Miracle-dz/UniFAR-FTUs huggingface dataset:
Neuraminidase-associated plasminogen recruitment enables systemic spread of natural avian Influenza viruses H3N1

Repeated outbreaks due to H3N1 low pathogenicity avian influenza viruses (LPAIV) in Belgium were associated with unusually high mortality in chicken in 2019. Those events caused considerable economic losses and prompted restriction measures normally implemented for eradicating high pathogenicity avian influenza viruses (HPAIV). Initial pathology investigations and infection studies suggested this virus to be able to replicate systemically, being very atypical for H3 LPAIV. Here, we investigate the pathogenesis of this H3N1 virus and propose a mechanism explaining its unusual systemic replication capability. By intravenous and intracerebral inoculation in chicken, we demonstrate systemic spread of this virus, extending to the central nervous system. Endoproteolytic viral hemagglutinin (HA) protein activation by either tissue-restricted serine peptidases or ubiquitous subtilisin-like proteases is the functional hallmark distinguishing (H5 or H7) LPAIV from HPAIV. However, luciferase reporter assays show that HA cleavage in case of the H3N1 strain in contrast to the HPAIV is not processed by intracellular proteases. Yet the H3N1 virus replicates efficiently in cell culture without trypsin, unlike LPAIVs. Moreover, this trypsin-independent virus replication is inhibited by 6-aminohexanoic acid, a plasmin inhibitor. Correspondingly, in silico analysis indicates that plasminogen is recruitable by the viral neuraminidase for proteolytic activation due to the loss of a strongly conserved N-glycosylation site at position 130. This mutation was shown responsible for plasminogen recruitment and neurovirulence of the mouse brain-passaged laboratory strain A/WSN/33 (H1N1). In conclusion, our findings provide good evidence in natural chicken strains for N1 neuraminidase-operated recruitment of plasminogen, enabling systemic replication leading to an unusual high pathogenicity phenotype. Such a gain of function in naturally occurring AIVs representing an established human influenza HA-subtype raises concerns over potential zoonotic threats.
Image Quality Assessment of Fetal Brain MRI Using Multi‐Instance Deep Learning Methods

Due to random motion of fetuses and maternal respirations, image quality of fetal brain MRIs varies considerably. To address this issue, visual inspection of the images is performed during acquisition phase and after 3D‐reconstruction, and the images are re‐acquired if they are deemed to be of insufficient quality. However, this process is time‐consuming and subjective. Multi‐instance (MI) deep learning methods (DLMs) may perform this task automatically.
Exploring SERS from complex patterns fabricated by multi-exposure laser interference lithography

Designing uniform plasmonic surfaces in a large area is highly recommended for surface-enhanced Raman scattering (SERS). As periodic morphologies exhibit uniform SERS and optical tunability, diverse fabrication methods of periodic nanostructures have been reported for SERS applications. Laser interference lithography (LIL) is one of the most versatile tools since it can rapidly fabricate periodic patterns without the usage of photomasks. Here, we explore complex interference patterns for spatially uniform SERS sensors and its cost-effective fabrication method termed multi-exposure laser interference lithography (MELIL). MELIL can produce nearly periodic profiles along every direction confirmed by mathematical background, and in virtue of periodicity, we show that highly uniform Raman scattering (relative standard deviation <6%) can also be achievable in complex geometries as the conventional hole patterns. We quantitatively characterize the Raman enhancement of the MELIL complex patterns after two different metal deposition processes, Au e-beam evaporation and Ag electroplating, which results in 0.387 × 105 and 1.451 × 105 in enhancement factor respectively. This alternative, vacuum-free electroplating method realizes an even more cost-effective process with enhanced performance. We further conduct the optical simulation for MELIL complex patterns which exhibits the broadened and shifted absorption peaks. This result supports the potential of the expanded optical tunability of the suggested process.
The UK Dangerous Dogs Act: Improved, but legally and ethically flawed.

BACKGROUND The Dangerous Dogs Act (DDA) is considered among the most controversial pieces of legislation ever passed in the UK. Its effectiveness and how it works in practice, up until a dog and its owner are charged, has been subjected to considerable analysis. However, there has been little examination of how the DDA works after charging, nor of how courts are interpreting it. METHOD We accessed legal cases from 1992 to 2019, the period in which the DDA has been in force. Each case was examined from a legal and ethical perspective, using doctrinal legal methodology and the principlism approach to ethics described by Beauchamp and Childress. RESULTS Analysis showed that while improvements to the function of the act have been made, substantial legal and ethical failings remain, particularly with Section 1 and the therein breed specific legislation (BSL). CONCLUSION Legal failings could be partially resolved by removing the reversed burden of proof placed on dog owners and allowing a change of ownership for banned breeds. However, ethical failings could only be resolved through the abolition of BSL. Further study into whether judicial bias exists against certain breeds found to be dangerously out of control is warranted.
Evaluation of Hsp90 and mTOR inhibitors as potential drugs for the treatment of TSC1/TSC2 deficient cancer

Inactivating mutations in either TSC1 or TSC2 cause Tuberous Sclerosis Complex, an autosomal dominant disorder, characterized by multi-system tumor and hamartoma development. Mutation and loss of function of TSC1 and/or TSC2 also occur in a variety of sporadic cancers, and rapamycin and related drugs show highly variable treatment benefit in patients with such cancers. The TSC1 and TSC2 proteins function in a complex that inhibits mTORC1, a key regulator of cell growth, which acts to enhance anabolic biosynthetic pathways. In this study, we identified and validated five cancer cell lines with TSC1 or TSC2 mutations and performed a kinase inhibitor drug screen with 197 compounds. The five cell lines were sensitive to several mTOR inhibitors, and cell cycle kinase and HSP90 kinase inhibitors. The IC50 for Torin1 and INK128, both mTOR kinase inhibitors, was significantly increased in three TSC2 null cell lines in which TSC2 expression was restored. Rapamycin was significantly more effective than either INK128 or ganetespib (an HSP90 inhibitor) in reducing the growth of TSC2 null SNU-398 cells in a xenograft model. Combination ganetespib-rapamycin showed no significant enhancement of growth suppression over rapamycin. Hence, although HSP90 inhibitors show strong inhibition of TSC1/TSC2 null cell line growth in vitro, ganetespib showed little benefit at standard dosage in vivo. In contrast, rapamycin which showed very modest growth inhibition in vitro was the best agent for in vivo treatment, but did not cause tumor regression, only growth delay.
Synthesis of 3,4,5-Trimethoxybenzoylsolanesylamide

Trimethoxybenzoyloxysolanesylamide(8) was first synthesized from solanesol in four steps. Thus, solanesyl bromide(5) prepared by the reaction of solanesol(4) and PBr_3 was reacted with potassium phthalimide to give N-solanesylphthalimide(6), which was refluxed with N_2H_4·H_2O in 95%EtOH to give solanesylamine(7). Compound 7 was then reacted with 3,4,5-trimethoxybenzoyloxyl chloride to give the title compound. Its structure has been confirmed by IR, 1H NMR, MS and elemental analysis.
Enteric Viruses and Pepper Mild Mottle Virus Show Significant Correlation in Select Mid-Atlantic Agricultural Waters

Microbiological analysis of agricultural waters is fundamental to ensure microbial food safety. The highly variable nature of nontraditional sources of irrigation water makes them particularly difficult to test for the presence of viruses. ABSTRACT Enteric viruses (EVs) are the largest contributors to foodborne illnesses and outbreaks globally. Their ability to persist in the environment, coupled with the challenges experienced in environmental monitoring, creates a critical aperture through which agricultural crops may become contaminated. This study involved a 17-month investigation of select human EVs and viral indicators in nontraditional irrigation water sources (surface and reclaimed waters) in the Mid-Atlantic region of the United States. Real-time quantitative PCR was used for detection of Aichi virus, hepatitis A virus, and norovirus genotypes I and II (GI and GII, respectively). Pepper mild mottle virus (PMMoV), a common viral indicator of human fecal contamination, was also evaluated, along with atmospheric (air and water temperature, cloud cover, and precipitation 24 h, 7 days, and 14 days prior to sample collection) and physicochemical (dissolved oxygen, pH, salinity, and turbidity) data, to determine whether there were any associations between EVs and measured parameters. EVs were detected more frequently in reclaimed waters (32% [n = 22]) than in surface waters (4% [n = 49]), similar to PMMoV detection frequency in surface (33% [n = 42]) and reclaimed (67% [n = 21]) waters. Our data show a significant correlation between EV and PMMoV (R2 = 0.628, P < 0.05) detection levels in reclaimed water samples but not in surface water samples (R2 = 0.476, P = 0.78). Water salinity significantly affected the detection of both EVs and PMMoV (P < 0.05), as demonstrated by logistic regression analyses. These results provide relevant insights into the extent and degree of association between human (pathogenic) EVs and water quality data in Mid-Atlantic surface and reclaimed waters, as potential sources for agricultural irrigation. IMPORTANCE Microbiological analysis of agricultural waters is fundamental to ensure microbial food safety. The highly variable nature of nontraditional sources of irrigation water makes them particularly difficult to test for the presence of viruses. Multiple characteristics influence viral persistence in a water source, as well as affecting the recovery and detection methods that are employed. Testing for a suite of viruses in water samples is often too costly and labor-intensive, making identification of suitable indicators for viral pathogen contamination necessary. The results from this study address two critical data gaps, namely, EV prevalence in surface and reclaimed waters of the Mid-Atlantic region of the United States and subsequent evaluation of physicochemical and atmospheric parameters used to inform the potential for the use of indicators of viral contamination.
Multifocal Annular Pink Plaques With a Central Violaceous Hue.

An otherwise healthy 78-year-old woman presented with a diffuse, mildly itchy rash of 5 days’ duration with associated fatigue, chills, decreased appetite, and nausea. She reported waking up with her arms “feeling like they weigh a ton. ” She denied any pain, bleeding, or oozing and was unsure if new spots were continuing to develop. The patient reported having allergies to numerous medications but denied any new medications or recent illnesses. She had recently spent time on a farm in Minnesota, and upon further questioning she recalled a tick bite 2 months prior to presentation. She stated that she removed the nonengorged tick and that it could not have been attached for more than 24 hours. Her medical and family history were unremarkable. Physical examination showed multiple annular pink plaques with a central violaceous hue in a generalized distribution involving the face, trunk, arms, and legs with mild erythema of the palms. The plantar surfaces were clear, and there was no evidence of lymphadenopathy. The remainder of the physical examination and review of systems was negative. Laboratory screening was notable for an elevated erythrocyte sedimentation rate and C-reactive protein level with negative antinuclear antibodies.
Dydrogesterone versus medroxyprogesterone acetate co-treatment ovarian stimulation for IVF: a matched cohort study of 236 freeze-all-IVF cycles

Abstract This matched cohort study was retrospectively performed, with cycles extracted from freeze-all-IVF treatments performed between March and November 2019, to compare the efficacy of flexible-start dydrogesterone (DYG) co-treatment ovarian stimulations (OS) with flexible-start medroxyprogesterone acetate (MPA) co-treatment OS. DYG cycles were matched 1:1 with MPA cycles using female age and antral follicle count, resulting in 236 matched cycles. OS durations and total FSH doses were similar in DYG and MPA OS cycles. The numbers of mature oocytes retrieved were similar; however, the mature oocyte retrieval rate was significantly lower (66.7 vs. 78.2%; p = .001) and the cycle cancellation rates were higher (29.2 vs. 21.2%; p = .056) in DYG co-treatments. A linear regression selected OS co-treatment protocol (0.53 DYG (0.356–0.776), p = . 001) into the final model to predict a ≥ 80% mature oocyte retrieval rate. The per transfer (47.2 vs. 49.7; p = .721) and per treatment ongoing pregnancy rates (32.2 vs. 38.1%, p = .210) were similar in the two co-treatment groups. Flexible-start DYG co-treatment OS was as effective in blastocyst freeze-all-IVF cycles as MPA co-treatment, with similar ongoing pregnancy rates; however, mature oocyte retrieval was significantly decreased and cycle cancellation increased in DYG cycles. Impact statement What is already known on this subject? Progestin (i.e. artificial progesterone) co-treatment has long been known to be a feasible alternative to conventional GnRH-analogue co-treatment in OS for IVF, because of the long-standing evidence that progestin formulations have in oral contraceptive therapies. The recent evolution of effective freeze-all-IVF (in which high mid-cycle progesterone levels is not of concern because of the postponement of embryo transfer) has now made it possible to investigate progestin co-treatment OS in IVF. What do the results of this study add? Ongoing pregnancy rates from blastocyst frozen embryo transfers in flexible-start dydrogesterone (DYG) co-treatment ovarian stimulation (OS) cycles were similar to rates in flexible-start medroxyprogesterone acetate (MPA) co-treatment OS cycles. The mature oocyte retrieval rate was significantly lower and the cycle cancellation rate higher in DYG than in MPA cycles. What are the implications of these findings for clinical practice and/or further research? The evidence suggests that MPA co-treatment should be preferred in OS for IVF. Further investigation is required to refine progestin co-treatment protocols, because of their potential to reduce the number of viable blastocysts.
Dementia care from behind the mask? Maintaining well‐being during COVID‐19 pandemic restrictions: Observations from Dementia Care Mapping on NHS mental health hospital wards in Wales

Accessible summary What is known on the subject? Coronavirus disease 2019 (COVID‐19) is a new infectious disease that has spread across the world and infected a large number of people many of whom have died. People with moderate to severe dementia are at very high risk of becoming infected as the disease mainly impacts on older people with other health problems and once infected the person with dementia is more likely to become seriously ill than other people. To prevent infection, people are required to wear masks and isolate from contact with others. It is believed that these measures can reduce the quality of life and general well‐being of people with moderate to severe dementia in hospital or social care. This belief has not yet been demonstrated by research. What does this paper add to the existing knowledge? We show that people with moderate to severe dementia receiving care on mental health hospital wards and subject to strict infection prevention measures can still achieve high levels of well‐being. We show that mental health nurses alter the focus of their care to deliberately overcome the challenges and particularly the restrictions on visiting by families. What are the implications for practice? We believe that the changes in practice we observed can occur in other healthcare and social care settings and that whilst restrictions remain in place care staff can protect and possibly enhance well‐being for people with moderate to severe dementia. Abstract Introduction The effect of coronavirus (COVID‐19) on people living with dementia is potentially severe in its clinical impacts. More widely, for this vulnerable group, the social restrictions to limit the spread of infection may be emotionally and psychologically damaging. Aim To explore the impact of restrictions on well‐being for people with moderate to severe dementia in acute mental health hospital care. Method “Dementia Care Mapping” was the observational tool used to determine well‐ or ill‐being. Observations were undertaken in two mental health hospital wards during a time of restrictions and the use of personal protective equipment. Results We report levels of well‐being that are higher than might be expected alongside a change in the focus of psychological care delivered through mental health nursing interventions aimed at enhancing well‐being. Discussion—We postulate that mental health nurses faced with an unprecedented challenge respond by changing practice to mitigate for infection prevention measures and to compensate for family absence. Implications for practice We suggest that the desirable enhancing actions by nursing staff which raise well‐being in these hospital settings are readily transferable to other settings that are aiming to maintain well‐being but also practising under COVID‐19 restrictions.
FIBexDB: A New Online Transcriptome Platform to Analyze Development of Plant Cellulosic Fibers.

Plant fibers constitute a major part of renewable biomass and are a valuable resource for various industries, composite material chemistry, and bioconversion processes. Plant fibers are specialized long cells with thick cell walls that are a convenient model for investigating fundamental issues such as individual cell biogenesis, cell wall formation, and cell specialization. Plant fibers usually accumulate secondary cell walls, which contain lignin, cellulose, and hemicelluloses like xylan, and are laid over thin primary cell walls.
Cell surface nucleolin as active bait for nanomedicine in cancer therapy: a promising option

Conventional chemotherapy used against cancer is mostly limited due to their non-targeted nature, affecting normal tissue and causing undesirable toxic effects to the affected tissue. With the aim of improving these treatments both therapeutically and in terms of their safety, numerous studies are currently being carried out using nanoparticles (NPs) as a vector combining tumor targeting and carrying therapeutic tools. In this context, it appears that nucleolin, a molecule over-expressed on the surface of tumor cells, is an interesting therapeutic target. Several ligands, antagonists of nucleolin of various origins, such as AS1411, the F3 peptide and the multivalent pseudopeptide N6L have been developed and studied as therapeutic tools against cancer. Over the last ten years or so, numerous studies have been published demonstrating that these antagonists can be used as tumor targeting agents with NPs from various origins. Focusing on nucleolin ligands, the aim of this article is to review the literature recently published or under experimentation in our research team to evaluate the efficacy and future development of these tools as anti-tumor agents.
Increased VWF and Decreased ADAMTS-13 in COVID-19: Creating a Milieu for (Micro)Thrombosis

Abstract von Willebrand factor (VWF) is a large adhesive multimeric protein involved in hemostasis. The larger the size (or number of VWF multimers), the greater the functionality of the protein. A deficiency or defect of VWF can lead to von Willebrand disease (VWD) and cause bleeding. Conversely, an increase in VWF may create an environment that promotes thrombosis. ADAMS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), sometimes called VWF-cleaving protease, is primarily responsible for controlling the size of VWF. The most severe deficiency (<10% of normal levels) of ADAMTS-13 arises in thrombotic thrombocytopenic purpura, a condition characterized by the presence of ultralarge VWF and clinically resulting in enhanced risk of thrombosis. However, ADAMTS-13 deficiency may result from other pathological processes. Of relevance is the recent finding that COVID-19 (coronavirus disease 2019) is associated with both increased levels and activity of VWF as well as generally decreased (or occasionally normal) activity levels of ADAMTS-13. Thus, in COVID-19 there is an alteration in the VWF/ADAMTS-13 axis, most often described by increased VWF/ADAMTS-13 ratio (or reduced ADAMTS-13/VWF ratio). COVID-19 is also associated with high prothrombotic risk. Thus, the imbalance of VWF and ADAMTS-13 in COVID-19 may be providing a milieu that promotes (micro)thrombosis, in a clinical picture resembling a secondary thrombotic microangiopathy in some patients. This review therefore assesses the literature on VWF, ADAMTS-13, and COVID-19. Whenever reported in COVID-19, VWF has always been identified as raised (compared with normal reference ranges or control populations). Reports have included VWF level (i.e., VWF antigen) and in some cases one or more VWF “activity” (e.g., collagen binding; platelet glycoprotein Ib [GPIb] binding, using ristocetin cofactor or more modern versions including VWF:GPIbR [recombinant] and VWF:GPIbM [mutant]). Whenever reported, ADAMTS-13 has been reported as “normal” or reduced; however, it should be recognized that “normal” levels may still identify a relative reduction in individual cases. Some reports also discuss the raised VWF/ADAMTS-13 (or reduced ADAMTS-13/VWF) ratio, but very few provide actual numerical data.
X-ray Natural Circular Dichroism

Natural Circular Dichroism was only recently discovered in the x-ray range[1]. This effect stems from the interference terms which mix multipole transition moments of opposite parity: the Electric Dipole-Electric Quadrupole (E1.E2) and the Electric Dipole-Magnetic Dipole (E1.M1) exist only in structures with broken space inversion symmetry. The scalar E1.M1 term known to be responsible for Circular Dichroism at optical wavelengths is usually considered to be vanishingly small for core level spectroscopies. The E1.E2 interference term, on the contrary, can be large in the X-ray region, but it is a parity odd second rank tensor and therefore observable only in 13 non-centrosymmetric crystal classes. X-ray Natural Circular Dichroism has now been detected in the XANES region for several uniaxial and biaxial crystals. It can give access to the absolute configuration of chiral absorbing centers. On the other hand, Chiral-EXAFS, i.e. the analog of Magnetic-EXAFS for Natural Circular Dichroism has also been measured recently using a uniaxial optically active crystal of paratellurite (TeO2). Chiral-EXAFS originates from symmetry allowed multiple scattering paths. In this presentation, we wish to report on recent advances in X-ray natural circular dichroism and its applications. Determination of absolute configuration is illustrated with measurements of both E1.E2 and E1.M1 terms in chiral alpha-Ni(H2O)6Â·SO4 single crystals. Manifestation of X-ray optical acitivity in magnetoelectric crystals will be illustrated with various dichroisms measured at the Fe K-edge in multiferroic GaFeO3 crystal. Finally, we will review briefly the perspectives open by our experiments.