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Background The COVID-19 vaccination campaign in several European countries involved collaboration between public health and Primary Health Care (PHC).Objective To highlight the role of PHC professionals in the COVID-19 vaccination rollout, specifically in terms of vaccine administration, communication and contributing to vaccination population coverage.Methods A descriptive retrospective study of the COVID-19 vaccination campaign across 28 European countries was conducted, covering data from December 2020 to November 2021. Data were collected by key informants recruited from each country, who were health professionals involved in their national vaccination campaigns. Utilising an ad-hoc semi-structured questionnaire, information was gathered on organisation, communication strategies, priority groups, vaccine types, and vaccination pathways in PHC.Results PHC participated in communication strategies in 10 out of 28 countries, and vaccination was voluntary in most of them. The priority groups for vaccination varied across Europe, and the availability of vaccines in PHC differed between countries within the European Union (EU) and non-EU countries. The BioNTech Pfizer vaccine was the most widely available vaccine in most countries, followed by Moderna and AstraZeneca. PHC administered COVID-19 vaccines to the population, being the nurses the most involved, followed by general practitioners. Vaccination appointments were available online in 18/28 or by phone in 15/28, direct appointments at health centres were available in 8/28. In several countries, healthcare professionals who administered vaccines were given extra compensation for their role.Conclusion PHC professionals played a crucial role in the successful distribution and administration of COVID-19 vaccines in European countries.

Abstract Sensory neurons are afferent neurons in sensory systems that convert stimuli and transmit information to the central nervous system as electrical signals. Primary afferent neurons that are affected by non-noxious and noxious stimuli are present in the dorsal root ganglia (DRG), and the DRG sensory neurons are used as an in vitro model of the nociceptive response. However, DRG derived from mouse or rat give a low yield of neurons, and they are difficult to culture. To help alleviate this problem, we characterized human induced pluripotent stem cell (hiPSC) derived sensory neurons. They can solve the problems of interspecies differences and supply stability. We investigated expressions of sensory neuron related proteins and genes, and drug responses by Multi-Electrode Array (MEA) to analyze the properties and functions of sensory neurons. They expressed nociceptor, mechanoreceptor and proprioceptor related genes and proteins. They constitute a heterogeneous population of their subclasses. We confirmed that they could respond to both noxious and non-noxious stimuli. We showed that histamine inhibitors reduced histamine-induced neuronal excitability. Furthermore, incubation with a ProTx-II and Nav1.7 inhibitor reduced the spontaneous neural activity in hiPSC-derived sensory neurons. Their responsiveness was different from each drug. We have demonstrated that hiPSC-derived sensory neurons combined with MEA are good candidates for drug discovery studies where DRG in vitro modeling is necessary.

IntroductionThis descriptive retrospective study analyzed coronial recommendations for natural deaths in sport and recreation from January 2006 to December 2019 using data from the Bureau du coroner du Québec.MethodsReports with recommendations were analyzed by sex, age group, cause of death, context, and activity. The nature of recommendations was assessed using a public health-based model. Thematic analysis was conducted following a four-phase approach in which themes developed were emphasized and further connected with existing literature.ResultsReports involving individuals aged 18–24 and reports related to ice hockey were significantly more likely to contain recommendations. Reports related to individuals ≥45 years old, or related to cycling or hunting had higher death frequencies, but relatively low recommendation rates. Most recommendations aligned with the public health-based model but specifying implementation time frames was rare (11.7%). Nearly 60% of coroner’s recommendations focused on automated external defibrillator implementation, delivery and training.DiscussionMitigation of sudden cardiac arrest risk for individuals ≥45 years old, timely treatment of life-threatening arrhythmias especially for activity practiced in remote regions and specifying implementation time frames were identified as improvement areas. The multi-faceted approach to enhancing public access defibrillation developed by the International Liaison Committee on Resuscitation in 2022 addresses recurrent themes covered by coroners and holds the potential to inform evidence-based decision making.

AbstractBackground Most COVID-19 patients were treated in primary health care (PHC) in Europe.Objectives To demonstrate the scope of PHC workflow during the COVID-19 pandemic emphasising similarities and differences of patient’s clinical pathways in Europe.Methods Descriptive, cross-sectional study with data acquired through a semi-structured questionnaire in PHC in 30 European countries, created ad hoc and agreed upon among all researchers who participated in the study. GPs from each country answered the approved questionnaire. Main variable: PHC COVID-19 acute clinical pathway. All variables were collected from each country as of September 2020.Results COVID-19 clinics in PHC facilities were organised in 8/30. Case detection and testing were performed in PHC in 27/30 countries. RT-PCR and lateral flow tests were performed in PHC in 23/30, free of charge with a medical prescription. Contact tracing was performed mainly by public health authorities. Mandatory isolation ranged from 5 to 14 days. Sick leave certification was given exclusively by GPs in 21/30 countries. Patient hotels or other resources to isolate patients were available in 12/30. Follow-up to monitor the symptoms and/or new complementary tests was made mainly by phone call (27/30). Chest X-ray and phlebotomy were performed in PHC in 18/30 and 23/30 countries, respectively. Oxygen and low-molecular-weight heparin were available in PHC (21/30).Conclusion In Europe PHC participated in many steps to diagnose, treat and monitor COVID-19 patients. Differences among countries might be addressed at European level for the management of future pandemics.

We aimed to document vaccination coverage for five vaccines, predictors of each vaccine’s uptake and attitudes regarding adult vaccination. Adults visiting four pharmacies were randomly invited to participate during summer 2022. Among 395 participants (mean age 51.2 years, range 19–96), vaccination rates were 78.1% for influenza and 25.8% for herpes zoster (≥60 years old), 64.3% for pneumococcal disease (≥65 years old), 33.1% for tetanus, while 11.4% had received two and 74.8% ≥3 COVID-19 vaccine doses. Half of participants (50.1%) voiced some degree of hesitancy, and 1.3% were refusers. The strongest predictor of each vaccine’s uptake was doctor’s recommendation (OR range 11.33–37.66, p < 0.001) and pharmacist’s recommendation (4.01–19.52, p < 0.05), except for the COVID-19 vaccine, where the Attitude Towards Adult VACcination (ATAVAC) value of adult vaccination subscale’s score was the only predictor (OR: 5.75, p < 0.001). Regarding insufficient coverage, thematic content analysis revealed seven main themes. Insufficient knowledge, the absence of health professionals’ recommendation, perception of low susceptibility to disease, negligence and dispute of vaccine effectiveness were universal themes, whereas safety concerns and distrust in authorities were reported solely for COVID-19 vaccination. Designing public interventions aiming to increase trust in adult vaccination is essential in the aftermath of the COVID-19 pandemic. Health professionals’ role in recommending strongly adult vaccination is crucial.

Abstract Background Spinal cord motor neurons (MNs) from human iPS cells (iPSCs) have wide applications in disease modeling and therapeutic development for amyotrophic lateral sclerosis (ALS) and other MN-associated neurodegenerative diseases. We need highly efficient MN differentiation strategies for generating iPSC-derived disease models that closely recapitulate the genetic and phenotypic complexity of ALS. An important application of these models is to understand molecular mechanisms of action of FDA-approved ALS drugs that only show modest clinical efficacy. Novel mechanistic insights will help us design optimal therapeutic strategies together with predictive biomarkers to achieve better efficacy. Methods We induce efficient MN differentiation from iPSCs in 4 days using synthetic mRNAs coding two transcription factors (Ngn2 and Olig2) with phosphosite modification. These MNs after extensive characterization were applied in electrophysiological and neurotoxicity assays as well as transcriptomic analysis, to study the neuroprotective effect and molecular mechanisms of edaravone, an FDA-approved drug for ALS, for improving its clinical efficacy. Results We generate highly pure and functional mRNA-induced MNs (miMNs) from control and ALS iPSCs, as well as embryonic stem cells. Edaravone alleviates H2O2-induced neurotoxicity and electrophysiological dysfunction in miMNs, demonstrating its neuroprotective effect that was also found in the glutamate-induced miMN neurotoxicity model. Guided by the transcriptomic analysis, we show a previously unrecognized effect of edaravone to induce the GDNF receptor RET and the GDNF/RET neurotrophic signaling in vitro and in vivo, suggesting a clinically translatable strategy to activate this key neuroprotective signaling. Notably, edaravone can replace required neurotrophic factors (BDNF and GDNF) to support long-term miMN survival and maturation, further supporting the neurotrophic function of edaravone-activated signaling. Furthermore, we show that edaravone and GDNF combined treatment more effectively protects miMNs from H2O2-induced neurotoxicity than single treatment, suggesting a potential combination strategy for ALS treatment. Conclusions This study provides methodology to facilitate iPSC differentiation and disease modeling. Our discoveries will facilitate the development of optimal edaravone-based therapies for ALS and potentially other neurodegenerative diseases. Graphical abstract

Measurement(s) surface reflectance • backscatter Technology Type(s) satellite imaging Sample Characteristic - Location Switzerland Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.14635485

Abstract Background Non-targeted cytotoxics with anticancer activity are often developed through preclinical stages using response criteria observed in cell lines and xenografts. A panel of the NCI-60 cell lines is frequently the first line to define tumor types that are optimally responsive. Open data on the gene expression of the NCI-60 cell lines, provides a unique opportunity to add another dimension to the preclinical development of such drugs by interrogating correlations with gene expression patterns. Machine learning can be used to reduce the complexity of whole genome gene expression patterns to derive manageable signatures of response. Application of machine learning in early phases of preclinical development is likely to allow a better positioning and ultimate clinical success of molecules. LP-184 is a highly potent novel alkylating agent where the preclinical development is being guided by a dedicated machine learning-derived response signature. We show the feasibility and the accuracy of such a signature of response by accurately predicting the response to LP-184 validated using wet lab derived IC50s on a panel of cell lines. Results We applied our proprietary RADR® platform to an NCI-60 discovery dataset encompassing LP-184 IC50s and publicly available gene expression data. We used multiple feature selection layers followed by the XGBoost regression model and reduced the complexity of 20,000 gene expression values to generate a 16-gene signature leading to the identification of a set of predictive candidate biomarkers which form an LP-184 response gene signature. We further validated this signature and predicted response to an additional panel of cell lines. Considering fold change differences and correlation between actual and predicted LP-184 IC50 values as validation performance measures, we obtained 86% accuracy at four-fold cut-off, and a strong (r = 0.70) and significant (p value 1.36e−06) correlation between actual and predicted LP-184 sensitivity. In agreement with the perceived mechanism of action of LP-184, PTGR1 emerged as the top weighted gene. Conclusion Integration of a machine learning-derived signature of response with in vitro assessment of LP-184 efficacy facilitated the derivation of manageable yet robust biomarkers which can be used to predict drug sensitivity with high accuracy and clinical value.

Background: The COVID-19 pandemic has necessitated changes in European healthcare systems, with a significant proportion of COVID-19 cases being managed on an outpatient basis in primary healthcare (PHC). To alleviate the burden on healthcare facilities, many European countries developed contact-tracing apps and symptom checkers to identify potential cases. As the pandemic evolved, the European Union introduced the Digital COVID-19 Certificate for travel, which relies on vaccination, recent recovery, or negative test results. However, the integration between these apps and PHC has not been thoroughly explored in Europe. Objective: To describe if governmental COVID-19 apps allowed COVID-19 patients to connect with PHC through their apps in Europe and to examine how the Digital COVID-19 Certificate was obtained. Methodology: Design and setting: Retrospective descriptive study in PHC in 30 European countries. An ad hoc, semi-structured questionnaire was developed to collect country-specific data on primary healthcare activity during the COVID-19 pandemic and the use of information technology tools to support medical care from 15 March 2020 to 31 August 2021. Key informants belong to the WONCA Europe network (World Organization of Family Doctors). The data were collected from relevant and reliable official sources, such as governmental websites and guidelines. Main outcome measures: Patient's first contact with health system, governmental COVID-19 app (name and function), Digital COVID-19 Certification, COVID-19 app connection with PHC. Results: Primary care was the first point of care for suspected COVID-19 patients in 28 countries, and 24 countries developed apps to complement classical medical care. The most frequently developed app was for tracing COVID-19 cases (24 countries), followed by the Digital COVID-19 Certificate app (17 countries). Bulgaria, Italy, Serbia, North Macedonia, and Romania had interoperability between PHC and COVID-19 apps, and Poland and Romania's apps considered social needs. Conclusions: COVID-19 apps were widely created during the first pandemic year. Contact tracing was the most frequent function found in the registered apps. Connection with PHC was scarcely developed. In future pandemics, connections between health system levels should be guaranteed to develop and implement effective strategies for managing diseases. [ABSTRACT FROM AUTHOR]

Abstract The ability to generate human‐induced pluripotent stem cell (hiPSC)‐derived neural cells displaying region‐specific phenotypes is of particular interest for modeling central nervous system biology in vitro. We describe a unique method by which spinal cord hiPSC‐derived astrocytes (hiPSC‐A) are cultured with spinal cord hiPSC‐derived motor neurons (hiPSC‐MN) in a multielectrode array (MEA) system to record electrophysiological activity over time. We show that hiPSC‐A enhance hiPSC‐MN electrophysiological maturation in a time‐dependent fashion. The sequence of plating, density, and age in which hiPSC‐A are cocultured with MN, but not their respective hiPSC line origin, are factors that influence neuronal electrophysiology. When compared to coculture with mouse primary spinal cord astrocytes, we observe an earlier and more robust electrophysiological maturation in the fully human cultures, suggesting that the human origin is relevant to the recapitulation of astrocyte/motor neuron crosstalk. Finally, we test pharmacological compounds on our MEA platform and observe changes in electrophysiological activity, which confirm hiPSC‐MN maturation. These findings are supported by immunocytochemistry and real‐time PCR studies in parallel cultures demonstrating human astrocyte mediated changes in the structural maturation and protein expression profiles of the neurons. Interestingly, this relationship is reciprocal and coculture with neurons influences astrocyte maturation as well. Taken together, these data indicate that in a human in vitro spinal cord culture system, astrocytes support hiPSC‐MN maturation in a time‐dependent and species‐specific manner and suggest a closer approximation of in vivo conditions. Stem Cells Translational Medicine 2019;8:1272&1285

Environmental scientific research is highly becoming data-driven and dependent on high performance computing infrastructures to process ever increasing large volume and diverse data sets. Consequently, there is a growing recognition of the need to share data, methods, algorithms, and infrastructure to make scientific research more effective, efficient, open, transparent, reproducible, accessible, and usable by different users. However, Earth Observations (EO) Open Science is still undervalued, and different challenges remains to achieve the vision of transforming EO data into actionable knowledge by lowering the entry barrier to massive-use Big Earth Data analysis and derived information products. Currently, FAIR-compliant digital repositories cannot fully satisfy the needs of EO users, while Spatial Data Infrastructures (SDI) are not fully FAIR-compliant and have difficulties in handling Big Earth Data. In response to these issues and the need to strengthen Open and Reproducible EO science, this paper presents SwissEnvEO, a Spatial Data Infrastructure complemented with digital repository capabilities to facilitate the publication of Ready to Use information products, at national scale, derived from satellite EO data available in an EO Data Cube in full compliance with FAIR principles.

Duchenne muscular dystrophy (DMD) remains an intractable genetic disease. Althogh there are several animal models of DMD, there is no human cell model that carries patient-specific DYSTROPHIN mutations. Here, we present a human DMD model using human induced pluripotent stem cells (hiPSCs). Our model reveals concordant disease-related phenotypes with patient-dependent variation, which are partially reversed by genetic and pharmacological approaches. Our “chemical-compound-based” strategy successfully directs hiPSCs into expandable myoblasts, which exhibit a myogenic transcriptional program, forming striated contractile myofibers and participating in muscle regeneration in vivo. DMD-hiPSC-derived myoblasts show disease-related phenotypes with patient-to-patient variability, including aberrant expression of inflammation or immune-response genes and collagens, increased BMP/TGFβ signaling, and reduced fusion competence. Furthermore, by genetic correction and pharmacological “dual-SMAD” inhibition, the DMD-hiPSC-derived myoblasts and genetically corrected isogenic myoblasts form “rescued” multi-nucleated myotubes. In conclusion, our findings demonstrate the feasibility of establishing a human “DMD-in-a-dish” model using hiPSC-based disease modeling.

This article proposes a methodology to measure the productivity of a construction site through the analysis of tower crane data. These data were obtained from a data logger that records a time series of spatial and load data from the lifting machine during the structural phase of a construction project. The first step was data collection, followed by preparation, which consisted of formatting and cleaning the dataset. Then, a visualization step identified which data was the most meaningful for the practitioners. From that, the activity of the tower crane was measured by extracting effective lifting operations using the load signal essentially. Having used such a sampling technique allows statistical analysis on the duration, load, and curvilinear distance of every extracted lifting operation. The build statistical distribution and indicators were finally used to compare construction site productivity.

Environmental sustainability is nowadays a major global issue that requires efficient and effective responses from governments. Essential variables (EV) have emerged in different scientific communities as a means to characterize and follow environmental changes through a set of measurements required to support policy evidence. To help track these changes, our planet has been under continuous observation from satellites since 1972. Currently, petabytes of satellite Earth observation (EO) data are freely available. However, the full information potential of EO data has not been yet realized because many big data challenges and complexity barriers hinder their effective use. Consequently, facilitating the production of EVs using the wealth of satellite EO data can be beneficial for environmental monitoring systems. In response to this issue, a comprehensive list of EVs that can take advantage of consistent time-series satellite data has been derived. In addition, a set of use-cases, using an Earth Observation Data Cube (EODC) to process large volumes of satellite data, have been implemented to demonstrate the practical applicability of EODC to produce EVs. The proposed approach has been successfully tested showing that EODC can facilitate the production of EVs at different scales and benefiting from the spatial and temporal dimension of satellite EO data for enhanced environmental monitoring.

Elite athletes in varied sports typically combine ergogenic strategies in the hope of enhancing physiological responses and competitive performance, but the scientific evidence for such practices is very scarce. The peculiar characteristics of speed skating contribute to impede blood flow and exacerbate deoxygenation in the lower limbs (especially the right leg). We investigated whether combining preconditioning strategies could modify muscular oxygenation and improve performance in that sport. Using a randomized, single-blind, placebo-controlled, crossover design, seven male elite long-track speed skaters performed on-ice 600-m time trials, preceded by either a combination of preconditioning strategies (COMBO) or a placebo condition (SHAM). COMBO involved performing remote ischemic preconditioning (RIPC) of the upper limbs (3 × 5-min compression at 180 mmHg and 5-min reperfusion) over 3 days (including an acute treatment before trials), with the addition of an inspiratory muscle warm-up [IMW: 2 × 30 inspirations at 40% maximal inspiratory pressure (MIP)] on the day of testing. SHAM followed the same protocol with lower intensities (10 mmHg for RIPC and 15% MIP). Changes in tissue saturation index (TSI), oxyhemoglobin–oxymyoglobin ([O2HbMb]), deoxyhemoglobin–deoxymyoglobin ([HHbMb]), and total hemoglobin–myoglobin ([THbMb]) in the right vastus lateralis muscle were monitored by near-infrared spectroscopy (NIRS). Differences between COMBO and SHAM were analyzed using Cohen’s effect size (ES) and magnitude-based inferences. Compared with SHAM, COMBO had no worthwhile effect on performance time while mean Δ[HHbMb] (2.7%, ES 0.48; -0.07, 1.03) and peak Δ[HHbMb] (1.8%, ES 0.23; -0.10, 0.57) were respectively likely and possibly higher in the last section of the race. These results indicate that combining ischemic preconditioning and IMW has no practical ergogenic impact on 600-m speed-skating performance in elite skaters. The low-sitting position in this sport might render difficult enhancing these physiological responses.