bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving Pediatric/Neonatology Residents' Newborn Resuscitation Skills With a Digital Serious Game: DIANA
Authors: Bardelli Serena , Del Corso Giulio , Ciantelli Massimiliano , Del Pistoia Marta , Lorenzoni Francesca , Fossati Nicoletta , Scaramuzzo Rosa T. , Cuttano Armando 
Published: April 2022

BackgroundSerious games, and especially digital game based learning (DGBL) methodologies, have the potential to strengthen classic learning methodology in all medical procedures characterized by a flowchart (e.g., neonatal resuscitation algorithm). However, few studies have compared short- and long-term knowledge retention in DGBL methodologies with a control group undergoing specialist training led by experienced operators. In particular, resident doctors' learning still has limited representation in simulation-based education literature.ObjectiveA serious computer game DIANA (DIgital Application in Newborn Assessment) was developed, according to newborn resuscitation algorithm, to train pediatric/neonatology residents in neonatal resuscitation algorithm knowledge and implementation (from procedure knowledge to ventilation/chest compressions rate). We analyzed user learning curves after each session and compared knowledge retention against a classic theoretical teaching session.MethodsPediatric/neonatology residents of the Azienda Ospedaliera Universitaria Pisana (AOUP) were invited to take part in the study and were split into a game group or a control group; both groups were homogeneous in terms of previous training and baseline scores. The control group attended a classic 80 min teaching session with a neonatal trainer, while game group participants played four 20 min sessions over four different days. Three written tests (pre/immediately post-training and at 28 days) were used to evaluate and compare the two groups' performances.ResultsForty-eight pediatric/neonatology residents participated in the study. While classic training by a neonatal trainer demonstrated an excellent effectiveness in short/long-term knowledge retention, DGBL methodology proved to be equivalent or better. Furthermore, after each game session, DGBL score improved for both procedure knowledge and ventilation/chest compressions rate.ConclusionsIn this study, DGBL was as effective as classic specialist training for neonatal resuscitation in terms of both algorithm memorization and knowledge retention. User appreciation for the methodology and ease of administration, including remotely, support the use of DGBL methodologies for pediatric/neonatology residents education.
Acute Retinal Necrosis: Clinical Features, Diagnostic Pitfalls, Treatment, and Outcome of an Insidious Disease in Children. Case Report and Review of the Literature
Authors: Mapelli Chiara , Milella Paolo , Donà Caterina , Nassisi Marco , Osnaghi Silvia , Viola Francesco , Agostoni Carlo , Minoia Francesca , Filocamo Giovanni 
Published: April 2022

ObjectiveThis study aims to explore clinical features, diagnostic work-up, treatment, and outcomes of pediatric patients with acute retinal necrosis (ARN), and to propose a standardized management of this condition in childhood.MethodsClinical manifestations, diagnostic work-up, and treatment of three pediatric cases with ARN were analyzed. Furthermore, a review of the literature was performed from January 1990 to November 2021, focused on 1) clinical presentation; 2) differential diagnosis, including both infectious and non-infectious conditions; 3) key role of diagnostic techniques; and 4) currently available treatments.ResultsData from 72 children with ARN (69 from literature and 3 from our center) were analyzed. The most frequent presenting symptoms were red eye resistant to topical treatment (57%) and altered vision (58%), 25 patients had bilateral involvement. In 30% a known history of herpetic infection was reported. PCR testing on anterior chamber and/or vitreous sampling was performed in 46 cases (64%) and was diagnostic in 88% of them, with herpes simplex virus (HSV) 2 being the most frequently identified pathogen (57%). All patients underwent systemic antiviral therapy (16% only oral); adjunctive intravitreal injections were performed in 21% of them.ConclusionsARN is a rare but severe ocular infection presenting as a panuveitis with occlusive retinal vasculitis and peripheral retinal necrosis. Varicella-zoster virus and HSV 1–2 are most frequently implicated. Due to a high incidence of rhegmatogenous retinal detachment and optic atrophy, ARN has a poor prognosis with a potentially severe impact on visual function. Although a prompt recognition is crucial to prevent complications, ARN diagnosis in children is still challenging.
Effect of Metformin on Myocardial Injury Induced by Hepatic Ischemia-Reperfusion in Rats
Authors: An Wen , Kang Ju-Seop 
Published: April 2022

Background: There is no effective medication for treatment or prevention of hepatic ischemia-reperfusion (HIR) injury caused by liver transplantation and hepatectomy. This study aimed to investigate the therapeutic effects of metformin on HIR injury and related myocardial injury in rats.Methods: Wistar male rats were randomly divided into four groups: sham group, ischemia-reperfusion group, and IR group treated with metformin 150 mg/kg and 100 mg/kg. Wistar male rats were administered metformin 150 mg/kg, 100 mg/kg or saline 30 min pre-operative and underwent 15 min ischemia and 6 h reperfusion (n = 4).Results: Metformin significantly alleviates the injury caused by HIR. Administration of metformin resulted in a significant reduction in the serum levels of alanine transaminase and aspartate transaminase and the activity of malondialdehyde, creatine kinase-MB, and lactate dehydrogenase but maintained high catalase and superoxide dismutase activity. Metformin significantly inhibited the IR-induced elevation of tumor necrosis factor-α in liver and heart tissue.Conclusion: Metformin can alleviate hepatic and myocardial injury induced by IR by inhibiting oxidative stress.
NUSAP1 Could be a Potential Target for Preventing NAFLD Progression to Liver Cancer
Authors: Zeng Taofei , Chen Guanglei , Qiao Xinbo , Chen Hui , Sun Lisha , Ma Qingtian , Li Na , Wang Junqi , Dai Chaoliu , Xu Feng 
Published: April 2022

Background: Non-alcoholic fatty liver disease (NAFLD) has gradually emerged as the most prevalent cause of chronic liver diseases. However, specific changes during the progression of NAFLD from non-fibrosis to advanced fibrosis and then hepatocellular carcinoma (HCC) are unresolved. Here, we firstly identify the key gene linking NAFLD fibrosis and HCC through analysis and experimental verification.Methods: Two GEO datasets (GSE89632, GSE49541) were performed for identifying differentially expressed genes (DEGs) associated with NAFLD progression from non-fibrosis to early fibrosis and eventually to advanced fibrosis. Subsequently, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis, protein-protein interaction (PPI) network were integrated to explore the potential function of the DEGs and hub genes. The expression of NUSAP1 was confirmed in vivo and in vitro NAFLD models at mRNA and protein level. Then, cell proliferation and migration under high fat conditions were verified by cell counting kit-8 (CCK-8) and wound-healing assays. The lipid content was measured with Oil Red O staining. Finally, the analysis of clinical survival curves was performed to reveal the prognostic value of the crucial genes among HCC patients via the online web-tool GEPIA2 and KM plotter.Results: 5510 DEGs associated with non-fibrosis NAFLD, 3913 DEGs about NAFLD fibrosis, and 739 DEGs related to NAFLD progression from mild fibrosis to advanced fibrosis were identified. Then, a total of 112 common DEGs were found. The result of enrichment analyses suggested that common DEGs were strongly associated with the glucocorticoid receptor pathway, regulation of transmembrane transporter activity, peroxisome, and proteoglycan biosynthetic process. Six genes, including KIAA0101, NUSAP1, UHRF1, RAD51AP1, KIF22, and ZWINT, were identified as crucial candidate genes via the PPI network. The expression of NUSAP1 was validated highly expressed in vitro and vivo NAFLD models at mRNA and protein level. NUSAP1 silence could inhibit the ability of cell proliferation, migration and lipid accumulation in vitro. Finally, we also found that NUSAP1 was significantly up-regulated at transcriptional and protein levels, and associated with poor survival and advanced tumor stage among HCC patients.Conclusion: NUSAP1 may be a potential therapeutic target for preventing NAFLD progression to liver cancer.
Herbal Medicine for the Treatment of Anorexia in Children: A Systematic Review and Meta-Analysis
Authors: Lee Boram , Kwon Chan-Young , Lee Sun Haeng , Chang Gyu Tae 
Published: April 2022

Background: Anorexia is a common obstacle to adequate nutrition in childhood, a critical period for physical growth. East Asian traditional medicine treatment modalities including herbal medicine (HM) a re considered an attractive therapeutic option, especially in East Asian countries. The purpose of this systematic review was to comprehensively examine the efficacy and safety of HM for anorexia in children.Methods: A total of 12 electronic databases from their inception date to June 2021 were searched for randomized controlled trials (RCTs) assessing the efficacy of HM for the treatment of anorexia in children. The primary outcome was an improvement in anorexia clinical symptoms after treatment. In this meta-analysis, continuous and binary outcomes were assessed, and the data are presented as the mean difference or standardized mean difference and risk ratio (RR) with their 95% confidence intervals (CIs). The risk of bias and quality of evidence were assessed using the Cochrane Collaboration’s risk of bias tool and Grading of Recommendations, Assessment, Development, and Evaluations tool.Results: A total of 205 RCTs were included. A comparison of HM with placebo revealed that the total effective rate based on anorexia symptom improvement was significantly higher in the HM group (RR 1.58, 95% CI 1.34, 1.85). In comparison with controls, HM as monotherapy or adjunctive therapy to dietary supplements or conventional medications led to significant improvements in anorexia symptoms, body measurements, levels of blood biomarkers related to gastrointestinal function, and nutrition indices, with a lower recurrence rate of anorexia. No serious adverse events related to HM were reported. The risk of bias of the included studies was generally unclear, and the quality of evidence was generally low to moderate.Conclusion: Our study showed that HM could improve clinical symptoms, some anthropometric outcomes, and some biological markers related to appetite and growth in children with anorexia. However, considering the high risk of bias of the included studies and the heterogeneity of the HMs used, future research should focus on the use of standardized HMs and the implementation of methodologically robust clinical trials.Systematic Review Registration: https://www.crd.york.ac.uk/prosperodisplay_record.php?ID=CRD42021274376, identifier CRD42021274376
Challenging T > MIC Using Meropenem vs. Escherichia coli and Pseudomonas aeruginosa
Authors: Nussbaumer-Pröll A. , Eberl S. , Kurdina E. , Schmidt L. , Zeitlinger M. 
Published: April 2022

Objective: For meropenem 40%T &gt; MIC is associated with optimal killing of P. aeruginosa and E. coli. However, it is unknown how the distribution of %T &gt; MIC through a treatment day impacts the antimicrobial effect in vitro. Therefore, we investigated the in vitro antibiotic activity of meropenem, precisely if 40%T &gt; MIC is achieved in one single long period (single dose), 2 × 20% periods (dosing-bid), or 3 × 13.3% (dosing t.i.d.) thereby keeping the overall period of T &gt; MIC constant.Material/Methods: Time kill curves (TKC) with P. aeruginosa-ATCC-27853 and E. coli-ATCC-25922 and five clinical isolates each were implemented over 24 h in CAMHB with concentrations from 0.25×MIC-32×MIC. Periods over and under MIC were simulated by centrifugation steps (discarding supernatant and refilling with fresh CAMHB). Double and triple dosing involved further addition and removal of antibiotic. Complementary growth controls (GC) with and without centrifugation steps were done and the emergence of phenotypical resistance was evaluated (repeated MIC-testing after antibiotic administration).Results: No impact of centrifugation on bacterial growth was seen. TKC with P. aeruginosa showed the best killing in the triple dosage, followed by the double and single dose. In multiple regimens at least a concentration of 4×MIC was needed to achieve a recommended 2-3 log10 killing. Likewise, a reduction of E. coli was best within the three short periods. Contrary to the TKCs with P. aeruginosa we could observe that after the inoculum reached a certain CFU/mL (≥10^8), no further addition of antibiotic could achieve bacterial killing (identified as the inoculum effect). For P. aeruginosa isolates resistance appeared within all regimens, the most pronounced was found in the 40%T &gt; MIC experiments indicating that a single long period might accelerate the emergence of resistance. Contrary, for E. coli no emergence of resistance was found.Conclusion/Outlook: We could show that not solely the %T &gt; MIC is decisive for an efficient bacterial eradication in vitro, but also the distribution of the selected %T &gt; MIC. Thus, dividing the 40%T &gt; MIC in three short periods requested lowers antibiotic concentrations to achieve efficient bacterial killing and reduces the emergence of resistance in P. aeruginosa isolates. The distribution of the %T &gt; MIC did impact the bacterial eradication of susceptible pathogens in vitro and might play an even bigger role in infections with intermediate or resistant pathogens.
Dexmedetomidine Alleviates Intracerebral Hemorrhage-Induced Anxiety-Like Behaviors in Mice Through the Inhibition of TRPV4 Opening
Authors: An Ping , Zhao Xiao-Chun , Liu Man-Jia , You Yu-Qing , Li Jing-Ya , Gong He-Song 
Published: April 2022

Post-stroke anxiety severely affects recovery in patients with intracerebral hemorrhage (ICH). Dexmedetomidine (Dex), a highly selective alpha 2 adrenal receptor (α2-AR) agonist, was recently found to exert an excellent protective effect against mental disorders including anxiety. The transient receptor potential vanilloid 4 (TRPV4) channel is involved in a series of diseases such as asthma, cancer, anxiety, and cardiac hypertrophy. This study examines whether Dex improved ICH-induced anxiety via the inhibition of TRPV4 channel opening. A rodent model of moderate ICH in the basal ganglia was established using autologous blood injection (20 μl). Mice were treated with Dex (25 μg/kg, intraperitoneal injection) every day for 3 days post-ICH. GSK1016790A (1 μmol/2 μl), an agonist of TRPV4, was administered via the left lateral ventricle. Thirty days post-ICH, post-stroke anxiety was evaluated by elevated plus-maze and open-field tests. Following behavioral tests, superoxide dismutase (SOD), malondialdehyde (MDA), astrocytic activation, and A1-and A2-type astrocytes were determined. Primary astrocytes were exposed to hemin to simulate ICH in vitro. Compared with sham-treated mice, Dex administration ameliorates ICH-induced decreases of distance and time in the open-arm, reduces distance and time in the central zone, increases astrocytic activation and A1-type astrocytes, elevates MDA content, downregulates total SOD contents, and decreases A2-type astrocytes. However, GSK1016790A partially reversed the neuroprotective effects of Dex. In addition, Dex significantly inhibited hemin-induced astrocytic activation in vitro. Dex improves ICH-induced anxiety-like behaviors in mice, and the mechanism might be associated with the inhibition of TRPV4-channel opening.
Preliminary Evidence That the Short Allele of 5-HTTLPR Moderates the Association of Psychiatric Symptom Severity on Suicide Attempt: The Example in Obsessive-Compulsive Disorder
Authors: Harika-Germaneau Ghina , Lafay-Chebassier Claire , Langbour Nicolas , Thirioux Bérangère , Wassouf Issa , Noël Xavier , Jaafari Nemat , Chatard Armand 
Published: April 2022

BackgroundThe severity of symptoms represents an important source of distress in patients with a psychiatric disease. However, the extent to which this endogenous stress factor interacts with genetic vulnerability factors for predicting suicide risks remains unclear.MethodsWe evaluated whether the severity of symptoms interacts with a genetic vulnerability factor (the serotonin transporter gene-linked promoter region variation) in predicting the frequency of lifetime suicide attempts in patients with a psychiatric disease. Symptom severity and 5-HTTLPR polymorphism were collected from a sample of 95 patients with obsessive-compulsive disorder (OCD). Lifetime suicide attempt was the primary outcome, and antecedent of multiple suicide attempts was the secondary outcome.ResultsThe gene-by-symptoms interaction was associated with an excess risk of suicide attempts (OR = 4.39, 95CI[1.44, 13.38], p &lt; 0.009) and of multiple suicide attempts (OR = 4.18, 95CI[1.04, 16.77], p = 0.043). Symptom severity (moderate, severe, or extreme) was associated with an approximately five-fold increase in the odds of a lifetime suicide attempt in patients carrying one or two copies of the short allele of 5-HTTLPR. No such relationship was found for patients carrying the long allele.ConclusionThis study provides preliminary evidence for the gene-by-stress interaction on suicide attempt when stress is operationalized as symptom severity. Progress in suicide research may come from efforts to investigate the gene-by-symptoms interaction hypothesis in a variety of diseases.
Mental Health Challenges, Parenting Stress, and Features of the Couple Relationship in Parents of Children With Fragile X Syndrome
Authors: Potter Sarah Nelson , Harvey Danielle J. , Sterling Audra , Abbeduto Leonard 
Published: April 2022

BackgroundIndividuals with fragile X syndrome (FXS) have significant delays in cognition and language, as well as anxiety, symptoms of autism spectrum disorder, and challenging behaviors such as hyperactivity and aggression. Biological mothers of children with FXS, who are themselvesFMR1premutation or full mutation carriers, are at elevated risk for mental health challenges in addition to experiencing stress associated with parenting a child with significant disabilities. However, little is known about fathers in these families, including the ways in which parental well-being influences the mother-father relationship and the impact of child characteristics on paternal and couple functioning.MethodThe current study examined features of, and relationships between, parental well-being, couple well-being, and child functioning in 23 families of young boys with FXS. Mothers and fathers independently completed multiple questionnaires about their individual well-being, couple functioning, and child behavior. One parent per family also completed an interview about the child’s adaptive skills.ResultsResults suggest that both mothers and fathers in these families experience clinically significant levels of mental health challenges and elevated rates of parenting stress relative to the general population. Findings also indicate that the couples’ relationship may be a source of strength that potentially buffers against some of the daily stressors faced by these families. Additionally, parents who reported less parenting stress had higher couples satisfaction and dyadic coping. Finally, parents of children with less severe challenging behaviors exhibited fewer mental health challenges, less parenting stress, and higher levels of both couples satisfaction and dyadic coping. Parents of children with higher levels of adaptive behavior also reported less parenting stress and higher couples satisfaction.ConclusionOverall, this study provides evidence that families of children with FXS need access to services that not only target improvements in the child’s functioning, but also ameliorate parental stress. Family-based services that include both mothers and fathers would lead to better outcomes for all family members.
Clergy's Viewpoint Change Toward Mental Health and Stigma on Mental Illness: A Short Course Training
Authors: Taghva Arsia , Noorbala Ahmad Ali , Khademi Mojgan , Shahriari Alireza , Nasr Esfahani Mahdi , Asadi Ali , Mohsenifar Jafar , Yousefifard Ali , Abolhassani Moussa , Bolhari Jafar , Hajebi Ahmad , Rahnejat Amir Mohsen , Shahed-haghghadam Haleh 
Published: April 2022

BackgroundAs stigma is one of the main barriers in promoting the mental health, the present study was designed with the purpose of reviewing clergy's viewpoint regarding the effect of mental health workshops on these barriers.MethodsFor this study, by order of Iran's Health Ministry, a questionnaire was designed to examine the clergy's viewpoint related to mental illnesses and the consequent stigma. Ten faculty members and psychiatrists confirmed the questionnaire's validity after some modifications. In this research, 30 members of the clergy from the main religious city in Iran's “Qom” Seminary attended the training workshops for 2 days. The data obtained from the clergy's responses were analyzed using the SPSS software (ver.16) and descriptive and analytical tests. Also, the significance level was considered p &lt; 0.05 in all tests. The results exhibited that the mean and standard deviation (Mean ± SD) of the clergy's attitude domain and awareness before the workshop was 1.90 ± 26.30 and 8.31 ± 1.64, respectively. Also, average and standard deviation (Mean ± SD) of their attitude domain and awareness after the workshop was 1.95 ± 29.73 and 1.18 ± 10.70, respectively.DiscussionThe present study, which was designed to examine the clergy's viewpoint toward mental illnesses and the consequent stigma in the most considerable religious base in the country, illustrated that one strategy for reducing mental illness stigma in religious communities can be by holding training sessions to promote the clergy's awareness of and attitude toward mental health.ConclusionThere was a significant statistical difference between their awareness and attitude scores before and after the workshop (p &lt; 0.01). In the present research, the awareness and attitude of clergy toward mental health and stigma due to mental illness was relatively good and significantly increased by holding the workshop.