bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of train-the-trainer programs on the continued professional development of nurses: a systematic review
Authors: Nexø Mette Andersen , Kingod Natassia Rosewood , Eshøj Signe Hornsleth , Kjærulff Emilie Mølholm , Nørgaard Ole , Andersen Tue Helms 
Published: January 2024

Abstract
Background
Train-the-trainer (TTT) programs are widely applied to disseminate knowledge within healthcare systems, but evidence of the effectiveness of this educational model remains unclear. We systematically reviewed studies evaluating the impact of train-the-trainer models on the learning outcomes of nurses.

Methods
The reporting of our systematic review followed PRISMA 2020 checklist. Records identified from MEDLINE, Embase, CINAHL, and ERIC were independently screened by two researchers and deemed eligible if studies evaluated learning outcomes of a train-the-trainer intervention for trainers or trainees targeting nurses. Study quality was assessed with Joanna Briggs Institute’s critical appraisal tools and data of study characteristics extracted (objective, design, population, outcomes, results). Heterogeneity of outcomes ruled out meta-analysis; a narrative synthesis and vote counting based on direction of effects (p < 0.05) synthesized the results.
All records were uploaded and organized in EPPI-Reviewer.

Results
Of the 3800 identified records 11 studies were included. The included studies were published between 1998 and 2021 and mostly performed in the US or Northern Europe. Nine studies had quasi-experimental designs and two were randomized controlled trials. All evaluated effects on nurses of which two also included nurses’ assistants. The direction of effects of the 13 outcomes (knowledge, n = 10; skills, n = 2; practice, n = 1) measured in the 11 included studies were all beneficial. The statistical analysis of the vote counting showed that train-the-trainer programs could significantly (p < 0.05) improve trainees’ knowledge, but the number of outcomes measuring impact on skills or practice was insufficient for synthesis.

Conclusions
Train-the-trainer models can successfully disseminate knowledge to nurses within healthcare systems. Considering the nurse shortages faced by most Western healthcare systems, train-the-trainer models can be a timesaving and sustainable way of delivering education. However, new comparative studies that evaluate practice outcomes are needed to conclude whether TTT programs are more effective, affordable and timesaving alternatives to other training programs.

Trial registration
The protocol was registered in Research Registry (https://www.researchregistry.com, unique identifying number 941, 29 June 2020).
Evaluation of the nurse-assisted eHealth intervention ‘eHealth@Hospital-2-Home’ on self-care by patients with heart failure and colorectal cancer post-hospital discharge: protocol for a randomised controlled trial
Authors: Storm Marianne , Morken Ingvild Margreta , Austin Rosalynn C. , Nordfonn Oda , Wathne Hege Bjøkne , Urstad Kristin Hjorthaug , Karlsen Bjørg , Dalen Ingvild , Gjeilo Kari Hanne , Richardson Alison , Elwyn Glyn , Bru Edvin , Søreide Jon Arne , Kørner Hartwig , Mo Rune , Strömberg Anna , Lurås Hilde , Husebø Anne Marie Lunde 
Published: January 2024

Abstract
Background
Patients with heart failure (HF) and colorectal cancer (CRC) are prone to comorbidity, a high rate of readmission, and complex healthcare needs. Self-care for people with HF and CRC after hospitalisation can be challenging, and patients may leave the hospital unprepared to self-manage their disease at home. eHealth solutions may be a beneficial tool to engage patients in self-care.

Methods
A randomised controlled trial with an embedded evaluation of intervention engagement and cost-effectiveness will be conducted to investigate the effect of eHealth intervention after hospital discharge on the self-efficacy of self-care. Eligible patients with HF or CRC will be recruited before discharge from two Norwegian university hospitals. The intervention group will use a nurse-assisted intervention—eHealth@Hospital-2-Home—for six weeks. The intervention includes remote monitoring of vital signs; patients’ self-reports of symptoms, health and well-being; secure messaging between patients and hospital-based nurse navigators; and access to specific HF and CRC health-related information. The control group will receive routine care. Data collection will take place before the intervention (baseline), at the end of the intervention (Post-1), and at six months (Post-2). The primary outcome will be self-efficacy in self-care. The secondary outcomes will include measures of burden of treatment, health-related quality of life and 30- and 90-day readmissions. Sub-study analyses are planned in the HF patient population with primary outcomes of self-care behaviour and secondary outcomes of medication adherence, and readmission at 30 days, 90 days and 6 months. Patients’ and nurse navigators’ engagement and experiences with the eHealth intervention and cost-effectiveness will be investigated. Data will be analysed according to intention-to-treat principles. Qualitative data will be analysed using thematic analysis.

Discussion
This protocol will examine the effects of the eHealth@ Hospital-2-Home intervention on self-care in two prevalent patient groups, HF and CRC. It will allow the exploration of a generic framework for an eHealth intervention after hospital discharge, which could be adapted to other patient groups, upscaled, and implemented into clinical practice.

Trial registration
Clinical trials.gov (ID 301472).
Risk factors for prolonged mechanical ventilation in critically ill patients with influenza-related acute respiratory distress syndrome
Authors: Hsu Pai-Chi , Lin Yi-Tsung , Kao Kuo-Chin , Peng Chung-Kan , Sheu Chau-Chyun , Liang Shinn-Jye , Chan Ming-Cheng , Wang Hao-Chien , Chen Yu-Mu , Chen Wei-Chih , Yang Kuang-Yao ,   TSIRC (Taiwan Severe Influenza Research Consortium), Hu Han-Chung , Perng Wann-Cherng , Tsai Ming-Ju , Wu Chieh-Liang , Chien Ying-Chun , Fang Wen-Feng 
Published: January 2024

Abstract
Background
Patients with influenza-related acute respiratory distress syndrome (ARDS) are critically ill and require mechanical ventilation (MV) support. Prolonged mechanical ventilation (PMV) is often seen in these cases and the optimal management strategy is not established. This study aimed to investigate risk factors for PMV and factors related to weaning failure in these patients.

Methods
This retrospective cohort study was conducted by eight medical centers in Taiwan. All patients in the intensive care unit with virology-proven influenza-related ARDS requiring invasive MV from January 1 to March 31, 2016, were included. Demographic data, critical illness data and clinical outcomes were collected and analyzed. PMV is defined as mechanical ventilation use for more than 21 days.

Results
There were 263 patients with influenza-related ARDS requiring invasive MV enrolled during the study period. Seventy-eight patients had PMV. The final weaning rate was 68.8% during 60 days of observation. The mortality rate in PMV group was 39.7%. Risk factors for PMV were body mass index (BMI) > 25 (kg/m2) [odds ratio (OR) 2.087; 95% confidence interval (CI) 1.006–4.329], extracorporeal membrane oxygenation (ECMO) use (OR 6.181; 95% CI 2.338–16.336), combined bacterial pneumonia (OR 4.115; 95% CI 2.002–8.456) and neuromuscular blockade use over 48 h (OR 2.8; 95% CI 1.334–5.879). In addition, risk factors for weaning failure in PMV patients were ECMO (OR 5.05; 95% CI 1.75–14.58) use and bacteremia (OR 3.91; 95% CI 1.20–12.69).

Conclusions
Patients with influenza-related ARDS and PMV have a high mortality rate.
Risk factors for PMV include BMI > 25, ECMO use, combined bacterial pneumonia and neuromuscular blockade use over 48 h. In addition, ECMO use and bacteremia predict unsuccessful weaning in PMV patients.
Causal relationship between gut microbiota and tuberculosis: a bidirectional two-sample Mendelian randomization analysis
Authors: Yuan Zongxiang , Kang Yiwen , Mo Chuye , Huang Shihui , Qin Fang , Zhang Junhan , Wang Fengyi , Jiang Junjun , Yang Xiaoxiang , Liang Hao , Ye Li 
Published: January 2024

Abstract
Background
Growing evidence from observational studies and clinical trials suggests that the gut microbiota is associated with tuberculosis (TB). However, it is unclear whether any causal relationship exists between them and whether causality is bidirectional.

Methods
A bidirectional two-sample Mendelian randomization (MR) analysis was performed. The genome-wide association study (GWAS) summary statistics of gut microbiota were obtained from the MiBioGen consortium, while the GWAS summary statistics of TB and its specific phenotypes [respiratory tuberculosis (RTB) and extrapulmonary tuberculosis (EPTB)] were retrieved from the UK Biobank and the FinnGen consortium. And 195 bacterial taxa from phylum to genus were analyzed. Inverse variance weighted (IVW), MR-Egger regression, maximum likelihood (ML), weighted median, and weighted mode methods were applied to the MR analysis. The robustness of causal estimation was tested using the heterogeneity test, horizontal pleiotropy test, and leave-one-out method.

Results
In the UK Biobank database, we found that 11 bacterial taxa had potential causal effects on TB. Three bacterial taxa genus.Akkermansia, family.Verrucomicrobiacea, order.Verrucomicrobiales were validated in the FinnGen database. Based on the results in the FinnGen database, the present study found significant differences in the characteristics of gut microbial distribution between RTB and EPTB. Four bacterial taxa genus.LachnospiraceaeUCG010, genus.Parabacteroides, genus.RuminococcaceaeUCG011, and order.Bacillales were common traits in relation to both RTB and TB, among which order.Bacillales showed a protective effect. Additionally, family.Bacteroidacea and genus.Bacteroides were identified as common traits in relation to both EPTB and TB, positively associating with a higher risk of EPTB. In reverse MR analysis, no causal association was identified. No significant heterogeneity of instrumental variables (IVs) or horizontal pleiotropy was found.

Conclusion
Our study supports a one-way causal relationship between gut microbiota and TB, with gut microbiota having a causal effect on TB. The identification of characteristic gut microbiota provides scientific insights for the potential application of the gut microbiota as a preventive, diagnostic, and therapeutic tool for TB.
New insights into nanotherapeutics for periodontitis: a triple concerto of antimicrobial activity, immunomodulation and periodontium regeneration
Authors: Li Jiaxin , Wang Yuxiao , Tang Maomao , Zhang Chengdong , Fei Yachen , Li Meng , Li Mengjie , Gui Shuangying , Guo Jian 
Published: January 2024

AbstractPeriodontitis is a chronic inflammatory disease caused by the local microbiome and the host immune response, resulting in periodontal structure damage and even tooth loss. Scaling and root planning combined with antibiotics are the conventional means of nonsurgical treatment of periodontitis, but they are insufficient to fully heal periodontitis due to intractable bacterial attachment and drug resistance. Novel and effective therapeutic options in clinical drug therapy remain scarce. Nanotherapeutics achieve stable cell targeting, oral retention and smart release by great flexibility in changing the chemical composition or physical characteristics of nanoparticles. Meanwhile, the protectiveness and high surface area to volume ratio of nanoparticles enable high drug loading, ensuring a remarkable therapeutic efficacy. Currently, the combination of advanced nanoparticles and novel therapeutic strategies is the most active research area in periodontitis treatment. In this review, we first introduce the pathogenesis of periodontitis, and then summarize the state-of-the-art nanotherapeutic strategies based on the triple concerto of antibacterial activity, immunomodulation and periodontium regeneration, particularly focusing on the therapeutic mechanism and ingenious design of nanomedicines. Finally, the challenges and prospects of nano therapy for periodontitis are discussed from the perspective of current treatment problems and future development trends.
Graphical Abstract
Red blood cell-derived arginase release in hemolytic uremic syndrome
Authors: Friberg Niklas , Arvidsson Ida , Tontanahal Ashmita , Kristoffersson Ann-Charlotte , Gram Magnus , Kaplan Bernard S. , Karpman Diana 
Published: January 2024

Abstract
Background
Hemolysis is a cardinal feature of hemolytic uremic syndrome (HUS) and during hemolysis excess arginase 1 is released from red blood cells. Increased arginase activity leads to reduced L-arginine, as it is converted to urea and L-ornithine, and thereby reduced nitric oxide bioavailability, with secondary vascular injury. The objective of this study was to investigate arginase release in HUS patients and laboratory models and correlate arginase levels to hemolysis and kidney injury.

Methods
Two separate cohorts of patients (n = 47 in total) with HUS associated with Shiga toxin-producing enterohemorrhagic E. coli (EHEC) and pediatric controls (n = 35) were investigated. Two mouse models were used, in which mice were either challenged intragastrically with E. coli O157:H7 or injected intraperitoneally with Shiga toxin 2. An in vitro model of thrombotic microangiopathy was developed in which Shiga toxin 2- and E. coli O157 lipopolysaccharide-stimulated human blood cells combined with ADAMTS13-deficient plasma were perfused over glomerular endothelial cells. Two group statistical comparisons were performed using the Mann–Whitney test, multiple groups were compared using the Kruskal–Wallis test followed by Dunn’s procedure, the Wilcoxon signed rank test was used for paired data, or linear regression for continuous variables.

Results
HUS patients had excessively high plasma arginase 1 levels and activity (conversion of L-arginine to urea and L-ornithine) during the acute phase, compared to remission and controls. Arginase 1 levels correlated with lactate dehydrogenase activity, indicating hemolysis, as well as the need for dialysis treatment. Patients also exhibited high levels of plasma alpha-1-microglobulin, a heme scavenger. Both mouse models exhibited significantly elevated plasma arginase 1 levels and activity. Plasma arginase 1 levels correlated with lactate dehydrogenase activity, alpha-1-microglobulin and urea levels, the latter indicative of kidney dysfunction. In the in vitro model of thrombotic microangiopathy, bioactive arginase 1 was released and levels correlated to the degree of hemolysis.

Conclusions
Elevated red blood cell-derived arginase was demonstrated in HUS patients and in relevant in vivo and in vitro models. The excessively high arginase levels correlated to the degree of hemolysis and kidney dysfunction. Thus, arginase inhibition should be investigated in HUS.
A rare manifestation of STING-associated vasculopathy with onset in infancy: a case report
Authors: Weidler Sophia , Koss Sarah , Wolf Christine , Lucas Nadja , Brunner Jürgen , Lee-Kirsch Min Ae 
Published: January 2024

Abstract
Background
STING-associated vasculopathy with onset in infancy (SAVI) is a rare type I interferonopathy caused by heterozygous variants in the STING gene. In SAVI, STING variants confer a gain-of-function which causes overactivation of type I interferon (IFN) signaling leading to autoinflammation and various degrees of immunodeficiency and autoimmunity.

Case presentation
We report the case of a 5 year old child and his mother, both of whom presented with systemic inflammatory symptoms yet widely varying organ involvement, disease course and therapeutic response. Genetic testing revealed a heterozygous STING variant, R281Q, in the child and his mother that had previously been associated with SAVI. However, in contrast to previously reported SAVI cases due to the R281Q variant, our patients showed an atypical course of disease with alopecia totalis in the child and a complete lack of lung involvement in the mother.

Conclusions
Our findings demonstrate the phenotypic breadth of clinical SAVI manifestations. Given the therapeutic benefit of treatment with JAK inhibitors, early genetic testing for SAVI should be considered in patients with unclear systemic inflammation involving cutaneous, pulmonary, or musculoskeletal symptoms, and signs of immunodeficiency and autoimmunity.
Juvenile idiopathic recurrent parotitis (JIRP) treated with short course steroids, a case series study and one decade follow up for potential autoimmune disorder
Authors: Salehzadeh Farhad , Molatefi Rasol , Mardi Ali , Nahanmoghaddam Negin 
Published: January 2024

Abstract
Background
Juvenile idiopathic recurrent parotitis (JIRP) in children is a condition characterized with recurrent episodes of idiopathic parotid gland inflammation. Since there are no definitive guidelines for diagnosis and management of this condition, we present a consecutive case series of patients with more than one decade follow up and their dramatic response to short course treatment by prednisolone.

Methods
We conducted this study by retrospectively reviewed medical charts of children who were diagnosed with JIRP, from 1 January 2002 to 29 February 2023. We performed usual serological tests to exclude some possible background. We administered short course prednisolone on first day of episode as divided dosage (0.5 mg /kg).

Results
In this case series of 10 patients (70%) were male, median age of onset was 5 years, duration of episodes 5 days, and the mean course of disease were 3.8 years. The average follows up of patients was near 10 years. In comparison with their natural course of disease all patients showed a dramatic response to treatment on the first day of administration of prednisolone (P Value 0.005). For ten years follow up there was not any additional accompanying autoimmune disorder.

Conclusion
Short course prednisolone on first day of each episode and its dramatic and meaningful response in our patients, introduce a new, effective, fast, and inexpensive regimen of therapy in patients with JIRP.
Oxidative stress and inflammation cause auditory system damage via glial cell activation and dysregulated expression of gap junction proteins in an experimental model of styrene-induced oto/neurotoxicity
Authors: Paciello Fabiola , Pisani Anna , Rolesi Rolando , Montuoro Raffaele , Mohamed-Hizam Veronica , Boni Giammarco , Ripoli Cristian , Galli Jacopo , Sisto Renata , Fetoni Anna Rita , Grassi Claudio 
Published: January 2024

Abstract
Background
Redox imbalance and inflammation have been proposed as the principal mechanisms of damage in the auditory system, resulting in functional alterations and hearing loss. Microglia and astrocytes play a crucial role in mediating oxidative/inflammatory injury in the central nervous system; however, the role of glial cells in the auditory damage is still elusive.

Objectives
Here we investigated glial-mediated responses to toxic injury in peripheral and central structures of the auditory pathway, i.e., the cochlea and the auditory cortex (ACx), in rats exposed to styrene, a volatile compound with well-known oto/neurotoxic properties.

Methods
Male adult Wistar rats were treated with styrene (400 mg/kg daily for 3 weeks, 5/days a week). Electrophysiological, morphological, immunofluorescence and molecular analyses were performed in both the cochlea and the ACx to evaluate the mechanisms underlying styrene-induced oto/neurotoxicity in the auditory system.

Results
We showed that the oto/neurotoxic insult induced by styrene increases oxidative stress in both cochlea and ACx. This was associated with macrophages and glial cell activation, increased expression of inflammatory markers (i.e., pro-inflammatory cytokines and chemokine receptors) and alterations in connexin (Cxs) and pannexin (Panx) expression, likely responsible for dysregulation of the microglia/astrocyte network. Specifically, we found downregulation of Cx26 and Cx30 in the cochlea, and high level of Cx43 and Panx1 in the ACx.

Conclusions
Collectively, our results provide novel evidence on the role of immune and glial cell activation in the oxidative/inflammatory damage induced by styrene in the auditory system at both peripheral and central levels, also involving alterations of gap junction networks. Our data suggest that targeting glial cells and connexin/pannexin expression might be useful to attenuate oxidative/inflammatory damage in the auditory system.
The artificial amino acid change in the sialic acid-binding domain of the hemagglutinin neuraminidase of newcastle disease virus increases its specificity to HCT 116 colorectal cancer cells and tumor suppression effect
Authors: Jung Bo-Kyoung , An Yong Hee , Jang Sung Hoon , Jang Jin-Ju , Kim Seonhee , Jeon Joo Hee , Kim Jinju , Song Jason Jungsik , Jang Hyun 
Published: January 2024

Abstract
Background
Oncolytic viruses are being studied and developed as novel cancer treatments. Using directed evolution technology, structural modification of the viral surface protein increases the specificity of the oncolytic virus for a particular cancer cell. Newcastle disease virus (NDV) does not show specificity for certain types of cancer cells during infection; therefore, it has low cancer cell specificity. Hemagglutinin is an NDV receptor-binding protein on the cell surface that determines host cell tropism. NDV selectivity for specific cancer cells can be increased by artificial amino acid changes in hemagglutinin neuraminidase HN proteins via directed evolution, leading to improved therapeutic effects.

Methods
Sialic acid-binding sites (H domains) of the HN protein mutant library were generated using error-prone PCR. Variants of the H domain protein were screened by enzyme-linked immunosorbent assay using HCT 116 cancer cell surface molecules. The mutant S519G H domain protein showed the highest affinity for the surface protein of HCT 116 cells compared to that of different types of cancer cells. This showed that the S519G mutant H domain protein gene replaced the same part of the original HN protein gene, and S519G mutant recombinant NDV (rNDV) was constructed and recovered. S519G rNDV cancer cell killing effects were tested using the MTT assay with various cancer cell types, and the tumor suppression effect of the S519G mutant rNDV was tested in a xenograft mouse model implanted with cancer cells, including HCT 116 cells.

Results
S519G rNDV showed increased specificity and enhanced killing ability of HCT 116 cells among various cancer cells and a stronger suppressive effect on tumor growth than the original recombinant NDV. Directed evolution using an artificial amino acid change in the NDV HN (S519G mutant) protein increased its specificity and oncolytic effect in colorectal cancer without changing its virulence.

Conclusion
These results provide a new methodology for the use of directed evolution technology for more effective oncolytic virus development.