Miracle-dz/UniFAR-FTUs huggingface dataset:
ReliableGenome: annotation of genomic regions with high/low variant calling concordance

Motivation: The increasing adoption of clinical whole-genome resequencing (WGS) demands for highly accurate and reproducible variant calling (VC) methods. The observed discordance between state-of-the-art VC pipelines, however, indicates that the current practice still suffers from non-negligible numbers of false positive and negative SNV and INDEL calls that were shown to be enriched among discordant calls but also in genomic regions with low sequence complexity. Results: Here, we describe our method ReliableGenome (RG) for partitioning genomes into high and low concordance regions with respect to a set of surveyed VC pipelines. Our method combines call sets derived by multiple pipelines from arbitrary numbers of datasets and interpolates expected concordance for genomic regions without data. By applying RG to 219 deep human WGS datasets, we demonstrate that VC concordance depends predominantly on genomic context rather than the actual sequencing data which manifests in high recurrence of regions that can/cannot be reliably genotyped by a single method. This enables the application of pre-computed regions to other data created with comparable sequencing technology and software. RG outperforms comparable efforts in predicting VC concordance and false positive calls in low-concordance regions which underlines its usefulness for variant filtering, annotation and prioritization. RG allows focusing resource-intensive algorithms (e.g. consensus calling methods) on the smaller, discordant share of the genome (20–30%) which might result in increased overall accuracy at reasonable costs. Our method and analysis of discordant calls may further be useful for development, benchmarking and optimization of VC algorithms and for the relative comparison of call sets between different studies/pipelines. Availability and Implementation: RG was implemented in Java, source code and binaries are freely available for non-commercial use at https://github.com/popitsch/wtchg-rg/. Contact: niko@wtchg.ox. ac.uk Supplementary information: Supplementary data are available at Bioinformatics online.
Effects of structural components of artificial turf on the transmission of impacts in football players

Abstract The third generation of artificial turf systems (ATS) has matched the mechanical behaviour of natural grass, but today a high heterogeneity at structural level and mechanical behaviour in the new ATS also exists. The objective was to analyse the effect of the structural components of ATS football pitches and running speed on the capacity of impact attenuation. A total of 12 athletes were evaluated at three speed conditions (3.33 m/s, 4 m/s and maximum speed) on four different ATS, classifying them by their components (length of fibre, type of in-fill and sub-base). Impact attenuation was significantly higher in ATS3, characterised by longer fibre compared to other ATS with less fibre length. The ATS4 with a higher length fibre and built on compacted granular material proportioned significantly lower values in the maximum peaks of tibia acceleration. Finally, as speed increases, the peak tibia impacts were significantly higher. Longer fibre length and the capacity to accommodate a higher quantity of infill facilitate higher impact attenuation. Equally, a compacted granular sub-base is related to lower magnitude of maximum tibia peaks. Finally, the magnitude of the tibia acceleration peaks is dependent of running speed for all ATS analysed, being higher as speed increases.
Netrin‐1 and multiple sclerosis: a new biomarker for neuroinflammation?

Netrin‐1, an axon guidance protein, reduces serum levels of pro‐inflammatory mediators and stabilizes the blood−brain barrier limiting the entrance of immune cells into the central nervous system. The aim was to investigate its presence in the experimental autoimmune encephalomyelitis (EAE) model and in multiple sclerosis (MS) patients with and without clinical activity.
Downregulation of Autolysin-Encoding Genes by Phage-Derived Lytic Proteins Inhibits Biofilm Formation in Staphylococcus aureus

ABSTRACT Phage-derived lytic proteins are a promising alternative to conventional antimicrobials. One of their most interesting properties is that they do not readily select for resistant strains, which is likely due to the fact that their targets are essential for the viability of the bacterial cell. Moreover, genetic engineering allows the design of new “tailor-made” proteins that may exhibit improved antibacterial properties. One example of this is the chimeric protein CHAPSH3b, which consists of a catalytic domain from the virion-associated peptidoglycan hydrolase of phage vB_SauS-phiIPLA88 (HydH5) and the cell wall binding domain of lysostaphin. CHAPSH3b had previously shown the ability to kill Staphylococcus aureus cells. Here, we demonstrate that this lytic protein also has potential for the control of biofilm-embedded S. aureus cells. Additionally, subinhibitory doses of CHAPSH3b can decrease biofilm formation by some S. aureus strains. Transcriptional analysis revealed that exposure of S. aureus cells to this enzyme leads to the downregulation of several genes coding for bacterial autolysins. One of these proteins, namely, the major autolysin AtlA, is known to participate in staphylococcal biofilm development. Interestingly, an atl mutant strain did not display inhibition of biofilm development when grown at subinhibitory concentrations of CHAPSH3b, contrary to the observations made for the parental and complemented strains. Also, deletion of atl led to low-level resistance to CHAPSH3b and the endolysin LysH5. Overall, our results reveal new aspects that should be considered when designing new phage-derived lytic proteins aimed for antimicrobial applications.
Crashworthiness Analysis of Bi-Tubular Aluminium Tubes with Varying Shapes in LS-Dyna

The viability of thin-walled energy absorbers as impacts attenuators for Formula SAE racing cars was studied. The crashworthiness of bi-tubular tubes of varying geometries were explored. 9 designs grouped into 3 batches, were axially crush simulated in LS-Dyna. The tubes were set to 50mm long and made of aluminium 6061-T6. A convergence study was conducted, and the tubes were simulated using a meshing size of 1.5mm. The crushing energy applied is 490J. The LS-Dyna settings used were validated using experimental data from previous studies. It was found that the tube with an outer hexagon shape and an inner square shape had the best SEA. It was also observed that square-shaped geometries were the best in absorbing energy, with the most amount of energy being absorbed by a bi-tubular tube with outer and inner square geometries. Tubes with hexagonal geometries absorbed slightly less energy compared to tubes with square geometries, but they only differ by a small margin.
Effect of high pressure processing on milk coagulation properties

Raw milk cheeses are known to have more intense and strong flavour and different texture due to natural microbiota and enzymes. Nevertheless, there are concerns about safety of these products. For microbial inactivation heat treatment of milk is used, but it can adversely affect the flavour, taste and texture of the product. Therefore, applying non-thermal technology such as high pressure processing is attracting alternative. The aim of this study was to examine the effects of high pressure treatment of cow`s milk at a wide range of pressures (400 600 MPa) on milk rennet coagulation time, curd firmness and curd yield. Processed milk samples were subjected to enzymatic coagulation using commercial rennet to determine rennet coagulation time, yield of coagulum and curd firmness. High pressure processing insignificantly influences coagulation properties of whole milk. However, the magnitude of changes depended on applied pressure. Rennet coagulation time and curd yield were significantly different (p < 0.05) among the pressure treated milk samples. The higher firmness of the curd form pressurized milk than that of raw or pasteurized milk, evaluated positively. The main effects of high pressure treatment in milk appeared to involve dissociation of casein micelles from the colloidal to the soluble phase. This study suggests that high pressure treatments of milk at 500 MPa or 550 MPa for 15 min may be beneficial for improving the coagulation properties of milk. These positive effects indicated that high pressure processing may have potential for new cheese varieties development.
Cortical Circuit for Binding Object Identity and Location During Multiple-Object Tracking

Abstract Sustained multifocal attention for moving targets requires binding object identities with their locations. The brain mechanisms of identity‐location binding during attentive tracking have remained unresolved. In 2 functional magnetic resonance imaging experiments, we measured participants’ hemodynamic activity during attentive tracking of multiple objects with equivalent (multiple‐object tracking) versus distinct (multiple identity tracking, MIT) identities. Task load was manipulated parametrically. Both tasks activated large frontoparietal circuits. MIT led to significantly increased activity in frontoparietal and temporal systems subserving object recognition and working memory. These effects were replicated when eye movements were prohibited. MIT was associated with significantly increased functional connectivity between lateral temporal and frontal and parietal regions. We propose that coordinated activity of this network subserves identity‐location binding during attentive tracking.
Catheter-Based Approaches for the Treatment of Acute Pulmonary Embolism

Abstract Except when contraindicated, anticoagulation should be initiated when pulmonary embolism (PE) is strongly suspected and the bleeding risk is perceived to be low, even if the evaluation has not been completed. Low-risk patients with acute PE are simply continued on anticoagulation. Severely ill patients with high-risk (massive) PE require aggressive therapy, and if the bleeding risk is acceptable, systemic thrombolysis should be considered. However, despite clear evidence that parenteral thrombolytic therapy leads to more rapid clot resolution than anticoagulation alone, the risk of major bleeding including intracranial bleeding is significantly higher with thrombolytic therapy. It has been demonstrated that right ventricular dysfunction as well as abnormal biomarkers (troponin and brain natriuretic peptide) are associated with increased mortality in acute PE. In spite of this, intermediate-risk (submassive) PE comprises a fairly broad clinical spectrum so that there is not a solid evidence base permitting a consistent algorithm for clinicians to follow. Thus, for several decades, thromboembolism basic scientists, clinical trialists, and clinicians have worked toward a lower risk solution for treatment of patients with more than simply low-risk PE. Catheter-based therapy, consisting of various devices and techniques, with or without low-dose thrombolytic therapy, offers one potential solution and continues to evolve.
Markers of Microbial Translocation and Immune Activation Predict Cognitive Processing Speed in Heavy-Drinking Men Living with HIV

HIV infection and alcohol use disorder are associated with deficits in neurocognitive function. Emerging evidence points to pro-inflammatory perturbations of the gut-brain axis as potentially contributing to neurocognitive impairment in the context of HIV and chronic heavy alcohol use. This study examined whether plasma markers of microbial translocation (LPS) from the gastrointestinal tract and related immune activation (sCD14, EndoCAb) were associated with neurocognition in 21 men living with HIV who were virally suppressed on antiretroviral therapy. All participants met federal criteria for heavy drinking and were enrolled in a randomized controlled trial (RCT) of a brief alcohol intervention. This secondary analysis utilized blood samples and cognitive scores (learning, memory, executive function, verbal fluency, and processing speed) obtained at baseline and three-month follow-up of the RCT. In generalized estimating equation models, LPS, sCD14, and EndoCAb individually were significant predictors of processing speed. In a model with all biomarkers, higher LPS and sCD14 both remained significant predictors of lower processing speed. These preliminary findings suggest that inflammation stemming from HIV and/or alcohol could have negative effects on the gut-brain axis, manifested as diminished processing speed. Associations of microbial translocation and immune activation with processing speed in heavy-drinking PLWH warrant further investigation in larger-scale studies.
People living with facial disfigurement after having had noma disease: A systematic review of the literature

Noma disease often results in impairment, morbidity and severe facial disfigurement. This article reports a systematic review of literatures published between 2006 and 2015 to establish existing knowledge about social stigma associated with facial disfigurements. Five databases were searched and 114 citations were screened, of which only 15 met the relevant criteria. Titles and abstracts of the retrieved articles were independently reviewed. The research was heterogeneous; therefore, overall synthesis using meta-analysis was inappropriate. It can be seen that the review demonstrates that facial disfigurements are far more complex than was previously thought.
Fat mass and obesity‐associated gene variations are related to fatty liver disease in HIV‐infected patients

Fatty liver disease (FLD) is frequently observed in HIV‐infected patients. Obesity and type 2 diabetes mellitus (T2DM) are strongly associated with FLD. Because genetic variants within the fat mass and obesity‐associated (FTO) gene have been associated with both pathologies, our aim was to evaluate the association of single nucleotide polymorphisms (SNPs) within the FTO, previously related to obesity or T2DM, with FLD in HIV‐infected patients.
Anti‐epidermal growth factor receptor therapy concurrently with induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma

Little is known about the efficacy and toxicity of anti‐epidermal growth factor receptor therapy concurrently with induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (LA‐NPC). The present study aimed to address this question. We identified 2848 patients with newly diagnosed LA‐NPC receiving IC between January 2012 and May 2015. The propensity score matching (PSM) method was used to balance various factors and to match patients. Survival outcomes and toxicities between different groups were compared. In total, 596 patients were selected at a 1:3 ratio, with 149 in the IC + CTX/NTZ group and 447 in the IC alone group. The 3‐year disease‐free survival, overall survival, distant metastasis‐free survival and locoregional relapse‐free survival rates for IC + CTX/NTZ vs IC alone were 84.3% vs 75.2% (P = .059), 94.0% vs 87.9% (P = .053), 88.0% vs 84.9% (P = .412) and 93.3% vs 88.2% (P = .242). Multivariate analysis established a treatment group (IC vs IC + CTX/NTZ) as a prognostic predictor for DFS (hazard ratio [HR], 1.497; 95% confidence interval [CI], 1.016‐2.206; P = .041) and OS (HR, 1.984; 95%, CI, 1.023‐3.848; P = .043). Grade 3‐4 skin reaction (15.4% vs 0.4%, P < .001) and mucositis (10.1% vs 2.7%, P < .001) were more common in the IC + CTX/NTZ group than that in the IC alone group. Our findings suggested that CTX/NTZ in combination with IC may be a more effective and promising strategy for patients with LA‐NPC treated with intensity‐modulated radiotherapy.
Hydrogel composition and laser micropatterning to regulate sciatic nerve regeneration

Treatment of peripheral nerve injuries has evolved over the past several decades to include the use of sophisticated new materials endowed with trophic and topographical cues that are essential for in vivo nerve fibre regeneration. In this research, we explored the use of an advanced design strategy for peripheral nerve repair, using biological and semi‐synthetic hydrogels that enable controlled environmental stimuli to regenerate neurons and glial cells in a rat sciatic nerve resection model. The provisional nerve growth conduits were composed of either natural fibrin or adducts of synthetic polyethylene glycol and fibrinogen or gelatin. A photo‐patterning technique was further applied to these 3D hydrogel biomaterials, in the form of laser‐ablated microchannels, to provide contact guidance for unidirectional growth following sciatic nerve injury. We tested the regeneration capacity of subcritical nerve gap injuries in rats treated with photo‐patterned materials and compared these with injuries treated with unpatterned hydrogels, either stiff or compliant. Among the factors tested were shear modulus, biological composition, and micropatterning of the materials. The microchannel guidance patterns, combined with appropriately matched degradation and stiffness properties of the material, proved most essential for the uniform tissue propagation during the nerve regeneration process.
Factors protecting against the development of suicidal ideation in military veterans

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RA2: Predicting Simulation Execution Time for Cloud-Based Design Space Explorations

Design space exploration refers to the evaluation of implementation alternatives for many engineering and design problems. A popular exploration approach is to run a large number of simulations of the actual system with varying sets of configuration parameters to search for the optimal ones. Due to the potentially huge resource requirements, cloud-based simulation execution strategies should be considered in many cases. In this paper, we look at the issue of running large-scale simulation-based design space exploration problems on commercial Infrastructure-as-a-Service clouds, namely Amazon EC2, Microsoft Azure and Google Compute Engine. To efficiently manage cloud resources used for execution, the key problem would be to accurately predict the running time for each simulation instance in advance. This is not trivial due to the currently wide range of cloud resource types which offer varying levels of performance. In addition, the widespread use of virtualization techniques in most cloud providers often introduces unpredictable performance interference. In this paper, we propose a resource and application-aware (RA2) prediction approach to combat performance variability on clouds. In particular, we employ neural network based techniques coupled with non-intrusive monitoring of resource availability to obtain more accurate predictions. We conducted extensive experiments on commercial cloud platforms using an evacuation planning design problem over a month-long period. The results demonstrate that it is possible to predict simulation execution times in most cases with high accuracy. The experiments also provide some interesting insights on how we should run similar simulation problems on various commercially available clouds.
A chemical genetic approach to engineer phototropin kinases for substrate labeling

Protein kinases (PKs) control many aspects of plant physiology by regulating signaling networks through protein phosphorylation. Phototropins (phots) are plasma membrane–associated serine/threonine PKs that control a range of physiological processes that collectively serve to optimize photosynthetic efficiency in plants. These include phototropism, leaf positioning and flattening, chloroplast movement, and stomatal opening. Despite their identification over two decades ago, only a handful of substrates have been identified for these PKs. Progress in this area has been hampered by the lack of a convenient means to confirm the identity of potential substrate candidates. Here we demonstrate that the kinase domain of Arabidopsis phot1 and phot2 can be successfully engineered to accommodate non-natural ATP analogues by substituting the bulky gatekeeper residue threonine for glycine. This approach circumvents the need for radioactivity to track phot kinase activity and follow light-induced receptor autophosphorylation in vitro by incorporating thiophosphate from N6-benzyl-ATPγS. Consequently, thiophosphorylation of phot substrate candidates can be readily monitored when added or co-expressed with phots in vitro. Furthermore, gatekeeper-modified phot1 retained its functionality and its ability to accommodate N6-benzyl-ATPγS as a phosphodonor when expressed in Arabidopsis. We therefore anticipate that this chemical genetic approach will provide new opportunities for labeling and identifying substrates for phots and other related AGC kinases under in vitro and near-native in vivo conditions.
Linear Degrees of Freedom for $K$ -user MISO Interference Channels With Blind Interference Alignment

In this paper, we characterize the degrees of freedom (DoF) for <inline-formula> <tex-math notation="LaTeX">$K$ </tex-math></inline-formula>-user <inline-formula> <tex-math notation="LaTeX">$M \times 1$ </tex-math></inline-formula> multiple-input single-output interference channels with reconfigurable antennas, which have <inline-formula> <tex-math notation="LaTeX">$N$ </tex-math></inline-formula>-preset modes at the receivers, assuming linear coding strategies in the absence of channel state information at the transmitters, i.e., blind interference alignment. Our linear DoF converse builds on the lemma that if a set of transmit symbols is aligned at their common unintended receivers, those symbols must have independent signal subspace at their corresponding receivers. This lemma arises from the inherent feature that channel state’s changing patterns of the links towards the same receiver are always identical, assuming that the coherence time of the channel is long enough. We derive an upper bound for the linear sum DoF, and propose an achievable scheme that exactly achieves the linear sum DoF upper bound when both of the <inline-formula> <tex-math notation="LaTeX">${n^{*}}/{M}=R_{1}$ </tex-math></inline-formula> and <inline-formula> <tex-math notation="LaTeX">${MK}/{n^{*}}=R_{2}$ </tex-math></inline-formula> are integers, where <inline-formula> <tex-math notation="LaTeX">$n^{*}$ </tex-math></inline-formula> denotes the optimal number of preset modes out of <inline-formula> <tex-math notation="LaTeX">$N$ </tex-math></inline-formula> preset modes. For the other cases, where either <inline-formula> <tex-math notation="LaTeX">$R_{1}$ </tex-math></inline-formula> or <inline-formula> <tex-math notation="LaTeX">$R_{2}$ </tex-math></inline-formula> is not an integer, we only give some guidelines how the interfering signals are aligned at the receivers to achieve the upper bound. As an extension, we also show the linear sum DoF upper bound for downlink/uplink cellular networks.