bluuebunny/crossref_metadata_2025 huggingface dataset:
The selective NLRP3 inhibitor MCC950 hinders atherosclerosis development by attenuating inflammation and pyroptosis in macrophages
Authors: Zeng Wenyun , Wu Danbin , Sun Yingxin , Suo Yanrong , Yu Qun , Zeng Miao , Gao Qing , Yu Bin , Jiang Xijuan , Wang Yijing
Published: September 2021

NLRP3 inflammasome is a vital player in macrophages pyroptosis, which is a type of proinflammatory cell-death and takes part in the pathogenesis of atherosclerosis. In this study, we used apoE−/− mice and ox-LDL induced THP-1 derived macrophages to explore the mechanisms of MCC950, a selective NLRP3 inhibitor in treating atherosclerosis. For the in vivo study, MCC950 was intraperitoneal injected to 8-week-old apoE−/− mice fed with high-fat diet for 12 weeks. For the in vitro study, THP-1 derived macrophages were treated with ox-LDL and MCC950 for 48 h. MCC950 administration reduced plaque areas and macrophages contents, but did not improve the serum lipid profiles in aortic root of apoE−/− mice. MCC950 inhibited the activation of NLRP3/ASC/Caspase-1/GSDMD-N axis, and alleviated macrophages pyroptosis and the production of IL-1β and IL-18 both in aorta and in cell lysates. However, MCC950 did not affect the expression of TLR4 or the mRNA levels of NLRP3 inflammasome and its downstream proteins, suggesting that MCC950 had no effects on the priming of NLRP3 inflammasome activation in macrophages. The anti-atherosclerotic mechanisms of MCC950 on attenuating macrophages inflammation and pyroptosis involved in inhibiting the assembly and activation of NLRP3 inflammasome, rather than interrupting its priming.
BTN2A2 protein negatively regulates T cells to ameliorate collagen-induced arthritis in mice
Authors: He Xueping , Hu Rong , Luo Peng , Gao Jie , Yang Wenjiang , Li Jiaju , Huang Youjiao , Han Feng , Lai Laijun , Su Min
Published: September 2021

Rheumatoid arthritis (RA) is an autoimmune disorder characterized by persistent inflammatory responses in target tissues and organs, resulting in the destruction of joints. Collagen type II (CII)-induced arthritis (CIA) is the most used animal model for human RA. Although BTN2A2 protein has been previously shown to inhibit T cell functions in vitro, its effect on autoimmune arthritis has not been reported. In this study, we investigate the ability of a recombinant BTN2A2-IgG2a Fc (BTN2A2-Ig) fusion protein to treat CIA. We show here that administration of BTN2A2-Ig attenuates established CIA, as compared with control Ig protein treatment. This is associated with reduced activation, proliferation and Th1/Th17 cytokine production of T cells in BTN2A2-Ig-treated CIA mice. BTN2A2-Ig also inhibits CII-specific T cell proliferation and Th1/Th17 cytokine production. Although the percentage of effector T cells is decreased in BTN2A2-Ig-treated CIA mice, the proportions of naive T cells and regulatory T cells is increased. Furthermore, BTN2A2-Ig reduces the percentage of proinflammatory M1 macrophages but increases the percentage of anti-inflammatory M2 macrophages in the CIA mice. Our results suggest that BTN2A2-Ig protein has the potential to be used in the treatment of collagen-induced arthritis models.
Proteasome inhibition by bortezomib parallels a reduction in head and neck cancer cells growth, and an increase in tumor-infiltrating immune cells
Authors: Benvenuto Monica , Ciuffa Sara , Focaccetti Chiara , Sbardella Diego , Fazi Sara , Scimeca Manuel , Tundo Grazia Raffaella , Barillari Giovanni , Segni Maria , Bonanno Elena , Manzari Vittorio , Modesti Andrea , Masuelli Laura , Coletta Massimo , Bei Roberto
Published: September 2021

Head and neck cancer (HNC) has frequently an aggressive course for the development of resistance to standard chemotherapy. Thus, the use of innovative therapeutic drugs is being assessed. Bortezomib is a proteasome inhibitor with anticancer effects. In vitro antitumoral activity of Bortezomib was investigated employing human tongue (SCC-15, CAL-27), pharynx (FaDu), salivary gland (A-253) cancer cell lines and a murine cell line (SALTO-5) originated from a salivary gland adenocarcinoma arising in BALB-neuT male mice transgenic for the oncogene neu. Bortezomib inhibited cell proliferation, triggered apoptosis, modulated the expression and activation of pro-survival signaling transduction pathways proteins activated by ErbB receptors and inhibited proteasome activity in vitro. Intraperitoneal administration of Bortezomib delayed tumor growth of SALTO-5 cells transplanted in BALB-neuT mice, protracted mice survival and adjusted tumor microenvironment by increasing tumor-infiltrating immune cells (CD4+ and CD8+ T cells, B lymphocytes, macrophages, and Natural Killer cells) and by decreasing vessels density. In addition, Bortezomib modified the expression of proteasome structural subunits in transplanted SALTO-5 cells. Our findings further support the use of Bortezomib for the treatment of HNC and reveal its ineffectiveness in counteracting the activation of deregulated specific signaling pathways in HNC cell lines when resistance to proteasome inhibition is developed.
Hemoglobin and hematocrit levels are positively associated with blood pressure in children and adolescents 10 to 18 years old
Authors: Jeong Hwal Rim , Shim Young Suk , Lee Hae Sang , Hwang Jin Soon
Published: September 2021

To investigate the associations between hemoglobin (Hb) concentration and hematocrit (Hct), and blood pressure (BP) in children and adolescents. The study population consisted of 7950 subjects total (4229 boys and 3721 girls) aged 10–18 years who participated in the Korea National Health and Nutrition Examination Surveys conducted between 2007 and 2017. The prevalence of hypertension was 19.19% (21.51% for boys and 16.5% for girls) among the study population, and the prevalence of obesity was 9.59% (10.5% for boys and 8.6% for girls). Hb count and Hct tended to increase with the degree of obesity and BP elevation. Systolic BP (SBP) and diastolic BP (DBP) positively correlated with Hb count and Hct in both sexes. Following multiple linear regression analysis, Hb count and Hct presented a positive association with SBP and DBP after adjusting for age, BMI SDS, alcohol consumption, smoking status, physical activity, rural residence, household income, diagnosis of T2DM, hypertension, and dyslipidemia. Hb count and Hct were positively associated with SBP and DBP in children and adolescents 10–18 years old.
Flexural behaviour and evaluation of ultra-high-performance fibre reinforced concrete beams cured at room temperature
Authors: Huang Jinlin , He Zhiying , Khan Muhammad Basit Ehsan , Zheng Xiaohong , Luo Zhibin
Published: September 2021

Heat treatment is often required for ultra-high-performance concrete (UHPC) to achieve high strength. To broad its use in construction, the effect of different curing conditions on the properties of UHPC has been developed for many years. The experimental investigation of large scale ultra-high-performance fibre reinforced concrete (UHPFRC) beams is limited. In the present study, UHPFRC specimens and concrete cured at 20 °C were prepared to investigate the properties and flexural behaviour. The standard cubic compressive strength of UHPFRC specimens cannot be achieved at curing temperature of 20 °C. The bearing capacity under flexure was enhanced with the increase of reinforcement ratio. The failure modes of beams changed from ductile to brittle as the reinforcement ratio increased from 1.26 to 9.50%. The flexural behaviour of UHPFRC beams cured at room temperature was in accordance with the UHPFRC beams cured at high temperature in previous studies. In addition, the calculation model of CECS38-2004 underestimated the bending moment capacity of the under-reinforced UHPFRC beams (with reinforcement ratio from 0 to 7.85%) and overestimated the bending moment capacity of the UHPFRC beams with high reinforcement ration of 9.50%.
Sleep quality, autonomic dysfunction and renal function in diabetic patients with pre-CKD phase
Authors: Kadoya Manabu , Morimoto Akiko , Miyoshi Akio , Kakutani-Hatayama Miki , Kosaka-Hamamoto Kae , Konishi Kosuke , Kusunoki Yoshiki , Shoji Takuhito , Koyama Hidenori
Published: September 2021

Diabetes has been established as a strong risk factor for chronic kidney disease (CKD). Sleep apnea, poor sleep quality (PSQ), and autonomic imbalance are also considered to be potential risk factors for decline in renal function, though no known study has examined their integrated predictive value in diabetic and non-diabetic patients without CKD. The present cohort consisted of 754 serial patients (diabetes; n = 231, non-diabetes; n = 523) without CKD registered in the Hyogo Sleep Cardio-Autonomic Atherosclerosis (HSCAA) study. Patients underwent examinations to determine respiratory event index and objective sleep quality using actigraphy, as well as heart rate variability (HRV). Renal outcome was defined as a decline in estimated glomerular filtration rate to less than 60 ml/min/1.73 m2 for more than 3 months. Kaplan–Meier analysis showed that diabetic patients with PSQ or low HRV, but not sleep apnea, had a significantly increased risk for renal outcome. Furthermore, Cox proportional hazards analysis revealed that PSQ was significantly associated with elevated risk of renal outcome (HR: 2.57; 95% CI: 1.01–6.53, p = 0.045) independent of sleep apnea and classical risk factors. Low HRV tended to be, but not significantly (p = 0.065), associated with the outcome. In non-diabetic patients, PSQ was also significantly and independently associated with renal outcome, whereas sleep apnea and low HRV were not. In conclusion, PSQ and low HRV appear to be important predictors of decline in renal function in diabetic patients without CKD.
Somatic embryogenesis in mature zygotic embryos of Picea pungens
Authors: Tao Jing , Chen Shigang , Qin Caiyun , Li Qingmei , Cai Jufeng , Sun Changbin , Wang Weiming , Weng Yuhui
Published: September 2021

This study developed somatic embryogenesis protocols for Picea pungens (Engelm), an important ornamental species, including initiation, proliferation, maturation, germination, and acclimation. Somatic embryogenic tissues were induced from mature zygotic embryos of five families, with a frequency of $$\ge $$
≥
 22% for each. Embryogenic tissues (ET) from 13 clones of three families were proliferated for one week, achieving an average rate of 179.1%. The ET of 38 clones of three families were cultured in maturation medium for six weeks; 188 mature embryos on average were counted per gram ET cultured, of which $$\ge $$
≥
 81.1% appeared normal, and each clone developed at least 28 normally matured embryos. A total of 69.9% or more of cotyledonary somatic embryos germinated normally and developed into normal emblings. The experiment of transplanting the emblings into a greenhouse had an average survival rate of 68.5%. Considerable variation among and within families during initiation and proliferation was observed, but this variation decreased in the maturation and germination. Changing the concentration of plant growth regulator of the initiation medium did not significantly change the initiation frequency. We recommend incorporating these protocols into the current Picea pungens practical programs, although further research is essential to increase efficiencies and reduce cost.
Dissection of the bone marrow microenvironment in hairy cell leukaemia identifies prognostic tumour and immune related biomarkers
Authors: Koldej Rachel M. , Prabahran Ashvind , Tan Chin Wee , Ng Ashley P. , Davis Melissa J. , Ritchie David S.
Published: September 2021

Hairy cell leukaemia (HCL) is a rare CD20+ B cell malignancy characterised by rare “hairy” B cells and extensive bone marrow (BM) infiltration. Frontline treatment with the purine analogue cladribine (CDA) results in a highly variable response duration. We hypothesised that analysis of the BM tumour microenvironment would identify prognostic biomarkers of response to CDA. HCL BM immunology pre and post CDA treatment and healthy controls were analysed using Digital Spatial Profiling to assess the expression of 57 proteins using an immunology panel. A bioinformatics pipeline was developed to accommodate the more complex experimental design of a spatially resolved study. Treatment with CDA was associated with the reduction in expression of HCL tumour markers (CD20, CD11c) and increased expression of myeloid markers (CD14, CD68, CD66b, ARG1). Expression of HLA-DR, STING, CTLA4, VISTA, OX40L were dysregulated pre- and post-CDA. Duration of response to treatment was associated with greater reduction in tumour burden and infiltration by CD8 T cells into the BM post-CDA. This is the first study to provide a high multiplex analysis of HCL BM microenvironment demonstrating significant immune dysregulation and identify biomarkers of response to CDA. With validation in future studies, prospective application of these biomarkers could allow early identification and increased monitoring in patients at increased relapse risk post CDA.
Behavioral responses to a cyber attack in a hospital environment
Authors: Willing Markus , Dresen Christian , Gerlitz Eva , Haering Maximilian , Smith Matthew , Binnewies Carmen , Guess Tim , Haverkamp Uwe , Schinzel Sebastian
Published: September 2021

Technical and organizational steps are necessary to mitigate cyber threats and reduce risks. Human behavior is the last line of defense for many hospitals and is considered as equally important as technical security. Medical staff must be properly trained to perform such procedures. This paper presents the first qualitative, interdisciplinary research on how members of an intermediate care unit react to a cyberattack against their patient monitoring equipment. We conducted a simulation in a hospital training environment with 20 intensive care nurses. By the end of the experiment, 12 of the 20 participants realized the monitors’ incorrect behavior. We present a qualitative behavior analysis of high performing participants (HPP) and low performing participants (LPP). The HPP showed fewer signs of stress, were easier on their colleagues, and used analog systems more often than the LPP. With 40% of our participants not recognizing the attack, we see room for improvements through the use of proper tools and provision of adequate training to prepare staff for potential attacks in the future.
Large-bodied birds are over-represented in unstructured citizen science data
Authors: Callaghan Corey T. , Poore Alistair G. B. , Hofmann Max , Roberts Christopher J. , Pereira Henrique M.
Published: September 2021

Citizen science platforms are quickly accumulating hundreds of millions of biodiversity observations around the world annually. Quantifying and correcting for the biases in citizen science datasets remains an important first step before these data are used to address ecological questions and monitor biodiversity. One source of potential bias among datasets is the difference between those citizen science programs that have unstructured protocols and those that have semi-structured or structured protocols for submitting observations. To quantify biases in an unstructured citizen science platform, we contrasted bird observations from the unstructured iNaturalist platform with that from a semi-structured citizen science platform—eBird—for the continental United States. We tested whether four traits of species (body size, commonness, flock size, and color) predicted if a species was under- or over-represented in the unstructured dataset compared with the semi-structured dataset. We found strong evidence that large-bodied birds were over-represented in the unstructured citizen science dataset; moderate evidence that common species were over-represented in the unstructured dataset; strong evidence that species in large groups were over-represented; and no evidence that colorful species were over-represented in unstructured citizen science data. Our results suggest that biases exist in unstructured citizen science data when compared with semi-structured data, likely as a result of the detectability of a species and the inherent recording process. Importantly, in programs like iNaturalist the detectability process is two-fold—first, an individual organism needs to be detected, and second, it needs to be photographed, which is likely easier for many large-bodied species. Our results indicate that caution is warranted when using unstructured citizen science data in ecological modelling, and highlight body size as a fundamental trait that can be used as a covariate for modelling opportunistic species occurrence records, representing the detectability or identifiability in unstructured citizen science datasets. Future research in this space should continue to focus on quantifying and documenting biases in citizen science data, and expand our research by including structured citizen science data to understand how biases differ among unstructured, semi-structured, and structured citizen science platforms.
GABAB receptor signaling in the caudate putamen is involved in binge-like consumption during a high fat diet in mice
Authors: Sun Runan , Tsunekawa Taku , Hirose Tomonori , Yaginuma Hiroshi , Taki Keigo , Mizoguchi Akira , Miyata Takashi , Kobayashi Tomoko , Sugiyama Mariko , Onoue Takeshi , Takagi Hiroshi , Hagiwara Daisuke , Ito Yoshihiro , Iwama Shintaro , Suga Hidetaka , Banno Ryoichi , Bettler Bernhard , Arima Hiroshi
Published: September 2021

Previous studies suggest that signaling by the gamma-aminobutyric acid (GABA) type B receptor (GABABR) is involved in the regulation of binge eating, a disorder which might contribute to the development of obesity. Here, we show that intermittent access to a high fat diet (HFD) induced binge-like eating behavior with activation of dopamine receptor d1 (drd1)-expressing neurons in the caudate putamen (CPu) and nucleus accumbens (NAc) in wild-type (WT) mice. The activation of drd1-expressing neurons during binge-like eating was substantially increased in the CPu, but not in the NAc, in corticostriatal neuron-specific GABABR-deficient knockout (KO) mice compared to WT mice. Treatment with the GABABR agonist, baclofen, suppressed binge-like eating behavior in WT mice, but not in KO mice, as reported previously. Baclofen also suppressed the activation of drd1-expressing neurons in the CPu, but not in the NAc, during binge-like eating in WT mice. Thus, our data suggest that GABABR signaling in CPu neurons expressing drd1 suppresses binge-like consumption during a HFD in mice.
Real-time polarization microscopy of fibrillar collagen in histopathology
Authors: Keikhosravi Adib , Shribak Michael , Conklin Matthew W. , Liu Yuming , Li Bin , Loeffler Agnes , Levenson Richard M. , Eliceiri Kevin W.
Published: September 2021

Over the past two decades, fibrillar collagen reorganization parameters such as the amount of collagen deposition, fiber angle and alignment have been widely explored in numerous studies. These parameters are now widely accepted as stromal biomarkers and linked to disease progression and survival time in several cancer types. Despite all these advances, there has not been a significant effort to make it possible for clinicians to explore these biomarkers without adding steps to the clinical workflow or by requiring high-cost imaging systems. In this paper, we evaluate previously described polychromatic polarization microscope (PPM) to visualize collagen fibers with an optically generated color representation of fiber orientation and alignment when inspecting the sample by a regular microscope with minor modifications. This system does not require stained slides, but is compatible with histological stains such as H&E. Consequently, it can be easily accommodated as part of regular pathology review of tissue slides, while providing clinically useful insight into stromal composition.
TYROBP, TLR4 and ITGAM regulated macrophages polarization and immune checkpoints expression in osteosarcoma
Authors: Liang Tuo , Chen Jiarui , Xu GuoYong , Zhang Zide , Xue Jiang , Zeng Haopeng , Jiang Jie , Chen Tianyou , Qin Zhaojie , Li Hao , Ye Zhen , Nie Yunfeng , Liu Chong , Zhan Xinli
Published: September 2021

We established a relationship among the immune-related genes, tumor-infiltrating immune cells (TIICs), and immune checkpoints in patients with osteosarcoma. The gene expression data for osteosarcoma were downloaded from UCSC Xena and GEO database. Immune-related differentially expressed genes (DEGs) were detected to calculate the risk score. “Estimate” was used for immune infiltrating estimation and “xCell” was used to obtain 64 immune cell subtypes. Furthermore, the relationship among the risk scores, immune cell subtypes, and immune checkpoints was evaluated. The three immune-related genes (TYROBP, TLR4, and ITGAM) were selected to establish a risk scoring system based on their integrated prognostic relevance. The GSEA results for the Hallmark and KEGG pathways revealed that the low-risk score group exhibited the most gene sets that were related to immune-related pathways. The risk score significantly correlated with the xCell score of macrophages, M1 macrophages, and M2 macrophages, which significantly affected the prognosis of osteosarcoma. Thus, patients with low-risk scores showed better results with the immune checkpoints inhibitor therapy. A three immune-related, gene-based risk model can regulate macrophage activation and predict the treatment outcomes the survival rate in osteosarcoma.
Effects of hypoxia and nanocarrier size on pH-responsive nano-delivery system to solid tumors
Authors: Soltani M. , Souri Mohammad , Moradi Kashkooli Farshad
Published: September 2021

One of the special features of solid tumors is the acidity of the tumor microenvironment, which is mainly due to the presence of hypoxic regions. Therefore, pH-responsive drug delivery systems have recently been highly welcomed. In the present study, a comprehensive mathematical model is presented based on extravascular drug release paradigm. Accordingly, drug delivery system using pH-responsive nanocarriers is taken into account to examine the impacts of hypoxic regions as well as the size of nanocarriers for cancerous cell-death. The extent of hypoxic regions is controlled by vascular density. This means that regions with very low vascular density represent regions of hypoxia. Using this mathematical model, it is possible to simulate the extracellular and intracellular concentrations of drug by considering the association/disassociation of the free drug to the cell-surface receptors and cellular uptake. Results show that nanocarriers with smaller sizes are more effective due to higher accumulation in the tumor tissue interstitium. The small size of the nanocarriers also allows them to penetrate deeper, so they can expose a larger portion of the tumor to the drug. Additionally, the presence of hypoxic regions in tumor reduces the fraction of killed cancer cells due to reduced penetration depth. The proposed model can be considered for optimizing and developing pH-sensitive delivery systems to reduce both cost and time of the process.
Mouse lipidomics reveals inherent flexibility of a mammalian lipidome
Authors: Surma Michał A. , Gerl Mathias J. , Herzog Ronny , Helppi Jussi , Simons Kai , Klose Christian
Published: September 2021

Lipidomics has become an indispensable method for the quantitative assessment of lipid metabolism in basic, clinical, and pharmaceutical research. It allows for the generation of information-dense datasets in a large variety of experimental setups and model organisms. Previous studies, mostly conducted in mice (Mus musculus), have shown a remarkable specificity of the lipid compositions of different cell types, tissues, and organs. However, a systematic analysis of the overall variation of the mouse lipidome is lacking. To fill this gap, in the present study, the effect of diet, sex, and genotype on the lipidomes of mouse tissues, organs, and bodily fluids has been investigated. Baseline quantitative lipidomes consisting of 796 individual lipid molecules belonging to 24 lipid classes are provided for 10 different sample types. Furthermore, the susceptibility of lipidomes to the tested parameters is assessed, providing insights into the organ-specific lipidomic plasticity and flexibility. This dataset provides a valuable resource for basic and pharmaceutical researchers working with murine models and complements existing proteomic and transcriptomic datasets. It will inform experimental design and facilitate interpretation of lipidomic datasets.
Melting of micro/nanoparticles considering anisotropy of surface energy
Authors: Yang C. M. , Chen M. W. , Zheng G. J. , Wang Z. D.
Published: September 2021

The effect of surface energy on the melting of micro/nanoparticles is studied using the asymptotic method. The asymptotic solution of the dynamic model for micro/nanoparticle melting reveals the dependence of the particle melting temperature on the particle size and the anisotropy of surface energy. Specifically, as the particle radius decreases, the isotropic surface energy reduces the melting temperature and accelerates the interface melting of the particle. Along certain crystal orientations, the anisotropy of surface energy enhances the melting temperature of the micro/nanoparticles, whereas depresses the melting temperature of the micro/nanoparticle along other crystal orientations. The anisotropy of surface energy enhances the melting speed of the micro/nanoparticles along certain crystal orientations, whereas reduces the melting speed of the micro/nanoparticles along other crystal orientations. The result of the asymptotic solution is in good agreement with the experimental data.
Assessing effectiveness of Komagataeibacter strains for producing surface-microstructured cellulose via guided assembly-based biolithography
Authors: Brugnoli Marcello , Robotti Francesco , La China Salvatore , Anguluri Kavitha , Haghighi Hossein , Bottan Simone , Ferrari Aldo , Gullo Maria
Published: September 2021

In this study, a medical device made of surface microstructured bacterial cellulose was produced using cellulose-producing acetic acid bacteria wild-type strains in combination with guided assembly-based biolithography. The medical device aims at interfering with the cell's focal adhesion establishment and maturation around implantable devices placed in soft tissues by the symmetrical array on its surface. A total of 25 Komagataeibacter strains was evaluated over a three-step selection. In the first step, the ability of strains to produce a suitable bacterial cellulose layer with high production yield was examined, then nine strains, with a uniform and smooth layer of bacterial cellulose, were cultured in a custom-made silicone bioreactor and finally the characteristics of the symmetrical array of topographic features on the surface were analysed. Selected strains showed high inter and intra species variability in bacterial cellulose production. The devices obtained by K2G30, K1G4, DSM 46590 (Komagataeibacter xylinus), K2A8 (Komagataeibacter sp.) and DSM 15973T (Komagataeibacter sucrofermentas) strains were pouched-formed with hexagonal surface pattern required for reducing the formation of fibrotic tissue around devices, once they are implanted in soft tissues. Our findings revealed the effectiveness of the selected Komagataeibacter wild-type strains in producing surface microstructured bacterial cellulose pouches for making biomedical devices.
Novel attempt at discrimination of a bullet-shaped siphonophore (Family Diphyidae) using matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-ToF MS)
Authors: Park Nayeon , Yeom Jisu , Jeong Raehyuk , Lee Wonchoel
Published: September 2021

One major difficulty in identifying the gelatinous bodied bullet-shaped Siphonophore, Diphyids, is that their shape is deformed following ethanol fixation. Ethanol often is preferred over other fixatives, since samples fixed in ethanol can be used for molecular studies that can supplement morphological findings. To overcome this problem, we obtained protein mass spectra of ten species of Diphyidae found in the waters of the Kuroshio Current (Northwest Pacific and South Coast of South Korea) to test whether MALDI-ToF MS could be used as a methodology for species identification. In addition, a number of morphological characteristics that can be used with ethanol-treated samples was summarized. Concatenated phylogenetic analysis was also performed to determine the phylogenetic relationship by obtaining partial sequences of four genes (mtCOI, 16S rRNA, 18S rRNA, and ITS regions). Based on our integrative analysis, MALDI-ToF MS was evaluated as a potentially fast, inexpensive, and accurate tool for species identification along with conventional morphological and DNA barcoding for Diphyidae.
Necro-inflammatory activity grading in chronic viral hepatitis with three-dimensional multifrequency MR elastography
Authors: Garteiser Philippe , Pagé Gwenaël , d’Assignies Gaspard , Leitao Helena S. , Vilgrain Valérie , Sinkus Ralph , Van Beers Bernard E.
Published: September 2021

The purpose of this study was to assess the diagnostic value of multifrequency MR elastography for grading necro-inflammation in the liver. Fifty participants with chronic hepatitis B or C were recruited for this institutional review board-approved study. Their liver was examined with multifrequency MR elastography. The storage, shear and loss moduli, and the damping ratio were measured at 56 Hz. The multifrequency wave dispersion coefficient of the shear modulus was calculated. The measurements were compared to reference markers of necro-inflammation and fibrosis with Spearman correlations and multiple regression analysis. Diagnostic accuracy was assessed. At multiple regression analysis, necro-inflammation was the only determinant of the multifrequency dispersion coefficient, whereas fibrosis was the only determinant of the storage, loss and shear moduli. The multifrequency dispersion coefficient had the largest AUC for necro-inflammatory activity A ≥ 2 [0.84 (0.71–0.93) vs. storage modulus AUC: 0.65 (0.50–0.79), p = 0.03], whereas the storage modulus had the largest AUC for fibrosis F ≥ 2 [AUC (95% confidence intervals) 0.91 (0.79–0.98)] and cirrhosis F4 [0.97 (0.88–1.00)]. The measurement of the multifrequency dispersion coefficient at three-dimensional MR elastography has the potential to grade liver necro-inflammation in patients with chronic vial hepatitis.
A pilot study of 3D tissue-engineered bone marrow culture as a tool to predict patient response to therapy in multiple myeloma
Authors: Alhallak Kinan , Jeske Amanda , de la Puente Pilar , Sun Jennifer , Fiala Mark , Azab Feda , Muz Barbara , Sahin Ilyas , Vij Ravi , DiPersio John F. , Azab Abdel Kareem
Published: September 2021

Cancer patients undergo detrimental toxicities and ineffective treatments especially in the relapsed setting, due to failed treatment attempts. The development of a tool that predicts the clinical response of individual patients to therapy is greatly desired. We have developed a novel patient-derived 3D tissue engineered bone marrow (3DTEBM) technology that closely recapitulate the pathophysiological conditions in the bone marrow and allows ex vivo proliferation of tumor cells of hematologic malignancies. In this study, we used the 3DTEBM to predict the clinical response of individual multiple myeloma (MM) patients to different therapeutic regimens. We found that while no correlation was observed between in vitro efficacy in classic 2D culture systems of drugs used for MM with their clinical efficacious concentration, the efficacious concentration in the 3DTEBM were directly correlated. Furthermore, the 3DTEBM model retrospectively predicted the clinical response to different treatment regimens in 89% of the MM patient cohort. These results demonstrated that the 3DTEBM is a feasible platform which can predict MM clinical responses with high accuracy and within a clinically actionable time frame. Utilization of this technology to predict drug efficacy and the likelihood of treatment failure could significantly improve patient care and treatment in many ways, particularly in the relapsed and refractory setting. Future studies are needed to validate the 3DTEBM model as a tool for predicting clinical efficacy.
Predictors for depressive symptoms by four types of disability
Authors: Jung Sun Wook , Yoon Jin-Ha , Lee Wanhyung
Published: September 2021

This study aimed to examine the longitudinal relationship between disability and depressive symptoms, by comparing four types of disability in community-dwelling individuals with disabilities in South Korea. A total of 3347 South Koreans with disabilities from the second wave of the Panel Survey of Employment for the Disabled was utilized. Depressive symptomatology was assessed by whether the participant had experienced depressive symptoms for more than two weeks during the past year. A multivariate logistic regression model was used to calculate the odds ratio (OR) for depressive symptoms, and a Cox proportional hazards model to calculate the hazard ratio (HR) for two-year survival analysis. Persons who acquired mental disability from accident or industrial disaster and persons with congenital physical-internal disability were at higher risk for depressive symptoms. Maintaining employment was found to be an effective way to decrease the risk of depressive symptoms in persons with physical-external disability, sensory/speech disability, or mental disability. In contrast, in physical-internal disability, retaining normal ability to work seemed to be the key to reduce the risk of depressive symptoms. Predictors of depressive symptoms were found to differ depending on the type of disability. Such differences should be reflected in clinical and policy-level interventions to address the specific psychiatric needs of persons with different disabilities.
Establishment of appropriate glaucoma models using dexamethasone or TGFβ2 treated three-dimension (3D) cultured human trabecular meshwork (HTM) cells
Authors: Watanabe Megumi , Ida Yosuke , Ohguro Hiroshi , Ota Chiaki , Hikage Fumihito
Published: September 2021

To establish appropriate ex vivo models for a glaucomatous trabecular meshwork (TM), two-dimensional (2D) and three-dimensional (3D) cultures of human trabecular meshwork cells (HTM) were prepared in the presence of 250 nM dexamethasone (DEX) or 5 ng/mL TGFβ2, and characterized by the following analyses; transendothelial electrical resistance (TEER) measurements, FITC dextran permeability, scanning electron microscopy and the expression of the extracellular matrix (ECM) including collagen (COL)1, 4 and 6, and fibronectin (FN), α-smooth muscle actin (α-SMA), tissue inhibitor of metalloproteinase (TIMP)1–4, and matrix metalloproteinase (MMP)2, 9 and 14. DEX and TGFβ2 both caused a significant increase or decrease in the TEER values and FITC dextran permeability. During the 3D spheroid culture, DEX or TGFβ2 induced a mild and significant down-sizing and an increase in stiffness, respectively. TGFβ2 induced a significant up-regulation of COL1 and 4, FN, α-SMA, and MMP 2 and 14 (2D) or COL1 and 6, and TIMP2 and 3 (3D), and DEX induced a significant up-regulation of FN (3D) and TIMP4 (2D and 3D). The findings presented herein indicate that DEX or TGFβ2 resulted in mild and severe down-sized and stiff 3D HTM spheroids, respectively, thus making them viable in vitro HTM models for steroid-induced and primary open angle glaucoma.
Combination of FIB-4 with ultrasound surface nodularity or elastography as predictors of histologic advanced liver fibrosis in chronic liver disease
Authors: Moini Maryam , Onofrio Fernanda , Hansen Bettina E. , Adeyi Oyedele , Khalili Korosh , Patel Keyur
Published: September 2021

Reliable and available non-invasive methods for hepatic fibrosis assessment are important in chronic liver disease (CLD). Our aim was to compare stepwise algorithms combining standard ultrasound with serum markers and transient elastography (TE) for detecting advanced fibrosis (F3-4) and cirrhosis. Retrospective single center study between 2012 and 2018 of CLD patients with biopsy, TE, blood tests, and liver ultrasound parameters of surface nodularity (SN), lobar redistribution, and hepatic vein nodularity. Our cohort included 157 patients (51.6% males), mean age 47.6 years, predominantly non-alcoholic fatty liver disease and viral hepatitis (61%), with F3-4 prevalence of 60.5%. Area under the curve for F3-4 was 0.89 for TE ≥ 9.6 kPa and 0.80 for FIB-4 > 3.25. In multivariate modeling, TE ≥ 9.6 kPa (OR 21.78) and SN (OR 3.81) had independent association with F3-4; SN (OR 5.89) and TE ≥ 10.2 kPa (OR 15.73) were independently associated with cirrhosis. Two stepwise approaches included FIB-4 followed by SN or TE; sensitivity and specificity of stepwise SN were 0.65 and 1.00, and 0.89 and 0.33 for TE ≥ 9.6 kPa, respectively. Ultrasound SN and TE were independently predictive of F3-4 and cirrhosis in our cohort. FIB-4 followed by SN had high specificity for F3-4.
Improvement in the physical and mechanical properties of the cement-based composite with the addition of nanostructured BN–Fe3O4 reinforcement
Authors: Ghazanlou Siavash Imanian , Ghazanlou Siamak Imanian , Ashraf Warda
Published: September 2021

In this work, the performance of modified cement by nanostructures consisting of boron nitride (BN) and iron oxide inorganic nanoparticles (Fe3O4) was analyzed. The mechanical strength, electrical resistivity, and the degree of cement hydration as well as the microstructure were investigated in detail. A hybrid filler boron nitride-iron oxide (BN–F) composed of Fe3O4and BN was successfully synthesized using a chemical reaction. Transmission electron microscope (TEM) results showed proper binding of BN–F nanostructures. Addition of the hybrid nanostructured BN–F5 (containing 0.5 wt.% Fe3O4and 0.5 wt.% BN) into the cement matrix increased the compressive strength and flexural strength by 65%, and 74%, respectively, after 28 days of curing. The improvement in mechanical strength is attributed to the increased surface friction induced by the Fe3O4nanoparticles on the BN surfaces, resulting in increased interaction with the matrix. Microstructural studies, such as scanning electron microscope (SEM), showed the formation of a dense structure due to improved dispersion in the cement environment and hybrid performance in preventing crack growth, which is the main reason for the overall improvement in mechanical properties. The concrete resistance gauge (RCON, Giatec) and simultaneous thermal analysis (STA) tests revealed a significant increase in thermal and electrical conductivity in composite reinforced with nanostructured BN–F.
Development of coronary dysfunction in adult progeny after maternal engineered nanomaterial inhalation during gestation
Authors: Fournier Sara B. , Lam Vincent , Goedken Michael J. , Fabris Laura , Stapleton Phoebe A.
Published: September 2021

Maternal exposure to environmental contaminants during pregnancy can profoundly influence the risk of developing cardiovascular disease in adult offspring. Our previous studies have demonstrated impaired cardiovascular health, microvascular reactivity, and cardiac function in fetal and young adult progeny after maternal inhalation of nano-sized titanium dioxide (nano-TiO2) aerosols during gestation. The present study was designed to evaluate the development of cardiovascular and metabolic diseases later in adulthood. Pregnant Sprague–Dawley rats were exposed to nano-TiO2 aerosols (~ 10 mg/m3, 134 nm median diameter) for 4 h per day, 5 days per week, beginning on gestational day (GD) 4 and ending on GD 19. Progeny were delivered in-house. Body weight was recorded weekly after birth. After 47 weeks, the body weight of exposed progeny was 9.4% greater compared with controls. Heart weight, mean arterial pressure, and plasma biomarkers of inflammation, dyslipidemia, and glycemic control were recorded at 3, 9 and 12 months of age, with no significant adaptations. While no clinical risk factors (i.e., hypertension, dyslipidemia, or systemic inflammation) emerged pertaining to the development of cardiovascular disease, we identified impaired endothelium-dependent and -independent arteriolar dysfunction and cardiac morphological alterations consistent with myocardial inflammation, degeneration, and necrosis in exposed progeny at 12 months. In conclusion, maternal inhalation of nano-TiO2 aerosols during gestation may promote the development of coronary disease in adult offspring.
The importance of input data on landslide susceptibility mapping
Authors: Gaidzik Krzysztof , Ramírez-Herrera María Teresa
Published: September 2021

Landslide detection and susceptibility mapping are crucial in risk management and urban planning. Constant advance in digital elevation models accuracy and availability, the prospect of automatic landslide detection, together with variable processing techniques, stress the need to assess the effect of differences in input data on the landslide susceptibility maps accuracy. The main goal of this study is to evaluate the influence of variations in input data on landslide susceptibility mapping using a logistic regression approach. We produced 32 models that differ in (1) type of landslide inventory (manual or automatic), (2) spatial resolution of the topographic input data, (3) number of landslide-causing factors, and (4) sampling technique. We showed that models based on automatic landslide inventory present comparable overall prediction accuracy as those produced using manually detected features. We also demonstrated that finer resolution of topographic data leads to more accurate and precise susceptibility models. The impact of the number of landslide-causing factors used for calculations appears to be important for lower resolution data. On the other hand, even the lower number of causative agents results in highly accurate susceptibility maps for the high-resolution topographic data. Our results also suggest that sampling from landslide masses is generally more befitting than sampling from the landslide mass center. We conclude that most of the produced landslide susceptibility models, even though variable, present reasonable overall prediction accuracy, suggesting that the most congruous input data and techniques need to be chosen depending on the data quality and purpose of the study.
Time-of-day dependent changes in guinea pig bladder afferent mechano-sensitivity
Authors: Christie Stewart , Zagorodnyuk Vladimir
Published: September 2021

The voiding of urine has a clear circadian rhythm with increased voiding during active phases and decreased voiding during inactive phases. Bladder spinal afferents play a key role in the regulation of bladder storage and voiding, but it is unknown whether they exhibit themselves a potential circadian rhythm. Therefore, this study aimed to determine the mechano- and chemo- sensitivity of three major bladder afferent classes at two opposite day-night time points. Adult female guinea pigs underwent conscious voiding monitoring and bladder ex vivo single unit extracellular afferent recordings at 0300 h and 1500 h to determine day-night modulation of bladder afferent activity. All guinea pigs voided a higher amount of urine at 1500 h compared to 0300 h. This was due to an increased number of voids at 1500 h. The mechano-sensitivity of low- and high-threshold stretch-sensitive muscular-mucosal bladder afferents to mucosal stroking and stretch was significantly higher at 1500 h compared to 0300 h. Low-threshold stretch-insensitive mucosal afferent sensitivity to stroking was significantly higher at 1500 h compared to 0300 h. Further, the chemosensitivity of mucosal afferents to N-Oleoyl Dopamine (endogenous TRPV1 agonist) was also significantly increased at 1500 h compared to 0300 h. This data indicates that bladder afferents exhibit a significant time-of-day dependent variation in mechano-sensitivity which may influence urine voiding patterns. Further studies across a 24 h period are warranted to reveal potential circadian rhythm modulation of bladder afferent activity.
Developmental models of the carrion beetle Thanatophilus rugosus (Linnaeus, 1758) (Coleoptera: Silphidae)
Authors: Montoya-Molina S. , Jakubec P. , Qubaiová J. , Novák M. , Šuláková H. , Růžička J.
Published: September 2021

Coleoptera are currently considered a fundamental tool to help solve criminal investigations, allowing forensic entomologists to estimate post-mortem intervals and obtain other ecology-related information. Thanatophilus rugosus (Linnaeus, 1758) is an important necrophagous beetle distributed through most of the Palaearctic region, where it is readily found on human bodies and animal carcasses. In this study, the new thermal summation models for all the developmental stages of Thanatophilus rugosus are provided. Beetles were reared at six different constant and ecologically relevant temperatures (12, 14, 16, 18, 20, and 22 °C), and their developmental times were measured. Thermal summation constants were calculated for each developmental stage (egg, three larval instars, post-feeding stage, and pupa).
Bovine NK-lysin peptides exert potent antimicrobial activity against multidrug-resistant Salmonella outbreak isolates
Authors: Dassanayake Rohana P. , Atkinson Briony M. , Mullis Adam S. , Falkenberg Shollie M. , Nicholson Eric M. , Casas Eduardo , Narasimhan Balaji , Bearson Shawn M. D.
Published: September 2021

Multidrug-resistant (MDR)Salmonellais a threat to public health. Non-antibiotic therapies could serve as important countermeasures to control MDRSalmonellaoutbreaks. In this study, antimicrobial activity of cationic α-helical bovine NK-lysin-derived antimicrobial peptides was evaluated against MDRSalmonellaoutbreak isolates. NK2A and NK2B strongly inhibited MDRSalmonellagrowth while NK1 and NK2C showed minimum-to-no growth inhibition. Scrambled-NK2A, which is devoid of α-helicity but has the same net positive charge as NK2A, also failed to inhibit bacterial growth. Incubation of negatively charged MDRSalmonellawith NK2A showed increased Zeta potential, indicating bacterial-peptide electrostatic attraction. Confocal and transmission electron microscopy studies revealed NK2A-mediated damage to MDRSalmonellamembranes. LPS inhibited NK2A-mediated growth suppression in a dose-dependent response, suggesting irreversible NK2A-LPS binding. LPS-NK2A binding and bacterial membrane disruption was also confirmed via electron microscopy using gold nanoparticle-NK2A conjugates. Finally, NK2A-loaded polyanhydride nanoparticles showed sustained peptide delivery and anti-bacterial activity. Together, these findings indicate that NK2A α-helicity and positive charge are prerequisites for antimicrobial activity and that MDRSalmonellakilling is mediated by direct interaction of NK2A with LPS and the inner membrane, leading to bacterial membrane permeabilization. With further optimization using nano-carriers, NK2A has the potential to become a potent anti-MDRSalmonellaagent.