Miracle-dz/UniFAR-FTUs huggingface dataset:
Drug–Drug Interactions in Elderly Patients with Potentially Inappropriate Medications in Primary Care, Nursing Home and Hospital Settings: A Systematic Review and a Preliminary Study

Drug–drug interactions (DDI) occurring with potentially inappropriate medications (PIM) are additional risk factors that may increase the inappropriate character of PIM. The aim of this study was (1) to describe the prevalence and severity of DDI in patients with PIM and (2) to evaluate the DDI specifically regarding PIM. This systematic review is based on a search carried out on PubMed and Web-of-Science from inception to June 30, 2020. We extracted data of original studies that assessed the prevalence of both DDI and PIM in elderly patients in primary care, nursing home and hospital settings. Four hundred and forty unique studies were identified: 91 were included in the qualitative analysis and 66 were included in the quantitative analysis. The prevalence of PIM in primary care, nursing home and hospital were 19.1% (95% confidence intervals (CI): 15.1–23.0%), 29.7% (95% CI: 27.8–31.6%) and 44.6% (95% CI: 28.3–60.9%), respectively. Clinically significant severe risk-rated DDI averaged 28.9% (95% CI: 17.2–40.6), in a hospital setting; and were approximately 7-to-9 lower in primary care and nursing home, respectively. Surprisingly, only four of these studies investigated DDI involving specifically PIM. Hence, given the high prevalence of severe DDI in patients with PIM, further investigations should be carried out on DDI involving specifically PIM which may increase their inappropriate character, and the risk of adverse drug reactions.
Thrombotic Thrombocytopenic Purpura After Live Liver Donation: Villain or Scapegoat?

Living donor liver transplantation is a complex surgery, where the donor’s safety is of paramount importance. Despite all precautions, donor morbidity may be inevitable, and long-term follow-up data attest to this fact. However, being a “past donor” all ailments are intuitively attributed to the donation process, which may not always be the case. We present the case of a 47-year-old lady, who developed thrombotic thrombocytopenic purpura secondary to systemic lupus erythematosus 18 months following her liver donation, when she detected to be anti-nuclear antibody (ANA) positive. She developed neurological signs and was managed successfully with therapeutic plasma exchange and steroids. She was discharged home on immunosuppression and remains well on follow-up. We present the medical and social issues that were addressed in the case and highlight the need for a more stringent follow-up protocol in those who are ANA positive. This would also help detect morbidities that may be unrelated to the donation process.
Oral Sucrosomial Iron Is as Effective as Intravenous Ferric Carboxy-Maltose in Treating Anemia in Patients with Ulcerative Colitis

Anemia is a frequent complication of ulcerative colitis, and is frequently caused by iron deficiency. Oral iron supplementation displays high rates of gastrointestinal adverse effects. However, the formulation of sucrosomial iron (SI) has shown higher tolerability. We performed a prospective study to compare the effectiveness and tolerability of oral SI and intravenous ferric carboxy-maltose (FCM) in patients with ulcerative colitis in remission and mild-to-moderate anemia. Patients were randomized 1:1 to receive 60 mg/day for 8 weeks and then 30 mg/day for 4 weeks of oral SI or intravenous 1000 mg of FCM at baseline. Hemoglobin and serum levels of iron and ferritin were assessed after 4, 8, and 12 weeks from baseline. Hemoglobin and serum iron increased in both groups after 4 weeks of therapy, and remained stable during follow up, without significant treatment or treatment-by-time interactions (p = 0.25 and p = 0.46 for hemoglobin, respectively; p = 0.25 and p = 0.26 for iron, respectively). Serum ferritin did not increase over time during SI supplementation, while it increased in patients treated with FCM (treatment effect, p = 0.0004; treatment-by-time interaction effect, p = 0.0002). Overall, this study showed that SI and FCM displayed similar effectiveness and tolerability for treatment of mild-to-moderate anemia in patients with ulcerative colitis under remission.
Uremic Toxins in the Progression of Chronic Kidney Disease and Cardiovascular Disease: Mechanisms and Therapeutic Targets

Chronic kidney disease (CKD) is a progressive loss of renal function. The gradual decline in kidney function leads to an accumulation of toxins normally cleared by the kidneys, resulting in uremia. Uremic toxins are classified into three categories: free water-soluble low-molecular-weight solutes, protein-bound solutes, and middle molecules. CKD patients have increased risk of developing cardiovascular disease (CVD), due to an assortment of CKD-specific risk factors. The accumulation of uremic toxins in the circulation and in tissues is associated with the progression of CKD and its co-morbidities, including CVD. Although numerous uremic toxins have been identified to date and many of them are believed to play a role in the progression of CKD and CVD, very few toxins have been extensively studied. The pathophysiological mechanisms of uremic toxins must be investigated further for a better understanding of their roles in disease progression and to develop therapeutic interventions against uremic toxicity. This review discusses the renal and cardiovascular toxicity of uremic toxins indoxyl sulfate, p-cresyl sulfate, hippuric acid, TMAO, ADMA, TNF-α, and IL-6. A focus is also placed on potential therapeutic targets against uremic toxicity.
Tribological Performance of Additively Manufactured AISI H13 Steel in Different Surface Conditions

Additive manufacturing of metallic tribological components offers unprecedented degrees of freedom, but the surface roughness of most as-printed surfaces impedes the direct applicability of such structures, and postprocessing is necessary. Here, the tribological performance of AISI H13 steel samples was studied. These were additively manufactured through laser powder bed fusion (L-PBF), also referred to as selective laser melting (SLM). Samples were tested in four different surface conditions: as-printed, polished, ground and polished, and laser-surface-textured (LST) with round dimples. Friction experiments were conducted in a pin-on-disk fashion against bearing steel disks under lubrication with an additive-free mineral base oil for sliding speeds between 20 and 170 mm/s. Results demonstrated that, among the four surface treatments, grinding and polishing resulted in the lowest friction coefficient, followed by the as-printed state, while both polishing alone and laser-surface texturing increased the friction coefficient. Surprisingly, direct correlation between surface roughness and friction coefficient, i.e., the rougher the surface was, the higher the friction force, was not observed. Wear was minimal in all cases and below what could be detected by gravimetrical means. These results highlight the need for an adequate post-processing treatment of additively manufactured parts that are to be employed in tribological systems.
Genetic Characterization of Fungal Biodiversity in Storage Grains: Towards Enhancing Food Safety in Northern Uganda

Worldwide fungal contamination leads to both quantitative and qualitative grain losses during crop growth and/or storage. A greater proportion of grains contamination with toxins often occurs in sub-Saharan Africa, where control measures are limited. We determined fungal diversity and their toxin production ability in household grains meant for human consumption to highlight the risk of mycotoxin exposure among people from northern Uganda. The study underlines the high diversity of fungi that group into 15 genera; many of which are plant pathogens with toxigenic potential. Fusarium verticillioides was the most common fungal species isolated from household grains. The study also indicates that northern Uganda is favored by a high proportion of toxigenic isolates of F. verticillioides, F. andiyazi, and F. proliferatum, which are characterized by a high fumonisins production capability. The fumonisins production ability was not dependent on the species, grain types, and haplotype group to which the isolates belong. The contamination of most household grains with fungi capable of producing a high amount of toxin shows that most people are exposed to an elevated amount of mycotoxins, which shows the frequent problems with mycotoxins that have been reported in most parts of sub-Saharan Africa.
Pangenomics of the Symbiotic Rhizobiales. Core and Accessory Functions Across a Group Endowed with High Levels of Genomic Plasticity

Pangenome analyses reveal major clues on evolutionary instances and critical genome core conservation. The order Rhizobiales encompasses several families with rather disparate ecological attitudes. Among them, Rhizobiaceae, Bradyrhizobiaceae, Phyllobacteriacreae and Xanthobacteriaceae, include members proficient in mutualistic symbioses with plants based on the bacterial conversion of N2 into ammonia (nitrogen-fixation). The pangenome of 12 nitrogen-fixing plant symbionts of the Rhizobiales was analyzed yielding total 37,364 loci, with a core genome constituting 700 genes. The percentage of core genes averaged 10.2% over single genomes, and between 5% to 7% were found to be plasmid-associated. The comparison between a representative reference genome and the core genome subset, showed the core genome highly enriched in genes for macromolecule metabolism, ribosomal constituents and overall translation machinery, while membrane/periplasm-associated genes, and transport domains resulted under-represented. The analysis of protein functions revealed that between 1.7% and 4.9% of core proteins could putatively have different functions.
Omega-3 Polyunsaturated Fatty Acids Prevent Nonalcoholic Steatohepatitis (NASH) and Stimulate Adipogenesis

The increasing impact of obesity on global human health intensifies the importance of studies focusing on agents interfering with the metabolism and remodeling not only of the white adipose tissue (WAT) but also of the liver. In the present study, we have addressed the impact of n-3 PUFA in adipose cells’ proliferation and adipogenesis, as well as in the hepatic lipid profile and morphology. Mice were induced to obesity by the consumption of a high-fat diet (HFD) for 16 weeks. At the 9th week, the treatment with fish oil (FO) was initiated and maintained until the end of the period. The FO treatment reduced the animals’ body mass, plasma lipids, glucose, plasma transaminases, liver mass, triacylglycerol, and cholesterol liver content when compared to animals consuming only HFD. FO also decreased the inguinal (ing) WAT mass, reduced adipocyte volume, increased adipose cellularity (hyperplasia), and increased the proliferation of adipose-derived stromal cells (AdSCs) which corroborates the increment in the proliferation of 3T3-L1 pre-adipocytes or AdSCs treated in vitro with n-3 PUFA. After submitting the in vitro treated (n-3 PUFA) cells, 3T3-L1 and AdSCs, to an adipogenic cocktail, there was an increase in the mRNA expression of adipogenic transcriptional factors and other late adipocyte markers, as well as an increase in lipid accumulation when compared to not treated cells. Finally, the expression of browning-related genes was also higher in the n-3 PUFA treated group. We conclude that n-3 PUFA exerts an attenuating effect on body mass, dyslipidemia, and hepatic steatosis induced by HFD. FO treatment led to decreasing adiposity and adipocyte hypertrophy in ingWAT while increasing hyperplasia. Data suggest that FO treatment might induce recruitment (by increased proliferation and differentiation) of new adipocytes (white and/or beige) to the ingWAT, which is fundamental for the healthy expansion of WAT.
The effects of transcranial direct current stimulation on attention and inhibitory control of children and adolescents with attention-deficit/hyperactivity disorder (ADHD)

Abstract Attention-deficit/hyperactivity disorder (ADHD) is characterized by a persistent pattern of inattention and hyperactivity/impulsivity. Despite the proven efficacy of pharmacological treatment, many individuals continue to suffer socially and academically and some experience significant side effects that negate the use psychotropic drugs. Transcranial direct current stimulation (tDCS) is a cortical neuromodulation feature that has shown positive results in the treatment of various neuropsychiatric conditions. Objectives: To investigate the effect of tDCS on the performance of children and adolescents with ADHD in the neuropsychological tests of visual attention, verbal, and inhibitory control. Methodology: Triple blind, randomized, sham-controlled, cross-over trial involving tDCS in children and adolescents with ADHD. Initial screening will be performed using Swanson, Nolan, and Pelham – IVand Wechsler intelligence scale for children fourth edition vocabulary and cube subtests. Individuals will be evaluated pre-tDCS and post-tDCS with the Wechsler intelligence scale for children fourth edition Digitus subtest, neuropsychological assessment battery second edition inhibiting responses subtest, Corsi cubes, and visual attention test-4.
Time-Dependent Pathological Changes in Hypoperfusion-Induced Abdominal Aortic Aneurysm

Simple Summary Abdominal aortic aneurysm (AAA) is a vascular disease that involves gradual dilation of the abdominal aorta and has a high mortality due to rupture. Hypoperfusion due to the obstruction of vasa vasorum, which is a blood supply system in the aortic wall, may be an important factor involved in AAA pathophysiology. A time-dependent analysis is important to understand the pathological cascade following hypoperfusion in the aortic wall. In our study, time-dependent analysis using a hypoperfusion-induced animal model showed that the dynamics of many AAA-related factors might be associated with the increased hypoxia-inducible factor-1α level. Hypoperfusion due to stenosis of the vasa vasorum might be a new drug target for AAA therapeutics. Abstract Hypoperfusion due to vasa vasorum stenosis can cause wall hypoxia and abdominal aortic aneurysm (AAA) development. Even though hypoperfusion is an important contributor toward pathological changes in AAA, the correlation between hypoperfusion and AAA is not fully understood. In this study, a time-dependent semi-quantitative pathological analysis of hypoperfusion-induced aortic wall changes was performed to understand the mechanisms underlying the gradual degradation of the aortic wall leading to AAA formation. AAA-related factors evaluated in this study were grouped according to the timing of dynamic change, and five groups were formed as follows: first group: angiotensin II type 1 receptor, endothelin-1 (ET-1), and malondialdehyde (MDA); second group: matrix metalloproteinase (MMP)-2, -9, -12, M1 macrophages (Mac387+ cells), and monocyte chemotactic protein-1; third group: synthetic smooth muscle cells (SMCs); fourth group: neutrophil elastase, contractile SMCs, and angiotensinogen; and the fifth group: M2 macrophages (CD163+ cells). Hypoxia-inducible factor-1α, ET-1, MDA, and MMP-9 were colocalized with alpha-smooth muscle actin cells in 3 h, suggesting that hypoperfusion-induced hypoxia directly affects the activities of contractile SMCs in the initial stage of AAA. Time-dependent pathological analysis clarified the cascade of AAA-related factors. These findings provide clues for understanding complicated multistage pathologies in AAA.
Targeting GRK5 for Treating Chronic Degenerative Diseases

G protein-coupled receptors (GPCRs) are the largest family of cell-surface receptors and they are responsible for the transduction of extracellular signals, regulating almost all aspects of mammalian physiology. These receptors are specifically regulated by a family of serine/threonine kinases, called GPCR kinases (GRKs). Given the biological role of GPCRs, it is not surprising that GRKs are also involved in several pathophysiological processes. Particular importance is emerging for GRK5, which is a multifunctional protein, expressed in different cell types, and it has been found located in single or multiple subcellular compartments. For instance, when anchored to the plasma membrane, GRK5 exerts its canonical function, regulating GPCRs. However, under certain conditions (e.g., pro-hypertrophic stimuli), GRK5 translocates to the nucleus of cells where it can interact with non-GPCR-related proteins as well as DNA itself to promote “non-canonical” signaling, including gene transcription. Importantly, due to these actions, several studies have demonstrated that GRK5 has a pivotal role in the pathogenesis of chronic-degenerative disorders. This is true in the cardiac cells, tumor cells, and neurons. For this reason, in this review article, we will inform the readers of the most recent evidence that supports the importance of targeting GRK5 to prevent the development or progression of cancer, cardiovascular, and neurological diseases.
Emerging Pharmacological and Non-Pharmacological Therapeutics for Prevention and Treatment of Chemotherapy-Induced Peripheral Neuropathy

Simple Summary Chemotherapy-induced peripheral neuropathy (CIPN) is a common and persistent complication of commonly used chemotherapy drugs. This article provides an overview of emerging therapeutics for the prevention and treatment of CIPN and focuses on pharmacological strategies that are derived from novel mechanistic insights and have the potential to be translated into clinically beneficial approaches. It is our contention to call for fostering collaboration between basic and clinical researchers to improve the development of effective strategies. Abstract Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse event of several first-line chemotherapeutic agents, including platinum compounds, taxanes, vinca alkaloids, thalidomide, and bortezomib, which negatively affects the quality of life and clinical outcome. Given the dearth of effective established agents for preventing or treating CIPN, and the increasing number of cancer survivors, there is an urgent need for the identification and development of new, effective intervention strategies that can prevent or mitigate this debilitating side effect. Prior failures in the development of effective interventions have been due, at least in part, to a lack of mechanistic understanding of CIPN and problems in translating this mechanistic understanding into testable hypotheses in rationally-designed clinical trials. Recent progress has been made, however, in the pathogenesis of CIPN and has provided new targets and pathways for the development of emerging therapeutics that can be explored clinically to improve the management of this debilitating toxicity. This review focuses on the emerging therapeutics for the prevention and treatment of CIPN, including pharmacological and non-pharmacological strategies, and calls for fostering collaboration between basic and clinical researchers to improve the development of effective strategies.
Comparison of Risk of Metachronous Advanced Colorectal Neoplasia in Patients with Sporadic Adenomas Aged < 50 Versus ≥ 50 years: A Systematic Review and Meta-Analysis

No specific recommendations are available for the surveillance of young patients aged <50 years undergoing polypectomy. We aimed to compare the risk of metachronous advanced colorectal neoplasia (ACRN) between patients aged ≥50 years and those aged <50 years who underwent polypectomy. Studies published between January 1980 and June 2020 that examined the risk of metachronous ACRN were searched. We performed a meta-analysis for the metachronous ACRN risk in patients with sporadic colorectal adenomas according to the age groups (≥50 vs. <50 years). Eight individual studies were included in the meta-analysis. The risk of metachronous ACRN was higher in patients aged ≥50 years than in those aged <50 years without significant heterogeneity (odds ratio (OR) (95% CI): 1.62 (1.34–1.96), I2 = 14%). The impact of the age group on the risk of metachronous ACRN was identified in both the low-risk (LRA) and high-risk (HRA) adenoma groups (≥50 vs. <50 years: LRA, OR 1.88 (95% CI 1.30–2.70); HRA, OR 1.50 [95% CI 1.13–2.00]). In conclusion, patients aged <50 years had a lower risk of metachronous ACRN than older patients. Young patients with sporadic adenomas do not require more intensive surveillance; rather, the surveillance interval may be extended in these patients.
Identification of Germline Genetic Variants that Increase Prostate Cancer Risk and Influence Development of Aggressive Disease

Simple Summary The potential importance of germline genetic variation for identifying men at increased risk of prostate cancer has become increasingly recognised in recent years. We present an extensive review of the major developments in the identification of genetic loci, genes and individual variants associated with greater risk of prostate cancer, and what is currently known regarding whether these heritable prostate cancer risk factors can also inform likelihood of experiencing clinically significant rather than indolent forms of the disease. We finally discuss how these research discoveries might serve to inform clinical germline genetic testing guidelines and treatment options for prostate cancer in the future. Abstract Prostate cancer (PrCa) is a heterogeneous disease, which presents in individual patients across a diverse phenotypic spectrum ranging from indolent to fatal forms. No robust biomarkers are currently available to enable routine screening for PrCa or to distinguish clinically significant forms, therefore late stage identification of advanced disease and overdiagnosis plus overtreatment of insignificant disease both remain areas of concern in healthcare provision. PrCa has a substantial heritable component, and technological advances since the completion of the Human Genome Project have facilitated improved identification of inherited genetic factors influencing susceptibility to development of the disease within families and populations. These genetic markers hold promise to enable improved understanding of the biological mechanisms underpinning PrCa development, facilitate genetically informed PrCa screening programmes and guide appropriate treatment provision. However, insight remains largely lacking regarding many aspects of their manifestation; especially in relation to genes associated with aggressive phenotypes, risk factors in non-European populations and appropriate approaches to enable accurate stratification of higher and lower risk individuals. This review discusses the methodology used in the elucidation of genetic loci, genes and individual causal variants responsible for modulating PrCa susceptibility; the current state of understanding of the allelic spectrum contributing to PrCa risk; and prospective future translational applications of these discoveries in the developing eras of genomics and personalised medicine.