bluuebunny/crossref_metadata_2025 huggingface dataset:
Decision support system for predicting metabolic risks in patients with comorbid non-alcoholic fatty liver disease and gallstone disease after cholecystectomy
Authors: Cherkashchenko N. A. , Livzan M. A. , Krolevets T. S. , Chebanenko E. V.
Published: December 2020

183 patients with non-alcoholic fatty liver disease (NAFLD) were included into the case control study. Objective. Development a medical decision support system to improve the prediction of metabolic risks in persons with comorbid NAFLD and gallstone disease (GD) after cholecystectomy. Materials and methods. The main group was represented by patients with NAFLD and GD (n = 88), of which 53 patients underwent cholecystectomy. The comparison group was represented by patients with NAFLD without GD (n = 95). A standard laboratory and instrumental examinations were performed, including elastometry to assess of the stage of liver fibrosis and assessment of the level of hormones leptin, its soluble receptor, adiponectin and insulin. Results. Patients suffering from GD and NAFLD had a symptom of dyspepsia and general weakness. High prevalence of type 2 diabetes (rs = 0.164; р ≤ 0.01) and сoronary heart disease (25.00 % versus 9.47 % in the comparison group; р ≤ 0.01), high level of LDL and GGT (rs = 0.228, р ≤ 0.01 and rs = 0.298, р ≤ 0.01) were found in patients with GD after cholecystectomy. The phenomenon of insulin and leptin resistance, high levels of adiponectin were detected in patients suffering from NAFLD and GD. Hyperleptinemia was observed in NAFLD patients with GD after cholecystectomy (H = 5.812, p ≤ 0.05, rs = 0.313, p ≤ 0.05). Cholecystectomy in patients suffering from GD and NAFLD was associated with the formation of progressive stages of liver fibrosis (rs = 0.366; р ≤ 0.01). Conclusion. We have developed a decision support system to assess of the possibility of cholecystectomy in patients with NAFLD and GD according to the level metabolic risk of cardiovascular diseases and NAFLD progression.
The Impacts of Government Policy on Covid-19 to Airlines Liability: A Case Study in Indonesia
Authors: Ratnawati Elfrida
Published: December 2020

The impact of Covid-19's impact on the air transportation sector, especially in Indonesia. This article will discuss the impact and responsibility of airlines on the policies adopted by the Indonesian government regarding the COVID-19 pandemic. This article uses a normative juridical legal approach, research based on literature or secondary material. Meanwhile, the data obtained through legal analysis and social phenomena that occur in society. The rules that must be obeyed by airlines require them to do flight restrictions and cancellations. As a consequence of the cancellation, the airline must return the funds to passengers who have purchased travel tickets and the airline cannot hide behind force majeure. As the party issuing policies, the Government must be able to see a balance in social life and provide appropriate legal protection. In addition, the Government may not issue policies that can lead to different interpretations of those who read the policies. These strict regulations are needed so that passenger rights can be realized which is the responsibility of the airline.
An Integrative and Modular Framework to Recapitulate Emergent Behavior in Cell Migration
Authors: Cuenca Marina B. , Canedo Lucía , Perez-Castro Carolina , Grecco Hernan E.
Published: December 2020

Cell migration has been a subject of study in a broad variety of biological systems, from morphogenetic events during development to cancer progression. In this work, we describe single-cell movement in a modular framework from which we simulate the collective behavior of glioblastoma cells, the most prevalent and malignant primary brain tumor. We used the U87 cell line, which can be grown as a monolayer or spatially closely packed and organized in 3D structures called spheroids. Our integrative model considers the most relevant mechanisms involved in cell migration: chemotaxis of attractant factor, mechanical interactions and random movement. The effect of each mechanism is integrated into the overall probability of the cells to move in a particular direction, in an automaton-like approach. Our simulations fit and reproduced the emergent behavior of the spheroids in a set of migration assays where single-cell trajectories were tracked. We also predicted the effect of migration inhibition on the colonies from simple experimental characterization of single treated cell tracks. The development of tools that allow complementing molecular knowledge in migratory cell behavior is relevant for understanding essential cellular processes, both physiological (such as organ formation, tissue regeneration among others) and pathological perspectives. Overall, this is a versatile tool that has been proven to predict individual and collective behavior in U87 cells, but that can be applied to a broad variety of scenarios.
Recent Progress in Developing Monolithic Perovskite/Si Tandem Solar Cells
Authors: Liu Na , Wang Lina , Xu Fan , Wu Jiafeng , Song Tinglu , Chen Qi
Published: December 2020

Monolithic perovskite/Silicon tandem solar cells have reached a certified efficiency of 29. 1% in recent years. In this review, we discuss material design for monolithic perovskite/Si tandem solar cells, with the focus on the top-cell development to improve their performance. Firstly, we introduce different types of transparent electrodes with high transmittance and low sheet-resistance used in tandem solar cells. We then discuss the development of the wide-bandgap perovskite absorber for top-cells, especially the strategies to obtain the perovskite layers with good efficiency and stability. In addition, as a special functional layer in tandem solar cells, the recombination layers play an important role in device performance, wherein different configurations are summarized. Furthermore, tandem device cost analysis is discussed. This review summarizes the progress of monolithic perovskite/Silicon tandem solar cells in a pragmatic perspective, which may promote the commercialization of this technology.
Interleukin-1 Receptor Modulation Using β-Substituted α-Amino-γ-Lactam Peptides From Solid-Phase Synthesis and Diversification
Authors: Geranurimi Azade , Cheng Colin W. H. , Quiniou Christiane , Côté France , Hou Xin , Lahaie Isabelle , Boudreault Amarilys , Chemtob Sylvain , Lubell William D.
Published: December 2020

As a key cytokine mediator of inflammation, interleukin-1β (IL-1β) binds to the IL-1 receptor (IL-1R) and activates various downstream signaling mediators, including NF-κB, which is required for immune vigilance and cellular protection. Toward the development of IL-1-targeting therapeutics which exhibit functional selectivity, the all-D-amino acid peptide 1 (101.10, H-D-Arg-D-Tyr-D-Thr-D-Val-D-Glu-D-Leu-D-Ala-NH2) was conceived as an allosteric IL-1R modulator that conserves NF-κB signaling while inhibiting other IL-1-activated pathways. Employing β-hydroxy-α-amino-γ-lactam (Hgl) stereoisomers to study the conformation about the Thr3 residue in 1, [(3R,4S)-Hgl3]-1 (2b), among all possible diastereomers, was found to exhibit identical in vitro and in vivo activity as the parent peptide and superior activity to the α-amino-γ-lactam (Agl) counterpart. Noting the relevance of the β-hydroxyl substituent and configuration for the activity of (3R,4S)-2b, fifteen different β-substituted-Agl3 analogs of 1 (e.g., 2c-q) have now been synthesized by a combination of solution- and solid-phase methods employing N-Fmoc-β-substituted-Agl3-Val-OH dipeptide building blocks. Introduction of a β-azido-Agl3 residue into the resin bound peptide and subsequent reduction and CuAAC chemistry gave access to a series of amine and triazole derivatives (e.g., 2h-q). β-Substituted-[Agl3]-1 analogs 2c-q exhibited generally similar circular dichroism (CD) spectra as that of Hgl analog 2b in water, presenting curve shapes indicative of β-turn structures. The relevance of the β-substituent was indicated in rodent models of preterm labor and retinopathy of prematurity (ROP), in which certain analogs inhibited preterm birth and vaso-obliteration, respectively, with activity similar to 1 and 2b. The β-substituted-[Agl3]-1 analogs exhibited functional selectivity on IL-1-induced signaling pathways. The described solid-phase method has provided discerning probes for exploring peptide structure-activity relationships and valuable leads for developing prototypes to treat inflammatory events leading to prematurity and retinopathy of prematurity, which are leading causes of infant morbidity and blindness respectively.
Targeting PAI-1 in Cardiovascular Disease: Structural Insights Into PAI-1 Functionality and Inhibition
Authors: Sillen Machteld , Declerck Paul J.
Published: December 2020

Plasminogen activator inhibitor-1 (PAI-1), a member of the serine protease inhibitor (serpin) superfamily with antiprotease activity, is the main physiological inhibitor of tissue-type (tPA) and urokinase-type (uPA) plasminogen activators (PAs). Apart from being crucially involved in fibrinolysis and wound healing, PAI-1 plays a pivotal role in various acute and chronic pathophysiological processes, including cardiovascular disease, tissue fibrosis, cancer, and age-related diseases. In the prospect of treating the broad range of PAI-1-related pathologies, many efforts have been devoted to developing PAI-1 inhibitors. The use of these inhibitors, including low molecular weight molecules, peptides, antibodies, and antibody fragments, in various animal disease models has provided ample evidence of their beneficial effectin vivoand moved forward some of these inhibitors in clinical trials. However, none of these inhibitors is currently approved for therapeutic use in humans, mainly due to selectivity and toxicity issues. Furthermore, the conformational plasticity of PAI-1, which is unique among serpins, poses a real challenge in the identification and development of PAI-1 inhibitors. This review will provide an overview of the structural insights into PAI-1 functionality and modulation thereof and will highlight diverse approaches to inhibit PAI-1 activity.
A Comparison of Frequency Domain Electro-Magnetometry, Electrical Resistivity Tomography and Borehole Temperatures to Assess the Presence of Ice in a Rock Glacier
Authors: Boaga Jacopo , Phillips Marcia , Noetzli Jeannette , Haberkorn Anna , Kenner Robert , Bast Alexander
Published: December 2020

Alpine permafrost is currently warming, leading to changes such as active layer deepening and talik formation. Frequency domain electro-magnetometry (FDEM) measurements were tested as a simple and efficient method to investigate ground characteristics along two transects on the ice-rich Schafberg rock glacier in the Eastern Swiss Alps. The results were compared with electrical resistivity tomography (ERT) and ground temperature data acquired simultaneously in boreholes. FDEM provides information on the electrical properties of the ground, allowing to investigate ground-ice distribution. Our device allowed measurements to a depth of around 7 m. In ice-rich permafrost, FDEM can provide an approximation of the active layer thickness, and ice-free zones within the permafrost such as intra-permafrost taliks can be identified. This rapidly applicable geophysical method can be used to monitor ground ice distribution easily and efficiently, making it an ideal complement to borehole temperature data, which only provide point information and are costly to install and maintain. At the Schafberg site the three methods FDEM, electrical resistivity tomography and borehole temperature measurements provided similar results, with regard to active layer thickness and the presence of unfrozen zones within the ice-rich permafrost.
Evidence That Baseline Levels of Low-Density Lipoproteins Cholesterol Affect the Clinical Response of Graves’ Ophthalmopathy to Parenteral Corticosteroids
Authors: Naselli Adriano , Moretti Diletta , Regalbuto Concetto , Arpi Maria Luisa , Lo Giudice Fabrizio , Frasca Francesco , Belfiore Antonino , Le Moli Rosario
Published: December 2020

Background

High dose intravenous glucocorticoid (ivGC) therapy is the first line treatment in moderate to severe Graves’ ophthalmopathy (GO) and is associated with a clinical response rate ranging from 50% to 80%. Recently, a positive correlation between total cholesterol and low-density lipoproteins cholesterol (LDLc) with GO presentation and activity has been described.

Objective

We aimed at evaluating whether, in patients with moderate to severe active GO treated with ivGC therapy, cholesterol, and LDLc could represent valuable predictive factors of medium-term GO outcome.

Methods

This single center retrospective study was conducted in a consecutive series of 87 patients undergone ivGC therapy because affected by moderate to severe active GO. Clinical outcome of GO was evaluated at week 6 (W6) and 12 (W12) in respect to baseline conditions (week 0) by the seven points CAS according to EUGOGO recommendations. Univariate analysis and binary logistic regression were performed for the outcome variable W12CAS.

Results

In patients with active GO, an early positive clinical response to ivGC therapy (as evaluated by CAS at 6W) was a strong determinant (OR=13) of the clinical outcome at week 12. Moreover, high levels of LDLc at baseline were positively associated with a reduction in the likelihood of being classified as improved at 12W. Patients with LDLc >193.6 mg/dl were very likely to respond negatively to ivGC therapy independently from the response at 6W. Based on these results, we propose a predictive decision-making model to be tested in future prospective studies.

Discussion

We found that, in patients with active GO, both an early clinical response to ivGC therapy and baseline LDLc levels are significant determinants of GO outcome (W12CAS). These data support the need of a cholesterol-lowering treatment before addressing these patients to ivGC therapy.
Contrasting Trends of Population Size Change for Two Eurasian Owlet Species—Athene brama and Glaucidium radiatum From South Asia Over the Late Quaternary
Authors: Natesh Meghana , Vinay K. L. , Ghosh Samriddha , Jayapal Rajah , Mukherjee Shomita , Vijay Nagarjun , Robin V. V.
Published: December 2020

Climatic oscillations over the Quaternary have had a lasting impact on species’ distribution, evolutionary history, and genetic composition. Many species show dramatic population size changes coinciding with the last glacial period. However, the extent and direction of change vary across biogeographic regions, species-habitat associations, and species traits. Here we use genomic data to assess population size changes over the late Quaternary using the Pairwise Sequential Markovian Coalescent (PSMC) approach in two Eurasian Owlet species—the Spotted Owlet, Athene brama, and the Jungle Owlet, Glaucidium radiatum. While Spotted Owlets are typically associated with open habitats, Jungle Owlets are found in deciduous forests and scrublands. We find that the effective population size for the Spotted Owlet increased after the Interglacial period till the Last Glacial Maxima and subsequently declined toward the Mid-Holocene. On the other hand, effective population size estimates for the Jungle Owlet increased gradually throughout this period. These observations are in line with climatic niche model-based predictions for range size change for both species from a previous study and suggest that habitat associations at the local scale are important in determining responses to past climatic and vegetational changes. The Spotted Owlet result also aligns well with the expectation of open habitat expansion during the arid Glacial Maxima, whereas for the Jungle Owlet the contrasting expectation does not hold. Therefore, assessing the impacts of glacial history on population trajectories of multiple species with different habitat associations is necessary to understand the impacts of past climate on South Asian taxa.
CRISPR Technology for Ocular Angiogenesis
Authors: Chung Sook Hyun , Sin Tzu-Ni , Ngo Taylor , Yiu Glenn
Published: December 2020

Among genome engineering tools, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based approaches have been widely adopted for translational studies due to their robustness, precision, and ease of use. When delivered to diseased tissues with a viral vector such as adeno-associated virus, direct genome editing can be efficiently achieved in vivo to treat different ophthalmic conditions. While CRISPR has been actively explored as a strategy for treating inherited retinal diseases, with the first human trial recently initiated, its applications for complex, multifactorial conditions such as ocular angiogenesis has been relatively limited. Currently, neovascular retinal diseases such as retinopathy of prematurity, proliferative diabetic retinopathy, and neovascular age-related macular degeneration, which together constitute the majority of blindness in developed countries, are managed with frequent and costly injections of anti-vascular endothelial growth factor (anti-VEGF) agents that are short-lived and burdensome for patients. By contrast, CRISPR technology has the potential to suppress angiogenesis permanently, with the added benefit of targeting intracellular signals or regulatory elements, cell-specific delivery, and multiplexing to disrupt different pro-angiogenic factors simultaneously. However, the prospect of permanently suppressing physiologic pathways, the unpredictability of gene editing efficacy, and concerns for off-target effects have limited enthusiasm for these approaches. Here, we review the evolution of gene therapy and advances in adapting CRISPR platforms to suppress retinal angiogenesis. We discuss different Cas9 orthologs, delivery strategies, and different genomic targets including VEGF, VEGF receptor, and HIF-1α, as well as the advantages and disadvantages of genome editing vs. conventional gene therapies for multifactorial disease processes as compared to inherited monogenic retinal disorders. Lastly, we describe barriers that must be overcome to enable effective adoption of CRISPR-based strategies for the management of ocular angiogenesis.
Pyramiding of High Grain Weight With Stripe Rust and Leaf Rust Resistance in Elite Indian Wheat Cultivar Using a Combination of Marker Assisted and Phenotypic Selection
Authors: Kaur Satinder , Kaur Jaspreet , Mavi G. S. , Dhillon Guriqbal Singh , Sharma Achla , Singh Rohtas , Devi Urmila , Chhuneja Parveen
Published: December 2020

Wheat (Triticum aestivum L.) is an important cereal crop globally as well as in India and yield improvement programs encounter a strong impediment from ever-evolving rust pathogens. Hence, durable rust resistance is always a priority trait for wheat breeders globally. Grain weight, represented as thousand grain weight (TGW), is the most important yield-contributing trait in wheat. In the present study high TGW has been transferred into two elite Indian wheat cultivars PBW343 and PBW550 from a high TGW genotype, Rye selection 111, selected from local germplasm. In the background of PBW343 and PBW550, an increase in TGW upto 27.34 and 18% was observed, respectively (with respect to recipient parents), through conventional backcross breeding with phenotypic selections in 3 years replicated RBD trials. Resistance to leaf rust and stripe rust has been incorporated in the high TGW version of PBW550 through marker assisted pyramiding of stripe rust resistance gene Yr15 using marker Xuhw302, and a pair of linked leaf rust and stripe rust resistance genes Lr57-Yr40 using marker Ta5DS-2754099_kasp23. Improved versions of PBW550 with increased TGW ranging from 45.0 to 46.2 g (up to a 9% increase) and stacked genes for stripe and leaf rust resistance have been developed. This study serves as proof of utilizing conventional breeding and phenotypic selection combined with modern marker assisted selection in improvement of important wheat cultivars as a symbiont of conventional and moderan techniques.
Extratubular Polymerized Uromodulin Induces Leukocyte Recruitment and Inflammation In Vivo
Authors: Immler Roland , Lange-Sperandio Bärbel , Steffen Tobias , Beck Heike , Rohwedder Ina , Roth Jonas , Napoli Matteo , Hupel Georg , Pfister Frederik , Popper Bastian , Uhl Bernd , Mannell Hanna , Reichel Christoph A. , Vielhauer Volker , Scherberich Jürgen , Sperandio Markus , Pruenster Monika
Published: December 2020

Uromodulin (UMOD) is produced and secreted by tubular epithelial cells. Secreted UMOD polymerizes (pUMOD) in the tubular lumen, where it regulates salt transport and protects the kidney from bacteria and stone formation. Under various pathological conditions, pUMOD accumulates within the tubular lumen and reaches extratubular sites where it may interact with renal interstitial cells. Here, we investigated the potential of extratubular pUMOD to act as a damage associated molecular pattern (DAMP) molecule thereby creating local inflammation. We found that intrascrotal and intraperitoneal injection of pUMOD induced leukocyte recruitmentin vivoand led to TNF-α secretion by F4/80 positive macrophages. Additionally, pUMOD directly affected vascular permeability and increased neutrophil extravasation independent of macrophage-released TNF-α. Interestingly, pUMOD displayed no chemotactic properties on neutrophils, did not directly activate β2 integrins and did not upregulate adhesion molecules on endothelial cells. In obstructed neonatal murine kidneys, we observed extratubular UMOD accumulation in the renal interstitium with tubular atrophy and leukocyte infiltrates. Finally, we found extratubular UMOD deposits associated with peritubular leukocyte infiltration in kidneys from patients with inflammatory kidney diseases. Taken together, we identified extratubular pUMOD as a strong inducer of leukocyte recruitment, underlining its critical role in mounting an inflammatory response in various kidneys pathologies.
Experimental Nanovaccine Offers Protection Against Repeat Exposures to Trypanosoma cruzi Through Activation of Polyfunctional T Cell Response
Authors: Chowdhury Imran H. , Lokugamage Nandadeva , Garg Nisha Jain
Published: December 2020

A parasitic protozoan Trypanosoma cruzi (T. cruzi) is the etiologic agent of Chagas disease. Previously, we have identified T. cruzi antigens TcG2 and TcG4 as potential vaccine candidates, cloned in eukaryotic expression vector pCDNA3.1 (referred as p2/4) and tested their ability to elicit protection from T. cruzi infection. In the present study, we subcloned the two antigens in a nanoplasmid that is optimized for delivery, antigen expression, and regulatory compliance standards, and evaluated the nanovaccine (referred as nano2/4) for prophylactic protection against repeat T. cruzi infections. For this, C57BL/6 mice were immunized with two doses of p2/4 or nano2/4 at 21 days interval, challenged with T. cruzi 21 days after 2nd immunization, and euthanized at 10- and 21-days post-infection (pi) corresponding to parasite dissemination and replication phase, respectively. Some mice were re-challenged 21 days pi and monitored at 7 days after re-infection. Without the help of a vaccine, T. cruzi elicited delayed and sub-par T cell activation and low levels of effector molecules that failed to control tissue dissemination and replication of the parasite and provided no protection against repeat challenge infection. The nano2/4 was most effective in eliciting an early activation and production of IFN-γ by CD4+T effector/effector memory (TEM) cells and cytolytic perforin (PFN) and granzyme B (GZB) molecules by CD4+ and CD8+ TEM subsets at 10 days pi that was followed by robust expansion of CD4+ and CD8+ TEM and TCM cells with further increase in IFN-γ production at 21 days pi. Consequently, nano2/4-immunized mice exhibited potent control of parasite dissemination at 10 days pi, and tissue parasite burden and tissue inflammatory infiltrate and necrosis were barely detectable at 21 days pi. Furthermore, nano2/4-immunized mice responded to re-challenge infection with high levels of effector molecules production by CD4+ and CD8+ TEM subpopulations that offered even better control of tissue parasite burden than was observed after 1st infection. In comparison, non-vaccinated/infected mice exhibited clinical features of sickness and 59% mortality within 7 days after re-infection. In conclusion, we show that delivery of TcG2 and TcG4 in nanoplasmid offers excellent, protective T cell immunity against repeat T. cruzi infections.
Fatal Rhinofacial Mycosis Due to Aspergillus nomiae: Case Report and Review of Published Literature
Authors: Zhou Ya Bin , Li Dong Ming , Houbraken Jos , Sun Ting Ting , de Hoog G. Sybren
Published: December 2020

Background

A 73-year-old female suffering from acute myeloid leukemia presented with progressive rhinofacial mycosis. Suspecting it to be mucormycosis, the antifungal amphotericin B (AMB) was administered empirically, but the patient did not respond as planned. The fungus was then isolated from the biopsied tissue and morphologically identified as a species of Aspergillus. Necrosis progressed and she died of cerebral hemorrhage. Since Aspergillus flavus is susceptible to AMB, and several other Aspergillus species can be misidentified as A. flavus, the observed resistance necessitated a re-examination of the fungal isolate.

Methods

The fungal strain was re-isolated and re-examined morphologically. Additionally, genomic DNA was extracted from the fungus and sequences were obtained from three genomic regions [the rDNA internal transcribed spacer (ITS) region, and portions of the β-tubulin and calmodulin genes] to more accurately identify this Aspergillus strain. Its antifungal susceptibility was assessed using multiple compounds and our findings were compared with literature data.

Results

The fungal culture again yielded an Aspergillus isolate morphologically identical to A. flavus. Molecular analyses, however, revealed the strain to be A. nomiae, a close relative of A. flavus in section Flavi, and it exhibited resistance to AMB. Reviewing the literature, only five other cases of A. nomiae infection in humans have been reported worldwide.

Conclusion and Clinical Importance

The rhinofacial mycosis of the patient was actually due to A. nomiae. The initial misidentification of the fungus, coupled with its resistance to AMB, could be the reason treatment did not help the patient. We postulate that clinical A. nomiae infections may be underreported and that accurate and speedy pathogen identification is important so that an effective antifungal regimen can be administered.
Cultivation-Independent Analysis of the Bacterial Community Associated With the Calcareous Sponge Clathrina clathrus and Isolation of Poriferisphaera corsica Gen. Nov., Sp. Nov., Belonging to the Barely Studied Class Phycisphaerae in the Phylum Planctomycetes
Authors: Kallscheuer Nicolai , Wiegand Sandra , Kohn Timo , Boedeker Christian , Jeske Olga , Rast Patrick , Müller Ralph-Walter , Brümmer Franz , Heuer Anja , Jetten Mike S. M. , Rohde Manfred , Jogler Mareike , Jogler Christian
Published: December 2020

Marine ecosystems serve as global carbon sinks and nutrient source or breeding ground for aquatic animals. Sponges are ancient parts of these important ecosystems and can be found in caves, the deep-sea, clear waters, or more turbid environments. Here, we studied the bacterial community composition of the calcareous sponge Clathrina clathrus sampled close to the island Corsica in the Mediterranean Sea with an emphasis on planctomycetes. We show that the phylum Planctomycetes accounts for 9% of the C. clathrus-associated bacterial community, a 5-fold enrichment compared to the surrounding seawater. Indeed, the use of C. clathrus as a yet untapped source of novel planctomycetal strains led to the isolation of strain KS4T. The strain represents a novel genus and species within the class Phycisphaerae in the phylum Planctomycetes and displays interesting cell biological features, such as formation of outer membrane vesicles and an unexpected mode of cell division.
Development of a Directly Visualized Recombinase Polymerase Amplification–SYBR Green I Method for the Rapid Detection of African Swine Fever Virus
Authors: Zhang Shuai , Sun Aijun , Wan Bo , Du Yongkun , Wu Yanan , Zhang Angke , Jiang Dawei , Ji Pengchao , Wei Zhanyong , Zhuang Guoqing , Zhang Gaiping
Published: December 2020

African swine fever (ASF) is a lethal disease in swine caused by etiologic African swine fever virus (ASFV). The global spread of ASFV has resulted in huge economic losses globally. In the absence of effective vaccines or drugs, pathogen surveillance has been the most important first-line intervention to prevent ASF outbreaks. Among numerous diagnostic methods, recombinase polymerase amplification (RPA)-based detection is capable of producing sensitive and specific results without relying on the use of expensive instruments. However, currently used gene-specific, probe-based RPA for ASFV detection is expensive and time-consuming. To improve the efficiency of ASFV surveillance, a novel directly visualized SYBR Green I-staining RPA (RPAS) method was developed to detect the ASFV genome. SYBR Green I was added to the amplified RPA products for direct visualization by the naked eye. The sensitivity and specificity of this method were confirmed using standard plasmid and inactivated field samples. This method was shown to be highly specific with a detection limit of 103 copies/μl of ASFV in 15 min at 35°C without any cross-reactions with other important porcine viruses selected. In summary, this method enables direct sample visualization with reproducible results for ASFV detection and hence has the potential to be used as a robust tool for ASF prevention and control.
Will We Ever Have Conscious Machines?
Authors: Krauss Patrick , Maier Andreas
Published: December 2020

The question of whether artificial beings or machines could become self-aware or conscious has been a philosophical question for centuries. The main problem is that self-awareness cannot be observed from an outside perspective and the distinction of being really self-aware or merely a clever imitation cannot be answered without access to knowledge about the mechanism's inner workings. We investigate common machine learning approaches with respect to their potential ability to become self-aware. We realize that many important algorithmic steps toward machines with a core consciousness have already been taken.
Critical Issues and Imminent Challenges in the Use of sEMG in Return-To-Work Rehabilitation of Patients Affected by Neurological Disorders in the Epoch of Human–Robot Collaborative Technologies
Authors: Ranavolo Alberto , Serrao Mariano , Draicchio Francesco
Published: December 2020

Patients affected by neurological pathologies with motor disorders when they are of working age have to cope with problems related to employability, difficulties in working, and premature work interruption. It has been demonstrated that suitable job accommodation plans play a beneficial role in the overall quality of life of pathological subjects. A well-designed return-to-work program should consider several recent innovations in the clinical and ergonomic fields. One of the instrument-based methods used to monitor the effectiveness of ergonomic interventions is surface electromyography (sEMG), a multi-channel, non-invasive, wireless, wearable tool, which allows in-depth analysis of motor coordination mechanisms. Although the scientific literature in this field is extensive, its use remains significantly underexploited and the state-of-the-art technology lags expectations. This is mainly attributable to technical and methodological (electrode-skin impedance, noise, electrode location, size, configuration and distance, presence of crosstalk signals, comfort issues, selection of appropriate sensor setup, sEMG amplitude normalization, definition of correct sEMG-related outcomes and normative data) and cultural limitations. The technical and methodological problems are being resolved or minimized also thanks to the possibility of using reference books and tutorials. Cultural limitations are identified in the traditional use of qualitative approaches at the expense of quantitative measurement-based monitoring methods to design and assess ergonomic interventions and train operators. To bridge the gap between the return-to-work rehabilitation and other disciplines, several teaching courses, accompanied by further electrodes and instrumentations development, should be designed at all Bachelor, Master and PhD of Science levels to enhance the best skills available among physiotherapists, occupational health and safety technicians and ergonomists.
Case Report: 18F-MK6240 Tau Positron Emission Tomography Pattern Resembling Chronic Traumatic Encephalopathy in a Retired Australian Rules Football Player
Authors: Krishnadas Natasha , Doré Vincent , Lamb Fiona , Groot Colin , McCrory Paul , Guzman Rodney , Mulligan Rachel , Huang Kun , O'Donnell Meaghan , Ponsford Jennie , Hopwood Malcolm , Villemagne Victor L. , Rowe Christopher C.
Published: December 2020

Introduction: It remains unclear if tau imaging may assist diagnosis of chronic traumatic encephalopathy (CTE). Flortaucipir PET has shown superior frontal with medial temporal tau binding consistent with the provisional neuropathological criteria for mid-stage CTE in group-level analyses of retired symptomatic NFL players and in one individual with pathologically confirmed CTE. 18F-MK6240 is a new PET ligand that has high affinity for tau. We present the case of a 63-year-old cognitively impaired, former Australian rules football player with distinct superior frontal and medial temporal 18F-MK6240 binding and show it to be significantly different to the pattern seen in prodromal Alzheimer's disease (AD).

Findings: The participant was recruited for a study of amyloid-β and tau several decades after traumatic brain injury. He had multiple concussions during his football career but no cognitive complaints at retirement. A thalamic stroke in his mid 50s left stable mild cognitive deficits but family members reported further short-term memory, behavioral, and personality decline preceding the study. Imaging showed extensive small vessel disease on MRI, a moderate burden of amyloid-β plaques, and 18F-MK6240 binding in bilateral superior frontal and medial temporal cortices. Voxel-wise analysis demonstrated that the frontally predominant pattern of the participant was significantly different to the posterior temporo-parietal predominant pattern of prodromal AD.

Conclusion: Although lacking neuropathological examination to distinguish CTE from a variant of AD, the clear demonstration of a CTE-like tau pattern in a single at-risk individual suggests further research on the potential of 18F-MK6240 PET for identifying CTE is warranted.
Role of Sirtuins in Modulating Neurodegeneration of the Enteric Nervous System and Central Nervous System
Authors: Chandramowlishwaran Pavithra , Vijay Anitha , Abraham Daniel , Li Ge , Mwangi Simon Musyoka , Srinivasan Shanthi
Published: December 2020

Neurodegeneration of the central and enteric nervous systems is a common feature of aging and aging-related diseases, and is accelerated in individuals with metabolic dysfunction including obesity and diabetes. The molecular mechanisms of neurodegeneration in both the CNS and ENS are overlapping. Sirtuins are an important family of histone deacetylases that are important for genome stability, cellular response to stress, and nutrient and hormone sensing. They are activated by calorie restriction (CR) and by the coenzyme, nicotinamide adenine dinucleotide (NAD+). Sirtuins, specifically the nuclear SIRT1 and mitochondrial SIRT3, have been shown to have predominantly neuroprotective roles in the CNS while the cytoplasmic sirtuin, SIRT2 is largely associated with neurodegeneration. A systematic study of sirtuins in the ENS and their effect on enteric neuronal growth and survival has not been conducted. Recent studies, however, also link sirtuins with important hormones such as leptin, ghrelin, melatonin, and serotonin which influence many important processes including satiety, mood, circadian rhythm, and gut homeostasis. In this review, we address emerging roles of sirtuins in modulating the metabolic challenges from aging, obesity, and diabetes that lead to neurodegeneration in the ENS and CNS. We also highlight a novel role for sirtuins along the microbiota-gut-brain axis in modulating neurodegeneration.
Transcriptome Analysis of Ovarian and Uterine Clear Cell Malignancies
Authors: Alldredge Jill , Randall Leslie , De Robles Gabriela , Agrawal Anshu , Mercola Dan , Liu Marisa , Randhawa Pavneet , Edwards Robert , McClelland Michael , Rahmatpanah Farah
Published: December 2020

Purpose

Ovarian and uterine clear cell carcinomas (CCCs) are rare but associated with poor prognosis. This study explored RNA transcription patterns characteristic of these tumors.

Experimental Design

RNA sequencing (RNA-seq) of 11 ovarian CCCs and five uterine CCCs was performed and compared to publicly available data from high grade serous ovarian cancers (HGSOCs). Ingenuity Pathway Analyses were performed. CIBERSORT analyses estimated relative fractions of 22 immune cell types in each RNA-seq sample. Sequencing data was correlated with PD-L1 immunohistochemical expression.

Results

RNA-seq revealed 1,613 downregulated and 1,212 upregulated genes (corrected p < 0.05, |FC |≥10) in ovarian CCC versus HGSOC. Two subgroups were identified in the ovarian CCC, characterized by ethnicity and expression differences in ARID1A. There were 3,252 differentially expressed genes between PD-L1+/− ovarian CCCs, revealing immune response, cell death, and DNA repair networks, negatively correlated with PD-L1 expression, whereas cellular proliferation networks positively correlated with expression. In clear cell ovarian versus clear cell uterine cancer, 1,607 genes were significantly upregulated, and 109 genes were significantly downregulated (corrected p < 0.05, |FC|≥10). Comparative pathway analysis of late and early stage ovarian CCCs revealed unique metabolic and PTEN pathways, whereas uterine CCCs had unique Wnt/Ca+, estrogen receptor, and CCR5 signaling. CIBERSORT analysis revealed that activated mast cells and regulatory T cell populations were relatively enriched in uterine CCCs. The PD-L1+ ovarian CCCs had enriched resting NK cells and memory B cell populations, while PD-L1− had enriched CD8 T-cells, monocytes, eosinophils, and activated dendritic cells.

Conclusions

Unique transcriptional expression profiles distinguish clear cell uterine and ovarian cancers from each other and from other more common histologic subtypes. These insights may aid in devising novel therapeutics.
The Role of Prebiotics and Probiotics in Prevention of Allergic Diseases in Infants
Authors: Sestito Simona , D'Auria Enza , Baldassarre Maria Elisabetta , Salvatore Silvia , Tallarico Valeria , Stefanelli Ettore , Tarsitano Flora , Concolino Daniela , Pensabene Licia
Published: December 2020

Allergic diseases have been linked to genetic and/or environmental factors, such as antibiotic use, westernized high fat and low fiber diet, which lead to early intestinal dysbiosis, and account for the rise in allergy prevalence, especially in western countries. Allergic diseases have shown reduced microbial diversity, including fewer lactobacilli and bifidobacteria, within the neonatal microbiota, before the onset of atopic diseases. Raised interest in microbiota manipulating strategies to restore the microbial balance for atopic disease prevention, through prebiotics, probiotics, or synbiotics supplementation, has been reported. We reviewed and discussed the role of prebiotics and/or probiotics supplementation for allergy prevention in infants. We searched PubMed and the Cochrane Database using keywords relating to “allergy” OR “allergic disorders,” “prevention” AND “prebiotics” OR “probiotics” OR “synbiotics.” We limited our evaluation to papers of English language including children aged 0–2 years old. Different products or strains used, different period of intervention, duration of supplementation, has hampered the draw of definitive conclusions on the clinical impact of probiotics and/or prebiotics for prevention of allergic diseases in infants, except for atopic dermatitis in infants at high-risk. This preventive effect on eczema in high-risk infants is supported by clear evidence for probiotics but only moderate evidence for prebiotic supplementation. However, the optimal prebiotic or strain of probiotic, dose, duration, and timing of intervention remains uncertain. Particularly, a combined pre- and post-natal intervention appeared of stronger benefit, although the definition of the optimal intervention starting time during gestation, the timing, and duration in the post-natal period, as well as the best target population, are still an unmet need.
Role of Dietary Amino Acids and Nutrient Sensing System in Pregnancy Associated Disorders
Authors: Hussain Tarique , Tan Bie , Murtaza Ghulam , Metwally Elsayed , Yang Huansheng , Kalhoro Muhammad Saleem , Kalhoro Dildar Hussain , Chughtai Muhammad Ismail , Yin Yulong
Published: December 2020

Defective implantation is related to pregnancy-associated disorders such as spontaneous miscarriage, intrauterine fetal growth restriction and others. Several factors proclaimed to be involved such as physiological, nutritional, environmental and managemental that leads to cause oxidative stress. Overloading of free radicals promotes oxidative stress, and the internal body system could not combat its ability to encounter the damaging effects and subsequently leading to pregnancy-related disorders. During pregnancy, essential amino acids display important role for optimum fetal growth and other necessary functions for continuing fruitful pregnancy. In this context, dietary amino acids have received much attention regarding the nutritional concerns during pregnancy. Arginine, glutamine, tryptophan and taurine play a crucial role in fetal growth, development and survival while ornithine and proline are important players for the regulation of gene expression, protein synthesis and angiogenesis. Moreover, amino acids also stimulate the mammalian target of rapamycin (mTOR) signaling pathway which plays a central role in the synthesis of proteins in placenta, uterus and fetus. This review article explores the significances of dietary amino acids in pregnancy development, regulation of nutrient-sensing pathways such as mTOR, peroxisome proliferator-activated receptors (PPARs), insulin/insulin-like growth factor signaling pathway (IIS) and 5′ adenosine monophosphate-activated protein kinase (AMPK) which exhibit important role in reproduction and its related problems. In addition, the antioxidant function of dietary amino acids against oxidative stress triggering pregnancy disorders and their possible outcomes will also be enlightened. Dietary supplementation of amino acids during pregnancy could help mitigate reproductive disorders and thereby improving fertility in animals as well as humans.
Genetics and Genomics Approaches for Diagnosis and Research Into Hereditary Anemias
Authors: Russo Roberta , Marra Roberta , Rosato Barbara Eleni , Iolascon Achille , Andolfo Immacolata
Published: December 2020

The hereditary anemias are a relatively heterogeneous set of disorders that can show wide clinical and genetic heterogeneity, which often hampers correct clinical diagnosis. The classical diagnostic workflow for these conditions generally used to start with analysis of the family and personal histories, followed by biochemical and morphological evaluations, and ending with genetic testing. However, the diagnostic framework has changed more recently, and genetic testing is now a suitable approach for differential diagnosis of these patients. There are several approaches to this genetic testing, the choice of which depends on phenotyping, genetic heterogeneity, and gene size. For patients who show complete phenotyping, single-gene testing remains recommended. However, genetic analysis now includes next-generation sequencing, which is generally based on custom-designed targeting panels and whole-exome sequencing. The use of next-generation sequencing also allows the identification of new causative genes, and of polygenic conditions and genetic factors that modify disease severity of hereditary anemias. In the research field, whole-genome sequencing is useful for the identification of non-coding causative mutations, which might account for the disruption of transcriptional factor occupancy sites andcis-regulatory elements. Moreover, advances in high-throughput sequencing techniques have now resulted in the identification of genome-wide profiling of the chromatin structures known as the topologically associating domains. These represent a recurrent disease mechanism that exposes genes to inappropriate regulatory elements, causing errors in gene expression. This review focuses on the challenges of diagnosis and research into hereditary anemias, with indications of both the advantages and disadvantages. Finally, we consider the future perspectives for the use of next-generation sequencing technologies in this era of precision medicine.
Autonomic Modulation for Cardiovascular Disease
Authors: Hadaya Joseph , Ardell Jeffrey L.
Published: December 2020

Dysfunction of the autonomic nervous system has been implicated in the pathogenesis of cardiovascular disease, including congestive heart failure and cardiac arrhythmias. Despite advances in the medical and surgical management of these entities, progression of disease persists as does the risk for sudden cardiac death. With improved knowledge of the dynamic relationships between the nervous system and heart, neuromodulatory techniques such as cardiac sympathetic denervation and vagal nerve stimulation (VNS) have emerged as possible therapeutic approaches for the management of these disorders. In this review, we present the structure and function of the cardiac nervous system and the remodeling that occurs in disease states, emphasizing the concept of increased sympathoexcitation and reduced parasympathetic tone. We review preclinical evidence for vagal nerve stimulation, and early results of clinical trials in the setting of congestive heart failure. Vagal nerve stimulation, and other neuromodulatory techniques, may improve the management of cardiovascular disorders, and warrant further study.