insight into the nutrigenomic response of dietary whole egg consumption during the progression of T2DM.
Pathway enrichment analysis of virus-host interactome and prioritization of novel compounds targeting the spike glycoprotein receptor binding domain–human angiotensin-converting enzyme 2 interface to combat SARS-CoV-2

Abstract SARS-CoV-2 has become a pandemic causing a serious global health concern. The absence of effective drugs for treatment of the disease has caused its rapid spread on a global scale. Similarly to the SARS-CoV, the SARS-CoV-2 is also involved in a complex interplay with the host cells. This infection is characterized by a diffused alveolar damage consistent with the Acute Respiratory Disease Syndrome (ARDS). To explore the complex mechanisms of the disease at the system level, we used a network medicine tools approach. The protein-protein interactions (PPIs) between the SARS-CoV and the associated human cell proteins are crucial for the viral pathogenesis. Since the cellular entry of SARS-CoV-2 is accomplished by binding of the spike glycoprotein binding domain (RBD) to the human angiotensin-converting enzyme 2 (hACE2), a molecule that can bind to the spike RDB-hACE2 interface could block the virus entry. Here, we performed a virtual screening of 55 compounds to identify potential molecules that can bind to the spike glycoprotein and spike-ACE2 complex interface. It was found that the compound ethyl 1-{3-[(2,4-dichlorobenzyl) carbamoyl]-1-ethyl-6-fluoro-4-oxo-1,4-dihydro-7-quinolinyl}-4-piperidine carboxylate (the S54 ligand) and ethyl 1-{3-[(2,4-dichlorobenzyl) carbamoyl]-1-ethyl-6-fluoro-4-oxo-1,4-dihydro-7-quinolinyl}-4 piperazine carboxylate (the S55 ligand) forms hydrophobic interactions with Tyr41A, Tyr505B and Tyr553B, Leu29A, Phe495B, respectively of the spike glycoprotein, the hotspot residues in the spike glycoprotein RBD-hACE2 binding interface. Furthermore, molecular dynamics simulations and free energy calculations using the MM-GBSA method showed that the S54 ligand is a stronger binder than a known SARS-CoV spike inhibitor SSAA09E3 (N-(9,10-dioxo-9, 10-dihydroanthracen-2-yl) benzamide). Communicated by Ramaswamy H. Sarma
Characteristics of urinary tract infections in older patients in a tertiary hospital in Greece

Urinary tract infections (UTIs) are commonly encountered. They are more commonly caused by Enterobacteriaceae, while antimicrobial resistance is an emerging problem in their management, with extended‐spectrum‐β‐lactamase (ESBL) producing Gram‐negative bacteria and multidrug‐resistant (MDR) Pseudomonas aeruginosa being increasingly common. The purpose of this study was to investigate the epidemiology and outcomes of UTIs in patients admitted in a tertiary hospital, which mostly admits geriatric patients, and compare the effects of antimicrobial resistance on patient outcomes.
Ethno-veterinary uses of Poaceae in Punjab, Pakistan

Plant species of the Poaceae family are not only used as fodder and forage but also contribute substantially to the treatment of various health disorders, particularly in livestock. Consequently, the present study was aimed to document the therapeutic uses of Poaceae practiced by the inhabitants of the Punjab Province for the treatment of various veterinary health disorders. Semi structured interviews, group discussion and field walks were conducted to collect the data. Quantitative indices including cultural significance index (CSI), relative frequency of citations (RFC), fidelity level (FL), relative popularity level (RPL), and Jaccard Index (JI) were used for the data analysis. Traditional uses of 149 species belonging to 60 genera and 16 tribes of 5 sub families of Poaceae were recorded. Whole plants and leaves were the most consistently used parts with 40.94 and 29.53%. The plants were mainly given orally as fodder (59 reports) without processing followed by decoction (35 reports). Most of the species were employed to treat infectious diseases (25.93%), and digestive disorders (14.10%). Triticum aestivum had the highest CSI, RFC and RPL levels at 8.00, 0.96, 1.00, respectively, followed by Oryza sativa and Poa annua. Likewise, T. aestivum and Saccharum spontaneum had 100% FL and ROP. Jaccard index ranged from 12.25 to 0.37. Twelve plant species namely Chrysopogon zizanioides (anti-inflammatory), Pennisetum lanatum (improve bull fertility), Cymbopogon citratus (glandular secretion), Sorghum saccharatum and Themeda triandra (malaria), Aristida funiculate (anticancer), Koeleria argentia (skin allergies), Tetrapogon villosus (antibacterial), Cynodon radiatus (eyes infection), Sporobolus nervosa (Jaundice), Enneapogon persicus (antifungal), and Panicum repens (dysfunctional cattle organs) were reported for the first time, with novel ethnoveterinary uses. The inhabitants of the study area had a strong association with their surrounding plant diversity and possessed significant knowledge on therapeutic uses of Poaceae to treat various health disorders in animals. Plant species with maximum cultural and medicinal values could be a potential source of novel drugs to cure health disorders in animals and human as well.