bluuebunny/crossref_metadata_2025 huggingface dataset:
Global Trends in Intertrochanteric Hip Fracture Research From 2001 to 2020: A Bibliometric and Visualized Study
Authors: Zhang Ze , Qiu Yudian , Zhang Yawen , Zhu Yi , Sun Fengpo , Liu Junchuan , Zhang Tongyi , Wen Liangyuan
Published: October 2021

Background: Intertrochanteric femur fractures, which are common geriatric osteoporotic fractures, have imposed a huge economic and social burden. This study clarified the global status of research on intertrochanteric fractures between 2001 and 2020 and predicted future research trends in this field using bibliometric and visualized studies.

Methods: Publications related to intertrochanteric fractures were retrieved from the Web of Science (WoS) database. All studies were published between 2001 and 2020. Bibliometric and co-occurrence analyses were conducted using VoS viewer software.

Results: In total, 2,632 studies were retrieved. The number of global publications regarding intertrochanteric fractures increased annually. The United States was the largest contributor, ranking first in total publications, citations, and the H-index. Switzerland had the highest average citation frequency among the 10 countries with the highest number of publications. The journal that published the most articles regarding intertrochanteric fractures was the Injury International Journal of The Care of The Injured, with 290 articles published. This journal also ranked first in the citation frequency. MJ Parker, an author, published the most papers in the field, and the University of California research team at San Francisco contributed the most publications in this field. During the co-occurrence analysis, all keywords were divided into four clusters: internal fixation study, complication study, risk-factor study, and survival and prognosis analysis study. The internal fixation and survival and prognosis analysis studies were predicted as the next hot topics in the field of intertrochanteric fractures.

Conclusions: Intertrochanteric fractures are gaining increasing research attention according to the current global trend, and the number of publications regarding intertrochanteric hip fractures will continue to increase. The United States currently publishes the most articles on intertrochanteric fractures. The number of studies related to internal fixation, survival, and prognosis analysis is increasing, suggesting that these topics may become the next research hotspots in the area of intertrochanteric fractures.
miR-F4-C12 Functions on the Regulation of Adipose Accumulation by Targeting PIK3R1 in Castrated Male Pigs
Authors: Xu Qiao , Chen Jie , Liu Ximing , Luo Yabiao , Wang Tianzuo , Fang Meiying
Published: October 2021

MicroRNAs (miRNAs) constitute small regulatory molecules for a wide array of biological activities (18~24 nucleotides in length), including adipogenesis and adipose deposition. Their effect is, however, incompletely defined in inducing fat accumulation in castrated male pigs. Based on our study, four nine-times miRNAs were selected to examine their functions in adipose formation activities. In 3T3-L1 cells and backfat tissues of castrated and intact male pigs, miR-F4-C12 was identified as a factor in adipose development utilizing quantitative real-time PCR (qRT-PCR). Further, miR-F4-C12 was identified to promote fat development, suggesting that miR-F4-C12 was involved in adipogenesis. Moreover, phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) was proposed by the TargetScan, miRDB and starBase as a target of miR-F4-C12 and verified through a two-luciferase reporter assay. The over-expression of miR-F4-C12 dramatically decreases the PIK3R1 protein level in 3T3-L1 cells. The mRNA and protein levels of PIK3R1 in castrated pigs are reduced relative to intact pigs, providing further evidence that PIK3R1 is involved in regulating adipose accumulation. These results suggest that miR-F4-C12 involves adipose development and may regulate subcutaneous adipose tissue accumulation by targeting PIK3R1 in castrated male pigs.
Corticosterone-Mediated Physiological Stress Alters Liver, Kidney, and Breast Muscle Metabolomic Profiles in Chickens
Authors: Brown Catherine L. J. , Zaytsoff Sarah J. M. , Montina Tony , Inglis G. Douglas
Published: October 2021

The impact of physiological stress on the metabolomes of liver, kidney, and breast muscle was investigated in chickens. To incite a stress response, birds were continuously administered corticosterone (CORT) in their drinking water at three doses (0, 10, and 30 mg L−1), and they were sampled 1, 5, and 12 days after the start of the CORT administration. To solubilize CORT, it was first dissolved in ethanol and then added to water. The administration of ethanol alone significantly altered branched chain amino acid metabolism in both the liver and the kidney, and amino acid and nitrogen metabolism in breast muscle. CORT significantly altered sugar and amino acid metabolism in all three tissues, but to a much greater degree than ethanol alone. In this regard, CORT administration significantly altered 11, 46, and 14 unique metabolites in liver, kidney, and breast muscle, respectively. Many of the metabolites that were affected by CORT administration, such as mannose and glucose, were previously linked to increases in glycosylation and gluconeogenesis in chickens under conditions of production stress. Moreover, several of these metabolites, such as dimethylglycine, galactose, and carnosine were also previously linked to reduced quality meat. In summary, the administration of CORT in chickens significantly modulated host metabolism. Moreover, results indicated that energy potentials are diverted from muscle anabolism to muscle catabolism and gluconeogenesis during periods of stress.
Refining Procedures within Regulatory Toxicology Studies: Improving Animal Welfare and Data
Authors: Prior Helen , Blunt Hollie , Crossman Lee , McGuire Aidan , Stow Ruth , Sewell Fiona
Published: October 2021

During the development of potential new medicines or agrochemicals, an assessment of the safety profile to humans and environmental species is conducted using a range of different in silico and in vitro techniques in conjunction with metabolism and toxicity studies using animals. The required studies are outlined within international regulatory guidelines which acknowledge and support the application of the 3Rs to reduce the number of animals used or to refine the procedures performed when these studies are deemed to be necessary. The continued development of new technologies and adoption of best-practice approaches to laboratory animal housing and study procedures has generated a series of refinements that can be incorporated into animal studies throughout the package. These refinements benefit the welfare of fish, mice, rats, rabbits, dogs, minipigs, and non-human primates (NHPs) whilst maintaining or improving data quality within general toxicology, metabolism, and other studies and can also bring efficiencies to processes that benefit study costs and timings. Examples are shared which cover the following topics: social housing of dogs and NHPs, surgical refinements in the rat bile duct cannulation model for collection of data for metabolism studies, whether fasting is really required prior to clinical pathology sampling, and the use of microsampling for toxicokinetics.
Introduction to Antibody-Drug Conjugates
Authors: Pettinato Mark C.
Published: October 2021

Antibody-drug conjugates (ADCs) are innovative biopharmaceutical products in which a monoclonal antibody is linked to a small molecule drug with a stable linker. Most of the ADCs developed so far are for treating cancer, but there is enormous potential for using ADCs to treat other diseases. Currently, ten ADCs have been approved by the United States Food and Drug Administration (FDA), and more than 90 ADCs are under worldwide clinical development. Monoclonal antibodies have evolved from research tools to powerful therapeutics in the past 30 years. Tremendous strides have been made in antibody discovery, protein bioengineering, formulation, and delivery devices. This manuscript provides an overview of the biology, chemistry, and biophysical properties of each component of ADC design. This review summarizes the advances and challenges in the field to date, with an emphasis on antibody conjugation, linker-payload chemistry, novel payload classes, drug-antibody ratio (DAR), and product development. The review emphasizes the lessons learned in the development of oncology antibody conjugates and look towards future innovations enabling other therapeutic indications. The review discusses resistance mechanisms to ADCs, and give an opinion on future perspectives.
Electrochemical Removal of Cesium Ions via Capacitive Deionization Using an Ion-Exchange Layer Coated on a Carbon Electrode
Authors: Lee Sang-Hun , Choi Mansoo , Moon Jei-Kwon , Lee Songbok , Choi Jihoon , Kim Seonbyeong
Published: October 2021

This study was conducted to evaluate the feasibility of using electrosorption to remove cesium (Cs+) ions from aqueous solutions using the membrane capacitive deionization (MCDI) process. The electrochemical properties were analyzed using cyclic voltammetry (CV) and impedance spectroscopy (EIS). The activated carbon electrode coated by a polymer layer showed higher specific adsorption capacity (SAC) and removal efficiency of Cs+ than the AC electrode. The effects of potential, flow rate, initial Cs+ concentration, and pH values were investigated to optimize the electrosorption performance. The electrosorption capacity increased with an increase in the applied potential and the concentration of Cs+ in the influent water. The pH value is an important parameter on electrosorption performance. The removal of Cs+ ions was affected by the pH of the influent water because H+ ions acted as competing ions during the electrosorption process. Cs+ was preferentially adsorbed to the electrode in the early stages of adsorption but was later replaced by H+. A higher presence of H+ ions could reduce the adsorption capacity of Cs+ ions. The ion-exchange layer coated AC electrode was shown to be favorable for the removal of Cs+, despite the limited electrosorption ability in a highly acidic solution.
The Health and Economic Benefits of Reduced Residential Solid Fuel Burning on the South African Highveld
Authors: Lindeque Louisa Farina , Burger Roelof Pertus , Piketh Stuart John
Published: October 2021

Emissions from residential solid fuel burning in densely populated low-income settlements is a significant source of air pollution over the South African Highveld. The area is densely populated and highly industrialized, resulting in high concentrations of pollutants over the area. Although emissions from industrial sources are much larger, exposure to household emissions poses the most significant risk to human health. Interventions aimed at reducing solid fuel burning in low-income settlements on the Highveld have the potential to reduce exposure, but quantifying their true impact remains a challenge. We aimed to estimate the health and associated economic benefits of the regional implementation of thermal insulation as intervention measure in low-income settlements to predict the potential impact on the regional scale. We used a land use type regression model to estimate pre-intervention PM2.5 concentrations over the Highveld and then used sampled post-intervention air quality data from a pilot offset programme to relate changes in air quality to changes in avoided premature mortalities. We estimate that the large-scale implementation of this intervention could result in 143 avoided premature mortalities with an estimated economic benefit of just under ZAR (2011) 341.6 million, equivalent to USD (2011) 49.4 million.
Associations of Immune Genetic Variability with Gulf War Illness in 1990–1991 Gulf War Veterans from the Gulf War Illness Consortium (GWIC) Multisite Case-Control Study
Authors: Coller Janet K. , Tuke Jonathan , Wain Taylor J. , Quinn Emily , Steele Lea , Abreu Maria , Aenlle Kristina , Klimas Nancy , Sullivan Kimberly
Published: October 2021

Gulf War illness (GWI) encompasses a constellation of persistent debilitating symptoms associated with significant changes in central nervous system (CNS) and immune functioning. Currently, there is no validated biomarker for GWI risk susceptibility. Given the impact of immune responses linked to GWI symptomology, genetic variability that causes persistent inflammatory/immune alterations may be key. This Boston University-based Gulf War Illness Consortium (GWIC) study investigated the impact of single nucleotide polymorphisms (SNPs) in variants of immune and pain genetic markers IL1B, IL2, IL6, IL6R, IL10, TNF, TGF, TLR2, TLR4, MD2, MYD88, BDNF, CRP, ICE, COMT and OPRM1 on GWI occurrence in a Caucasian subset of Gulf War (GW) veterans with (cases, n = 170) and without (controls, n = 34) GWI. Logistic regression modeling created a prediction model of GWI risk that associated genetic variability in TGF (rs1800469, p = 0.009), IL6R (rs8192284, p = 0.004) and TLR4 (rs4986791, p = 0.013) with GWI occurrence. This prediction model was specific and sensitive, with a receiver operator characteristic area under the curve of 71.4%. This is the first report of immune genetic variability being predictive of GWI and warrants validation in larger independent cohorts. Future reports will present interactions of these genetic risk factors with other characteristics of GW service.
Molecular-Genetic Portrait of Breast Cancer with Triple Negative Phenotype
Authors: Ibragimova Marina K. , Tsyganov Matvey M. , Litviakov Nikolai V.
Published: October 2021

Understanding of the genetic mechanisms and identification of the biological markers of tumor progression that form the individual molecular phenotype of transformed cells can characterize the degree of tumor malignancy, the ability to metastasize, the hormonal sensitivity, and the effectiveness of chemotherapy, etc. Breast cancer (BC) is a genetically heterogeneous disease with different molecular biological and clinical characteristics. The available knowledge about the genetic heterogeneity of the most aggressive molecular subtype of breast cancer—triple-negative (TN)—has led to discoveries in drug treatment, including the use of DNA damaging agents (platinum and PARP inhibitors) for these tumors, as well as the use of immunotherapy. Most importantly, the ability to prescribe optimal drug treatment regimens for patients with TNBC based on knowledge of the molecular-genetic characteristics of this subtype of BC will allow the achievement of high rates of overall and disease-free survival. Thus, identification of the molecular-genetic phenotype of breast cancer is an important prognostic factor of the disease and allows personalization of the patient’s treatment.
Association of FOXO3 Expression with Tumor Pathogenesis, Prognosis and Clinicopathological Features in Hepatocellular Carcinoma: A Systematic Review with Meta-Analysis
Authors: Fondevila Flavia , Fernández-Palanca Paula , Méndez-Blanco Carolina , Payo-Serafín Tania , Lozano Elisa , Marin Jose J. G. , González-Gallego Javier , Mauriz José L.
Published: October 2021

Forkhead box O3 (FOXO3), an essential transcription factor related to liver disease, has been linked to cancer progression. The most frequent primary liver tumor, hepatocellular carcinoma (HCC), has an elevated mortality rate and patient outcomes remain very poor. Here, we examined the diagnostic, prognostic and clinicopathological significance of FOXO3 expression in HCC. We systematically searched Cochrane, Embase, PubMed, Scopus and Web of Science. Articles analyzing FOXO3 levels in HCC patient samples and its relationship with tumor development, survival or clinicopathological factors were selected. Hazard ratios, odds ratios and 95% confidence intervals were extracted, estimated by Parmar method or calculated and pooled across studies. Heterogeneity was evaluated by chi-square-based Q and I2 tests, while publication bias by funnel plots and Egger’s test. Subgroup analysis was performed when heterogeneity was evident. The study protocol was registered in PROSPERO (CRD42021237321), and data were meta-analyzed employing STATA 16. Five studies involving 1059 HCC cases were finally included in this meta-analysis, finding that high FOXO3 levels significantly correlate with HCC development and shorter overall survival. Moreover, subgroup analysis revealed a significant association between positive FOXO3 expression and the risk of invasion. Thus, FOXO3 could function as a novel biomarker with diagnostic and prognostic value in HCC.
Monitoring the Levels of Cellular NF-κB Activation States
Authors: Meier-Soelch Johanna , Mayr-Buro Christin , Juli Jana , Leib Lisa , Linne Uwe , Dreute Jan , Papantonis Argyris , Schmitz M. Lienhard , Kracht Michael
Published: October 2021

The NF-κB signaling system plays an important regulatory role in the control of many biological processes. The activities of NF-κB signaling networks and the expression of their target genes are frequently elevated in pathophysiological situations including inflammation, infection, and cancer. In these conditions, the outcome of NF-κB activity can vary according to (i) differential activation states, (ii) the pattern of genomic recruitment of the NF-κB subunits, and (iii) cellular heterogeneity. Additionally, the cytosolic NF-κB activation steps leading to the liberation of DNA-binding dimers need to be distinguished from the less understood nuclear pathways that are ultimately responsible for NF-κB target gene specificity. This raises the need to more precisely determine the NF-κB activation status not only for the purpose of basic research, but also in (future) clinical applications. Here we review a compendium of different methods that have been developed to assess the NF-κB activation status in vitro and in vivo. We also discuss recent advances that allow the assessment of several NF-κB features simultaneously at the single cell level.
Somatic Hypomethylation of Pericentromeric SST1 Repeats and Tetraploidization in Human Colorectal Cancer Cells
Authors: González Beatriz , Navarro-Jiménez Maria , Alonso-De Gennaro María José , Jansen Sanne Marcia , Granada Isabel , Perucho Manuel , Alonso Sergio
Published: October 2021

Somatic DNA hypomethylation and aneuploidy are hallmarks of cancer, and there is evidence for a causal relationship between them in knockout mice but not in human cancer. The non-mobile pericentromeric repetitive elements SST1 are hypomethylated in about 17% of human colorectal cancers (CRC) with some 5–7% exhibiting strong age-independent demethylation. We studied the frequency of genome doubling, a common event in solid tumors linked to aneuploidy, in randomly selected single cell clones of near-diploid LS174T human CRC cells differing in their level of SST1 demethylation. Near-diploid LS174T cells underwent frequent genome-doubling events generating near-tetraploid clones with lower levels of SST1 methylation. In primary CRC, strong SST1 hypomethylation was significantly associated with global genomic hypomethylation and mutations in TP53. This work uncovers the association of the naturally occurring demethylation of the SST1 pericentromeric repeat with the onset of spontaneous tetraploidization in human CRC cells in culture and with TP53 mutations in primary CRCs. Altogether, our findings provide further support for an oncogenic pathway linking somatic hypomethylation and genetic copy number alterations in a subset of human CRC.
Molecular Imaging in Primary Staging of Prostate Cancer Patients: Current Aspects and Future Trends
Authors: Manafi-Farid Reyhaneh , Ranjbar Shaghayegh , Jamshidi Araghi Zahra , Pilz Julia , Schweighofer-Zwink Gregor , Pirich Christian , Beheshti Mohsen
Published: October 2021

Accurate primary staging is the cornerstone in all malignancies. Different morphological imaging modalities are employed in the evaluation of prostate cancer (PCa). Regardless of all developments in imaging, invasive histopathologic evaluation is still the standard method for the detection and staging of the primary PCa. Magnetic resonance imaging (MRI) and computed tomography (CT) play crucial roles; however, functional imaging provides additional valuable information, and it is gaining ever-growing acceptance in the management of PCa. Targeted imaging with different radiotracers has remarkably evolved in the past two decades. [111In]In-capromab pendetide scintigraphy was a new approach in the management of PCa. Afterwards, positron emission tomography (PET) tracers such as [11C/18F]choline and [11C]acetate were developed. Nevertheless, none found a role in the primary staging. By introduction of the highly sensitive small molecule prostate-specific membrane antigen (PSMA) PET/CT, as well as recent developments in MRI and hybrid PET/MRI systems, non-invasive staging of PCa is being contemplated. Several studies investigated the role of these sophisticated modalities in the primary staging of PCa, showing promising results. Here, we recapitulate the role of targeted functional imaging. We briefly mention the most popular radiotracers, their diagnostic accuracy in the primary staging of PCa, and impact on patient management.
Role and Function of O-GlcNAcylation in Cancer
Authors: Lee Jii Bum , Pyo Kyoung-Ho , Kim Hye Ryun
Published: October 2021

Cancer cells are able to reprogram their glucose metabolism and retain energy via glycolysis even under aerobic conditions. They activate the hexosamine biosynthetic pathway (HBP), and the complex interplay of O-linked N-acetylglucosaminylation (O-GlcNAcylation) via deprivation of nutrients or increase in cellular stress results in the proliferation, progression, and metastasis of cancer cells. Notably, cancer is one of the emerging diseases associated with O-GlcNAcylation. In this review, we summarize studies that delineate the role of O-GlcNAcylation in cancer, including its modulation in metastasis, function with receptor tyrosine kinases, and resistance to chemotherapeutic agents, such as cisplatin. In addition, we discuss the function of O-GlcNAcylation in eliciting immune responses associated with immune surveillance in the tumor microenvironment. O-GlcNAcylation is increasingly accepted as one of the key players involved in the activation and differentiation of T cells and macrophages. Finally, we discuss the prognostic role of O-GlcNAcylation and potential therapeutic agents such as O-linked β-N-acetylglucosamine-transferase inhibitors, which may help overcome the resistance mechanism associated with the reprogramming of glucose metabolism.
Application of High-Z Gold Nanoparticles in Targeted Cancer Radiotherapy—Pharmacokinetic Modeling, Monte Carlo Simulation and Radiobiological Effect Modeling
Authors: Li Wei Bo , Stangl Stefan , Klapproth Alexander , Shevtsov Maxim , Hernandez Alicia , Kimm Melanie A. , Schuemann Jan , Qiu Rui , Michalke Bernhard , Bernal Mario A. , Li Junli , Hürkamp Kerstin , Zhang Yibao , Multhoff Gabriele
Published: October 2021

High-Z gold nanoparticles (AuNPs) conjugated to a targeting antibody can help to improve tumor control in radiotherapy while simultaneously minimizing radiotoxicity to adjacent healthy tissue. This paper summarizes the main findings of a joint research program which applied AuNP-conjugates in preclinical modeling of radiotherapy at the Klinikum rechts der Isar, Technical University of Munich and Helmholtz Zentrum München. A pharmacokinetic model of superparamagnetic iron oxide nanoparticles was developed in preparation for a model simulating the uptake and distribution of AuNPs in mice. Multi-scale Monte Carlo simulations were performed on a single AuNP and multiple AuNPs in tumor cells at cellular and molecular levels to determine enhancements in the radiation dose and generation of chemical radicals in close proximity to AuNPs. A biologically based mathematical model was developed to predict the biological response of AuNPs in radiation enhancement. Although simulations of a single AuNP demonstrated a clear dose enhancement, simulations relating to the generation of chemical radicals and the induction of DNA strand breaks induced by multiple AuNPs showed only a minor dose enhancement. The differences in the simulated enhancements at molecular and cellular levels indicate that further investigations are necessary to better understand the impact of the physical, chemical, and biological parameters in preclinical experimental settings prior to a translation of these AuNPs models into targeted cancer radiotherapy.
A Mass Spectrometry Imaging Based Approach for Prognosis Prediction in UICC Stage I/II Colon Cancer
Authors: Martin Benedikt , Gonçalves Juliana P. L. , Bollwein Christine , Sommer Florian , Schenkirsch Gerhard , Jacob Anne , Seibert Armin , Weichert Wilko , Märkl Bruno , Schwamborn Kristina
Published: October 2021

Currently, pathological evaluation of stage I/II colon cancer, following the Union Internationale Contre Le Cancer (UICC) guidelines, is insufficient to identify patients that would benefit from adjuvant treatment. In our study, we analyzed tissue samples from 276 patients with colon cancer utilizing mass spectrometry imaging. Two distinct approaches are herein presented for data processing and analysis. In one approach, four different machine learning algorithms were applied to predict the tendency to develop metastasis, which yielded accuracies over 90% for three of the models. In the other approach, 1007 m/z features were evaluated with regards to their prognostic capabilities, yielding two m/z features as promising prognostic markers. One feature was identified as a fragment from collagen (collagen 3A1), hinting that a higher collagen content within the tumor is associated with poorer outcomes. Identification of proteins that reflect changes in the tumor and its microenvironment could give a very much-needed prediction of a patient’s prognosis, and subsequently assist in the choice of a more adequate treatment.
Recombinant Production of Arginyl Dipeptides by l-Amino Acid Ligase RizA Coupled with ATP Regeneration
Authors: Bordewick Sven , Mast Tim A. , Berger Ralf G. , Ersoy Franziska
Published: October 2021

Arginyl dipeptides like Arg-Ser, Arg-Ala, and Arg-Gly are salt-taste enhancers and can potentially be used to reduce the salt content of food. The l-amino acid ligase RizA from B. subtilis selectively synthesizes arginyl dipeptides. However, industrial application is prevented by the high cost of the cofactor adenosine triphosphate (ATP). Thus, a coupled reaction system was created consisting of RizA and acetate kinase (AckA) from E. coli providing ATP regeneration from acetyl phosphate. Both enzymes were recombinantly produced in E. coli and purified by affinity chromatography. Biocatalytic reactions were varied and analyzed by RP-HPLC with fluorescence detection. Under optimal conditions the system produced up to 5.9 g/L Arg-Ser corresponding to an ATP efficiency of 23 g Arg-Ser per gram ATP. Using similar conditions with alanine or glycine as second amino acid, 2.6 g/L Arg-Ala or 2.4 g/L Arg Gly were produced. The RizA/AckA system selectively produced substantial amounts of arginyl dipeptides while minimizing the usage of the expensive ATP.
Synthesis of 14-Substituted-14H-Dibenzo[a,j]Xanthene Derivatives in Presence of Effective Synergetic Catalytic System Bleaching Earth Clay and PEG-600
Authors: Atkore Sandeep T. , Bondle Giribala M. , Raithak Pranita V. , Kamble Vinod T. , Varala Ravi , Kuniyil Mufsir , Hatshan Mohammad Rafe , Shaik Baji , Adil Syed Farooq , Hussain Mohammed Althaf
Published: October 2021

The synthesis of 14-aryl 14H-dibenzo[a,j]xanthenes is achieved by a simple condensation reaction between β-naphthol with aryl or alkyl aldehydes in an effective synergetic catalytic system created by combining basic bleaching earth clay and PEG-600. The advantages of the present method include catalyst recyclability, superior product yield, a shorter reaction time and the avoidance of hazardous reagents. Synthesized xanthene derivatives were also screened for their antibacterial activity against Staphylococcus aureus (MTCC 96) and Pseudomonas aeruginosa (Wild).
Instructions for Flow Cytometric Detection of ASC Specks as a Readout of Inflammasome Activation in Human Blood
Authors: Wittmann Nico , Behrendt Ann-Kathrin , Mishra Neha , Bossaller Lukas , Meyer-Bahlburg Almut
Published: October 2021

Inflammasome activation is linked to the aggregation of the adaptor protein ASC into a multiprotein complex, known as the ASC speck. Redistribution of cytosolic ASC to this complex has been widely used as a readout for inflammasome activation and precedes the downstream proteolytic release of the proinflammatory cytokines, IL-1β and IL-18. Although inflammasomes are important for many diseases such as periodic fever syndromes, COVID-19, gout, sepsis, atherosclerosis and Alzheimer’s disease, only a little knowledge exists on the precise and cell type specific occurrence of inflammasome activation in patient samples ex vivo. In this report, we provide detailed information about the optimal conditions to reliably identify inflammasome activated monocytes by ASC speck formation using a modified flow cytometric method introduced by Sester et al. in 2015. Since no protocol for optimal sample processing exists, we tested human blood samples for various conditions including anticoagulant, time and temperature, the effect of one freeze–thaw cycle for PBMC storage, and the fast generation of a positive control. We believe that this flow cytometric protocol will help researchers to perform high quality translational research in multicenter studies, and therefore provide a basis for investigating the role of the inflammasome in the pathogenesis of various diseases.
A Microbiome-Derived Peptide Induces Apoptosis of Cells from Different Tissues
Authors: Saiki Haruko , Okano Yuko , Yasuma Taro , Toda Masaaki , Takeshita Atsuro , Abdel-Hamid Ahmed M. , Fridman D’Alessandro Valeria , Tsuruga Tatsuki , D’Alessandro-Gabazza Corina N. , Katayama Kan , Sugimoto Masahiko , Fujimoto Hajime , Yamanaka Keiichi , Kobayashi Tetsu , Cann Isaac , Gabazza Esteban C.
Published: October 2021

Apoptosis is a programmed cell death involved in embryogenesis and tissue homeostasis under physiological conditions. However, abnormalities in the process of apoptosis are implicated in the pathogenesis of various diseases. The human microbiota may release products that induce apoptosis of host cells. We recently identified a novel microbiome-derived peptide called corisin that worsens lung fibrosis by inducing apoptosis of lung epithelial cells. We hypothesized that corisin and a corisin-like peptide might also induce apoptosis of cells from different tissues. We cultured podocytes, renal tubular epithelial cells, keratinocytes, retinal and intestinal cells treated with corisin and evaluated apoptosis by flow cytometry and Western blotting. Although at different grades, flow cytometry analysis and Western blotting showed that corisin and a corisin-like peptide induced apoptosis of podocytes, keratinocytes, tubular epithelial cells, retinal, and intestinal cells. In addition, we found that corisin synergistically enhances the proapoptotic activity of transforming growth factor-β1 on podocytes. In conclusion, these results suggest that corisin and corisin-like peptides may play a role in the pathogenesis of disease in different organs by promoting apoptosis of parenchymal cells.
Taste Receptors: The Gatekeepers of the Airway Epithelium
Authors: Martens Katleen , Steelant Brecht , Bullens Dominique M. A.
Published: October 2021

Taste receptors are well known for their role in the sensation of taste. Surprisingly, the expression and involvement of taste receptors in chemosensory processes outside the tongue have been recently identified in many organs including the airways. Currently, a clear understanding of the airway-specific function of these receptors and the endogenous activating/inhibitory ligands is lagging. The focus of this review is on recent physiological and clinical data describing the taste receptors in the airways and their activation by secreted bacterial compounds. Taste receptors in the airways are potentially involved in three different immune pathways (i.e., the production of nitric oxide and antimicrobial peptides secretion, modulation of ciliary beat frequency, and bronchial smooth muscle cell relaxation). Moreover, genetic polymorphisms in these receptors may alter the patients’ susceptibility to certain types of respiratory infections as well as to differential outcomes in patients with chronic inflammatory airway diseases such as chronic rhinosinusitis and asthma. A better understanding of the function of taste receptors in the airways may lead to the development of a novel class of therapeutic molecules that can stimulate airway mucosal immune responses and could treat patients with chronic airway diseases.
Toxicological Analysis of Hepatocytes Using FLIM Technique: In Vitro versus Ex Vivo Models
Authors: Rodimova Svetlana , Elagin Vadim , Karabut Maria , Koryakina Irina , Timin Alexander , Zagainov Vladimir , Zyuzin Mikhail , Zagaynova Elena , Kuznetsova Daria
Published: October 2021

The search for new criteria indicating acute or chronic pathological processes resulting from exposure to toxic agents, testing of drugs for potential hepatotoxicity, and fundamental study of the mechanisms of hepatotoxicity at a molecular level still represents a challenging issue that requires the selection of adequate research models and tools. Microfluidic chips (MFCs) offer a promising in vitro model for express analysis and are easy to implement. However, to obtain comprehensive information, more complex models are needed. A fundamentally new label-free approach for studying liver pathology is fluorescence-lifetime imaging microscopy (FLIM). We obtained FLIM data on both the free and bound forms of NAD(P)H, which is associated with different metabolic pathways. In clinical cases, liver pathology resulting from overdoses is most often as a result of acetaminophen (APAP) or alcohol (ethanol). Therefore, we have studied and compared the metabolic state of hepatocytes in various experimental models of APAP and ethanol hepatotoxicity. We have determined the potential diagnostic criteria including the pathologically altered metabolism of the hepatocytes in the early stages of toxic damage, including pronounced changes in the contribution from the bound form of NAD(P)H. In contrast to the MFCs, the changes in the metabolic state of hepatocytes in the ex vivo models are, to a greater extent, associated with compensatory processes. Thus, MFCs in combination with FLIM can be applied as an effective tool set for the express modeling and diagnosis of hepatotoxicity in clinics.
The Different Inclusions’ Characteristics between Natural and Heat-Treated Tanzanite: Evidence from Raman Spectroscopy
Authors: Yang Shuqi , Ye Huijuan , Liu Yingxin
Published: October 2021

In this paper, Raman spectroscopy experiments were used to distinguish the characteristics of inclusions (calcite, anatase, graphite etc.) between natural and heat-treated tanzanite. These characteristics were preliminarily divided according to their pleochroism. In natural unheated tanzanite (N5), calcite inclusion is often interspersed with dolomite and has Raman shifts around 156, 283, 710, and 1087 cm−1. In other high temperature treatment samples, the baseline of calcite increased and their Raman peaks gradually shifted towards lower frequencies. Anatase inclusions in natural tanzanite (N5) have four characteristic Raman peaks around 146, 394, 514, and 641 cm−1. Because of the longer Ti-O bond and the wider bond angle distribution caused by high temperature, fewer Raman peaks were observed and the peaks’ intensities were weakened in the heat-treated T7 sample. The black graphite inclusions are often scattered or have a dotted distribution. The most obvious difference between natural and heat-treated samples is that the latter lack the characteristic 1350 cm−1 Raman peak of graphite, thus representing the order and structural incompleteness of graphite. In addition, there are other inclusions in natural unheated tanzanite, such as lead-grey molybdenite with strong metallic luster, randomly scattered prehnite with white dots, orange-yellow rounded rutile, and metallic luster hematite.
Diversity of Endophytic and Pathogenic Fungi of Saffron (Crocus sativus) Plants from Cultivation Sites in Italy
Authors: Belfiori Beatrice , Rubini Andrea , Riccioni Claudia
Published: October 2021

Crocus sativus is an important crop for the production of saffron and bioactive compounds. Plant endophytic fungi are a source of secondary metabolites additional to those produced by the plant itself. We analysed the biodiversity of endophytic fungi present in corms, stems, leaves, tepals, and stigmas of C. sativus from ten Italian sites; furthermore, we isolated putative pathogenic fungi from rotten plants. We used an in vitro isolation approach followed by molecular analysis of the internal transcribed spacer (ITS rDNA) region. We obtained 165 strains belonging to 39 OTUs, spreading over 26 genera and 29 species. Dark septate endophytes of the genus Cadophora and the species Talaromyces pinophilus dominated in corms, while Alternaria alternata, Epicoccum spp., T. pinophilus, Mucor fragilis, and Stemphylium vesicarium dominated in other tissues. The most frequently isolated pathogens were Fusarium oxysporum and Rhizopus oryzae. Endophytic communities significantly differed among tissues and life stages, whereas differences among cultivation sites were not statistically supported. Several endophytes were hypothesized to have changing trophic modes and/or to be latent pathogens in C. sativus. All strains were conserved ex-situ for future bioactivity tests and production of metabolites.
A New Shrimp Genus (Crustacea: Decapoda) from the Deep Atlantic and an Unusual Cleaning Mechanism of Pelagic Decapods
Authors: Vereshchaka Alexander , Kulagin Dmitry , Lunina Anastasiia
Published: October 2021

The deep sea is the largest biome on Earth and hosts the majority of as yet undescribed species; description of these may trigger a new mindset about evolution and function of characters. We describe and diagnose a new genus and species Sclerodora crosnieri sp. nov. belonging to the superfamily Oplophoroidea. We examined and coded 81 characters for morphological analyses and used four gene markers for molecular analyses involving the new taxon and representatives of all other genera of Oplophoroidea. Retrieved morphological and molecular trees were similar and suggested that the new genus is a sister group to Hymenodora and both form a clade sister to the rest of Acanthephyridae. We provide an amended key to all genera of Oplophoroidea. We found an unusual chelate structure on the dactyl of the fifth pereopod, tested and confirmed a hypothesis that this structure is common for the whole family Acanthephyridae. We suggest that this derived structure is linked to an active cleaning of branchia—a function associated with chelipeds in some other carid shrimps. Convergent chelate structures are likely efficient for cleaning branchia, whichever appendage is adapted for these functions. In Oplophoridae (sister to Acanthephyridae), cleaning function is carried out by well-developed epipods.
Neuroptera Diversity from Tacaná Volcano, Mexico: Species Composition, Altitudinal and Biogeographic Pattern of the Fauna
Authors: Cancino-López Rodolfo J. , Martins Caleb C. , Contreras-Ramos Atilano
Published: October 2021

Approximately 340 species of ten families of Neuroptera have been recorded from Mexico. The Tacaná volcano, reaching an elevation of 4092 m a.s.l., is the northernmost representative of the Central American Nucleus volcanic range. Recent survey efforts of the Neuroptera diversity of the Tacaná volcano, Chiapas, along an altitudinal gradient, increased the known fauna of this order in Mexico by 31 species and two genera: Biramus Oswald, 1993 (Hemerobiidae), and Titanochrysa Sosa & Freitas, 2012 (Chrysopidae), with extension of the known distributional range of 25 species of five families. Most of the new country records are from species previously known only from Central and South America. The lacewing fauna of Chiapas is updated from 91 to 147 species. The Neuroptera of the Tacaná volcano is mostly Neotropical with some taxa of Nearctic affinity restricted to medium and high elevations. More than 80% of the Tacaná volcano lacewing species also occur in the Brazilian subregion, especially the Mesoamerican and Pacific domains. Neuropteran species were recorded from 650 to more than 3500 m a.s.l. A higher species richness was present between 600 and 1700 m, with a few species occurring at altitudes above 3000 m. A species checklist and an identification key to the genera of Neuroptera of the Tacaná volcano are provided.
Forest Management, Conflict and Social–Ecological Systems in a Changing World
Authors: Fernández-Manjarrés Juan F. , MacHunter Josephine , Zavala Miguel A.
Published: October 2021

Conflicts are ubiquitous in forest management because of several overlapping temporal and spatial issues (see examples in tropical and temperate areas [...]
COVIDNet: Implementing Parallel Architecture on Sound and Image for High Efficacy
Authors: Murugappan Manickam , Thomas John Victor Joshua , Fiore Ugo , Jinila Yesudas Bevish , Radhakrishnan Subhashini
Published: October 2021

The present work relates to the implementation of core parallel architecture in a deep learning algorithm. At present, deep learning technology forms the main interdisciplinary basis of healthcare, hospital hygiene, biological and medicine. This work establishes a baseline range by training hyperparameter space, which could be support images, and sound with further develop a parallel architectural model using multiple inputs with and without the patient’s involvement. The chest X-ray images input could form the model architecture include variables for the number of nodes in each layer and dropout rate. Fourier transformation Mel-spectrogram images with the correct pixel range use to covert sound acceptance at the convolutional neural network in embarrassingly parallel sequences. COVIDNet the end user tool has to input a chest X-ray image and a cough audio file which could be a natural cough or a forced cough. Three binary classification models (COVID-19 CXR, non-COVID-19 CXR, COVID-19 cough) were trained. The COVID-19 CXR model classifies between healthy lungs and the COVID-19 model meanwhile the non-COVID-19 CXR model classifies between non-COVID-19 pneumonia and healthy lungs. The COVID-19 CXR model has an accuracy of 95% which was trained using 1681 COVID-19 positive images and 10,895 healthy lungs images, meanwhile, the non-COVID-19 CXR model has an accuracy of 91% which was trained using 7478 non-COVID-19 pneumonia positive images and 10,895 healthy lungs. The reason why all the models are binary classification is due to the lack of available data since medical image datasets are usually highly imbalanced and the cost of obtaining them are very pricey and time-consuming. Therefore, data augmentation was performed on the medical images datasets that were used. Effects of parallel architecture and optimization to improve on design were investigated.
Comparison of Two Different Analytical Forms of Response for Fractional Oscillation Equation
Authors: Duan Jun-Sheng , Hu Di-Chen , Li Ming
Published: October 2021

The impulse response of the fractional oscillation equation was investigated, where the damping term was characterized by means of the Riemann–Liouville fractional derivative with the order α satisfying 0≤α≤2. Two different analytical forms of the response were obtained by using the two different methods of inverse Laplace transform. The first analytical form is a series composed of positive powers of t, which converges rapidly for a small t. The second form is a sum of a damped harmonic oscillation with negative exponential amplitude and a decayed function in the form of an infinite integral, where the infinite integral converges rapidly for a large t. Furthermore, the Gauss–Laguerre quadrature formula was used for numerical calculation of the infinite integral to generate an analytical approximation to the response. The asymptotic behaviours for a small t and large t were obtained from the two forms of response. The second form provides more details for the response and is applicable for a larger range of t. The results include that of the integer-order cases, α= 0, 1 and 2.
The Hybridisation of Conflict: A Prospect Theoretic Analysis
Authors: Balcaen Pieter , Du Bois Cind , Buts Caroline
Published: October 2021

Revisionist actors are increasingly operationalising a broad number of non-violent threats in their quest to change the status quo, popularly described as hybrid conflict. From a defensive point of view, this proliferation of threats compels nations to make difficult choices in terms of force posture and composition. We examine the choice process associated with this contemporary form of state competition by modelling the interactions between two actors, i.e., a defender and a challenger. As these choices are characterised by a high degree of uncertainty, we study the choice from the framework of prospect theory. This behavioural–economic perspective indicates that the defender will give a higher weight and a higher subjective value to conventional threats, inducing a higher vulnerability in the domain of hybrid deterrence. As future conflict will increasingly involve choice dilemmas, we must balance threats according to their probability of occurrence and their consequences. This article raises awareness regarding our cognitive biases when making these choices.
Optimal Voluntary Vaccination of Adults and Adolescents Can Help Eradicate Hepatitis B in China
Authors: Scheckelhoff Kristen , Ejaz Ayesha , Erovenko Igor V. , Rychtář Jan , Taylor Dewey
Published: October 2021

Hepatitis B (HBV) is one of the most common infectious diseases, with a worldwide annual incidence of over 250 million people. About one-third of the cases are in China. While China made significant efforts to implement a nationwide HBV vaccination program for newborns, a significant number of susceptible adults and teens remain. In this paper, we analyze a game-theoretical model of HBV dynamics that incorporates government-provided vaccination at birth coupled with voluntary vaccinations of susceptible adults and teens. We show that the optimal voluntary vaccination brings the disease incidence to very low levels. This result is robust and, in particular, due to a high HBV treatment cost, essentially independent from the vaccine cost.
Low Temperature Antioxidant Activity QTL Associate with Genomic Regions Involved in Physiological Cold Stress Tolerance Responses in Rice (Oryza sativa L.)
Authors: Phan Huy , Schläppi Michael
Published: October 2021

Boosting cold stress tolerance in crop plants can minimize stress-mediated yield losses. Asian rice (Oryza sativa L.), one of the most consumed cereal crops, originated from subtropical regions and is generally sensitive to low temperature environments. Within the two subspecies of rice, JAPONICA, and INDICA, the cold tolerance potential of its accessions is highly variable and depends on their genetic background. Yet, cold stress tolerance response mechanisms are complex and not well understood. This study utilized 370 accessions from the Rice Diversity Panel 1 (RDP1) to investigate and correlate four cold stress tolerance response phenotypes: membrane damage, seedling survivability, and catalase and anthocyanin antioxidative activity. Most JAPONICA accessions, and admixed accessions within JAPONICA, had lower membrane damage, higher antioxidative activity, and overall, higher seedling survivability compared to INDICA accessions. Genome-wide association study (GWAS) mapping was done using the four traits to find novel quantitative trait loci (QTL), and to validate and fine-map previously identified QTL. A total of 20 QTL associated to two or more traits were uncovered by our study. Gene Ontology (GO) term enrichment analyses satisfying four layers of filtering retrieved three potential pathways: signal transduction, maintenance of plasma membrane and cell wall integrity, and nucleic acids metabolism as general mechanisms of cold stress tolerance responses involving antioxidant activity.