Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacokinetics and complementary evaluation system-based guidance on prophylaxis of paediatric patients with haemophilia A in China with Kovaltry: protocol of the LEAP study

Introduction Haemophilia A is a rare inherited bleeding disease caused by the deficiency of coagulation factor VIII (FVIII). The main treatment protocol is to administer regular exogenous FVIII concentrate infusions. With the discovery of variability in individualised pharmacokinetics (PK) and bleeding phenotype, the previous weight-based approach needs to be replaced by more advanced PK-tailored prophylaxis with an accurate evaluation system. In this study, we combine individualised PK profiles and a complementary evaluation system to guide prophylaxis in paediatric patients with haemophilia A. Methods and analysis This is a single-centre, prospective single-arm study. The aim of this study is to assess the effectiveness of a new strategy combining PK and a complementary evaluation system to treat haemophilia A in Chinese paediatric patients. Sixty paediatric patients with haemophilia will be recruited. After PK testing, they will receive a PK-guided stepup prophylaxis in the next 2 years. The dosing regimen will be determined according to individualised PK profiles and complementary evaluation findings. Related indicators at the end of the study will be compared with the values at treatment initiation to examine the effectiveness of this new strategy. The demographic data of the investigated patients will be summarised by descriptive statistics. Quantitative data will be described by summary statistics, including arithmetic median, range, mean and arithmetic SD. Analyses will use t-test to compare indicators such as bleeding rate and imaging score at both ends of the study as well as during follow-up. Ethics and dissemination The study has been approved by the Ethics Committee of Beijing Children’s Hospital (Number 2020-Z-095). The findings will be presented at international meetings such as World Federation of Hemophilia World Congress. Related manuscripts will be submitted to peer-review journals such as Blood and Hemophilia. Trial registration number ChiCTR2000037821; Pre-results.
Inflamed brain: Targeting immune changes and inflammation for treatment of depression

Although there are a number of clinically effective treatments for depression, many patients exhibit treatment resistance. Recent clinical and preclinical studies reveal that peripheral and brain immune changes and inflammation are involved in the pathophysiology of depression. This ‘Inflamed Brain’ research provides critical clues for understanding of disease pathophysiology and many candidate molecules that are potentially useful for identifying novel drug targets for the treatment of depression. In this review, we will present clinical evidence on the role of inflammation in the pathophysiology of depression. We will also summarize current clinical trials which test drugs targeting inflammation for the treatment of patients with depression. Furthermore, we will briefly provide preclinical evidence demonstrating altered immune system function and inflammation in stress‐induced animal models and will discuss the future potential of inflammation‐related drug targets. Collectively, inflammatory signatures identified in clinical and preclinical studies may allow us to stratify depressive patients based on biotypes, contributing to the development of novel mechanism‐based interventions that target specific patient populations.
Mechanistic Aspects of Medicinal Plants and Secondary Metabolites against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

BACKGROUND AND OBJECTIVE The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a highly pathogenic virus, is responsible for a respiratory disease termed coronavirus disease 2019 (COVID-19). SARS-CoV-2 genome encodes various structural and non-structural proteins, which are necessary for viral entry and replication. Among these proteins, papain-like protease (PLpro), 3C-like protease (3CLpro), RNA-dependent RNA polymerase (RdRp), helicase, a serine protease, and spike protein are potential targets of herbal remedies and phytocompounds for inhibition of viral infection and replication. There is at present no confirmed cure for the COVID-19. Various plants and their components have been introduced against SARS-Co-2. A number of review articles have also been published on them. This article is focusing on the mechanistic aspects of these plants and their derivatives on SARS-CV-2. METHOD The material in this review article was prepared from significant scientific databases, including Web of Science, PubMed, Science Direct, Scopus and Google Scholar. RESULTS Different medicinal plants and their phytocompounds interact with important structural and non-structural of SARS-CoV-2 proteins. Natural compounds form strong bonds with the active site of SARS-CoV-2 protease and make large conformational changes. These phytochemicals are potential inhibitors of structural and non-structural of SARS-CoV-2 proteins such as Spike protein, PLpro, and 3CLpro. Some important anti-SARS-CoV-2 actions of medicinal plants and their metabolites are inhibition of the virus replication or entry, blocking the angiotensin-converting enzyme 2 (ACE-2) receptor and "Transmembrane protease, serine 2 (TMPRSS2)" regulation of inflammatory mediators, inhibition of endothelial activation, toll-like receptors (TLRs) and activation of the nuclear factor erythroid-derived 2-related factor 2 (Nrf2). Some of these important natural immune boosters that are helpful for prevention and curing various symptoms related to COVID-19 include Allium sativum, Nigella sativa, Glycyrrhiza glabra Zingiber officinalis, Ocimum sanctum, Withania somnifera, Tinospora cordifolia, and Scutellaria baicalensis. Also, Kaempferol, Quercetin, Baicalin, Scutellarin, Glycyrrhizin, Curcumin, Apigenin, Ursolic acid, and Chloroquine are the best candidates for treating the symptoms associated with SARS-CoV-2 infection. CONCLUSION Medicinal plants and/or their bioactive compounds with inhibitory effects against SARS-CoV-2 support the human immune system and help in fighting against COVID-19 and rejuvenating the immune system.
Investigating organisational justice and job satisfaction as perceived by nurses, and its relationship to organizational citizenship behaviour.

BACKGROUND Organisational justice refers to the extent to which employees perceive workplace procedures, interactions, and outcomes to be fair in nature. Previous research has found that organisational justice has been associated with an employee's commitment to their organisation, job satisfaction, and intention to leave their role. Organisational justice has also been linked to organisational citizenship behaviours, and the likelihood of these behaviours being demonstrated by employees. AIM To investigate staff nurses' perceptions of organisational justice and job satisfaction and its relationship to their levels of organisational citizenship behaviour. METHOD Perceived levels of organisational justice, job satisfaction, and levels of organisational citizenship behaviour were evaluated among 175 nurses working in two hospitals in Egypt. Analysis was undertaken to ascertain whether a correlation existed between organisational justice or job satisfaction and levels of organisational citizenship behaviour. RESULTS The majority of nurses in this study were found to perceive moderate levels of organisational justice. Organisational justice was positively correlated with levels of organisational citizenship behaviour, as was job satisfaction. CONCLUSION This study found that nurses in two hospitals in Egypt perceived moderate levels of organisational justice in their place of work. Nurse managers should pay extra attention to strategies that promote organisational justice among nurses.
Hepatectomy outcomes in patients with hepatitis C virus-related hepatocellular carcinoma with or without cirrhosis.

Introduction Although hepatocellular carcinoma (HCC) is rare in hepatitis C virus (HCV) patients without cirrhosis, little is known about the postoperative results of these patients. We performed this study to compare the outcomes of cirrhotic and non-cirrhotic HCV patients with solitary treatment-naïve HCC and to assess ability of non-invasive markers to predict prognosis in these patients. Methods Two hundred seven adult hepatectomy patients with HCV-related HCC were prospectively identified at our institution between July 2005 and May 2019. Results One hundred sixteen (56%) hepatectomy patients had HCC in a non-cirrhotic liver. The non-cirrhotic group had better liver function than the cirrhotic group. Consistently, the FIB-4 grade, ALBI grade, and APRI were higher in the cirrhotic group than in the non-cirrhotic group. The cumulative disease-free survival rates and patient survival rates in the non-cirrhotic group were significantly better than in the cirrhotic group. HCC recurrence is related to major liver resection (LR) and alpha-fetoprotein (AFP) > 40 ng/mL, death is related to long hospitalization, and AFP > 40 in multivariate analysis. APRI was the only predisposing factor for HCC recurrence in non-cirrhotic patients in multivariate analysis. The FIB-4 grade, ALBI grade, and the presence of cirrhosis were not related to HCC recurrence or patient survival in multivariate analyses. Conclusions The non-cirrhotic group had a higher survival than the cirrhotic group after curative LR, although the difference was not significant in multivariate analysis. The factors influencing HCC recurrence and patient survival were different in the cirrhotic and non-cirrhotic groups.
Training women's pelvic floor muscles during pregnancy and postpartum at primary health centers: a best practice implementation project.

INTRODUCTION AND AIMS Pelvic floor muscle training (PFMT) enhances muscle strength and coordination, and prevents urinary incontinence associated with giving birth. The goal was to improve women's PFMT during pregnancy and postpartum in La Rioja, Spain. METHODS This evidence implementation project used the JBI evidence implementation framework. First, we conducted the PFMT baseline audit: to assess the criteria for midwife training, we sent a questionnaire to all midwives. To measure the criteria for PFMT and urinary incontinence risk assessment, we reviewed the medical records of 60 women selected through consecutive sampling and 15 other women at risk of urinary tract infections (UTIs) for the inclusion criteria in a PFMT program. Second, we used the Getting Research into Practice guidelines to identify barriers to the fulfillment of each criterion and design and implement strategies to improve compliance. Finally, we repeated the audit to measure compliance and verify the changes. RESULTS The midwives received updated PFMT, optimizing compliance with the first criterion from 67 to 100%. The remaining criteria - providing PFMT for pregnant women, identifying women at high risk of incontinence, and facilitating a supervised PFMT program for women at high risk of UTIs - went from 0% compliance to 17, 96, and 67%, respectively. CONCLUSION This project was effective in building consensus, improving midwives' practice, and facilitating mothers' PFMT. The project continued during the novel coronavirus [coronavirus disease 2019 (COVID-19)] epidemic in Spain as the midwives, women, and managers were involved in the change because of a well designed registration system and the use of online tools for communication between midwives and women.
The non-specific nature of mental health and structural brain outcomes following childhood trauma

Abstract Background Childhood trauma (CT) is associated with an increased risk of mental health disorders; however, it is unknown whether this represents a diagnosis-specific risk factor for specific psychopathology mediated by structural brain changes. Our aim was to explore whether (i) a predictive CT pattern for transdiagnostic psychopathology exists, and whether (ii) CT can differentiate between distinct diagnosis-dependent psychopathology. Furthermore, we aimed to identify the association between CT, psychopathology and brain structure. Methods We used multivariate pattern analysis in data from 643 participants of the Personalised Prognostic Tools for Early Psychosis Management study (PRONIA), including healthy controls (HC), recent onset psychosis (ROP), recent onset depression (ROD), and patients clinically at high-risk for psychosis (CHR). Participants completed structured interviews and self-report measures including the Childhood Trauma Questionnaire, SCID diagnostic interview, BDI-II, PANSS, Schizophrenia Proneness Instrument, Structured Interview for Prodromal Symptoms and structural MRI, analyzed by voxel-based morphometry. Results (i) Patients and HC could be distinguished by their CT pattern with a reasonable precision [balanced accuracy of 71.2% (sensitivity = 72.1%, specificity = 70.4%, p ≤ 0.001]. (ii) Subdomains ‘emotional neglect’ and ‘emotional abuse’ were most predictive for CHR and ROP, while in ROD ‘physical abuse’ and ‘sexual abuse’ were most important. The CT pattern was significantly associated with the severity of depressive symptoms in ROD, ROP, and CHR, as well as with the PANSS total and negative domain scores in the CHR patients. No associations between group-separating CT patterns and brain structure were found. Conclusions These results indicate that CT poses a transdiagnostic risk factor for mental health disorders, possibly related to depressive symptoms. While differences in the quality of CT exposure exist, diagnostic differentiation was not possible suggesting a multi-factorial pathogenesis.
Pediatric Posterior Sternoclavicular Dislocation Closed Reduction and Management.

SUMMARY Posterior sternoclavicular joint (SCJ) dislocations are rare shoulder girdle injuries. Despite the paucity of cases, posterior SCJ dislocations pose an important threat to patient safety because of the proximity of the medial clavicle to the mediastinum, resulting in possible compression and/or injury to these structures. Current guidelines recommend attempting closed reduction in the acute setting followed by open reduction if closed reduction is unsuccessful. This video highlights a case of posterior SCJ dislocation in a pediatric patient who presented with dyspnea after a football injury.
Upper Airway Characteristics in Young Individuals With Class II Division 1 Malocclusion: A Retrospective Inter-Ethnic Cephalometric Comparison

Supplemental Digital Content is available in the text Abstract This study aimed to compare the upper-airway morphology between strictly matched Syrian (n = 43) and Hungarian (n = 43) adolescents with Class II/1 malocclusion and identify potential associations between upper airway depths and skeletofacial characteristics. Lateral cephalograms were analyzed, and independent-samples tests and correlation coefficients were used for the statistical analyses. The upper-pharyngeal airway was significantly narrower and the soft palate angle was significantly greater in the Syrian adolescents. Alternatively, the hyoid bone was more posteriorly positioned in the Hungarian adolescents when compared to their counterparts. Depths of the upper and middle pharynx were moderately correlated with sagittal and vertical skeletal dimensions only among Syrian subjects. The depth of the lower pharynx was moderately correlated with hyoid bone position, cervical length, and lip–chin–throat angle only among Hungarian subjects. These findings might have potential implications for optimizing the effects of orthognathic/orthodontic treatments on airway structures in these 2 groups.
Towards More Predictive, Physiological and Animal-free In Vitro Models: Advances in Cell and Tissue Culture 2020 Conference Proceedings

Experimental systems that faithfully replicate human physiology at cellular, tissue and organ level are crucial to the development of efficacious and safe therapies with high success rates and low cost. The development of such systems is challenging and requires skills, expertise and inputs from a diverse range of experts, such as biologists, physicists, engineers, clinicians and regulatory bodies. Kirkstall Limited, a biotechnology company based in York, UK, organised the annual conference, Advances in Cell and Tissue Culture (ACTC), which brought together people having a variety of expertise and interests, to present and discuss the latest developments in the field of cell and tissue culture and in vitro modelling. The conference has also been influential in engaging animal welfare organisations in the promotion of research, collaborative projects and funding opportunities. This report describes the proceedings of the latest ACTC conference, which was held virtually on 30th September and 1st October 2020, and included sessions on in vitro models in the following areas: advanced skin and respiratory models, neurological disease, cancer research, advanced models including 3-D, fluid flow and co-cultures, diabetes and other age-related disorders, and animal-free research. The roundtable session on the second day was very interactive and drew huge interest, with intriguing discussion taking place among all participants on the theme of replacement of animal models of disease.
High quality interfacial sulfur passivation via H2S pre-deposition annealing for an atomic-layer-deposited HfO2 film on a Ge substrate

The effects of sulfur passivation of the Ge substrate were studied through (NH4)2S solution treatment and the rapid thermal annealing under an H2S atmosphere prior to atomic-layer-deposition (ALD) of HfO2. While a chemically unstable and uneven sulfur layer was formed by (NH4)2S solution treatment, a stable, highly uniform and dense sulfur layer with a thickness of ∼2 nm was formed by H2S annealing on Ge substrates. The sulfur concentration at the interface increased with H2S annealing temperature. Sulfur passivation suppressed the diffusion of Ge into the HfO2 film and any interfacial layer growth during ALD, which resulted in a decreased equivalent oxide thickness of gate insulator. The interface properties, such as interface defect state density and hysteresis in capacitance–voltage behavior, were also improved by sulfur passivation through H2S annealing. H2S annealing is much more compatible with a mass-production process compared to the conventional (NH4)2S solution treatment process.
Reliable and valid assessment of procedural skills in resuscitative endovascular balloon occlusion of the aorta

Supplemental digital content is available in the text. BACKGROUND Valid and reliable assessment of skills is essential for improved and evidence-based training concepts. In a recent study, we presented a novel tool to assess procedural skills in resuscitative endovascular balloon occlusion of the aorta (REBOA), REBOA-RATE, based on international expert consensus. Although expert consensus is a strong foundation, the performance of REBOA-RATE has not been explored. The study aimed to examine the reliability and validity of REBOA-RATE. METHODS This was an experimental simulation-based study. We enrolled doctors with three levels of expertise to perform two REBOA procedures in a simulated scenario of out-of-hospital cardiac arrest. Procedures were video-recorded, and videos were blinded and randomized. Three clinical experts independently rated all procedures using REBOA-RATE. Data were analyzed using Messick’s framework for validity evidence, including generalizability analysis of reliability and determination of a pass/fail standard. RESULTS Forty-two doctors were enrolled: 16 novices, 13 anesthesiologists, and 13 endovascular experts. They all performed two procedures, yielding 84 procedures and 252 ratings. The REBOA-RATE assessment tool showed high internal consistency (Cronbach’s α = 0.95) and excellent interrater reliability (intraclass correlation coefficient, 0.97). Assessment using one rater and three procedures could ensure overall reliability suitable for high-stakes testing (G-coefficient >0.80). Mean scores (SD) for the three groups in the second procedure were as follows: novices, 32% (24%); anesthesiologists, 55% (29%); endovascular experts, 93% (4%) (p < 0.001). The pass/fail standard was set at 81%, which all experts but no novices passed. CONCLUSION Data strongly support the reliability and validity of REBOA-RATE, which successfully discriminated between all experience levels. The REBOA-RATE assessment tool requires minimal instruction, and one rater is sufficient for reliable assessment. Together, these are strong arguments for the use of REBOA-RATE to assess REBOA skills, allowing for competency-based training and certification concepts. LEVEL OF EVIDENCE Diagnostic test, no or poor gold standard, level V.
Packing a punch: understanding how flavours are produced in lager fermentations

ABSTRACT Beer is one of the most popular beverages in the world and it has an irreplaceable place in culture. Although invented later than ale, lager beers dominate the current market. Many factors relating to the appearance (colour, clarity and foam stability) and sensory characters (flavour, taste and aroma) of beer, and other psychological determinants affect consumers’ perception of the product and defines its drinkability. This review takes a wholistic approach to scrutinise flavour generation in the brewing process, focusing particularly on the contribution of the raw ingredients and the yeasts to the final flavour profiles of lager beers. In addition, we examine current developments to improve lager beer flavour profiles for the modern consumers.
Accelerated Stability Study of the Ester Prodrug Remdesivir; Recently FDA Approved Covid-19 Antiviral Using RP-HPLC with Fluorimetric and Diode Array Detection.

Remdesivir is the first antiviral drug, approved by the Food and Drug Administration, to treat SARS-CoV-2. Remdesivir is a relatively new chemical entity, "ester prodrug", with no reported stability profile. Due to the urge of its use and thus, fast production, it is important to develop a stability-indicating method for its assay. Chromatographic separation was carried on C18 (250 x 4.6 mm, 5 μm) column with dual detection; Diode-array at 240 nm and fluorescence at λex/em 245/390 nm. Isocratic elution of acetonitrile and distilled water (acidified with phosphoric acid, pH 4) in ratio of 55: 45, v/v respectively was used. HPLC-DAD linearity range was 0.1-15 μg/mL while with fluorimetric detection the range was 0.05-15 μg/mL. As per International Conference on Harmonization guidelines, Remdesivir, has been degraded by accelerated: alkaline, acidic, neutral hydrolysis, oxidative, heat and photolytic stress conditions. Possible degradation hypothesis of the parent molecule was suggested and illustrated. Proposed methods have achieved selective determination of the intact drug with no peaks overlapping in all assumptions. Extensive degradation confirms threatened drug stability at thermal and basic hydrolytic stressing. Developed methods were fully validated and proved suitable for quality control routine analysis of Remdesivir in raw material and pharmaceutical dosage form.