Miracle-dz/UniFAR-FTUs huggingface dataset:
Suicidal behaviour and non-suicidal self-injury in children and adolescents seen at an Italian paediatric emergency department.

INTRODUCTION Increasing rates of non-fatal self-harm amongst adolescents represent growing concern. The objective of the study is to describe non-fatal self-harm - including suicidal behaviour (SB), suicidal ideation (SI) and non-suicidal self-injury (NSSI) - observed at an Italian paediatric emergency department (ED). METHODS Retrospective analysis of the clinical records of patients admitted to ED from 2011 to 2016, who underwent child psychiatry consultation (CPc). We analyzed: rates of CPc for SB, SI and NSSI; risk factors for SB and SI in patients admitted to the hospital's Child Psychiatry Unit after a CPc; and, correlations between NSSI and SB/SI. RESULTS The rate of CPc for SB, SI and NSSI switched from 7.7% in 2011 to 19% in 2016, with a statistically significant increase over the years (p < 0.001), a 2.2:1 female/male ratio, and an average age of 15.5 ± 1.8 years. SB consisted mainly in drug poisoning (53%), with a significant prevalence in female. Mood disorder was identified in 82.5% of patients hospitalized for SB or SI. Substance abuse was more frequently found in patients admitted for SB when compared to the SI group. Almost half (48%) of the patients admitted for SB or SI reported a current or lifelong history of NSSI. In patients admitted for SB or SI, 3 factors were significantly and independently associated with NSSI: being female, substance abuse, and more severe depressive symptoms. CONCLUSIONS Between 2011 and 2016, there was a significant growing need for CP consultations for suicidal behaviours, mainly in female adolescents. The subjects admitted for SI or SB, who also presented NSSI, were mainly substance abusers, and presented with more severe depressive symptoms.
Evaluation of a Bacterial Single-Cell Protein in Compound Diets for Rainbow Trout (Oncorhynchus mykiss) Fry as an Alternative Protein Source

Simple Summary Fish meal (FM), as the main protein source, is used in aquafeeds due to its good nutritional profile and palatability. In recent years, because of the high cost and uncertainty in FM supply, studies have been focused to identify and evaluate alternative protein ingredients to minimize FM and reducethe cost of formulated feeds. Currently, plant protein ingredients and animal by-products are used as alternative protein sources to FM, but these components have some nutritional limitations, such as beingrich in anti-nutritional elements and deficient in certain essential amino acids. Among alternative protein sources, single-cell protein (SCP) such as bacteria, yeasts and microalgae, is considered a promising substitute for animal- or plant-derived ingredients. In this work, we aimed to evaluate the replacement of FM with a bacterial SCP, a by-product of the monosodium L-glutamic acid produced by microbial fermentation of vegetal raw materials, in diets for rainbow trout (Oncorhynchus mykiss) fry. Results indicated that the maximum replacement of FM by SCP in terms of growth and feed efficiency performance was up to 50%, while the broken-line regression analyses using DHA muscle content and weight gain showed that this value ranged between 46.9 to 52% SCP depending on the parameter considered. Abstract A 60-day trial was conducted in rainbow trout (Oncorhynchus mykiss) fry (initial weight = 2.5 ± 0.6 g) to evaluate the potential use of a bacterial single-cell protein (SCP) as an alternative protein source. Five experimental diets with different levels of fishmeal replacement (0, 25, 50, 75 and 100%) and no amino acid supplementation were tested. At the end of the trial, we found that fry fed diets, replacing 25 and 50% of fishmeal with bacterial SCP, were 9.1 and 21.8% heavier, respectively, than those fed the control diet (p < 0.05), while Feed Conversion Ratio (FCR) values were also lower in comparison to the reference group. These results were also supported by Protein Efficiency Ratio (PER) and Lipid Efficiency Ratio (LER) values that improved in fish fed diets replacing 50% fishmeal by bacterial SCP. The inclusion of SCP enhanced Feed intake (FI) (p < 0.05), although FI was reduced at higher inclusion levels (>50%), which was associated to feed palatability. High levels of bacterial SCP (>50%) affected the muscular amino acid and fatty acid profiles, imbalances that were associated to their dietary content. The broken-line regression analysis using muscle DHA content and weight gain data showed that the maximum levels of fishmeal replacement by bacterial SCP were 46.9 and 52%, respectively.
The Duffy-null genotype and risk of infection

Abstract Many medical treatments, from oncology to psychiatry, can lower white blood cell counts and thus access to these treatments can be restricted to individuals with normal levels of white blood cells, principally in order to minimize risk of serious infection. This adversely affects individuals of African or Middle Eastern ancestries who have on average a reduced number of circulating white blood cells, because of the Duffy-null (CC) genotype at rs2814778 in the ACKR1 gene. Here, we investigate whether the Duffy-null genotype is associated with the risk of infection using the UK Biobank sample and the iPSYCH Danish case-cohort study, two population-based samples from different countries and age ranges. We found that a high proportion of those with the Duffy-null genotype (21%) had a neutrophil count below the threshold often used as a cut-off for access to relevant treatments, compared with 1% of those with the TC/TT genotype. In addition we found that despite its strong association with lower average neutrophil counts, the Duffy-null genotype was not associated with an increased risk of infection, viral or bacterial. These results have widespread implications for the clinical treatment of individuals of African ancestry and indicate that neutrophil thresholds to access treatments could be lowered in individuals with the Duffy-null genotype without an increased risk of infection.
Observed reduction in the diagnosis of acute lymphoblastic leukaemia in children during the COVID‐19 pandemic

To contain the spread of the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), the Norwegian government implemented lock-down restrictions from 13.03. 2020: schools, day cares and after-school activities were closed, 2-week quarantine was required following international travel, physical distancing (2 metres) was recommended and groups were restricted to 5 people.
Control of Cytoskeletal Dynamics by β-Arrestin1/Myosin Vb Signaling Regulates Endosomal Sorting and Scavenging Activity of the Atypical Chemokine Receptor ACKR2

The atypical chemokine receptor ACKR2, formerly named D6, is a scavenger chemokine receptor with a non-redundant role in the control of inflammation and immunity. The scavenging activity of ACKR2 depends on its trafficking properties, which require actin cytoskeleton rearrangements downstream of a β-arrestin1-Rac1-PAK1-LIMK1-cofilin-dependent signaling pathway. We here demonstrate that in basal conditions, ACKR2 trafficking properties require intact actin and microtubules networks. The dynamic turnover of actin filaments is required to sustain ACKR2 constitutive endocytosis, while both actin and microtubule networks are involved in processes regulating ACKR2 constitutive sorting to rapid, Rab4-dependent and slow, Rab11-dependent recycling pathways, respectively. After chemokine engagement, ACKR2 requires myosin Vb activity to promote its trafficking from Rab11-positive recycling endosomes to the plasma membrane, which sustains its scavenging activity. Other than cofilin phosphorylation, induction of the β-arrestin1-dependent signaling pathway by ACKR2 agonists also leads to the rearrangement of microtubules, which is required to support the myosin Vb-dependent ACKR2 upregulation and its scavenging properties. Disruption of the actin-based cytoskeleton by the apoptosis-inducing agent staurosporine results in impaired ACKR2 internalization and chemokine degradation that is consistent with the emerging scavenging-independent activity of the receptor in apoptotic neutrophils instrumental for promoting efficient efferocytosis during the resolution of inflammation. In conclusion, we provide evidence that ACKR2 activates a β-arrestin1-dependent signaling pathway, triggering both the actin and the microtubule cytoskeletal networks, which control its trafficking and scavenger properties.
Evaluation of Circulating Tumor DNA for Methylated BCAT1 and IKZF1 to Detect Recurrence of Stage II/Stage III Colorectal Cancer (CRC)

Background: Most recurrences of early-stage colorectal cancer detected with current surveillance measures are widespread and incurable. Circulating tumor DNA (ctDNA) may facilitate earlier diagnosis of recurrent colorectal cancer and improve cancer-related outcomes. Methods: Plasma from patients undergoing standard surveillance after definitive treatment for stage II/III colorectal cancer was assayed with COLVERA and carcinoembryonic antigen (CEA) at a single time point. Results were correlated with radiographic imaging. Assay performance, including sensitivity and specificity for recurrence, were compared. Impact of potentially confounding variables was also explored. Results: 322 patients were included in the final analysis, and 27 recurrences were documented over a median follow-up period of 15 months. Sensitivity for recurrence was 63% [confidence interval (CI), 42.4–80.6] and 48% (CI, 28.7–68.1) for COLVERA and CEA (≥5 ng/mL), respectively (P = 0.046), while specificity was 91.5% (CI, 87.7–94.4) and 96.3% (CI, 93.4–98.1), respectively (P = 0.016). Smoking and age were independent predictors of CEA but not COLVERA positivity. Conclusions: COLVERA was more sensitive but less specific than CEA in detecting recurrent colorectal cancer. Short median follow-up may have been responsible for apparent false positives in COLVERA. Studies with serial sampling and longer follow-up are needed to assess whether earlier detection of colorectal cancer recurrence translates into clinical benefit. Impact: This prospective study showed that COLVERA (a two-gene ctDNA assay) was more sensitive for detection of recurrence in a cohort of patients undergoing surveillance after definitive therapy for stages II and III colorectal cancer.
Glioblastoma cell differentiation trajectory predicts the immunotherapy response and overall survival of patients

Glioblastoma (GBM) is the most common and lethal primary brain tumor. In this study, we aimed to investigate the differentiation states of GBM cells and their clinical relevance. Integrated single-cell RNA-sequencing (scRNA-seq) data and bulk RNA-seq data from GBM samples were used for analysis. Two subsets of GBM cells in distinct differentiation states were characterized, and 498 GBM cell differentiation-related genes (GDRGs) were identified. GDRGs were significantly correlated with immune regulation and metabolic pathways. We classified the GBM patients into two groups based on the expression of GDRGs in tumors and found that the cell differentiation-based classification successfully predicted patient overall survival (OS), immune checkpoint expression and likelihood of immunotherapy response in GBMs. FN1, APOE, RPL7A and GSTM2 were the 4 most significant survival-predicting GDRGs, and patients with different expression levels of each of these genes had distinct survival outcomes. Finally, a nomogram composed of the GDRG signature, age, pharmacotherapy, radiotherapy, IDH mutations and MGMT promoter methylation was generated and validated in two large GBM cohorts to predict GBM prognosis. This study highlights the significant roles of cell differentiation in predicting the clinical outcomes of GBM patients and their potential response to immunotherapy, suggesting promising therapeutic targets for GBM.
The impact of previous cancer on overall survival of bladder cancer patients and the establishment of nomogram for overall survival prediction

Abstract To investigate the role of previous cancer on overall survival in patients with bladder cancer (BCa) and to establish an effective prognostic tool for individualized overall survival prediction. A total of 78,660 patients diagnosed with BCa between 2000 and 2013 were selected from the Surveillance, Epidemiology, and End Results (SEER) database, among which 8915 patients had a history of other cancers. We compared the overall survival between patients with and without previous cancer after propensity score matching and we further established a nomogram for overall survival prediction. Univariate and multivariate Cox analyses were used to determine independent prognostic factors. The calibration curve and concordance index (C-index) were used to assess the accuracy of the nomogram. Cox proportional hazards models and Kaplan–Meier analysis were used to compare survival outcomes. BCa patients with previous cancer had worse overall survival compared with those without previous cancer (HR = 1.37; 95%CI = 1.32–1.42, P < .001). Cancers in lung prior to BCa had the most adverse impact on overall survival (HR = 2.35; 95%CI = 2.10–2.63; P < .001), and the minimal impact was located in prostate (HR = 1.16; 95%CI = 1.10–1.22; P < .001) for male and in gynecological (HR = 1.15; 95%CI = 1.02–1.30; P = .027) for female. The shorter interval time between 2 cancers and the higher stage of the previous cancer development, the higher risk of death. Age, race, sex, marital status, surgery, radiation, grade, stage, type of previous cancer as the independent prognostic factors were selected into the nomogram. The favorable calibration curve and C-index value (0.784, 95%CI = 0.782–0.786) indicated the nomogram could accurately predict the 1-, 3-, and 5-year overall survival rate of BCa patients. Previous cancer has a negative impact on the overall survival of BCa patients and requires more effective clinical management. The nomogram provides accurate survival prediction for BCa patients and might be helpful for clinical treatment selection and follow-up strategy adjustment.
Human parainfluenza virus fusion complex glycoproteins imaged in action on authentic viral surfaces

Infection by human parainfluenza viruses (HPIVs) causes widespread lower respiratory diseases, including croup, bronchiolitis, and pneumonia, and there are no vaccines or effective treatments for these viruses. HPIV3 is a member of the Respirovirus species of the Paramyxoviridae family. These viruses are pleomorphic, enveloped viruses with genomes composed of single-stranded negative-sense RNA. During viral entry, the first step of infection, the viral fusion complex, comprised of the receptor-binding glycoprotein hemagglutinin-neuraminidase (HN) and the fusion glycoprotein (F), mediates fusion upon receptor binding. The HPIV3 transmembrane protein HN, like the receptor-binding proteins of other related viruses that enter host cells using membrane fusion, binds to a receptor molecule on the host cell plasma membrane, which triggers the F glycoprotein to undergo major conformational rearrangements, promoting viral entry. Subsequent fusion of the viral and host membranes allows delivery of the viral genetic material into the host cell. The intermediate states in viral entry are transient and thermodynamically unstable, making it impossible to understand these transitions using standard methods, yet understanding these transition states is important for expanding our knowledge of the viral entry process. In this study, we use cryo-electron tomography (cryo-ET) to dissect the stepwise process by which the receptor-binding protein triggers F-mediated fusion, when forming a complex with receptor-bearing membranes. Using an on-grid antibody capture method that facilitates examination of fresh, biologically active strains of virus directly from supernatant fluids and a series of biological tools that permit the capture of intermediate states in the fusion process, we visualize the series of events that occur when a pristine, authentic viral particle interacts with target receptors and proceeds from the viral entry steps of receptor engagement to membrane fusion.
Mitochondrial dysfunction in cardiovascular disease: Current status of translational research/clinical and therapeutic implications

Mitochondria provide energy to the cell during aerobic respiration by supplying ~95% of the adenosine triphosphate (ATP) molecules via oxidative phosphorylation. These organelles have various other functions, all carried out by numerous proteins, with the majority of them being encoded by nuclear DNA (nDNA). Mitochondria occupy ~1/3 of the volume of myocardial cells in adults, and function at levels of high‐efficiency to promptly meet the energy requirements of the myocardial contractile units. Mitochondria have their own DNA (mtDNA), which contains 37 genes and is maternally inherited. Over the last several years, a variety of functions of these organelles have been discovered and this has led to a growing interest in their involvement in various diseases, including cardiovascular (CV) diseases. Mitochondrial dysfunction relates to the status where mitochondria cannot meet the demands of a cell for ATP and there is an enhanced formation of reactive‐oxygen species. This dysfunction may occur as a result of mtDNA and/or nDNA mutations, but also as a response to aging and various disease and environmental stresses, leading to the development of cardiomyopathies and other CV diseases. Designing mitochondria‐targeted therapeutic strategies aiming to maintain or restore mitochondrial function has been a great challenge as a result of variable responses according to the etiology of the disorder. There have been several preclinical data on such therapies, but clinical studies are scarce. A major challenge relates to the techniques needed to eclectically deliver the therapeutic agents to cardiac tissues and to damaged mitochondria for successful clinical outcomes. All these issues and progress made over the last several years are herein reviewed.
Computer- and Telephone-Delivered Interventions on Patient Outcomes and Resource Utilization in Patients With Orthopaedic Conditions

BACKGROUND: As the number of patients with orthopaedic conditions has risen continuously, hospital-based healthcare resources have become limited. Delivery of additional services is needed to adapt to this trend. PURPOSE: The purpose of this study was to describe the current literature of computer- and telephone-delivered interventions on patient outcomes and resource utilization in patients with orthopaedic conditions. METHODS: The systematic review was conducted in January 2019. The standardized checklist for randomized controlled trials was used to assess the quality of the relevant studies. A meta-analysis was not possible due to heterogeneity in the included studies, and a narrative synthesis was conducted to draw informative conclusions relevant to current research, policy, and practice. RESULTS: A total of 1,173 articles were retrieved. Six randomized controlled trials met the inclusion criteria, providing evidence from 434 individuals across four countries. Two studies reported findings of computer-delivered interventions and four reported findings of telephone-delivered interventions. The patients who received both computer- and telephone-delivered interventions showed improvements in patient outcomes that were similar or better to those of patients receiving conventional care. This was without any increase in adverse events or costs. CONCLUSION: Computer- and telephone-delivered interventions are promising and safe alternatives to conventional care. This review, however, identifies a gap in evidence of high-quality studies exploring the effects of computer- and telephone-delivered interventions on patient outcomes and resource utilization. In future, these interventions should be evaluated from the perspective of intervention content, self-management, and patient empowerment. In addition, they should consider the whole care journey and the development of the newest technological innovations. Additionally, future surgery studies should take into account the personalized needs of special, high-risk patient groups and focus on patient-centric care to reduce postdischarge health problems and resource utilization in this population.
Biodegradable Electrospun Nonwovens Releasing Propolis as a Promising Dressing Material for Burn Wound Treatment

The selection of dressing is crucial for the wound healing process. Traditional dressings protect against contamination and mechanical damage of an injured tissue. Alternatives for standard dressings are regenerating systems containing a polymer with an incorporated active compound. The aim of this research was to obtain a biodegradable wound dressing releasing propolis in a controlled manner throughout the healing process. Dressings were obtained by electrospinning a poly(lactide-co-glycolide) copolymer (PLGA) and propolis solution. The experiment consisted of in vitro drug release studies and in vivo macroscopic treatment evaluation. In in vitro studies released active compounds, the morphology of nonwovens, chemical composition changes of polymeric material during degradation process, weight loss and water absorption were determined. For in vivo research, four domestic pigs, were used. The 21-day experiment consisted of observation of healing third-degree burn wounds supplied with PLGA 85/15 nonwovens without active compound, with 5 wt % and 10 wt % of propolis, and wounds rinsed with NaCl. The in vitro experiment showed that controlling the molar ratio of lactidyl to glycolidyl units in the PLGA copolymer gives the opportunity to change the release profile of propolis from the nonwoven. The in vivo research showed that PLGA nonwovens with propolis may be a promising dressing material in the treatment of severe burn wounds.
Ex Vivo Administration of Mesenchymal Stromal Cells in Kidney Grafts Against Ischemia Reperfusion Injury - Effective Delivery Without Kidney Function Improvement Posttransplant.

BACKGROUND Mesenchymal stromal cell (MSC) therapy may improve renal function after ischemia-reperfusion injury in transplantation. Ex vivo renal intraarterial administration is a targeted delivery method, avoiding the lung vasculature, a known barrier for cellular therapies. In a randomized and blinded study, we tested the feasibility and effectiveness of MSC therapy in a donation after circulatory death autotransplantation model to improve posttransplant kidney function, using an ex vivo MSC delivery method similar to the clinical standard procedure of pretransplant cold graft flush. METHODS Kidneys exposed to 75 min of warm ischemia and 16 hrs of static cold storage were intraarterially infused ex vivo with 10 million male porcine MSCs (Tx-MSC, n=8) or vehicle (Tx-control, n=8). Afterwards, the kidneys were autotransplanted after contralateral nephrectomy. Biopsies an hour after reperfusion confirmed the presence of MSCs in the renal cortex. Animals were observed for 14 days. RESULTS Postoperatively, peak p-creatinine was 1230 and 1274 µmol/L (Tx-controls vs Tx-MSC, p=0.69). During follow up, no significant differences over time were detected between groups regarding p-creatinine, p-NGAL, or u-NGAL/creatinine ratio. At day 14 measured glomerular filtration rates were 40 and 44 mL/min, p=0.66. Renal collagen content and fibrosis related mRNA expression were increased in both groups but without significant differences between the groups.In conclusion, we demonstrated intraarterial MSC infusion to transplant kidneys as a safe and effective method to deliver MSCs to the graft. However, we could not detect any positive effects of this cell treatment within 14 days of observation.