bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and Trends in Low Bone Density, Osteopenia and Osteoporosis in U.S. Adults With Non-Alcoholic Fatty Liver Disease, 2005–2014
Authors: Zhai Tianyu , Chen Qi , Xu Jing , Jia Xi , Xia Pu
Published: January 2022

Background & Aims

Non-alcoholic fatty liver disease (NAFLD) is suggested to be associated with bone mineral density (BMD) alterations; however, this has not been ascertained. The current study aimed to investigate the changes in BMD and the prevalence of osteopenia/osteoporosis in US adults with or without NAFLD and to evaluate their association.

Methods

The study was conducted based on data collected from the U.S. National Health and Nutrition Examination Survey (NHANES) during the period 2005–2014. A total of 13 837 and 6 177 participants aged > 20 years were eligible for conducting the Hepatic Steatosis Index (HSI) and the US Fatty Liver Index (USFLI) analysis, respectively.

Results

From 2005–2014, a downward trend in femoral neck BMD was observed in subjects with NAFLD aged ≥ 40. After adjustment for potential confounders, an upward shift occurred in the prevalence of osteopenia/osteoporosis at the femoral neck in adults aged ≥ 40, particularly in women ≥ 60 years old and men below the age of 60. Moreover, a negative association was found between BMD and NAFLD markers (USFLI, HSI), whereas NAFLD with advanced fibrosis was positively associated with the prevalence of spine fractures.

Conclusions

There was a trend toward lower BMD and higher prevalence of osteopenia/osteoporosis at the femoral neck in US adults with NAFLD aged ≥ 40 years during the period of 2005–2014. NAFLD with advanced fibrosis was positively associated with a higher risk of spine fracture. More research is required to fully investigate the mechanism and consequence of poor bone health in NAFLD patients and consider optimum management of osteopenia/osteoporosis for this population.
The NGS Magic Pudding: A Nanopore-Led Long-Read Genome Assembly for the Commercial Australian Freshwater Crayfish, Cherax destructor
Authors: Austin Christopher M. , Croft Laurence J. , Grandjean Frederic , Gan Han Ming
Published: January 2022

Cherax destructor, the yabby, is an iconic Australian freshwater crayfish species, which, similar to other major invertebrate groups, is grossly under-represented in genomic databases. The yabby is also the principal commercial freshwater crustacean species in Australia subject to explotation via inland fisheries and aquaculture. To address the genomics knowledge gap for this species and explore cost effective and efficient methods for genome assembly, we generated 106.8 gb of Nanopore reads and performed a long-read only assembly of the Cherax destructor genome. On a mini-server configured with an ultra-fast swap space, the de novo assembly took 131 h (∼5.5 days). Genome polishing with 126.3 gb of PCR-Free Illumina reads generated an assembled genome size of 3.3 gb (74.6% BUSCO completeness) with a contig N50 of 80,900 bp, making it the most contiguous for freshwater crayfish genome assemblies. We found an unusually large number of cellulase genes within the yabby genome which is relevant to understanding the nutritional biology, commercial feed development, and ecological role of this species and crayfish more generally. These resources will be useful for genomic research on freshwater crayfish and our methods for rapid and super-efficient genome assembly will have wide application.
Analysis of Placental Arteriovenous Formation Reveals New Insights Into Embryos With Congenital Heart Defects
Authors: Kalisch-Smith Jacinta I. , Morris Emily C. , Strevens Mary A. A. , Redpath Andia N. , Klaourakis Kostantinos , Szumska Dorota , Outhwaite Jennifer E. , Sun Xin , Vieira Joaquim Miguel , Smart Nicola , De Val Sarah , Riley Paul R. , Sparrow Duncan B.
Published: January 2022

The placental vasculature provides the developing embryo with a circulation to deliver nutrients and dispose of waste products. However, in the mouse, the vascular components of the chorio-allantoic placenta have been largely unexplored due to a lack of well-validated molecular markers. This is required to study how these blood vessels form in development and how they are impacted by embryonic or maternal defects. Here, we employed marker analysis to characterize the arterial/arteriole and venous/venule endothelial cells (ECs) during normal mouse placental development. We reveal that placental ECs are potentially unique compared with their embryonic counterparts. We assessed embryonic markers of arterial ECs, venous ECs, and their capillary counterparts—arteriole and venule ECs. Major findings were that the arterial tree exclusively expressed Dll4, and venous vascular tree could be distinguished from the arterial tree by Endomucin (EMCN) expression levels. The relationship between the placenta and developing heart is particularly interesting. These two organs form at the same stages of embryogenesis and are well known to affect each other’s growth trajectories. However, although there are many mouse models of heart defects, these are not routinely assessed for placental defects. Using these new placental vascular markers, we reveal that mouse embryos from one model of heart defects, caused by maternal iron deficiency, also have defects in the formation of the placental arterial, but not the venous, vascular tree. Defects to the embryonic cardiovascular system can therefore have a significant impact on blood flow delivery and expansion of the placental arterial tree.
Screening and Identification of the First Non-CRISPR/Cas9-Treated Chinese Miniature Pig With Defective Porcine Endogenous Retrovirus pol Genes
Authors: Ma Yuyuan , Jia Junting , Fan Rui , Lu Ying , Zhao Xiong , Zhong Yadi , Yang Jierong , Ma Limin , Wang Yanlin , Lv Maomin , Yang Haiyuan , Mou Lisha , Dai Yifan , Feng Shutang , Zhang Jingang
Published: January 2022

Pig to human xenotransplantation is considered to be a possible approach to alleviate the shortage of human allografts. Porcine endogenous retrovirus (PERV) is the most significant pathogen in xenotransplantation. We screened for pigs that consistently did not transmit human-tropic replication competent PERVs (HTRC PERVs), namely, non-transmitting pigs. Then, we conducted whole-genome resequencing and full-length transcriptome sequencing to further investigate the sequence characteristics of one non-transmitting pig. Using in vitro transmission assays, we found 5 (out of 105) pigs of the Chinese Wuzhishan minipig inbred line that did not transmit PERV to human cells, i.e., non-transmitting pigs. Whole-genome resequencing and full-length transcriptome sequencing of one non-transmitting pig showed that all of the pol genes were defective at both the genome and transcript levels. We speculate that the defective PERV pol genes in this pig might be attributable to the long-term inbreeding process. This discovery is promising for the development of a strain of highly homozygous and genetically stable pigs with defective PERV pol genes as a source animal species for xenotransplantation.
Interkit Reproducibility of the Indirect Immunofluorescence Assay on HEp-2 Cells Depends on the Immunofluorescence Reactivity Intensity and Pattern
Authors: Silva Mônica Jesus , Dellavance Alessandra , Baldo Danielle Cristiane , Rodrigues Silvia Helena , Grecco Marcelle , Prado Monica Simon , Agustinelli Renan , Andrade Luís Eduardo Coelho
Published: January 2022

Introduction

The indirect immunofluorescence assay on HEp-2 cells (HEp-2/IFA) is used worldwide for screening for autoantibodies to cellular antigens. Cell culture and fixation methods influence the cell distribution of autoantigens and the preservation of epitopes. Therefore, discrepancy of results obtained using different HEp-2/IFA kits (interkit nonreproducibility) is a common phenomenon in the clinical laboratory routine.

Objective

This study evaluated the interkit nonreproducibility of HEp-2/IFA results using samples from patients with systemic autoimmune disease (SAD), nonautoimmune diseases (NAD), and healthy blood donors (HBD).

Methods

Serum from 275 SAD patients, 293 NAD patients, and 300 HBD were processed at 1:80 dilution using four HEp-2 kits according to the manufacturers’ instructions. Interkit reproducibility was determined for positive/negative results and patterns. The agreement of positive/negative results among kits for each sample was determined as the reactivity agreement score (RAS). The pattern reproducibility score (PRS) in each sample was calculated as a function of the number of kits showing equivalent patterns. Qualitative variables and ordinal variables were analyzed by the Chi-square and Mann-Whitney U tests, respectively.

Results

A total of 402 samples were nonreactive in all kits and were considered devoid of autoantibodies. Further analysis included the 466 reactive samples (238 SAD, 119 NAD, 109 HBD). Reactivity to the nucleus had the highest interkit reproducibility (RAS = 83.6), followed by the metaphase plate (RAS = 78.9), cytoplasm (RAS = 77.4), and nucleolus (RAS = 72.4). Interkit reproducibility was higher in SAD (RAS = 78.0) than in NAD (RAS = 70.6) and HBD (RAS = 71.3) groups. Samples with strong reactivity (++++/4 and +++/4) had higher interkit reproducibility than those with weak reactivity (+/4). In the SAD group, RAS for nuclear reactivity was 87.5% for strongly reactive samples as opposed to 4.4% for weakly reactive samples, and the same was observed for NAD and HBD samples. The most robust patterns were the centromere AC-3 (PRS = 78.4), multiple nuclear dots AC-6 (PRS = 73.6), nuclear coarse speckled AC-5 (PRS = 71.3), nuclear homogeneous AC-1 (PRS = 67.9), and the reticular cytoplasmic AC-21 (PRS = 68.6).

Conclusion

Interkit nonreproducibility in HEp-2/IFA is prevalent and occurs with the highest frequency with weakly reactive samples. International initiatives with the engagement of in vitro diagnostic industry are encouraged to promote the harmonization of the properties and performance of HEp-2/IFA commercial kits.
Donor-But Not Recipient-Derived Cells Produce Collagen-1 in Chronically Rejected Cardiac Allografts
Authors: Balam Saidou , Buchtler Simone , Winter Frederike , Schmidbauer Kathrin , Neumayer Sophia , Talke Yvonne , Renner Kerstin , Geissler Edward K. , Mack Matthias
Published: January 2022

Fibrosis is a prominent feature of chronic allograft rejection, caused by an excessive production of matrix proteins, including collagen-1. Several cell types produce collagen-1, including mesenchymal fibroblasts and cells of hematopoietic origin. Here, we sought to determine whether tissue-resident donor-derived cells or allograft-infiltrating recipient-derived cells are responsible for allograft fibrosis, and whether hematopoietic cells contribute to collagen production. A fully MHC-mismatched mouse heterotopic heart transplantation model was used, with transient depletion of CD4+ T cells to prevent acute rejection. Collagen-1 was selectively knocked out in recipients or donors. In addition, collagen-1 was specifically deleted in hematopoietic cells. Tissue-resident macrophages were depleted using anti-CSF1R antibody. Allograft fibrosis and inflammation were quantified 20 days post-transplantation. Selective collagen-1 knock-out in recipients or donors showed that tissue-resident cells from donor hearts, but not infiltrating recipient-derived cells, are responsible for production of collagen-1 in allografts. Cell-type-specific knock-out experiments showed that hematopoietic tissue-resident cells in donor hearts substantially contributed to graft fibrosis. Tissue resident macrophages, however, were not responsible for collagen-production, as their deletion worsened allograft fibrosis. Donor-derived cells including those of hematopoietic origin determine allograft fibrosis, making them attractive targets for organ preconditioning to improve long-term transplantation outcomes.
Neuroinflammation Associated With Inborn Errors of Immunity
Authors: Lindahl Hannes , Bryceson Yenan T.
Published: January 2022

The advent of high-throughput sequencing has facilitated genotype-phenotype correlations in congenital diseases. This has provided molecular diagnosis and benefited patient management but has also revealed substantial phenotypic heterogeneity. Although distinct neuroinflammatory diseases are scarce among the several thousands of established congenital diseases, elements of neuroinflammation are increasingly recognized in a substantial proportion of inborn errors of immunity, where it may even dominate the clinical picture at initial presentation. Although each disease entity is rare, they collectively can constitute a significant proportion of neuropediatric patients in tertiary care and may occasionally also explain adult neurology patients. We focus this review on the signs and symptoms of neuroinflammation that have been reported in association with established pathogenic variants in immune genes and suggest the following subdivision based on proposed underlying mechanisms: autoinflammatory disorders, tolerance defects, and immunodeficiency disorders. The large group of autoinflammatory disorders is further subdivided into IL-1β-mediated disorders, NF-κB dysregulation, type I interferonopathies, and hemophagocytic syndromes. We delineate emerging pathogenic themes underlying neuroinflammation in monogenic diseases and describe the breadth of the clinical spectrum to support decisions to screen for a genetic diagnosis and encourage further research on a neglected phenomenon.
Filling the Gaps in Antagonist CCR5 Binding, a Retrospective and Perspective Analysis
Authors: Amerzhanova Yerkezhan , Vangelista Luca
Published: January 2022

The large number of pathologies that position CCR5 as a central molecular determinant substantiates the studies aimed at understanding receptor-ligand interactions, as well as the development of compounds that efficiently block this receptor. This perspective focuses on CCR5 antagonism as the preferred landscape for therapeutic intervention, thus the receptor active site occupancy by known antagonists of different origins is overviewed. CCL5 is a natural agonist ligand for CCR5 and an extensively studied scaffold for CCR5 antagonists production through chemokine N-terminus modification. A retrospective 3D modeling analysis on recently developed CCL5 mutants and their contribution to enhanced anti-HIV-1 activity is reported here. These results allow us to prospect the development of conceptually novel amino acid substitutions outside the CCL5 N-terminus hotspot. CCR5 interaction improvement in regions distal to the chemokine N-terminus, as well as the stabilization of the chemokine hydrophobic core are strategies that influence binding affinity and stability beyond the agonist/antagonist dualism. Furthermore, the development of allosteric antagonists topologically remote from the orthosteric site (e.g., intracellular or membrane-embedded) is an intriguing new avenue in GPCR druggability and thus a conceivable novel direction for CCR5 blockade. Ultimately, the three-dimensional structure elucidation of the interaction between various ligands and CCR5 helps illuminate the active site occupancy and mechanism of action.
Rare Earth Based Magnesium Alloys—A Review on WE Series
Authors: Calado Lénia M. , Carmezim Maria J. , Montemor M. Fátima
Published: January 2022

Magnesium and magnesium alloys have attracted growing attention over the last decades as lightweight materials for a wide range of applications. In particular, WE series magnesium alloys have experienced growing interest over the last years due to their favourable mechanical properties at room and elevated temperatures. In addition, it has been reported that these rare earth-containing alloys possess superior corrosion resistance compared to other commonly used magnesium alloys, such as AZ series. This review aims at providing a concise overview of the research efforts made during recent years regarding the properties of WE series magnesium alloys (e.g., mechanical properties, corrosion behaviour), how these properties can be enhanced by controlling the microstructure of these materials, and the role of specific alloying elements that are used for the WE series. The widespread use of these materials has been limited, mainly due to their susceptibility to corrosion. Thus, in the present review, strong emphasis has been given to recent work studying the corrosion behaviour of the WE series alloys, and to protective strategies that can be employed to mitigate their degradation.
Bioinformatic Analyses of the Ferroptosis-Related lncRNAs Signature for Ovarian Cancer
Authors: Zheng Jianfeng , Guo Jialu , Wang Yahui , Zheng Yingling , Zhang Ke , Tong Jinyi
Published: January 2022

Both ferroptosis and lncRNAs are significant for ovarian cancer (OC). Whereas, the study of ferroptosis-related lncRNAs (FRLs) still few in ovarian cancer. We first constructed an FRL-signature for patients with OC in the study. A total of 548 FRLs were identified for univariate Cox regression analysis, and 21 FRLs with significant prognosis were identified. The prognostic characteristics of nine FRLs was constructed and validated, showing opposite prognosis in two subgroups based on risk scores. The multivariate Cox regression analysis and nomogram further verified the prognostic value of the risk model. By calculating ferroptosis score through ssGSEA, we found that patients with higher risk scores exhibited higher ferroptosis scores, and high ferroptosis score was a risk factor. There were 40 microenvironment cells with significant differences in the two groups, and the difference of Stromal score between the two groups was statistically significant. Six immune checkpoint genes were expressed at different levels in the two groups. In addition, five m6A regulators (FMR1, HNRNPC, METTL16, METTL3, and METTL5) were higher expressed in the low-risk group. GSEA revealed that the risk model was associated with tumor-related pathways and immune-associated pathway. We compared the sensitivity of chemotherapy drugs between the two risk groups. We also explored the co-expression, ceRNA relation, cis and trans interaction of ferroptosis-related genes and lncRNAs, providing a new idea for the regulatory mechanisms of FRLs. Moreover, the nine FRLs were selected for detecting their expression levels in OC cells and tissues.
Assessing Histology Structures by Ex Vivo MR Microscopy and Exploring the Link Between MRM-Derived Radiomic Features and Histopathology in Ovarian Cancer
Authors: Tardieu Marion , Lakhman Yulia , Khellaf Lakhdar , Cardoso Maida , Sgarbura Olivia , Colombo Pierre-Emmanuel , Crispin-Ortuzar Mireia , Sala Evis , Goze-Bac Christophe , Nougaret Stephanie
Published: January 2022

The value of MR radiomic features at a microscopic scale has not been explored in ovarian cancer. The objective of this study was to probe the associations of MR microscopy (MRM) images and MRM-derived radiomic maps with histopathology in high-grade serous ovarian cancer (HGSOC). Nine peritoneal implants from 9 patients with HGSOC were imaged ex vivo with MRM using a 9.4-T MR scanner. All MRM images and computed pixel-wise radiomics maps were correlated with the slice-matched stroma and tumor proportion maps derived from whole histopathologic slide images (WHSI) of corresponding peritoneal implants. Automated MRM-derived segmentation maps of tumor and stroma were constructed using holdout test data and validated against the histopathologic gold standard. Excellent correlation between MRM images and WHSI was observed (Dice index = 0.77). Entropy, correlation, difference entropy, and sum entropy radiomic features were positively associated with high stromal proportion (r = 0.97,0.88, 0.81, and 0.96 respectively, p < 0.05). MR signal intensity, energy, homogeneity, auto correlation, difference variance, and sum average were negatively associated with low stromal proportion (r = –0.91, –0.93, –0.94, –0.9, –0.89, –0.89, respectively, p < 0.05). Using the automated model, MRM predicted stromal proportion with an accuracy ranging from 61.4% to 71.9%. In this hypothesis-generating study, we showed that it is feasible to resolve histologic structures in HGSOC using ex vivo MRM at 9.4 T and radiomics.
Insulin-Like Growth Factor 2 mRNA Binding Protein 3 Promotes Cell Proliferation of Malignant Mesothelioma Cells by Downregulating p27Kip1
Authors: Endo Ihiro , Amatya Vishwa Jeet , Kushitani Kei , Kambara Takahiro , Nakagiri Tetsuya , Fujii Yutaro , Takeshima Yukio
Published: January 2022

Malignant mesothelioma is a tumor with a poor prognosis, mainly caused by asbestos exposure and with no adequate treatment yet. To develop future therapeutic targets, we analyzed the microarray dataset GSE 29370 of malignant mesothelioma and reactive mesothelial hyperplasia, downloaded from the Gene Expression Omnibus (GEO) database. We identified insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) as one of the significantly upregulated genes in malignant mesothelioma. IGF2BP3 functions as an oncoprotein in many human cancers; however, to our knowledge, this is the first study on the biological function of IGF2BP3 in malignant mesothelioma cells. The knockdown of IGF2BP3 in malignant mesothelioma cells resulted in the suppression of cell proliferation with an increase in the proportion of cells in the G1 phase of the cell cycle. Furthermore, knockdown of IGF2BP3 inhibited cell migration and invasion. We focused on the cell cycle assay to investigate the role of IGF2BP3 in cell proliferation in malignant mesothelioma. Among the various proteins involved in cell cycle regulation, the expression of p27 Kip1 (p27) increased significantly upon IGF2BP3 knockdown. Next, p27 siRNA was added to suppress the increased expression of p27. The results showed that p27 knockdown attenuated the effects of IGF2BP3 knockdown on cell proliferation and G1 phase arrest. In conclusion, we found that IGF2BP3 promotes cell proliferation, a critical step in tumorigenesis, by suppressing the expression of p27 in malignant mesothelioma.
Impact of Periosteal Branches and Septo-Cutaneous Perforators on Free Fibula Flap Outcome: A Retrospective Analysis of Computed Tomography Angiography Scans in Virtual Surgical Planning
Authors: Knitschke Michael , Baumgart Anna Katrin , Bäcker Christina , Adelung Christian , Roller Fritz , Schmermund Daniel , Böttger Sebastian , Streckbein Philipp , Howaldt Hans-Peter , Attia Sameh
Published: January 2022

Background

Virtual surgical planning (VSP) for jaw reconstruction with free fibula flap (FFF) became a routine procedure and requires computed tomography angiography (CTA) for preoperative evaluation of the lower limbs vascular system and the bone. The aim of the study was to assess whether the distribution and density of periosteal branches (PB) and septo-cutaneous perforators (SCP) of the fibular artery have an impact on flap success.

Method

This retrospective clinical study assessed preoperative CTA of the infra-popliteal vasculature and the small vessel system of 72 patients who underwent FFF surgery. Surgical outcome of flap transfer includes wound healing, subtotal, and total flap loss were matched with the segmental vascular supply.

Result

A total of 72 patients (28 females, 38.9 %; 44 males, 61.1 %) fulfilled the study inclusion criteria. The mean age was 58.5 (± 15.3 years). Stenoses of the lower limbs’ vessel (n = 14) were mostly detected in the fibular artery (n = 11). Flap success was recorded in n = 59 (82.0%), partial flap failure in n = 4 (5.5%) and total flap loss in n = 9 (12.5%). The study found a mean number (± SD) of 2.53 ± 1.60 PBs and 1.39 ± 1.03 SCPs of the FA at the donor-site. The proximal FFF segment of poly-segmental jaw reconstruction showed a higher rate of PB per flap segment than in the distal segments. Based on the total number of prepared segments (n = 121), 46.7% (n = 7) of mono-, 40.4% (n = 21) of bi-, and 31.5 % (n = 17) of tri-segmental fibula flaps were at least supplied by one PB in the success group. Overall, this corresponds to 37.2% (45 out of 121) of all successful FFF. For total flap loss (n = 14), a relative number of 42.9% (n = 6) of distinct supplied segments was recorded. Wound healing disorder of the donor site was not statistically significant influenced by the detected rate of SCP.

Conclusion

In general, a correlation between higher rates of PB and SCP and the flap success could not be statistically proved by the study sample. We conclude, that preoperative PB and SCP mapping based on routine CTA imaging is not suitable for prediction of flap outcome.
Synthesis, Characterization, and in vivo Evaluation of a Novel Potent Autotaxin-Inhibitor
Authors: Hunziker Daniel , Reinehr Sabrina , Palmhof Marina , Wagner Natalie , Biniasch Thomas , Stute Gesa , Mattei Patrizio , Schmitz Petra , DiGiorgio Patrick , Hert Jérôme , Rudolph Markus G. , Benz Joerg , Stihle Martine , Gsell Bernard , Müller Stephan , Gasser Rodolfo , Schonhoven Nina , Ullmer Christoph , Joachim Stephanie C.
Published: January 2022

The autotaxin-lysophosphatidic acid (ATX-LPA) signaling pathway plays a role in a variety of autoimmune diseases, such as rheumatoid arthritis or neurodegeneration. A link to the pathogenesis of glaucoma is suggested by an overactive ATX-LPA axis in aqueous humor samples of glaucoma patients. Analysis of such samples suggests that the ATX-LPA axis contributes to the fibrogenic activity and resistance to aqueous humor outflow through the trabecular meshwork. In order to inhibit or modulate this pathway, we developed a new series of ATX-inhibitors containing novel bicyclic and spirocyclic structural motifs. A potent lead compound (IC50 against ATX: 6 nM) with good in vivo PK, favorable in vitro property, and safety profile was generated. This compound leads to lowered LPA levels in vivo after oral administration. Hence, it was suitable for chronic oral treatment in two rodent models of glaucoma, the experimental autoimmune glaucoma (EAG) and the ischemia/reperfusion models. In the EAG model, rats were immunized with an optic nerve antigen homogenate, while controls received sodium chloride. Retinal ischemia/reperfusion (I/R) was induced by elevating the intraocular pressure (IOP) in one eye to 140 mmHg for 60 min, followed by reperfusion, while the other untreated eye served as control. Retinae and optic nerves were evaluated 28 days after EAG or 7 and 14 days after I/R induction. Oral treatment with the optimized ATX-inhibitor lead to reduced retinal ganglion cell (RGC) loss in both glaucoma models. In the optic nerve, the protective effect of ATX inhibition was less effective compared to the retina and only a trend to a weakened neurofilament distortion was detectable. Taken together, these results provide evidence that the dysregulation of the ATX-LPA axis in the aqueous humor of glaucoma patients, in addition to the postulated outflow impairment, might also contribute to RGC loss. The observation that ATX-inhibitor treatment in both glaucoma models did not result in significant IOP increases or decreases after oral treatment indicates that protection from RGC loss due to inhibition of the ATX-LPA axis is independent of an IOP lowering effect.
Salvia miltiorrhiza Bge. (Danshen) for Inflammatory Bowel Disease: Clinical Evidence and Network Pharmacology-Based Strategy for Developing Supplementary Medical Application
Authors: Zhang Siyuan , Luo Hua , Sun Shiyi , Zhang Yating , Ma Jiaqi , Lin Yuting , Yang Lin , Tan Dechao , Fu Chaomei , Zhong Zhangfeng , Wang Yitao
Published: January 2022

Inflammatory bowel disease (IBD) is a non-specific colorectal disease caused by multifaceted triggers. Although conventional treatments are effective in the management of IBD, high cost and frequent side effects limit their applications and have turned sufferers toward alternative and complementary approaches. Salvia miltiorrhiza Bge (Danshen) is an herbal medicine that reportedly alleviates the symptoms of IBD. A large body of research, including clinical trials in which Danshen-based products or botanical compounds were used, has unmasked its multiple mechanisms of action, but no review has focused on its efficacy as a treatment for IBD. Here, we discussed triggers of IBD, collected relevant clinical trials and analyzed experimental reports, in which bioactive compounds of Danshen attenuated rodent colitis in the management of intestinal integrity, gut microflora, cell death, immune conditions, cytokines, and free radicals. A network pharmacology approach was applied to describe sophisticated mechanisms in a holistic view. The safety of Danshen was also discussed. This review of evidence will help to better understand the potential benefits of Danshen for IBD treatment and provide insights for the development of innovative applications of Danshen.
Enhanced Measurement Accuracy for Nanostructures Using Hybrid Metrology
Authors: Hansen Poul-Erik , Johannsen Sabrina Rostgaard , Jensen Søren Alkærsig , Madsen Jonas Skovlund Møller
Published: January 2022

Light-matter interplay is widely used for analyzing the topology of surfaces on small scales for use in areas such as nanotechnology, nanoelectronics, photonics, and advanced materials. Conventional optical microscope imaging methods are limited in resolution to a value comparable to the wavelength, the so-called Abbe limit, and cannot be used to measure nano-sized structures. Scatterometry and Mueller ellipsometry are spectroscopic optical methods that can measure structures smaller than the wavelength. However, the relative uncertainties of the structure dimensions measured with scatterometry increase with decreasing structure size, and the industry is therefore replacing simple intensity based scatterometry with Mueller ellipsometry for the most demanding measurements. The accuracy of Mueller ellipsometry and scatterometry are closely related to the ability of the employed regression and regularization algorithms to extract the structural dimension. In this work, we demonstrate how the measurement accuracy on three-dimensional periodic structures may be increased by measuring the same periodic structure with multiple techniques and applying a χ2-regression method that finds the best solution based on the input from all the instruments. We furthermore report on a new and improved calibration method for Mueller ellipsometry and demonstrate how the Mueller matrix may be used to find the geometrical anisotropy of the structure.
Stability Analysis and Heterotic Studies in Maize (Zea mays L.) Inbreds to Develop Hybrids With Low Phytic Acid and High-Quality Protein
Authors: Lydia Pramitha J. , Joel John , Rajasekaran Ravikesavan , Uma D. , Vinothana Kumari , Balakrishnan Meenakumari , Sathyasheela K. R. V. , Muthurajan Raveendran , Hossain Firoz
Published: January 2022

Maize is a major staple crop with high value as food and feed in the poultry sector. Considering the overall nutritional value, maize-based diets comprise two major constraints, i.e., higher phytic acid (PA) and lack of tryptophan. To overcome these issues, a set of identified stable donors for low PA (lpa) and higher tryptophan were crossed in a line × tester fashion, and the hybrids obtained were evaluated at three locations with two replications. Among the inbreds for yield, UMI 1201 and UMI 1205 were the stable good combiners, and for PA, UMI 447 and LPA-2-285 were identified as efficient combiners across locations. Subsequently, 72 hybrids developed from these inbreds had a reduced phytate and higher tryptophan compared with checks having alterations in their yield levels. From Additive Main Effects and Multiplicative Interaction (AMMI) and Genotype main effect plus genotype-by-environment interaction (GGE) biplots, DMR-QPM-09-13-1 × UMI 1099 (PA:9.38 mg/g, trp:0.06%, and yield:184.35 g) and UMI 1205 × UMI 467 (PA:7.04 mg/g, trp:0.06%, and yield:166.39 g) were stable for their high yield with medium PA and tryptophan. Also, across environments, UMI 1200 × UMI 467 had a stable average yield of 129.91 g along with the lowest PA of 4.50 mg/g and higher tryptophan of 0.07%. Thus, these hybrids could be selected and evaluated in upcoming biofortification trials to benefit the poultry sector. Furthermore, the parental inbreds utilized were grouped into heterotic pools to serve as a source population for the development oflpahybrids in future programs.
The Cognitive-Enhancing Effects of Dendrobium nobile Lindl Extract in Sleep Deprivation-Induced Amnesic Mice
Authors: Jiang Ning , Li Yu-jiao , Wang Meng-di , Huang Hong , Chen Shanguang , Li Yinghui , Qu Lina , Wang Fengzhong , Liu Xinmin , Wang Qiong
Published: January 2022

Chronic sleep deprivation (SD) causes neurological and neurodegenerative dysfunction including learning and memory deficit. The orchid Dendrobium nobile Lindl (DNL), is widely used as a Yin tonic and medicinal food throughout Asia, and has many reported pharmacological effects. This study focused on the cognitive-enhancing effects of DNL in sleep deprivation-induced amnesia in mice and its biochemical mechanisms. Our results showed that the mice displayed significant cognitive deficits after 2-week SD while treatment with the extract of DNL prevented these impairments. In the novel object recognition and object location recognition tasks, a significant increase in the discrimination index was observed in DNL-treated (200 and 400 mg/kg) mice. In the MWM test, DNL (200 and 400 mg/kg) treatment shorten the prolongation of latency and increased the crossing numbers compared with SD mice. The biochemical analysis of brain tissue showed a decrease in NE, dismutase (T-SOD) and catalase (CAT) activity and an increase in 5-HT and malondialdehyde (MDA) concentration after the treatment with DNL in mice. Our findings indicated that DNL exerted a positive effect in preventing and improving cognitive impairment induced by SD, which may be mediated via the regulation of neurotransmitters and alleviation of oxidative stress.
The Impact of Aging on the Lung Alveolar Environment, Predetermining Susceptibility to Respiratory Infections
Authors: Torrelles Jordi B. , Restrepo Blanca I. , Bai Yidong , Ross Corinna , Schlesinger Larry S. , Turner Joanne
Published: January 2022

Respiratory infections are one of the top causes of death in the elderly population, displaying susceptibility factors with increasing age that are potentially amenable to interventions. We posit that with increasing age there are predictable tissue-specific changes that prevent the immune system from working effectively in the lung. This mini-review highlights recent evidence for altered local tissue environment factors as we age focusing on increased tissue oxidative stress with associated immune cell changes, likely driven by the byproducts of age-associated inflammatory disease. Potential intervention points are presented.
Study on Automatic 3D Facial Caricaturization: From Rules to Deep Learning
Authors: Olivier Nicolas , Kerbiriou Glenn , Arguelaguet Ferran , Avril Quentin , Danieau Fabien , Guillotel Philippe , Hoyet Ludovic , Multon Franck
Published: January 2022

Facial caricature is the art of drawing faces in an exaggerated way to convey emotions such as humor or sarcasm. Automatic caricaturization has been explored both in the 2D and 3D domain. In this paper, we propose two novel approaches to automatically caricaturize input facial scans, filling gaps in the literature in terms of user-control, caricature style transfer, and exploring the use of deep learning for 3D mesh caricaturization. The first approach is a gradient-based differential deformation approach with data driven stylization. It is a combination of two deformation processes: facial curvature and proportions exaggeration. The second approach is a GAN for unpaired face-scan-to-3D-caricature translation. We leverage existing facial and caricature datasets, along with recent domain-to-domain translation methods and 3D convolutional operators, to learn to caricaturize 3D facial scans in an unsupervised way. To evaluate and compare these two novel approaches with the state of the art, we conducted the first user study of facial mesh caricaturization techniques, with 49 participants. It highlights the subjectivity of the caricature perception and the complementarity of the methods. Finally, we provide insights for automatically generating caricaturized 3D facial mesh.
Theoretical Refinements to the Heliospheric Upwind eXtrapolation Technique and Application to in-situ Measurements
Authors: Issan Opal , Riley Pete
Published: January 2022

The large-scale structure and evolution of the solar wind are typically reproduced with reasonable fidelity using three-dimensional magnetohydrodynamic (MHD) models. However, such models are difficult to implement by the scientific community in general, because they require technical expertise and significant computational resources. Previously, we demonstrated how a simplified two-dimensional surrogate solar wind model, the Heliospheric Upwind eXtrapolation (HUX) technique, could reconstruct MHD solutions in the ecliptic plane, given either an inner (or outer) radial boundary condition. Here, we further develop the HUX technique and apply it to a range of solar wind in-situ datasets. Specifically, we: (1) provide a thorough mathematical analysis of the underlying reduced momentum equation describing the solar wind. (2) Propose flux-limiter numerical schemes that more accurately capture stream interaction regions and rarefaction regions; and (3) Apply the HUX technique to a variety of in-situ spacecraft measurements, focusing on Helios (1 and 2) and near-Earth spacecraft (Wind/ACE), for which near-latitudinal alignments occurred. We suggest that this refined HUX tool can be used for both retrospective studies as well as real-time predictions to better understand and forecast the large-scale structure and origin of the solar wind.
Retoryka w Polsce po 1989 r. Przegląd kierunków badań
Authors: Bendrat Anna , Budzyńska-Daca Agnieszka , Kampka Agnieszka , Modrzejewska Ewa , Załęska Maria
Published: January 2022

This paper is dedicated to the development of rhetoric in Poland after 1989
taking into account adaptation processes at two levels: communication practices
and research refl ection. The sociopolitical transformations have enabled an
unrestricted development of rhetorical activities, which were impracticable in the
former Eastern Bloc countries: advertising and marketing, political debates, civic
engagement, academic freedom. The adaptation has taken place at the level of
communication habits of citizens and rhetorical practices of rhetoric researchers
themselves. The study adopts the descriptive methodology and focuses on several
aspects: the process of internal differentiation of rhetorical studies, the infl uence
of the American rhetorical criticism on the studies, the rhetorical perspective
in linguistic research, media studies, and politics. The paper emphasises the
cultural characteristics of Polish rhetorical studies, which draw inspiration from
three main sources: 1) Old Polish oratory and its modern analyses from the
perspective of literary studies; 2) analyses of the propaganda of the times of
the Polish People’s Republic, including the media; 3) modern concepts from
the areas of argumentation, rhetorical criticism, discourse analysis, and media
studies. The overview shows that, after 1989, rhetorical studies can be described
as a self-organising system cre ated by dense intertextual relations, relationship
networks, and institutional frameworks rather than as a compilation of sparse
individual works.
Żydki, gudłaje, parchy i inne wyrazy haniebne.
Antysemityzm odciśnięty w dawnej i współczesnej leksyce polskiej
Authors: Zdunkiewicz-Jedynak Dorota
Published: January 2022

The paper analyses the Polish lexis, recorded in dictionaries (since the
19th century) and the National Corpus of Polish (NKJP), which refl ects the
social attitudes that could be described as anti-Semitic. It discusses words
expressing aversion, contempt, hostility, which carry a strong markedness that
refers to the established negative stereotype of the Jew. Ethnonyms and their
colloquial equivalents, words derived from an ethnonym, and its metaphorical
neosematisms were used as the material for the description (the already
examined paroemia and idiomatic expressions are outside the scope of the
author’s interests).
Operatory gradacji maksymalnie, minimalnie – różnice
w zakresie łączliwości z przymiotnikami i przysłówkami
Authors: Piotrowska Adrianna
Published: January 2022

This paper presents an analysis of semantic and lexical connectivity of lexical
units assuming the form maksymalnie (maximally), minimalnie (minimally). They
are treated as metapredicative operators, or – to be more precise – as operators
of gradation, while in fact they are representatives of metalevels. The paper
focuses in particular on presenting limitations to the connectivity between the
examined operators and the adjectives and adverbs that are called parametric
and evaluative in the relevant literature. The analysed lexemes collocate with
adjectives and adverbs that are relative in nature. The analyses were conducted
based on the dictionary descriptions and examples of usage of the units derived
from the National Corpus of Polish (NKJP). The paper uses methods applied in
structural grammar and semantics.
O pozostałych i reszcie czegoś jako wykładnikach referencji
Authors: Wołk Mariola
Published: January 2022

This paper focuses on pozostali / pozostałe (the remaining) and reszta czegoś
(the rest of something), which function as indicators of reference. It is the aim
of the undertaken analysis to determine how these indicators participate in the
mechanism of delineating a set of objects. Additionally, the analysis is intended
to describe the semantic relationship which occurs between the examined units,
and in particular to verify the hypothesis that they are equivalent. Also, the
study concerns the dependencies between the abovementioned expressions and
a simpler qualifi er inny (another) (in its plural forms inni / inne (other / the
others)). All of the considered units are indicators of general reference, i.e. they
identify a set, and it is their characteristic that this set is relativised to another
set delineated earlier. However, they are not synonyms. Differences between
pozostali / pozostałe and reszta czegoś are noticeable at the level of defi ning the
identifi ed sets (opposition: distributivity – collectivity), while inny (inni / inne),
an expression that is juxtaposed with them, is their hypernym. The study offers
detailed reasons for the solutions developed in the course of the analysis.
An Evasion Attack against Stacked Capsule Autoencoder
Authors: Dai Jiazhu , Xiong Siwei
Published: January 2022

Capsule networks are a type of neural network that use the spatial relationship between features to classify images. By capturing the poses and relative positions between features, this network is better able to recognize affine transformation and surpass traditional convolutional neural networks (CNNs) when handling translation, rotation, and scaling. The stacked capsule autoencoder (SCAE) is a state-of-the-art capsule network that encodes an image in capsules which each contain poses of features and their correlations. The encoded contents are then input into the downstream classifier to predict the image categories. Existing research has mainly focused on the security of capsule networks with dynamic routing or expectation maximization (EM) routing, while little attention has been given to the security and robustness of SCAEs. In this paper, we propose an evasion attack against SCAEs. After a perturbation is generated based on the output of the object capsules in the model, it is added to an image to reduce the contribution of the object capsules related to the original category of the image so that the perturbed image will be misclassified. We evaluate the attack using an image classification experiment on the Mixed National Institute of Standards and Technology Database (MNIST), Fashion-MNIST, and German Traffic Sign Recognition Benchmark (GTSRB) datasets, and the average attack success rate can reach 98.6%. The experimental results indicate that the attack can achieve high success rates and stealthiness. This finding confirms that the SCAE has a security vulnerability that allows for the generation of adversarial samples. Our work seeks to highlight the threat of this attack and focus attention on SCAE’s security.
Itchy Toxicodendron Plant Dermatitis
Authors: Labib Angelina , Yosipovitch Gil
Published: January 2022

Plants such as the Toxicodendron species, consisting of poison ivy, poison oak, and poison sumac, largely contribute to allergic contact dermatitis with itch as a predominate symptom. Many individuals are affected by this skin condition, with approximately 50% to 70% of adults in North America demonstrating a degree of clinical sensitivity to this species of plants. In this review, we discuss the prevalence, pathophysiology, and clinical features of this contact dermatitis, as well as both treatment and prevention directed towards alleviation of itch. Updated research is emphasized throughout this review, although it is evident that this field is evolving, and more research is necessary to enhance treatment.
Intensification of Penaeid Shrimp Culture: An Applied Review of Advances in Production Systems, Nutrition and Breeding
Authors: Emerenciano Maurício G. C. , Rombenso Artur N. , Vieira Felipe d. N. , Martins Mateus A. , Coman Greg J. , Truong Ha H. , Noble Tansyn H. , Simon Cedric J.
Published: January 2022

Intensification of the shrimp sector, also referred to as vertical expansion, has been predominately driven by consecutive incidences of global disease outbreaks, which have caused enormous economic loss for the main producer countries. A growing segment of the shrimp farming industry has opted to use production systems with higher density, biosecurity, and operating control to mitigate the risks posed by disease. However, successful super-intensive shrimp production is reliant on an advanced understanding of many important biological and economic parameters in the farming system, coupled with effective monitoring, to maintain optimal production. Compared to traditional extensive or semi-intensive systems, super-intensive systems require higher inputs of feed, energy, labor, and supplements. These systems are highly sensitive to the interactions between these different inputs and require that the biological and economical parameters of farming are carefully balanced to ensure success. Advancing nutritional knowledge and tools to support consistent and efficient production of shrimp in these high-cost super-intensive systems is also necessary. Breeding programs developing breeding-lines selected for these challenging super-intensive environments are critical. Understanding synergies between the key areas of production systems, nutrition, and breeding are crucial for super-intensive farming as all three areas coalesce to influence the health of shrimp and commercial farming success. This article reviews current strategies and innovations being used for Litopenaeus vannamei in production systems, nutrition, and breeding, and discusses the synergies across these areas that can support the production of healthy and high-quality shrimp in super-intensive systems. Finally, we briefly discuss some key issues of social license pertinent to the super-intensive shrimp farming industry.