Miracle-dz/UniFAR-FTUs huggingface dataset:
Ethics issues identified by applicants and ethics experts in Horizon 2020 grant proposals

Background: We assessed the ethics review of proposals selected for funding under the Marie Skłodowska-Curie Actions (MSCA) and the European Research Council (ERC) in Horizon 2020, EU’s framework programme for research and innovation, 2014-2020. Methods: We analysed anonymized datasets for 3,054 MSCA individual fellowships (IF), 417 MSCA Innovative Training Networks (ITN), and 1,465 ERC main-listed proposals with ethics conditional clearance, over four years (2016 to 2019). The datasets included the information on ethics issues identified by applicants in their proposal and ethics issues and requirements identified by ethics experts during the ethics review. Results: 42% of proposals received ethical clearance. For proposals with conditional ethics clearance (n=3546), most of the identified ethics issues by both applicants and ethics experts were in the ethics categories related to humans; protection of personal data; environment, health and safety; and non-EU countries. Ethics experts identified twice as many ethics issues compared to applicants across funding schemes, years, and from high- and low-research performing countries. ERC grants had the highest number of ethics requirements per proposal (median (Md)=8, interquartile range (IQR=4-14), compared to ITN (Md=6, IQR=3-13) and IF grants (Md=3, IQR=2-6). The majority of requirements had to be fulfilled after grant agreement: 99.4% for IF, 99.5% for ITN, and 26.0% for ERC. For 9% of the proposals, the requirements included the appointment of an independent ethics advisor and 1% of the proposals had to appoint an ethics advisory board. Conclusions: Many applicants for highly competitive H2020 funding schemes lack awareness of ethics issues raised by their proposed research. There is a need for better training of researchers at all career stages about ethics issues in research, more support to researchers from research organizations to follow the funding agencies requirements, as well as further development and harmonization of the ethics appraisal process during grant assessment.
Development of a Three-Dimensionally Printed Ultrasound-Guided Peripheral Intravenous Catheter Phantom

Introduction Ultrasound-guided peripheral intravenous catheter (US-PIVC) placement is an effective technique to establish PIV access when the traditional approach fails. Many training programs utilize commercial or homemade phantoms for procedural training. However, commercial products tend to be expensive and lack realism, while homemade blocks tend to be single-use and degrade easily. Thanks to the increasing availability of three-dimensional (3D) printers in academic settings, we sought to design and develop a reusable 3D-printed US-PIVC phantom and to evaluate its utility in terms of time needed to achieve IV placement and perceived realism compared to a commercial model among a group of emergency medicine (EM) physicians. Methods The upper extremity vascular phantom was constructed using 3D printing and casting techniques. A convenience sampling of EM physicians was timed by placing a US-PIVC in the 3D-printed and commercial models. Participants were also surveyed to assess their impression of the realism of the models. The primary outcome was the time required for US-PIVC placement in the 3D-printed model compared to the commercial model. Secondary outcomes were the assessment of differences in perceived realism and total cost between the two models. Results Twenty-one EM physicians completed the study. There were no significant differences in the mean time (seconds) for US-PIVC placement in the 3D-printed model (31, SD: 21) compared to the commercial model (30, SD: 18), p=0.77. Mean realism score trended higher for the 3D-printed model (3.6, SD: 0.9) compared to the commercial model (3.1, SD: 1.0), p=0.10. The total cost for the 3D-printed model was $120, with the interchangeable replacement part costing $21, which was much cheaper compared to the commercial phantom, which cost $549. Conclusion We developed a 3D-printed reusable US-PIVC phantom, and it proved to be more economical without sacrificing the realism and time required for US-PIVC placement when compared to a commercial phantom.
The Psychological Impact of Coronavirus Pandemic Restrictions in Italy. The Mediating Role of the Fear of COVID-19 in the Relationship between Positive and Negative Affect with Positive and Negative Outcomes

Italy was quickly hit hard by the coronavirus. ‘Lockdown’ has significantly impacted the psychological health, personal wellbeing and quality of life of the people. The study aims to explore the relationship between positive and negative affect, as well as positive (spiritual well-being and flourishing) and negative outcomes (psychological distress caused by a traumatic life event in terms of perception of PTSD symptoms) on Italian adults during the lockdown period. Data was collected between April and May 2020. The participants were 281 Italian adults aged between 18 and 73 years. The survey was composed of the following measures: Flourishing Scale, Jarel Spiritual Well-Being scale, Positive and Negative Affect Schedule, Impact of Event Scale—Revised, Fear of COVID-19. The mediational analysis shows that fear of COVID-19 fully mediates the relationship between negative affect and spiritual well-being and flourishing; fear of COVID-19 partially mediates the relationship between negative affect and PTSD symptoms; the positive affect shows only direct effects on positive outcomes. Therefore, fear of COVID-19 does not play any mediation role. Implications for psychological interventions and future research will be discussed.
Posterolateral corner knee injuries: a narrative review

Limited knowledge of the anatomy and biomechanics of the posterolateral corner (PLC) of the knee, coupled with poor patient outcomes with non-operative management, resulted in the PLC often being labelled as the ‘dark side’ of the knee. In the last two decades, extensive research has resulted in a better understanding of the anatomy and function of the PLC, and has led to the development of anatomic reconstructions that have resulted in improved patient outcomes. Despite considerable attention in the clinical orthopaedic literature (nearly 400 articles published in the last decade), a standardized algorithm for the diagnosis and treatment of the PLC is still lacking, and much controversy remains. Considering the literature review, there is not a reconstruction technique that clearly prevails over the others. As anatomic, biomechanical, and clinical knowledge of PLC injuries continues to progress, finding the balance between re-creating native anatomy and safely performing PLC reconstruction provides a big challenge. Treatment decisions should be made on a case-by-case basis. Cite this article: EFORT Open Rev 2021;6:676-685. DOI: 10.1302/2058-5241.6. 200096
The impact of COVID‐19 on consumer evaluation of authentic advertising messages

Abstract This study investigates the relationship between the COVID‐19 threat and consumer evaluation of a product with authenticity appeals in advertisements. We propose that threatening situations like COVID‐19 motivate consumers to lower their uncertainty and increase their preference for products with authentic advertising messages. Because individuals react differently to threatening environments according to their early‐life experiences, commonly reflected in childhood socioeconomic status, we examined whether childhood socioeconomic status moderates the relationship between threat and consumer evaluation of authenticity in advertisements. First, secondary data from Google Trends provided empirical support for our predictions. In additional experimental studies, participants evaluated different target products in four studies that either manipulated (Studies 2 and 3) or measured (Studies 4 and 5) COVID‐19 threat. Our results provide converging evidence that consumers positively evaluate products with authentic advertising messages under the COVID‐19 threat. Consumers' motivation to lower their uncertainty underlies the effect of COVID‐19 threat on their evaluation of authentic messages (Study 3). This attempt to reduce uncertainty is more likely to occur for consumers with relatively higher childhood socioeconomic status (Studies 4 and 5). These findings suggest that using authenticity appeals during a pandemic could effectively reduce consumers' perceived uncertainty and generate positive consumer evaluations.
Potato Leaf Disease Diagnosis and Detection System Based on Convolution Neural Network

For decades, agriculture has been an essential food source. According to related statics, over 60% of the total earth population mainly depend on agriculture’s sources for their primary feed. Unfortunately, one of the disaster problems that affect badly on agriculture production is plant diseases. There are about 25% of agriculture production lost annually because of plant diseases. Late and Early Blight diseases are one of the most destructive diseases that infect potato crop. Although, the late and inaccurate detection of plant diseases increases the losing percentage for the crop. The main approach of our proposed system is to detect early the plant diseases to decrease the plant’s production losses by using a diagnosis and detection system based on the Convolution Neural Network (CNN). We used CNN to extract the diseases features from the input images of the supported training dataset for classification purposes. For model training, 1700 of potato leaf images were used, then the testing process is done by using approximately 300 images and 100 images for fine tuning and parameters calibration against any biased data. Our proposed CNN architecture archives 98.2% accuracy, which is higher compared with other approaches run on the same dataset.
Soluble CD127 potentiates IL‐7 activity in vivo in healthy mice

Soluble forms of cytokine receptors can be involved in the endogenous regulation of cytokine activity. Soluble interleukin 7 receptor α (sCD127) naturally binds IL‐7, therefore there is interest in its potential application as an immunotherapeutic agent to regulate IL‐7. With the hypothesis that sCD127 enhances IL‐7 activity, thus promoting T‐cell proliferation in vivo, we sought to assess the effect of sCD127, IL‐7 or IL‐7 + sCD127 treatment on CD4+ and CD8+ T‐cells in the blood and spleen of mice.
Computational drug repositioning of atorvastatin for ulcerative colitis

Abstract Objective Ulcerative colitis (UC) is a chronic inflammatory disorder with limited effective therapeutic options for long-term treatment and disease maintenance. We hypothesized that a multi-cohort analysis of independent cohorts representing real-world heterogeneity of UC would identify a robust transcriptomic signature to improve identification of FDA-approved drugs that can be repurposed to treat patients with UC. Materials and Methods We performed a multi-cohort analysis of 272 colon biopsy transcriptome samples across 11 publicly available datasets to identify a robust UC disease gene signature. We compared the gene signature to in vitro transcriptomic profiles induced by 781 FDA-approved drugs to identify potential drug targets. We used a retrospective cohort study design modeled after a target trial to evaluate the protective effect of predicted drugs on colectomy risk in patients with UC from the Stanford Research Repository (STARR) database and Optum Clinformatics DataMart. Results Atorvastatin treatment had the highest inverse-correlation with the UC gene signature among non-oncolytic FDA-approved therapies. In both STARR (n = 827) and Optum (n = 7821), atorvastatin intake was significantly associated with a decreased risk of colectomy, a marker of treatment-refractory disease, compared to patients prescribed a comparator drug (STARR: HR = 0.47, P = .03; Optum: HR = 0.66, P = .03), irrespective of age and length of atorvastatin treatment. Discussion & Conclusion These findings suggest that atorvastatin may serve as a novel therapeutic option for ameliorating disease in patients with UC. Importantly, we provide a systematic framework for integrating publicly available heterogeneous molecular data with clinical data at a large scale to repurpose existing FDA-approved drugs for a wide range of human diseases.
Multiple basic amino acids in the cleavage site of H7N9 hemagglutinin contribute to high virulence in mice

Background Avian influenza A (H7N9) virus has caused more than 1,500 cases of human infection since its emergence in early 2013. Displaying little or no pathogenicity in poultry, but a 40% case-fatality rate in humans, five waves of H7N9 human infections occurred in China during 2013–2017, caused solely by a low pathogenicity strain. However, avian isolates possessing a polybasic connecting peptide in the hemagglutinin (HA) protein were detected in mid-2016, indicating that a highly pathogenic virus had emerged and was co-circulating with the low pathogenicity strains. Methods Here we characterize the pathogenicity of a newly emerged human H7N9 variant with a PEVPKRKRTAR/GLF insertion motif at the cleavage site of the HA protein in vitro and in vivo. Results This variant replicates in MDCK cells independently of TPCK-trypsin, which is indicative of high pathogenicity in chickens. The 50% mouse lethal dose (MLD50) of this novel isolate was less than 10 plaque forming units (PFU), compared with 3.16×104 for an identical virus lacking the polybasic insertion, indicating a high virulence phenotype. Conclusions Our results demonstrate that the multiple basic amino acid insertion in the HA protein of the H7N9 variant confers high virulence in mammals, highlighting a potential risk to humans. Continuous viral surveillance is therefore necessary in the China region to improve pandemic preparedness.
Does Mammotome biopsy affect surgery option and margin status of breast conserving surgery in breast cancer?

Background The Mammotome, an image-guided, usually ultrasound-guided vacuum-assisted breast biopsy (US-VABB) system, has been widely used in the early diagnosis of breast disease and the complete excision of benign lesions. However, in some malignant lesions underestimated by U.S., whether Mammotome biopsy would affect the surgery option, especially the margin status in breast-conserving surgery (BCS), has never been studied. Methods Between 2015 and 2019, 198 patients with 200 lesions who have been diagnosed with breast cancer by Mammotome elsewhere received surgery by pathological confirmation in our center. The clinicopathological characteristics, surgery options, therapies, and the details of the specimen, such as margin status of BCS, tumor residual after VABB, and hematoma were reviewed. Results Among 200 lesions, 90% were evaluated below US-BIRADS 4b before Mammotome biopsy and 94.5% with a tumor size ≤3 cm. 131 patients received mastectomy (66.2%) and 67 received BCS (33.8%). Hematoma and tumor residual were observed in 37.5% and 71.5% of all lesions, respectively. There is a higher incidence of hematoma in the mastectomy group than in the BCS group (44.4% vs. 23.9%, P=0.005). In BCS group, the positive margin was found in 7 patients at first examination including four focals with re-excision, two extensive with mastectomy and one focal but refusing further surgery. The ultimate success rate of BCS was 95.5%. Margin positivity correlated with tumor residual (P=0.044) but not with hematoma. Conclusions Mammotome biopsy might lead to hematoma and tumor residual; however, it is not the determinant factor for a surgery option, and BCS is feasible through a complete excision of tumor residual to acquire negative margin.
Wolframin-1–expressing neurons in the entorhinal cortex propagate tau to CA1 neurons and impair hippocampal memory in mice

Description Wolframin-1–positive neurons in the entorhinal cortex of mouse brain propagate tau to the hippocampal CA1 region resulting in memory impairment. A neuronal highway for tau Abnormally phosphorylated tau has been observed in the entorhinal cortex layer II (ECII) of the brain and from there spreads to the hippocampal CA1 region during the early stages of Alzheimer’s disease. Here, Delpech et al. develop an animal model that recapitulates this early tau spreading pathology. They show that expressing human mutant tau specifically in Wolframin-1–positive neurons of the ECII of mouse brain resulted in transfer of tau specifically to the hippocampal CA1 area. This was accompanied by memory impairment and reduced activity of CA1 pyramidal neurons, suggesting that this neuronal pathway should be investigated further in Alzheimer’s disease. Abnormally phosphorylated tau, an early neuropathologic marker of Alzheimer’s disease (AD), first occurs in the brain’s entorhinal cortex layer II (ECII) and then spreads to the CA1 field of the hippocampus. Animal models of tau propagation aiming to recapitulate this phenomenon mostly show tau transfer from ECII stellate neurons to the dentate gyrus, but tau pathology in the dentate gyrus does not appear until advanced stages of AD. Wolframin-1–expressing (Wfs1+) pyramidal neurons have been shown functionally to modulate hippocampal CA1 neurons in mice. Here, we report that Wfs1+ pyramidal neurons are conserved in the ECII of postmortem human brain tissue and that Wfs1 colocalized with abnormally phosphorylated tau in brains from individuals with early AD. Wfs1+ neuron–specific expression of human P301L mutant tau in mouse ECII resulted in transfer of tau to hippocampal CA1 pyramidal neurons, suggesting spread of tau pathology as observed in the early Braak stages of AD. In mice expressing human mutant tau specifically in the ECII brain region, electrophysiological recordings of CA1 pyramidal neurons showed reduced excitability. Multielectrode array recordings of optogenetically stimulated Wfs1+ ECII axons resulted in reduced CA1 neuronal firing. Chemogenetic activation of CA1 pyramidal neurons showed a reduction in c-fos+ cells in the CA1. Last, a fear conditioning task revealed deficits in trace and contextual memory in mice overexpressing human mutant tau in the ECII. This work demonstrates tau transfer from the ECII to CA1 in mouse brain and provides an early Braak stage preclinical model of AD.
Infection hospitalisation in systemic lupus in Sweden

Objective Immune dysregulation in SLE and the corresponding immune-modulating and immunosuppressive nature of the treatments may play key roles in infection risk. We compared serious infection rates among individuals with incident SLE with the general population, and examined the role of treatment initiation in SLE. Methods Newly diagnosed patients with SLE (2006–2013) and general population comparators from the Swedish Lupus Linkage cohort were followed for serious infection through 2016. Adjusted Cox and frailty models estimated the relative risk of first and recurrent infections, respectively. Using a new-user design, rates of serious infections were compared between disease-modifying antirheumatic drugs (DMARDs) and hydroxychloroquine (HCQ) initiators. We then evaluated three DMARDs (azathioprine, mycophenolate mofetil and methotrexate) in multivariable-adjusted models. Results Individuals with SLE experienced more infections (22% vs 6%), especially during the first year of follow-up, and recurrent serious infections were also more common (HR=2.22, 95% CI 1.93 to 2.56). DMARDs were associated with a higher rate of serious infection versus HCQ (HR=1.82, 95% CI 1.27 to 2.60), which attenuated after multivariable-adjustment (HR=1.30, 95% CI 0.86 to 1.95). Among DMARDs, azathioprine was associated with infection (HR=2.19, 95% CI 1.14 to 4.21) and mycophenolate mofetil yielded an HR=1.39 (95% CI 0.65 to 2.96) in multivariable-adjusted models compared with methotrexate. Results were comparable across numerous sensitivity analyses. Conclusion Individuals with incident SLE were 2–4 times more likely to be hospitalised for infection and experienced more recurrent infections than the general population. Among DMARD initiators, azathioprine was associated with the highest rate.
Elucidating the Potential Side Effects of Current Anti-Seizure Drugs for Epilepsy

Over the decades, various interventions have been developed and utilized to treat epilepsy. However, the majority of epileptic patients are often first prescribed anti-epileptic drugs (AED), now known as anti-seizure drugs (ASD), as the first line of defense to suppress their seizures and regain their quality of life. ASDs exert their anti-convulsant effects through various mechanisms of action, including regulation of ion channels, blocking glutamate-mediated stimulating neurotransmitter interaction, and enhancing the inhibitory GABA transmission. About one-third of epileptic patients are often resistant to anti-convulsant drugs, while others develop numerous side effects, which may lead to treatment discontinuation and further deterioration of quality of life. Common side effects of ASDs include headache, nausea and dizziness. However, more adverse effects, such as auditory and visual problems, skin problems, liver dysfunction, pancreatitis and kidney disorders may also be witnessed. Some ASDs may even result in life-threatening conditions as well as serious abnormalities, especially in patients with comorbidities and in pregnant women. Nevertheless, some clinicians had observed a reduction in the development of side effects post individualized ASD treatment. This suggests that a careful and well-informed ASD recommendation to patients may be crucial for an effective and side-effect-free control of their seizures. Therefore, this review aimed to elucidate the anticonvulsant effects of ASDs as well as their side effect profile by discussing their mechanism of action and reported adverse effects based on clinical and preclinical studies, thereby providing clinicians with a greater understanding of the safety of current ASDs.
Connection During COVID-19: Pilot Study of a Telehealth Group Parenting Intervention.

OBJECTIVE The COVID-19 pandemic has resulted in considerable stress for families, placing parents at risk for heightened psychological distress, while prompting widespread changes in mental health service delivery. This study evaluated treatment engagement, acceptability, and psychiatric distress among participants in the telehealth adaptation of the Connecting and Reflecting Experience (CARE) program after the onset of COVID-19. METHODS CARE is a transdiagnostic, bigenerational, mentalizing-focused group parenting intervention based out of an outpatient child mental health clinic in an underserved urban community. Individuals participating in CARE during the clinic's transition to telehealth services were recruited for participation in this pre-post design pilot study. Participants (N=12) completed self-report surveys before and after their first telehealth group session and at their 20-week follow-up. Quantitative and qualitative measures were used to evaluate psychiatric symptoms, treatment engagement, and preliminary acceptability of the adaptation. RESULTS Self-reported mood and anxiety symptoms decreased significantly after 20 weeks of telehealth therapy. Participants reported high levels of therapeutic alliance and group cohesion in the telehealth format. Results also showed minimal participant-reported privacy concerns and a trend toward increased treatment engagement. CONCLUSIONS These findings have implications regarding the acceptability of teletherapy interventions for caregivers of children during this period of heightened vulnerability and limited access to social support and health services. They also are relevant to establishing the preliminary acceptability of mentalizing-focused parenting inventions delivered via telehealth.