Miracle-dz/UniFAR-FTUs huggingface dataset:
D-Dimer Combined with Fibrinogen Predicts the Risk of Venous Thrombosis in Fracture Patients

Objective While D-dimer can successfully diagnose venous thrombosis due to its excellent negative predictive value (NPV), it cannot be used to detect venous thromboembolism (VTE) because of its low positive predictive value (PPV). This study aims to investigate if a combination of using D-dimer and fibrinogen can improve PPV in the VTE diagnosis. Methods We retrospectively analyzed various data including D-dimer, fibrinogen, C-reactive protein, ultrasound, and others collected from 10775 traumatic fracture patients and categorized them into two groups of VTE and non-VTE. By comparing the difference between the two groups, we employ multiple logistic regression to find risk factors that are useful to detect VTE. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic yield of using fibrinogen, D-dimer, and their combination, respectively. Also, these data were classified into quartiles by patient age. We perform the same analysis on the quartiles and find if the patient's age has an impact on diagnosing VTE. Results The univariate analysis demonstrated that five factors of age, D-dimer, fibrinogen, C-reactive protein, and high-density lipoprotein cholesterol were significant to predict VTE. ROC showed that D-dimer was more useful than fibrinogen for the diagnosis of VTE, while the area under the curve (AUC) was 0.7296 for D-dimer and 0.5209 for fibrinogen. The cutoff point of D-dimer and fibrinogen was 424.89 ng/ml and 3.543 g/L, respectively. The specificity of fibrinogen was 0.777 which was better than D-dimer, while the sensitivity of fibrinogen was lower than that of D-dimer. Both PPV and NPV were similar in D-dimer and fibrinogen. The PPV of combining D-dimer and fibrinogen in ages Q3 (60 < age ≤ 70) and Q4 (age > 70) was better than using either D-dimer or fibrinogen. Conclusions Fibrinogen is a promising strategy for the diagnosis of subclinical VTE and postoperative VTE. In particular, a combination of D-dimer and fibrinogen can improve the PPV to successfully diagnose VTE in traumatic fracture patients who are more than 60 years old. Levels of Evidence. This assay is a diagnostic test at level II.
Prophylactic Faecalibacterium prausnitzii treatment prevents the acute breakdown of colonic epithelial barrier in a preclinical model of pelvic radiation disease

ABSTRACT Every year, millions of people around the world benefit from radiation therapy to treat cancers localized in the pelvic area. Damage to healthy tissue in the radiation field can cause undesirable toxic effects leading to gastrointestinal complications called pelvic radiation disease. A change in the composition and/or function of the microbiota could contribute to radiation-induced gastrointestinal toxicity. In this study, we tested the prophylactic effect of a new generation of probiotic like Faecalibacterium prausnitzii (F. prausnitzii) on acute radiation-induced colonic lesions. Experiments were carried out in a preclinical model of pelvic radiation disease. Rats were locally irradiated at 29 Gray in the colon resulting in colonic epithelial barrier rupture. Three days before the irradiation and up to 3 d after the irradiation, the F. prausnitzii A2-165 strain was administered daily (intragastrically) to test its putative protective effects. Results showed that prophylactic F. prausnitzii treatment limits radiation-induced para-cellular hyperpermeability, as well as the infiltration of neutrophils (MPO+ cells) in the colonic mucosa. Moreover, F. prausnitzii treatment reduced the severity of the morphological change of crypts, but also preserved the pool of Sox-9+ stem/progenitor cells, the proliferating epithelial PCNA+ crypt cells and the Dclk1+/IL-25+ differentiated epithelial tuft cells. The benefit of F. prausnitzii was associated with increased production of IL-18 by colonic crypt epithelial cells. Thus, F. prausnitzii treatment protected the epithelial colonic barrier from colorectal irradiation. New-generation probiotics may be promising prophylactic treatments to reduce acute side effects in patients treated with radiation therapy and may improve their quality of life.
Snake River sockeye and Chinook salmon in a changing climate: Implications for upstream migration survival during recent extreme and future climates

In 2015, the Pacific marine heat wave, low river flows, and record high water temperatures in the Columbia River Basin contributed to a near-complete failure of the adult migration of endangered Snake River sockeye salmon (Oncorhynchus nerka, NOAA Fisheries 2016). These extreme weather events may become the new normal due to anthropogenic climate change, with catastrophic consequences for endangered species. Existing anthropogenic pressures may amplify vulnerability to climate change, but these potential synergies have rarely been quantified. We examined factors affecting survival of endangered sockeye (Oncorhynchus nerka) and threatened Chinook salmon (O. tshawytscha) as they migrated upstream through eight dams and reservoirs to spawning areas in the Snake River Basin. Our extensive database included histories of 17,279 individual fish that migrated since 2004. A comparison between conditions in 2015 and daily temperatures and flows in a regulated basin forced by output from global climate models showed that 2015 did have many characteristics of projected future mean conditions. To evaluate potential salmon responses, we modeled migration timing and apparent survival under historical and future climate scenarios (2040s). For Chinook salmon, adult survival from the first dam encountered to spawning grounds dropped by 4-15%, depending on the climate scenario. For sockeye, survival dropped by ~80% from their already low levels. Through sensitivity analyses, we observed that the adult sockeye migration would need to shift more than 2 weeks earlier than predicted to maintain survival rates typical of those seen during 2008-2017. Overall, the greater impacts of climate change on adult sockeye compared with adult Chinook salmon reflected differences in life history and environmental sensitivities, which were compounded for sockeye by larger effect sizes from other anthropogenic factors. Compared with Chinook, sockeye was more negatively affected by a history of juvenile transportation and by similar temperatures and flows. The largest changes in temperature and flow were projected to be upstream from the hydrosystem, where direct mitigation through hydrosystem management is not an option. Unfortunately, Snake River sockeye have likely lost much of their adaptive capacity with the loss of the wild population. Further work exploring habitat restoration or additional mitigation actions is urgently needed.
Learnable Uncertainty under Laplace Approximations

Laplace approximations are classic, computationally lightweight means for constructing Bayesian neural networks (BNNs). As in other approximate BNNs, one cannot necessarily expect the induced predictive uncertainty to be calibrated. Here we develop a formalism to explicitly "train" the uncertainty in a decoupled way to the prediction itself. To this end we introduce uncertainty units for Laplace-approximated networks: Hidden units with zero weights that can be added to any pre-trained, point-estimated network. Since these units are inactive, they do not affect the predictions. But their presence changes the geometry (in particular the Hessian) of the loss landscape around the point estimate, thereby affecting the network's uncertainty estimates under a Laplace approximation. We show that such units can be trained via an uncertainty-aware objective, making the Laplace approximation competitive with more expensive alternative uncertainty-quantification frameworks.
Repeatability, reproducibility, agreement, and safety of Tono-Pen tip cover for intraocular measurement using latex and polyethylene wrap

Purpose To evaluate repeatability, reproducibility, and agreement of intraocular pressure measurement with Tono-Pen using Ocufilm and polyethylene wrap tip cover in human eyes. Methods This is a cross-sectional, experimental study. A gas-sterilized, polyethylene wrap was used as an alternative for Tono-Pen tip cover. For the right eye, 4 measurements using polyethylene wrap tip cover were done by two examiners (A and B) in random order to assess intra-observer repeatability and inter-observer reproducibility. For the left eye, 4 measurements were done by examiner A using both polyethylene wrap tip cover and Ocufilm in random order to assess intra-observer repeatability and agreement. Bland-Altman plot and intraclass correlation coefficient (ICC) were used in all analyses. Cost minimization analysis was evaluated. Results For examiner A, the repeatability of polyethylene wrap tip cover was -0.34, 95% limits of agreement (LOA) were -3.04 to 2.36, and ICC was 0.93 in the right eyes. As for the left eyes, the repeatability of polyethylene wrap tip cover was -0.33, 95% LOA were -3.01 to 2.36, and ICC was 0.93. For examiner B, the repeatability of polyethylene wrap tip cover was -0.02, 95% LOA were -2.88 to 2.83, and ICC was 0.92. The inter-observer reproducibility of polyethylene wrap tip cover was 0.36, 95% LOA were -3.34 to 4.07, and ICC was 0.90. The repeatability of Ocufilm was -0.42, 95% LOA were -2.75 to 1.91, and ICC was 0.95. The agreement of polyethylene wrap tip cover and Ocufilm was -0.71, 95% LOA were -5.18 to 3.76, and ICC was 0.83. There were no allergic reactions or serious complications. From the cost minimization analysis, the local cost for polyethylene tip cover was approximately 8 times lower compared to Ocufilm. Conclusions Tono-pen with Ocufilm and polyethylene wrap tip cover were used to measure the intraocular pressure. The polyethylene wrap tip cover demonstrated acceptable repeatability, reproducibility, and agreement with Ocufilm in normotensive eyes, and had a good safety profile.
Genomic and phylogenetic characterisation of an imported case of SARS-CoV-2 in Amazonas State, Brazil

A new coronavirus [severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)] is currently causing a life-threatening pandemic. In this study, we report the complete genome sequencing and genetic characterisation of a SARS-CoV-2 detected in Manaus, Amazonas, Brazil, and the protocol we designed to generate high-quality SARS-CoV-2 full genome data. The isolate was obtained from an asymptomatic carrier returning from Madrid, Spain. Nucleotide sequence analysis showed a total of nine mutations in comparison with the original human case in Wuhan, China, and support this case as belonging to the recently proposed lineage A.2. Phylogeographic analysis further confirmed the likely European origin of this case. To our knowledge, this is the first SARS-CoV-2 genome obtained from the North Brazilian Region. We believe that the information generated in this study may contribute to the ongoing efforts toward the SARS-CoV-2 emergence.
Warming Climate Is Reducing the Diversity of Dominant Microbes in the Largest High Arctic Lake

Temperatures in the Arctic are expected to increase dramatically over the next century, and transform high latitude watersheds. However, little is known about how microbial communities and their underlying metabolic processes will be affected by these environmental changes in freshwater sedimentary systems. To address this knowledge gap, we analyzed sediments from Lake Hazen, NU Canada. Here, we exploit the spatial heterogeneity created by varying runoff regimes across the watershed of this uniquely large high-latitude lake to test how a transition from low to high runoff, used as one proxy for climate change, affects the community structure and functional potential of dominant microbes. Based on metagenomic analyses of lake sediments along these spatial gradients, we show that increasing runoff leads to a decrease in taxonomic and functional diversity of sediment microbes. Our findings are likely to apply to other, smaller, glacierized watersheds typical of polar or high latitude ecosystems; we can predict that such changes will have far reaching consequences on these ecosystems by affecting nutrient biogeochemical cycling, the direction and magnitude of which are yet to be determined.
Quantitative Digitography Measures Fine Motor Disturbances in Chronically Treated HIV Similar to Parkinson’s Disease

Introduction: Motor and cognitive deficits were compared in aging, chronically treated human immunodeficiency virus (HIV) people, people with mild-to-moderate stage Parkinson’s disease (PD), and healthy controls. Methods: Groups consisted of 36 people with PD, 28 with HIV infection, and 28 healthy controls. Motor function was assessed with the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS-III) and a rapid alternating finger tapping (RAFT) task on an engineered keyboard known as Quantitative Digitography (QDG). Executive function, verbal memory, and visuospatial processing were assessed using standard neuropsychological tests. Results: HIV demonstrated RAFT deficits similar to PD such as reduced amplitude (P = 0.023) and greater amplitude variability (P = 0.019) in the index finger when compared to controls. This fine motor disturbance correlated with HIV’s immune health, measured by their CD4+ T cell count (P < 0.01). The UPDRS did not yield motor differences between HIV and controls. Executive function and verbal memory were impaired in HIV (P = 0.006, P = 0.016, respectively), but not in PD; visuospatial processing was similarly impaired in HIV and PD (P < 0.05) although motor deficits predominated in PD. Conclusions: Fine motor bradykinesia measured quantitatively by QDG RAFT holds promise as a marker of motor decline related to current immune health in aging HIV patients and may be useful in longitudinal studies regarding mechanisms of immunosenescence vs. potential toxicity of combination antiretroviral therapy (cART) in this population. Additionally, motor and cognitive networks in HIV may be affected differently as the disease progresses as observed in the differential patterns of impairment between HIV and PD, providing insight into the mechanisms of brain deterioration in HIV.
Circular RNA Expression Profiling Identifies Glaucoma-Related Circular RNAs in Various Chronic Ocular Hypertension Rat Models

Circular RNAs are characterized as a class of covalently closed circular RNA transcripts and are associated with a variety of cellular processes and neurological diseases by sponging microRNAs. Expression profiling of circular RNAs in glaucoma, which is a form of optic neuropathy, has not been performed to date. The most common characteristic of all forms of glaucoma is the loss of retinal ganglion cells. While the pathogenesis of glaucoma is not fully understood, intraocular pressure is unquestionably the only proven modifiable factor which makes chronic ocular hypertension (COH) animals the classical glaucoma models. Based on these findings, we completed the first in-depth study of rat retinal circular RNA expression profiling to identify probable biomarkers for the diagnosis of glaucoma. Two ocular hypertension models were induced by episcleral vein ligation (EVL) and microbead injection in rats. Overall, 15,819 circular RNA were detected. Furthermore, 3,502 differentially expressed circular RNAs verified in both COH rats were identified, of which 691 were upregulated and 2,811 were downregulated. Seven significantly downregulated (both log2FoldChange < −2.5 and adjusted P < 0.001) and seven significantly upregulated (both log2FoldChange > 2.5 and adjusted P < 0.001) circular RNAs were shown. Six target microRNAs aligned with the top 14 circular RNAs were identified. According to the construction of the circular RNA-microRNA network and circBase information, only RNO_CIRCpedia_1775 had the homologous hsa_circ_0023826 in the human genome. The hsa_circ_0023826 and mRNA of the host gene TENM4 (teneurin transmembrane protein 4) were validated in aqueous humor samples of five glaucoma patients and five cataract control patients. The expression of hsa_circ_0023826 showed a significant decrease in glaucoma patients, while TENM4 mRNA showed no significant difference compared to cataract patients (P = 0.024 and P = 0.294, respectively). The results of this study comprehensively characterized the expression profiles of circular RNA in glaucoma-affected eyes, as verified by two different ocular hypertension rat models. Together with the target microRNAs underlying the top differentially expressed circular RNAs, a new target of hsa_circ_0023826 and its host gene TENM4 were identified and further verified in the aqueous humor of glaucoma patients, indicating a promising biomarker for the disease.
Iron Metabolism in Ferroptosis

Ferroptosis is a form of regulated cell death that is characterized by iron-dependent oxidative damage and subsequent plasma membrane ruptures and the release of damage-associated molecular patterns. Due to the role of iron in mediating the production of reactive oxygen species and enzyme activity in lipid peroxidation, ferroptosis is strictly controlled by regulators involved in many aspects of iron metabolism, such as iron uptake, storage, utilization, and efflux. Translational and transcriptional regulation of iron homeostasis provide an integrated network to determine the sensitivity of ferroptosis. Impaired ferroptosis is implicated in various iron-related pathological conditions or diseases, such as cancer, neurodegenerative diseases, and ischemia-reperfusion injury. Understanding the molecular mechanisms underlying the regulation of iron metabolism during ferroptosis may provide effective strategies for the treatment of ferroptosis-associated diseases. Indeed, iron chelators effectively prevent the occurrence of ferroptosis, which may provide new approaches for the treatment of iron-related disorders. In this review, we summarize recent advances in the theoretical modeling of iron-dependent ferroptosis, and highlight the therapeutic implications of iron chelators in diseases.
Fast Hollow Fiber Liquid-Phase Microextraction as a Greener Alternative for the Determination of N,N-Dimethyltryptamine and Harmala Alkaloids in Human Urine

Ayahuasca tea is an entheogen hallucinogenic beverage used for shamanic and spiritual purposes, prepared by the decoction of different Amazonian plants containing N,N-dimethyltryptamine (DMT) and harmala alkaloids. Since the therapeutic potential of this tea has been broadly studied in recent years, mainly for the treatment of psychiatric disorders, the determination of the ayahuasca tea components in human and animal matrices is of utmost importance. In order to avoid the use of large amounts of toxic solvents, typically employed in traditional sample preparation methods, hollow fiber liquid-phase microextraction (HF-LPME) presents a greener and time-saving alternative. The present study aims to fully develop and apply an HF-LPME method for the determination of DMT, harmine (HRM), harmaline (HRL), and tetrahydroharmine (THH) in human urine samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Fractional factorial and Box–Behnken designs were used to identify and optimize significant method variables. Once optimized, validation has shown a limit of detection (LoD) of 1.0 ng/ml for DMT and 2.0 ng/ml for the harmala alkaloid. The limit of quantification (LoQ) was of 5.0 ng/ml for all analytes. The method has shown to be linear over a concentration range of 5–200 ng/ml (r2 ≥ 0.99). Intra/inter-day precision and accuracy met the acceptance criteria at the three quality control (QC) levels studied (15.0, 90.0, and 170.0 ng/ml, n = 6, each). Matrix effect evaluation showed predominant ion enhancement and recovery values were above 80%. Dilution factors of 10- and 20-fold have shown acceptable values of accuracy. Selectivity studies showed no interferences. Analysis of eight authentic samples collected from four subjects proved method feasibility. A simple, time-saving and green alternative for the analysis of DMT and harmala alkaloids in human urine samples was developed, optimized using design of experiments, fully validated and applied to authentic samples.
Student and Teacher Meet in a Shared Virtual Reality: A one-on-one Tutoring System for Anatomy Education

We introduce a Virtual Reality (VR) one-on-one tutoring system to support anatomy education. A student uses a fully immersive VR headset to explore the anatomy of the base of the human skull. A teacher guides the student by using the semi-immersive zSpace. Both systems are connected via network and each action is synchronized between both systems. The teacher is provided with various features to direct the student through the immersive learning experience. She can influence the student's navigation or provide annotations on the fly and, hereby, improve the students learning experience. The system is implemented using the \textit{Unity} game engine. A qualitative user study demonstrates that the one-on-one tutoring approach is feasible and sets a solid base for future research in the area of shared virtual environments for anatomy education.
Mechanisms of Dysregulated Antibody Response in Lyme Disease

Lyme disease (LD), caused by the spirochetal bacterium Borrelia burgdorferi, is transmitted by the black-legged tick Ixodes scapularis (Hu, 2016). LD is the fastest growing global tick-borne disease and annually affects>300,000 people in the U.S. alone (Steere et al., 2016). The economic impact is a staggering $1.3 billion dollars per year (Adrion et al., 2015). LD can cause long-term, debilitating symptoms, including arthritis, carditis, and neurological complications (Hu, 2016; Steere et al., 2016). A longstanding question is why antibodies produced during primary infection are not able to completely clear spirochetes or confer protective immunity (Barbour et al., 2008). Antibody titers can remain for years in some LD patients while in others, they wane over time or never develop at all (Kalish et al., 2001). Herein, we describe animal studies that reveal mechanisms behind dysregulated development of adaptive immunity and provide insights that may be relevant to human immunity to B. burgdorferi infection.
Trophodynamics of three decapod crustaceans in a temperate estuary using stable isotope and fatty acid analyses

Temporal variations in stable isotope ratios and fatty acid composition were examined in 3 crustacean species and their potential food sources in a temperate estuary. We hypothesized that the shrimp Palaemon peringueyi, the mud prawn Upogebia africana and the sand prawn Callichirus kraussi have disparate diets due to interspecific differences in metabolism and feeding mode and that diets of the crustaceans all change temporally due to variations in available food. The species with the most variable diet was expected to have the greatest niche differentiation. We sampled the 3 crustaceans and their food sources on occasions spanning 4 seasons. The diet of P. peringueyi changed from a dominance of benthic microalgae in spring and winter to increased contributions of particulate organic matter (POM) in summer, with preferential sequestration of 22:6ω3. U. africana showed a stable dependence on estuarine POM as the main source of its energy, while C. kraussi relied more on marine POM, except in winter, when benthic microalgae was an important energy source. The 2 infaunal prawns showed elevated proportions of 16:1ω7 and 20:5ω3 throughout most of the year, probably originating from diatoms. P. peringueyi showed a different preferred diet than the 2 prawns, resulting in an isotopic niche segregation from the infaunal prawns, but the fatty acid niche of the shrimp overlapped with the prawns. Stable isotope values revealed the temporal variations in the origins and proportions of different food sources contributing to the diet of each species, while fatty acid data provided information on finer-scale trophic interactions. Temporal variations in estuarine consumer diets should be con sidered in estuarine food web studies whenever possible.