Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of virtual reality simulation training on the response capability of public health emergency reserve nurses in China: a quasiexperimental study

Objective To develop a virtual reality simulation training programme, and further verify the effect of the programme on improving the response capacity of emergency reserve nurses confronting public health emergencies. Design A prospective quasiexperimental design with a control group. Participants A total of 120 nurses were recruited and randomly divided into the control group and the intervention group. Intervention Participants underwent a 3-month training. The control group received the conventional training of emergency response (eg, theoretical lectures, technical skills and psychological training), while the intervention group underwent the virtual reality simulation training in combination with skills training. The COVID-19 cases were incorporated into the intervention group training, and the psychological training was identical to both groups. At the end of the training, each group conducted emergency drills twice. Before and after the intervention, the two groups were assessed for the knowledge and technical skills regarding responses to fulminate respiratory infectious diseases, as well as the capacity of emergency care. Furthermore, their pandemic preparedness was assessed with a disaster preparedness questionnaire. Results After the intervention, the scores of the relevant knowledge, the capacity of emergency care and disaster preparedness in the intervention group significantly increased (p<0.01). The score of technical skills in the control group increased more significantly than that of the intervention group (p<0.01). No significant difference was identified in the scores of postdisaster management in two groups (p>0.05). Conclusion The virtual reality simulation training in combination with technical skills training can improve the response capacity of emergency reserve nurses as compared with the conventional training. The findings of the study provide some evidence for the emergency training of reserve nurses in better response to public health emergencies and suggest this methodology is worthy of further research and popularisation.
Glutathione contributes to resistance responses to TMV through a differential modulation of salicylic acid and reactive oxygen species

Abstract Systemic acquired resistance (SAR) is induced by pathogens and confers protection against a broad range of pathogens. Several SAR signals have been characterized, but the nature of the other unknown signalling by small metabolites in SAR remains unclear. Glutathione (GSH) has long been implicated in the defence reaction against biotic stress. However, the mechanism that GSH increases plant tolerance against virus infection is not entirely known. Here, a combination of a chemical, virus‐induced gene‐silencing‐based genetics approach, and transgenic technology was undertaken to investigate the role of GSH in plant viral resistance in Nicotiana benthamiana. Tobacco mosaic virus (TMV) infection results in increasing the expression of GSH biosynthesis genes NbECS and NbGS, and GSH content. Silencing of NbECS or NbGS accelerated oxidative damage, increased accumulation of reactive oxygen species (ROS), compromised plant resistance to TMV, and suppressed the salicylic acid (SA)‐mediated signalling pathway. Application of GSH or l‐2‐oxothiazolidine‐4‐carboxylic acid (a GSH activator) alleviated oxidative damage, decreased accumulation of ROS, elevated plant local and systemic resistance, enhanced the SA‐mediated signalling pathway, and increased the expression of ROS scavenging‐related genes. However, treatment with buthionine sulfoximine (a GSH inhibitor) accelerated oxidative damage, elevated ROS accumulation, compromised plant systemic resistance, suppressed the SA‐mediated signalling pathway, and reduced the expression of ROS‐regulating genes. Overexpression of NbECS reduced oxidative damage, decreased accumulation of ROS, increased resistance to TMV, activated the SA‐mediated signalling pathway, and increased the expression of the ROS scavenging‐related genes. We present molecular evidence suggesting GSH is essential for both local and systemic resistance of N. benthamiana to TMV through a differential modulation of SA and ROS.
The benefits of early intervention using lenalidomide for high-risk smoldering multiple myeloma: emerging data and its promising clinical impact

ABSTRACT Introduction Multiple myeloma is preceded by the early stages: monoclonal gammopathy of unknown significance (M.G.U.S.) and smoldering myeloma (S.M.M.), which are less genomically complex and where patients are overall healthier with preserved quality of life. Areas covered This review focuses on the current evidence in risk stratification and initial therapy for these patients with the goal to delay progression to and/or cure multiple myeloma. Expert opinion Advances in the understanding of the factors that contribute to myeloma evolution coupled with new therapeutics that have high efficacy and limited toxicity have revolutionized our approach to early myeloma. Although our current recommendation continues to be to observe S.M. M. outside of clinical trials, the clinical benefit of lenalidomide sets the stage for combinations with immunotherapy, which, in our opinion, will likely lead to regulatory approvals and more widespread treatment of early myeloma.
Predictive Value of MRP-1 in Localized High-Risk Soft Tissue Sarcomas: A Translational Research Associated to ISG-STS 1001 Randomized Phase III Trial

MRP-1 is implicated in multidrug resistance and was described as prognostic in high-risk patients with soft-tissue sarcoma (STS) in a previous study. The current research aimed to validate MRP-1 prognostic/predictive value in localized sarcomas treated with anthracyclines plus ifosfamide within the ISG-1001 phase III study. In addition, the inhibitory activity on MRP-1 was investigated in preclinical studies to identify new combinations able to increase the efficacy of standard chemotherapy in STS. MRP-1 expression was assessed by IHC in tissue microarrays from patients with STS and tested for correlation with disease-free survival (DFS) and overall survival (OS). In vitro studies tested the efficacy of MRP-1 inhibitors (nilotinib, ripretinib, selumetinib, and avapritinib) in sarcoma cell lines. The effect of combinations of the most active MRP-1 inhibitors and chemotherapy was measured on the basis of apoptosis. MRP-1 was evaluable in 231 of 264 cases who entered the study. MRP-1 expression (strong intensity) was independently associated with worse DFS [HR, 1.78; 95% confidence interval (CI), 1.11–2.83; P = 0.016], in the multivariate analysis, with a trend for a worse OS (HR, 1.78; 95% CI, 0.97–3.25; P = 0.062). In vitro studies showed that the addition of MRP-1 inhibitors (nilotinib or avapritinib) to doxorubicin plus palifosfamide, significantly increased cell death in SK-UT-1 and CP0024 cell lines. MRP-1 is an adverse predictive factor in localized high-risk patients with STS treated with neoadjuvant anthracyclines plus ifosfamide followed by surgery. In vitro findings support the clinical assessment of the combination of chemotherapy and MRP-1 inhibitors as a promising strategy to overcome the drug ceiling effect for chemotherapy.
The cost-effectiveness of an adjuvanted quadrivalent influenza vaccine in the United Kingdom

ABSTRACT In the United Kingdom (UK), both the MF59-adjuvanted quadrivalent influenza vaccine (aQIV) and the high-dose QIV (QIV-HD) are preferred for persons aged 65 years and older but only aQIV is reimbursed by the National Health Service (NHS). The objective was to determine the potential cost-effectiveness of vaccinating adults aged 65 years and above with aQIV compared with QIV-HD in the UK. A dynamic transmission model, calibrated to match infection data from the UK, was used to estimate the impact of vaccination in 10 influenza seasons. Vaccine effectiveness was based on a meta-analysis that concluded the vaccines were not significantly different. Vaccine coverage, physician visits, hospitalizations, deaths, utility losses and NHS costs were estimated using published UK sources. The list price of aQIV was £11.88 while a range of prices were tested for QIV-HD. The price of the trivalent high-dose vaccine (TIV-HD) is £20.00 but a list price for QIV-HD is not yet available. The projected differences between the vaccines in terms of clinical cases and influenza treatment costs are minimal. Our analysis demonstrates that in order to be cost-effective, the price of QIV-HD must be similar to that of aQIV and may range from £7.57 to £12.94 depending on the relative effectiveness of the vaccines. The results of the analysis were most sensitive to variation in vaccine effectiveness and the rate of hospitalization due to influenza. Given the evidence, aQIV is cost-saving unless QIV-HD is priced lower than the existing list price of TIV-HD.
Safety and Efficacy of Direct Oral Anticoagulants in Patients With Moderate to Severe Cirrhosis

Background: Direct oral anticoagulants (DOACs) remain mostly investigational in patients with moderate to severe hepatic cirrhosis, yet are often selected over traditional anticoagulants including warfarin and enoxaparin in this setting. Objective: To determine the safety and efficacy of DOACs in patients with moderate to severe hepatic cirrhosis as compared with traditional anticoagulation. Methods: This was a retrospective, single-center cohort study evaluating inpatients and outpatients who were prescribed a DOAC, warfarin, or enoxaparin for therapeutic anticoagulation with Child-Turcotte-Pugh (CTP) B or C status at the time that the prescription was written. Included patients were followed until first bleeding or thromboembolic event, or until discontinuation of anticoagulation therapy. Data were collected by manual chart review. The primary outcomes included both bleeding events and thromboembolic events in the DOAC population as compared with traditional anticoagulation. Results: A total of 101 patients were included in the study, 69 treated with DOAC therapy and 32 with traditional anticoagulation. Bleeding events occurred in 36% of patients in the DOAC group and 22% of patients in the traditional group (P = 0.149). In both groups, bleeds were most commonly gastrointestinal. Thromboembolic events occurred in 4% of the DOAC population and no patients in the traditional population (P = 0.55). No fatal bleeding or thromboembolic events occurred. Conclusion and Relevance: DOACs do not appear to be more harmful than traditional anticoagulation in patients with CTP B or C status. These results support the use of DOACs in patients with CTP B or C hepatic cirrhosis when considering safety, efficacy, and convenience.
ZNF598 co-translationally titrates poly(GR) protein implicated in the pathogenesis of C9ORF72-associated ALS/FTD

Abstract C9ORF72-derived dipeptide repeat proteins have emerged as the pathogenic cause of neurodegeneration in amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). However, the mechanisms underlying their expression are not fully understood. Here, we demonstrate that ZNF598, the rate-limiting factor for ribosome-associated quality control (RQC), co-translationally titrates the expression of C9ORF72-derived poly(GR) protein. A Drosophila genetic screen identified key RQC factors as potent modifiers of poly(GR)-induced neurodegeneration. ZNF598 overexpression in human neuroblastoma cells inhibited the nuclear accumulation of poly(GR) protein and decreased its cytotoxicity, whereas ZNF598 deletion had opposing effects. Poly(GR)-encoding sequences in the reporter RNAs caused translational stalling and generated ribosome-associated translation products, sharing molecular signatures with canonical RQC substrates. Furthermore, ZNF598 and listerin 1, the RQC E3 ubiquitin-protein ligase, promoted poly(GR) degradation via the ubiquitin-proteasome pathway. An ALS-relevant ZNF598R69C mutant displayed loss-of-function effects on poly(GR) expression, as well as on general RQC. Moreover, RQC function was impaired in C9-ALS patient-derived neurons, whereas lentiviral overexpression of ZNF598 lowered their poly(GR) expression and suppressed proapoptotic caspase-3 activation. Taken together, we propose that an adaptive nature of the RQC-relevant ZNF598 activity allows the co-translational surveillance to cope with the atypical expression of pathogenic poly(GR) protein, thereby acquiring a neuroprotective function in C9-ALS/FTD.
Guillain-Barré syndrome after SARS-CoV-2 infection in an international prospective cohort study

Abstract In the wake of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, an increasing number of patients with neurological disorders, including Guillain-Barré syndrome (GBS), have been reported following this infection. It remains unclear, however, if these cases are coincidental or not, as most publications were case reports or small regional retrospective cohort studies. The International GBS Outcome Study is an ongoing prospective observational cohort study enrolling patients with GBS within 2 weeks from onset of weakness. Data from patients included in this study, between 30 January 2020 and 30 May 2020, were used to investigate clinical and laboratory signs of a preceding or concurrent SARS-CoV-2 infection and to describe the associated clinical phenotype and disease course. Patients were classified according to the SARS-CoV-2 case definitions of the European Centre for Disease Prevention and Control and laboratory recommendations of the World Health Organization. Forty-nine patients with GBS were included, of whom eight (16%) had a confirmed and three (6%) a probable SARS-CoV-2 infection. Nine of these 11 patients had no serological evidence of other recent preceding infections associated with GBS, whereas two had serological evidence of a recent Campylobacter jejuni infection. Patients with a confirmed or probable SARS-CoV-2 infection frequently had a sensorimotor variant 8/11 (73%) and facial palsy 7/11 (64%). The eight patients who underwent electrophysiological examination all had a demyelinating subtype, which was more prevalent than the other patients included in the same time window [14/30 (47%), P = 0.012] as well as historical region and age-matched control subjects included in the International GBS Outcome Study before the pandemic [23/44 (52%), P = 0.016]. The median time from the onset of infection to neurological symptoms was 16 days (interquartile range 12–22). Patients with SARS-CoV-2 infection shared uniform neurological features, similar to those previously described in other post-viral GBS patients. The frequency (22%) of a preceding SARS-CoV-2 infection in our study population was higher than estimates of the contemporaneous background prevalence of SARS-CoV-2, which may be a result of recruitment bias during the pandemic, but could also indicate that GBS may rarely follow a recent SARS-CoV-2 infection. Consistent with previous studies, we found no increase in patient recruitment during the pandemic for our ongoing International GBS Outcome Study compared to previous years, making a strong relationship of GBS with SARS-CoV-2 unlikely. A case-control study is required to determine if there is a causative link or not.
The patellar ligament: A comprehensive review

The patellar ligament (PL) is an epiphyseal ligament and is part of the extensor complex of the knee. The ligament has gained attention due to its clinical relevance to autograft and tendinopathy. A variety of anatomical variations of the PL such as aplasia, numerical variations, and vascularity are being reported recently by clinicians and anatomists. The aim of this literature was to review the available literature to provide a consensus regarding anatomic variations of the PL, neurovasculature surrounding the PL, histology of the PL, and various aspects of PL measurements with relevance to the surgical considerations and sex and age‐related differences. A narrative review of the patellar ligament was performed by conducting a detailed literature search and review of relevant articles. A total of 90 articles on the patellar ligament were included and were categorized into studies based on anatomical variations, neurovasculature, morphometrics, microanatomy, sex and age‐related difference, and ACL reconstruction. The anatomical variations and morphometrics of the PL were found to correlate with the frequency of strain injuries, tendinopathy, and efficacy of the PL autograft in anterior cruciate ligament reconstruction. The sex differences in PL measurements and the effect of estrogen on collagen synthesis explained a higher incidence of patellar tendinopathy in women. An awareness of its variations enables careful selection of surgical incisions, thereby avoiding complications related to nerve injury. Accurate knowledge of the PL microanatomy assists in understanding the mechanism of ligament degeneration, rupture, autograft harvesting, and ligamentization results.
COVID‐19 and dental workers: The Italian Society of Periodontology and Implantology (SIdP) survey

Abstract Objectives To evaluate the proportion of COVID‐19 infections among a population of Italian Dental workers across different geographical area of Italy and to analyze the impact of both the preventive measures/strategies adopted and the psychological influences. Subjects and Methods The current cross‐sectional survey was administered with a web‐based form. To be eligible for the study, participants had to be 18 years and being dentists or dental hygienists members of the Italian Society of Periodontology and Implantology (SIdP). A 23‐item questionnaire concerning positiveness to COVID‐19, clinical strategies and psychological attitude within the pandemic was administered. Sub‐group analysis was conducted according to geographical macro‐area. Results A total of 790 dentists and dental hygienists were included. A total of 4.7% participants developed a positive diagnosis to COVID‐19. The Northwest of Italy experienced almost double of COVID‐19‐positive participants (p < 0.05). Preoperatory mouthwashes together with natural air change/ventilation were the most frequent approaches used to prevent COVID‐19 outbreak. Positive and proactive attitudes were predominant among participants. Only a reduced proportion feels some concerns for the future. Conclusions Prevalence of positive COVID‐19 among dental workers in Italy was double in Northwest area in comparison with the whole country proportion. Preventive strategies comprise mainly ultrasound reduction and preoperative mouthwashes.
Cx32 inhibits the autophagic effect of Nur77 in SH-SY5Y cells and rat brain with ischemic stroke

The pathogenesis of cerebral ischemia-reperfusion (I/R) is complex. Cx32 expression has been reported to be up-regulated in ischemic lesions of aged human brain. Nevertheless, the function of Cx32 during cerebral I/R is poorly understood. Autophagy is of vital importance in the pathogenesis of cerebral I/R. In the current study, we found that oxygen-glucose deprivation/reoxygenation (OGD/R) or I/R insult significantly induced the up-regulation of Cx32 and activation of autophagy. Inhibition of Cx32 alleviated OGD/R or I/R injury, and further activated autophagy. In addition, Nur77 expression was found to be up-regulated after OGD/R or I/R. After inhibiting Cx32, the expression of Nur77 was further increased and Nur77 was translocated from nucleus to mitochondrial. Inhibition of Cx32 also activated mitophagy by promoting autophagosome formation and up-regulating the expression of mitochondrial autophagy marker molecules. Of note, in the siNur77-transfected cells, the number of dysfunctional mitochondrial was increased, and mitophagy was suppressed, which aggravated OGD/R-induced neuronal injury. In conclusion, Cx32 might act as a regulatory factor of Nur77 controlling neuronal autophagy in the brains. Understanding the mechanism of this regulatory pathway will provide new insight into the role Cx32 and Nur77 in cerebral ischemia, offering new opportunities for therapeutics.
Speed of Movement, Fatness, and the Change in Cardiometabolic Risk Factors in Children

Abstract We aimed to examine speed of movement and its interactive association with fatness to changes in cardiometabolic risk factors over one year in children. The analysis included 8345 children aged 6–13 years. Cardiometabolic risk score was computed by summing Z-scores of waist circumference, the average of systolic and diastolic blood pressure, fasting glucose, high-density lipoprotein cholesterol (multiplied by −1), and triglycerides. Both high baseline and improvement in speed of movement were associated with favourable changes in percent body fat, lipids, and cardiometabolic risk score. Percentages of the association between baseline speed of movement and changes in cardiometabolic risk score, triglycerides, and high-density lipoprotein cholesterol explained by baseline BMI were 24.6% (19.6–29.1%), 26.2% (19.7–31.1%), and 12.5% (9.6–15.4%), respectively. The corresponding number for percent body fat was 47.0% (40.4–54.1%), 43.3% (36.7–51.7%), and 29.8% (25.0–34.6%), respectively. Speed of movement mediated the association between fatness and cardiometabolic risk factors. Improved speed of movement was associated with a lower increase in blood pressure in obese children only. Speed of movement is a strong predictor of changes in cardiometabolic risk factors. Fatness and speed of movement are interactively associated with cardiometabolic risk factors. Speed of movement may attenuate the positive association between fatness and blood pressure.
Clinical efficacy and safety of novel lipoglycopeptides in the treatment of acute bacterial skin and skin structure infections: a systematic review and meta-analysis of randomized controlled trials

ABSTRACT Background This systematic review and meta-analysis aimed to investigate the clinical efficacy and safety of novel lipoglycopeptides in treating acute bacterial skin and skin structure infections (ABSSSIs). Research design and methods PubMed, Embase, Cochrane Central Register of Controlled Trials, Turning Research into Practice, and ClinicalTrials.gov were searched from inception to 20 May 2021. Randomized controlled trials (RCTs) comparing the clinical efficacy and safety of lipoglycopeptides with other comparators in treating adult patients with ABSSSIs were included. The primary outcome was clinical response. Results Eight RCTs (6416 patients; lipoglycopeptides: 3359, comparators: 3057) were enrolled. Clinical response rate was not significantly different between lipoglycopeptides and comparators at early-clinical-evaluation (odds ratio [95% confidence interval]: 1.01 [0.85–1.20], I 2 = 34%), end-of-treatment (0.94 [0.80–1.11], I 2 = 0%), and test-of-cure (1.05 [0.85–1.30], I 2 = 0%). Lipoglycopeptides showed a similar overall microbiological eradication rate (1.12 [0.90–1.38], I 2 = 21%) but a borderline higher microbiological eradication rate for methicillin-resistant Staphylococcus aureus (1.37 [1.00–1.86], I 2 = 0%) than the comparators. Lipoglycopeptides were not associated with a higher risk than comparators. Conclusions Lipoglycopeptides can achieve similar clinical and microbiological responses to other comparators in treating ABSSSIs. In addition, lipoglycopeptides are as tolerable as their comparators.