Starting Conversations toward Inclusion.

Communal discussions on anti-racism and inclusion are crucial to addressing the history of racism in scientific communities. Unfortunately, universities are not universally implementing these conversations. We provide a blueprint for initiating and executing student-led discussions to empower young scientists to take action toward making science more welcoming and inclusive.

Breast density quantification in dual-energy mammography using virtual anthropomorphic phantoms.

PURPOSE: Breast density is a significant risk factor for breast cancer and can impact the sensitivity of screening mammography. Area-based breast density measurements may not provide an accurate representation of the tissue distribution, therefore volumetric breast density (VBD) measurements are preferred. Dual-energy mammography enables volumetric measurements without additional assumptions about breast shape. In this work we evaluated the performance of a dual-energy decomposition technique for determining VBD by applying it to virtual anthropomorphic phantoms. METHODS: The dual-energy decomposition formalism was used to quantify VBD on simulated dual-energy images of anthropomorphic virtual phantoms with known tissue distributions. We simulated 150 phantoms with volumes ranging from 50 to 709 mL and VBD ranging from 15% to 60%. Using these results, we validated a correction for the presence of skin and assessed the method's intrinsic bias and variability. As a proof of concept, the method was applied to 14 sets of clinical dual-energy images, and the resulting breast densities were compared to magnetic resonance imaging (MRI) measurements. RESULTS: Virtual phantom VBD measurements exhibited a strong correlation (Pearson's r > 0.95 $r > 0.95$ ) with nominal values. The proposed skin correction eliminated the variability due to breast size and reduced the bias in VBD to a constant value of -2%. Disagreement between clinical VBD measurements using MRI and dual-energy mammography was under 10%, and the difference in the distributions was statistically non-significant. VBD measurements in both modalities had a moderate correlation (Spearman's ρ $\rho \ $ = 0.68). CONCLUSIONS: Our results in virtual phantoms indicate that the material decomposition method can produce accurate VBD measurements if the presence of a third material (skin) is considered. The results from our proof of concept showed agreement between MRI and dual-energy mammography VBD. Assessment of VBD using dual-energy images could provide complementary information in dual-energy mammography and tomosynthesis examinations.

Knowledge, attitudes, perceptions, and COVID-19 hesitancy in a large public university in Mexico city during the early vaccination rollout.

BACKGROUND: Vaccination against COVID-19 is a primary tool for controlling the pandemic. However, the spread of vaccine hesitancy constitutes a significant threat to reverse progress in preventing the disease. Studies conducted in Mexico have revealed that vaccination intention in Mexico among the general population ranges from 62 to 82%. OBJECTIVE: To know the prevalence of COVID-19 vaccine hesitancy and associated factors among academics, students, and administrative personnel of a public university in Mexico City. METHODS: We administered an online survey investigating sociodemographic aspects, knowledge, attitudes, practices, and acceptance/hesitancy regarding the COVID-19 vaccine. Using generalized linear Poisson models, we analyzed factors associated with vaccine hesitancy, defined as not intending to be vaccinated within the following six months or refusing vaccination. RESULTS: During May and June 2021, we studied 840 people, prevalence of vaccine hesitancy was 6%. Hesitancy was significantly associated with fear of adverse effects, distrust of physician's recommendations, lack of knowledge regarding handwashing, age younger than 40 years, refusal to use face masks, and not having received influenza vaccination during the two previous seasons. CONCLUSIONS: Vaccine hesitancy in this population is low. Furthermore, our results allowed us the identification of characteristics that can improve vaccine promotion.

DISPERSION OF A NEW CORONAVIRUS SARS-COV-2 BY AIRLINES IN 2020: TEMPORAL ESTIMATES OF THE OUTBREAK IN MEXICO.

BACKGROUND: On January 23, 2020, China imposed a quarantine on the city of Wuhan to contain the SARS-CoV-2 outbreak. Regardless of this measure, the new infection has spread to several countries around the world. OBJECTIVE: We developed a method to study the dissemination of this infection by airline routes and provide estimations of the time of arrival of the outbreak to different cities. METHODS: Using the Kermack and McKendrick model complemented with diffusion on a graph composed of nodes and edges, we made an analysis of COVID-19 dispersion to other cities by air travel. RESULTS: The estimation was accurate in that it was possible to predict in the middle of February 2020 the arrival of the first outbreak in Mexico, which eventually occurred between March 20 and 30. This estimation was robust with respect to small changes in epidemiological parameters at the other nodes. CONCLUSIONS: The estimation of the time of arrival of the outbreak from its epicenter, allows for a time period to implement and strengthen preventive measures aimed at the general population as well as to strengthen hospital infrastructure and training of human resources. In the present study, this estimation was accurate, as observed from the real data of the beginning of the outbreak in Mexico City up to April 6, 2020.

Evidence Supporting a Lymphatic Endothelium Origin for Angiomyolipoma, a TSC2(-) Tumor Related to Lymphangioleiomyomatosis.

Angiomyolipoma (AML) is a tumor closely related to lymphangioleiomyomatosis (LAM). Both entities are characterized by the proliferation of smooth muscle actin and melanocytic glycoprotein 100 (recognized by antibody HMB-45)-positive spindle-shaped and epithelioid cells. AML and LAM are etiologically linked to mutations in the tsc2 and tsc1 genes in the case of LAM. These genes encode the proteins tuberous sclerosis complex (TSC)-1 and TSC2, which are directly involved in suppressing the mechanistic target of rapamycin cell growth signaling pathway. Although significant progress has been made in characterizing and pharmacologically slowing the progression of AML and LAM with rapamycin, our understanding of their pathogenesis lacks an identified cell of origin. We used an AML-derived cell line to determine whether TSC2 restitution brings about the cell type from which AML arises. We found that AML cells express lymphatic endothelial cell markers consistent with lymphatic endothelial cell precursors in vivo and in vitro. Moreover, on TSC2 correction, AML cells mature into adult lymphatic endothelial cells and have functional attributes characteristic of this cell lineage, suggesting a lymphatic endothelial cell of origin for AML. These effects are dependent on TSC2-mediated mechanistic target of rapamycin inactivation. Finally, we demonstrate the in vitro effectiveness of norcantharidin, a lymphangiogenesis inhibitor, as a potential co-adjuvant therapy in the treatment of AML.

Vaccination strategies for SIR vector-transmitted diseases.

Vector-borne diseases are one of the major public health problems in the world with the fastest spreading rate. Control measures have been focused on vector control, with poor results in most cases. Vaccines should help to reduce the diseases incidence, but vaccination strategies should also be defined. In this work, we propose a vector-transmitted SIR disease model with age-structured population subject to a vaccination program. We find an expression for the age-dependent basic reproductive number R(0), and we show that the disease-free equilibrium is locally stable for R(0) ≤ 1, and a unique endemic equilibrium exists for R(0) > 1. We apply the theoretical results to public data to evaluate vaccination strategies, immunization levels, and optimal age of vaccination for dengue disease.

Applying social life cycle assessment in the informal recycling sector: Understanding challenges and limitations.

The transition towards Circular Economy (CE) is a promising approach to sustainable development that may cause significant social impacts. Despite the benefits of CE initiatives, key players such as informal recyclers face serious social issues such as poverty, lack of social security, and discrimination. Although evaluating social impacts remains a considerable challenge, Social Life Cycle Assessment (SLCA) is recognized as a suitable methodology with a life cycle perspective. While most SLCA experiences are conducted in the formal sector, it is important to consider the informal sector, which plays a crucial role in developing countries. This article presents an analysis of SLCA studies in informal recycling settings in order to identify the challenges and adjustments required for informal settings. The analysis is based on a literature review and a documentary review of a pilot application of SLCA in the informal recycling system in Cuenca, Ecuador. The results show that SLCA requires adaptation to be applied in informal settings. There are particular challenges in delineating boundaries due to the fuzzy nature and variability of informal activities. Tasks such as establishing specific indicators, developing reference scales and data collection, require careful planning and active stakeholder participation. For instance, indicators regarding Fair Salary or Working hours were adapted based on best practices. Furthermore, tasks such as verifying and disseminating results should be included in interpretation phases to generate long-term impacts and influence behaviors. The study underscores SLCA's multidimensional view but highlights the need for further standardization and adaptation for informal sectors.

Modeling the roles of cohesotaxis, cell-intercalation, and tissue geometry in collective cell migration of Xenopus mesendoderm.

Collectively migrating Xenopus mesendoderm cells are arranged into leader and follower rows with distinct adhesive properties and protrusive behaviors. In vivo, leading row mesendoderm cells extend polarized protrusions and migrate along a fibronectin matrix assembled by blastocoel roof cells. Traction stresses generated at the leading row result in the pulling forward of attached follower row cells. Mesendoderm explants removed from embryos provide an experimentally tractable system for characterizing collective cell movements and behaviors, yet the cellular mechanisms responsible for this mode of migration remain elusive. We introduce a novel agent-based computational model of migrating mesendoderm in the Cellular-Potts computational framework to investigate the respective contributions of multiple parameters specific to the behaviors of leader and follower row cells. Sensitivity analyses identify cohesotaxis, tissue geometry, and cell intercalation as key parameters affecting the migration velocity of collectively migrating cells. The model predicts that cohesotaxis and tissue geometry in combination promote cooperative migration of leader cells resulting in increased migration velocity of the collective. Radial intercalation of cells towards the substrate is an additional mechanism contributing to an increase in migratory speed of the tissue. Model outcomes are validated experimentally using mesendoderm tissue explants.

Modeling the roles of cohesotaxis, cell-intercalation, and tissue geometry in collective cell migration of Xenopus mesendoderm.

Collectively migrating Xenopus mesendoderm cells are arranged into leader and follower rows with distinct adhesive properties and protrusive behaviors. In vivo, leading row mesendoderm cells extend polarized protrusions and migrate along a fibronectin matrix assembled by blastocoel roof cells. Traction stresses generated at the leading row result in the pulling forward of attached follower row cells. Mesendoderm explants removed from embryos provide an experimentally tractable system for characterizing collective cell movements and behaviors, yet the cellular mechanisms responsible for this mode of migration remain elusive. We introduce an agent-based computational model of migrating mesendoderm in the Cellular-Potts computational framework to investigate the relative contributions of multiple parameters specific to the behaviors of leader and follower row cells. Sensitivity analyses identify cohesotaxis, tissue geometry, and cell intercalation as key parameters affecting the migration velocity of collectively migrating cells. The model predicts that cohesotaxis and tissue geometry in combination promote cooperative migration of leader cells resulting in increased migration velocity of the collective. Radial intercalation of cells towards the substrate is an additional mechanism to increase migratory speed of the tissue. Summary Statement: We present a novel Cellular-Potts model of collective cell migration to investigate the relative roles of cohesotaxis, tissue geometry, and cell intercalation on migration velocity of Xenopus mesendoderm.

Applying a multi-strain dengue model to epidemics data.

Dengue disease transmission is a complex vector-borne disease, mainly due to the co-circulation of four serotypes of the virus. Mathematical models have proved to be a useful tool to understand the complexity of this disease. In this work, we extend the model studied by Esteva et al., 2003, originally proposed for two serotypes, to four circulating serotypes. Using epidemic data of dengue fever in Iquitos (Peru) and San Juan (Puerto Rico), we estimate numerically the co-circulation parameter values for selected outbreaks using a bootstrap method, and we also obtained the Basic Reproduction Number, R0, for each serotype, using both analytical calculations and numerical simulations. Our results indicate that the impact of co-circulation of serotypes in population dynamics of dengue infection is such that there is a reduced effect from DENV-3 to DENV-4 in comparison to no-cross effect for epidemics in Iquitos. Concerning San Juan epidemics, also comparing to no-cross effect, we also observed a reduced effect from the predominant serotype DENV-3 to both DENV-2 and DENV-1 epidemics neglecting the very small number of cases of DENV-4.

3D mesenchymal cell migration is driven by anterior cellular contraction that generates an extracellular matrix prestrain.

We describe a cellular contractile mechanism employed by fibroblasts and mesenchymal cancer cells to migrate in 3D collagen gels. During 3D spreading, fibroblasts strongly deform the matrix. They protrude, polarize, and initiate migration in the direction of highest extracellular matrix (ECM) deformation (prestrain). This prestrain is maintained through anterior cellular contractions behind the leading edge prior to protrusion, coordinating a distinct 3D migration cycle that varies between cell types. Myosin IIA is required for strain polarization, generating anterior contractions, and maintaining prestrain for efficient directional cell migration. Local matrix severing disrupts the matrix prestrain, suppressing directional protrusion. We show that epithelial cancer and endothelial cells rarely demonstrate the sustained prestrain or anterior contractions. We propose that mesenchymal cells sense ECM stiffness in 3D and generate their own matrix prestrain. This requires myosin IIA to generate polarized periodic anterior contractions for maintaining a 3D migration cycle.

Stopping a reaction-diffusion front.

We revisit the problem of pinning a reaction-diffusion front by a defect, in particular by a reaction-free region. Using collective variables for the front and numerical simulations, we compare the behaviors of a bistable and monostable front. A bistable front can be pinned as confirmed by a pinning criterion, the analysis of the time independent problem, and simulations. Conversely, a monostable front can never be pinned, it gives rise to a secondary pulse past the defect and we calculate the time this pulse takes to appear. These radically different behaviors of bistable and monostable fronts raise issues for modelers in particular areas of biology, as for example, the study of tumor growth in the presence of different tissues.

Bilateral Sesamoiditis as First Manifestation of Gout.

Sesamoiditis secondary to gout is an extremely rare condition with few case reports in the literature. It is an important differential diagnosis because the treatment depends on targeted therapy, unlike the main causes of sesamoiditis that often involves immobilization with special orthoses and prescription of anti-inflammatory drugs. We report here a case of a 38-year-old male, athlete, with bipartite medial sesamoid, who had insidious pain in the base of the left hallux. Laboratory tests showed no alterations, and imaging examinations demonstrated sesamoiditis with suspicion of stress fracture. The patient was initially prescribed an immobilization boot and analgesic and anti-inflammatory drugs, but he did not respond to the measures taken. After the onset of the same condition in the contralateral foot and getting the same imaging findings, we began an investigation of systemic disease, focusing on gout, because of a positive family history, which was confirmed by dual-energy computed tomography.

Seasonality and outbreaks in West Nile virus infection.

In this paper we analyze the impact of seasonal variations on the dynamics of West Nile Virus infection. We are interested in the generation of new epidemic peaks starting from an endemic state. In many cases, the oscillations generated by seasonality in the dynamics of the infection are too small to be observable. The interplay of this seasonality with the epidemic oscillations can generate new outbreaks starting from the endemic state through a mechanism of parametric resonance. Using experimental data we present specific cases where this phenomenon is numerically observed.

Brain creatine kinase activity is inhibited after hepatic failure induced by carbon tetrachloride or acetaminophen.

Encephalopathy is an important cause of morbidity and mortality in patients with severe hepatic failure and the mechanisms underlying hepatic encephalopathy are still not fully known. Considering that creatine kinase (CK) play a crucial role in brain energy homeostasis and is inhibited by free radicals, and that oxidative stress is probably involved in the pathogenesis of hepatic encephalopathy, we evaluated CK activity in hippocampus, striatum, cerebellum, cerebral cortex and prefrontal cortex of rats submitted to acute administration of carbon tetrachloride or acetaminophen. The effects of the administration of antioxidants, N-acetylcysteine (NAC) plus deferoxamine (DFX) in association, and taurine, were also evaluated. Our findings demonstrated that carbon tetrachloride inhibited CK activity in cerebellum; acetaminophen inhibited the enzyme in cerebellum and hippocampus. CK activity was not affected in other brain areas. The administration of NAC plus DFX reversed the inhibition of CK activity caused by carbon tetrachloride in cerebellum and by acetaminophen in cerebellum and hippocampus. On the other hand, taurine was not able to reverse the inhibition in CK activity. Although it is difficult to extrapolate our findings to the human condition, the inhibition of brain CK activity after hepatic failure may be involved in the pathogenesis of hepatic encephalopathy.

Mounier-Kuhn Syndrome Mimicking Lymphangioleiomyomatosis.

We present the case of a man with Mounier-Kuhn syndrome (MKS), or tracheobronchomegaly, who was referred to the National Institutes of Health Clinical Research Center because of a potential diagnosis of lymphangioleiomyomatosis (LAM), a rare condition in men. The patient was evaluated using ongoing protocols and provided written informed consent. The case demonstrates the presence of chronic inflammation surrounding the dilated airways and histologic changes of the lung parenchyma with emphysematouslike disruption in areas adjacent to the dilated airways. This finding suggests that damage to the lung parenchyma is an ongoing phenomenon in MKS. Moreover, our analysis of CT images indicates similar abnormalities in areas remote from the dilated airways. Finally, because of increased anatomic dead space, calculation of lung diffusion capacity by the single-breath method yielded abnormally low values that required making a correction for the large anatomic dead space, which can be measured by the single-breath nitrogen washout test.

[Treatment of atrial fibrillation at different levels of health care]. / Tratamiento de la fibrilación auricular en los distintos niveles asistenciales de un área sanitaria.

BACKGROUND AND OBJECTIVE: Atrial fibrillation is managed in multiple settings by different specialists. We sought to analyze treatment and compliance of the prevailing guidelines of patients with atrial fibrillation attended at different levels of health care and to quantify interventions to correct treatment inadequacies. PATIENTS AND METHOD: We included all adult patients with atrial fibrillation who presented during a 14 day-period to different levels of health care of a tertiary hospital and a related primary care clinic (family physician, cardiologist, emergency department, hospitalization). In all of them, clinical and epidemiological data in relation to atrial fibrillation, and all data referring to treatment and compliance of guidelines, were recorded prospectively. RESULTS: 293 patients were included. Clinical and epidemiological data were similar in the different settings. A great diversity in atrial fibrillation treatment was observed. In 30 and 33% of the patients, antiarrhythmic and antithrombotic treatment, respectively, did not meet the recommendations of the prevailing guidelines. The adequacy was inferior in primary care. The adequacy percentages increased slightly after the medical attention (2 and 3% respectively, p non significant) with no differences in this increase between the different settings. CONCLUSIONS: There are no epidemiological differences between patients with atrial fibrillation treated at different levels of health care. An important number of patients do not follow the recommendations of the prevailing guidelines. There is a clear medical abstention in incorrectly treated cases.

Dispersion of a new coronavirus SARS-COV-2 by airlines in 2020: temporal estimates of the outbreak in Mexico

ABSTRACT Background: On January 23, 2020, China imposed a quarantine on the city of Wuhan to contain the SARS-CoV-2 outbreak. Regardless of this measure, the new infection has spread to several countries around the world. Objective: We developed a method to study the dissemination of this infection by airline routes and provide estimations of the time of arrival of the outbreak to different cities. Methods: Using the Kermack and McKendrick model complemented with diffusion on a graph composed of nodes and edges, we made an analysis of COVID-19 dispersion to other cities by air travel. Results: The estimation was accurate in that it was possible to predict in the middle of February 2020 the arrival of the first outbreak in Mexico, which eventually occurred between March 20 and 30. This estimation was robust with respect to small changes in epidemiological parameters at the other nodes. Conclusions: The estimation of the time of arrival of the outbreak from its epicenter, allows for a time period to implement and strengthen preventive measures aimed at the general population as well as to strengthen hospital infrastructure and training of human resources. In the present study, this estimation was accurate, as observed from the real data of the beginning of the outbreak in Mexico City up to April 6, 2020.