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Abstract Aims The objective of this study was to perform a cost–benefit analysis of the CardioMEMS HF System (Abbott Laboratories, Abbott Park, IL, USA) in a heart failure (HF) clinic in Spain by evaluating the real‐time remote monitoring of pulmonary artery pressures, which has been shown to reduce HF‐related hospitalizations and improve the quality of life for selected HF patients. Particularly, the study aimed to determine the value of CardioMEMS in Southern Europe, where healthcare costs are significantly lower and its effectiveness remains uncertain. Methods and results This single‐centre study enrolled all consecutive HF patients (N = 43) who had been implanted with a pulmonary artery pressure sensor (CardioMEMS HF System); 48.8% were females, aged 75.5 ± 7.0 years, with both reduced and preserved left ventricular ejection fraction; 67.4% of them were in New York Heart Association Class III. The number of HF hospitalizations in the year before and the year after the sensor implantation was compared. Quality‐adjusted life years gained based on a literature review of previous studies were calculated. The rate of HF hospitalizations was significantly lower at 1 year compared with the year before CardioMEMS implantation (0.25 vs. 1.10 events/patient‐year, hazard ratio 0.22, P = 0.001). At the end of the first year, the usual management outperformed the CardioMEMS HF System. By the end of the second year, the CardioMEMS system is estimated to reduce costs compared with usual management (net benefits of €346). Conclusions Based on the results, we suggest that remote monitoring of pulmonary artery pressure with the CardioMEMS HF System represents a midterm and long‐term efficient strategy in a healthcare setting in Southern Europe.

Abstract Background The use of peripherally inserted central catheters and midline catheters is growing due to their potential benefits. These devices can increase patient safety and satisfaction while reducing the use of resources. As a result, many hospitals are establishing vascular access specialist teams staffed by nurses who are trained in the insertion and maintenance of these catheters. The objective of the study is to evaluate previously to the implementation whether the benefits of introducing ultrasound-guided peripheral venous catheters, midline catheters and peripherally inserted central catheters compared to current practice by a vascular access specialist team outweigh their costs. Methods Cost-benefit analysis from the perspective of the healthcare provider based on administrative data. The study estimates the reduction in resources used when changing the current practice for the use of ultrasound-guided midline and PICC catheters, as well as the additional resources required for their use. Results The use of an ultrasound-guided device on peripherally inserted central carheter, results in a measurable resource reduction of approximately €31. When 3 peripheral venous catheters are replaced by an ultrasound-guided peripherally inserted central catheter, the saving is €63. Similarly, the use of an ultrasound-guided device on a midline catheter, results in a reduction of €16, while each ultrasound-guided midline catheter replacing 3 peripheral venous catheters results in a reduction of €96. Conclusion The benefits of using ultrasound-guided midline and PICC catheters compared to current practice by introducing a vascular access specialist team trained in the implantation of ultrasound-guided catheters, outweigh its cost mainly because of the decrease in hospital stay due to the lowered risk of phebitis. These results motivate the implementation of the service, adding to previous experience suggesting that it is also preferable from the point of view of patient safety and satisfaction.

Abstract BackgroundThe outbreak of COVID-19 has turned the care model of health systems around the world upside down. The health care crisis has led to opportunities for digital health to deliver quality care, and the system has been redirected toward telemedicine. In Catalonia, Spain, as of March 2020, the pattern of visits in primary care pediatric consultations changed, such that face-to-face visits decreased in favor of non–face-to-face visits. ObjectiveThis study aimed to analyze variations in the types of pediatric visits in primary care centers in Catalonia before and after the onset of COVID-19. MethodsThis was a descriptive observational study based on administrative data. The number and type of visits to primary care pediatric services in Catalonia between January 2019 and December 2022 were studied. ResultsA drop of more than 80% in face-to-face visits and an increase of up to 15 times in remote visits were observed as of March 2020 compared to the previous year. Subsequently, the face-to-face attendance rate began to recover, although it did not reach the same rate as before COVID-19. Non–face-to-face visits were maintained, representing more than 20% of the total after more than 2 years of the pandemic. ConclusionsCOVID-19 has been the trigger for a transition in the types of visits to primary care pediatric services. The COVID-19 pandemic was a clear catalyst for the integration of telemedicine in Catalan pediatric health care. In this context, although face-to-face consultations have recovered in absolute numbers, after the pandemic period, the weight of telemedicine has increased.

BackgroundFor years, in Catalonia and in the rest of Spain, there has been a deficit and an unequal geographical distribution of health professionals specializing in pediatrics, especially in rural areas. Among the proposals to improve this situation is the promotion of the use of information and communication technologies (ICT) among users and professionals. Moreover, with the outbreak of COVID-19, the use of telehealth has become an essential tool, with an overall increase in non–face-to-face visits, including in primary care pediatrics. In this context, telemedicine, when used in primary care pediatrics, can be an effective means of improving families’ access to medical care. Currently, in Catalonia, telemedicine involving patients and health professionals is used in pediatric primary care through telephone consultation and asynchronous teleconsultation (eConsulta). Video consultation is in practice not used, although it could have different applications. ObjectiveThe aim of this study is to evaluate the feasibility of a video consultation process with physical examination in acute pediatric pathology in rural areas among primary care professionals. In addition, the level of satisfaction with these remote consultations will be assessed from the perspective of both the users and the health care professionals. MethodsWe will conduct a prospective experimental study to analyze the possibility of using video consultation in pediatric acute care in primary care in central Catalonia (Spain). A minimum of 170 children aged between 0 and 14 years attending the primary care center (PCC) for acute illness for a period of 1 year will be included in the study. Initially, the telemetric visit, including a physical examination, will include a nurse at the patient and family’s side and a pediatrician who will participate remotely. Subsequently, the pediatrician will visit the patient in person and the physical examination and diagnosis made during the remote visit will be compared with the physical examination and diagnosis of the face-to-face visit, which is considered the gold standard. ResultsRecruitment was planned to begin in the second half of 2023 and continue for at least 1 year. It is anticipated to be a good resource for a variety of acute pediatric conditions in primary care. The evaluation will focus on the feasibility of performing live remote visits and comparing their diagnostic accuracy with that of face-to-face visits. ConclusionsWe believe that this study could provide evidence on the feasibility and diagnostic accuracy of video consultation in pediatric acute primary care in a rural setting, as well as on satisfaction with video consultations among both users and professionals. If proven useful in addressing the acute needs of children in a variety of situations, it could become a digital health tool that improves the overall pediatric primary care service in rural areas, for both families and professionals. International Registered Report Identifier (IRRID)PRR1-10.2196/52946

While EGFR-targeted therapies have clinical benefit, drug-resistant brain metastases present a major obstacle. Here, the authors identify a genetic signature in brain metastatic lesions associated with osimertinib resistance and find RhoA to have an important role in the resulting phenotype.

The role of mitochondrial activity in angiogenesis is not entirely understood. Here, the authors show that mitochondria as a signaling hub and their dysfunction causes augmented TGFβ signaling to induce retinal sprouting retardation and vascular malformations.

BackgroundThe high failure rate of innovation projects motivates us to understand the perceptions about resistances and barriers of the main stakeholders to improving success rates. ObjectiveThis study aims to analyze the readiness for change in the implementation of a 3D printing project in a Catalan tertiary hospital prior to its implementation. MethodsWe used a web-based, voluntary, and anonymous survey using the Normalization Measurement Development questionnaire (NoMAD) to gather views and perceptions from a selected group of health care professionals at Germans Trias i Pujol University Hospital. ResultsIn this study, 58 professionals, including heads of service (n=30, 51%), doctors (n=18, 31%), nurses (n=7, 12%), and support staff (n=3, 5%), responded to the questionnaire. All groups saw the value of the project and were willing to enroll and support it. Respondents reported the highest scores (out of 5) in cognitive participation (mean 4.45, SD 0.04), coherence (mean 3.72, SD 0.13), and reflective monitoring (mean 3.80, SD 0.25). The weakest score was in collective action (mean 3.52, SD 0.12). There were no statistically significant differences in scores among professions in the survey. ConclusionsThe 3D printing project implementation should pay attention to preparing, defining, sharing, and supporting the operational work involved in its use and implementation. It should also understand, assess, and communicate the ways in which the new set of practices can affect the users and others around them. We suggest that health officers and politicians consider this experience as a solid ground toward the development of a more efficient health innovation system and as a catalyst for transformation.

Introduction: The evaluation of integrated care programmes for high-need high-cost older people is a challenge. We aim to share the early implementation results of the ProPCC programme in the North-Barcelona metropolitan area, in Catalonia, Spain. Methods: We analysed the intervention with retrospective data from May 2018 to December 2021 by describing the cohort complexity and by showing its 6-months pre-post impact on time spent at home and resources used: primary care visits, emergency department visits, hospital admissions and hospital stay. Findings: 264 cases were included (91% at home; 9% in nursing homes). 6-month pre vs. 6-months post results were (mean, p-value): primary care visits 8.2 vs. 11.5 (p < 0.05); emergency department visits 1.4 vs. 0.9 (p < 0.05); hospital admissions 0.7 vs. 0.5 (p < 0.05); hospital stay 12.8 vs. 7.9 days (p < 0.05). Time spent at home was 169.2 vs.174.2 days (p < 0.05). Conclusion: Early implementation of the ProPCC programme results in an increase in time spent at home (up to 3%) and significant reductions in emergency department attendance (–37.2%) and hospital stays (–38.3%). The increased use of primary care resources is compensated by the hospital resources savings, with a result in the average total cost of –46.3%.

BackgroundImported schistosomiasis is an emerging issue in European countries as a result of growing global migration from schistosomiasis-endemic countries, mainly in sub-Saharan Africa. Undetected infection may lead to serious long-term complications with an associated high cost for public healthcare systems especially among long-term migrants.ObjectiveTo evaluate from a health economics perspective the introduction of schistosomiasis screening programs in non-endemic countries with high prevalence of long-term migrants.MethodologyWe calculated the costs associated with three approaches-presumptive treatment, test-and-treat and watchful waiting-under different scenarios of prevalence, treatment efficacy and the cost of care resulting from long-term morbidity. Costs were estimated for our study area, in which there are reported to reside 74,000 individuals who have been exposed to the infection. Additionally, we methodically reviewed the potential factors that could affect the cost/benefit ratio of a schistosomiasis screening program and need therefore to be ascertained.ResultsAssuming a 24% prevalence of schistosomiasis in the exposed population and 100% treatment efficacy, the estimated associated cost per infected person of a watchful waiting strategy would be €2,424, that of a presumptive treatment strategy would be €970 and that of a test-and-treat strategy would be €360. The difference in averted costs between test-and-treat and watchful waiting strategies ranges from nearly €60 million in scenarios of high prevalence and treatment efficacy, to a neutral costs ratio when these parameters are halved. However, there are important gaps in our understanding of issues such as the efficacy of treatment in infected long-term residents, the natural history of schistosomiasis in long-term migrants and the feasibility of screening programs.ConclusionOur results support the roll-out of a schistosomiasis screening program based on a test-and-treat strategy from a health economics perspective under the most likely projected scenarios, but important knowledge gaps should be addressed for a more accurate estimations among long-term migrants.

IntroductionPre-Exposure Prophylaxis (PrEP) for HIV prevention has been implemented in several countries. Previous literature has shown that its cost-effectiveness (and, under some specifications, cost-saving character) is dependent on the reduction in price due to generics, the time-horizon and its effectiveness. The intervention has never been studied in Catalonia after the approval of the PrEP, a territory with extensive implementation.MethodsEconomic evaluation of the implementation of HIV pre-exposition prophylaxis using administrative data from Men who have Sex with Men (MSM) who receive the treatment (at the generic price) compared with non-implementation. A deterministic compartmental model and a social perspective with a micro-costing approach over the time horizon 2022-2062 are used. A baseline 86% effectiveness of PrEP is assumed.ResultsDaily oral PrEP is found to be cost-saving: discounted savings in costs are attained after 16 years, and after 40 years they reach 81 million euros. In terms of health indicators, 10,322 additional discounted QALYs are generated by the intervention. Results are sensitive to sexual behavioral patterns among MSM, the price of PrEP (reduced if offered on-demand), its effectiveness and the discount rate.ConclusionsThe use and promotion of PrEP in Catalonia is predicted to result in substantial health and monetary benefits because of reductions in HIV infections. Short-term investments in the promotion of PrEP will result in important cost-savings in the long term.

This paper presents a numerical study on the vertical (axial) and lateral (flexure) behavior of CFST (Concrete-Filled Steel Tube) columns with active hoop prestress achieved by bolting together two steel half-tubes. Twelve prototype CFST column specimens differing in the prestressing force (three levels) and in the gravity loading ratio (four levels) are analyzed; they are selected to represent typical ground columns of mid-rise buildings. Their structural behavior is simulated with a nonlinear model implemented in Abaqus; concrete and steel behavior are described with a damage-plasticity and a plasticity model, respectively. The concrete-steel interaction is represented by a hard (compression-only) surface-to-surface contact model. The calculations involve three consecutive loading steps: (i) transverse prestress, (ii) axial force, and (iii) lateral loading (shear force and bending moment). The calculation results show that the axial-flexural capacity of the prototype CFST columns is adequate. However, the hoop prestress benefit on axial compressive performance is not outstanding because the tube transverse Poisson expansion impairs the concrete confinement. The benefit in the flexural performance is smaller, due to the lack of sectional lateral expansion during bending. Preliminary studies on mid-rise buildings equipped with the prototype CFST columns show that their gravity and wind capacities are largely enough; conversely, their seismic strength is sufficient only for moderate earthquakes.

Resumen: El nuevo coronavirus SARS-CoV-2 es un virus de ARN monocatenario positivo que puede traducirse inmediatamente e integrarse en la célula huésped con su propio mensajero de ARN, facilitando la replicación dentro de la célula y la infectividad. La rápida progresión de la enfermedad presenta un verdadero desafío en todas las partes del mundo. A medida que se excede la capacidad habitual de atención sanitaria a los ciudadanos pueden generarse tensiones entre los profesionales de la salud y los gobiernos. Una de las estrategias más importantes para reducir y mitigar el avance de la epidemia son las medidas de distanciamiento social. Aquí es donde la telemedicina puede ayudar y brindar apoyo a los sistemas de salud, especialmente en las áreas de salud, prevención y prácticas clínicas, tal como se está están haciendo en otros sectores.La telemedicina conecta la conveniencia, el bajo costo y la fácil accesibilidad de la información y la comunicación relacionadas con la salud a través de Internet y las tecnologías asociadas. La telemedicina durante la epidemia de coronavirus ha sido la primera línea de defensa de los sanitarios para para frenar la propagación del coronavirus, brindando servicios por teléfono o videoconferencia para atención personalizada en casos leves y limitando los recursos sanitarios para los casos más urgentes. Abstract: The novel coronavirus SARS-CoV-2 is a positive single-stranded RNA virus that can be immediately translated and integrated into the host cell with its own RNA messenger, facilitating replication inside the cell and infectivity. The rapid progression of the disease presents a real challenge for the whole world. As the usual capacity for citizen care is exceeded, health professionals and governments struggle. One of the most important strategies to reduce and mitigate the advance of the epidemic are social distance measures; this is where telemedicine can help, and provide support to the healthcare systems, especially in the areas of public health, prevention and clinical practices, just as it is doing in others sectors.Telemedicine connects the convenience, low cost, and ready accessibility of health-related information and communication using the Internet and associated technologies. Telemedicine during the coronavirus epidemic has been the doctors’ first line of defense to slow the spread of the coronavirus, keeping social distancing and providing services by phone or videoconferencing for mild to focus personal care and limited supplies to the most urgent cases.

BackgroundAlthough home hospitalization has been a well-known and widespread practice for some time in the adult population, it has not been the same case in the pediatric setting. Simultaneously, telemedicine tools are a facilitator of the change in the health care model, which is increasingly focused on home care. In a pioneering way in Spain, the in-home hospitalization program of the Hospital Sant Joan de Déu in Barcelona allows the child to be in their home environment at the time they are being monitored and clinically followed by the professionals. Besides being the preferred option for families, previous experience suggests that pediatric home hospitalization reduces costs, primarily thanks to savings on the structural cost of the stay. ObjectiveThe aim of this study is to compare the average cost of a discharge by tele–home care with the usual care and to analyze the main drivers of the differential costs of both care models. MethodsA cost-minimization analysis is conducted under a hospital’s perspective, based on observational data, and estimated retrospectively. A historical control group of similar patients in terms of clinical casuistry to children hospitalized at home was used for comparison. ResultsA 24-hour stay at the hospital costs US $574.19, while the in-home hospitalization costs US $301.71 per day, representing a saving of almost half (48%) of the cost compared to usual care. The main saving drivers were the personnel costs (US $102.83/US $284.53, 35.5% of the total), intermediate noncare costs (US $6.09/US $284.53, 33.17%), and structural costs (US $55.16/US $284.53, 19.04%). Home hospitalization involves a total stay 27.61% longer, but at almost half the daily cost, and thus represents a saving of US $176.70 (9.01%) per 24-hour stay. ConclusionsThe cost analysis conducted under a hospital perspective shows that pediatric tele–home care is 9% cheaper compared to regular hospital care. These results motivate the most widespread implementation of the service from the point of view of economic efficiency, adding to previous experiences that suggest that it is also preferable from the perspective of user satisfaction.

Resumen: Objetivo: Se realiza un estudio observacional antes y después para valorar el efecto de la consulta virtual (eConsulta) sobre la frecuentación posterior que realiza el paciente a su centro de atención primaria una vez ha realizado su primera consulta virtual. Emplazamiento: Población asignada de los Centros de Atención Primaria Masnou-Alella y Ocata-Teià del Institut Català de la Salut. Participantes: Se realiza un muestreo aleatorizado y se comparan 329 pacientes que realizaron eConsultas respecto de 329 pacientes estadísticamente similares en edad, sexo y complejidad médica que no realizaron ninguna eConsulta. Mediciones principales: Se midieron las visitas realizadas con medicina primaria y enfermería de su equipo, tanto presenciales, telefónicas y eConsultas, durante el periodo de estudio. Resultados: Los pacientes que realizaron consultas virtuales mostraron una frecuentación previa en la atención primaria mayor que aquellos que no realizaron eConsultas (4,44 visitas médicas/año versus 3,11). Tras el uso de la eConsulta, después de un año de seguimiento, su frecuentación se redujo hasta niveles del grupo control (3,16 visitas médicas/año versus 3,00). Tras la primera visita virtual, los pacientes redujeron las visitas presenciales en un 28,7%. Conclusiones: La eConsulta podría ser una herramienta eficaz para dar respuesta a las necesidades de los pacientes que no requieran de una visita presencial, en especial en los pacientes más frecuentadores. Abstract: Objective: A «before and after» type observational study was carried out to assess the impact of the virtual consultation (eConsulta) on the frequency with which the patient visits their primary care center once they have had their first virtual consultation. Setting: Assigned population of the primary care center of Masnou-Alella and Ocata-Teià, Catalan Health Institute. Participants: A random sampling was performed and 329 patients who engaged in eConsulta were compared with 329 statistically similar patients in age, sex and medical complexity who did not engage in eConsulta. Principal mediations: Visits with primary care and nursing in their team are measured, both face-to-face, telephone and eConsulta, over the study period. Results: Patients who performed virtual consultations showed a previous frequent attendance in primary care higher than those who did not perform eConsulta (4.44 medical visits year/versus 3.11). Following the use of the eConsulta, after a year of follow-up, frequency was reduced to levels of the control group (3.16 medical visits/year versus 3.00). After the first virtual visit, patients reduced face-to-face visits by 28.7%. Conclusions: The eConsulta could be an effective tool to respond to the needs of patients who do not require a face-to-face visit, especially in the most frequent patients.

Abstract Fungi in the class Leotiomycetes are ecologically diverse, including mycorrhizas, endophytes of roots and leaves, plant pathogens, aquatic and aero-aquatic hyphomycetes, mammalian pathogens, and saprobes. These fungi are commonly detected in cultures from diseased tissue and from environmental DNA extracts. The identification of specimens from such character-poor samples increasingly relies on DNA sequencing. However, the current classification of Leotiomycetes is still largely based on morphologically defined taxa, especially at higher taxonomic levels. Consequently, the formal Leotiomycetes classification is frequently poorly congruent with the relationships suggested by DNA sequencing studies. Previous class-wide phylogenies of Leotiomycetes have been based on ribosomal DNA markers, with most of the published multi-gene studies being focussed on particular genera or families. In this paper we collate data available from specimens representing both sexual and asexual morphs from across the genetic breadth of the class, with a focus on generic type species, to present a phylogeny based on up to 15 concatenated genes across 279 specimens. Included in the dataset are genes that were extracted from 72 of the genomes available for the class, including 10 new genomes released with this study. To test the statistical support for the deepest branches in the phylogeny, an additional phylogeny based on 3156 genes from 51 selected genomes is also presented. To fill some of the taxonomic gaps in the 15-gene phylogeny, we further present an ITS gene tree, particularly targeting ex-type specimens of generic type species. A small number of novel taxa are proposed: Marthamycetales ord. nov., and Drepanopezizaceae and Mniaeciaceae fams. nov. The formal taxonomic changes are limited in part because of the ad hoc nature of taxon and specimen selection, based purely on the availability of data. The phylogeny constitutes a framework for enabling future taxonomically targeted studies using deliberate specimen selection. Such studies will ideally include designation of epitypes for the type species of those genera for which DNA is not able to be extracted from the original type specimen, and consideration of morphological characters whenever genetically defined clades are recognized as formal taxa within a classification.

BackgroundTelemedicine has become a necessary component of clinical practice for the purpose of providing safer patient care during lockdowns due to the COVID-19 pandemic. It has been used to support the health care needs of patients with COVID-19 and routine primary care patients alike. However, this change has not been fully consolidated. ObjectiveThe objective of this study was to analyze the determinants of health care professionals’ intention to use the eConsulta digital clinical consultation tool in the post–COVID-19 context. MethodsA literature review of the Technology Acceptance Model allowed us to construct a theoretical model and establish a set of hypotheses on the influence of a variety of different factors relating to health care professionals, as well as the institutions where they work, on their intention to use eConsulta. In order to confirm the proposed model, a mixed qualitative and quantitative methodology was used, and a questionnaire was designed to serve as the data collection instrument. The data were analyzed using univariate and bivariate analysis techniques. To confirm the theoretical model, exploratory factor analysis and binary logistic regression were applied. ResultsThe most important variables were related to perceived benefits (B=2.408) and the type of use that individuals habitually made of eConsulta (B=0.715). Environmental pressure (B=0.678), experience with technology (B=0.542), gender (B=0.639), and the degree to which eConsulta had been implemented (B=0.266) were other variables influencing the intention to use the tool in the post–COVID-19 context. When replicating the previous analysis according to professional group, experience with technology and gender in the physician group, and experience with tool use and the center where a professional worked in the nurse group, were found to be of considerable importance. ConclusionsThe implementation and use of eConsulta had increased significantly as a consequence of the COVID-19 pandemic, and the majority of health care professionals were satisfied with its use in practice and planned to incorporate it into their practices in the post–COVID-19 context. Perceived benefits and environmental pressure were determining factors in their attitude toward and intention to use eConsulta.

The Neurospora crassa GUL-1 is part of the COT-1 pathway, which plays key roles in regulating polar hyphal growth and cell wall remodeling. We show that GUL-1 is a bona fide RNA-binding protein (RBP) that can associate with 828 “core” mRNA species. When cell wall integrity (CWI) is challenged, expression of over 25% of genomic RNA species are modulated (2,628 mRNAs, including the GUL-1 mRNA). GUL-1 binds mRNAs of genes related to translation, cell wall remodeling, circadian clock, endoplasmic reticulum (ER), as well as CWI and MAPK pathway components. GUL-1 interacts with over 100 different proteins, including stress-granule and P-body proteins, ER components and components of the MAPK, COT-1, and STRIPAK complexes. Several additional RBPs were also shown to physically interact with GUL-1. Under stress conditions, GUL-1 can localize to the ER and affect the CWI pathway—evident via altered phosphorylation levels of MAK-1, interaction with mak-1 transcript, and involvement in the expression level of the transcription factor adv-1. We conclude that GUL-1 functions in multiple cellular processes, including the regulation of cell wall remodeling, via a mechanism associated with the MAK-1 pathway and stress-response.

The nature of saprophytic and mycoparasitic hyphal growth of Trichoderma spp. has been studied extensively, yet its initiation via conidial germination in this genus is less well understood. Using near-synchronous germinating cultures of Trichoderma asperelloides, we followed the morphological progression from dormant conidia to initial polar growth to germling formation and to evidence for first branching. We found that the stage-specific transcriptional profile of T. asperelloides is one of the most dynamic described to date: transcript abundance of over 5000 genes—comprising approximately half of the annotated genome—was unremittingly reduced in the transition from dormancy to polar growth. Conversely, after the onset of germination, the transcript abundance of approximately a quarter of the genome was unremittingly elevated during the transition from elongation to initial branching. These changes are a testimony to the substantial developmental events that accompany germination. Bayesian network analysis identified several chitinase- and glucanase-encoding genes as active transcriptional hubs during germination. Furthermore, the expression of specific members of the chitin synthase and glucan elongase families was significantly increased during germination in the presence of Rhizoctonia solani—a known host of the mycoparasite—indicating that host recognition can occur during the early stages of mycoparasite development.

BackgroundPrimary care is the major point of access in most health systems in developed countries and therefore for the detection of coronavirus disease 2019 (COVID-19) cases. The quality of its IT systems, together with access to the results of mass screening with Polymerase chain reaction (PCR) tests, makes it possible to analyse the impact of various concurrent factors on the likelihood of contracting the disease.Methods and findingsThrough data mining techniques with the sociodemographic and clinical variables recorded in patient's medical histories, a decision tree-based logistic regression model has been proposed which analyses the significance of demographic and clinical variables in the probability of having a positive PCR in a sample of 7,314 individuals treated in the Primary Care service of the public health system of Catalonia. The statistical approach to decision tree modelling allows 66.2% of diagnoses of infection by COVID-19 to be classified with a sensitivity of 64.3% and a specificity of 62.5%, with prior contact with a positive case being the primary predictor variable.ConclusionsThe use of a classification tree model may be useful in screening for COVID-19 infection. Contact detection is the most reliable variable for detecting Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases. The model would support that, beyond a symptomatic diagnosis, the best way to detect cases would be to engage in contact tracing.

Summary: Trigeminal neuralgia (TN) is a common, debilitating neuropathic face pain syndrome often resistant to therapy. The familial clustering of TN cases suggests that genetic factors play a role in disease pathogenesis. However, no unbiased, large-scale genomic study of TN has been performed to date. Analysis of 290 whole exome-sequenced TN probands, including 20 multiplex kindreds and 70 parent-offspring trios, revealed enrichment of rare, damaging variants in GABA receptor-binding genes in cases. Mice engineered with a TN-associated de novo mutation (p.Cys188Trp) in the GABAA receptor Cl− channel γ-1 subunit (GABRG1) exhibited trigeminal mechanical allodynia and face pain behavior. Other TN probands harbored rare damaging variants in Na+ and Ca+ channels, including a significant variant burden in the α-1H subunit of the voltage-gated Ca2+ channel Cav3.2 (CACNA1H). These results provide exome-level insight into TN and implicate genetically encoded impairment of GABA signaling and neuronal ion transport in TN pathogenesis.

Breast cancer is the most prevalent malignancy among women worldwide and hereditary breast cancer (HBC) accounts for about 5–10% of the cases. Today, the most recurrent genes known are BRCA1 and BRCA2, accounting for around 25% of familial cases. Although thousands of loss-of-function variants in more than twenty predisposing genes have been found, the majority of familial cases of HBC remain unexplained. The aim of this study was to identify new predisposing genes for HBC in three non-BRCA families with autosomal dominant inheritance pattern using whole-exome sequencing and functional prediction tools. No pathogenic variants in known hereditary cancer-related genes could explain the breast cancer susceptibility in these families. Among 2122 exonic variants with maximum minor allele frequency (MMAF) < 0.1%, between 17–35 variants with combined annotation-dependent depletion (CADD) > 20 segregated with disease in the three analyzed families. Selected candidate genes, i.e., UBASH3A, MYH13, UTP11L, and PAX7, were further evaluated using protein expression analysis but no alterations of cancer-related pathways were observed. In conclusion, identification of new high-risk cancer genes using whole-exome sequencing has been more challenging than initially anticipated, in spite of selected families with pronounced family history of breast cancer. A combination of low- and intermediate-genetic-risk variants may instead contribute the breast cancer susceptibility in these families.

Transient aneuploidy enables cells to survive sudden environmental changes before longterm cellular adaptations are established. Here, the authors show that yeast cells respond to the acute loss of Ulp2 SUMO protease by rapid induction of aneuploidy, and reveal predictable long-term adaptation mechanisms that restore euploidy.

The correction of genetic defects in utero could allow for improved outcomes of gene therapy. Here, the authors demonstrate safe delivery of nanoparticles to fetal mouse tissues, and show that nanoparticles containing peptide nucleic acids to edit the beta-globin gene are effective in a mouse model of beta-thalassemia.

(1) Background: In epidemiological terms, it has been possible to calculate the savings in health resources and the reduction in the health effects of COVID vaccines. Conducting an economic evaluation, some studies have estimated its cost-effectiveness; the vaccination shows highly favorable results, cost-saving in some cases. (2) Methods: Cost–benefit analysis of the vaccination campaign in the North Metropolitan Health Region (Catalonia). An epidemiological model based on observational data and before and after comparison is used. The information on the doses used and the assigned resources (conventional hospital beds, ICU, number of tests) was extracted from administrative data from the largest primary care provider in the region (Catalan Institute of Health). A distinction was made between the social perspective and the health system. (3) Results: the costs of vaccination are estimated at 137 million euros (€48.05/dose administered). This figure is significantly lower than the positive impacts of the vaccination campaign, which are estimated at 470 million euros (€164/dose administered). Of these, 18% corresponds to the reduction in ICU discharges, 16% to the reduction in conventional hospital discharges, 5% to the reduction in PCR tests and 1% to the reduction in RAT tests. The monetization of deaths and cases that avoid sequelae account for 53% and 5% of total savings, respectively. The benefit/cost ratio is estimated at 3.4 from a social perspective and 1.4 from a health system perspective. The social benefits of vaccination are estimated at €116.67 per vaccine dose (€19.93 from the perspective of the health system). (4) Conclusions: The mass vaccination campaign against COVID is cost-saving. From a social perspective, most of these savings come from the monetization of the reduction in mortality and cases with sequelae, although the intervention is equally widely cost-effective from the health system perspective thanks to the reduction in the use of resources. It is concluded that, from an economic perspective, the vaccination campaign has high social returns.

Functional deficits persist after spinal cord injury (SCI) because axons in the adult mammalian central nervous system (CNS) fail to regenerate. However, modest levels of spontaneous functional recovery are typically observed after trauma and are thought to be mediated by the plasticity of intact circuitry. The mechanisms underlying intact circuit plasticity are not delineated. Here, we characterize the in vivo transcriptome of sprouting intact neurons from Ngr1 null mice after partial SCI. We identify the lysophosphatidic acid signaling modulators LPPR1 and LPAR1 as intrinsic axon growth modulators for intact corticospinal motor neurons after adjacent injury. Furthermore, in vivo LPAR1 inhibition or LPPR1 overexpression enhances sprouting of intact corticospinal tract axons and yields greater functional recovery after unilateral brainstem lesion in wild-type mice. Thus, the transcriptional profile of injury-induced sprouting of intact neurons reveals targets for therapeutic enhancement of axon growth initiation and new synapse formation.

ABSTRACT The origins and maintenance of the rich fungal diversity have been longstanding issues in evolutionary biology. To investigate how differences in expression regulation contribute to divergences in development and ecology among closely related species, transcriptomes were compared between Chaetomium globosum, a homothallic pathogenic fungus thriving in highly humid ecologies, and Neurospora crassa, a heterothallic postfire saprotroph. Gene expression was quantified in perithecia at nine distinct morphological stages during nearly synchronous sexual development. Unlike N. crassa, expression of all mating loci in C. globosum was highly correlated. Key regulators of the initiation of sexual development in response to light stimuli—including orthologs of N. crassa sub-1, sub-1-dependent gene NCU00309, and asl-1—showed regulatory dynamics matching between C. globosum and N. crassa. Among 24 secondary metabolism gene clusters in C. globosum, 11—including the cochliodones biosynthesis cluster—exhibited highly coordinated expression across perithecial development. C. globosum exhibited coordinately upregulated expression of histidine kinases in hyperosmotic response pathways—consistent with gene expression responses to high humidity we identified in fellow pathogen Fusarium graminearum. Bayesian networks indicated that gene interactions during sexual development have diverged in concert with the capacities both to reproduce asexually and to live a self-compatible versus self-incompatible life cycle, shifting the hierarchical roles of genes associated with conidiation and heterokaryon incompatibility in N. crassa and C. globosum. This divergence supports an evolutionary history of loss of conidiation due to unfavorable combinations of heterokaryon incompatibility in homothallic species. IMPORTANCE Fungal diversity has amazed evolutionary biologists for decades. One societally important aspect of this diversity manifests in traits that enable pathogenicity. The opportunistic pathogen Chaetomium globosum is well adapted to a high-humidity environment and produces numerous secondary metabolites that defend it from predation. Many of these chemicals can threaten human health. Understanding the phases of the C. globosum life cycle in which these products are made enables better control and even utilization of this fungus. Among its intriguing traits is that it both is self-fertile and lacks any means of propagule-based asexual reproduction. By profiling genome-wide gene expression across the process of sexual reproduction in C. globosum and comparing it to genome-wide gene expression in the model filamentous fungus N. crassa and other closely related fungi, we revealed associations among mating-type genes, sexual developmental genes, sexual incompatibility regulators, environmentally responsive genes, and secondary metabolic pathways.

Decidua is a transient uterine tissue shared by mammals with hemochorial placenta and is essential for pregnancy. The decidua is infiltrated by many immune cells promoting pregnancy. Adult bone marrow (BM)-derived cells (BMDCs) differentiate into rare populations of nonhematopoietic endometrial cells in the uterus. However, whether adult BMDCs become nonhematopoietic decidual cells and contribute functionally to pregnancy is unknown. Here, we show that pregnancy mobilizes mesenchymal stem cells (MSCs) to the circulation and that pregnancy induces considerable adult BMDCs recruitment to decidua, where some differentiate into nonhematopoietic prolactin-expressing decidual cells. To explore the functional importance of nonhematopoietic BMDCs to pregnancy, we used Homeobox a11 (Hoxa11)-deficient mice, having endometrial stromal-specific defects precluding decidualization and successful pregnancy. Hoxa11 expression in BM is restricted to nonhematopoietic cells. BM transplant (BMT) from wild-type (WT) to Hoxa11-/- mice results in stromal expansion, gland formation, and marked decidualization otherwise absent in Hoxa11-/- mice. Moreover, in Hoxa11+/- mice, which have increased pregnancy losses, BMT from WT donors leads to normalized uterine expression of numerous decidualization-related genes and rescue of pregnancy loss. Collectively, these findings reveal that adult BMDCs have a previously unrecognized nonhematopoietic physiologic contribution to decidual stroma, thereby playing important roles in decidualization and pregnancy.

Gene editing approaches are widely used for correcting mutations, but their application is largely limited to cells and not living animals. Here the authors show that in vivoγPNA-mediated editing of a β-globin mutation is promoted by SCF and leads to sustained normalization of blood haemoglobin levels β-thalassemic mice.

L’article constitueix un relat explicatiu sobre el procés de conversió de Barcelona en una ciutat turística, particularment al llarg de les dues últimes dècades. S’aporten dades evolutives dels diferents components del sistema turístic i es contextualitza el significat de les activitats turístiques en les estructures de la ciutat i en el seu funcionament. Aquest procés ha estat complex i es mostra inacabat. Es parteix de dues premisses específiques: a) són diversos els factors que expliquen l’origen i el desenvolupament del procés, i entre ells destaca el paper de la gestió pública del turisme, del seu model de promoció i foment, que és valorat com un model d’èxit; b) en el seu nou estatus com a ciutat turística, Barcelona té el repte de dissenyar un model de gestió de la ciutat (turística) basat en la relació turisme-ciutat que prevegi minimitzar els conflictes i afavorir les sinergies.

Achievement of the best balance between the accuracy and efficiency is always an important issue when searching a tree space of large data sets. In the 5th issue in 2009, Rodrigo et al used bootstrapped topologies as fixed genealogies to distribute an MCMC analysis across a cluster of computers, resulting in an efficiency yielding results 37 times faster than in the standard MCMC methods. Tree searches can seldom be guided with certainty, so that such snapshots sampling partial but “more-likely” tree space facilitated by parallel programs on computer clusters may provide great promise among a few choices that are computationally affordable when tree space is large and complicated.

El artículo constituye un relato explicativo sobre el proceso de conversión de Barcelona en una ciudad turística, particularmente a lo largo de las dos últimas décadas. Se aportan datos evolutivos de los distintos componentes del sistema turístico y se contextualiza el significado de las actividades turísticas en las estructuras de la ciudad y en su funcionamiento. Dicho proceso ha sido complejo y se muestra inacabado. Se parte de dos premisas específicas: a) son diversos los factores que explican el origen y el desarrollo del proceso, y entre ellos destaca el papel de la gestión pública del turismo, de su modelo de promoción y fomento, que es valorado como un modelo de éxito; b) en su nuevo estatus como ciudad turística, Barcelona tiene el reto de diseñar un modelo de gestión de la ciudad (turística) basado en la relación turismo-ciudad que prevea minimizar los conflictos y favorecer las sinergias.

Many fungi form complex three-dimensional fruiting bodies, within which the meiotic machinery for sexual spore production has been considered to be largely conserved over evolutionary time. Indeed, much of what we know about meiosis in plant and animal taxa has been deeply informed by studies of meiosis in Saccharomyces and Neurospora. Nevertheless, the genetic basis of fruiting body development and its regulation in relation to meiosis in fungi is barely known, even within the best studied multicellular fungal model Neurospora crassa. We characterized morphological development and genome-wide transcriptomics in the closely related species Neurospora crassa, Neurospora tetrasperma, and Neurospora discreta, across eight stages of sexual development. Despite diverse life histories within the genus, all three species produce vase-shaped perithecia. Transcriptome sequencing provided gene expression levels of orthologous genes among all three species. Expression of key meiosis genes and sporulation genes corresponded to known phenotypic and developmental differences among these Neurospora species during sexual development. We assembled a list of genes putatively relevant to the recent evolution of fruiting body development by sorting genes whose relative expression across developmental stages increased more in N. crassa relative to the other species. Then, in N. crassa, we characterized the phenotypes of fruiting bodies arising from crosses of homozygous knockout strains of the top genes. Eight N. crassa genes were found to be critical for the successful formation of perithecia. The absence of these genes in these crosses resulted in either no perithecium formation or in arrested development at an early stage. Our results provide insight into the genetic basis of Neurospora sexual reproduction, which is also of great importance with regard to other multicellular ascomycetes, including perithecium-forming pathogens, such as Claviceps purpurea, Ophiostoma ulmi, and Glomerella graminicola.

BACKGROUND: Ancestral reconstructions of mammalian genomes have revealed that evolutionary breakpoint regions are clustered in regions that are more prone to break and reorganize. What is still unclear to evolutionary biologists is whether these regions are physically unstable due solely to sequence composition and/or genome organization, or do they represent genomic areas where the selection against breakpoints is minimal. METHODOLOGY AND PRINCIPAL FINDINGS: Here we present a comprehensive study of the distribution of tandem repeats in great apes. We analyzed the distribution of tandem repeats in relation to the localization of evolutionary breakpoint regions in the human, chimpanzee, orangutan and macaque genomes. We observed an accumulation of tandem repeats in the genomic regions implicated in chromosomal reorganizations. In the case of the human genome our analyses revealed that evolutionary breakpoint regions contained more base pairs implicated in tandem repeats compared to synteny blocks, being the AAAT motif the most frequently involved in evolutionary regions. We found that those AAAT repeats located in evolutionary regions were preferentially associated with Alu elements. SIGNIFICANCE: Our observations provide evidence for the role of tandem repeats in shaping mammalian genome architecture. We hypothesize that an accumulation of specific tandem repeats in evolutionary regions can promote genome instability by altering the state of the chromatin conformation or by promoting the insertion of transposable elements.

Achievement of the best balance between the accuracy and efficiency is always an important issue when searching a tree space of large data sets. In the 5th issue in 2009, Rodrigo et al used bootstrapped topologies as fixed genealogies to distribute an MCMC analysis across a cluster of computers, resulting in an efficiency yielding results 37 times faster than in the standard MCMC methods. Tree searches can seldom be guided with certainty, so that such snapshots sampling partial but “more-likely” tree space facilitated by parallel programs on computer clusters may provide great promise among a few choices that are computationally affordable when tree space is large and complicated.

This paper is the result of both experimental and numeric analyses on pallet rack components. Two cyclic testing protocols for beam‐end connectors of adjustable racking systems are compared; such experiments are named as "code type" and "Castiglioni". Both protocols share the same test mock‐up: an assembly of a doubly‐pinned upright segment with a cantilever beam specimen. These tests consist in an up‐to‐failure increasing push‐pull process at the free beam end. In the "code type" test, the imposed displacement loops are centered around zero; conversely, in the "Castiglioni" tests, both upward and downward displacement segment runs are centered around a vertical static equilibrium situation (to take the gravitational load into account). The "code type" test is expected to result in a higher number of cycles than the "Castiglioni" one because of the two following features of the latter: (i) the gravitational load is always present, thus resulting in a higher demanding test, and (ii) the failure point is precisely predefined and usually produced before the total breakdown. This paper describes and compares experiments using both protocols. Additionally, these tests are numerically simulated. [ABSTRACT FROM AUTHOR]

Background: eConsulta—that is, asynchronous, two-way teleconsultation in primary care—is one of the most important telemedicine developments in the Catalan public health system, a service that has been heavily boosted by the onset of the COVID-19 pandemic. It is vital to know the characteristics of its users in order to be able to meet their needs and understand the coverage of this service in a context where there is reduced accessibility to the health system. Objective: This study aims to analyze the profile of the citizens who use the eConsulta tool and the reasons for their use, as well as to gain an understanding of the elements that characterize their decision to use it while distinguishing between those who used it before and those who have used it since the onset of the COVID-19 pandemic. Methods: A descriptive, observational study based on administrative data was performed. This study differentiates between the COVID-19 pandemic era and the period preceding it, considering the day the state of emergency was declared in Spain (ie, March 12, 2020) as the cut-off point. It also differentiates between eConsulta users who send messages and those who only receive them. Results: During the pandemic, the number of unique users of this teleconsultation service had almost tripled, with up to 33.10 visits per 1000 inhabitants per month reported in the first three months. For the two user profiles analyzed, most users since the start of the COVID-19 outbreak were predominantly female, systematically younger, more actively employed, and with less complex pathologies. Furthermore, eConsulta users received more messages proactively from the health professionals. There was also a relative decrease in the number of conversations initiated by higher-income urban users and an increase in conversations initiated by users in rural areas. Conclusions: The COVID-19 pandemic has helped to generalize the use of telemedicine as a tool to compensate, to some extent, for the decline in face-to-face visits, especially among younger citizens in Catalonia. Telemedicine has made it possible to maintain contact between citizens and the health care system in the context of maximum complexity. [ABSTRACT FROM AUTHOR]

Background: Primary care is the major point of access in most health systems in developed countries and therefore for the detection of coronavirus disease 2019 (COVID-19) cases. The quality of its IT systems, together with access to the results of mass screening with Polymerase chain reaction (PCR) tests, makes it possible to analyse the impact of various concurrent factors on the likelihood of contracting the disease. Methods and findings: Through data mining techniques with the sociodemographic and clinical variables recorded in patient's medical histories, a decision tree-based logistic regression model has been proposed which analyses the significance of demographic and clinical variables in the probability of having a positive PCR in a sample of 7,314 individuals treated in the Primary Care service of the public health system of Catalonia. The statistical approach to decision tree modelling allows 66.2% of diagnoses of infection by COVID-19 to be classified with a sensitivity of 64.3% and a specificity of 62.5%, with prior contact with a positive case being the primary predictor variable. Conclusions: The use of a classification tree model may be useful in screening for COVID-19 infection. Contact detection is the most reliable variable for detecting Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases. The model would support that, beyond a symptomatic diagnosis, the best way to detect cases would be to engage in contact tracing. [ABSTRACT FROM AUTHOR]

Radial spokes (RS) are T-shaped multiprotein complexes on the axonemal microtubules. Repeated RS1, RS2, and RS3 couple the central pair to modulate ciliary and flagellar motility. Despite the cell type specificity of RS3 substructures, their molecular components remain largely unknown. Here, we report that a leucine-rich repeat-containing protein, LRRC23, is an RS3 head component essential for its head assembly and flagellar motility in mammalian spermatozoa. From infertile male patients with defective sperm motility, we identified a splice site variant of LRRC23. A mutant mouse model mimicking this variant produces a truncated LRRC23 at the C-terminus that fails to localize to the sperm tail, causing male infertility due to defective sperm motility. LRRC23 was previously proposed to be an ortholog of the RS stalk protein RSP15. However, we found that purified recombinant LRRC23 interacts with an RS head protein RSPH9, which is abolished by the C-terminal truncation. Evolutionary and structural comparison also shows that LRRC34, not LRRC23, is the RSP15 ortholog. Cryo-electron tomography clearly revealed that the absence of the RS3 head and the sperm-specific RS2-RS3 bridge structure in LRRC23 mutant spermatozoa. Our study provides new insights into the structure and function of RS3 in mammalian spermatozoa and the molecular pathogenicity of LRRC23 underlying reduced sperm motility in infertile human males.

Lineage-specific genes (LSGs) have long been postulated to play roles in the establishment of genetic barriers to intercrossing and speciation. In the genome of Neurospora crassa, most of the 670 Neurospora LSGs that are aggregated adjacent to the telomeres are clustered with 61% of the HET-domain genes, some of which regulate self-recognition and define vegetative incompatibility groups. In contrast, the LSG-encoding proteins possess few to no domains that would help to identify potential functional roles. Possible functional roles of LSGs were further assessed by performing transcriptomic profiling in genetic mutants and in response to environmental alterations, as well as examining gene knockouts for phenotypes. Among the 342 LSGs that are dynamically expressed during both asexual and sexual phases, 64% were detectable on unusual carbon sources such as furfural, a wildfire-produced chemical that is a strong inducer of sexual development, and the structurally-related furan 5-hydroxymethyl furfural (HMF). Expression of a significant portion of the LSGs was sensitive to light and temperature, factors that also regulate the switch from asexual to sexual reproduction. Furthermore, expression of the LSGs was significantly affected in the knockouts of adv-1 and pp-1 that regulate hyphal communication, and expression of more than one quarter of the LSGs was affected by perturbation of the mating locus. These observations encouraged further investigation of the roles of clustered lineage-specific and HET-domain genes in ecology and reproduction regulation in Neurospora, especially the regulation of the switch from the asexual growth to sexual reproduction, in response to dramatic environmental conditions changes.

Acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), cause severe endothelial dysfunction in the lung, and vascular endothelial growth factor (VEGF) is elevated in ARDS. We found that the levels of a VEGF-regulated microRNA, microRNA-1 (miR-1), were reduced in the lung endothelium after acute injury. Pulmonary endothelial cell–specific (EC-specific) overexpression of miR-1 protected the lung against cell death and barrier dysfunction in both murine and human models and increased the survival of mice after pneumonia-induced ALI. miR-1 had an intrinsic protective effect in pulmonary and other types of ECs; it inhibited apoptosis and necroptosis pathways and decreased capillary leak by protecting adherens and tight junctions. Comparative gene expression analysis and RISC recruitment assays identified miR-1 targets in the context of injury, including phosphodiesterase 5A (PDE5A), angiopoietin-2 (ANGPT2), CNKSR family member 3 (CNKSR3), and TNF-α–induced protein 2 (TNFAIP2). We validated miR-1–mediated regulation of ANGPT2 in both mouse and human ECs and found that in a 119-patient pneumonia cohort, miR-1 correlated inversely with ANGPT2. These findings illustrate a previously unknown role of miR-1 as a cytoprotective orchestrator of endothelial responses to acute injury with prognostic and therapeutic potential.

BackgroundVaccination is one of the most successful public health interventions for the prevention of COVID-19. Toward the end of April 2021, UNICEF (United Nations International Children’s Emergency Fund), alongside other organizations, were promoting the hashtag #VaccinesWork. ObjectiveThe aim of this paper is to analyze the #VaccinesWork hashtag on Twitter in the context of the COVID-19 pandemic, analyzing the main messages shared and the organizations involved. MethodsThe data set used in this study consists of 11,085 tweets containing the #VaccinesWork hashtag from the 29th to the 30th of April 2021. The data set includes tweets that may not have the hashtag but were replies or mentions in those tweets. The data were retrieved using NodeXL, and the network graph was laid out using the Harel-Koren fast multiscale layout algorithm. ResultsThe study found that organizations such as the World Health Organization, UNICEF, and Gavi were the key opinion leaders and had a big influence on the spread of information among users. Furthermore, the most shared URLs belonged to academic journals with a high impact factor. Provaccination users had other vaccination-promoting hashtags in common, not only in the COVID-19 scenario. ConclusionsThis study investigated the discussions surrounding the #VaccinesWork hashtag. Social media networks containing conspiracy theories tend to contain dubious accounts leading the discussions and are often linked to unverified information. This kind of analysis can be useful to detect the optimal moment for launching health campaigns on Twitter.