Miracle-dz/UniFAR-FTUs huggingface dataset:
Safety and Tolerability of Bacteriophage Therapy for Chronic Rhinosinusitis Due to Staphylococcus aureus.

Importance Staphylococcus aureus infections are associated with recalcitrant chronic rhinosinusitis (CRS). The emerging threat of multidrug-resistant S aureus infections has revived interest in bacteriophage (phage) therapy. Objective To investigate the safety, tolerability, and preliminary efficacy of ascending multiple intranasal doses of investigational phage cocktail AB-SA01 in patients with recalcitrant CRS due to S aureus. Design, Setting, and Participants This phase 1, first-in-humans, open-label clinical trial of multiple ascending doses was conducted at a single tertiary referral center from December 1, 2015, through September 30, 2016, with follow-up completed on December 31, 2016. Patients with recalcitrant CRS (aged 18-70 years) in whom surgical and medical treatment had failed and who had positive S aureus cultures sensitive to AB-SA01 were recruited. Findings were analyzed from February 2 through August 31, 2017. Interventions Three patient cohorts (3 patients/cohort) received serial doses of twice-daily intranasal irrigations with AB-SA01 at a concentration of 3 × 108 plaque-forming units (PFU) for 7 days (cohort 1), 3 × 108 PFU for 14 days (cohort 2), and 3 × 109 PFU for 14 days (cohort 3). Main Outcomes and Measures The primary study outcome was the safety and tolerability of intranasal AB-SA01. Safety observations included vital signs, physical examinations, clinical laboratory test results, and adverse events. The secondary outcome was preliminary efficacy assessed by comparing pretreatment and posttreatment microbiology results, disease-relevant endoscopic Lund-Kennedy Scores, and symptom scores using a visual analog scale and Sino-Nasal Outcome Test-22. Results All 9 participants (4 men and 5 women; median age, 45 years [interquartile range, 41.0-71.5 years]) completed the trial. Intranasal phage treatment was well tolerated, with no serious adverse events or deaths reported in any of the 3 cohorts. No change in vital signs occurred before and 0.5 and 2.0 hours after administration of AB-SA01 and at the exit visit. No changes in biochemistry were found except for 1 participant in cohort 3 who showed a decrease in blood bicarbonate levels on exit visit, with normal results of physical examination and vital signs. All biochemistry values were normalized 8 days later. No changes in temperature were recorded before, during, or after treatment. Six adverse effects were reported in 6 participants; all were classified as mild treatment-emergent adverse effects and resolved by the end of the study. Preliminary efficacy results indicated favorable outcomes across all cohorts, with 2 of 9 patients showing clinical and microbiological evidence of eradication of infection. Conclusions and Relevance Intranasal irrigation with AB-SA01 of doses to 3 × 109 PFU for 14 days was safe and well tolerated, with promising preliminary efficacy observations. Phage therapy could be an alternative to antibiotics for patients with CRS. Trial Registration http://anzctr.org. au identifier: ACTRN12616000002482.
Streptomyces cyaneochromogenes sp. nov., a blue pigment-producing actinomycete from manganese-contaminated soil.

A novel actinomycete isolate, designated strain MK-45T, was isolated from soil sampled at a manganese-contaminated area in Xiangtan, China. The isolate formed extensively branched substrate mycelia and aerial mycelia that differentiated into tightly coiled or spiral spore chains with smooth-surfaced spores. The cell-wall hydrolysates contained ll-diaminopimelic acid and traces of meso-diaminopimelic acid. The major menaquinones consisted of MK-9(H4), MK-9(H6) and MK-9(H8). The major polar lipids contained diphosphatidylgycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphotidylinositol and phosphotidylinositol mannosides. The predominant cellular fatty acids were iso-C16 : 0, C16 : 0 and summed feature 3. Phylogenetic analysis based on the 16S rRNA gene sequences and concatenated partial sequences of the five protein-coding genes indicated that strain MK-45T was a member of the genus Streptomyces and most closely related to Streptomyces caeruleatus GIMN4.002T (99.5 % similarity), Streptomyces curacoi CGMCC 4.1680T (99.5 %), Streptomyces shaanxiensis CCNWHQ 0031T (99.4 %) and Streptomyces cinnabarinus NRRL B12382T (98.9 %), respectively. However, the digital DNA-DNA hybridization values, the average nucleotide identity values and MLSA evolutionary distances between strain MK-45T and them showed that it belonged to a distinct species. Furthermore, the results of morphological, physiological and biochemical tests allowed further phenotypic differentiation of strain MK-45T from the four closely related type strains mentioned above and other species of the genus Streptomyces with which this strain has 98.0-99.2 % 16S rRNA gene sequence similarity. Therefore, it is concluded that strain MK-45T represents a novel species of the genus Streptomyces, for which the name Streptomycescyaneochromogenes sp. nov. is proposed, with MK-45T (=CICC 11045T=KCTC 49099T) as the type strain.
Tobacco Use and Cognitive Functioning in Veterans of the Conflicts in Iraq and Afghanistan

ABSTRACT Tobacco use is a prevalent problem in the general population as well as among military veterans. Despite the fact that tobacco users are at an increased risk of many medical and psychiatric comorbidities, the risk of cognitive impairment in younger active tobacco users is less studied. Military veterans from the conflicts in Iraq and Afghanistan (n = 113) were administered a neuropsychological protocol. Even after controlling for the severity of PTSD symptoms, tobacco use was negatively related to performance on measures of processing speed, memory, and executive functioning. The current findings have implications for the neuropsychological evaluation of tobacco users.
Avances en la representación y modelado computacionales de la estructura del espacio

This article proposes a new method for robust and accurate de tection of the orientation and the location of an object on low-contras t surfaces in an industrial context. To be more efficient and effective, ou r method employs only artificial vision. Therefore, productivity is in creased since it avoids the use of additional mechanical devices to ensure th e accuracy of the system. The technical core is the treatment of straight line contour s that occur in close neighbourhood to each other and with similar orient ations. It is a particular problem in stacks of objects but can also occur i n other applications. New techniques are introduced to ensure the rob ustness of the system and to tackle the problem of noise, such as an auto-thr eshold segmentation process, a new type of histogram and a robust regre ssion method used to compute the result with a higher precision.
A new lipoxygenase from the agaric fungus Agrocybe aegerita: Biochemical characterization and kinetic properties

Oxylipins are metabolites with a variety of biological functions. However, the biosynthetic pathway is widely unknown. It is considered that the first step is the oxygenation of polyunsaturated fatty acids like linoleic acid. Therefore, a lipoxygenase (LOX) from the edible basidiomycete Agrocybe aegerita was investigated. The AaeLOX4 was heterologously expressed in E. coli and purified via affinity chromatography and gel filtration. Biochemical properties and kinetic parameters of the purified AaeLOX4 were determined with linoleic acid and linolenic acid as substrates. The obtained Km, vmax and kcat values for linoleic acid were 295.5 μM, 16.5 μM · min-1 · mg-1 and 103.9 s-1, respectively. For linolenic acid Km, vmax and kcat values of 634.2 μM, 19.5 μM · min-1 · mg-1 and 18.3 s-1 were calculated. Maximum activities were observed at pH 7.5 and 25 °C. The main product of linoleic acid conversion was identified with normal-phase HPLC. This analysis revealed an explicit production of 13-hydroperoxy-9,11-octadecadienoic acid (13-HPOD). The experimental regio specificity is underpinned by the amino acid residues W384, F450, R594 and V635 considered relevant for regio specificity in LOX. In conclusion, HPLC-analysis and alignments revealed that AaeLOX4 is a 13-LOX.
For comparing phylogenetic diversity among communities, go ahead and use synthesis phylogenies

Should we build our own phylogenetic trees based on gene sequence data, or can we simply use available synthesis phylogenies? This is a fundamental question that any study involving a phylogenetic framework must face at the beginning of the project. Building a phylogeny from gene sequence data (purpose-built phylogeny) requires more effort and expertise than subsetting an already available phylogeny (synthesis-based phylogeny). If phylogenetic diversity estimates based on these two types of phylogenies are highly correlated, using readily available synthesis-based phylogenies is justified for comparing phylogenetic diversity among communities. However, a comparison of how these two approaches to building phylogenetic trees influence the calculation of phylogenetic diversity has not been explicitly tested. We generated threepurpose-built phylogenies and their corresponding synthesis-based trees (two from Phylomatic and one from the Open Tree of Life). We then used a simulation approach to generate 1000 communities with a fixed number of species per site and compared the effects of different trees on estimates of phylogenetic alpha and beta diversity using Spearman’s rank-based correlation and linear mixed models. Synthesis-based phylogenies generally over-estimated phylogenetic diversity when compared to purpose-built ones. However, their resulting measures of phylogenetic diversity were highly correlated (Spearman’s r > 0.8 in most cases). Mean pairwise distance (both alpha and beta) is the index that is most robust to the differences in tree construction that we tested. Measures of phylogenetic diversity based on the Open Tree of Life showed the highest correlation with measures based on the purpose-built phylogenies. For comparing phylogenetic diversity among communities, our results justify taking advantage of recently developed and continuously improving synthesis trees such as the Open Tree of Life.
Bi-Modality Medical Image Synthesis Using Semi-Supervised Sequential Generative Adversarial Networks

In this paper, we propose a bi-modality medical image synthesis approach based on sequential generative adversarial network (GAN) and semi-supervised learning. Our approach consists of two generative modules that synthesize images of the two modalities in a sequential order. A method for measuring the synthesis complexity is proposed to automatically determine the synthesis order in our sequential GAN. Images of the modality with a lower complexity are synthesized first, and the counterparts with a higher complexity are generated later. Our sequential GAN is trained end-to-end in a semi-supervised manner. In supervised training, the joint distribution of bi-modality images are learned from real paired images of the two modalities by explicitly minimizing the reconstruction losses between the real and synthetic images. To avoid overfitting limited training images, in unsupervised training, the marginal distribution of each modality is learned based on unpaired images by minimizing the Wasserstein distance between the distributions of real and fake images. We comprehensively evaluate the proposed model using two synthesis tasks based on three types of evaluate metrics and user studies. Visual and quantitative results demonstrate the superiority of our method to the state-of-the-art methods, and reasonable visual quality and clinical significance. Code is made publicly available at https://github.com/hust- linyi/Multimodal-Medical-Image-Synthesis.
Speech Emotion Recognition with Heterogeneous Feature Unification of Deep Neural Network

Automatic speech emotion recognition is a challenging task due to the gap between acoustic features and human emotions, which rely strongly on the discriminative acoustic features extracted for a given recognition task. We propose a novel deep neural architecture to extract the informative feature representations from the heterogeneous acoustic feature groups which may contain redundant and unrelated information leading to low emotion recognition performance in this work. After obtaining the informative features, a fusion network is trained to jointly learn the discriminative acoustic feature representation and a Support Vector Machine (SVM) is used as the final classifier for recognition task. Experimental results on the IEMOCAP dataset demonstrate that the proposed architecture improved the recognition performance, achieving accuracy of 64% compared to existing state-of-the-art approaches.
Microhomology-mediated end joining drives complex rearrangements and overexpression of MYC and PVT1 in multiple myeloma

MYC is a widely acting transcription factor and its deregulation is a crucial event in many human cancers. MYC is important biologically and clinically in multiple myeloma, but the mechanisms underlying its dysregulation are poorly understood. We show that MYC rearrangements are present in 36.0% of newly diagnosed myeloma patients, as detected in the largest set of next generation sequencing data to date (n=1,267). Rearrangements were complex and associated with increased expression of MYC and PVT1, but not other genes at 8q24. The highest effect on gene expression was detected in cases where the MYC locus is juxtaposed next to super-enhancers associated with genes such as IGH, IGK, IGL, TXNDC5/BMP6, FAM46C and FOXO3. We identified three hotspots of recombination at 8q24, one of which is enriched for IGH-MYC translocations. Breakpoint analysis indicates primary myeloma rearrangements involving the IGH locus occur through non-homologous end joining, whereas secondary MYC rearrangements occur through microhomology-mediated end joining. This mechanism is different to lymphomas, where non-homologous end joining generates MYC rearrangements. Rearrangements resulted in overexpression of key genes and chromatin immunoprecipitation-sequencing identified that HK2, a member of the glucose metabolism pathway, is directly over-expressed through binding of MYC at its promoter.
Do manufactured and natural objects evoke similar motor information? The case of action priming

There is considerable evidence that visually presented manipulable objects evoke motor information, supporting the existence of affordance effects during object perception. However, most arguments come from stimulus–response compatibility paradigms, raising the issue of the automaticity of affordance effects. Action priming paradigms overcome this issue but show less reliable results, possibly because affordance effects are moderated by additional factors. The present study aimed to assess whether affordance effects highlighted in action priming paradigms could be affected by object category (manufactured or natural). A total of 24 young adults performed a semantic categorisation task on natural and manufactured target objects presented after neutral (non-grasping hand postures) or action (congruent power or precision grips) primes. Results revealed a modulation of action priming effects as a function of object category. Object semantic categorisation was faster after action than neutral primes, but only for manufactured objects. Results suggest that natural and manufactured objects evoke distinct types of affordances and that action priming paradigms favour the evocation of functional affordances during object semantic categorisation. This finding fuels the debate on the nature of the motor information evoked by visual objects.
Anterior-enriched filopodia create the appearance of asymmetric membrane microdomains in polarizing C. elegans zygotes

ABSTRACT The association of molecules within membrane microdomains is critical for the intracellular organization of cells. During polarization of the C. elegans zygote, both polarity proteins and actomyosin regulators associate within dynamic membrane-associated foci. Recently, a novel class of asymmetric membrane-associated structures was described that appeared to be enriched in phosphatidylinositol 4,5-bisphosphate (PIP2), suggesting that PIP2 domains could constitute signaling hubs to promote cell polarization and actin nucleation. Here, we probe the nature of these domains using a variety of membrane- and actin cortex-associated probes. These data demonstrate that these domains are filopodia, which are stimulated transiently during polarity establishment and accumulate in the zygote anterior. The resulting membrane protrusions create local membrane topology that quantitatively accounts for observed local increases in the fluorescence signal of membrane-associated molecules, suggesting molecules are not selectively enriched in these domains relative to bulk membrane and that the PIP2 pool as revealed by PHPLCδ1 simply reflects plasma membrane localization. Given the ubiquity of 3D membrane structures in cells, including filopodia, microvilli and membrane folds, similar caveats are likely to apply to analysis of membrane-associated molecules in a broad range of systems. Summary: Apparent accumulation of PIP2 and cortex/polarity-related proteins within plasma membrane microdomains in polarizing C. elegans zygotes reflects local membrane topology induced by filopodia, not selective enrichment within signaling domains.
Influence of Diets with Varying Essential/Nonessential Amino Acid Ratios on Mouse Lifespan

An adequate intake of essential (EAA) and non-essential amino acids (NEAA) is crucial to preserve cell integrity and whole-body metabolism. EAA introduced with diet may be insufficient to meet the organismal needs, especially under increased physiological requirements or in pathological conditions, and may condition lifespan. We therefore examined the effects of iso-caloric and providing the same nitrogenous content diets, any diet containing different stoichiometric blends of EAA/NEAA, on mouse lifespan. Three groups of just-weaned male Balb/C mice were fed exclusively with special diets with varying EAA/NEAA ratios, ranging from 100%/0% to 0%/100%. Three additional groups of mice were fed with different diets, two based on casein as alimentary proteins, one providing the said protein, one reproducing the amino acidic composition of casein, and the third one, the control group, was fed by a standard laboratory diet. Mouse lifespan was inversely correlated with the percentage of NEAA introduced with each diet. Either limiting EAA, or exceeding NEAA, induced rapid and permanent structural modifications on muscle and adipose tissue, independently of caloric intake. These changes significantly affected food and water intake, body weight, and lifespan. Dietary intake of varying EAA/NEAA ratios induced changes in several organs and profoundly influenced murine lifespan. The balanced content of EAA provided by dietary proteins should be considered as the preferable means for “optimal” nutrition and the elevated or unbalanced intake of NEAA provided by food proteins may negatively affect the health and lifespan of mice.
3D Electron Microscopy Study of Synaptic Organization of the Normal Human Transentorhinal Cortex and Its Possible Alterations in Alzheimer’s Disease

Abstract The transentorhinal cortex (TEC) is an obliquely oriented cortex located in the medial temporal lobe and, together with the entorhinal cortex, is one of the first affected areas in Alzheimer’s disease (AD). One of the most widely accepted hypotheses is that synaptopathy (synaptic alterations and loss) represents the major structural correlate of the cognitive decline observed in AD. However, very few electron microscope (EM) studies are available; the most common method to estimate synaptic density indirectly is by counting, at the light microscopic level, immunoreactive puncta using synaptic markers. To investigate synaptic morphology and possible alterations related to AD, a detailed three-dimensional (3D) ultrastructural analysis using focused ion beam/scanning EM (FIB/SEM) was performed in the neuropil of Layer II of the TEC in human brain samples from non-demented subjects and AD patients. Evaluation of the proportion and shape of asymmetric synapses (AS) and symmetric synapses (SS) targeting spines or dendritic shafts was performed using 3D reconstructions of every synapse. The 3D analysis of 4722 synapses revealed that the preferable targets were spine heads for AS and dendritic shafts for SS, both in control and AD cases. However, in AD patients, we observed a reduction in the percentage of synapses targeting spine heads. Regarding the shape of synapses, in both control cases and AD samples, the vast majority of synapses had a macular shape, followed by perforated or horseshoe-shaped synapses, with fragmented synapses being the least frequent type. Moreover, comparisons showed an increased number of fragmented AS in AD patients.
An Advanced Deep Generative Framework for Temporal Link Prediction in Dynamic Networks

Temporal link prediction in dynamic networks has attracted increasing attention recently due to its valuable real-world applications. The primary challenge of temporal link prediction is to capture the spatial–temporal patterns and high nonlinearity of dynamic networks. Inspired by the success of image generation, we convert the dynamic network into a sequence of static images and formulate the temporal link prediction as a conditional image generation problem. We propose a novel deep generative framework, called NetworkGAN, to tackle the challenging temporal link prediction task efficiently, which simultaneously models the spatial and temporal features in the dynamic networks via deep learning techniques. The proposed NetworkGAN inherits the advantages of the graph convolutional network (GCN), the temporal matrix factorization (TMF), the long short-term memory network (LSTM), and the generative adversarial network (GAN). Specifically, an attentive GCN is first designed to automatically learn the spatial features of dynamic networks. Second, we propose a TMF enhanced attentive LSTM (TMF-LSTM) to capture the temporal dependencies and evolutionary patterns of dynamic networks, which predicts the network snapshot at next timestamp based on the network snapshots observed at previous timestamps. Furthermore, we employ a GAN framework to further refine the performance of temporal link prediction by using a discriminative model to guide the training of the deep generative model (i.e., TMF-LSTM) in an adversarial process. To verify the effectiveness of the proposed model, we conduct extensive experiments on five real-world datasets. Experimental results demonstrate the significant advantages of NetworkGAN compared to other strong competitors.