Miracle-dz/UniFAR-FTUs huggingface dataset:
Human influenza A virus causes myocardial and cardiac-specific conduction system infections associated with early inflammation and premature death

Abstract Aims Human influenza A virus (hIAV) infection is associated with important cardiovascular complications, although cardiac infection pathophysiology is poorly understood. We aimed to study the ability of hIAV of different pathogenicity to infect the mouse heart, and establish the relationship between the infective capacity and the associated in vivo, cellular and molecular alterations. Methods and results We evaluated lung and heart viral titres in mice infected with either one of several hIAV strains inoculated intranasally. 3D reconstructions of infected cardiac tissue were used to identify viral proteins inside mouse cardiomyocytes, Purkinje cells, and cardiac vessels. Viral replication was measured in mouse cultured cardiomyocytes. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were used to confirm infection and study underlying molecular alterations associated with the in vivo electrophysiological phenotype. Pathogenic and attenuated hIAV strains infected and replicated in cardiomyocytes, Purkinje cells, and hiPSC-CMs. The infection was also present in cardiac endothelial cells. Remarkably, lung viral titres did not statistically correlate with viral titres in the mouse heart. The highly pathogenic human recombinant virus PAmut showed faster replication, higher level of inflammatory cytokines in cardiac tissue and higher viral titres in cardiac HL-1 mouse cells and hiPSC-CMs compared with PB2mut-attenuated virus. Correspondingly, cardiac conduction alterations were especially pronounced in PAmut-infected mice, associated with high mortality rates, compared with PB2mut-infected animals. Consistently, connexin43 and NaV1.5 expression decreased acutely in hiPSC-CMs infected with PAmut virus. YEM1L protease also decreased more rapidly and to lower levels in PAmut-infected hiPSC-CMs compared with PB2mut-infected cells, consistent with mitochondrial dysfunction. Human IAV infection did not increase myocardial fibrosis at 4-day post-infection, although PAmut-infected mice showed an early increase in mRNAs expression of lysyl oxidase. Conclusion Human IAV can infect the heart and cardiac-specific conduction system, which may contribute to cardiac complications and premature death.
The effect of nitrogen starvation on PSI and PSII activity in pea ( pisum sativum)

This investigation addresses how photosynthetic efficiency is affected when pea (Pisum sativum) plants are restricted to a sole nitrogen source (i.e. ammonium or nitrate). The pea plants were watered with different nutrient solutions without NO3- or NH4+ for different time-periods in order to assay for nitrogen content. The soluble ammonium and nitrate content was measured throughout the entire growth period. No major differences were observed in nitrogen content during the starvation period up to 25 days. For technical reasons, cultivation of plants could not be extended beyond this time. The chloroplasts and thylakoids were isolated after 25 days and assayed for chlorophyll contents and photosynthetic activity.The outcome of these tests indicates a small but unambiguous decrease in the photosynthesis activity for all treatments, relative the control.
Progressive increase in FIX level in males with haemophilia B Leyden and c.35G > A mutation in early childhood not related to androgen effect

Additional supporting information may be found online in the Supporting Information section at the end of the article. Fig S1. Clinical benefit in patients treated with low-dose decitabine plus bortezomib and dexamethasone. Fig S2. Clinical benefit in patients treated with low-dose decitabine plus bortezomib and dexamethasone. Fig S3. Clinical benefit in patients treated with low-dose decitabine plus bortezomib and dexamethasone. Table SI. Most common adverse events during treatment. Table SII. PFS and response analysis.
Decreased Ratio of VEGF165b/VEGF in Aqueous Humor Predicts Progression of Diabetic Retinopathy

Background: Different splicing of vascular endothelial growth factor (VEGF) gene results in 2 families of VEGF, the proangiogenic isoforms (VEGFxxxa) and the antiangiogenic isoforms (VEGFxxxb). VEGF165b is the major antiangiogenic isoform of VEGF and the most studied member of the VEGFxxxb family so far. Objectives: To determine the concentration of VEGF165b and VEGF in the aqueous humor (AH) in diabetic eyes with or without diabetic retinopathy (DR) and to address the predictive value of VEGF165b/VEGF ratio for progression of DR. Methods: AH samples from 20 eyes in healthy controls (CON group), 40 eyes in diabetic patients without DR (nDR group), and 30 eyes in diabetic patients with mild nonproliferative DR (DR group) were collected. All of the patients were followed up for at least 5 years. VEGF165b and VEGF levels of AH samples were measured by enzyme-linked immunosorbent assay (ELISA). The predictive value of the initial VEGF165b/VEGF ratio for progression of DR was studied. Results: The mean concentration of VEGF165b significantly decreased in diabetic eyes vs. controls. The mean concentration of VEGF significantly increased in the DR group vs. the CON group. The VEGF165b/VEGF ratio was significantly lower in diabetic patients compared to the CON group. The VEGF165b/VEGF ratio was significantly lower in diabetic patients compared to the control group. The mean follow-up was 66.1months (range 60–71 months). The risk of DR progression was greater with a lower VEGF165b/VEGF ratio. Conclusion: The VEGF165b/VEGF ratio is lower in the AH of DR patients and the decreased ratio of VEGF165b/VEGF predicts DR progression.
Indignation for moral violations suppresses the tongue motor cortex: preliminary TMS evidence

Abstract We commonly label moral violations in terms of ‘disgust’, yet it remains unclear whether metaphorical expressions linking disgust and morality are genuinely shared at the cognitive/neural level. Using transcranial magnetic stimulation (TMS), we provide new insights into this debate by measuring motor-evoked potentials (MEPs) from the tongue generated by TMS over the tongue primary motor area (tM1) in a small group of healthy participants presented with vignettes of moral transgressions and non-moral vignettes. We tested whether moral indignation, felt while evaluating moral vignettes, affected tM1 excitability. Vignettes exerted a variable influence on MEPs with no net effect of the moral category. However, in accordance with our recent study documenting reduced tM1 excitability during exposure to pictures of disgusting foods or facial expressions of distaste, we found that the vignettes of highly disapproved moral violations reduced tM1 excitability. Moreover, tM1 excitability and moral indignation were linearly correlated: the higher the moral indignation, the lower the tM1 excitability. Respective changes in MEPs were not observed in a non-oral control muscle, suggesting a selective decrease of tM1 excitability. These preliminary findings provide neurophysiological evidence supporting the hypothesis that morality might have originated from the more primitive experience of oral distaste.
Mutations Upstream of the TBX5 and PITX1 Transcription Factor Genes Are Associated with Feathered Legs in the Domestic Chicken

Abstract Feathered leg is a trait in domestic chickens that has undergone intense selection by fancy breeders. Previous studies have shown that two major loci controlling feathered leg are located on chromosomes 13 and 15. Here, we present genetic evidence for the identification of candidate causal mutations at these loci. This was accomplished by combining classical linkage mapping using an experimental cross segregating for feathered leg and high-resolution identical-by-descent mapping using whole-genome sequence data from 167 samples of chicken with or without feathered legs. The first predicted causal mutation is a single-base change located 25 kb upstream of the gene for the forelimb-specific transcription factor TBX5 on chromosome 15. The second is a 17.7-kb deletion located ∼200 kb upstream of the gene for the hindlimb-specific transcription factor PITX1 on chromosome 13. These mutations are predicted to activate TBX5 and repress PITX1 expression, respectively. The study reveals a remarkable convergence in the evolution of the feathered-leg phenotype in domestic chickens and domestic pigeons, as this phenotype is caused by noncoding mutations upstream of the same two genes. Furthermore, the PITX1 causal variants are large overlapping deletions, 17.7 kb in chicken and 44 kb in pigeons. The results of the present study are consistent with the previously proposed model for pigeon that feathered leg is caused by reduced PITX1 expression and ectopic expression of TBX5 in hindlimb buds resulting in a shift of limb identity from hindlimb to more forelimb-like identity.
Inhibiting Monocyte Recruitment to Prevent the Pro-Tumoral Activity of Tumor-Associated Macrophages in Chondrosarcoma

Chondrosarcomas (CHS) are malignant cartilaginous neoplasms with diverse morphological features, characterized by resistance to chemo- and radiation therapies. In this study, we investigated the role of tumor-associated macrophages (TAM)s in tumor tissues from CHS patients by immunohistochemistry. Three-dimensional organotypic co-cultures were set up in order to evaluate the contribution of primary human CHS cells in driving an M2-like phenotype in monocyte-derived primary macrophages, and the capability of macrophages to promote growth and/or invasiveness of CHS cells. Finally, with an in vivo model of primary CHS cells engrafted in nude mice, we tested the ability of a potent peptide inhibitor of cell migration (Ac-d-Tyr-d-Arg-Aib-d-Arg-NH2, denoted RI-3) to reduce recruitment and infiltration of monocytes into CHS neoplastic lesions. We found a significant correlation between alternatively activated M2 macrophages and intratumor microvessel density in both conventional and dedifferentiated CHS human tissues, suggesting a link between TAM abundance and vascularization in CHS. In 3D and non-contact cu-culture models, soluble factors produced by CHS induced a M2-like phenotype in macrophages that, in turn, increased motility, invasion and matrix spreading of CHS cells. Finally, we present evidence that RI-3 successfully prevent both recruitment and infiltration of monocytes into CHS tissues, in nude mice.
Application of Radio Environment Map Reconstruction Techniques to Platoon-based Cellular V2X Communications

Vehicle platoons involve groups of vehicles travelling together at a constant inter-vehicle distance, with different common benefits such as increasing road efficiency and fuel saving. Vehicle platooning requires highly reliable wireless communications to keep the group structure and carry out coordinated maneuvers in a safe manner. Focusing on infrastructure-assisted cellular vehicle to anything (V2X) communications, the amount of control information to be exchanged between each platoon vehicle and the base station is a critical factor affecting the communication latency. This paper exploits the particular structure and characteristics of platooning to decrease the control information exchange necessary for the channel acquisition stage. More precisely, a scheme based on radio environment map (REM) reconstruction is proposed, where geo-localized received power values are available at only a subset of platoon vehicles, while large-scale channel parameters estimates for the rest of platoon members are provided through the application of spatial Ordinary Kriging (OK) interpolation. Distinctive features of the vehicle platooning use case are explored, such as the optimal patterns of vehicles within the platoon with available REM values for improving the quality of the reconstruction, the need for an accurate semivariogram modeling in OK, or the communication cost when establishing a centralized or a distributed architecture for achieving REM reconstruction. The evaluation results show that OK is able to reconstruct the REM in the platoon with acceptable mean squared estimation error, while reducing the control information for REM acquisition in up to 64% in the best-case scenario.
Effects of Ultrasonic Bending Vibration Introduced by an L-Shaped Ultrasonic Rod on the Microstructure and Properties of a 1060 Aluminum Alloy Strip Formed by Twin-Roll Casting

In order to achieve the industrial application of ultrasonic energy in the continuous casting and rolling production of aluminum alloy, a new type of L-shaped ultrasonic rod was used to introduce an ultrasonic bending vibration into the aluminum melt in the launder during the horizontal twin-roll continuous casting and rolling process of a 1060 aluminum alloy. The effects of the ultrasonic bending vibration on the microstructure and properties of the 1060 aluminum alloy cast rolling strip and its subsequent cold rolling strip were studied experimentally, and the effect of the ultrasonic-assisted refining with different amounts of Al-Ti-B refiner was explored. The results show that under the same addition amount of Al-Ti-B refiner, the ultrasonic bending vibration can refine the grains of the cast rolling strip, make the distribution of precipitates more uniform, reduce the slag inclusion defects, and improve the mechanical properties to a certain extent. The microstructure and properties of the ultrasonic cast rolling strip with 0.18 wt% Al-Ti-B refiner or 0.12 wt% Al-Ti-B refiner are better than those of the conventional cast rolling strip, but the microstructure and properties of the ultrasonic cast rolling strip with 0.09 wt% Al-Ti-B refiner are slightly worse than those of the conventional cast rolling strip. Moreover, after cold rolling, the effect of the ultrasonic bending vibration on the improvement of the microstructure and properties of the aluminum alloy strip is inherited. A comprehensive analysis shows that the use of ultrasonic energy in this paper cannot completely replace the effect of the Al-Ti-B refiner, but it can reduce the addition amount of the Al-Ti-B refiner by 1/3.
Antimicrobial Peptides as Probes in Biosensors Detecting Whole Bacteria: A Review

Bacterial resistance is becoming a global issue due to its rapid growth. Potential new drugs as antimicrobial peptides (AMPs) are considered for several decades as promising candidates to circumvent this threat. Nonetheless, AMPs have also been used more recently in other settings such as molecular probes grafted on biosensors able to detect whole bacteria. Rapid, reliable and cost-efficient diagnostic tools for bacterial infection could prevent the spread of the pathogen from the earliest stages. Biosensors based on AMPs would enable easy monitoring of potentially infected samples, thanks to their powerful versatility and integrability in pre-existent settings. AMPs, which show a broad spectrum of interactions with bacterial membranes, can be tailored in order to design ubiquitous biosensors easily adaptable to clinical settings. This review aims to focus on the state of the art of AMPs used as the recognition elements of whole bacteria in label-free biosensors with a particular focus on the characteristics obtained in terms of threshold, volume of sample analysable and medium, in order to assess their workability in real-world applications.
Unique Role of Histone Methyltransferase PRDM8 in the Tumorigenesis of Virus-Negative Merkel Cell Carcinoma

Merkel cell carcinoma (MCC) is a deadly skin cancer, and about 80% of its cases have been shown to harbor integrated Merkel polyomavirus in the tumor cell genome. Viral oncoproteins expressed in the tumor cells are considered as the oncogenic factors of these virus-positive Merkel cell carcinoma (VP-MCC). In contrast, the molecular pathogenesis of virus-negative MCC (VN-MCC) is less well understood. Using gene expression analysis of MCC cell lines, we found histone methyltransferase PRDM8 to be elevated in VN-MCC. This finding was confirmed by immunohistochemical analysis of MCC tumors, revealing that increased PRDM8 expression in VN-MCC is also associated with increased H3K9 methylation. CRISPR-mediated silencing of PRDM8 in MCC cells further supported the histone methylating role of this protein in VN-MCC. We also identified miR-20a-5p as a negative regulator of PRDM8. Taken together, our findings provide insights into the role of PRDM8 as a histone methyltransferase in VN-MCC tumorigenesis.
The Effect of Size, Maturation, Global Asphyxia, Cerebral Ischemia, and Therapeutic Hypothermia on the Pharmacokinetics of High-Dose Recombinant Erythropoietin in Fetal Sheep

High-dose human recombinant erythropoietin (rEPO) is a promising potential neuroprotective treatment in preterm and full-term neonates with hypoxic-ischemic encephalopathy (HIE). There are limited data on the pharmacokinetics of high-dose rEPO in neonates. We examined the effects of body weight, gestation age, global asphyxia, cerebral ischemia, hypothermia and exogenous rEPO on the pharmacokinetics of high-dose rEPO in fetal sheep. Near-term fetal sheep on gestation day 129 (0.87 gestation) (full term 147 days) received sham-ischemia (n = 5) or cerebral ischemia for 30 min followed by treatment with vehicle (n = 4), rEPO (n = 8) or combined treatment with rEPO and hypothermia (n = 8). Preterm fetal sheep on gestation day 104 (0.7 gestation) received sham-asphyxia (n = 1) or complete umbilical cord occlusion for 25 min followed by i.v. infusion of vehicle (n = 8) or rEPO (n = 27) treatment. rEPO was given as a loading bolus, followed by a prolonged continuous infusion for 66 to 71.5 h in preterm and near-term fetuses. A further group of preterm fetal sheep received repeated bolus injections of rEPO (n = 8). The plasma concentrations of rEPO were best described by a pharmacokinetic model that included first-order and mixed-order elimination with linear maturation of elimination with gestation age. There were no detectable effects of therapeutic hypothermia, cerebral ischemia, global asphyxia or exogenous treatment on rEPO pharmacokinetics. The increase in rEPO elimination with gestation age suggests that to maintain target exposure levels during prolonged treatment, the dose of rEPO may have to be adjusted to match the increase in size and growth. These results are important for designing and understanding future studies of neuroprotection with high-dose rEPO.
Time-Interleaved SAR ADC with Background Timing-Skew Calibration for UWB Wireless Communication in IoT Systems

Ultra-wideband (UWB) wireless communication is prospering as a powerful partner of the Internet-of-things (IoT). Due to the ongoing development of UWB wireless communications, the demand for high-speed and medium resolution analog-to-digital converters (ADCs) continues to grow. The successive approximation register (SAR) ADCs are the most powerful candidate to meet these demands, attracting both industries and academia. In particular, recent time-interleaved SAR ADCs show that multi-giga sample per second (GS/s) can be achieved by overcoming the challenges of high-speed implementation of existing SAR ADCs. However, there are still critical issues that need to be addressed before the time-interleaved SAR ADCs can be applied in real commercial applications. The most well-known problem is that the time-interleaved SAR ADC architecture requires multiple sub-ADCs, and the mismatches between these sub-ADCs can significantly degrade overall ADC performance. And one of the most difficult mismatches to solve is the sampling timing skew. Recently, research to solve this timing-skew problem has been intensively studied. In this paper, we focus on the cutting-edge timing-skew calibration technique using a window detector. Based on the pros and cons analysis of the existing techniques, we come up with an idea that increases the benefits of the window detector-based timing-skew calibration techniques and minimizes the power and area overheads. Finally, through the continuous development of this idea, we propose a timing-skew calibration technique using a comparator offset-based window detector. To demonstrate the effectiveness of the proposed technique, intensive works were performed, including the design of a 7-bit, 2.5 GS/s 5-channel time-interleaved SAR ADC and various simulations, and the results prove excellent efficacy of signal-to-noise and distortion ratio (SNDR) and spurious-free dynamic range (SFDR) of 40.79 dB and 48.97 dB at Nyquist frequency, respectively, while the proposed window detector occupies only 6.5% of the total active area, and consumes 11% of the total power.
Inhibition of Pro-Inflammatory Cytokines by Metabolites of Streptomycetes—A Potential Alternative to Current Anti-Inflammatory Drugs?

Current treatment of chronic diseases includes, among others, application of cytokines, monoclonal antibodies, cellular therapies, and immunostimulants. As all the underlying mechanisms of a particular diseases are not always fully clarified, treatment can be inefficient and associated with various, sometimes serious, side effects. Small secondary metabolites produced by various microbes represent an attractive alternative as future anti-inflammatory drug leads. Compared to current drugs, they are cheaper, can often be administered orally, but still can keep a high target-specificity. Some compounds produced by actinomycetes or fungi have already been used as immunomodulators—tacrolimus, sirolimus, and cyclosporine. This work documents strong anti-inflammatory features of another secondary metabolite of streptomycetes—manumycin-type polyketides. We compared the effect of four related compounds: manumycin A, manumycin B, asukamycin, and colabomycin E on activation and survival of human monocyte/macrophage cell line THP-1. The anti-cancer effect of manucycine A has been demonstrated; the immunomodulatory capacities of manumycin A are obvious when using micromolar concentrations. The application of all four compounds in 0.25–5 μM concentrations leads to efficient, concentration-dependent inhibition of IL-1β and TNF expression in THP-1 upon LPS stimulation, while the three latter compounds show a significantly lower pro-apoptotic effect than manumycin A. We have demonstrated the anti-inflammatory capacity of selected manumycin-type polyketides.
The Complications of Myopia: A Review and Meta-Analysis

Purpose To determine the risk between degree of myopia and myopic macular degeneration (MMD), retinal detachment (RD), cataract, open angle glaucoma (OAG), and blindness. Methods A systematic review and meta-analyses of studies published before June 2019 on myopia complications. Odds ratios (OR) per complication and spherical equivalent (SER) degree (low myopia SER < –0.5 to > –3.00 diopter [D]; moderate myopia SER ≤ –3.00 to > –6.00 D; high myopia SER ≤ –6.00 D) were calculated using fixed and random effects models. Results Low, moderate, and high myopia were all associated with increased risks of MMD (OR, 13.57, 95% confidence interval [CI], 6.18–29.79; OR, 72.74, 95% CI, 33.18–159.48; OR, 845.08, 95% CI, 230.05–3104.34, respectively); RD (OR, 3.15, 95% CI, 1.92–5.17; OR, 8.74, 95% CI, 7.28–10.50; OR, 12.62, 95% CI, 6.65–23.94, respectively); posterior subcapsular cataract (OR, 1.56, 95% CI, 1.32–1.84; OR, 2.55, 95% CI, 1.98–3.28; OR, 4.55, 95% CI, 2.66–7.75, respectively); nuclear cataract (OR, 1.79, 95% CI, 1.08–2.97; OR, 2.39, 95% CI, 1.03–5.55; OR, 2.87, 95% CI, 1.43–5.73, respectively); and OAG (OR, 1.59, 95% CI, 1.33–1.91; OR, 2.92, 95% CI, 1.89–4.52 for low and moderate/high myopia, respectively). The risk of visual impairment was strongly related to longer axial length, higher myopia degree, and age older than 60 years (OR, 1.71, 95% CI, 1.07–2.74; OR, 5.54, 95% CI, 3.12–9.85; and OR, 87.63, 95% CI, 34.50–222.58 for low, moderate, and high myopia in participants aged >60 years, respectively). Conclusions Although high myopia carries the highest risk of complications and visual impairment, low and moderate myopia also have considerable risks. These estimates should alert policy makers and health care professionals to make myopia a priority for prevention and treatment.