Miracle-dz/UniFAR-FTUs huggingface dataset:
Mutations in the H7 HA and PB1 genes of avian influenza a viruses increase viral pathogenicity and contact transmission in guinea pigs

ABSTRACT Avian influenza A viruses (AIV) of the H7 subtype continue to evolve posing a pandemic threat. However, molecular markers of H7N7 AIV pathogenicity and transmission in mammals remain poorly understood. In this study, we performed a systematic in vitro and in vivo analysis by comparing an H7N7 highly pathogenic AIV and its ferret adapted variant. Passaging an H7N7 AIV in ferrets led to six mutations in genes encoding the viral polymerase complex and the viral surface proteins. Here, we show that mutations in the H7 hemagglutinin gene cause increased pathogenicity in mice. Contact transmission between guinea pigs required additional mutations in the gene encoding the polymerase subunit PB1. Thus, particular vigilance is required with respect to HA and PB1 mutations as predictive molecular markers to assess the pandemic risk posed by emerging H7 avian influenza viruses.
The challenge of reading music notation for pianists with low vision: An exploratory qualitative study using a head-mounted display

ABSTRACT Reading musical notation while interpreting it on a musical instrument poses problems for musicians with a visual impairment (VI). This study sought to describe the visual aids, adaptations and compensatory strategies used by five amateur pianists with low vision when reading music, to identify the problems they face when using these aids, and to verify whether a head-mounted display (HMD) such as eSight Eyewear can be used to overcome some of them. In this exploratory study, the participants read and interpreted two excerpts of musical notation using eSight Eyewear. The data, collected through interviews, were coded using a qualitative method and a phenomenological approach. The results suggest that musicians with a VI use various visual aids, adaptations and compensatory strategies. However, these approaches are not without significant problems, particularly when they involve magnification. On the other hand, eSight Eyewear allows users to adjust magnification, have their hands free and use adapted musical notation. Many magnification-related problems are overcome with this HMD, which can be used to simultaneously read and interpret standard musical notation. However, reading sheet music with such a device remains a complex task, given the need to control head movements accordingly.
Enhanced antitumour effect for hepatocellular carcinoma in the advanced stage using a cyclodextrin-sorafenib-chaperoned inclusion complex.

Hepatocellular carcinoma (HCC) is a hypervascular tumour characterized by tumour-driven neovascularization. The degrees of blood oxygen saturation (DBOS), microvessel density (MVD) and tumour size (TS) are indicators in identifying the development stage of HCC. Herein, we proposed an HCC staging model using HepG2 tumour-bearing mice based on DBOS, MVD and TS. According to the patterns of these three criteria, HCC was classified into four stages: early, intermediate, advanced and end stages. The advanced stage was characterized by MVD of 50-90 (number per mm2), DBOS of 12-16% and TS of 250-600 mm3, which poses a critical challenge in HCC therapy. In order to efficiently control and treat HCC in the advanced stage, we developed a cyclodextrin (CD)-based chaperoned inclusion complex using Sorafenib (Sor), β-CD and γ-CD (SCD) via the co-crystallization method. The structural study manifested that CDs could encapsulate Sor with the hydrophobic cavities at a 1 : 1 stoichiometry ratio. The crystallographic analysis indicated that Sor-β-CD presented a diagonal stacking pattern, while Sor-γ-CD possessed a channel-type structure. The resultant chaperoned inclusion complexes significantly improved the solubility, dissolution rate and drug release of Sor, leading to superior pharmacokinetics, biodistribution and biosafety through oral administration. The antitumour effect was then evaluated on a mouse model with advanced HCC through oral administration and intratumour injection. The treatment involving the oral administration of SCDs showed a promising therapeutic effect on advanced HCC, which efficiently blocked angiogenesis and inhibited tumour progression. For the treatments using intratumour injections, only Sor-γ-CD exhibited a satisfactory anti-tumour effect with reduction in TS, MVD and DBOS. The enhanced therapeutic performance of Sor-γ-CD was attributed to its channel-type structure, which had an impact on the dissociation and release of the drug. Thus, Sor-γ-CD can be used as a potential pro-drug for clinical medicine and basic research to treat HCC.
Sensitive Troponin Assays: Diagnostic and Prognostic Use in Cardiology

Cardiac troponins (cTns) are the recommended biochemical markers in the diagnosis of myocardial infarction (MI). They are very sensitive and tissue-specific but are limited by their delayed appearance in the circulation. Biochemical markers with more rapid release kinetics, e.g. myoglobin and especially heart-type fatty acid-binding protein (H-FABP), have been used to enhance the early identification of MI. The implementation of cTns into clinical practice has shown that cardiomyocyte injury occurs in many other clinical conditions than MI. The aim of this study was to evaluate the impact of modern and highly sensitive cTnI assays on the early diagnosis of MI. In a patient cohort with suspected MI, such a sensitive cTnI assay enhanced the early diagnostic accuracy when compared to a less sensitive cTnI assay and to myoglobin. When compared to H-FABP during the early hours after symptom onset, the sensitive cTnI assay showed at least similar and, after 6 hours, superior diagnostic accuracy. A positive cTnI test result had superior prognostic value when compared to H-FABP, even among early presenters. The prognostic value of cTn in acute heart failure (AHF) was evaluated in 364 patients who participated in the FINN-AKVA study. The patients presented with AHF but no acute coronary syndrome (ACS). Up to half of the patients had elevated cTn levels which were associated with higher 6-month mortality. The magnitude of cTn elevation was directly proportional to mortality. Finally, the clinical spectrum of cTnI elevations was evaluated in 991 cTnI positive emergency department (ED) patients. 83% of the patients had MI and 17% had cTnI elevation due to other clinical conditions. The latter patient group was characterized by lower absolute cTnI levels and – importantly – higher in-hospital mortality when compared to the MI patients. In conclusion, the use of a highly sensitive cTnI assay enhances the early diagnostic accuracy and risk stratification in suspected MI patients. Cardiac troponin elevations are highly prevalent also in other acute clinical conditions and indicate an adverse outcome of these patients.
Genome-Wide Variant Identification and High-Density Genetic Map Construction Using RADseq for Platycladus orientalis (Cupressaceae)

Platycladus orientalis is an ecologically important native conifer in Northern China and exotic species in many parts of the world; however, knowledge about the species’ genetics and genome are very limited. The availability of well-developed battery of genetic markers, with large genome coverage, is a prerequisite for the species genetic dissection of adaptive attributes and efficient selective breeding. Here, we present a genome-wide genotyping method with double-digestion restriction site associated DNA sequencing (ddRAD-seq) that is effective in generating large number of Mendelian markers for genome mapping and other genetic applications. Using 139 megagametophytes collected from a single mother tree, we assembled 397,226 loci, of which 108,683 (27.4%) were polymorphic. After stringent filtering for 1:1 segregation ratio and missing rate of <20%, the remaining 23,926 loci (22% of the polymorphic loci) were ordered into 11 linkage groups (LGs) and distributed across 7,559 unique positions, with a total map length of 1,443 cM and an average spacing of 0.2 cM between adjacent unique positions. The 11 LGs correspond to the species’ 11 haploid genome chromosome number. This genetic map is among few high-density maps available for conifers to date, and represents the first genetic map for P. orientalis. The information generated serves as a solid foundation not only for marker-assisted breeding efforts, but also for comparative conifer genomic studies.
Clinical development of CT-P6 in HER2 positive breast cancer

ABSTRACT Introduction: CT-P6 (trastuzumab-pkrb, Herzuma) is a trastuzumab biosimilar approved for use in HER2 positive breast cancer and HER2 positive gastric cancer. CT-P6 has been shown to exhibit similar safety and efficacy profiles to its reference product, trastuzumab. Preclinical and clinical studies have been performed to prove equivalence between CT-P6 and the trastuzumab originator. Areas Covered: In this review, we examine the evidence comparing CT-P6 with its reference product, trastuzumab. Both monoclonal antibodies function to target cells that overexpress HER2 on the cell surface. Preclinical pharmacologic modeling of CT-P6 shows a similar mechanism of action to trastuzumab, similar pharmacologic properties and a phase I trial in healthy volunteers showed similar pharmacokinetics. A multicenter phase III randomized clinical trial in patients with early breast cancer showed equivalent safety and efficacy between CT-P6 and trastuzumab. One-year follow-up of patients showed identical rates of cardiotoxicity. Expert Opinion: Preclinical and clinical studies showed CT-P6 pharmacologic profile, safety and efficacy are equivalent to trastuzumab. As such, it is a safe and effective alternative for use in patients with HER2 positive breast cancer and gastric cancer. Its implementation into clinical practice can potentially increase patient access and help financially alleviate overburdened health-care systems.
Thyroid Related Quality of Life in Elderly with Subclinical Hypothyroidism and Improvement on Levothyroxine is Distinct from that in Young Patients (TSAGE)

Abstract The aim of this study was to investigate in a longitudinal approach whether levothyroxine (LT4) substitution has a different impact on quality of life (QoL) and thyroid related QoL in younger (<40 years) and older subjects (>60 years) with elevated thyroid-stimulating hormone (TSH) concentrations. The study included male and female patients with newly diagnosed, untreated subclinical hypothyroidism defined by TSH>8 mU/l. Patients were recruited throughout Germany from 2013–2016 and evaluated by clinical assessment, blood sampling and questionnaires for health related QoL and thyroid-disease thyroid-related QoL (ThyPRO) at time of diagnosis and six months after initiation of LT4 treatment. We found significantly lower QoL in both young and old patients with subclinical hypothyroidism compared to age-matched healthy individuals. Higher scores on follow-up were found in all patients irrespective of age, indicating better QoL on LT4 therapy. Analysis of the ThyPRO questionnaire showed that old patients experienced less Emotional Susceptibility, Tiredness, and Impaired Day Life on LT4, while young patients reported less Cognitive Complaints, Emotional Susceptibility, and Impaired Day Life compared to baseline assessment. Hypothyroidism with TSH concentrations>8 mU/l is associated with impairment in general and ThyPRO QoL in young and old age. Older patients benefited from LT4 therapy and remarkably show similar degree of improvement as younger patients, albeit with some thematic variation in ThyPRO QoL. Our data confirm current recommendations on initiation of LT4 substitution and suggest that this should not be withheld in elderly with TSH concentration above 8–10 mU/l.
Direct Electrical Stimulation of Premotor Areas: Different Effects on Hand Muscle Activity during Object Manipulation

Abstract Dorsal and ventral premotor (dPM and vPM) areas are crucial in control of hand muscles during object manipulation, although their respective role in humans is still debated. In patients undergoing awake surgery for brain tumors, we studied the effect of direct electrical stimulation (DES) of the premotor cortex on the execution of a hand manipulation task (HMt). A quantitative analysis of the activity of extrinsic and intrinsic hand muscles recorded during and in absence of DES was performed. Results showed that DES applied to premotor areas significantly impaired HMt execution, affecting task-related muscle activity with specific features related to the stimulated area. Stimulation of dorsal vPM induced both a complete task arrest and clumsy task execution, characterized by general muscle suppression. Stimulation of ventrocaudal dPM evoked a complete task arrest mainly due to a dysfunctional recruitment of hand muscles engaged in task execution. These results suggest that vPM and dPM contribute differently to the control of hand muscles during object manipulation. Stimulation of both areas showed a significant impact on motor output, although the different effects suggest a stronger relationship of dPM with the corticomotoneuronal circuit promoting muscle recruitment and a role for vPM in supporting sensorimotor integration.
A Calibration-Free Method Based on Grey Relational Analysis for Heterogeneous Smartphones in Fingerprint-Based Indoor Positioning

The fingerprint method has been widely adopted in Wi-Fi indoor positioning because of its advantage in non-line-of-sight channels between access points (APs) and mobile users. However, the received signal strength (RSS) during the fingerprint positioning process generally varies due to the dissimilar hardware configurations of heterogeneous smartphones. This difference may degrade the accuracy of fingerprint matching between fingerprint and test data. Thus, this paper puts forward a fingerprint method based on grey relational analysis (GRA) to approach the challenge of heterogeneous smartphones and to improve positioning accuracy. Initially, the grey relational coefficient (GRC) between the RSS comparability sequence of each reference point (RP) and the RSS reference sequence of the test point (TP) is calculated. Subsequently, the grey relational degree (GRD) between each RP and TP is determined on the basis of GRC, and the K most relational RPs are selected in accordance with the value of GRD. Finally, the user location is determined by weighting the K most relational RPs that correspond to the coordinates. The main advantage of this GRA method is that it does not require device calibration when handling heterogeneous smartphone problems. We further carry out extensive experiments using heterogeneous Android smartphones in an office environment to verify the positioning performance of the proposed method. Experimental results indicate that the proposed method outperforms the existing ones no matter whether heterogeneous smartphones are used.
The Root Endophytic Fungi Community Structure of Pennisetum sinese from Four Representative Provinces in China

Pennisetum sinese is a good forage grass with high biomass production and crude proteins. However, little is known about the endophytic fungi diversity of P. sinese, which might play an important role in the plant’s growth and biomass production. Here, we used high throughput sequencing of the Internal Transcribed Spacer (ITS) sequences based on primers ITS5-1737 and ITS2-2043R to investigate the endophytic fungi diversity of P. sinese roots at the maturity stage, as collected from four provinces (Shaanxi province, SX; Fujian province, FJ; the Xinjiang Uyghur autonomous prefecture, XJ and Inner Mongolia, including sand (NS) and saline-alkali land (NY), China). The ITS sequences were processed using QIIME and R software. A total of 374,875 effective tags were obtained, and 708 operational taxonomic units (OTUs) were yielded with 97% identity in the five samples. Ascomycota and Basidiomycota were the two dominant phyla in the five samples, and the genera Khuskia and Heydenia were the most abundant in the FJ and XJ samples, respectively, while the most abundant tags in the other three samples could not be annotated at the genus level. In addition, our study revealed that the FJ sample possessed the highest OTU numbers (242) and the NS sample had the lowest (86). Moreover, only 22 OTUs were present in all samples simultaneously. The beta diversity analysis suggested a division of two endophytic fungi groups: the FJ sample from the south of China and the other four samples from north or northwest China. Correlation analysis between the environmental factors and endophytic fungi at the class level revealed that Sordariomycetes and Pucciniomycetes had extremely significant positive correlations with the total carbon, annual average precipitation, and annual average temperature, while Leotiomycetes showed an extremely significant negative correlation with quick acting potassium. The results revealed significant differences in the root endophytic fungi diversity of P. sinese in different provinces and might be useful for growth promotion and biomass production in the future.
P40 polyester sheet plastination technique for brain and body slices: The vertical and horizontal flat chamber methods

The P40 technique produces high‐quality brain and body slices and is the user‐friendliest of the polyester techniques. The P40 polyester technique follows the same classical steps for plastination. That is, preparation of the specimen, fixation (optional), dehydration by freeze substitution, forced impregnation and curing. Two methods used to prepare two different types of specimens, that is, brain slices and body slices are described. Each method has its own characteristics depending on the specimen type used. Brain slices were used to illustrate the vertical small chamber method while the body slices were used to illustrate the horizontal large chamber method. The brain slices obtained using P40 are of very good quality presenting good contrast between grey and white matter. The body slices are also of very good quality. The physical appearance of these slices makes them an exceptional instrument for diagnostic imaging and anatomical correlation. Body slices prepared with P40 retain the natural colour of the tissue and preserve the anatomical relationships.
Entomopathogenic nematodes increase predation success by inducing cadaver volatiles that attract healthy herbivores

Herbivore natural enemies protect plants by regulating herbivore populations. Whether they can alter the behavior of their prey to increase predation success is unknown. We investigate if and how infection by the entomopathogenic nematode Heterorhabditis bacteriophora changes the behavior of healthy larvae of the western corn rootworm (Diabrotica virgifera), a major pest of maize. We found that nematode-infected rootworm cadavers are attractive to rootworm larvae, and that this behavior increases nematode reproductive success. Nematode-infected rootworms release distinct volatile bouquets, including the unusual volatile butylated hydroxytoluene (BHT). BHT alone attracts rootworms, and increases nematode reproductive success. A screen of different nematode and herbivore species shows that attraction of healthy hosts to nematode-infected cadavers is widespread and likely involves species-specific volatile cues. This study reveals a new facet of the biology of herbivore natural enemies that boosts their predation success by increasing the probability of host encounters.
Prognostic Value of Prealbumin in Liver Cancer: A Systematic Review and Meta-Analysis

Abstract Accumulated studies have reported the prognostic significance of prealbumin in liver cancer, but the results were not conclusive. The aim of this study was to evaluate the association between pretreatment serum prealbumin and clinical outcome of liver cancer patients through a meta-analysis. We comprehensively searched EMBASE, PubMed, Web of Science and the Cochrane library to identify eligible studies. The pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) were utilized to evaluate the prognostic value of pretreatment serum prealbumin in overall survival (OS) and recurrence-free survival (RFS) of liver cancer patients. A total of 3470 patients from 10 eligible studies were finally included for analysis. The combined effects of prealbumin on liver cancer patients’ OS and RFS were HR = 1.83, 95% CI: 1.46–2.30, P < 0.001 and HR = 1.47, 95% CI: 1.01–2.14, P = 0.045, respectively. Sensitivity and subgroup analysis showed that the pooled HR of prealbumin on liver cancer patients’ OS was stable. Since potential publication bias was identified in the OS studies, the trim-and-fill method therefore was performed to explore publication bias, and the results showed reliability. This meta-analysis shows that low pretreatment serum prealbumin is significantly associated with poor prognosis of liver cancer patients.
Twist1 Inactivation in Dmp1-Expressing Cells Increases Bone Mass but Does Not Affect the Anabolic Response to Sclerostin Neutralization

Wnt signaling plays a major role in bone metabolism. Advances in our understanding of secreted regulators of Wnt have yielded several therapeutic targets to stimulate osteoanabolism—the most promising of which is the Wnt inhibitor sclerostin. Sclerostin antibody recently gained approval for clinical use to treat osteoporosis, but the biology surrounding sclerostin antagonism is still incompletely understood. Numerous factors regulate the efficacy of sclerostin inhibition on bone formation, a process known as self-regulation. In previous communications we reported that the basic helix-loop-helix transcription factor Twist1—a gene know to regulate skeletal development—is highly upregulated among the osteocyte cell population in mice treated with sclerostin antibody. In this communication, we tested the hypothesis that preventing Twist1 upregulation by deletion of Twist1 from late-stage osteoblasts and osteocytes would increase the efficacy of sclerostin antibody treatment, since Twist1 is known to restrain osteoblast activity in many models. Twist1-floxed loss-of-function mice were crossed to the Dmp1-Cre driver to delete Twist1 in Dmp1-expressing cells. Conditional Twist1 deletion was associated with a mild but significant increase in bone mass, as assessed by dual energy x-ray absorptiometry (DXA) and microCT (µCT) for many endpoints in both male and female mice. Biomechanical properties of the femur were not affected by conditional mutation of Twist1. Sclerostin antibody improved all bone properties significantly, regardless of Twist1 status, sex, or endpoint examined. No interactions were detected when Twist1 status and antibody treatment were examined together, suggesting that Twist1 upregulation in the osteocyte population is not an endogenous mechanism that restrains the osteoanabolic effect of sclerostin antibody treatment. In summary, Twist1 inhibition in the late-stage osteoblast/osteocyte increases bone mass but does not affect the anabolic response to sclerostin neutralization.