Miracle-dz/UniFAR-FTUs huggingface dataset:
A prospective observational study of the rapid detection of clinically‐relevant plasma direct oral anticoagulant levels following acute traumatic injury

In urgent clinical situations, such as trauma, urgent surgery or before thrombolysis, rapid quantification of direct oral anticoagulant plasma drug levels is warranted. Using the ClotPro® analyser, we assessed two novel viscoelastic tests for detection of clinically‐relevant plasma drug levels in trauma patients. The ecarin clotting time was used to assess the plasma concentration of dabigatran and Russell´s viper venom clotting time to determine the plasma concentration of direct factor Xa inhibitors. In parallel, plasma concentrations were analysed using plasma‐based chromogenic assays. A total of 203 simultaneous measurements were performed. Strong to very strong linear correlations were detected between ecarin clotting time and plasma concentration of dabigatran (r = 0.9693), and between Russell´s viper venom clotting time and plasma concentrations of apixaban (r = 0.7391), edoxaban (r = 0.9251) and rivaroxaban (r = 0.8792), all p < 0.001. An ecarin clotting time ≥ 189 seconds provided 100% sensitivity and 90% specificity for detecting plasma dabigatran concentrations ≥ 50 ng.ml‐1. Corresponding Russell´s viper venom clotting time cut‐off values were ≥ 136 seconds for apixaban (80% sensitivity, 88% specificity), ≥ 168 seconds for edoxaban (100% sensitivity, 100% specificity) and ≥ 177 seconds for rivaroxaban (90% sensitivity, 100% specificity). Detection of drug levels ≥ 100 ng.ml‐1 was also investigated: for dabigatran, an ecarin clotting time ≥ 315 seconds yielded 92% sensitivity and 100% specificity; while Russell´s viper venom clotting time cut‐offs of 191, 188 and 196 seconds were calculated for apixaban (67% sensitivity, 88% specificity), edoxaban (100% sensitivity, 75% specificity) and rivaroxaban (100% sensitivity, 91% specificity), respectively. We have demonstrated strong positive correlations between plasma drug levels and clotting time values in the specific ClotPro assays. Cut‐off values for detecting clinically‐relevant drug levels showed high levels of sensitivity and specificity.
Overview of the management of primary tumors of the spine

Abstract Study design Narrative review. Objective To provide a narrative review for diagnosis and management of Primary spine tumors. Methods A detailed review of literature was done to identify relevant and well cited manuscripts to construct this narrative review. Results Primary tumors of the spine are rare with some racial differences reported. There are numerous adjuvant technologies and developments that influence the way we currently manage these tumors. Collimated radiation allows for heavy dosage to be delivered and have been reported to give good local control both as an adjuvant and neoadjuvant setting. These have made surgical decision making even more intricate needing a multicentric approach. Dedicated care has been shown to significantly improve health quality of life measures and survival. Conclusion While, it is beyond the scope of this paper to discuss all primary tumors subtypes individually, this review highlights the developments and approach to primary spine tumors.
Innate, non-cytolytic CD8+ T cell-mediated suppression of HIV replication by MHC-independent inhibition of virus transcription

MHC-I-restricted, virus-specific cytotoxic CD8+ T cells (CTLs) may control human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication via the recognition and killing of productively infected CD4+ T cells. Several studies in SIV-infected macaques suggest that CD8+ T cells may also decrease virus production by suppressing viral transcription. Here, we show that non-HIV-specific, TCR-activated non-cytolytic CD8+ T cells suppress HIV transcription via a virus- and MHC-independent immunoregulatory mechanism that modulates CD4+ T cell proliferation and activation. We also demonstrate that this CD8+ T cell-mediated effect promotes the survival of infected CD4+ T cells harboring integrated, inducible virus. Finally, we used RNA sequencing and secretome analyses to identify candidate cellular pathways that are involved in the virus-silencing mediated by these CD8+ T cells. This study characterizes a previously undescribed mechanism of immune-mediated HIV silencing that may be involved in the establishment and maintenance of the reservoir under antiretroviral therapy and therefore represent a major obstacle to HIV eradication.
Effect of structural complexities in head modeling on the accuracy of EEG source localization in neonates

Objective. Neonatal electroencephalography (EEG) source localization is highly prone to errors due to head modeling deficiencies. In this study, we investigated the effect of head model complexities on the accuracy of EEG source localization in full term neonates using a realistic volume conductor head model. Approach. We performed numerical simulations to investigate source localization errors caused by cerebrospinal fluid (CSF) and fontanel exclusion and gray matter (GM)/white matter (WM) distinction using the finite element method. Main results. Our results showed that the exclusion of CSF from the head model could cause significant localization errors mostly for sources closer to the inner surface of the skull. With a less pronounced effect compared to the CSF exclusion, the discrimination between GM and WM also widely affected all sources, especially those located in deeper structures. The exclusion of the fontanels from the head model led to source localization errors for sources located in areas beneath the fontanels. Our finding clearly shows that the CSF inclusion and GM/WM distinction in EEG inverse modeling can substantially reduce EEG source localization errors. Moreover, fontanels should be included in neonatal head models, particularly in source localization applications, in which sources of interest are located beneath or in vicinity of fontanels. Significance. Our ﬁndings have practical implications for a better understanding of the impact of head model complexities on the accuracy of EEG source localization in neonates.
Virtual reality telerehabilitation for spatial neglect post-stroke: perspectives from stroke survivors, carers and clinicians

Spatial neglect is a common and severe cognitive consequence of stroke, yet there is currently no effective rehabilitation tool. Virtual Reality (VR) telerehabilitation tools have the potential to provide multisensory and enjoyable neuropsychological therapies and remotely monitor adherence without the presence of a therapist at all times. In order to inform the development of these tools researchers and industry need to better understand end-user perspectives about these technologies to ensure these are acceptable and user-friendly to ultimately optimize adherence and efficacy. Therefore, this study explored end-user perspectives on the use of self-administered VR telerehabilitation for spatial neglect. We used a mixed-method design including focus groups, self-administered questionnaires and individual interviews with stroke survivors (N = 7), their carers (N = 3) and stroke clinicians (N = 6). End-user perspectives identified clarity of instructions, equipment (cost, available resources) and for some, level of experience with technology as barriers of use. Perceived facilitators of use were performance feedback, engagement and enjoyment, and psychological benefits associated by self-administered VR telerehabilitation. Overall, end-users were positive and interested in using VR telerehabilitation for spatial neglect. These perspectives enabled us to produce practical recommendations to inform future development, enhance engagement and uptake of self-administered VR telerehabilitation.
The burden of cardiovascular diseases in Ethiopia from 1990 to 2017: evidence from the Global Burden of Disease Study

Abstract In Ethiopia, evidence on the national burden of cardiovascular diseases (CVDs) is limited. To address this gap, this systematic analysis estimated the burden of CVDs in Ethiopia using the Global Burden of Disease (GBD) 2017 study data. The age-standardized CVD prevalence, disability-adjusted life years (DALYs) and mortality rates in Ethiopia were 5534 (95% uncertainty interval [UI] 5310.09 - 5774.0), 3549.6 (95% UI 3229.0 - 3911.9) and 182.63 (95% UI 165.49 - 203.9) per 100 000 population, respectively. Compared with 1990, the age-standardized CVD prevalence rate in 2017 showed no change. But significant reductions were observed in CVD mortality (54.7%), CVD DALYs (57.7%) and all-cause mortality (53.4%). The top three prevalent CVDs were ischaemic heart disease, rheumatic heart disease and stroke in descending order. The reduction in the mortality rate due to CVDs is slower than for communicable, maternal, neonatal and nutritional disease mortalities. As a result, CVDs are the leading cause of mortality in Ethiopia. These findings urge Ethiopia to consider CVDs as a priority public health problem.
Time-Optimal Path Tracking for Cooperative Manipulators: A Convex Optimization Approach

This paper studies the time-optimal path tracking problem for a team of cooperating robotic manipulators carrying an object. Considering the problem for rigidly grasped objects, we show that it can be cast as a convex optimization problem and solved efficiently with a guarantee of optimality. When formulating the problem, we avoid using a particular wrench distribution and exploit the full actuation available to the system. Then, we consider the problem for grasps using frictional forces and show that this problem also, under a force-closure grasp assumption, can be formulated as a convex optimization problem and solved efficiently and to optimality. To ensure a firm grasp, internal forces have been taken into account in this approach.
Automatic identification of a stable QRST complex for non-invasive evaluation of human cardiac electrophysiology

Background A vectorcardiography approach to electrocardiology contributes to the non-invasive assessment of electrical heterogeneity in the ventricles of the heart and to risk stratification for cardiac events including sudden cardiac death. The aim of this study was to develop an automatic method that identifies a representative QRST complex (QRSonset to Tend) from a Frank vectorcardiogram (VCG). This method should provide reliable measurements of morphological VCG parameters and signal when such measurements required manual scrutiny. Methods Frank VCG was recorded in a population-based sample of 1094 participants (550 women) 50–65 years old as part of the Swedish CArdioPulmonary bioImage Study (SCAPIS) pilot. Standardized supine rest allowing heart rate stabilization and adaptation of ventricular repolarization preceded a recording period lasting ≥5 minutes. In the Frank VCG a recording segment during steady-state conditions and with good signal quality was selected based on QRST variability. In this segment a representative signal-averaged QRST complex from cardiac cycles during 10s was selected. Twenty-eight morphological parameters were calculated including both conventional conduction intervals and VCG-derived parameters. The reliability and reproducibility of these parameters were evaluated when using completely automatic and automatic but manually edited annotation points. Results In 1080 participants (98.7%) our automatic method reliably selected a representative QRST complex where its instability measure effectively identified signal variability due to both external disturbances (”noise”) and physiologic and pathophysiologic variability, such as e.g. sinus arrhythmia and atrial fibrillation. There were significant sex-related differences in 24 of 28 VCG parameters. Some VCG parameters were insensitive to the instability value, while others were moderately sensitive. Conclusion We developed an automatic process for identification of a signal-averaged QRST complex suitable for morphologic measurements which worked reliably in 99% of participants. This process is applicable for all non-invasive analyses of cardiac electrophysiology including risk stratification for cardiac death based on such measurements.
Incidence, predictors, and timing of post-operative stroke following elective total hip arthroplasty and total knee arthroplasty

Background Postoperative stroke is a rare but potentially devastating complication following total hip arthroplasty (THA) and total knee arthroplasty (TKA). The purpose of the current study was to determine the incidence, independent risk factors, and timing of stroke following THA and TKA utilizing the National Surgical Quality Improvement (NSQIP) database. Methods Patients who underwent elective primary THA and TKA were identified in the 2005–2016 NSQIP database. Thirty-day postoperative strokes were identified, timing was characterized, and an incidence curve was created. Multivariate analyses determined the independent predictors of these strokes. Results Of 333,117 patients identified, 286 (0.09%) experienced a stroke. Given that THA vs TKA was not a univariate predictor of stroke, the two procedures were considered together. The majority (65%) of strokes occurred before discharge. Of the strokes observed, 25% occurred by postoperative day one, 50% by postoperative day two, and 75% by postoperative day nine. Independent risk factors for postoperative stroke were: age (60–69 years old odds ratio [OR] = 4.2; 70–79 years old OR = 8.1; ≤80 years old OR = 16.1), higher American Society of Anesthesiologists (ASA) score (ASA≥3 OR = 1.7), and smoking [OR = 1.6). Conclusion The incidence of stroke after THA/TKA was low at 0.09%, with the majority occurring prior to discharge and half occurring by postoperative day two. Patients who were older, sicker, or who were smokers were at greater risk of postoperative stroke. These findings can be used to council patients and to optimize patient care. Level of evidence Level III, Retrospective comparative study.
An Exploratory Study of Speech and Language Therapy Intervention for Children Born With Cleft Palate ± Lip

Introduction: Children born with a cleft palate ± lip are at risk of developing speech and language difficulties, which may require intervention from a speech and language therapist (SLT). To date, there is no strong evidence to support one approach to intervention over another, neither is it clear which approaches or methods of provision are commonly used. Objectives: To describe the range of speech and language therapy interventions being used with children born with cleft palate in the United Kingdom up to 5 years of age. To explore the different ways, interventions are being delivered. Design: A prospective study to conduct 9 semi-structured focus groups. Iterative content analysis was completed. Setting: Regional Cleft Lip and Palate Centers in the United Kingdom. Participants: Sixty-two speech and language therapy professionals from specialist cleft teams and community services. Results: Four main codes were identified: “intervention approaches,” “service delivery models,” “decision-making and rationale,” and “patient-centered care. ” Participants frequently discussed how they adopt an eclectic style when delivering intervention, the importance of an individualized approach for each child and service delivery constraints, such as a lack of resources. Conclusion: Insight into the multitude of intervention approaches used by SLTs, aspects which influence their decision-making and the variability of service delivery models were gained. Uncertainty regarding which intervention approaches and methods for delivery are most effective provides rationale for future research, to improve the effectiveness of speech and language intervention for children with cleft palate ± lip.
Investigating effects of soil chemicals on density of small mammal bioindicators using spatial capture-recapture models

Monitoring the ecological impacts of environmental pollution and the effectiveness of remediation efforts requires identifying relationships between contaminants and the disruption of biological processes in populations, communities, or ecosystems. Wildlife are useful bioindicators, but traditional comparative experimental approaches rely on a staunch and typically unverifiable assumption that, in the absence of contaminants, reference and contaminated sites would support the same densities of bioindicators, thereby inferring direct causation from indirect data. We demonstrate the utility of spatial capture-recapture (SCR) models for overcoming these issues, testing if community density of common small mammal bioindicators was directly influenced by soil chemical concentrations. By modeling density as an inhomogeneous Poisson point process, we found evidence for an inverse spatial relationship between Peromyscus density and soil mercury concentrations, but not other chemicals, such as polychlorinated biphenyls, at a site formerly occupied by a nuclear reactor. Although the coefficient point estimate supported Peromyscus density being lower where mercury concentrations were higher (β = –0.44), the 95% confidence interval overlapped zero, suggesting no effect was also compatible with our data. Estimated density from the most parsimonious model (2.88 mice/ha; 95% CI = 1.63–5.08), which did not support a density-chemical relationship, was within the range of reported densities for Peromyscus that did not inhabit contaminated sites elsewhere. Environmental pollution remains a global threat to biodiversity and ecosystem and human health, and our study provides an illustrative example of the utility of SCR models for investigating the effects that chemicals may have on wildlife bioindicator populations and communities.
Combination of High Dose Hypofractionated Radiotherapy with Anti-PD1 Single Dose Immunotherapy Leads to a Th1 Immune Activation Resulting in a Complete Clinical Response in a Melanoma Patient

The development of immunotherapy has recently modified the anti-tumor therapeutic arsenal; particularly, immune checkpoint inhibitors have led to a significant increase in overall survival. The current challenge is now to select good responder patients by identifying early biomarkers to propose therapeutic combinations that potentiate the efficacy of the therapy. Here we report the case of a 60-year-old man with superficial melanoma treated with high-dose hypo fractionated radiotherapy (H-SRT) combined with a single dose of anti-PD1 immunotherapy (Nivolumab) for a metastatic lymph node recurrence due to cancer progression. In this study, we present the results obtained regarding the activation of the Th1 immune response after H-SRT treatment followed by anti PD-1 therapeutic protocol. These results were correlated with clinical data to identify potential immunological biomarkers of treatment efficacy. This exceptional case report shows that a combination of H-SRT with a single dose of anti-PD1 immunotherapy may allow a better activation of the immune response in favor of a complete clinical response.
From Red to Green Luminescence via Surface Functionalization. Effect of 2-(5-Mercaptothien-2-yl)-8-(thien-2-yl)-5-hexylthieno[3,4-c]pyrrole-4,6-dione Ligands on the Photoluminescence of Alloyed Ag–In–Zn–S Nanocrystals

A semiconducting molecule containing a thiol anchor group, namely 2-(5-mercaptothien-2-yl)-8-(thien-2-yl)-5-hexylthieno[3,4-c]pyrrole-4,6-dione (abbreviated as D-A-D-SH), was designed, synthesized, and used as a ligand in nonstoichiometric quaternary nanocrystals of composition Ag1.0In3. 1Zn1.0S4. 0(S6.1) to give an inorganic/organic hybrid. Detailed NMR studies indicate that D-A-D-SH ligands are present in two coordination spheres in the organic part of the hybrid: (i) inner in which the ligand molecules form direct bonds with the nanocrystal surface and (ii) outer in which the ligand molecules do not form direct bonds with the inorganic core. Exchange of the initial ligands (stearic acid and 1-aminooctadecane) for D-A-D-SH induces a distinct change of the photoluminescence. Efficient red luminescence of nanocrystals capped with initial ligands (λmax = 720 nm, quantum yield = 67%) is totally quenched and green luminescence characteristic of the ligand appears (λmax = 508 nm, quantum yield = 10%). This change of the photoluminescence mechanism can be clarified by a combination of electrochemical and spectroscopic investigations. It can be demonstrated by cyclic voltammetry that new states appear in the hybrid as a consequence of D-A-D-SH binding to the nanocrystals surface. These states are located below the nanocrystal LUMO and above its HOMO, respectively. They are concurrent to deeper donor and acceptor states governing the red luminescence. As a result, energy transfer from the nanocrystal HOMO and LUMO levels to the ligand states takes place, leading to effective quenching of the red luminescence and appearance of the green one.
Development of Gross Motor Evaluation for Children Aged 18 to 42 Months

ABSTRACT Purpose To test the reliability and validity of the gross motor items making up a new instrument, Hong Kong Comprehensive Assessment Scales for Toddlers (HKCAS-T) for quantifying gross motor development among children aged 18 to 42 months. Methods The 37 items were administered to 330 children, including 258 typically developing children and 72 children with gross motor delay. Results Rasch analyzes indicated that the fit statistics of the 37 items were within the acceptable range. The assessment was found able to differentiate between typically developing children and those with gross motor delay and among children of different ages. The raw score reliability (KR-20) was 0.94. Conclusion The new instrument is a promising alternative for assessing young children’s gross motor development.
Phosphate Deprivation Can Impair Mechano-Stimulated Cytosolic Free Calcium Elevation in Arabidopsis Roots

The root tip responds to mechanical stimulation with a transient increase in cytosolic free calcium as a possible second messenger. Although the root tip will grow through a heterogeneous soil nutrient supply, little is known of the consequence of nutrient deprivation for such signalling. Here, the effect of inorganic phosphate deprivation on the root’s mechano-stimulated cytosolic free calcium increase is investigated. Arabidopsis thaliana (cytosolically expressing aequorin as a bioluminescent free calcium reporter) is grown in zero or full phosphate conditions, then roots or root tips are mechanically stimulated. Plants also are grown vertically on a solid medium so their root skewing angle (deviation from vertical) can be determined as an output of mechanical stimulation. Phosphate starvation results in significantly impaired cytosolic free calcium elevation in both root tips and whole excised roots. Phosphate-starved roots sustain a significantly lower root skewing angle than phosphate-replete roots. These results suggest that phosphate starvation causes a dampening of the root mechano-signalling system that could have consequences for growth in hardened, compacted soils.
Serum canine thymus and activation‐regulated chemokine (TARC/CCL17) concentrations correlate with disease severity and therapeutic responses in dogs with atopic dermatitis

Background – Thymus and activation‐regulated chemokine (TARC/CCL17) has been implicated in the pathogenesis of canine atopic dermatitis (cAD). Serum TARC concentrations are a reliable biomarker for human atopic dermatitis; however, their potential as a biomarker for cAD has not been investigated. Hypothesis/Objectives – To investigate whether serum TARC concentrations correlate with disease severity and therapeutic responses for cAD. Conclusions and clinical relevance – Serum TARC concentrations have potential as a clinical and research tool for the objective evaluation of disease severity and therapeutic responses for cAD.