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According to the World Health Organization (WHO), dengue is the most common acute arthropod-borne viral infection in the world. The spread of dengue and other infectious diseases is closely related to human activity and mobility. In this paper we analyze the effect on the total number of dengue cases within a population after introducing mobility restrictions as a public health policy. To perform the analysis, we use a complex metapopulation in which we implement a compartmental propagation model coupled with the mobility of individuals between the patches. This model is used to investigate the spread of dengue in the municipalities of Caldas (CO). Two scenarios corresponding to different types of mobility restrictions are applied. In the first scenario, the effect of restricting mobility is analyzed in three different ways: a) limiting the access to the endemic node but allowing the movement of its inhabitants, b) restricting the diaspora of the inhabitants of the endemic node but allowing the access of outsiders, and c) a total isolation of the inhabitants of the endemic node. In this scenario, the best simulation results are obtained when endemic nodes are isolated during a dengue outbreak, obtaining a reduction of up to 22.51% of dengue cases. Finally, the second scenario simulates a total isolation of the network,i.e., mobility between nodes is completely limited. We have found that this control measure reduces the number of total dengue cases in the network by up to 42.67%.Author summaryFor the World Health Organization, dengue is a disease of public health concern. In recent years there is an increasing trend in the number of dengue cases despite existing prevention and control campaigns. The mobility of the population is considered an important factor in dengue dispersion. In this paper, we are interested in addressing how restrictions to human mobility might affect the incidence of dengue in a region. Our research is relevant because the model can be adapted to other regions or scales, and the mobility control measures can be taken into account for the development of public health policies in endemic regions.

Background Although COVID-19 vaccination has shown to be clearly beneficial in children and adolescents to reduce hospitalization and potentially transmission, there is still a lot of hesitation among parents due to concerns about vaccine safety and efficacy, especially in children under 12 years of age. Methods We conducted a comparative study in Peru to evaluate the trends in parents’ intention to vaccinate their children under 12 years of age against COVID-19, for which an online survey was administered. The survey was distributed through social networks (Facebook, Twitter, etc.), and was applied during two periods: 11/25/2021 to 12/06/2022 (Period 1) and 01/16/2022 to 01/24/2022 (Period 2). We also assessed the factors associated with the intention to vaccinate in each period through crude (cPR) and adjusted prevalence rates (aPR). Results During period 1, there were 673 participants (69.7% women). In period 2, we had 1139 respondents (77.7% women). Regarding intention to vaccinate, 83.5% of parents intended to vaccinate their children under 12 years of age during period 1. This percentage was almost the same during period 2 (83.3%). During period 1, the factors associated with a decrease in this intention were to believe that the vaccine was not necessary (aPR 0.65; 95% CI 0.44 – 0.94, p=0.022), that it would not protect (aPR: 0.14; 95% CI 0.03 – 0.63, p=0.011), that it would not be safe (aPR: 0.80; 95% CI 0.70 – 0.92, p=0.001), that it could cause long-term side effects (aPR: 0.92; 95% CI 0.85 – 1.00, p=0.037), and to think it should not be mandatory (aPR: 0.89; 95% CI 0.80-0.99, p=0.038). During period 2, besides the factors identified in period 1, not knowing about COVID-19 infection risk in children (aPR: 0.92; 95% CI 0.85-1.00, p=0.042) was also associated with a decrease in the intention. Living on the highlands or jungle was associated with an increase in the intention in both periods. Conclusion A high rate of intention to vaccinate children under 12 years of age was noted among parents in Peru, which was maintained until the end of January of 2022, right before COVID-19 vaccination started for this age group. There was a perception in some parents that the vaccine might not be necessary or safe, leading to a lower intention to vaccinate their children. Disclosures All Authors: No reported disclosures.

While significant effort has been devoted to understand the role of intraurban characteristics on sustainability and growth, much remains to be understood about the effect of interurban interactions and the role cities have in determining each other’s urban welfare. Here we consider a global mobility network of population flows between cities as a proxy for the communication between these regions, and analyze how it correlates with socioeconomic indicators. We use several measures of centrality to rank cities according to their importance in the mobility network, finding PageRank to be the most effective measure for reflecting these prosperity indicators. Our analysis reveals that the characterization of the welfare of cities based on mobility information hinges on their corresponding development stage. Namely, while network-based predictions of welfare correlate well with economic indicators in mature cities, for developing urban areas additional information about the prosperity of their mobility neighborhood is needed. We develop a simple generative model for the allocation of population flows out of a city that balances the costs and benefits of interaction with other cities that are successful, finding that it provides a strong fit to the flows observed in the global mobility network and highlights the differences in flow patterns between developed and developing urban regions. Our results hint towards the importance of leveraging interurban connections in service of urban development and welfare.

Oxytosis/ferroptosis is a form of non-apoptotic regulated cell death characterized by glutathione depletion and dysregulated production of mitochondrial reactive oxygen species that results in lethal lipid peroxidation. As the significance of oxytosis/ferroptosis to age-associated human diseases is now beginning to be appreciated, the development of innovative approaches to identify novel therapeutics that target the oxytosis/ferroptosis pathway could not be more timely. Due to their sessile nature, plants are exposed to a variety of stresses that trigger physiological changes similar to those found in oxytosis/ferroptosis. As such, they have evolved a rich array of chemical strategies to deal with those challenging conditions. This review details a drug discovery approach for identifying potent inhibitors of oxytosis/ferroptosis from plants for the treatment of Alzheimer's disease and related dementias, thereby highlighting the tremendous potential of plant-based research for developing new medicines while simultaneously being a catalyst for sustainability.

Mathematical modeling of disease outbreaks can infer the future trajectory of an epidemic, allowing for making more informed policy decisions. Another task is inferring the origin of a disease, which is relatively difficult with current mathematical models. Such frameworks, across varying levels of complexity, are typically sensitive to input data on epidemic parameters, case counts, and mortality rates, which are generally noisy and incomplete. To alleviate these limitations, we propose a maximum entropy framework that fits epidemiological models, provides calibrated infection origin probabilities, and is robust to noise due to a prior belief model. Maximum entropy is agnostic to the parameters or model structure used and allows for flexible use when faced with sparse data conditions and incomplete knowledge in the dynamical phase of disease-spread, providing for more reliable modeling at early stages of outbreaks. We evaluate the performance of our model by predicting future disease trajectories based on simulated epidemiological data in synthetic graph networks and the real mobility network of New York State. In addition, unlike existing approaches, we demonstrate that the method can be used to infer the origin of the outbreak with accurate confidence. Indeed, despite the prevalent belief on the feasibility of contact-tracing being limited to the initial stages of an outbreak, we report the possibility of reconstructing early disease dynamics, including the epidemic seed, at advanced stages.

BACKGROUND The initial wave of the COVID-19 pandemic placed a tremendous strain on health care systems worldwide. To mitigate the spread of the virus, many countries implemented stringent nonpharmaceutical interventions (NPIs), which significantly altered human behavior both before and after their enactment. Despite these efforts, a precise assessment of the impact and efficacy of these NPIs, as well as the extent of human behavioral changes, remained elusive. OBJECTIVE In this study, we conducted a retrospective analysis of the initial wave of COVID-19 in Spain to better comprehend the influence of NPIs and their interaction with human behavior. Such investigations are vital for devising future mitigation strategies to combat COVID-19 and enhance epidemic preparedness more broadly. METHODS We used a combination of national and regional retrospective analyses of pandemic incidence alongside large-scale mobility data to assess the impact and timing of government-implemented NPIs in combating COVID-19. Additionally, we compared these findings with a model-based inference of hospitalizations and fatalities. This model-based approach enabled us to construct counterfactual scenarios that gauged the consequences of delayed initiation of epidemic response measures. RESULTS Our analysis demonstrated that the pre–national lockdown epidemic response, encompassing regional measures and heightened individual awareness, significantly contributed to reducing the disease burden in Spain. The mobility data indicated that people adjusted their behavior in response to the regional epidemiological situation before the nationwide lockdown was implemented. Counterfactual scenarios suggested that without this early epidemic response, there would have been an estimated 45,400 (95% CI 37,400-58,000) fatalities and 182,600 (95% CI 150,400-233,800) hospitalizations compared to the reported figures of 27,800 fatalities and 107,600 hospitalizations, respectively. CONCLUSIONS Our findings underscore the significance of self-implemented prevention measures by the population and regional NPIs before the national lockdown in Spain. The study also emphasizes the necessity for prompt and precise data quantification prior to enacting enforced measures. This highlights the critical interplay between NPIs, epidemic progression, and human behavior. This interdependence presents a challenge in predicting the impact of NPIs before they are implemented.

The oxytosis/ferroptosis regulated cell death pathway recapitulates many features of mitochondrial dysfunction associated with the aging brain and has emerged as a potential key mediator of neurodegeneration. It has thus been proposed that the oxytosis/ferroptosis pathway can be used to identify novel drug candidates for the treatment of age-associated neurodegenerative diseases that act by preserving mitochondrial function. Previously, we identified cannabinol (CBN) as a potent neuroprotector. Here, we demonstrate that not only does CBN protect nerve cells from oxytosis/ferroptosis in a manner that is dependent on mitochondria and it does so independently of cannabinoid receptors. Specifically, CBN directly targets mitochondria and preserves key mitochondrial functions including redox regulation, calcium uptake, membrane potential, bioenergetics, biogenesis, and modulation of fusion/fission dynamics that are disrupted following induction of oxytosis/ferroptosis. These protective effects of CBN are at least partly mediated by the promotion of endogenous antioxidant defenses and the activation of AMP-activated protein kinase (AMPK) signaling. Together, our data highlight the potential of mitochondrially-targeted compounds such as CBN as novel oxytotic/ferroptotic inhibitors to rescue mitochondrial dysfunction as well as opportunities for the discovery and development of future neurotherapeutics.

Because old age is the greatest risk factor for Alzheimer's disease (AD), it is critical to target the pathological events that link aging to AD in order to develop an efficient treatment that acts upon the primary causes of the disease. One such event might be the activation of oxytosis/ferroptosis, a unique cell death mechanism characterized by mitochondrial dysfunction and lethal lipid peroxidation. Here, a comprehensive library of900 natural compounds was screened for protection against oxytosis/ferroptosis in nerve cells with the goal of better understanding the chemical nature of inhibitors of oxytosis/ferroptosis. Although the compounds tested spanned structurally diverse chemical classes from animal, microbial, plant and synthetic origins, a small set of very potent anti-oxytotic/ferroptotic compounds was identified that was highly enriched in plant quinones. The ability of these compounds to protect against oxytosis/ferroptosis strongly correlated with their ability to protect against in vitro ischemia and intracellular amyloid-beta toxicity in nerve cells, indicating that aspects of oxytosis/ferroptosis also underly other toxicities that are relevant to AD. Importantly, the anti-oxytotic/ferroptotic character of the quinone compounds relied on their capacity to target and directly prevent lipid peroxidation in a manner that required the reducing activity of cellular redox enzymes, such as NAD(P)H:quinone oxidoreductase 1 (NQO1) and ferroptosis suppressor protein 1 (FSP1). Because some of the compounds increased the production of total reactive oxygen species while decreasing lipid peroxidation, it appears that the pro-oxidant character of a compound can coexist with an inhibitory effect on lipid peroxidation and, consequently, still prevent oxytosis/ferroptosis. These findings have significant implications for the understanding of oxytosis/ferroptosis and open new approaches to the development of future neurotherapies.

Amyloid beta (Aβ) accumulates within neurons in the brains of early stage Alzheimer’s disease (AD) patients. However, the mechanism underlying its toxicity remains unclear. Here, a triple omics approach was used to integrate transcriptomic, proteomic, and metabolomic data collected from a nerve cell model of the toxic intracellular aggregation of Aβ. It was found that intracellular Aβ induces profound changes in the omics landscape of nerve cells that are associated with a pro-inflammatory, metabolic reprogramming that predisposes cells to die via the oxytosis/ferroptosis regulated cell death pathway. Notably, the degenerative process included substantial alterations in glucose metabolism and mitochondrial bioenergetics. Our findings have implications for the understanding of the basic biology of proteotoxicity, aging, and AD as well as for the development of future therapeutic interventions designed to target the oxytosis/ferroptosis regulated cell death pathway in the AD brain.

A pseudoaneurysm of the uterine artery or its branches is usually a result of vascular trauma during invasive procedures such as a cesarean section, vaginal delivery, myomectomy, hysterotomy, or dilatation and curettage. A uterine artery pseudoaneurysm rupture is a rare, yet life-threatening event. Deep infiltrating endometriosis usually involves a decrease in symptoms and imaging findings throughout pregnancy, with the notable exception of the phenomenon of decidualization. We present the case of a pregnant woman with a recent diagnosis of endometriosis, who conceived spontaneously and presented with disabling pain at 13 weeks' gestation. She was diagnosed with a left, huge (and rapidly growing) retrocervical endometriosis nodule encompassing a uterine artery pseudoaneurysm. Selective transarterial embolization was performed at 22 weeks' gestation owing to enlargement of the pseudoaneurysm sac, and the pseudoaneurysm was obliterated successfully. The patient was followed intensively throughout the pregnancy and the baby was delivered at term by cesarean section. After delivery, the nodule returned to the pregestational size.

Health informatics and biomedical computing have introduced the use of computer methods to analyze clinical information and provide tools to assist clinicians during the diagnosis and treatment of diverse clinical conditions. With the amount of information that can be obtained in the healthcare setting, new methods to acquire, organize, and analyze the data are being developed each day, including new applications in the world of big data and machine learning. In this review, first we present the most basic concepts in data science, including the structural hierarchy of information and how it is managed. A section is dedicated to discussing topics relevant to the acquisition of data, importantly the availability and use of online resources such as survey software and cloud computing services. Along with digital datasets, these tools make it possible to create more diverse models and facilitate collaboration. After, we describe concepts and techniques in machine learning used to process and analyze health data, especially those most widely applied in rheumatology. Overall, the objective of this review is to aid in the comprehension of how data science is used in health, with a special emphasis on the relevance to the field of rheumatology. It provides clinicians with basic tools on how to approach and understand new trends in health informatics analysis currently being used in rheumatology practice. If clinicians understand the potential use and limitations of health informatics, this will facilitate interdisciplinary conversations and continued projects relating to data, big data, and machine learning.

Objetivos: Evaluar las percepciones e intención de los padres de vacunar a sus hijos menores de 12 años en Perú. Metodología: Estudio transversal analítico a partir de una encuesta en línea (25 de noviembre al 6 de diciembre del 2021) para padres de niños menores de 12 años que recopiló la percepción sobre el riesgo de contagio por COVID-19 en sus hijos, sobre la necesidad de vacunación y sobre los eventos adversos relacionados con la vacuna. Evaluamos los factores asociados a la intención de vacunación mediante razones de prevalencia crudas (RPc) y ajustadas (RPa) con intervalos de confianza al 95% (IC 95%). Resultados: El 83.5% de los padres tenían la intención de vacunar a sus hijos menores de 12 años. En el análisis multivariado, los factores asociados a una disminución de la intención de vacunación fueron pensar que la vacuna no es necesaria (RPa: 0.65; IC 95% 0.44 – 0,94), que no protegería (RPa: 0.14; IC 95% 0.03 – 0.63), que no sería segura (RPa: 0.80; IC 95% 0.70 – 0.92) y que ocasionaría efectos negativos a largo plazo (RPa: 0.92; IC 95% 0.85 – 1.00). Por otro lado, residir en la Selva (RPa: 1.09; IC 95%: 1.03 – 1.15) o en la Sierra (RPa: 1.06; IC 95%: 1.00 – 1.11) se asoció a una mayor prevalencia de intención. Conclusiones: En Perú, un 16.5% de padres no vacunaría a sus hijos menores de 12 años, ya que perciben que la vacuna no es necesaria y no protegería contra la COVID-19, además de tener la preocupación de posibles eventos adversos.

The oxytosis/ferroptosis regulated cell death pathway recapitulates many features of mitochondrial dysfunction associated with the aging brain and has emerged as a potential key mediator of neurodegeneration. It has thus been proposed that the oxytosis/ferroptosis pathway can be used to identify novel drug candidates for the treatment of age-associated neurodegenerative diseases that act by preserving mitochondrial function. Previously, we identified cannabinol (CBN) as a potent neuroprotector. Here, we demonstrate that not only does CBN protect nerve cells from oxytosis/ferroptosis in a manner that is dependent on mitochondria and it does so independently of cannabinoid receptors. Specifically, CBN directly targets mitochondria and preserves key mitochondrial functions including redox regulation, calcium uptake, membrane potential, bioenergetics, biogenesis, and modulation of fusion/fission dynamics that are disrupted following induction of oxytosis/ferroptosis. These protective effects of CBN are at least partly mediated by the promotion of endogenous antioxidant defenses and the activation of AMP-activated protein kinase (AMPK) signaling. Together, our data highlight the potential of mitochondrially-targeted compounds such as CBN as novel oxytotic/ferroptotic inhibitors to rescue mitochondrial dysfunction as well as opportunities for the discovery and development of future neurotherapeutics.

The lack of medical treatments and vaccines upon the arrival of the SARS-CoV-2 virus has made non-pharmaceutical interventions the best allies in safeguarding human lives in the face of the COVID-19 pandemic. Here we propose a self-organized epidemic model with multi-scale control policies that are relaxed or strengthened depending on the extent of the epidemic outbreak. We show that optimizing the balance between the effects of epidemic control and the associated socio-economic cost is strongly linked to the stringency of control measures. We also show that non-pharmaceutical interventions acting at different spatial scales, from creating social bubbles at the household level to constraining mobility between different cities, are strongly interrelated. We find that policy functionality changes for better or worse depending on network connectivity, meaning that some populations may allow for less restrictive measures than others if both have the same resources to respond to the evolving epidemic.

The rise of twistronics has revolutionized the field of condensed matter physics, and more specifically the future applications of two-dimensional materials. At small twist angles, the microscopic world becomes strongly correlated, and unexpected physical phenomena such as superconductivity emerge. For magnetic layers, stacking plays a crucial role in the magnetic exchange coupling between the layers leading to non-trivial spin configurations and flat spin-wave dispersion when twisted. In this work, we give a short overview of the most recent theoretical and experimental works reporting the effect of twist angles on two-dimensional magnets. Besides, we discuss the effect of the twist angle and the local antiferromagnetic interlayer exchange coupling on the formation of antiferromagnetic domains in chromium trihalides. Finally, we show some preliminary results on the effect of the stacking and the twist angle on the spin-wave dispersion of bilayer CrI$_3$, Comment: To appear in the special issue on the 60th anniversary of Physica Status Solidi (RRL)

The spatiotemporal propagation patterns of recent infectious diseases, originated as localized epidemic outbreaks and eventually becoming global pandemics, are highly influenced by human mobility. Case exportation from endemic areas to the rest of the countries has become unavoidable because of the striking growth of the global mobility network, helping to overcome the physical distance existing between faraway regions. In this context, understanding the features driving contagions upon the arrival of an index case in local environments constitutes an essential task to devise policies aimed at avoiding the community transmission of these diseases and the subsequent case exportation to other unaffected areas. In this review, an overview of the different models addressing this topic is given, focusing on the movement–interaction–return model and different subsequent frameworks introduced to explain the complex interplay between the recurrent movements and contagion dynamics.

Because old age is the greatest risk factor for Alzheimer’s disease (AD), it is critical to target the pathological events that link aging to AD in order to develop an efficient treatment that acts upon the primary causes of the disease. One such event might be the activation of oxytosis/ferroptosis, a unique cell death mechanism characterized by mitochondrial dysfunction and lethal lipid peroxidation. Here, a comprehensive library of > 900 natural compounds was screened for protection against oxytosis/ferroptosis in nerve cells with the goal of better understanding the chemical nature of inhibitors of oxytosis/ferroptosis. Although the compounds tested spanned structurally diverse chemical classes from animal, microbial, plant and synthetic origins, a small set of very potent anti-oxytotic/ferroptotic compounds was identified that was highly enriched in plant quinones. The ability of these compounds to protect against oxytosis/ferroptosis strongly correlated with their ability to protect against in vitro ischemia and intracellular amyloid-beta toxicity in nerve cells, indicating that aspects of oxytosis/ferroptosis also underly other toxicities that are relevant to AD. Importantly, the anti-oxytotic/ferroptotic character of the quinone compounds relied on their capacity to target and directly prevent lipid peroxidation in a manner that required the reducing activity of cellular redox enzymes, such as NAD(P)H:quinone oxidoreductase 1 (NQO1) and ferroptosis suppressor protein 1 (FSP1). Because some of the compounds increased the production of total reactive oxygen species while decreasing lipid peroxidation, it appears that the pro-oxidant character of a compound can coexist with an inhibitory effect on lipid peroxidation and, consequently, still prevent oxytosis/ferroptosis. These findings have significant implications for the understanding of oxytosis/ferroptosis and open new approaches to the development of future neurotherapies.

We explore charge and spin transport properties of bilayer CrI 3 controlled by an external electric field. To this aim, we focus on two different device structures, namely ML-source/BL-channel/ML-drain CrI 3 and BL-source/BL-channel/BL-drain CrI 3 , where ML and BL stand for monolayer and bilayer crystals respectively. The electric field is only applied to the central BL-channel of the structure. In the first device, we inject only a single spin from the ferromagnetic ML CrI 3 which allows us to study the effect of the electric field in the spin transport properties, i.e. the operation of a spin transistor. The second structure is based on the injection of both spins, that are later filtered by electrically mediated spin-splitting effects, resulting in spin-filter device.

The increasing agglomeration of people in dense urban areas coupled with the existence of efficient modes of transportation connecting such centers, make cities particularly vulnerable to the spread of epidemics. Here we develop a data-driven approach combines with a meta-population modeling to capture the interplay between population density, mobility and epidemic spreading. We study 163 cities, chosen from four different continents, and report a global trend where the epidemic risk induced by human mobility increases consistently in those cities where mobility flows are predominantly between high population density centers. We apply our framework to the spread of SARS-CoV-2 in the United States, providing a plausible explanation for the observed heterogeneity in the spreading process across cities. Based on this insight, we propose realistic mitigation strategies (less severe than lockdowns), based on modifying the mobility in cities. Our results suggest that an optimal control strategy involves an asymmetric policy that restricts flows entering the most vulnerable areas but allowing residents to continue their usual mobility patterns. The evolution of epidemic outbreaks in urban settings is known to stem from the interplay between demographic, structural, and economical characteristics. Here, the authors combine a data driven approach with meta-population modelling to show that the epidemic vulnerability of cities hinges on the morphology of human flows, and propose how a city’s mobility backbone could be modified to minimize the epidemic risk.

Ferroptosis was first described in 2012 as an iron- and lipid peroxidation-dependent form of regulated cell death. Since its initial description, these two characteristics have informed numerous cell culture studies where inhibitors of lipid peroxidation and/or iron chelators have been shown to prevent cell death induced by a wide range of insults. However, it is not clear whether these two characteristics are sufficient to distinguish ferroptosis from other forms of regulated cell death. Thus, the primary goal of this study was to determine whether a unique combination of features could be identified that would provide an approach to more clearly separate ferroptosis from other forms of regulated cell death. To this end, multiple pharmacological inhibitors based on a variety of studies were tested. Many of these inhibitors were previously shown to protect cells from oxytosis, a regulated cell death pathway that mechanistically overlaps with ferroptosis and is induced by some of the same chemicals as ferroptosis. These inhibitors were not only tested against both known ferroptosis and oxytosis inducers but also a number of other insults that have been suggested to induce ferroptosis. The results show that a pharmacological fingerprint for ferroptosis can be established and used to categorize toxic insults into those that overlap with oxytosis/ferroptosis and those that do not.

A very simple epidemic model proposed a century ago is the linchpin of the current mathematical models of the epidemic spreading of the COVID-19 Nowadays, the abstracted compartmentalisation of the population in susceptible, infected and recovered individuals, combined with precise information about the networks of mobility flows within geographical territories, is the best weapon of the physics community to forecast the possible evolution of contagions in the current pandemic scenario © European Physical Society, EDP Sciences, 2020