Miracle-dz/UniFAR-FTUs huggingface dataset:
Detection of somatic mutations in cell-free DNA in plasma and correlation with overall survival in patients with solid tumors

A suitable clinical-grade platform is required for detection of somatic mutations with high sensitivity in cell-free DNA (cfDNA) of patients with solid tumors. In this study, we evaluated in parallel ultra-deep NGS with MassARRAY and allele-specific droplet digital PCR (ddPCR) for cfDNA genotyping and correlated cfDNA yield and mutation status with overall survival (OS) of patients. We assessed plasma samples from 46 patients with various advanced metastatic solid tumors and known mutations by deep sequencing using an Ampliseq cancer hotspot panel V2 on Ion Proton. A subset of these samples with DNA availability was tested by ddPCR and UltraSEEK MassARRAY for mutation detection in 5 genes (IDH1, PIK3CA, KRAS, BRAF, and NRAS). Sixty one of 104 expected tissue mutations and 6 additional mutations not present in the tissue were detected in cfDNA. ddPCR and MassARRAY showed 83% and 77% concordance with NGS for mutation detection with 100% and 79% sensitivity, respectively. The median OS of patients with lower cfDNA yield (74 vs 50 months; P < 0.03) and cfDNA negative for mutations (74.2 vs 53 months; p < 0.04) was significantly longer than in patients with higher cfDNA yield and positive for mutations. A limit-of-detection of 0.1% was demonstrated for ddPCR and MassARRAY platforms using a serially diluted positive cfDNA sample. The MassARRAY and ddPCR systems enable fast and cost-effective genotyping for a targeted set of mutations and can be used for single gene testing to guide response to chemotherapy or for orthogonal validation of NGS results.
A Review of Co-Saliency Detection Algorithms

Co-saliency detection is a newly emerging and rapidly growing research area in the computer vision community. As a novel branch of visual saliency, co-saliency detection refers to the discovery of common and salient foregrounds from two or more relevant images, and it can be widely used in many computer vision tasks. The existing co-saliency detection algorithms mainly consist of three components: extracting effective features to represent the image regions, exploring the informative cues or factors to characterize co-saliency, and designing effective computational frameworks to formulate co-saliency. Although numerous methods have been developed, the literature is still lacking a deep review and evaluation of co-saliency detection techniques. In this article, we aim at providing a comprehensive review of the fundamentals, challenges, and applications of co-saliency detection. Specifically, we provide an overview of some related computer vision works, review the history of co-saliency detection, summarize and categorize the major algorithms in this research area, discuss some open issues in this area, present the potential applications of co-saliency detection, and finally point out some unsolved challenges and promising future works. We expect this review to be beneficial to both fresh and senior researchers in this field and to give insights to researchers in other related areas regarding the utility of co-saliency detection algorithms.
Achieving Geometric Convergence for Distributed Optimization Over Time-Varying Graphs

This paper considers the problem of distributed optimization over time-varying graphs. For the case of undirected graphs, we introduce a distributed algorithm, referred to as DIGing, based on a combination of a distributed inexact gradient method and a gradient tracking technique. The DIGing algorithm uses doubly stochastic mixing matrices and employs fixed step-sizes and, yet, drives all the agents' iterates to a global and consensual minimizer. When the graphs are directed, in which case the implementation of doubly stochastic mixing matrices is unrealistic, we construct an algorithm that incorporates the push-sum protocol into the DIGing structure, thus obtaining Push-DIGing algorithm. The Push-DIGing uses column stochastic matrices and fixed step-sizes, but it still converges to a global and consensual minimizer. Under the strong convexity assumption, we prove that the algorithms converge at R-linear (geometric) rates as long as the step-sizes do not exceed some upper bounds. We establish explicit estimates for the convergence rates. When the graph is undirected it shows that DIGing scales polynomially in the number of agents. We also provide some numerical experiments to demonstrate the efficacy of the proposed algorithms and to validate our theoretical findings.
Multiple Scan Data Association by Convex Variational Inference

Data association, the reasoning over correspondence between targets and measurements, is a problem of fundamental importance in target tracking. Recently, belief propagation (BP) has emerged as a promising method for estimating the marginal probabilities of measurement to target association, providing fast, accurate estimates. The excellent performance of BP in the particular formulation used may be attributed to the convexity of the underlying free energy, which it implicitly optimizes. This paper studies multiple scan data association problems, i.e., problems that reason over correspondence between targets and several sets of measurements, which may correspond to different sensors or different time steps. We find that the multiple scan extension of the single scan BP formulation is nonconvex and demonstrate the undesirable behavior that can result. A convex free energy is constructed using the recently proposed fractional free energy (FFE). A convergent, BP-like algorithm is provided for the single scan FFE, and employed in optimizing the multiple scan free energy using primal-dual coordinate ascent. Finally, based on a variational interpretation of joint probabilistic data association (JPDA), we develop a sequential variant of the algorithm that is similar to JPDA, but retains consistency constraints from prior scans. The performance of the proposed methods is demonstrated on a bearings only target localization problem.
How Does Food Taste in Anorexia and Bulimia Nervosa? A Protocol for a Quasi-Experimental, Cross-Sectional Design to Investigate Taste Aversion or Increased Hedonic Valence of Food in Eating Disorders

Background: Despite on-going efforts to better understand dysregulated eating, the olfactory-gustatory deficits and food preferences in eating disorders (ED), and the mechanisms underlying the perception of and responses to food properties in anorexia nervosa (AN) and bulimia nervosa (BN) remain largely unknown; both during the course of the illness and compared to healthy populations. It is, therefore, necessary to systematically investigate the gustatory perception and hedonics of taste in patients with AN and BN. To this end, we will examine whether aversions to the taste of high-calorie food is related to the suppression of energy intake in restricting-type AN, and whether an increased hedonic valence of sweet, caloric-dense foods may be part of the mechanisms triggering binge-eating episodes in BN. In addition, the role of cognitions influencing these mechanisms will be examined. Method: In study 1, four mixtures of sweet-fat stimuli will be presented in a sensory two-alternative forced-choice test involving signal detection analysis. In study 2, a full-scale taste reactivity test will be carried out, including psychophysiological and behavioral measures to assess subtle and covert hedonic changes. We will compare the responses of currently-ill AN and BN patients to those who have recovered from AN and BN, and also to those of healthy normal-weight and underweight individuals without any eating disorder pathology. Discussion: If taste response profiles are differentially linked to ED types, then future studies should investigate whether taste responsiveness represents a useful diagnostic measure in the prevention, assessment and treatment of EDs. The expected results on cognitive mechanisms in the top-down processes of food hedonics will complement current models and contribute to the refinement of interventions to change cognitive aspects of taste aversions, to establish functional food preferences and to better manage food cravings associated with binge-eating episodes. No trial registration was required for this protocol, which was approved by the Swiss ethics committee (CER-VD, n° 2016-02150) and the Ethics Review Panel of the University of Luxembourg.
The Nature of the Dietary Protein Impacts the Tissue-to-Diet 15N Discrimination Factors in Laboratory Rats

Due to the existence of isotope effects on some metabolic pathways of amino acid and protein metabolism, animal tissues are 15N-enriched relative to their dietary nitrogen sources and this 15N enrichment varies among different tissues and metabolic pools. The magnitude of the tissue-to-diet discrimination (Δ15N) has also been shown to depend on dietary factors. Since dietary protein sources affect amino acid and protein metabolism, we hypothesized that they would impact this discrimination factor, with selective effects at the tissue level. To test this hypothesis, we investigated in rats the influence of a milk or soy protein-based diet on Δ15N in various nitrogen fractions (urea, protein and non-protein fractions) of blood and tissues, focusing on visceral tissues. Regardless of the diet, the different protein fractions of blood and tissues were generally 15N-enriched relative to their non-protein fraction and to the diet (Δ15N>0), with large variations in the Δ15N between tissue proteins. Δ15N values were markedly lower in tissue proteins of rats fed milk proteins compared to those fed soy proteins, in all sampled tissues except in the intestine, and the amplitude of Δ15N differences between diets differed between tissues. Both between-tissue and between-diet Δ15N differences are probably related to modulations of the relative orientation of dietary and endogenous amino acids in the different metabolic pathways. More specifically, the smaller Δ15N values observed in tissue proteins with milk than soy dietary protein may be due to a slightly more direct channeling of dietary amino acids for tissue protein renewal and to a lower recycling of amino acids through fractionating pathways. In conclusion, the present data indicate that natural Δ15N of tissue are sensitive markers of the specific subtle regional modifications of the protein and amino acid metabolism induced by the protein dietary source.
Semantic Parsing Natural Language into SPARQL: Improving Target Language Representation with Neural Attention

Semantic parsing is the process of mapping a natural language sentence into a formal representation of its meaning. In this work we use the neural network approach to transform natural language sentence into a query to an ontology database in the SPARQL language. This method does not rely on handcraft-rules, high-quality lexicons, manually-built templates or other handmade complex structures. Our approach is based on vector space model and neural networks. The proposed model is based in two learning steps. The first step generates a vector representation for the sentence in natural language and SPARQL query. The second step uses this vector representation as input to a neural network (LSTM with attention mechanism) to generate a model able to encode natural language and decode SPARQL.
HRS/ACC/AHA expert consensus statement on the use of implantable cardioverter-defibrillator therapy in patients who are not included or not well represented in clinical trials.

1. Introduction 95 2. Current Guidelines that Address ICD Use 95 3. Randomized Controlled Trials of ICD Therapy for Primary Prevention of Sudden Cardiac Death 96 4. ICD Implantation in the Context of an Abnormal Troponin that Is Not Due to a Myocardial Infarction 100 5. ICD Implantation Within 40 Days of a Myocardial Infarction 101 6. ICD Implantation Within 90 Days of Revascularization 105 7. ICD Implantation < 9 Months from the Initial Diagnosis of Nonischemic Cardiomyopathy 110 8. Dual-Chamber vs Single-Chamber ICD Recommendations 114 9. Documentation of Clinical Decisions 116 10. Future Research and Directions 117 The implantable cardioverter defibrillator (ICD) has emerged as an important treatment option for selected patients who are at risk of sudden cardiac death. Randomized trials have consistently shown that ICD implantation reduces mortality in patients with heart failure and reduced left ventricular function, as well as in patients who have suffered a cardiac arrest.1–3 Recommendations on the use of the ICD in clinical practice have been provided in four important guideline documents sponsored by the American College of Cardiology (ACC), the American Heart Association (AHA), Heart Rhythm Society (HRS), and the European Society of Cardiology (ESC). 4–7 For each indication for ICD therapy, both a Class of indication (I, II, or III) and level of evidence for the indication (A, B, or C) are provided. To ensure that recommendations are evidence-based, Class I recommendations are typically based on the results of prospective randomized clinical trials. For example, in the ACC/AHA/HRS 2012 Focused Update of the …
Defining Obesity Cut-Off Points for Migrant South Asians

Background Body mass index (BMI) and waist circumference (WC) are used to define cardiovascular and type 2 diabetes risk. We aimed to derive appropriate BMI and WC obesity cut-off points in a migrant South Asian population. Methods 4688 White Europeans and 1333 South Asians resident in the UK aged 40–75 years inclusive were screened for type 2 diabetes. Principal components analysis was used to derive a glycaemia, lipid, and a blood pressure factor. Regression models for each factor, adjusted for age and stratified by sex, were used to identify BMI and WC cut-off points in South Asians that correspond to those defined for White Europeans. Findings For South Asian males, derived BMI obesity cut-off points equivalent to 30.0 kg/m2 in White Europeans were 22.6 kg/m2 (95% Confidence Interval (95% CI) 20.7 kg/m2 to 24.5 kg/m2) for the glycaemia factor, 26.0 kg/m2 (95% CI 24.7 kg/m2 to 27.3 kg/m2) for the lipid factor, and 28.4 kg/m2 (95% CI 26.5 kg/m2 to 30.4 kg/m2) for the blood pressure factor. For WC, derived cut-off points for South Asian males equivalent to 102 cm in White Europeans were 83.8 cm (95% CI 79.3 cm to 88.2 cm) for the glycaemia factor, 91.4 cm (95% CI 86.9 cm to 95.8 cm) for the lipid factor, and 99.3 cm (95% CI 93.3 cm to 105.2 cm) for the blood pressure factor. Lower ethnicity cut-off points were seen for females for both BMI and WC. Conclusions Substantially lower obesity cut-off points are needed in South Asians to detect an equivalent level of dysglycemia and dyslipidemia as observed in White Europeans. South Asian ethnicity could be considered as a similar level of risk as obesity (in White Europeans) for the development of type 2 diabetes.
Management of therapeutic anticoagulation in patients with intracerebral haemorrhage and mechanical heart valves

Aims Evidence is lacking regarding acute anticoagulation management in patients after intracerebral haemorrhage (ICH) with implanted mechanical heart valves (MHVs). Our objective was to investigate anticoagulation reversal and resumption strategies by evaluating incidences of haemorrhagic and thromboembolic complications, thereby defining an optimal time‐window when to restart therapeutic anticoagulation (TA) in patients with MHV and ICH. Methods and results We pooled individual patient‐data (n = 2504) from a nationwide multicentre cohort‐study (RETRACE, conducted at 22 German centres) and eventually identified MHV‐patients (n = 137) with anticoagulation‐associated ICH for outcome analyses. The primary outcome consisted of major haemorrhagic complications analysed during hospital stay according to treatment exposure (restarted TA vs. no‐TA). Secondary outcomes comprised thromboembolic complications, the composite outcome (haemorrhagic and thromboembolic complications), timing of TA, and mortality. Adjusted analyses involved propensity‐score matching and multivariable cox‐regressions to identify optimal timing of TA. In 66/137 (48%) of patients TA was restarted, being associated with increased haemorrhagic (TA = 17/66 (26%) vs. no‐TA = 4/71 (6%); P < 0.01) and a trend to decreased thromboembolic complications (TA = 1/66 (2%) vs. no‐TA = 7/71 (10%); P = 0.06). Controlling treatment crossovers provided an incidence rate‐ratio [hazard ratio (HR) 10.31, 95% confidence interval (CI) 3.67‐35.70; P < 0.01] in disadvantage of TA for haemorrhagic complications. Analyses of TA‐timing displayed significant harm until Day 13 after ICH (HR 7.06, 95% CI 2.33‐21.37; P < 0.01). The hazard for the composite—balancing both complications, was increased for restarted TA until Day 6 (HR 2.51, 95% CI 1.10‐5.70; P = 0.03). Conclusion Restarting TA within less than 2 weeks after ICH in patients with MHV was associated with increased haemorrhagic complications. Optimal weighing—between least risks for thromboembolic and haemorrhagic complications—provided an earliest starting point of TA at Day 6, reserved only for patients at high thromboembolic risk. Figure. No Caption available.
The complete chloroplast genome of an irreplaceable dietary and model crop, foxtail millet (Setaria italica)

Abstract The complete chloroplast genome sequence of foxtail millet (Setaria italica), an important food and fodder crop in the family Poaceae, is first reported in this study. The genome consists of 1 35 516 bp containing a pair of inverted repeats (IRs) of 21 804 bp separated by a large single-copy (LSC) region and a small single-copy (SSC) region of 79 896 bp and 12 012 bp, respectively. Coding sequences constitute 58.8% of the genome harboring 111 unique genes, 71 of which are protein-coding genes, 4 are rRNA genes, and 36 are tRNA genes. Phylogenetic analysis indicated foxtail millet clustered with Panicum virgatum and Echinochloa crus-galli belonging to the tribe Paniceae of the subfamily Panicoideae. This newly determined chloroplast genome will provide valuable information for the future breeding programs of valuable cereal crops in the family Poaceae.
The Effect of Antiamoebic Agents on Viability, Proliferation and Migration of Human Epithelial Cells, Keratocytes and Endothelial Cells, In Vitro

ABSTRACT Purpose: To analyze the effect of diamidines (hexamidine-diisethionat (HD), propamidin-isethionate (PD), dibromopropamidine-diisethionat (DD)), and biguanides (polyhexamethylen biguanid (PHMB), chlorhexidine (CH)) on human corneal epithelial cell, keratocyte and endothelial cell viability, proliferation, and migration, in vitro. Methods: For epithelial and endothelial cells a human cell line and for keratocytes primary cultures were used (n = 6 each). We used 3.9x10−4–0.1% HD, PD or DD, 3.9x10−4–0.0125% PD, 7.8x10−5–0.02% PHMB or CH concentration for 24 h to determine viability (Cell Proliferation Kit XTT), proliferation (Cell Proliferation ELISA BrdU kit), and migration using wound healing assay. Viability/proliferation/migration values of each drug were summarized as “area under curve” (AUC) together with a Mann–Whitney test. Results: HCEC, keratocyte, and HCEC-12 viability AUC, comparing PD and PHMB (p ≤ 0.014 for all; PD better) or PD and HD (p ≤ 0.011 for all; PD better) differed significantly. Keratocyte and HCEC-12 viability AUC comparing CH and HD (p ≤ 0.027; CH better), HCEC-12 viability AUC comparing PD and HD (p = 0.005; PD better) and HCEC viability AUC comparing CH and PHMB (p = 0.014; CH better) differed significantly. HCEC proliferation AUC, comparing PD with PHMB, CH, DD, HD (p ≤ 0.016; PD worse for all) and keratocyte proliferation AUC, comparing PHMB with HD, PD (p = 0.004; p = 0.002; PHMB better for both), CH with HD, PD (p ≤ 0.001; CH better for both) and DD with PD (p = 0.043; DD better) differed significantly. Keratocyte migration AUC comparing PD with control, PHMB, CH, DD and HD differed significantly (p ≤ 0.012; PD worse for all). Conclusions: Propamidin-isethionate as diamidine and chlorhexidin as biguanide may be used clinically to reduce cytotoxicity of antiamoebic treatment on human corneal cells. Diamidines reduce proliferation of human epithelial cells and keratocytes more than biguanides and propamidin-isethionate reduces migration of keratocytes. Therefore, in spite of lower cytotoxicity, the inhibitory effect on proliferation and migration indicates that extended use of propamidin-isethionate should be avoided in patients.
Arctic Ocean Microbial Community Structure before and after the 2007 Record Sea Ice Minimum

Increasing global temperatures are having a profound impact in the Arctic, including the dramatic loss of multiyear sea ice in 2007 that has continued to the present. The majority of life in the Arctic is microbial and the consequences of climate-mediated changes on microbial marine food webs, which are responsible for biogeochemical cycling and support higher trophic levels, are unknown. We examined microbial communities over time by using high-throughput sequencing of microbial DNA collected between 2003 and 2010 from the subsurface chlorophyll maximum (SCM) layer of the Beaufort Sea (Canadian Arctic). We found that overall this layer has freshened and concentrations of nitrate, the limiting nutrient for photosynthetic production in Arctic seas, have decreased. We compared microbial communities from before and after the record September 2007 sea ice minimum and detected significant differences in communities from all three domains of life. In particular, there were significant changes in species composition of Eukarya, with ciliates becoming more common and heterotrophic marine stramenopiles (MASTs) accounting for a smaller proportion of sequences retrieved after 2007. Within the Archaea, Marine Group I Thaumarchaeota, which earlier represented up to 60% of the Archaea sequences in this layer, have declined to <10%. Bacterial communities overall were less diverse after 2007, with a significant decrease of the Bacteroidetes. These significant shifts suggest that the microbial food webs are sensitive to physical oceanographic changes such as those occurring in the Canadian Arctic over the past decade.
Downregulation of GluA2 AMPA Receptor Subunits Reduces the Dendritic Arborization of Developing Spinal Motoneurons

AMPA receptors lacking the GluA2 subunit allow a significant influx of Ca2+ ions. Although Ca2+-permeable AMPA receptors are a familiar feature at early stages of development, the functional significance of these receptors during the maturation of the nervous system remains to be established. Chicken lumbar motoneurons express Ca2+-permeable AMPA receptors at E6 but the Ca2+ permeability of AMPA receptors decreases ∼3-fold by E11. Considering that activity-dependent changes in intracellular Ca2+ regulates dendritic outgrowth, in this study we investigated whether downregulation of GluA2 expression during a critical period of development alters the dendritic arborization of spinal motoneurons in ovo. We use an avian replication-competent retroviral vector RCASBP (B) carrying the marker red fluorescent protein (RFP) and a GluA2 RNAi construct to downregulate GluA2 expression. Chicken embryos were infected at E2 with one of the following constructs: RCASBP(B)-RFP, RCASBP(B)-RFP-scrambled RNAi, or RCASBP(B)-RFP-GluA2 RNAi. Infection of chicken embryos at E2 resulted in widespread expression of RFP throughout the spinal cord with ≥60% of Islet1/2-positive motoneurons infected, resulting in a significant reduction in GluA2 protein expression. Downregulation of GluA2 expression had no effect on the dendritic arborization of E6 motoneurons. However, downregulation of GluA2 expression caused a significant reduction in the dendritic arborization of E11 motoneurons. Neither motoneuron survival nor maturation of network activity was affected by changes in GluA2 expression. These findings demonstrate that increased GluA2 expression and changes in the Ca2+ permeability of AMPA receptors regulate the dendritic arborization of spinal cord motoneurons during a critical period of development.