Miracle-dz/UniFAR-FTUs huggingface dataset:
Long-Term Cognitive Outcomes and Associated Quality of Life of Young Adults Who Experienced Liver Transplantation in Early Childhood

We evaluated long term outcomes in infants born between 1992 and 2002 with cholestatic liver disease (CLD) who underwent successful liver transplantation (LT). A total of 160 children with CLD were identified: 68 had developmental assessments before and after LT of whom 32 were excluded because they were followed up elsewhere; 16/36 consented to complete measures of IQ, anxiety, depression, health related quality of life (HRQoL), and a habits/employment survey. Illness severity and developmental attainment prior to LT were comparable with the 32 excluded and 20 patients who declined to take part. The IQ of young adults after LT (mean score = 91.13, range 75–108, SD 10.4) was not significantly improved compared to pre-LT scores (mean score = 85.7 range 50–111, SD 17), but was inversely correlated with stunting of growth and duration of disease before LT, highlighting the need for timely LT in CLD. HRQoL scores ranged from 22 to 99 (mean 64.5 SD 20.7), comparable to scores in other LT recipients. Five (31%) had mild-moderate depression; 5 (31%) had moderate-severe anxiety associated with reduced HRQoL (P = 0.01 and P = 0.06, respectively); and nine had problematic fatigue which correlated with reduced HRQoL (r2 = 0.4 P = 0.007). Reduced medication adherence was associated with fatigue (Spearman correlation r2 = 0.267; P = 0.09) and anxiety (Spearman correlation r2 = 0.597; P = 0.02). Raised body mass index was also associated with reduced and health-related quality of life scores PeLTQL© (r2 = 0.379 P = 0.011). Fifteen (94%) were undergoing education or were employed. The long-term neuro-cognitive and psychosocial outcomes of young adults transplanted as babies is encouraging, although anxiety/depression was more common than in the healthy population. Psychosocial questionnaires help identify those young adult LT recipients who may benefit from support.
A Rapid Systematic Review of Worldwide Alcohol Use Disorders and Brief Alcohol Interventions in the Criminal Justice System

Although the relationship is complex, there is an association between alcohol use and offending behavior with an interplay between the amount drank, the pattern of drinking and individual and contextual factors. Alcohol brief interventions have been shown to be effective in primary healthcare, however there is currently a lack of compelling evidence in the criminal justice system. We carried out a rapid systematic review of the literature, which updated our review conducted in 2016. Following systematic searches, we included 36 papers on prevalence and 13 papers on effectiveness. Between 26 and 88% of individuals in the policy custody setting scored positive for an alcohol use disorder. In the magistrates court this was 95%; 31–86% in the probation setting and between 19 and 86% in the prison system. In relation to probable dependence, between 21 and 38% of individuals were shown to have probable alcohol dependence in the police custody suite setting; 39 per cent in the magistrate court system; 17–36% in the probation setting and between 18 and 48% in the prison system. This compares to 6% in the general population. We included 13 studies of effectiveness with differing outcome measures and outcomes. We conclude more studies are needed in the field to develop the current evidence base.
Virulence Factors of Pseudomonas Aeruginosa and Antivirulence Strategies to Combat Its Drug Resistance

Pseudomonas aeruginosa is an opportunistic pathogen causing nosocomial infections in severely ill and immunocompromised patients. Ubiquitously disseminated in the environment, especially in hospitals, it has become a major threat to human health due to the constant emergence of drug-resistant strains. Multiple resistance mechanisms are exploited by P. aeruginosa, which usually result in chronic infections difficult to eradicate. Diverse virulence factors responsible for bacterial adhesion and colonization, host immune suppression, and immune escape, play important roles in the pathogenic process of P. aeruginosa. As such, antivirulence treatment that aims at reducing virulence while sparing the bacterium for its eventual elimination by the immune system, or combination therapies, has significant advantages over traditional antibiotic therapy, as the former imposes minimal selective pressure on P. aeruginosa, thus less likely to induce drug resistance. In this review, we will discuss the virulence factors of P. aeruginosa, their pathogenic roles, and recent advances in antivirulence drug discovery for the treatment of P. aeruginosa infections.
Multi-Omics Techniques Make it Possible to Analyze Sepsis-Associated Acute Kidney Injury Comprehensively

Sepsis-associated acute kidney injury (SA-AKI) is a common complication in critically ill patients with high morbidity and mortality. SA-AKI varies considerably in disease presentation, progression, and response to treatment, highlighting the heterogeneity of the underlying biological mechanisms. In this review, we briefly describe the pathophysiology of SA-AKI, biomarkers, reference databases, and available omics techniques. Advances in omics technology allow for comprehensive analysis of SA-AKI, and the integration of multiple omics provides an opportunity to understand the information flow behind the disease. These approaches will drive a shift in current paradigms for the prevention, diagnosis, and staging and provide the renal community with significant advances in precision medicine in SA-AKI analysis.
A Cross-Sectional Study on Associations Between BDNF, CRP, IL-6 and Clinical Symptoms, Cognitive and Personal Performance in Patients With Paranoid Schizophrenia

Background Cognitive impairment is among the core dimensions in schizophrenia and is a significant predictor of everyday functioning in people with schizophrenia. Given the enormous burden of schizophrenia, the search for its clinically relevant biomarkers is essential. Researchers have been trying to elucidate factors of cognitive impairment as well as personal performance, but the search is still ongoing. The aim of the study was to search for associations between BDNF, CRP, IL-6 and clinical symptoms, cognitive and personal performance in patients with paranoid schizophrenia. Methods A total of 86 patients (53.5% women, mean age 31.1 ± 6.5) with paranoid schizophrenia (F20.0; ICD-10) in remission were examined. Clinical and neuropsychological examination included the Positive and Negative Syndrome Scale, Personal and Social Performance Scale, Calgary Depression Scale for Schizophrenia and the Brief Assessment of Cognitive Function in Schizophrenia. IL-6, BDNF, CRP levels were determined in the patients' blood serum. Results Cognitive impairment was revealed in 79.1% of patients and was more profound in patients with higher number of hospitalizations (p = 0.006). The average BDNF levels were 13.38 ± 15.84 ng/ml, CRP concentration was 2.09 ± 2.54 mg/l, and IL-6 levels were 12.14 ± 5.88 pg/ml. There were no differences in biomarker levels or BACS results in patients that had different antipsychotic therapy or differed in the presence of anticholinergic therapy. CRP levels were higher in patients with longer disease duration, lower age of onset, more impaired personal social performance and processing speed. IL-6 was higher in individuals with lower working memory scores. PANSS negative subscale score negatively correlated and PSP score positively correlated with most cognitive domains. A linear regression established that the first episode vs. multiple episodes of schizophrenia could statistically significantly predict personal and social performance and cognition, including speech fluency and planning, as well as CRP levels. Conclusions This study continues the search for biomarkers of schizophrenia and cognitive impairment in schizophrenia to improve the reliability of diagnosing the disorder and find new treatment approaches. The role of the number of psychoses experienced (first episode vs. multiple episodes of schizophrenia) in cognition, personal and social performance and inflammation is shown.
Development of Screening Tools to Predict Medication-Related Problems Across the Continuum of Emergency Department Care: A Prospective, Multicenter Study

Background: Medication-related problems (MRPs) occur across the continuum of emergency department (ED) care: they may contribute to ED presentation, occur in the ED/short-stay unit (SSU), at hospital admission, or shortly after discharge to the community. This project aimed to determine predictors for MRPs across the continuum of ED care and incorporate these into screening tools (one for use at ED presentation and one at ED/SSU discharge), to identify patients at greatest risk, who could be targeted by ED pharmacists. Methods: A prospective, observational, multicenter study was undertaken in nine EDs, between July 2016 and August 2017. Blocks of ten consecutive adult patients presenting at pre-specified times were identified. Within 1 week of ED discharge, a pharmacist interviewed patients and undertook a medical record review to determine a medication history, patient understanding of treatment, risk factors for MRPs and to manage the MRPs. Logistic regression was undertaken to determine predictor variables. Multivariable regression beta coefficients were used to develop a scoring system for the two screening tools. Results: Of 1,238 patients meeting all inclusion criteria, 904 were recruited. Characteristics predicting MRPs related to ED presentation were: patient self-administers regular medications (OR = 7.95, 95%CI = 3.79–16.65), carer assists with medication administration (OR = 15.46, 95%CI = 6.52–36.67), or health-professional administers (OR = 5.01, 95%CI = 1.77–14.19); medication-related ED presentation (OR = 9.95, 95%CI = 4.92–20.10); age ≥80 years (OR = 3.63, 95%CI = 1.96–6.71), or age 65–79 years (OR = 2.01, 95%CI = 1.17–3.46); potential medication adherence issue (OR = 2.27, 95%CI = 1.38–3.73); medical specialist seen in past 6-months (OR = 2.02, 95%CI = 1.42–2.85); pharmaceutical benefit/pension/concession cardholder (OR = 1.89, 95%CI = 1.28–2.78); inpatient in previous 4-weeks (OR = 1.60, 95%CI = 1.02–2.52); being male (OR = 1.48, 95%CI = 1.05–2.10); and difficulties reading labels (OR = 0.63, 95%CI = 0.40–0.99). Characteristics predicting MRPs related to ED discharge were: potential medication adherence issue (OR = 6.80, 95%CI = 3.97–11.64); stay in ED > 8 h (OR = 3.23, 95%CI = 1.47–7.78); difficulties reading labels (OR = 2.33, 95%CI = 1.30–4.16); and medication regimen changed in ED (OR = 3.91, 95%CI = 2.43–6.30). For ED presentation, the model had a C-statistic of 0.84 (95% CI 0.81–0.86) (sensitivity = 80%, specificity = 70%). For ED discharge, the model had a C-statistic of 0.78 (95% CI 0.73–0.83) (sensitivity = 82%, specificity = 57%). Conclusion: Predictors of MRPs are readily available at the bedside and may be used to screen for patients at greatest risk upon ED presentation and upon ED/SSU discharge to the community. These screening tools now require external validation and implementation studies to evaluate the impact of using such tools on patient care outcomes.
Executive Function Skills and Classroom Behaviors of U.S. Prekindergartners With Special Needs

This study explores the executive function (EF) skills in a sample of 4-year-old children enrolled in inclusive prekindergarten (pre-k) classrooms. We compare the EF skills and important classroom behaviors of children with and without identified special needs as well as a sample of English language learners (ELL) in the same classrooms. Identification of special needs and ELL status were each examined as these factors have previously been shown to be associated with young children’s EF skills. Compared to their classroom peers, children with identified special needs not only began the year with lower EF skills but made fewer gains over the school year, a similar pattern was observed for children identified as ELL. Compared to their peers, children with identified special needs were observed as engaging in lower levels of involvement, sequential behaviors, and social learning interactions and higher levels of unoccupied and disruptive behaviors, a pattern that was also found for children’s entering EF skills (e.g., lower entering EF scores associated with lower levels of involvement). Lastly, children’s classroom behaviors differed across teacher-directed and children-directed learning with level of involvement and social-learning interactions higher during child-directed learning, and sequential behaviors higher in teacher-directed learning, a pattern that held across all groups of children.
Constructing Injectable Bone-Forming Units by Loading a Subtype of Osteoprogenitors on Decellularized Bone Matrix Powders for Bone Regeneration

Bone defects resulting from trauma or tumor are one of the most challenging problems in clinical settings. Current tissue engineering (TE) strategies for managing bone defects are insufficient, owing to without using optimal osteoconductive material and seeding cells capable of superior osteogenic potential; thus their efficacy is instable. Herein, a novel TE strategy was developed for treating bone defects. First, the decellularized bone matrix (DBM) was manufactured into powders, and these DBM powders preserved the ultrastructural and compositional properties of native trabecular bone, are non-cytotoxic and low-immunogenic, and are capable of inducing the interacted stem cells differentiating into osteogenic lineage. Then, a subtype of osteoprogenitors was isolated from mouse long bones, and its high osteogenic potential was identified in vitro. After that, we constructed a “bone-forming unit” by seeding the special subtype of osteoprogenitors onto the DBM powders. In vivo performance of the “bone-forming units” was determined by injecting into the defect site of a mouse femoral epiphysis bone defect model. The results indicated that the “bone-forming unit” was capable of enhancing bone defect healing by regulating new bone formation and remodeling. Overall, the study establishes a protocol to construct a novel “bone-forming unit,” which may be an alternative strategy in future bone TE application.
Relationship and Alliance Formation Processes in Psychotherapy: A Dual-Perspective Qualitative Study

Objective To explore how therapists and clients act dyadically to establish a therapeutic relationship during the first five sessions of psychotherapy. The study aimed to identify both relational facilitative and hindering processes occurring in routine care. Methods Using the method ‘interpersonal process recall’ (IPR), we videotaped the third and fifth session of 12 psychotherapy dyads, and conducted video-assisted interviews with each therapist and client separately. In total, the data material consist of 47 IPR interviews. Data were analyzed using a thematic approach. Results The analysis process revealed two main groups. The first group consisted of dyads with a positive relational outcome, and the second group consisted of dyads with a troubled or frail relational outcome. During the initial phase of therapy, clients described feeling overwhelmed by fear and shame. Positive relational development occurred when these emotions were successfully accommodated and replaced with a growing sense of safety with the therapist. However, the relationship became troubled when the client experienced an increase in shame and/or fear during the first sessions. When forming a therapeutic relationship, it is vital that the client experience the therapist as genuine and skilled, and that the therapist is able to engage and connect deeply with the client on a person-to-person level. The article further provides a discussion on how these dyadic experiences align with the working alliance and real relationship, and how the two consolidate during the first sessions of psychotherapy. Conclusion The current study explored the complex relational processes underlying the formation of the therapeutic relationship. Core aspects of the real relationship are prerequisites to forming a collaborative working alliance in which both therapist and client are actively engaged. Facilitating a positive relationship is crucial in the early phase of psychotherapy, and therapists can actively identify and repair ruptures at this time.
The Pathogenesis of HCC Driven by NASH and the Preventive and Therapeutic Effects of Natural Products

Nonalcoholic steatohepatitis (NASH) is a clinical syndrome with pathological changes that are similar to those of alcoholic hepatitis without a history of excessive alcohol consumption. It is a specific form of nonalcoholic fatty liver disease (NAFLD) that is characterized by hepatocyte inflammation based on hepatocellular steatosis. Further exacerbation of NASH can lead to cirrhosis, which may then progress to hepatocellular carcinoma (HCC). There is a lack of specific and effective treatments for NASH and NASH-driven HCC, and the mechanisms of the progression of NASH to HCC are unclear. Therefore, there is a need to understand the pathogenesis and progression of these diseases to identify new therapeutic approaches. Currently, an increasing number of studies are focusing on the utility of natural products in NASH, which is likely to be a promising prospect for NASH. This paper reviews the possible mechanisms of the pathogenesis and progression of NASH and NASH-derived HCC, as well as the potential therapeutic role of natural products in NASH and NASH-derived HCC.
Universal Newborn Screening for Congenital Cytomegalovirus Infection – From Infant to Maternal Infection: A Prospective Multicenter Study

Introduction: Most infants at risk for cytomegalovirus (CMV)-associated sensorineural hearing loss (SNHL) are unrecognized because of the absence of a universal neonatal CMV screening. The search of CMV-DNA by molecular methods in salivary swabs was demonstrated to be a reliable approach. This study describes the results obtained by carrying out a universal screening for congenital CMV (cCMV) infection including all live-born newborns in three Italian sites, as well as the therapeutic interventions and clinical outcome of the CMV-infected neonates. Moreover, CMV maternal infection's characteristics were evaluated. Methods To confirm or exclude cCMV infection, a CMV-DNA-positive result on a first salivary swab was followed by repeated saliva and urine samples collected within 21 days of age. Breast milk samples were also collected. The search of CMV-DNA was performed with a single automated quantitative commercial real-time PCR assay, regardless of the type of samples used. Results A total of 3,151 newborns were enrolled; 21 (0.66%) of them were congenitally infected (median saliva viral load at screening, 6.65 [range, 5.03–7.17] log10 IU/ml). Very low/low viral load in screening saliva samples (median value, 1.87 [range, 1.14–2.59] log10 IU/ml) was associated with false-positive results (n = 54; 1.7%). CMV-DNA was detected in almost half of the breast milk samples of mother–infant pairs with a false-positive result, suggesting that contamination from breast milk may not be the only explanation in the study population. cCMV infection confirmation with the search of CMV-DNA in a urine sample proved to be the gold standard strategy, since false-positive results were observed in 4/54 (7.5%) of the repeated saliva samples. Symptomatic cCMV infection was observed in 3/21 (14.3%) infants; notably, one (4.7%) developed moderate unilateral SNHL at 5 months after birth. Finally, two symptomatic cCMV infections were associated with primary maternal infection acquired in the first trimester of gestation; one newborn with severe cCMV symptoms was born to a mother with no CMV checkups in pregnancy. Conclusion Without universal neonatal CMV screening, some infected infants who develop late neurological sequelae may not be recognized and, consequently, they are not able to benefit early from instrumental and therapeutic interventions to limit and/or treat CMV disease.
Increased Expression of Multiple Co-Inhibitory Molecules on Malaria-Induced CD8+ T Cells Are Associated With Increased Function Instead of Exhaustion

Activated cytotoxic CD8+ T cells can selectively kill target cells in an antigen-specific manner. However, their prolonged activation often has detrimental effects on tissue homeostasis and function. Indeed, overwhelming cytotoxic activity of CD8+ T cells can drive immunopathology, and therefore, the extent and duration of CD8+ T cell effector function needs to be tightly regulated. One way to regulate CD8+ T cell function is their suppression through engagement of co-inhibitory molecules to their cognate ligands (e.g., LAG-3, PD-1, TIM-3, TIGIT and CTLA-4). During chronic antigen exposure, the expression of co-inhibitory molecules is associated with a loss of T cell function, termed T cell exhaustion and blockade of co-inhibitory pathways often restores T cell function. We addressed the effect of co-inhibitory molecule expression on CD8+ T cell function during acute antigen exposure using experimental malaria. To this end, we infected OT-I mice with a transgenic P. berghei ANKA strain that expresses ovalbumin (PbTG), which enables the characterization of antigen-specific CD8+ T cell responses. We then compared antigen-specific CD8+ T cell populations expressing different levels of the co-inhibitory molecules. High expression of LAG-3 correlated with high expression of PD-1, TIGIT, TIM-3 and CTLA-4. Contrary to what has been described during chronic antigen exposure, antigen-specific CD8+ T cells with the highest expression of LAG-3 appeared to be fully functional during acute malaria. We evaluated this by measuring IFN-γ, Granzyme B and Perforin production and confirmed the results by employing a newly developed T cell cytotoxicity assay. We found that LAG-3high CD8+ T cells are more cytotoxic than LAG-3low or activated but LAG-3neg CD8+ T cells. In conclusion, our data imply that expression of co-inhibitory molecules in acute malaria is not necessarily associated with functional exhaustion but may be associated with an overwhelming T cell activation. Taken together, our findings shed new light on the induction of co-inhibitory molecules during acute T cell activation with ramifications for immunomodulatory therapies targeting these molecules in acute infectious diseases.