Miracle-dz/UniFAR-FTUs huggingface dataset:
Atherogenesis in the Carotid Artery with and without Interrupted Blood Flow of Two Hyperlipidemic Mouse Strains

Purpose: Atherosclerosis in the carotid arteries is a common cause of ischemic stroke. We examined atherogenesis in the left carotid artery with and without interrupted blood flow of C57BL/6 (B6) and C3H-Apoe-deficient (Apoe–/–) mouse strains. Methods: Blood flow was interrupted by ligating the common carotid artery near its bifurcation in one group of mice and another group was not interrupted. Results: Without interference with blood flow, C3H-Apoe–/– mice developed no atherosclerosis in the carotid artery, while B6-Apoe–/– mice formed advanced atherosclerotic lesions (98,019 ± 10,594 μm2/section) after 12 weeks of a Western diet. When blood flow was interrupted by ligating the common carotid artery near its bifurcation, C3H-Apoe–/– mice showed fatty streak lesions 2 weeks after ligation, and by 4 weeks fibrous lesions had formed, although they were smaller than in B6-Apoe–/– mice. Neutrophil adhesion to endothelium and infiltration in lesions was observed in ligated arteries of both strains. Treatment of B6-Apoe–/– mice with antibody against neutrophils had little effect on lesion size. Conclusions: These findings demonstrate the dramatic influences of genetic backgrounds and blood flow on atherogenesis in the carotid artery of hyperlipidemic mice.
VAR2CSA Serology to Detect Plasmodium falciparum Transmission Patterns in Pregnancy

Pregnant women constitute a promising sentinel group for continuous monitoring of malaria transmission. To identify antibody signatures of recent Plasmodium falciparum exposure during pregnancy, we dissected IgG responses against VAR2CSA, the parasite antigen that mediates placental sequestration. We used a multiplex peptide-based suspension array in 2,354 samples from pregnant women from Mozambique, Benin, Kenya, Gabon, Tanzania, and Spain. Two VAR2CSA peptides of limited polymorphism were immunogenic and targeted by IgG responses readily boosted during infection and with estimated half-lives of <2 years. Seroprevalence against these peptides reflected declines and rebounds of transmission in southern Mozambique during 2004–2012, reduced exposure associated with use of preventive measures during pregnancy, and local clusters of transmission that were missed by detection of P. falciparum infections. These data suggest that VAR2CSA serology can provide a useful adjunct for the fine-scale estimation of the malaria burden among pregnant women over time and space.
Updated overview on von Willebrand disease: focus on the interest of genotyping

ABSTRACT Introduction: Von Willebrand disease (VWD) is the most common inherited bleeding disorder, characterized by a quantitative or qualitative defect of von Willebrand factor (VWF), a multimeric glycoprotein crucial for primary hemostasis and coagulation. VWD pathophysiology is heterogeneous as it includes several types and subtypes which therapeutic management is different. The mainstays of VWD treatment are desmopressin and replacement therapy based on both plasma-derived concentrates and a recently developed recombinant VWF. VWD definitive diagnosis is achieved by a battery of phenotypic biologic assays and genotyping is currently performed mostly for research. Areas covered: This narrative review will firstly present a general overview on VWD epidemiology, pathophysiology, classification, clinics, phenotypic biologic diagnosis, and treatment. Secondly, a focus on VWD genotyping will be presented with specific emphasis on the evolution of its technical aspects, its applications for research dedicated to a better understanding of VWD pathophysiology and epidemiology and its interest in both a faster diagnosis and an optimal treatment of VWD. Expert opinion: Based on analysis of the literature, it can be concluded that the fast evolution of genetic techniques together with the development of innovating treatments may significantly change diagnostic flow charts for VWD and their use for specific and personalized treatment.
Response by Jordan et al to Letter Regarding Article, "Left Atrial Volume Index Is Associated With Cardioembolic Stroke and Atrial Fibrillation Detection After Embolic Stroke of Undetermined Source".

In Response: We thank Ho et al for their letter in response to our article “Left Atrial Volume Index Is Associated With Cardioembolic Stroke and Atrial Fibrillation Detection After Embolic Stroke of Undetermined Source. ” The authors highlight an important discussion on the relationship between left atrial enlargement and left ventricular diastolic dysfunction (LVDD), and the implications this relationship has on our understanding of thromboembolic risk. As Ho et al point out, multiple studies have demonstrated a clear association between increased left atrial volume index (LAVI) and diastolic dysfunction. In fact, the association seems to be graded and one study expressed this relationship with the following equation—(Indexed LA volume =8.67 [diastolic function grade] + 21.30 [P=0.001, r=0.78]). Furthermore, both LAVI and LVDD have be shown to be associated with increased thromboembolic risk and cardiovascular outcomes, particularly with respect to development of atrial fibrillation and ischemic stroke risk. Therefore, it is likely these 2 entities play a complex role in the pathogenesis of thromboembolic risk. While the role of left atrial dysfunction in thromboembolic risk has been more extensively studied, the role of LVDD has been a poorly studied area. Increasing awareness to the role of LVDD in thromboembolism should greatly improve our understanding of cardioembolic stroke risk and inform secondary prevention strategies. LVDD has long been implicated as a driver of left atrial dysfunction and dilatation. One study of 1589 ischemic stroke patients demonstrated an independent association between atrial fibrillation and grade II LVDD (odds ratio, 4.37; CI, 2.99–6.41; P≤0.001), grade III LVDD (odds ratio, 5.6; CI, 3.42–9.17; P<0.001), and left atrial enlargement (odds ratio, 5.19; CI, 3.67– 7.35; P<0.001). To our knowledge, no study at present has independently associated both LAVI and LVDD with cardioembolic stroke. The importance and value of LVDD as an independent cardiac biomarker, however, would only be demonstrated if the association between LVDD and thromboembolic risk is shown to be independent of other markers of atrial cardiopathy such as N-terminal B-type natriuretic peptide, left atrial enlargement, and increased p-wave terminal force in lead V1 on ECG. These have been shown to be independent predictors of stroke risk. We did not include LVDD as a parameter in our multivariate analysis comparing the association of LAVI and stroke subtype (CE and ESUS). We look forward to the evolving discourse on LVDD and LAVI with regarding to thromboembolic risk and hope these biomarkers prove useful in our understanding of appropriate strategies for mitigating recurrent stroke risk in patients with cryptogenic stroke and ESUS.
Integrated Environmental Assessment and Management

Despite widespread acceptance of the utility of population modeling and advocacy of this approach for a more ecologically relevant perspective, it is not routinely incorporated in ecological risk assessments (ERA). A systematic framework for situation‐ specific model development is one of the major challenges to broadly adopting population models in ERA. As risk assessors confront the multitude of species and chemicals requiring evaluation, an adaptable stepwise guide for model parameterization would facilitate this process. Additional guidance on interpretation of model output and evaluating uncertainty would further contribute to establishing consensus on good modeling practices. We build on previous work that created a framework and decision guide for developing population models for ERA by focusing on data types, model structure, and extrinsic stressors relevant to anuran amphibians. Anurans have a unique life cycle with varying habitat requirements and high phenotypic plasticity. These species belong to the amphibian class, which is facing global population decline in large part due to anthropogenic stressors, including chemicals. We synthesize information from databases and literature relevant to amphibian risks to identify traits that influence exposure likelihood, inherent sensitivity, population vulnerability, and environmental constraints. We link these concerns with relevant population modeling methods and structure in order to evaluate pesticide effects with appropriate scale and parameterization. A standardized population modeling approach, with additional guidance for anuran ERA, offers an example method for quantifying population risks and evaluating long‐term impacts of chemical stressors to populations. Integr Environ Assess Manag 2020;16:223–233. © 2019 SETAC
Fibular Plate Fixation and Correlated Short-term Complications

Background. The most common method of surgical stabilization of fibular fractures is plate osteosynthesis. Despite its ubiquity, there is a dearth of large series reporting implant-related outcomes and complications. The purpose of this study was to report on short-term complications and hardware removal after plate fixation of distal fibula fractures. Methods. A retrospective chart analysis and review of radiographic images was performed of 461 ankle fractures between 2011 and 2017. In 404 cases, a fibular fracture was treated surgically; 94.1% underwent tubular and 5.9% locking plate fixation. The primary outcome was radiographic union, with a mean follow-up of 11.6 months. Minor, intermediate, and major complications were recorded as well as the rate of hardware removal. Results. The union-rate with plate fixation was 99.5% (402/404). The overall complication rate was 19.3% (n = 78/404). Of these complications, 79.5% (62/78) were considered minor. These complications included erythema, heterotopic ossification, neurapraxia, delayed union, and deep-vein thrombosis; 20.5% (16/78) of the complications were considered intermediate (9/78, 11.5%) or major (7/78, 9.0%). Intermediate and major complications included deep infection, nonunion/malunion, and osteomyelitis. Subsequent surgery was needed in 7 cases (1.7%, 7/404). In another 93 patients, hardware-related symptoms were identified: 23 (5.7%) underwent syndesmosis screw removal and 54 (13.4%) hardware removal. No correlation to the fixation technique was identified. Conclusion. This study shows a relatively low rate of major complications and a high union rate of 99.5% for fibular plate osteosynthesis in a large cohort. Any other treatment, including other fixation techniques, will need to show an equivalent or better complication and reoperation profile. Level of Evidence: Level III: Retrospective, comparative study
Randomised controlled clinical trial of a structured cognitive rehabilitation in patients with attention deficit following mild traumatic brain injury: study protocol

Objectives To measure the clinical, structural and functional changes of an individualised structured cognitive rehabilitation in mild traumatic brain injury (mTBI) population. Setting A single centre study, Malaysia. Participants Adults aged between 18 and 60 years with mTBI as a result of road traffic accident, with no previous history of head trauma, minimum of 9 years education and abnormal cognition at 3 months will be included. The exclusion criteria include pre-existing chronic illness or neurological/psychiatric condition, long-term medication that affects cognitive/psychological status, clinical evidence of substance intoxication at the time of injury and major polytrauma. Based on multiple estimated calculations, the minimum intended sample size is 50 participants (Cohen’s d effect size=0.35; alpha level of 0.05; 85% power to detect statistical significance; 40% attrition rate). Interventions Intervention group will receive individualised structured cognitive rehabilitation. Control group will receive the best patient-centred care for attention disorders. Therapy frequency for both groups will be 1 hour per week for 12 weeks. Outcome measures Primary: Neuropsychological Assessment Battery-Screening Module (S-NAB) scores. Secondary: Diffusion Tensor Imaging (DTI) parameters and Goal Attainment Scaling score (GAS). Results Results will include descriptive statistics of population demographics, CogniPlus cognitive program and metacognitive strategies. The effect of intervention will be the effect size of S-NAB scores and mean GAS T scores. DTI parameters will be compared between groups via repeated measure analysis. Correlation analysis of outcome measures will be calculated using Pearson’s correlation coefficient. Conclusion This is a complex clinical intervention with multiple outcome measures to provide a comprehensive evidence-based treatment model. Ethics and dissemination The study protocol was approved by the Medical Research Ethics Committee UMMC (MREC ID NO: 2016928–4293). The findings of the trial will be disseminated through peer-reviewed journals and scientific conferences. Trial registration number NCT03237676
The performance of different case definitions for severe influenza surveillance among HIV-infected and HIV-uninfected children aged <5 years in South Africa, 2011–2015

In 2014, the World Health Organization (WHO) proposed a new severe influenza surveillance case definition, which has not been evaluated in a high human immunodeficiency virus (HIV) prevalence setting. Our study aimed to assess the performance of this proposed case definition in identifying influenza among HIV-uninfected and HIV-infected children aged <5 years in South Africa. We prospectively enrolled children aged <5 years hospitalised with physician-diagnosed lower respiratory tract infection (LRTI) at two surveillance sites from January 2011 to December 2015. Epidemiologic and clinical data were collected. We tested nasopharyngeal aspirates for influenza using reverse transcription polymerase chain reaction. We used logistic regression to assess factors associated with influenza positivity among HIV-infected and HIV-uninfected children. We calculated sensitivity and specificity for different signs and symptoms and combinations of these for laboratory-confirmed influenza. We enrolled 2,582 children <5 years of age with LRTI of whom 87% (2,257) had influenza and HIV results, of these 14% (318) were HIV-infected. The influenza detection rate was 5% (104/1,939) in HIV-uninfected and 5% (16/318) in HIV-infected children. Children with measured fever (≥38°C) were two times more likely to test positive for influenza than those without measured fever among the HIV-uninfected (OR 2.2, 95% Confidence Interval (CI) 1.5–3.4; p<0.001). No significant association was observed between fever and influenza infection among HIV-infected children. Cough alone had sensitivity of 95% (95% CI 89–98%) in HIV-uninfected and of 100% (95% CI 79–100%) in HIV-infected children but low specificity: 7% (95% CI 6–8%) and 6% (95% CI 3–9%) in HIV-uninfected and HIV-infected children, respectively. The WHO post-2014 case definition for severe acute respiratory illness (SARI—an acute respiratory infection with history of fever or measured fever of ≥ 38°C and cough; with onset within the last ten days and requires hospitalization), had a sensitivity of 66% (95% CI 56–76%) and specificity of 46% (95% CI 44–48%) among HIV-uninfected and a sensitivity of 63% (95% CI 35–84%) and a specificity of 42% (95% CI 36–48%) among HIV-infected children. The sensitivity and specificity of the WHO post-2014 case definition for SARI were similar among HIV-uninfected and HIV-infected children. Our findings support the adoption of the 2014 WHO case definition for children aged <5 years irrespective of HIV infection status.
Limited reproducibility of MUCH and WUCH: evidence from the ELSA study.

AIMS To evaluate the long-term reproducibility of masked (MUCH) and white-coat uncontrolled hypertension (WUCH), an information crucial for determining the long-term prognostic impact of these conditions. METHODS AND RESULTS Reproducibility of MUCH and WUCH was assessed in 1664 hypertensive patients recruited for the European Lacidipine Study on Atherosclerosis and treated with atenolol or lacidipine (±additional drugs) during a 4-year period. Office and 24 h blood pressure (BP) was measured at baseline and every year during treatment, allowing repeated classification of either condition. After 1 year of treatment 21.1% and 17.8% of the patients were classified as MUCH and WUCH, respectively. For both conditions the prevalence was similar in the following years, although with a large change in patients composition because only about 1/3 of patients classified as MUCH or WUCH at one set of office and ambulatory BP measurements maintained the same classification at a subsequent set of measurements. In only 4.5% and 6.2% MUCH and WUCH persisted throughout the treatment period. MUCH and WUCH reproducibility was worse than that of patients showing control or lack of control of both office and ambulatory BP, i.e. controlled and uncontrolled hypertension, respectively. CONCLUSION Both MUCH and WUCH display poor reproducibility over time. This should be taken into account in studies assessing the long-term prognostic value of these conditions based on only one set of BP measurements.
Genome-Wide Association Study on the Early-Phase Insulin Response to a Liquid Mixed Meal: Results From the NEO Study

Early-phase insulin secretion is a determinant of postprandial glucose homeostasis. In this study, we aimed to identify novel genetic variants associated with the early-phase insulin response to a liquid mixed meal by a genome-wide association study using a discovery and replication design embedded in the Netherlands Epidemiology of Obesity (NEO) study. The early-phase insulin response was defined as the difference between the natural logarithm–transformed insulin concentrations of the postprandial state at 30 min after a meal challenge and the fasting state (Δinsulin). After Bonferroni correction, rs505922 (β: −6.5% [minor allele frequency (MAF) 0.32, P = 3.3 × 10−8]) located in the ABO gene reached genome-wide significant level (P < 5 × 10−8) and was also replicated successfully (β: −7.8% [MAF 0.32, P = 7.2 × 10−5]). The function of the ABO gene was assessed using in vitro shRNA-mediated knockdown of gene expression in the murine pancreatic β-cell line MIN6. Knocking down the ABO gene led to decreased insulin secretion in the murine pancreatic β-cell line. These data indicate that the previously identified elevated risk of type 2 diabetes for carriers of the ABO rs505922:C allele may be caused by decreased early-phase insulin secretion.
Strengths-Based Assessment for Suicide Prevention: Reasons for Life as a Protective Factor From Yup’ik Alaska Native Youth Suicide

Suicide is the second leading cause of death among American Indian and Alaska Native youth, and within the Alaska Native youth subpopulation, the leading cause of death. In response to this public health crisis, American Indian and Alaska Native communities have created strategies to protect their young people by building resilience using localized Indigenous well-being frameworks and cultural strengths. These approaches to suicide prevention emphasize promotion of protective factors over risk reduction. A measure of culturally based protective factors from suicide risk has potential to assess outcomes from these strengths-based, culturally grounded suicide prevention efforts, and can potentially address several substantive concerns regarding direct assessment of suicide risk. We report on the Reasons for Life (RFL) scale, a measure of protective factors from suicide, testing psychometric properties including internal structure with 302 rural Alaska Native Yup’ik youth. Confirmatory factor analyses revealed the RFL is best described through three distinct first-order factors organized under one higher second-order factor. Item response theory analyses identified 11 satisfactorily functioning items. The RFL correlates with other measures of more general protective factors. Implications of these findings are described, including generalizability to other American Indian and Alaska Native, other Indigenous, and other culturally distinct suicide disparities groups.
Impairment of Sharp-Wave Ripples in a Murine Model of Dravet Syndrome

Dravet syndrome (DS) is a severe early-onset epilepsy associated with heterozygous loss-of-function mutations in SCN1A. Animal models of DS with global Scn1a haploinsufficiency recapitulate the DS phenotype, including seizures, premature death, and impaired spatial memory performance. Spatial memory requires hippocampal sharp-wave ripples (SPW-Rs), which consist of high-frequency field potential oscillations (ripples, 100–260 Hz) superimposed on a slower SPW. Published in vitro electrophysiologic recordings in DS mice demonstrate reduced firing of GABAergic inhibitory neurons, which are essential for the formation of SPW-R complexes. Here, in vivo electrophysiologic recordings of hippocampal local field potential in both male and female mice demonstrate that Scn1a haploinsufficiency slows intrinsic ripple frequency and reduces the rate of SPW-R occurrence. In DS mice, peak ripple-band power is shifted to lower frequencies, average intertrough intervals of individually detected ripples are slower, and the rate of SPW-R generation is reduced, while SPW amplitude remains unaffected. These alterations in SPW-R properties, in combination with published reductions in interneuron function in DS, suggest a direct link between reduced inhibitory neuron excitability and impaired SPW-R function. A simple interconnected, conductance-based in silico interneuron network model was used to determine whether reduced sodium conductance is sufficient to slow ripple frequency, and stimulation with a modeled SPW demonstrates that reduced sodium conductance alone is sufficient to slow oscillatory frequencies. These findings forge a potential mechanistic link between impaired SPW-R generation and Scn1a mutation in DS mice, expanding the set of disorders in which SPW-R dysfunction contributes to impaired memory. SIGNIFICANCE STATEMENT Disruption of sharp-wave ripples, a characteristic hippocampal rhythm coordinated by the precise timing of GABAergic interneurons, impairs spatial learning and memory. Prior in vitro patch-clamp recordings in brain slices from genetic mouse models of Dravet syndrome (DS) reveal reduced sodium current and excitability in GABAergic interneurons but not excitatory cells, suggesting a causal role for impaired interneuron activity in seizures and cognitive impairment. Here, heterozygous Scn1a mutation in DS mice reduces hippocampal sharp-wave ripple occurrence and slows internal ripple frequency in vivo and a simple in silico model demonstrates reduction in interneuron function alone is sufficient to slow model oscillations. Together, these findings provide a plausible pathophysiologic mechanism for Scn1a gene mutation to impair spatial memory.