Miracle-dz/UniFAR-FTUs huggingface dataset:
The devil is in the details—Host disease and co‐infections are associated with zoonotic pathogen carriage in Norway rats (Rattus norvegicus)

Traditionally, zoonotic pathogen ecology studies in wildlife have focused on the interplay among hosts, their demographic characteristics and their pathogens. But pathogen ecology is also influenced by factors that traverse the hierarchical scale of biological organization, ranging from within‐host factors at the molecular, cellular and organ levels, all the way to the host population within a larger environment. The influence of host disease and co‐infections on zoonotic pathogen carriage in hosts is important because these factors may be key to a more holistic understanding of pathogen ecology in wildlife hosts, which are a major source of emerging infectious diseases in humans. Using wild Norway rats (Rattus norvegicus) as a model species, the purpose of this study was to investigate how host disease and co‐infections impact the carriage of zoonotic pathogens. Following a systematic trap and removal study, we tested the rats for the presence of two potentially zoonotic bacterial pathogens (Bartonella tribocorum and Leptospira interrogans) and assessed them for host disease not attributable to these bacteria (i.e., nematode parasites, and macroscopic and microscopic lesions). We fitted multilevel multivariable logistic regression models with pathogen status as the outcome, lesions and parasites as predictor variables and city block as a random effect. Rats had significantly increased odds of being infected with B. tribocorum if they had a concurrent nematode infection in one or more organ systems. Rats with bite wounds, any macroscopic lesion, cardiomyopathy or tracheitis had significantly increased odds of being infected with L. interrogans. These results suggest that host disease may have an important role in the ecology and epidemiology of rat‐associated zoonotic pathogens. Our multiscale approach to assessing complex intrahost factors in relation to zoonotic pathogen carriage may be applicable to future studies in rats and other wildlife hosts.
A Prospective Study of Toenail Trace Element Levels and Risk of Skin Cancer

Background: Few epidemiologic studies have investigated trace element exposure and skin cancer risk. Methods: Toenail levels of mercury, selenium, chromium, iron, and zinc were measured from 6,708 women in the Nurses' Health Study (1984–2012) and 3,730 men in the Health Professionals Follow-up Study (1986–2012) with data from prior nested case–control studies. Participants were free of skin cancer at toenail collection and followed for incident basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma. Cox proportional hazards models were used to compute hazard ratios (HR) and 95% confidence intervals (CI) of skin cancer associated with the elements in each study. We calculated pooled multivariable HRs using a fixed-effects model. During 26 to 28 years of follow-up, 2,433 BCC, 334 SCC, and 130 melanoma cases were documented. Results: Higher toenail mercury levels were associated with risk of BCC [pooled HR for top vs. bottom quintiles = 1.34 (95% CI, 1.18–1.52), Ptrend < 0.0001]. Similar direct associations were found with risks of SCC [pooled HR for top vs. bottom quartiles = 1.41 (95% CI, 1.03–1.94), Ptrend = 0.04] and melanoma [pooled HR for top vs. bottom quartiles = 1.88 (95% CI, 1.12–3.16), Ptrend = 0.02]. Chromium was positively associated with BCC in women only. No associations were found between other metals and skin cancer risk. Conclusions: Our prospective data found that increased toenail mercury concentrations were associated with increased skin cancer risk. Impact: If our novel findings are confirmed, mercury may play a role in skin carcinogenesis.
Multicentric osteolytic syndromes represent a phenotypic spectrum defined by defective collagen remodeling

Frank‐Ter Haar syndrome (FTHS), Winchester syndrome (WS), and multicentric osteolysis, nodulosis, and arthropathy (MONA) are ultra‐rare multisystem disorders characterized by craniofacial malformations, reduced bone density, skeletal and cardiac anomalies, and dermal fibrosis. These autosomal recessive syndromes are caused by homozygous mutation or deletion of respectively SH3PXD2B (SH3 and PX Domains 2B), MMP14 (matrix metalloproteinase 14), or MMP2. Here, we give an overview of the clinical features of 63 previously reported patients with an SH3PXD2B, MMP14, or MMP2 mutation, demonstrating considerable clinical overlap between FTHS, WS, and MONA. Interestingly, the protein products of SH3PXD2B, MMP14, and MMP2 directly cooperate in collagen remodeling. We review animal models for these three disorders that accurately reflect the major clinical features and likewise show significant phenotypical similarity with each other. Furthermore, they demonstrate that defective collagen remodeling is central in the underlying pathology. As such, we propose a nosological revision, placing these SH3PXD2B, MMP14, and MMP2 related syndromes in a novel “defective collagen‐remodelling spectrum (DECORS)”. In our opinion, this revised nosology better reflects the central role for impaired collagen remodeling, a potential target for pharmaceutical intervention.
Implementing a Framework to Evaluate the Impact of Food Intake Shifts on Risk of Illness Using a Case Study with Infant Cereal (P11-118-19).

Objectives We developed a framework to provide decision makers with a multi-faceted evaluation of the impact of dietary shifts on risk of illness in the U.S. population. Methods We collected representative data on prevalence and concentration of inorganic arsenic and aflatoxin in infant rice and oat cereal. Exposure to these contaminants through consumption and risk of illness from cancer were assessed per consumer based on data from the National Health and Nutrition Examination Survey and published dose-response and related data. The expected number of additional cases of illness and disability-adjusted life years (DALYs) for the U.S. population were estimated. The public health impact of shifts in consumption from one product to the other considered marginal and joint consumption and characterized uncertainty arising from estimates of contaminant concentrations, bioavailability and dose-response models. Monte Carlo simulations were developed in R and a Shiny app was created. Results Based on current consumption of infant rice and oat cereal, the estimated additional DALY for the total US population from inorganic arsenic and aflatoxin is 4,600 (CI 90% [370; 8,400]). If all consumers shift their consumption (maintaining equivalent servings) to only infant rice or only infant oat cereal, the estimated DALY increases to 1.4 and decreases to 0.4 relative to the baseline, respectively. Changes in contaminant concentrations or % consumers also significantly impact risk. Uncertainty in risk estimates is primarily driven by the dose-response models for this case study. The case study showcases applicability of the framework for a wide range of food safety and nutrition questions. Results support previous advice on varying grain intake in children. Conclusions The current risk-risk framework can provide decision makers with a nuanced understanding of the impact of consumption shifts on public health and reveal parameters that drive predicted changes in public health. The Shiny app provides a real-time visualization tool to facilitate understanding and allow direct query by decision makers. Funding Sources This work was carried out under official duties or contract with U.S. FDA.
Crimean-Congo Hemorrhagic Fever, Herat Province, Afghanistan, 2017

We studied the clinical and epidemiologic features of an outbreak of Crimean-Congo hemorrhagic fever in Herat Province, Afghanistan. The study comprised 63 patients hospitalized in 2017. The overall case-fatality rate was 22.2%; fatal outcome was significantly associated with a negative IgM test result, longer prothrombin time, and nausea.
Reference database and performance evaluation of methods for extraction of atrial fibrillatory waves in the ECG

Objective: This study proposes a reference database, composed of a large number of simulated ECG signals in atrial fibrillation (AF), for investigating the performance of methods for extraction of atrial fibrillatory waves (f-waves). Approach: The simulated signals are produced using a recently published and validated model of 12-lead ECGs in AF. The database is composed of eight signal sets together accounting for a wide range of characteristics known to represent major challenges in f-wave extraction, including high heart rates, high morphological QRST variability, and the presence of ventricular premature beats. Each set contains 30 5 min signals with different f-wave amplitudes. The database is used for the purpose of investigating the statistical association between different indices, designed for use with either real or simulated signals. Main results: Using the database, available at the PhysioNet repository of physiological signals, the performance indices unnormalized ventricular residue (uVR), designed for real signals, and the root mean square error, designed for simulated signals, were found to exhibit the strongest association, leading to the recommendation that uVR should be used when characterizing performance in real signals. Significance: The proposed database facilitates comparison of the performance of different f-wave extraction methods and makes it possible to express performance in terms of the error between simulated and extracted f-wave signals.
ANP32 Proteins Are Essential for Influenza Virus Replication in Human Cells

Influenza virus is the etiological agent behind some of the most devastating infectious disease pandemics to date, and influenza outbreaks still pose a major threat to public health. Influenza virus polymerase, the molecule that copies the viral RNA genome, hijacks cellular proteins to support its replication. Current anti-influenza drugs are aimed against viral proteins, including the polymerase, but RNA viruses like influenza tend to become resistant to such drugs very rapidly. An alternative strategy is to design therapeutics that target the host proteins that are necessary for virus propagation. Here, we show that the human proteins ANP32A and ANP32B are essential for influenza A and B virus replication, such that in their absence cells become impervious to the virus. We map the proviral activity of ANP32 proteins to one region in particular, which could inform future intervention. ABSTRACT ANP32 proteins have been implicated in supporting influenza virus replication, but most of the work to date has focused on the ability of avian Anp32 proteins to overcome restriction of avian influenza polymerases in human cells. Using a CRISPR approach, we show that the human acidic nuclear phosphoproteins (ANPs) ANP32A and ANP32B are functionally redundant but essential host factors for mammalian-adapted influenza A virus (IAV) and influenza B virus (IBV) replication in human cells. When both proteins are absent from human cells, influenza polymerases are unable to replicate the viral genome, and infectious virus cannot propagate. Provision of exogenous ANP32A or ANP32B recovers polymerase activity and virus growth. We demonstrate that this redundancy is absent in the murine Anp32 orthologues; murine Anp32A is incapable of recovering IAV polymerase activity, while murine Anp32B can do so. Intriguingly, IBV polymerase is able to use murine Anp32A. We show, using a domain swap and point mutations, that the leucine-rich repeat (LRR) 5 region comprises an important functional domain for mammalian ANP32 proteins. Our approach has identified a pair of essential host factors for influenza virus replication and can be harnessed to inform future interventions. IMPORTANCE Influenza virus is the etiological agent behind some of the most devastating infectious disease pandemics to date, and influenza outbreaks still pose a major threat to public health. Influenza virus polymerase, the molecule that copies the viral RNA genome, hijacks cellular proteins to support its replication. Current anti-influenza drugs are aimed against viral proteins, including the polymerase, but RNA viruses like influenza tend to become resistant to such drugs very rapidly. An alternative strategy is to design therapeutics that target the host proteins that are necessary for virus propagation. Here, we show that the human proteins ANP32A and ANP32B are essential for influenza A and B virus replication, such that in their absence cells become impervious to the virus. We map the proviral activity of ANP32 proteins to one region in particular, which could inform future intervention.
Health Ethics and Indigenous Ethnocide

In colonial societies such as Canada the implications of colonialism and ethnocide (or cultural genocide) for ethical decision-making are ill-understood yet have profound implications in health ethics and other spheres. They combine to shape racism in health care in ways, sometimes obvious, more often subtle, that are inadequately understood and often wholly unnoticed. Along with overt experiences of interpersonal racism, Indigenous people with health care needs are confronted by systemic racism in the shaping of institutional structures, hospital policies and in resource allocation decisions. Above all, racism is a function of state law - of the unilateral imposition of the settler society law on Indigenous communities. Indeed, the laws, including health laws, are social determinants of the ill-health of Indigenous peoples. This article describes the problem of Indigenous ethnocide and explores its ethical implications. It thereby problematizes the role of law in health ethics.
Magnetic Resonance Perfusion or Fractional Flow Reserve in Coronary Disease.

BACKGROUND In patients with stable angina, two strategies are often used to guide revascularization: one involves myocardial-perfusion cardiovascular magnetic resonance imaging (MRI), and the other involves invasive angiography and measurement of fractional flow reserve (FFR). Whether a cardiovascular MRI-based strategy is noninferior to an FFR-based strategy with respect to major adverse cardiac events has not been established. METHODS We performed an unblinded, multicenter, clinical-effectiveness trial by randomly assigning 918 patients with typical angina and either two or more cardiovascular risk factors or a positive exercise treadmill test to a cardiovascular MRI-based strategy or an FFR-based strategy. Revascularization was recommended for patients in the cardiovascular-MRI group with ischemia in at least 6% of the myocardium or in the FFR group with an FFR of 0.8 or less. The composite primary outcome was death, nonfatal myocardial infarction, or target-vessel revascularization within 1 year. The noninferiority margin was a risk difference of 6 percentage points. RESULTS A total of 184 of 454 patients (40.5%) in the cardiovascular-MRI group and 213 of 464 patients (45.9%) in the FFR group met criteria to recommend revascularization (P = 0.11). Fewer patients in the cardiovascular-MRI group than in the FFR group underwent index revascularization (162 [35.7%] vs. 209 [45.0%], P = 0.005). The primary outcome occurred in 15 of 421 patients (3.6%) in the cardiovascular-MRI group and 16 of 430 patients (3.7%) in the FFR group (risk difference, -0.2 percentage points; 95% confidence interval, -2.7 to 2.4), findings that met the noninferiority threshold. The percentage of patients free from angina at 12 months did not differ significantly between the two groups (49.2% in the cardiovascular-MRI group and 43.8% in the FFR group, P = 0.21). CONCLUSIONS Among patients with stable angina and risk factors for coronary artery disease, myocardial-perfusion cardiovascular MRI was associated with a lower incidence of coronary revascularization than FFR and was noninferior to FFR with respect to major adverse cardiac events. (Funded by the Guy's and St. Thomas' Biomedical Research Centre of the National Institute for Health Research and others; MR-INFORM ClinicalTrials.gov number, NCT01236807.).
Civic honesty around the globe

Honesty and selfishness across cultures Rationalist approaches to economics assume that people value their own interests over the interests of strangers. Cohn et al. wanted to examine the trade-off between material self-interest and more altruistic behaviors (see the Perspective by Shalvi). They distributed more than 17,000 wallets containing various sums of money in 355 cities across 40 countries. In contrast to what rationalist theories of economics predict, citizens were more likely to return wallets that contained more money. The findings also reveal a high level of civic honesty across nations. Science, this issue p. 70; see also p. 29 Honesty and selfishness across cultures Civic honesty is essential to social capital and economic development but is often in conflict with material self-interest. We examine the trade-off between honesty and self-interest using field experiments in 355 cities spanning 40 countries around the globe. In these experiments, we turned in more than 17,000 lost wallets containing varying amounts of money at public and private institutions and measured whether recipients contacted the owners to return the wallets. In virtually all countries, citizens were more likely to return wallets that contained more money. Neither nonexperts nor professional economists were able to predict this result. Additional data suggest that our main findings can be explained by a combination of altruistic concerns and an aversion to viewing oneself as a thief, both of which increase with the material benefits of dishonesty.
How Rhythmic Skills Relate and Develop in School-Age Children

Rhythmic expertise can be considered a multidimensional skill set, with clusters of distinct rhythmic abilities evident in young adults. In this article, we explore relationships in school-age children (ages 5-8 years) among 4 rhythmic tasks hypothesized to reflect different clusters of skills, namely, drumming to an isochronous beat, remembering rhythmic patterns, drumming to the beat in music, and clapping in time with feedback. We find that drumming to an isochronous beat and remembering rhythmic patterns are not related. In addition, clapping in time with feedback correlates with performance on the other 3 rhythm tasks. This study contributes to the taxonomy of rhythmic skills in school-age children. It also supports the use of clapping in time training as a way to possibly affect a broad spectrum of rhythmic abilities that are linked to language and literacy processes.
Mechanisms and biomedical implications of –1 programmed ribosome frameshifting on viral and bacterial mRNAs

Some proteins are expressed as a result of a ribosome frameshifting event that is facilitated by a slippery site and downstream secondary structure elements in the mRNA. This review summarizes recent progress in understanding mechanisms of –1 frameshifting in several viral genes, including IBV 1a/1b, HIV‐1 gag‐pol, and SFV 6K, and in Escherichia coli dnaX. The exact frameshifting route depends on the availability of aminoacyl‐tRNAs: the ribosome normally slips into the –1‐frame during tRNA translocation, but can also frameshift during decoding at condition when aminoacyl‐tRNA is in limited supply. Different frameshifting routes and additional slippery sites allow viruses to maintain a constant production of their key proteins. The emerging idea that tRNA pools are important for frameshifting provides new direction for developing antiviral therapies.
Analysis of tap-changer dynamics and construction of voltage stability regions

The destabilizing behavior of on-load tap-changers is an important mechanism responsible for the voltage collapse of power systems. The authors use a nonlinear dynamic model of the tap-changer, impedance loads, and decoupled reactive power-voltage relations to reconstruct the collapse. Based on the proposed M-bus network model, results presented include (1) a criterion for voltage stability, (2) a method to obtain a voltage region, and (3) qualitative characterizations of the equilibria. <<ETX>>
Conversational Games within Dialogue

An analysis of task oriented dialogue has been developed around goal-directed exchanges labelled conversational games. Games account for that aspect of discourse coherence that is manifested in initiation{response{feedback patterns, and they do so by relating the form of dialogue to underlying non-linguistic goals. The system applies to real, spontaneous dialogue and may prove useful in the design of computer dialogue systems. A study was conducted to determine agreement among analysts, upon coding two sets of dialogues. One expert and three novice analysts agreed on an average of 78% of the moves assigned. When certain consistent di(cid:11)erences are taken into account, however, the accuracy increases to 88%
Cell migration directionality and speed are independently regulated by RasG and Gβ in Dictyostelium cells in electrotaxis

ABSTRACT Motile cells manifest increased migration speed and directionality in gradients of stimuli, including chemoattractants, electrical potential and substratum stiffness. Here, we demonstrate that Dictyostelium cells move directionally in response to an electric field (EF) with specific acceleration/deceleration kinetics of directionality and migration speed. Detailed analyses of the migration kinetics suggest that migration speed and directionality are separately regulated by Gβ and RasG, respectively, in EF-directed cell migration. Cells lacking Gβ, which is essential for all chemotactic responses in Dictyostelium, showed EF-directed cell migration with the same increase in directionality in an EF as wild-type cells. However, these cells failed to show induction of the migration speed upon EF stimulation as much as wild-type cells. Loss of RasG, a key regulator of chemoattractant-directed cell migration, resulted in almost complete loss of directionality, but similar acceleration/deceleration kinetics of migration speed as wild-type cells. These results indicate that Gβ and RasG are required for the induction of migration speed and directionality, respectively, in response to an EF, suggesting separation of migration speed and directionality even with intact feedback loops between mechanical and signaling networks. Summary: Cell migration directionality and speed are independently regulated by RasG and Gβ, respectively, in electric field-directed cell migration in Dictyostelium, suggesting the points of molecular divergence of the two characteristics.