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Gene regulatory networks present a wide variety of dynamical responses to intrinsic and extrinsic perturbations. Arguably, one of the most important of such coordinated responses is the one of amplification cascades, in which activation of a few key-responsive transcription factors (termed master regulators, MRs) lead to a large series of transcriptional activation events. This is so since master regulators are transcription factors controlling the expression of other transcription factor molecules and so on. MRs hold a central position related to transcriptional dynamics and control of gene regulatory networks and are often involved in complex feedback and feedforward loops inducing non-trivial dynamics. Recent studies have pointed out to the myocyte enhancing factor 2C (MEF2C, also known as MADS box transcription enhancer factor 2, polypeptide C) as being one of such master regulators involved in the pathogenesis of primary breast cancer. In this work, we perform an integrative genomic analysis of the transcriptional regulation activity of MEF2C and its target genes to evaluate to what extent are these molecules inducing collective responses leading to gene expression deregulation and carcinogenesis. We also analyzed a number of induced dynamic responses, in particular those associated with transcriptional bursts, and nonlinear cascading to evaluate the influence they may have in malignant phenotypes and cancer. Received: 20 Novembre 2014, Accepted: 24 June 2015; Edited by: C. A. Condat, G. J. Sibona; DOI: http://dx.doi.org/10.4279/PIP.070011 Cite as: E Hernández-Lemus, K Baca-López, R Lemus, R García-Herrera, Papers in Physics 7, 070011 (2015)

When lipid-directed assembly of silicic acid precursors is conducted in the presence of living cells, the cells intervene, surrounding themselves with a fluid, multilayered lipid vesicle that interfaces coherently with an ordered silica mesophase. This bio/nano interface is unique in that its uniform nanostructure prevents excessive drying of water, maintaining cell viability, yet provides accessibility of the cell surface to small molecules. In comparison to existing immobilization schemes, such as encapsulation within sol–gel matrices, we show this interface to form by an active interplay between the living cell and surrounding matrix, which we refer to as cell-directed assembly(CDA). Importantly and perhaps uniquely, CDA creates a localized nanostructured microenvironment within which three-dimensional chemical gradients are established and maintained. [ABSTRACT FROM AUTHOR]

Screening for food insecurity and other social determinants of health is being integrated into oncology practice. We performed a pilot randomized trial to investigate whether an unconditional cash transfer (UCT) could be used to address food insecurity among female breast and gynecological cancer survivors. Food-insecure cancer survivors completed a baseline survey and were randomly assigned to receive $100/month for 3 months (UCT) or usual care (UC). Participants (n = 14) completed a follow-up survey after 3 months, and we compared changes in health-related quality of life, indicators of food insecurity, diet quality, and whether a participant had to forgo, delay, or make changes to medical care because of cost. The UCT was associated with higher physical health scores, fewer indicators of food insecurity, better diet quality, and a lower likelihood of forgoing medical care than those who received UC. Our results suggest that UCTs can improve outcomes for food-insecure cancer survivors., (© The Author(s) 2024. Published by Oxford University Press.)

Movement as medicine is the premise behind Running Medicine (RM), a community-based wellness program that began in 2016 in New Mexico. RM is centered in the Indigenous traditions of running and is oriented to improving the four dimensions of wellness-mind, body, spirit, and social. Using retroactive surveys of RM's Spring 2019 participants, we investigated the program's effectiveness in the realms of physical, mental, spiritual, and social wellness. Based on data from participant surveys, RM appears to be effective at improving the four realms of wellness. Indigenous participants improved to a greater degree in mental and social wellness than non-Indigenous participants, while the opposite was true for physical and spiritual wellness. For both groups, the largest effect size among the four domains was seen in social wellness. Among our participants, this culturally grounded approach to wellness appears to be effective at improving the four realms of physical, mental, spiritual, and social wellness., Competing Interests: None of the authors above have conflicts of interest related to this project

Background: Early identification of an acute respiratory infection is important for reducing transmission and enabling earlier therapeutic intervention. We aimed to prospectively evaluate the feasibility of home-based diagnostic self-testing of viral pathogens in individuals prompted to do so on the basis of self-reported symptoms or individual changes in physiological parameters detected via a wearable sensor., Methods: DETECT-AHEAD was a prospective, decentralised, randomised controlled trial carried out in a subpopulation of an existing cohort (DETECT) of individuals enrolled in a digital-only observational study in the USA. Participants aged 18 years or older were randomly assigned (1:1:1) with a block randomisation scheme stratified by under-represented in biomedical research status. All participants were offered a wearable sensor (Fitbit Sense smartwatch). Participants in groups 1 and 2 received an at-home self-test kit (Alveo be.well) for two acute respiratory viral pathogens: SARS-CoV-2 and respiratory syncytial virus. Participants in group 1 could be alerted through the DETECT study app to take the at-home test on the basis of changes in their physiological data (as detected by our algorithm) or due to self-reported symptoms; those in group 2 were prompted via the app to self-test only due to symptoms. Group 3 served as the control group, without alerts or home testing capability. The primary endpoints, assessed on an intention-to-treat basis, were the number of acute respiratory infections presented (self-reported) and diagnosed (electronic health record), and the number of participants using at-home testing in groups 1 and 2. This trial is registered with ClinicalTrials.gov, NCT04336020., Findings: Between Sept 28 and Dec 30, 2021, 450 participants were recruited and randomly assigned to group 1 (n=149), group 2 (n=151), or group 3 (n=150). 179 (40%) participants were male, 264 (59%) were female, and seven (2%) identified as other. 232 (52%) were from populations historically under-represented in biomedical research. 118 (39%) of the 300 participants in groups 1 and 2 were prompted to self-test, with 61 (52%) successfully completing self-testing. Participants were prompted to home-test more frequently due to symptoms (41 [28%] in group 1 and 51 [34%] in group 2) than due to detected physiological changes (26 [17%] in group 1). Significantly more participants in group 1 received alerts to test than did those in group 2 (67 [45%] vs 51 [34%]; p=0·047). Of the 61 individuals who were prompted to test and successfully did so, 19 (31%) tested positive for a viral pathogen-all for SARS-CoV-2. The individuals diagnosed as positive for SARS-CoV-2 in the electronic health record were eight (5%) in group 1, four (3%) in group 2, and two (1%) in group 3, but it was difficult to confirm if they were tied to symptomatic episodes documented in the trial. There were no adverse events., Interpretation: In this direct-to-participant trial, we showed early feasibility of a decentralised programme to prompt individuals to use a viral pathogen diagnostic test based on symptoms tracked in the study app or physiological changes detected using a wearable sensor. Barriers to adequate participation and performance were also identified, which would need to be addressed before large-scale implementation., Funding: Janssen Pharmaceuticals., Competing Interests: Declaration of interests JVi, KH, JVe, MA, LK, JWC, and DT are employed by Janssen Pharmaceuticals. JMR was supported by The Rockefeller Foundation and is now employed by Moderna. ER is employed by CareEvolution. KB-M is a consultant for CareEvolution and was on the Heartline Study Executive Committee. SRS is a consultant for PhysIQ and declares payment for being on the Heartline Study Executive Committee. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: To describe peer-reviewed literature on chiropractic faculty participation in research and identify important barriers and facilitators., Methods: We conducted a scoping review using comprehensive searches of relevant databases from inception through November 2022. English language publications of any design were included, with search terms consisting of subject headings specific to each database and free text words related to chiropractic, faculty, and research. Primary and secondary reviewer teams performed article screening and data abstraction using Covidence software, with primary reviewers responsible for consensus. Data were entered into evidence tables and analyzed descriptively., Results: A total of 330 articles were screened, with 14 deemed eligible including 8 cross-sectional/correlational studies and 6 narrative reviews/editorials. Article publication dates ranged from 1987 to 2017. No intervention studies were identified. Facilitators of chiropractic faculty research included research assignment as primary role, institutional culture promoting research, and dedicated release time. Barriers included teaching/clinic assignments, lack of incentives and mentorship, and teaching load. Qualitative results identified 5 domains impacting faculty research: demographics/professional roles; personal empowerment; research culture; institutional setting/policies; and research training., Conclusion: Our scoping review found a paucity of recently published articles on chiropractic faculty participation in research. Educational institutions building research capacity among chiropractic faculty must establish cultural environments where scholarship is expected, rewarded, and valued. Tangible support, such as research policies, resources, and space, advanced training, funding, and release time, must be available. Faculty are encouraged to build upon key facilitators, evaluate interventions to address barriers to chiropractic faculty research, and publish their results., (© 2023 Association of Chiropractic Colleges.)

Introduction: Maternal deaths increased in the United States during 2018-2021, with documented racial disparities. Respectful maternity care is a component of quality care that includes preventing harm and mistreatment, engaging in effective communication, and providing care equitably. Improving respectful maternity care can be part of multilevel strategies to reduce pregnancy-related deaths., Methods: CDC analyzed data from the PN View Moms survey administered during April 24-30, 2023, to examine the following components of respectful care: 1) experiences of mistreatment (e.g., violations of physical privacy, ignoring requests for help, or verbal abuse), 2) discrimination (e.g., because of race, ethnicity or skin color; age; or weight), and 3) reasons for holding back from communicating questions or concerns during maternity (pregnancy or delivery) care., Results: Among U.S. mothers with children aged <18 years, 20% reported mistreatment while receiving maternity care for their youngest child. Approximately 30% of Black, Hispanic, and multiracial respondents and approximately 30% of respondents with public insurance or no insurance reported mistreatment. Discrimination during the delivery of maternity care was reported by 29% of respondents. Approximately 40% of Black, Hispanic, and multiracial respondents reported discrimination, and approximately 45% percent of all respondents reported holding back from asking questions or discussing concerns with their provider., Conclusions and Implications for Public Health Practice: Approximately one in five women reported mistreatment during maternity care. Implementing quality improvement initiatives and provider training to encourage a culture of respectful maternity care, encouraging patients to ask questions and share concerns, and working with communities are strategies to improve respectful maternity care., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

The narrow-headed vole, collared lemming and common vole were the most abundant small mammal species across the Eurasian Late Pleistocene steppe-tundra environment. Previous ancient DNA studies of the collared lemming and common vole have revealed dynamic population histories shaped by climatic fluctuations. To investigate the extent to which species with similar adaptations share common evolutionary histories, we generated a dataset comprised the mitochondrial genomes of 139 ancient and 6 modern narrow-headed voles from several sites across Europe and northwestern Asia covering approximately the last 100 thousand years (kyr). We inferred Bayesian time-aware phylogenies using 11 radiocarbon-dated samples to calibrate the molecular clock. Divergence of the main mtDNA lineages across the three species occurred during marine isotope stages (MIS) 7 and MIS 5, suggesting a common response of species adapted to open habitat during interglacials. We identified several time-structured mtDNA lineages in European narrow-headed vole, suggesting lineage turnover. The timing of some of these turnovers was synchronous across the three species, allowing us to identify the main drivers of the Late Pleistocene dynamics of steppe- and cold-adapted species.

Traditional clinical research relies on conventional strategies to invite and enroll research participants. However, these strategies often fail to reach potential participants from marginalized communities or that reflect the diversity of the nation, such as race, ethnicity, or geography. As we discuss here, the digital clinical study model sets the stage for improved and equitable participation in biomedical research., Competing Interests: Declaration of interests E.R. is a current employee of CareEvolution, Inc, a health care technology company., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Traditional viral illness surveillance relies on in-person clinical or laboratory data, paper-based data collection, and outdated technology for data transfer and aggregation. We aimed to assess whether continuous sensor data can provide an early warning signal for COVID-19 activity as individual physiological and behavioural changes might precede symptom onset, care seeking, and diagnostic testing., Methods: This multivariable, population-based, modelling study recruited adult (aged ≥18 years) participants living in the USA who had a smartwatch or fitness tracker on any device that connected to Apple HealthKit or Google Fit and had joined the DETECT study by downloading the MyDataHelps app. In the model development cohort, we included people who had participated in DETECT between April 1, 2020, and Jan 14, 2022. In the validation cohort, we included individuals who had participated between Jan 15 and Feb 15, 2022. When a participant joins DETECT, they fill out an intake survey of demographic information, including their ZIP code (postal code), and surveys on symptoms, symptom onset, and viral illness test dates and results, if they become unwell. When a participant connects their device, historical sensor data are collected, if available. Sensor data continue to be collected unless a participant withdraws from the study. Using sensor data, we collected each participant's daily resting heart rate and step count during the entire study period and identified anomalous sensor days, in which resting heart rate was higher than, and step count was lower than, a specified threshold calculated for each individual by use of their baseline data. The proportion of users with anomalous data each day was used to create a 7-day moving average. For the main cohort, a negative binomial model predicting 7-day moving averages for COVID-19 case counts, as reported by the Centers for Disease Control and Prevention (CDC), in real time, 6 days in the future, and 12 days in the future in the USA and California was fitted with CDC-reported data from 3 days before alone (H 0 ) or in combination with anomalous sensor data (H 1 ). We compared the predictions with Pearson correlation. We then validated the model in the validation cohort., Findings: Between April 1, 2020, and Jan 14, 2022, 35 842 participants enrolled in DETECT, of whom 4006 in California and 28 527 in the USA were included in our main cohort. The H 1 model significantly outperformed the H 0 model in predicting the 7-day moving average COVID-19 case counts in California and the USA. For example, Pearson correlation coefficients for predictions 12 days in the future increased by 32·9% in California (from 0·70 [95% CI 0·65-0·73] to 0·93 [0·92-0·94]) and by 12·2% (from 0·82 [0·79-0·84] to 0·92 [0·91-0·93]) in the USA from the H 0 model to the H 1 model. Our validation model also showed significant correlations for predictions in real time, 6 days in the future, and 12 days in the future., Interpretation: Our study showed that passively collected sensor data from consenting participants can provide real-time disease tracking and forecasting. With a growing population of wearable technology users, these sensor data could be integrated into viral surveillance programmes., Funding: The National Center for Advancing Translational Sciences of the US National Institutes of Health, The Rockefeller Foundation, and Amazon Web Services., Competing Interests: Declaration of interests LMW works for The Rockefeller Foundation, which funded part of this study. VK is the principal and an employee of CareEvolution. ER is the principal science officer and an employee of CareEvolution and Scripps Research. JAP is an adviser for Angiotensin Therapeutics, Precision Health, Cardiosense, and Sense AI. GQ and JMR are supported in part under a grant from The Rockefeller Foundation and the National Center for Advancing Translational Sciences, the US National Institutes of Health. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Electronic health record (EHR) technology has become a central digital health tool throughout health care. EHR systems are responsible for a growing number of vital functions for hospitals and providers. More recently, patient-facing EHR tools are allowing patients to interact with their EHR and connect external sources of health data, such as wearable fitness trackers, personal genomics, and outside health services, to it. As patients become more engaged with their EHR, the volume and variety of digital health information will serve an increasingly useful role in health care and health research. Particularly due to the COVID-19 pandemic, the ability for the biomedical research community to pivot to fully remote research, driven largely by EHR data capture and other digital health tools, is an exciting development that can significantly reduce burden on study participants, improve diversity in clinical research, and equip researchers with more robust clinical data. In this viewpoint, we describe how patient engagement with EHR technology is poised to advance the digital clinical trial space, an innovative research model that is uniquely accessible and inclusive for study participants., (©Jeff Pawelek, Katie Baca-Motes, Jay A Pandit, Benjamin B Berk, Edward Ramos. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 08.07.2022.)

The ability to identify who does or does not experience the intended immune response following vaccination could be of great value in not only managing the global trajectory of COVID-19 but also helping guide future vaccine development. Vaccine reactogenicity can potentially lead to detectable physiologic changes, thus we postulated that we could detect an individual's initial physiologic response to a vaccine by tracking changes relative to their pre-vaccine baseline using consumer wearable devices. We explored this possibility using a smartphone app-based research platform that enabled volunteers (39,701 individuals) to share their smartwatch data, as well as self-report, when appropriate, any symptoms, COVID-19 test results, and vaccination information. Of 7728 individuals who reported at least one vaccination dose, 7298 received an mRNA vaccine, and 5674 provided adequate data from the peri-vaccine period for analysis. We found that in most individuals, resting heart rate (RHR) increased with respect to their individual baseline after vaccination, peaked on day 2, and returned to normal by day 6. This increase in RHR was greater than one standard deviation above individuals' normal daily pattern in 47% of participants after their second vaccine dose. Consistent with other reports of subjective reactogenicity following vaccination, we measured a significantly stronger effect after the second dose relative to the first, except those who previously tested positive to COVID-19, and a more pronounced increase for individuals who received the Moderna vaccine. Females, after the first dose only, and those aged <40 years, also experienced a greater objective response after adjusting for possible confounding factors. These early findings show that it is possible to detect subtle, but important changes from an individual's normal as objective evidence of reactogenicity, which, with further work, could prove useful as a surrogate for vaccine-induced immune response., (© 2022. The Author(s).)

Sex determination of the human pelvis has traditionally been done through visual analyses of morphoscopic traits and there are limited metric methods available to forensic anthropologists to add metric credibility to these analyses. The goal of this research was to create an improved metric method using three-dimensional geometric morphometrics to determine sex from both whole and modeled fragmented human pubic bones. The sample consisted of n = 378 pubic bones from the University of New Mexico's Maxwell Museum Documented Skeletal Collection and eight landmarks were collected from each bone. Statistical analyses and machine learning algorithms were used to predict the accuracy of the method's ability to classify a bone as male or female on both whole and simulated fragmented remains; this included tests run on each possible landmark combination of three or more landmarks to simulate fragmented bones (218 combinations). The results of the whole bone analysis resulted in 95.35% testing accuracy. The results of the modeled fragmentary analysis consisted of 164 combinations which exhibit a 90% or higher accuracy in sex prediction; and twelve combinations which exhibit 96% or higher accuracy in sex prediction. In particular, two landmarks clustered around the ventral arc of the pubic bone performed the best, indicating this is the most sexually dimorphic portion of the bone. These results indicate that three-dimensional geometric morphometrics is a valid method to be applied to sex determination in forensic anthropology., Competing Interests: The authors have declared that no competing interests exist.

Individual smartwatch or fitness band sensor data in the setting of COVID-19 has shown promise to identify symptomatic and pre-symptomatic infection or the need for hospitalization, correlations between peripheral temperature and self-reported fever, and an association between changes in heart-rate-variability and infection. In our study, a total of 38,911 individuals (61% female, 15% over 65) have been enrolled between March 25, 2020 and April 3, 2021, with 1118 reported testing positive and 7032 negative for COVID-19 by nasopharyngeal PCR swab test. We propose an explainable gradient boosting prediction model based on decision trees for the detection of COVID-19 infection that can adapt to the absence of self-reported symptoms and to the available sensor data, and that can explain the importance of each feature and the post-test-behavior for the individuals. We tested it in a cohort of symptomatic individuals who exhibited an AUC of 0.83 [0.81-0.85], or AUC = 0.78 [0.75-0.80] when considering only data before the test date, outperforming state-of-the-art algorithm in these conditions. The analysis of all individuals (including asymptomatic and pre-symptomatic) when self-reported symptoms were excluded provided an AUC of 0.78 [0.76-0.79], or AUC of 0.70 [0.69-0.72] when considering only data before the test date. Extending the use of predictive algorithms for detection of COVID-19 infection based only on passively monitored data from any device, we showed that it is possible to scale up this platform and apply the algorithm in other settings where self-reported symptoms can not be collected., (© 2021. The Author(s).)

Phantom Limb Pain (PLP) is a chronic condition frequent among individuals with acquired amputation. PLP has been often investigated with the use of functional MRI focusing on the changes that take place in the sensorimotor cortex after amputation. In the present study, we investigated whether a different type of data, namely electroencephalographic (EEG) recordings, can be used to study the condition. We acquired resting state EEG data from people with and without PLP and then used machine learning for a binary classification task that differentiates the two. Common Spatial Pattern (CSP) decomposition was used as the feature extraction method and two validation schemes were followed for the classification task. Six classifiers (LDA, Log, QDA, LinearSVC, SVC and RF) were optimized through grid search and their performance compared. Two validation approaches, namely all-subjects validation and leave-one-out cross-validation (LOOCV), resulted in high classification accuracy. Most notably, the 93.7% accuracy achieved with SVC in LOOCV holds promise for good diagnostic capabilities using EEG biomarkers. In conclusion, our findings indicate that EEG data is a promising target for future research aiming at elucidating the neural mechanisms underlying PLP and its diagnosis.

Background: Atrial fibrillation (AF) is common, often without symptoms, and is an independent risk factor for mortality, stroke and heart failure. It is unknown if screening asymptomatic individuals for AF can improve clinical outcomes., Methods: mSToPS was a pragmatic, direct-to-participant trial that randomized individuals from a single US-wide health plan to either immediate or delayed screening using a continuous-recording ECG patch to be worn for two weeks and 2 occasions, ~3 months apart, to potentially detect undiagnosed AF. The 3-year outcomes component of the trial was designed to compare clinical outcomes in the combined cohort of 1718 individuals who underwent monitoring and 3371 matched observational controls. The prespecified primary outcome was the time to first event of the combined endpoint of death, stroke, systemic embolism, or myocardial infarction among individuals with a new AF diagnosis, which was hypothesized to be the same in the two cohorts but was not realized., Results: Over the 3 years following the initiation of screening (mean follow-up 29 months), AF was newly diagnosed in 11.4% (n = 196) of screened participants versus 7.7% (n = 261) of observational controls (p<0.01). Among the screened cohort with incident AF, one-third were diagnosed through screening. For all individuals whose AF was first diagnosed clinically, a clinical event was common in the 4 weeks surrounding that diagnosis: 6.6% experienced a stroke,10.2% were newly diagnosed with heart failure, 9.2% had a myocardial infarction, and 1.5% systemic emboli. Cumulatively, 42.9% were hospitalized. For those diagnosed via screening, none experienced a stroke, myocardial infarction or systemic emboli in the period surrounding their AF diagnosis, and only 1 person (2.3%) had a new diagnosis of heart failure. Incidence rate of the prespecified combined primary endpoint was 3.6 per 100 person-years among the actively monitored cohort and 4.5 per 100 person-years in the observational controls., Conclusions: At 3 years, screening for AF was associated with a lower rate of clinical events and improved outcomes relative to a matched cohort, although the influence of earlier diagnosis of AF via screening on this finding is unclear. These observational data, including the high event rate surrounding a new clinical diagnosis of AF, support the need for randomized trials to determine whether screening for AF will yield a meaningful protection from strokes and other clinical events., Trail Registration: The mHealth Screening To Prevent Strokes (mSToPS) Trial is registered on ClinicalTrials.gov with the identifier NCT02506244., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Steve Steinhubl – NIH UL1TR002550 grant support; Qualcomm Foundation. Jill Waalen – No conflicts of interest Anirudh Sanyal - Employee, Healthagen, LLC Alison Edwards – Employee, Healthagen, LLC Lauren Ariniello - NIH UL1TR002550 grant support Gail Ebner - NIH UL1TR002550 grant support; Qualcomm Foundation Katie Baca-Motes - No conflicts of interest Bob Zambon- Employee, Janssen Pharmaceuticals (a subsidiary of Johnson & Johnson); Stockholder Johnson & Johnson. Troy Sarich – Employee, Johnson & Johnson; Stockholder Johnson & Johnson. Eric Topol – NIH UL1TR002550 grant support; Qualcomm Foundation This support does not alter our adherence to PLOS ONE policies on sharing data and materials.

Understanding the spatial and temporal patterns of mortality rates in a highly heterogeneous metropolis, is a matter of public policy interest. In this context, there is no, to the best of our knowledge, previous studies that correlate both spatio-temporal and age-specific mortality rates in Mexico City. Spatio-temporal Kriging modeling was used over five age-specific mortality rates (from the years 2000 to 2016 in Mexico City), to gain both spatial (borough and neighborhood) and temporal (year and trimester) data level description. Mortality age-specific patterns have been modeled using multilevel modeling for longitudinal data. Posterior tests were carried out to compare mortality averages between geo-spatial locations. Mortality correlation extends in all study groups for as long as 12 years and as far as 13.27 km. The highest mortality rate takes place in the Cuauhtémoc borough, the commercial, touristic and cultural core downtown of Mexico City. On the contrary, Tlalpan borough is the one with the lowest mortality rates in all the study groups. Post-productive mortality is the first age-specific cause of death, followed by infant, productive, pre-school and scholar groups. The combinations of spatio-temporal Kriging estimation and time-evolution linear mixed-effect models, allowed us to unveil relevant time and location trends that may be useful for public policy planning in Mexico City., Competing Interests: The authors have declared that no competing interests exist.

Assessment of the air quality in metropolitan areas is a major challenge in environmental sciences. Issues related include the distribution of monitoring stations, their spatial range, or missing information. In Mexico City, stations have been located spanning the entire Metropolitan zone for pollutants, such as CO, NO 2 , O 3 , SO 2 , PM 2.5 , PM 10 , NO, NO x , and PM CO . A fundamental question is whether the number and location of such stations are adequate to optimally cover the city. By analyzing spatio-temporal correlations for pollutant measurements, we evaluated the distribution and performance of monitoring stations in Mexico City from 2009 to 2018. Based on our analysis, air quality evaluation of those contaminants is adequate to cover the 16 boroughs of Mexico City, with the exception of SO 2 , since its spatial range is shorter than the one needed to cover the whole surface of the city. We observed that NO and NO x concentrations must be taken into account since their long-range dispersion may have relevant consequences for public health. With this approach, we may be able to propose policy based on systematic criteria to locate new monitoring stations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Baca-López, Fresno, Espinal-Enríquez, Martínez-García, Camacho-López, Flores-Merino and Hernández-Lemus.)

Traditional screening for COVID-19 typically includes survey questions about symptoms and travel history, as well as temperature measurements. Here, we explore whether personal sensor data collected over time may help identify subtle changes indicating an infection, such as in patients with COVID-19. We have developed a smartphone app that collects smartwatch and activity tracker data, as well as self-reported symptoms and diagnostic testing results, from individuals in the United States, and have assessed whether symptom and sensor data can differentiate COVID-19 positive versus negative cases in symptomatic individuals. We enrolled 30,529 participants between 25 March and 7 June 2020, of whom 3,811 reported symptoms. Of these symptomatic individuals, 54 reported testing positive and 279 negative for COVID-19. We found that a combination of symptom and sensor data resulted in an area under the curve (AUC) of 0.80 (interquartile range (IQR): 0.73-0.86) for discriminating between symptomatic individuals who were positive or negative for COVID-19, a performance that is significantly better (P < 0.01) than a model 1 that considers symptoms alone (AUC = 0.71; IQR: 0.63-0.79). Such continuous, passively captured data may be complementary to virus testing, which is generally a one-off or infrequent sampling assay.

Background: Screening for asymptomatic, undiagnosed atrial fibrillation (AF) has the potential to allow earlier treatment, possibly resulting in prevention of strokes, but also to increase medical resource utilization., Objective: To compare healthcare utilization rates during the year following initiation of screening among participants screened for AF by electrocardiogram (ECG) sensor patch compared with a matched observational control group., Methods: A total of 1718 participants recruited from a health care plan based on age and comorbidities who were screened with an ECG patch (actively monitored group) as part of a prospective, pragmatic research trial were matched by age, sex, and CHA 2 DS 2 -VASc score with 3371 members from the same health plan (observational control group). Healthcare utilization, including visits, prescriptions, procedures, and diagnoses, during the 1 year following screening was compared between the groups using health plan claims data., Results: Overall, the actively monitored group had significantly higher rates of cardiology visits (adjusted incidence rate ratio [aIRR] [95% confidence interval (CI)]: 1.43 [1.27, 1.60]), no difference in primary care provider visits (aIRR [95% CI]: 1.0 [0.95, 1.05]), but lower rates of emergency department (ED) visits and hospitalizations (aIRR [95% CI]: 0.80 [0.69, 0.92]) compared with controls. Among those with newly diagnosed AF, the reduction in ED visits and hospitalizations was even greater (aIRR [95% CI]: 0.27 [0.17, 0.43])., Conclusion: AF screening in an asymptomatic, moderate-risk population with an ECG patch was associated with an increase in cardiology outpatient visits but also significantly lower rates of ED visits and hospitalizations over the 1 year following screening., (© 2020 Heart Rhythm Society. Published by Elsevier Inc.)

During the Late Pleistocene, narrow-headed voles (Lasiopodomys gregalis) inhabited Eurasia's vast territories, frequently becoming the dominant small mammal species among steppe-tundra communities. We investigated the relationship between this species' European and Asiatic populations by sequencing the mtDNA genomes of two extant specimens from Russia and 10 individuals from five Central European sites, dated to the post-LGM period. Phylogenetic analyses based on a large portion of mtDNA genomes highly supported the positioning of L. gregalis within Arvicolinae. The phylogeny based on mtDNA cytochrome b sequences revealed a deep divergence of European narrow-headed voles from Asiatic ones and their sister position against the extant L. gregalis and L. raddei. The divergence of the European lineage was estimated to a minimum 230 thousand years ago. This suggest, contrary to the current biogeographic hypotheses, that during the interglacial periods narrow-headed vole did not retreat from Europe but survived the unfavourable conditions within the refugial areas. Based on this result, we propose to establish a cryptic species status for the Late Pleistocene European narrow-headed vole and to name this taxon Lasiopodomys anglicus.

Many barriers to primary healthcare accessibility in the United States exist including an increased opportunity cost associated with seeking primary care. New models of healthcare delivery aimed at addressing these problems are emerging. The potential impact that on-demand primary care physician house calls services can have on healthcare accessibility, patient care, and satisfaction by both patients and physicians is poorly characterized.We performed a retrospective observational analysis on data from 13,849 patients who utilized Heal, Inc, an application (app)-based, on-demand house calls platform between August 2016 and July 2017. We assessed house call wait time and visit duration, diagnoses by International Classification of Diseases, tenth revision, Inc (ICD10) codes, and house call outcomes by post-visit prescription and lab requests, and patient satisfaction survey.Patients who utilized this physician house call service had a bimodal age distribution peaking at age 1 year and 36 years. Same day acute sick exams (93.9% of pediatric (Ped) and 66.9% of adult requests) for fever and/or acute upper respiratory infection represented the most common use. The mean wait time for as soon as possible house calls were 96.1 minutes, with an overall mean house call duration of 27.1 minutes. A house call was primarily chosen over an Urgent Care Clinic or Doctor's office (46.2% and 41.6% of respondents, respectively), due to convenience or fastest appointment available (69.6% and 33.8% of respondents, respectively). Most survey respondents (94.2%) would schedule house calls again.On-demand physician house calls programs can expand access options to primary healthcare, primarily used by younger individuals with acute illness and preference for a smartphone app-based home visit.

Objectives: The advent of large databases, wearable technology, and novel communications methods has the potential to expand the pool of candidate research participants and offer them the flexibility and convenience of participating in remote research. However, reports of their effectiveness are sparse. We assessed the use of various forms of outreach within a nationwide randomized clinical trial being conducted entirely by remote means., Methods: Candidate participants at possibly higher risk for atrial fibrillation were identified by means of a large insurance claims database and invited to participate in the study by their insurance provider. Enrolled participants were randomly assigned to one of two groups testing a wearable sensor device for detection of the arrhythmia., Results: Over 10 months, the various outreach methods used resulted in enrollment of 2659 participants meeting eligibility criteria. Starting with a baseline enrollment rate of 0.8% in response to an email invitation, the recruitment campaign was iteratively optimized to ultimately include website changes and the use of a five-step outreach process (three short, personalized emails and two direct mailers) that highlighted the appeal of new technology used in the study, resulting in an enrollment rate of 9.4%. Messaging that highlighted access to new technology outperformed both appeals to altruism and appeals that highlighted accessing personal health information., Conclusions: Targeted outreach, enrollment, and management of large remote clinical trials is feasible and can be improved with an iterative approach, although more work is needed to learn how to best recruit and retain potential research participants., Trial Registration: Clinicaltrials.govNCT02506244. Registered 23 July 2015.

Importance: Opportunistic screening for atrial fibrillation (AF) is recommended, and improved methods of early identification could allow for the initiation of appropriate therapies to prevent the adverse health outcomes associated with AF., Objective: To determine the effect of a self-applied wearable electrocardiogram (ECG) patch in detecting AF and the clinical consequences associated with such a detection strategy., Design, Setting, and Participants: A direct-to-participant randomized clinical trial and prospective matched observational cohort study were conducted among members of a large national health plan. Recruitment began November 17, 2015, and was completed on October 4, 2016, and 1-year claims-based follow-up concluded in January 2018. For the clinical trial, 2659 individuals were randomized to active home-based monitoring to start immediately or delayed by 4 months. For the observational study, 2 deidentified age-, sex- and CHA2DS2-VASc-matched controls were selected for each actively monitored individual., Interventions: The actively monitored cohort wore a self-applied continuous ECG monitoring patch at home during routine activities for up to 4 weeks, initiated either immediately after enrolling (n = 1364) or delayed for 4 months after enrollment (n = 1291)., Main Outcomes and Measures: The primary end point was the incidence of a new diagnosis of AF at 4 months among those randomized to immediate monitoring vs delayed monitoring. A secondary end point was new AF diagnosis at 1 year in the combined actively monitored groups vs matched observational controls. Other outcomes included new prescriptions for anticoagulants and health care utilization (outpatient cardiology visits, primary care visits, or AF-related emergency department visits and hospitalizations) at 1 year., Results: The randomized groups included 2659 participants (mean [SD] age, 72.4 [7.3] years; 38.6% women), of whom 1738 (65.4%) completed active monitoring. The observational study comprised 5214 (mean [SD] age, 73.7 [7.0] years; 40.5% women; median CHA2DS2-VASc score, 3.0), including 1738 actively monitored individuals from the randomized trial and 3476 matched controls. In the randomized study, new AF was identified by 4 months in 3.9% (53/1366) of the immediate group vs 0.9% (12/1293) in the delayed group (absolute difference, 3.0% [95% CI, 1.8%-4.1%]). At 1 year, AF was newly diagnosed in 109 monitored (6.7 per 100 person-years) and 81 unmonitored (2.6 per 100 person-years; difference, 4.1 [95% CI, 3.9-4.2]) individuals. Active monitoring was associated with increased initiation of anticoagulants (5.7 vs 3.7 per 100 person-years; difference, 2.0 [95% CI, 1.9-2.2]), outpatient cardiology visits (33.5 vs 26.0 per 100 person-years; difference, 7.5 [95% CI, 7.2-7.9), and primary care visits (83.5 vs 82.6 per 100 person-years; difference, 0.9 [95% CI, 0.4-1.5]). There was no difference in AF-related emergency department visits and hospitalizations (1.3 vs 1.4 per 100 person-years; difference, 0.1 [95% CI, -0.1 to 0])., Conclusions and Relevance: Among individuals at high risk for AF, immediate monitoring with a home-based wearable ECG sensor patch, compared with delayed monitoring, resulted in a higher rate of AF diagnosis after 4 months. Monitored individuals, compared with nonmonitored controls, had higher rates of AF diagnosis, greater initiation of anticoagulants, but also increased health care resource utilization at 1 year., Trial Registration: ClinicalTrials.gov Identifier: NCT02506244.

A collaborative European DNA Profiling (EDNAP) Group exercise was undertaken to assess the performance of an earlier described SNaPshot™-based screening assay (denoted mini-mtSNaPshot) (Weiler et al., 2016) [1] that targets 18 single nucleotide polymorphism (SNP) positions in the mitochondrial (mt) DNA control region and allows for discrimination of major European mtDNA haplogroups. Besides the organising laboratory, 14 forensic genetics laboratories were involved in the analysis of 13 samples, which were centrally prepared and thoroughly tested prior to shipment. The samples had a variable complexity and comprised straightforward single-source samples, samples with dropout or altered peak sizing, a point heteroplasmy and two-component mixtures resulting in one to five bi-allelic calls. The overall success rate in obtaining useful results was high (97.6%) given that some of the participating laboratories had no previous experience with the typing technology and/or mtDNA analysis. The majority of the participants proceeded to haplotype inference to assess the feasibility of assigning a haplogroup and checking phylogenetic consistency when only 18 SNPs are typed. To mimic casework procedures, the participants compared the SNP typing data of all 13 samples to a set of eight mtDNA reference profiles that were described according to standard nomenclature (Parson et al., 2014) [2], and indicated whether these references matched each sample or not. Incorrect scorings were obtained for 2% of the comparisons and derived from a subset of the participants, indicating a need for training and guidelines regarding mini-mtSNaPshot data interpretation., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Fidelity has been identified as an important element in a subject's perception of realism and engagement in learning during a simulation experience. The purpose of this study was to determine whether an isolated visual and olfactory sensory change to the simulation environment affects the subjects' perceptions of realism during simulation cases., Methods: Using an electrosurgical unit applied to bovine muscle tissue, we created a model to simulate the characteristic operating room smoke and burning odor that occur during many procedures. Anesthesiologist subjects were randomly assigned to an intervention group that participated in a simulation involving the characteristic smoke and odor or a control group whose simulation involved no smoke or odor. Subjects completed a 7-question survey on the fidelity of the simulation, their perception of realism, and their learning engagement., Results: We enrolled 103 subjects over 22 simulation courses in our study (intervention, n = 52; control, n = 51). The subjects' reactions to the physical (P = 0.73), conceptual (P = 0.34), and emotional (P = 0.12) fidelity and their perception of realism (P = 0.71) did not differ between the intervention and control groups., Discussion: In a high-fidelity simulation environment, a visual and olfactory increment to physical fidelity did not affect subjects' overall ratings of fidelity, perceptions of realism, and engagement in the learning experience.

Copper-based chemotherapeutic compounds Casiopeínas, have been presented as able to promote selective programmed cell death in cancer cells, thus being proper candidates for targeted cancer therapy. DNA fragmentation and apoptosis-in a process mediated by reactive oxygen species-for a number of tumor cells, have been argued to be the main mechanisms. However, a detailed functional mechanism (a model) is still to be defined and interrogated for a wide variety of cellular conditions before establishing settings and parameters needed for their wide clinical application. In order to shorten the gap in this respect, we present a model proposal centered in the role played by intrinsic (or mitochondrial) apoptosis triggered by oxidative stress caused by the chemotherapeutic agent. This model has been inferred based on genome wide expression profiling in cervix cancer (HeLa) cells, as well as statistical and computational tests, validated via functional experiments (both in the same HeLa cells and also in a Neuroblastoma model, the CHP-212 cell line) and assessed by means of data mining studies.

Metabolic transformations have been reported as involved in neoplasms survival. This suggests a role of metabolic pathways as potential cancer pharmacological targets. Modulating tumor's energy production pathways may become a substantial research area for cancer treatment. The significant role of metabolic deregulation as inducing transcriptional instabilities and consequently whole-system failure, is thus of foremost importance. By using a data integration approach that combines experimental evidence for high-throughput genome wide gene expression, a non-equilibrium thermodynamics analysis, nonlinear correlation networks as well as database mining, we were able to outline the role that transcription factors MEF2C and MNDA may have as main master regulators in primary breast cancer phenomenology, as well as the possible interrelationship between malignancy and metabolic dysfunction. The present findings are supported by the analysis of 1191 whole genome gene expression experiments, as well as probabilistic inference of gene regulatory networks, and non-equilibrium thermodynamics of such data. Other evidence sources include pathway enrichment and gene set enrichment analyses, as well as motif comparison with a comprehensive gene regulatory network (of homologue genes) in Arabidopsis thaliana. Our key finding is that the non-equilibrium free energies provide a realistic description of transcription factor activation that when supplemented with gene regulatory networks made us able to find deregulated pathways. These analyses also suggest a novel potential role of transcription factor energetics at the onset of primary tumor development. Results are important in the molecular systems biology of cancer field, since deregulation and coupling mechanisms between metabolic activity and transcriptional regulation can be better understood by taking into account the way that master regulators respond to physicochemical constraints imposed by different phenotypic conditions.

Background: Abnormalities of chromosome 13 have been associated with bilateral retinoblastoma. Deletion of a retinoblastoma gene is a common primary mechanism. Other abnormalities are more rare. To our knowledge, a balanced translocation of the long arms of the X and 13 chromosomes associated with bilateral retinoblastoma has been reported five times. We report an unbalanced X;13 translocation resulting in partial trisomy 13 and an interstitial deletion of an RB locus., Methods: Case report., Results: A 19-month-old child presented with seizures to the emergency department. A CT scan revealed bilateral intraocular calcification, and retinoblastoma (RB) was confirmed with an ophthalmic exam. Abnormal facies and developmental delay were noted. A partial trisomy derived from the translocation of X;13 was observed in both bone marrow and peripheral blood cells. Fluorescence in-situ hybridization (FISH) studies confirmed triplication of a region on the q arm of chromosome 13 spanning the RB locus. One of the normal chromosome 13 homologues had an interstitial deletion of the RB locus since no signal was observed for the RB-1 probe despite the visible presence of the 13q14 region. Additional evidence of the interstitial deletion is supported by the typical facial features and developmental delay found. Presumably, the translocated X underwent X inactivation precluding systemic features typically observed in trisomy 13. Parental karyotypes were normal. The chromosomal abnormality was a de-novo constitutional event., Conclusions: Only two RB loci were present in this patient despite triplication of 13q. The third locus was deleted. We believe that the second locus was not expressed due to X inactivation of the RB gene on the der(X)t(Xq:13q) chromosome. The emergence of bilateral retinoblastoma points towards lack of heterozygosity at the third and last remaining RB loci in tumor cells. To our knowledge, an unbalanced translocation resulting in partial trisomy 13 with retinoblastoma has not been previously reported.

Selectively bred withdrawal seizure prone (WSP1 and WSP2) and withdrawal seizure resistant (WSR1 and WSR2) mice were used to test the extent to which severity of ethanol withdrawal response is predictive of the reinforcing effects of ethanol. Mice were systematically introduced to ethanol under a fixed ratio 1 (FR 1) schedule using adjunctive drinking methods. There were no significant differences in ethanol consumption between the lines during training. Subsequently, responding for ethanol concentrations of 8%, 0% (vehicle control), and 8% retest under a FR 1 schedule in the absence of food induction was measured. Group data showed that ethanol did not serve as a reinforcer in the test phase within any of the four lines, and there were no significant line differences in rate of responding, intake, or blood ethanol concentrations (BEC). Mice were next tested for responding for ethanol under a FR 4 schedule. Again, ethanol did not serve as a reinforcer for any of the four groups, and there were no significant differences between the lines. However, further analysis showed that there were individual differences in responding within each group, some animals were apparently reinforced by ethanol, while others showed no reinforcement and some appeared to avoid ethanol. There was no systematic pattern within or between groups for these individual differences in responding. Thus, both the group results as well as the behavior patterns of individual animals are consistent with the conclusion that genes regulating rewarding effects of ethanol appear to be segregating randomly across groups and are independent of genes mediating ethanol withdrawal severity.(ABSTRACT TRUNCATED AT 250 WORDS)