Miracle-dz/UniFAR-FTUs huggingface dataset:
Rapid Depletions of Subcutaneous Fat Mass and Skeletal Muscle Mass Predict Worse Survival in Patients with Hepatocellular Carcinoma Treated with Sorafenib

The aim of this study was to investigate whether rapid depletions of fat mass and skeletal muscle mass predict mortality in hepatocellular carcinoma (HCC) patients treated with sorafenib. This retrospective study evaluated 61 HCC patients. The cross-sectional areas of visceral and subcutaneous fat mass and skeletal muscle mass were measured by computed tomography, from which the visceral fat mass index (VFMI), subcutaneous fat mass index (SFMI), and skeletal muscle index (L3SMI) were obtained. The relative changes in these indices per 120 days (ΔVFMI, ΔSFMI, and ΔL3SMI) before and after sorafenib treatment were calculated in each patient. Patients within the 20th percentile cutoffs for these indices were classified into the rapid depletion (RD) group. Kaplan–Meier analysis revealed that with respect to ΔL3SMI (p = 0.0101) and ΔSFMI (p = 0.0027), the RD group had a significantly poorer survival. Multivariate analysis using the Cox proportional-hazards model also demonstrated that ΔL3SMI (≤−5.73 vs. >−5.73; hazard ratio [HR]: 4.010, 95% confidence interval [CI]: 1.799–8.938, p = < 0.001) and ΔSFMI (≤−5.33 vs. >−5.33; HR: 4.109, 95% CI: 1.967–8.584, p = < 0.001) were independent predictors. Rapid depletions of subcutaneous fat mass and skeletal muscle mass after the introduction of sorafenib indicate a poor prognosis.
Human Appropriated Net Primary Productivity of Complex Mosaic Landscapes

Quantifying human impact on the environment is increasingly important and particularly so in complex mosaic landscapes. Such landscapes are prolific in the developing world, notably in West African, small holder cocoa farming communities. Human Appropriated Net Primary Productivity (HANPP) is a metric which has been developed to quantify the human impact on the environment and has been used in a number of studies globally. However, most operationalization’s of HANPP have been done on a coarse global scale or a very local scale, and few studies exist of complex mosaic landscapes. This study utilizes Unmanned Autonomous Vehicles (UAV), or drones, to classify land use and HANPP for three cocoa farming regions in Ghana’s Central Region. The results of the study indicate while all regions differ in land use composition, the primary crop for all is cocoa, followed by palm and then land that was previously cultivated which has been left fallow. The average HANPP was 44% for all measured regions, calculated using net primary productivity (NPP) values of an adjacent natural tropical forest. The HANPP for the three regions studied was found to be approximately 6.69 Mg C ha-1 yr-1, 8.00 Mg C ha-1 yr-1 and 9.85 Mg C ha-1 yr-1. These values are higher than those that have been reported in some widely accepted global studies, and highlight the need for more regional and landscape scale studies to supplement global assessments of HANPP.
Mandatory Medication Indications in Electronic Systems - The Prescriber Perspective

As hospitals transition from paper to electronic medication charts, an opportunity exists to 'nudge' prescribers to document medication indications by making this data-entry field mandatory. The aim of this study was to explore hospital doctors' perceptions of mandatory documentation of indications in an electronic medication management (EMM) system. Ten junior doctors took part in brief semi-structured interviews. Participants identified improved communication among staff as a key benefit of indication documentation. Recording indications was also seen to act as a prompt for medication review. Despite these benefits, indication documentation for all medications would be challenging to implement in practice. Users of the EMM system (i.e. junior doctors) explained that they are time poor and are often tasked with transcribing medication orders into the electronic system with limited knowledge of why medications are being prescribed. Determining the indication for use would require additional time and effort, and prescribers reported a high risk of working around the system if indication documentation was made mandatory.
Sowing the Seeds of Seagrass Recovery Using Hessian Bags

Seagrass meadows are an important wetland habitat that has been degraded globally but has an important carbon storage role. In order to expand the restoration of these productive and biodiverse habitats methods are required, that can be used for large scale habitat creation across a range of environmental conditions. The spreading of seagrass seeds has been proven to be a successful method for restoring seagrass around the world, however in places where the tidal range is large such methods become limited by resultant water movements. Here we describe and test a method for deploying seagrass seeds of the species Zostera marina over large scales using a new, simple method ‘Bags of Seagrass Seeds Line (BoSSLine)’. This method involved planting seeds and sediment using natural fibre hessian bags deployed along strings anchored onto the seabed. When deployed in a suitable environment a 94% of bags developed mature seagrass shoots, unfortunately, one site subjected to a large storm event resulted in sediment burial of the bags and no seed germination. Bags were filled with 100 seeds with each leading to the development of 2.37 ± 2.41 mature shoots (206 ± 87 mm in length) 10 months after planting. The method was proven successful however the experiments illustrated the need to ensure habitat suitability prior to their use. The low seed success rate was comparable to other restoration studies however further trials are recommended to ensure ways to improve this rate. In conclusion, this study provides evidence for an effective, simple method ‘Bags of Seagrass Seeds Line (BoSSLine)’ for deploying seeds of the seagrass Zostera marina over large scales.
Antibodies to Human Herpesviruses in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients

Myalgic encephalomyelitis, also referred to as chronic fatigue syndrome (ME/CFS) is a debilitating disease characterized by myalgia and a sometimes severe limitation of physical activity and cognition. It is exacerbated by physical and mental activity. Its cause is unknown, but frequently starts with an infection. The eliciting infection (commonly infectious mononucleosis or an upper respiratory infection) can be more or less well diagnosed. Among the human herpesviruses (HHV-1-8), HHV-4 (Epstein-Barr virus; EBV), HHV-6 (including HHV-6A and HHV-6B), and HHV-7, have been implicated in the pathogenesis of ME/CFS. It was therefore logical to search for serological evidence of past herpesvirus infection/reactivation in several cohorts of ME/CFS patients (all diagnosed using the Canada criteria). Control samples were from Swedish blood donors. We used whole purified virus, recombinant proteins, and synthetic peptides as antigens in a suspension multiplex immunoassay (SMIA) for immunoglobulin G (IgG). The study on herpesviral peptides based on antigenicity with human sera yielded novel epitope information. Overall, IgG anti-herpes-viral reactivities of ME/CFS patients and controls did not show significant differences. However, the high precision and internally controlled format allowed us to observe minor relative differences between antibody reactivities of some herpesviral antigens in ME/CFS versus controls. ME/CFS samples reacted somewhat differently from controls with whole virus HHV-1 antigens and recombinant EBV EBNA6 and EA antigens. We conclude that ME/CFS samples had similar levels of IgG reactivity as blood donor samples with HHV-1-7 antigens. The subtle serological differences should not be over-interpreted, but they may indicate that the immune system of some ME/CFS patients interact with the ubiquitous herpesviruses in a way different from that of healthy controls.
Mortality Risk of Atypical Antipsychotics for Behavioral and Psychological Symptoms of Dementia: A Meta-Analysis, Meta-Regression, and Trial Sequential Analysis of Randomized Controlled Trials.

BACKGROUND Evidence suggests that atypical antipsychotics (AAPs) exert a short-term mortality risk in people with dementia. We assessed whether additional randomized clinical trials influence the current evidence and the potential effect modifiers. METHODS Electronic databases were systematically searched for randomized controlled trials from their inception through March 2018. A random-effects model was used for analysis. Potential effect modifiers were examined through meta-regression. Trial sequential analysis was performed to quantify the statistical reliability of data in the cumulative meta-analysis with adjustment of significance levels for sparse data and repetitive testing on accumulating data. Certainty of evidence and risk of bias were also evaluated. RESULTS We found that compared with placebos, AAPs may increase the risk of mortality (odds ratio [OR], 1.536; 95% confidence intervals [CIs], 1.028-2.296; P = 0.036, high certainty). In the subgroup analysis, the estimated ORs were the highest for olanzapine (1.919; P = 0.232), followed by those for quetiapine (1.663; P = 0.506), aripiprazole (1.649; P = 0.297), and risperidone (1.354; P = 0.277); however, the mortality risk presented by individual AAPs did not exhibit between-group differences. The meta-regression did not identify any effect modifiers, including the chlorpromazine equivalent dose, trial duration, and cognitive status. The trial sequential analysis revealed that future similar trials are unlikely to alter our findings. CONCLUSIONS Atypical antipsychotics are associated with increased short-term mortality risk, although a disease-drug interaction may contribute to such risk in people with dementia. Patients with dementia may still benefit by AAPs after appropriate assessment of the disease severity as well as the dosage of AAPs, treatment duration, and monitoring of AAPs.
Hate speech detection: Challenges and solutions

As online content continues to grow, so does the spread of hate speech. We identify and examine challenges faced by online automatic approaches for hate speech detection in text. Among these difficulties are subtleties in language, differing definitions on what constitutes hate speech, and limitations of data availability for training and testing of these systems. Furthermore, many recent approaches suffer from an interpretability problem—that is, it can be difficult to understand why the systems make the decisions that they do. We propose a multi-view SVM approach that achieves near state-of-the-art performance, while being simpler and producing more easily interpretable decisions than neural methods. We also discuss both technical and practical challenges that remain for this task.
Effect of Metalloproteinase Inhibitors on Bond Strength of a Self-etching Adhesive on Erosively Demineralized Dentin.

PURPOSE To analyze the influence of epigallocatechin-3-gallate (EGCG) and chlorhexidine (CHX) on adhesive-dentin bond strength of a self-etch adhesive to sound dentin (SD) and eroded dentin (ED). MATERIALS AND METHODS Thirty-six middle-dentin samples were assigned to six groups (n = 6) according to pretreatment (DW: distilled water, control; 0.1% EGCG; or 2% CHX) and erosive challenge (presence or absence). Specimens were subjected to 2-h acquired pellicle formation, then half of them were exposed to 1% citric acid three times a day for five days. SD and ED were treated with the tested solutions for 60 s, and then Clearfil SE Bond was applied before resin composite buildup. Bonded teeth were longitudinally sectioned into sticks and half were immediately tested, while the remaining specimens were tested after six months. The mode of fracture was examined and the microtensile bond strength (µTBS) measured. Statistical analysis was performed with ANOVA and Bonferroni tests. RESULTS At both time periods, regardless of the dentin substrate, EGCG groups did not show bond strengths that were significantly different from those obtained with DW (p > 0.05), while CHX generated lower values than did DW (p < 0.05). On SD, there was a bond strength reduction only in the CHX groups after six months. However, for ED, the bond strength significantly decreased in all groups. CONCLUSION CHX negatively affected both dentin substrates, while the pretreatment with EGCG did not affect µTBS over time on SD. µTBS may be influenced by the substrate over time and EGCG can be used as an alternative to CHX to maintain the bond strength of self-etching adhesives.
Model-Based Assessment of the Role of Uneven Partitioning of Molecular Content on Heterogeneity and Regulation of Differentiation in CD8 T-Cell Immune Responses

Activation of naive CD8 T-cells can lead to the generation of multiple effector and memory subsets. Multiple parameters associated with activation conditions are involved in generating this diversity that is associated with heterogeneous molecular contents of activated cells. Naive cell polarisation upon antigenic stimulation and the asymmetric division that results are known to be a major source of heterogeneity and cell fate regulation. The consequences of stochastic uneven partitioning of molecular content upon subsequent divisions remain unclear. Here we aim at studying the impact of uneven partitioning on molecular-content heterogeneity and then on the immune response dynamics at the cellular level. To do so, we introduce a multiscale mathematical model of the CD8 T-cell immune response in the lymph node. In the model, cells are described as agents evolving and interacting in a 2D environment while a set of differential equations, embedded in each cell, models the regulation of intra and extracellular proteins involved in cell differentiation. Based on the analysis of in silico data at the single cell level, we show that immune response dynamics can be explained by the molecular-content heterogeneity generated by uneven partitioning at cell division. In particular, uneven partitioning acts as a regulator of cell differentiation and induces the emergence of two coexisting subpopulations of cells exhibiting antagonistic fates. We show that the degree of unevenness of molecular partitioning, along all cell divisions, affects the outcome of the immune response and can promote the generation of memory cells.
Population-Based Evaluation of Lumbar Puncture Opening Pressures

Importance: Prior studies evaluating opening pressure (OP) have mostly involved lumbar puncture (LP) for diagnosis of neurologic disease or small cohorts of healthy volunteers and therefore the normal OP is not well-defined. Objective: The goal of this study was to establish the normal range of OP in a community-based population using the Mayo Clinic Study of Aging (MCSA) and to evaluate factors that contribute to OP variability. Design: LP OP were obtained from participants aged 32–95 years between 11/1/07 and 10/1/17, as part of routine data collection for the MCSA, a longitudinal, population-based study of residents of Olmsted County, Minnesota. Setting: A longitudinal, population-based study of residents of Olmsted County, Minnesota. Participants: There were 639 participants (56.8% male; 98.5% white) who underwent LP with recorded OP as part of the MCSA. Intervention: LP. Main Outcome(s) and Measure(s): LP OP was recorded along with variables that could possibly influence its variability, including age, body mass index (BMI), and obstructive sleep apnea (OSA). Results: Six hundred thirty-nine participants (56.8% men) underwent LP with recorded OP; average age was 71.0 years (SD 10.9) with a mean BMI of 28.0 (SD 4.6). Mean OP was 155.4 mmH2O (SD 41.9) with a 95% reference interval of 82–242 mmH2O (range 60–314; Q1, Q3: 124, 182). Increasing age was associated with lower OP (p < 0.001), while increasing BMI was associated with higher OP (p < 0.001). Twelve (2%) participants had OP ≥ 250 mmH2O; they were younger [58.5 (SD 8.2), p < 0.001], had higher BMI [33.6 (SD 4.6), p < 0.001], and were more likely to have OSA (75%, p < 0.001). Among the 79 participants with repeat LPs within 2.5 years, the coefficient of repeatability (CR) was 64.9. Ten (12.7%) had an OP difference ≥50 mmH2O between serial LPs. Conclusions and Relevance: This large population-based study showed that LP OP can vary significantly among individuals. Higher OPs were associated with higher BMI and younger age.
NK Cell Dysfunction and Checkpoint Immunotherapy

NK cells play important roles in the innate immune responses against tumors. The effector function of NK cells relies on the integration of activating and inhibitory signals. Emerging checkpoint receptors and molecules are being revealed to mediate NK cell dysfunction in the tumor microenvironment. Inhibition of some NK cell surface checkpoint receptors has displayed the potential to reverse NK cell dysfunction in tumors, and to boost anti-tumor immunity, both in clinical trials (anti-KIR and anti-NKG2A), and in preclinical studies (e.g., anti-TIGIT, and anti-CD96). To fully exploit the potential of NK–based checkpoint immunotherapy, more understanding of the regional features of NK cells in the tumor microenvironment is required. This will provide valuable information regarding the dynamic nature of NK cell immune response against tumors, as well as novel checkpoints or pathways to be targeted. In this Review, we discuss recent advances in the understanding of NK cell dysfunction in tumors, as well as emerging strategies of NK-based checkpoint immunotherapy for tumors.
Sickle Cell Trait, European Ancestry, and Longitudinal Tracking of HbA1c Among African Americans: The Jackson Heart Study

Studies of differences in glycosylated hemoglobin (HbA1c) have defined race/ethnicity as a social construct (1,2), not using objective biological parameters, and thus comparisons may have been confounded (3). Among blacks without diabetes, we investigated whether the proportion of European genetic ancestry (PEA) mediates the sickle cell trait (SCT) and HbA1c relation and whether PEA tracks HbA1c levels over time accounting for SCT. We used data from three Jackson Heart Study (JHS) visits (2000–2004, 2005–2008, and 2009–2013), occurring at 4-year intervals. We excluded participants with diabetes (use of glucose-lowering medication or fasting blood glucose [FBG] ≥126 mg/dL) or prediabetes (FBG ≥100 mg/dL) at visit 1. We estimated PEA using 1,444 ancestry-informative markers. The rs334 variant defined SCT, and rs1050828 indicated glucose-6-phosphate dehydrogenase (G6PD) deficiency. HbA1c was assessed by high-performance liquid chromatography (Tosoh analyzer; assays coefficient of variation 1.4–1.9%). Using visit 1 data, we estimated three relations (Fig. 1 A ) corresponding to regressions of 1 ) SCT on HbA1c ( c ), 2 ) SCT on PEA ( a ), and 3 ) both SCT and PEA on HbA1c levels ( c′ ). The indirect effect of PEA on HbA1c was estimated using the difference between c and c′. Complete mediation is observed when c′ = 0 and partial mediation when c − c′ ≠ 0 (Fig. 1 A ). Figure 1 A : Schematic conceptual framework …
Virtual Reality Assessment of Classroom – Related Attention: An Ecologically Relevant Approach to Evaluating the Effectiveness of Working Memory Training

Computerized cognitive interventions to improve working memory also purport to improve ADHD-related inattention and off task behavior. Such interventions have been shown to improve working memory, executive functioning, and fluid reasoning on standardized neuropsychological measures. However, debate continues as to whether such programs lead to improvement on ecologically relevant outcomes, such as classroom behavior. This study sought to propose a novel, ecologically relevant approach to evaluate the effectiveness of working memory training on real-world attention performance. Participants included 15 children, aged 6–15, identified as having attention problems were assessed via the virtual classroom continuous performance task (VCCPT) before and after completing 5 weeks of Cogmed working memory training. The VCCPT is a validated measure of sustained and selective attention set within a virtual reality (VR) environment. Several key areas of attention performance were observed to improve, including omission errors, reaction time, reaction time variability, and hit variability. Results suggest that working memory training led to substantial improvements in sustained attention in a real-life scenario of classroom learning. Moreover, the use of psychometrically validated VR measurement provides incremental validity beyond that of teacher or parent report of behavior. Observing such improvements on ecologically relevant measures of attention adds to the discussion around how to evaluate the effectiveness of working memory training as it pertains to real-life improvements and serves to inform consumer awareness of such products and their claims.
Viral Sequences Detection by High-Throughput Sequencing in Cerebrospinal Fluid of Individuals with and without Central Nervous System Disease

Meningitis, encephalitis, and myelitis are various forms of acute central nervous system (CNS) inflammation, which can coexist and lead to serious sequelae. Known aetiologies include infections and immune-mediated processes. Despite advances in clinical microbiology over the past decades, the cause of acute CNS inflammation remains unknown in approximately 50% of cases. High-throughput sequencing was performed to search for viral sequences in cerebrospinal fluid (CSF) samples collected from 26 patients considered to have acute CNS inflammation of unknown origin, and 10 patients with defined causes of CNS diseases. In order to better grasp the clinical significance of viral sequence data obtained in CSF, 30 patients without CNS disease who had a lumbar puncture performed during elective spinal anaesthesia were also analysed. One case of human astrovirus (HAstV)-MLB2-related meningitis and disseminated infection was identified. No other viral sequences that can easily be linked to CNS inflammation were detected. Viral sequences obtained in all patient groups are discussed. While some of them reflect harmless viral infections, others result from reagent or sample contamination, as well as index hopping. Altogether, this study highlights the potential of high-throughput sequencing in identifying previously unknown viral neuropathogens, as well as the interpretation issues related to its application in clinical microbiology.
Discovery of Ethyl 2-Nitro-3-Arylacrylates Molecules as T3SS Inhibitor Reducing the Virulence of Plant Pathogenic Bacteria Xanthomonas

Xanthomonas oryzae pv. oryzae (Xoo) is a gram-negative pathogen which causes leaf blight disease. Known traditional bactericides are not much more effective in inhibiting this bacteria than before. Selecting the virulence factor of the bacteria as the target without affecting their growth has been considered as a novel method for developing new anti-microbial drugs. Type III secretion systems (T3SS) are one of the important and highly conserved virulence factors in most gram-negative pathogens, which has been considered as an effective target to develop new anti-microbial drugs. In order to discover potential anti-microbial drugs against Xoo pathogens, a series of ethyl 2-nitro-3-arylacrylates compounds were screened. Among them, the compounds I-9, I-12, and I-13 could highly inhibit the promoter activity of a harpin gene hpa1, which were used to further check for the influence on bacterial growth and on the hypersensitive response (HR) caused by Xoo bacteria on non-host plants. The results showed that above compounds could reduce HR without affecting bacterial growth and survival. Moreover, qRT-PCR analysis indicated that treatment with the three inhibitors (I-9, I-12, and I-13) could suppress the expression of the Xoo T3SS in different extent. The mRNA levels of representative genes in the hrp cluster, including the key regulatory genes hrpG and hrpX, were decreased. Last but not least, in vivo test ensured that the above compounds reduced the disease symptoms of Xoo on the rice and Xcc on the Chinese radish.