bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract B09: Combining proteomics and genetic screens to identify KRAS synthetic lethal interactions
Authors: Sheth Shikha S. , Cook Danielle R. , Strasser Samantha D. , Martin Timothy D. , Menon Sneha , Popow Olesja , Paulo Joao A. , Elledge Steve J. , Haigis Kevin M.
Published: June 2021

KRAS is a member of the RAS superfamily of small GTPases, proteins that act as molecular switches regulating cellular pathways such as growth, survival, and membrane trafficking. Activating point mutations in KRAS are found in approximately 15% of all cancers and contribute to a malignant phenotype through deregulation of normal cell proliferation. Despite discovering RAS mutations in cancer over three decades ago and strong evidence that RAS mutations drive cancer progression and response to therapy, there have been limited advances in targeting RAS directly. In lieu of direct inhibitors, identifying synthetic lethal (SL) partners with mutant KRAS would reveal putative drug targets. This strategy has been employed previously but with limited success. We hypothesize that using tools such as novel conditional mutant KRAS isogenic cell lines and CRISPR-based loss-of-function screening will uncover pathways whose depletion selectively impairs mutant KRAS cells. Additionally, approaching this from a multi-omics angle, where we combine proteomics and CRISPR screening, will allow us to prioritize targets from each screen. We used CRISPR/Cas9-mediated genome engineering to generate a KRAS WT colon cancer cell line with conditional expression of mutant KRAS. Characterization of our isogenic cell lines confirms that KRAS G12D expression upregulates KRAS activity and enhances tumorigenicity. We used a CRISPR library targeting druggable genes and screened these isogenic cells in vitro, and additionally performed mass spectrometry on the isogenic pair to look at the differential regulation of proteins and phospho-proteins upon KRAS G12D expression. We plan to determine if the overlap of these datasets can provide us with a prioritized list of hits to validate, arguing for a multi-omics approach to better understand synthetic lethal interactions.

Citation Format: Shikha S. Sheth, Danielle R. Cook, Samantha D. Strasser, Timothy D. Martin, Sneha Menon, Olesja Popow, Joao A. Paulo, Steve J. Elledge, Kevin M. Haigis. Combining proteomics and genetic screens to identify KRAS synthetic lethal interactions [abstract]. In: Proceedings of the AACR Special Conference on Targeting RAS-Driven Cancers; 2018 Dec 9-12; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(5_Suppl):Abstract nr B09.
Abstract B29: SHANK3 in oncogenic RAS signaling
Authors: Lilja Johanna , Jcaquement Guillaume , Posada Itziar Martinez D. , Laasola Petra , Vesilahti Ella-Maria , Miihkinen Mitro , Salomaa Siiri , Kreienkamp Hans-Juergen , Barsukov Igor , Abankwa Daniel , Ivaska Johanna
Published: June 2021

RAS proteins play a direct causal role in human cancers, with activating mutations in RAS occurring in ∼30% of tumors. Despite comprehensive efforts, efficient targeting of RAS has not yet reached the clinic. Here, we report SHANK3, a synaptic scaffolding protein and a regulator of integrin activity, as a novel tumor suppressor targeting RAS proto-oncogenes, especially mutant KRAS. We previously found the N-terminal part of SHANK3 as an unexpected RAS-association domain with high affinity for active RAS proteins. Now we show that the direct binding of SHANK3 to active RAS abrogates the MAPK/ERK signaling and thereby inhibits the RAS-stimulated transformation and slows the growth of RAS-dependent tumor cells. SHANK3 expression is downregulated in RAS-driven human cancers, and high expression of SHANK3 correlates with improved patient survival in KRAS-driven pancreatic and lung adenocarcinoma. These data support that targeting the MAPK/ERK pathway by SHANK3 represents a novel promising therapeutic approach for RAS-driven cancers.

Citation Format: Johanna Lilja, Guillaume Jcaquement, Itziar Martinez D. Posada, Petra Laasola, Ella-Maria Vesilahti, Mitro Miihkinen, Siiri Salomaa, Hans-Juergen Kreienkamp, Igor Barsukov, Daniel Abankwa, Johanna Ivaska. SHANK3 in oncogenic RAS signaling [abstract]. In: Proceedings of the AACR Special Conference on Targeting RAS-Driven Cancers; 2018 Dec 9-12; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(5_Suppl):Abstract nr B29.
Abstract B36: Berberine induces apoptosis in cervical carcinoma cells by inducing DNA damage and inhibition of RAS MAPK pathway
Authors: Komal Komal , Athreyas Vidhya , Chaudhary Shilpi , Singh Mayank
Published: June 2021

Cervical cancer remains the leading cause of cancer mortality in females worldwide. Despite significant improvement in treatment modalities, the survival in advanced cervical cancer is still limited, resulting in poor survival. Berberine is an isoquinoline alkaloid isolated from Berberis vulgaris (barberry). Berberine is in focus for its preventive and therapeutic value in different cancers. Here we investigated how berberine modulated DNA damage response and survival pathway in cervical carcinoma cells. We carried out the current study in both HPV-positive and -negative cervical carcinoma cell lines. Our results indicate that berberine induced apoptosis in all the cervical carcinoma cells through activation of both caspase-dependent and -independent pathways. Berberine also induces accumulation of gamma H2AX foci in cervical carcinoma cells, which colocalized with proteins involved in DNA damage response, indicating accumulation of replication stress in berberine-treated cells. Berberine also repressed the proliferative RAS MAPK pathway, thereby reducing the proliferation of cervical carcinoma cells. Overall our data provide a novel insight into mechanism of berberine action in cervical carcinoma cells and underline its efficacy as a chemoadjuvant in treatment of cervical cancer.

Citation Format: Komal Komal, Vidhya Athreyas, Shilpi Chaudhary, Mayank Singh. Berberine induces apoptosis in cervical carcinoma cells by inducing DNA damage and inhibition of RAS MAPK pathway [abstract]. In: Proceedings of the AACR Special Conference on Targeting RAS-Driven Cancers; 2018 Dec 9-12; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(5_Suppl):Abstract nr B36.
Abstract IA09: Targeting K-RAS4B on biologic membranes
Authors: Ikura Mitsu
Published: June 2021

RAS proteins are frequently mutated in cancer (~30% of all human tumors) and an estimated worldwide death toll of RAS-associated cancers exceeds 2 million/yr. Despite enormous efforts in RAS research over three decades, there is no clinically approved RAS inhibitor and the RAS protein remains a challenging target for cancer therapy development. In order to overcome this challenge, we sought to better understand how RAS functions under physiologic conditions and alters related signaling pathways in the mutant RAS-driven tumors. Fully matured protein K-RAS4B, the major target for cancer therapeutics, is prenylated and methylated at the carboxy-terminus, which enables K-RAS4B to anchor to the plasma membrane where it receives an upstream signal and transmits the signal to a number of downsteam pathways. There is, however, a large gap in our understanding of how the matured K-RAS4B protein functions at the surface of the plasma membrane. As a first step, we sought to develop new conformational and functional assays for the RAS protein on lipid bilayers (i.e., nanodiscs) using various biochemical and biophysical techniques. We elucidated how the membrane environment dictates the conformation of K-RAS4B and how oncogenic mutations influence the membrane-dependent conformational states of the protein (Mazhab-Jafari et al., PNAS 2015). More recently, we have been investigating multiple aspects of K-RAS4B functions and I will discuss (i) how the biologic membrane influences K-RAS4B interaction with a binding domain of RAF kinases and (ii) how we could inhibit K-RAS4B at the membrane surface by small molecules (Fang et al., Cell Chem Biol 2018) and an engineered protein. Supported by CCS, CIHR, CFI and PMCF.

Citation Format: Mitsu Ikura. Targeting K-RAS4B on biologic membranes [abstract]. In: Proceedings of the AACR Special Conference on Targeting RAS-Driven Cancers; 2018 Dec 9-12; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(5_Suppl):Abstract nr IA09.
Abstract IA12: Targeting KRAS-regulated metabolic activities in pancreatic cancer
Authors: Bryant Kirsten L. , Hobbs G. Aaron , Der Channing J.
Published: June 2021

One promising direction for the development of therapeutic strategies for the treatment of KRAS-driven pancreatic ductal adenocarcinoma (PDAC) growth involves delineating the role of and mechanism for altered metabolism. KRAS-mutant PDAC is characterized by increased autophagy and macropinocytosis, processes that enhance nutrient availability that then supports the increased metabolic needs of PDAC. First, we addressed the role of KRAS in supporting autophagy-dependent PDAC growth. Surprisingly, we found that suppression of KRAS increased autophagic flux, as did pharmacologic inhibition of its effector ERK MAPK. We speculated that ERK inhibition might enhance PDAC dependence on autophagy by impairing KRAS-driven metabolic processes, and we demonstrate that either KRAS suppression or ERK inhibition decreased both glycolytic and mitochondrial functions. Furthermore, genetic or pharmacologic inhibition of autophagy synergistically enhanced ERK inhibitor-mediated antitumor activity. We conclude that concurrent inhibition of ERK and autophagy may be an effective PDAC treatment. Second, we evaluated mechanisms by which KRAS may drive macropinocytosis. These studies focused on KRAS G12R mutant PDAC. This mutation is rare in lung and colorectal cancers (~1%), yet high (~20%) in PDAC. We evaluated whether KRAS G12R is functionally distinct from the more common KRAS G12D/V mutant proteins. We found that KRAS G12D/V but not KRASG12R drives elevated macropinocytosis and that MYC is essential for this process in KRAS G12D/V but not KRAS G12R mutant PDAC. The KRAS G12R mutation uniquely disrupts interaction with a key effector, PI3K alpha, due to structural perturbations in the switch II region critical for effector interaction. Despite this defect, KRAS G12R-mutant PDAC displayed elevated macropinocytosis due to KRAS-independent PI3K gamma activity. Finally, the growth of KRAS G12R mutant PDAC in vitro and in vivo was preferentially sensitive to MEK-ERK inhibition compared to KRAS G12D/V. In summary, our elucidation of KRAS-dependent effector signaling mechanisms that drive altered metabolism identified novel therapeutic approaches for the treatment of PDAC.

Citation Format: Kirsten L. Bryant, G. Aaron Hobbs, Channing J. Der. Targeting KRAS-regulated metabolic activities in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Targeting RAS-Driven Cancers; 2018 Dec 9-12; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(5_Suppl):Abstract nr IA12.
Abstract PR01: Novel state I structures of oncogenic KRAS4b mutants bound to GTP analog
Authors: Chan Albert H. , Tran Timothy H. , Dharmaiah Srisathiyanarayanan , Nissley Dwight V. , Simanshu Dhirendra K.
Published: June 2021

The RAS family proteins alternate between active GTP-bound and inactive GDP-bound states. Due to the high affinity of GDP and GTP, and low intrinsic GTPase activity of RAS, switching between the two states is assisted by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). Many of the oncogenic RAS mutations result in impaired intrinsic and/or GAP-mediated GTPase function, leading to accumulation of constitutively active RAS. To understand the molecular mechanism behind the impairment, we crystallized and solved the structures of wild-type and six different KRAS4b oncogenic mutants bound to a non-hydrolysable GTP analog GMPPNP. Interestingly, we noticed variations in the conformation of the Switch I region, which contacts the nucleotide and many downstream effector proteins. In three of our mutants (G12C, G13D, Q61L), Switch I adopts an open conformation known as state I, which, similar to the GDP-bound state, does not contact the nucleotide and represents an inactive state of the RAS protein. Importantly, our state I structures revealed a new pocket created by the open Switch I loop that could be targeted in drug discovery. To screen for compounds that bind to this new Switch I pocket or other places of the protein, we started a fragment-screening campaign by X-ray crystallography using the KRAS4b-G13D-GMPPNP crystals. These crystals consistently diffracted to very high (~1.2 Å) resolutions, can be reproduced easily, are tolerant to DMSO soaking, and their putative fragment-binding pockets are unobstructed by lattice contacts, making them ideal for fragment-screening.

This abstract is also being presented as Poster A01.

Citation Format: Albert H. Chan, Timothy H. Tran, Srisathiyanarayanan Dharmaiah, Dwight V. Nissley, Dhirendra K. Simanshu. Novel state I structures of oncogenic KRAS4b mutants bound to GTP analog [abstract]. In: Proceedings of the AACR Special Conference on Targeting RAS-Driven Cancers; 2018 Dec 9-12; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(5_Suppl):Abstract nr PR01.
Abstract A30: Molecular insight into pathogen-associated molecular pattern signaling during TNFa and IL2 armed oncolytic adenovirus treatments
Authors: Heiniö Camilla , Havunen Riikka , Siurala Mikko , Hemminki Akseli
Published: June 2021

Adenoviral-mediated gene therapy is a promising new treatment for malignant tumors with poor responses to traditional cancer treatments. In this study, we investigate the effects of danger- and pathogen-associated molecular pattern (DAMP and PAMP) signaling responses to a chimeric, cytokine armed, oncolytic adenovirus (Ad5/3-E2F-d24-hTNFα-IRES-hIL2). It has previously been shown that this virus has a two-part mode of action against tumors. It simultaneously acts as an immunostimulatory agent while the virus itself lyses cancer cells. However, as this reaction is not fully understood on a molecular level, more in-depth information on the adenovirus-induced signaling cascades in the tumor microenvironment is needed. There are several pattern recognition receptors (PRR) in cells that are responsible for inducing the signaling cascades and consequent immune response towards DAMPs and PAMPs present during adenovirus infections. It has previously been reported that the most important PRRs and sensors include TLR9, NLRP3, RIG-1, cGAS, and AIM2. Binding of DAMPs and PAMPs to PRRs results in the activation of signaling cascades consisting of a plethora of proteins, finally culminating in the production and release of cytokines, pyroptosis or cellular activation and extracellular signaling, consequently affecting neighboring cells as well. In this study, several methods such as Western blot, flow cytometry and RNA-sequencing were used to study DAMP and PAMP signaling and the subsequent reactions in the tumor microenvironment. The knowledge gained about the signaling pathways in this study provides new insight into cell signaling, which can be used to further develop immuno- and virotherapy and to provide a new method of treating poorly responsive tumors.

Citation Format: Camilla Heiniö, Riikka Havunen, Mikko Siurala, Akseli Hemminki. Molecular insight into pathogen-associated molecular pattern signaling during TNFa and IL2 armed oncolytic adenovirus treatments [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr A30.
Abstract B73: Development of anti-human CLDN18.2 monoclonal antibody as cancer therapeutics
Authors: Lin Haishan , Zhang Richard
Published: June 2021

Claudin-18 (CLDN18) is a member of a large family of four-span transmembrane proteins, claudins. These proteins are the essential components of the mammalian tight junctions (TJs) in the epithelial cells. Claudin-18 has two splice variants, 18.1 and 18.2. While CLDN18.1 is specifically expressed in the lung tissue, CLDN18.2 expression in normal tissue is more restricted and is only detected in small patches of stomach mucosal. CLDN18.2 expression is elevated in many types of epithelial cancers including stomach, esophagus, pancreatic and ovarian cancers. The expression of CLDN18.2 is not only detected in primary tumors, but also in the metastatic sites. Therefore, CLDN18.2 is an ideal target for monoclonal antibody-based cancer therapies. Anti-CLDN18.2 monoclonal antibody claudiximab (IMAB362) demonstrated promising results in the phase II clinic trial for gastric cancer. CLDN18.2 specific antibodies are difficult to generate due to its high homology to CLDN18.1. There are only 7-8 amino acid differences between these two splice variants in the first extracellular loop. Using a combination of DNA, protein, and transfected cells as immunogens, coupled with high-throughput FACS-based hybridoma screening approach, we have generated a panel of mouse monoclonal antibodies that are highly specific for CLDN 18.2. These antibodies had high affinities for CLDN18.2 while they did not bind to CLDN18.1. The lead antibodies had similar or better binding affinity for CLDN18.2, compared to the IMAB362. The anti-CLDN18.2 antibodies bound to human gastric carcinoma cell line KATO III. Our IHC data showed that the antibody specifically bound to gastric and pancreatic cancer tissues. In addition, we demonstrated that anti-CLDN18.2 antibodies induced receptor internalization in CHO cell line expressing CLDN18.2. The humanized anti-CLDN18.2 antibodies have been generated and showed similar binding specificity as the mouse antibodies. Lead anti-CLDN18.2 antibodies have been selected for CMC optimization and preclinical studies for further development as cancer therapeutics.

Citation Format: Haishan Lin, Richard Zhang. Development of anti-human CLDN18.2 monoclonal antibody as cancer therapeutics [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr B73.
Immunoglobulin G4-Related Hepatic Inflammatory Pseudotumor Diagnosed with Endoscopic Ultrasound-Guided Fine-Needle Biopsy
Authors: Koiwai Akinobu , Hirota Morihisa , Satoh Mari , Takasu Atsuko , Meguro Takayoshi , Endo Katsuya , Kogure Takayuki , Murakami Keigo , Murakami Kazuhiro , Satoh Kennichi
Published: June 2021

A 71-year-old man with obstructive jaundice was referred to our department. He underwent cholangiojejunostomy 15 years ago for palliative drainage. At that time, he had obstructive jaundice caused by an unresectable pancreatic head tumor. Contrast-enhanced computed tomography (CE-CT) now revealed a mass with low enhancement in the hepatic hilum that occluded the hilar bile duct and infiltrated extensively along the portal vein and hepatic artery. CE-CT also showed marked atrophy of the left hepatic lobe. No swelling or tumors were observed in the pancreas. Serum immunoglobulin G4 (IgG4) levels were as high as 465 mg/dL. Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) was performed targeting the hepatic hilar lesion. Immunohistological results of the biopsy specimens suggested that the lesion was an IgG4-related hepatic inflammatory pseudotumor (IPT) with no atypical cells. Steroid treatment resulted in rapid clinical improvement. This case suggested the usefulness of EUS-FNB for diagnosing IgG4-related hepatic hilar IPT.
A Simple Prognostic Scoring System for Hepatocellular Carcinoma Treated with Selective Internal Radiation Therapy
Authors: op den Winkel Mark , Nagel Dorothea , de la Torre Aláez Manuel A. , Hempe Stephanie , De Toni Enrico N. , Paprottka Karolin J. , op den Winkel Philip , Stecher Stephanie-Susanne , Bourhis Hélène , Gerbes Alexander L. , Ricke Jens , Sangro Bruno , Kolligs Frank T.
Published: June 2021

Introduction: Selective internal radiation therapy (SIRT) is a local treatment option for patients with hepatocellular carcinoma (HCC). Its exact role next to other HCC therapies has yet to be defined. In order to identify patients most suitable for SIRT, a SIRT-specific prognostic score should be developed. Methods: A cohort of 72 SIRT patients treated at the University Hospital of Munich was retrospectively analyzed. The prognostic performance of 12 HCC staging systems and prognostic scores was assessed. Cox-regression analysis was used to identify independent prognostic factors, which formed the basis of the Munich-SIRT score (M-SIRT). All scores were ranked by calculating the c-Index and Akaike information criterion (AIC). External validation was performed in a cohort of 128 SIRT patients treated at the University Hospital of Pamplona, Spain. Results: median overall survival was 13 months (95% confidence interval 9.9–21.9). AFP (p = 0.005; hazard ratio [HR] 2.38), albumin (p < 0.001; HR 5.87), and alkaline phosphatase (p < 0.001; HR 8.38) were identified as independent prognostic factors. M-SIRT comprises 3 prognostic groups with a median survival of 38.9, 14.6, and 7.7 months, respectively (I vs. II: p = 0.003, II vs. III: p < 0.001). AIC (318) and concordance index (0.711) ranked M-SIRT superior to the established HCC staging systems, and the score successfully passed external validation in an independent SIRT cohort (I vs. II: p = 0.03; II vs. III: p = 0.007). Conclusion: Therapy-specific prognostic scores can facilitate treatment decisions and prognostication for HCC patients. Considering its performance in 200 SIRT patients, M-SIRT is a promising prognostic tool for HCC patients evaluated for SIRT.
Inventory of herbs plants at three different locations in forest education of Mulawarman University, Samarinda, East Kalimantan, Indonesia
Authors: Mercury Yasfini Hurum , Sutedjo  , Diana Rita
Published: June 2021

Many plants have the potential to be medicinal from the herbaceous group. Herbaceous plants have short, small steam and have a wet trunk because they contain many water and non-woody. This research aims to inventory species of herbaceous plants that can be medicinal plants and other uses in three different locations. The results showed that 12 species were found in the slope area, 340 individuals. The highest number of SDRn of 29.26% was Nephrolepis biserrata (SW.) Schott. In the ramp, the area has been found of 11 species of herbaceous, 215 individuals. The highest number of SDRn of 34.81% was Phrynium pubinerve Blume. In a hill, area has been found 16 species of herbaceous, 542 individuals. The highest number of SDRn of 38.72% was Phrynium pubinerve Blume. Dominance index (C) in three locations research was 0.26, 0.23 and 0.31. Similarity index (ISs) in three locations was 60.87% (slope-ramp: high), 59.26% (slope-hill: medium) and 57.14% (ramp-hill: medium). There were 11 species as medicinal plants, 17 species as ornamental plants, and 2 species as crafts.
Effects of botanical extracts and antibiotic on incidence and severity of bacterial blight of cotton incited by Xanthomonas axonopodis pv. Malvacearum
Authors: Bawa Iliya , Nahunnaro H. , Barde Luka Yelwa , Gaba Tabita Sule , Musa Alhaji
Published: June 2021

A multilocational field trial was conducted to investigate the effect of some plant extracts (Bolanite aegyptica, Eucalyptus camaldulensis and Citrus aurantium) and a synthetic antibiotic (Streptomycin) on the incidence and severity of angular leaf spot on five cotton geno-types namely SAMCOT-8, SAMCOT-9, SAMCOT-10, SAMCOT-11 and SAMCOT-12 in Yola and Jalingo, both located in the northern guinea savannah zone of Nigeria. The experiment was carried out on a split-plot design having three replications with cotton genotypes on the main plots and plant extracts on the sub-plots. Data collected on the incidence and severity of the disease were analysed using the Generalized Linear Model procedure and means separation at 5% level of probability by Duncan Multiple Range Test. Findings of the study revealed that Streptomycin and Bolanite aegyptiaca were able to reduce the disease incidence by 18.12% from 58.69% in Yola at 13 WAS. In Jalingo however, B. aegyptiaca was found to have re-duced the disease severity from 52.12% to 19.69% at 13 WAS. SAMCOT-8 consistently recorded lower incidence and severity means in Yola and Jalingo of 47.96%; 59.12% and 40.82%; 39.70% while SAMCOT-12 recorded higher means of 53.29%; 59.82% and 48.03%; 46.70% respectively.
Carotid Plaques From Symptomatic Patients Are Characterized by Local Increase in Xanthine Oxidase Expression
Authors: Ganji Morsaleh , Nardi Valentina , Prasad Megha , Jordan Kyra L. , Bois Melanie C. , Franchi Federico , Zhu Xiang Y. , Tang Hui , Young Melissa D. , Lerman Lilach O. , Lerman Amir
Published: June 2021

Background and Purpose:

XO (xanthine oxidase) is a key enzyme of uric acid metabolism and is thought to contribute to oxidative pathways that promote atherosclerotic plaque progression, yet its role in plaque destabilization is not well elucidated. We hypothesized that XO is expressed in carotid plaque from symptomatic patients in association with cardiovascular risk factors.

Methods:

Patients were stratified by symptoms, defined as presentation with an ipsilateral cerebral ischemic event. Carotid atherosclerotic plaques were obtained from 44 patients with symptomatic plaque and 44 patients without ischemic cerebral events. Protein expression of XO was evaluated by immunohistochemical staining and the percentage of cells expressing XO and CD68 (macrophage marker) compared between the groups. Biochemical and demographic cardiometabolic risk factors of study participants also were measured.

Results:

Carotid atherosclerotic plaques from symptomatic patients were associated with significantly higher XO expression versus asymptomatic plaque (median [interquartile range]: 1.24 [2.09] versus 0.16 [0.34];
P
<0.001) and with significantly higher circulating uric acid levels (mean±SD: 7.36±2.10 versus 5.37±1.79 mg/dL;
P
<0.001, respectively). In addition, XO expression in atherosclerotic carotid plaque was inversely associated with serum high-density lipoproteins cholesterol levels (
P
=0.010,
r
=−0.30) and directly with circulating uric acid levels (
P
<0.001,
r
=0.45). The average percentage of macrophages that expressed XO was significantly higher in symptomatic versus asymptomatic plaques (median [interquartile range]: 93.37% [25] versus 46.15% [21], respectively;
P
<0.001).

Conclusions:

XO overexpression in macrophages is associated with increased serum uric acid and low high-density lipoproteins cholesterol levels and may potentially have a mechanistic role in carotid plaque destabilization. The current study supports a potential role for uric acid synthesis pathway as a target for management of carotid atherosclerosis in humans.
Parasites differentially impact crayfish personality in different contexts
Authors: MacKay Rebecca Noel , Moore Paul A.
Published: June 2021

The expression of an individual animal’s behaviour can be placed along many different personality spectra. Parasite load can alter animal behaviour and, thus, fitness. The personality traits of rusty crayfish, Faxonius rusticus, were analysed in three different behavioural contexts: foraging, exploration, and threatened. Each crayfish was tested in each context 3 times, giving a total of 9 assays per crayfish. After assays were completed, crayfish were dissected, and the hepatopancreas of each crayfish was photo analysed to determine the parasite load of the trematode, Microphallus spp. A composite personality score for each assay and parasite load was loaded into a PCA. The PCA model showed that as parasite load increased, crayfish became bolder in threatening contexts and less exploratory in novel environments, whether or not a food stimulus was present. Thus, parasite load alters the placement of crayfish on different personality spectra, but this change is context specific.
Fifty spider species new to the Bulgarian fauna, with a review of some dubious species (Arachnida: Araneae)
Authors: NAUMOVA MARIA , BLAGOEV GERGIN , DELTSHEV CHRISTO
Published: June 2021

This study is a part of an ongoing comprehensive inventory of Bulgarian spiders. A total of fifty spider species belonging to thirteen families are reported for the first time from Bulgaria. Four species are rejected from the Bulgarian spider checklist due to misidentification: Callilepis concolor Simon, 1914, Centromerus capucinus (Simon, 1884), Hoplopholcus labyrinthi (Kulczyński, 1903) and Mansuphantes prope fragilis (Thorell, 1875). Another four species (Drassodes villosus (Thorell, 1856), Entelecara flavipes (Blackwall, 1834), Lepthyphantes notabilis Kulczyński, 1887 and Singa semiatra L. Koch, 1867) are rejected after a new interpretation of the locations. Six species were omitted from the list of Bulgarian spiders as obviously doubtful records (Dysdera nicaeensis Thorell, 1873, Haplodrassus rufipes (Lucas, 1846), Harpactea hispana (Simon, 1882), Macaroeris cata (Blackwall, 1867), Nomisia celerrima (Simon, 1914) and Tenuiphantes monachus (Simon, 1884)). A new synonymy is proposed for Cyclosa strandjae Drensky, 1915 (= Cyclosa sierrae Simon, 1870 syn. nov.). In addition, new images with essential taxonomic value are provided for twenty-five species to facilitate their identification or to illustrate their intraspecific variability. To ensure correct identification, DNA barcoding was additionally used in some species.
Three new species of the extinct spider genus Furcembolus (Araneae: Pacullidae) from Late Cretaceous Burmese amber
Authors: XIN YAFEI , JIANG TONGYAO , YAO ZHIYUAN , LI SHUQIANG
Published: June 2021

Three new species of the extinct spider genus †Furcembolus Wunderlich, 2008 from Late Cretaceous Burmese amber are described: Furcembolus chuandiani Jiang & Li spec. nov., F. fengzheni Jiang & Li spec. nov. and F. martensi Jiang & Li spec. nov. All types are deposited in the Institute of Zoology, Chinese Academy of Sciences in Beijing, China.
First record of Travunioidea (Arachnida: Opiliones: Laniatores) from China, with the description of a new monotypic genus from a cave
Authors: ZHANG CHAO , DERKARABETIAN SHAHAN
Published: June 2021

A new genus and species of troglobitic Opiliones, Sinonychia martensi gen. n. & sp. n., is described and illustrated. This is the first report of the superfamily Travunioidea Absolon & Kratochvíl, 1932 from China. The new species is assigned to Cladonychiidae Hadži, 1935 on the basis of morphology of midgut and male genitalia, and can be easily distinguished from related genera by several characters.
Assessment of Precipitation Error Propagation in Discharge Simulations over the Contiguous United States
Authors: Nanding Nergui , Wu Huan , Tao Jing , Maggioni Viviana , Beck Hylke E. , Zhou Naijun , Huang Maoyi , Huang Zhijun
Published: June 2021

This study characterizes precipitation error propagation through a distributed hydrological model based on the river basins across the Contiguous United States (CONUS), to better understand the relationship between errors in precipitation inputs and simulated discharge (i.e., P-Q error relationship). The NLDAS-2 precipitation and its simulated discharge are used as the reference to compare with TMPA-3B42 V7, TMPA-3B42RT V7, StageIV, CPC-U, MERRA-2, and MSWEP-2.2 for 1,548 well gauged river basins. The relative errors in multiple conventional precipitation products and their corresponding discharges are analysed for the period of 2002-2013. The results reveal positive linear P-Q error relationships at annual and monthly timescales, and the stronger linearity for larger temporal accumulations. Precipitation errors can be doubled in simulated annual accumulated discharge. Moreover, precipitation errors are strongly dampened in basins characterized by temperate and continental climate regimes, particularly for peak discharges, showing highly nonlinear relationships. Radar-based precipitation product consistently shows dampening effects on error propagation through discharge simulations at different accumulation timescales compared to the other precipitation products. Although basin size and topography also influence the P-Q error relationship and propagation of precipitation errors, their roles depend largely on precipitation products, seasons and climate regimes.
Preparing Organizations for Greater Turbulence
Authors: Schoemaker Paul J. H. , Day George
Published: June 2021

Vigilant organizations excel at seeing looming threats and embryonic opportunities sooner than rivals, which prepares them to act faster when needed. Four drivers distinguish vigilant from vulnerable organizations, which can be used to design a roadmap to improve organizational acuity and preparedness. The fulcrum of these changes rests with the leadership team by demonstrating a strong commitment to vigilance at all levels, and reinforcing this by making targeted investments in foresight capabilities. These strategic moves also need to be supported by corresponding changes in the strategy-making process and by ensuring accountability and coordination of vigilance activities throughout the enterprise.
Comparison of Bleeding Rates between Oral Anticoagulants in Combination with Dual Antiplatelet Therapy (Triple Therapy) in a Real-World Cohort
Authors: Chilbert Maya R. , Reidy Sarah E. , Clark Collin M. , Guszkowski Marissa , Gargala Emma , Woodruff Ashley E.
Published: June 2021

Background: Triple antithrombotic therapy including an anticoagulant, P2Y12 inhibitor, and aspirin increases bleed risk up to 27%. The components of this regimen can vary, which may impact bleed risk. Objective: To compare the safety of various triple antithrombotic regimens. Methods: An Institutional Review Board approved retrospective cohort study was conducted from 2014 to 2017. Patients admitted to a large urban health system on triple therapy were evaluated for inclusion. The primary outcome compared rates of International Society of Thrombosis and Hemostasis major and clinically relevant nonmajor bleeding during index admission or within 90 days in patients receiving warfarin, rivaroxaban, or apixaban; aspirin; and a P2Y12 inhibitor. A multivariable logistic regression assessed the association between bleeding, antithrombotic use, and relevant confounding variables. Results: Three hundred and seventy-two patients were included: 238 patients received warfarin, 63 received rivaroxaban, and 71 received apixaban. Forty-five patients (12.1%) experienced a bleed, 25 of which (55.6%) were major. The rate of bleeding was 12.2% (n = 29) with warfarin, 14.3% (n = 9) with rivaroxaban, and 9.9% (n = 7) with apixaban ( P = .7335). The use of prasugrel versus clopidogrel (OR 4.35, 95% CI 1.20-15.72; P = .025) and admission hemoglobin less than 12 mg/dL (OR 2.54, 95% CI 1.28-5.04; P = .008) were identified as risk factors associated with bleeding in the model. Conclusion: In patients on triple antithrombotic therapy, choice of oral anticoagulant did not impact bleeding rates, but use of prasugrel and a low baseline hemoglobin were associated with increased bleed rates which warrants further investigation.
Government technological capacity and public–private partnerships regarding digital service delivery: evidence from Chinese cities
Authors: Ma Liang , Christensen Tom , Zheng Yueping
Published: June 2021

Governments have increased their collaboration with the private sector regarding public service delivery, and their propensities to do so are largely shaped by their own in-house capacities. In this article, we theorize and analyze whether governments with an extremely low or extremely high technological capacity are more likely to collaborate with third-party platforms in order to jointly provide digital services. We expect there to be a U-shaped relationship between the technological capacity of those governments and their public–private partnership choices. An empirical analysis of digital service delivery across 290 prefecture-level cities in China corroborates this hypothesis. These results deepen our understanding of the competing motivations that drive the public–private partnership process.

Points for practitioners

Public–private collaboration has been widely adopted to promote digital service delivery. This article confirms the U-shaped relationship between government technological capacity and public–private collaboration in digital service delivery at the city level. To encourage the collaboration, it is crucial to target governments with varying capacities, which seems to be easier in large cities with high administrative rank and that are overall technologically mature and in a competitive environment technologically.
The Resilience of Female Sex Workers in the Wake of COVID-19 in Zimbabwe
Authors: Nyabeze Kudzai , Jakaza Tafadzwa Ngonidzashe , Chikoko Witness , Mwapaura Kudzai , Zvokuomba Kwashirai
Published: June 2021

The paper interrogates the resilience of female sex workers in the wake of COVID-19 in Zimbabwe. The paper draws literature from global, regional and national perspectives using the resilience theory. Major findings reveal that the COVID-19 lockdown measures have disrupted the livelihoods of female sex workers. Hence, female sex workers have resorted to online sex work and some entrepreneurship. There has also been consistent breaching of the lockdown regulations in a bid to make ends meet. Therefore, the study concludes by recommending the need to extend social protection floors to this vulnerable group.
An implicit multistep numerical method for real-time simulation of stiff systems
Authors: Lei Zhang , Jie Li , Menglu Wang , Mengya Liu
Published: June 2021

Simulating a physical system in real-time is widely used in equipment design, test, and validation. Though an implicit multistep numerical method excels at solving physical models that are usually composed of stiff ordinary differential equations, it is not suitable for real-time simulation because of state discontinuity and massive iterations for root finding. Thus, a method based on the backward differential formula is presented. It divides the main fixed step of real-time simulation into limited minor steps according to computing cost and accuracy demand. By analyzing and testing its capability, this method shows advantage and efficiency in real-time simulation, especially when the system contains stiff equations. A simulation application will have more flexibility while using this method.
Assessment of chemically and enzymatically modified chitosan with eugenol as a coating for viscose functionalization for potential medical use
Authors: Sauperl Olivera , Zemljic Lidija Fras , Valh Julija Volmajer , Tompa Jasna
Published: June 2021

The present work deals with the preparation of chemically and enzymatically eugenol-modified chitosan and its application as a green coating on viscose for the potential production of medical textiles. The elemental composition of chemically and enzymatically eugenol-modified chitosan was determined by attenuated total reflection Fourier transform infrared (ATR FT-IR) and proton nuclear magnetic resonance (1H NMR) spectroscopy. Moreover, potentiometric titration was used to estimate the number of accessible amino groups. The chitosan–eugenol formulation possesses a high antioxidant capacity level, as shown by the high content of phenolic compounds analyzed by the following methods: (a) Folin–Ciocalteu; (b) reduction of Fe3+ ions; and (c) α, α-diphenyl-β-picrylhydrazyl (DPPH•). Viscose coated with chitosan–eugenol formulations was evaluated by ATR FT-IR spectroscopy and Acid Orange VII spectrophotometric methods, the results of which demonstrated the successful deposition of these formulations on the fibers. Scanning electron microscopy showed the presence of the functional coating on the viscose. Finally, antimicrobial testing was performed to determine inhibition of selected pathogenic micro-organisms using the ASTM E 2149-01 standard. The antioxidant activity of the functionalized viscose was investigated spectrophotometrically by the DPPH• method. It was found that the coatings of eugenol-modified chitosan impart antimicrobial activity to the viscose against Gram-positive and Gram-negative bacteria as well as fungi, and cause inhibition of free radicals by introducing an antioxidant character. The chemical and enzymatic modification of chitosan offers many opportunities for the incorporation of many natural active ingredients into the chitosan system, which provides a good basis for further work related to the functionalization of chitosan for sanitary and medical use.
Investigation into the effects of yarn structure and yarn count on different types of core-spun yarns
Authors: Elrys Samah M E , Faheem El- Habiby Fawkia , Abd Elkhalek Rehab , Eldeeb Ahmed S , El-Hossiny Abdellatif M
Published: June 2021

The scope of this research is to study the effect of yarn structure and yarn count on properties of types of core-spun yarns, including elastic core/T400, elastic core/Lycra, dual core, and tri-core yarns. Five types of yarn structures and three yarn counts were produced. Mechanical properties, yarn irregularity, imperfections, and hairiness were measured. Full-factorial analysis and Tukey tests were performed on the test results. It was concluded from factorial analysis that yarn count, yarn structure, and two-way interaction had a significant effect on yarn properties, except for yarn hairiness where the effect of yarn structure and two-way interaction was not significant. A Tukey pairwise comparison was used in this study to specify exactly the subgroups of yarn count and yarn structure that have a significant mean difference. The scanning electron microscopy (SEM) images of the dual-core yarns and tri-core yarns were performed to illustrate the structure of these yarns.
Utility of loop-mediated isothermal amplification as a point-of-care test in diagnosis of amoebic liver abscess
Authors: Handa Dipti , Gupta Monica , Lehl Sarabmeet Singh , Gupta Amit , Singh Ram
Published: June 2021

Definitive diagnosis of amoebic liver abscess is challenging owing to the unavailability of sensitive commercial point-of-care molecular tests. The primary aim of our prospective diagnostic study was to compare available laboratory methods for the diagnosis of Entamoeba histolytica in clinical samples with loop-mediated isothermal amplification. We compared deoxyribonucleic acid (DNA) analysis methods, namely, loop-mediated isothermal amplification and reverse transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA) using pus, stool and blood samples from 200 patients with clinical and radiological diagnosis of amoebic liver abscess. Loop-mediated isothermal amplification had significantly higher sensitivity (88%) as compared to reverse transcriptase polymerase chain reaction (64%) and excellent specificity (100%).
Development of an application tool to support returnees in Fukushima
Authors: Ohba T. , Goto A. , Nakano H. , Nollet K.E. , Murakami M. , Koyama Y. , Honda K. , Yoshida K. , Yumiya Y. , Kuroda Y. , Kumagai A. , Ohira T. , Tanigawa K.
Published: June 2021

To promote radiation protection and health promotion among returning residents (returnees) in coastal areas of Fukushima, eHealth principles were used to develop a new application tool (app) that can record radiation exposure and health status while providing comprehensive support to returnees. Intended users are returnees and health and welfare workers. After assessing their needs, a flowchart and prototype for operational logic were created using commercially available software tools. Professional developers will focus on improving the user interface and ensuring data security. The finished app will be compatible with mobile telephones and tablets. Utility and ease of use are paramount to serve returnees of all ages effectively.
Enhancing data quality to mine credible patterns
Authors: Imran Muhammad , Ahmad Adnan
Published: June 2021

The importance of big data is widely accepted in various fields. Organisations spend a lot of money to collect, process and mine the data to identify patterns. These patterns facilitate their future decision-making process to improve the organisational performance and profitability. However, among discovered patterns, there are some meaningless and misleading patterns which restrict the effectiveness of decision-making process. The presence of data discrepancies, noise and outliers also impacts the quality of discovered patterns and leads towards missing strategic goals and objectives. Quality inception of these discovered patterns is vital before utilising them in making predictions, decision-making process or strategic planning. Mining useful and credible patterns over social media is a challenging task. Often, people spread targeted content for character assassination or defamation of brands. Recently, some studies have evaluated the credibility of information over social media based on users’ surveys, experts’ judgement and manually annotating Twitter tweets to predict credibility. Unfortunately, due to the large volume and exponential growth of data, these surveys and annotation-based information credibility techniques are not efficiently applicable. This article presents a data quality and credibility evaluation framework to determine the quality of individual data instances. This framework provides a way to discover useful and credible patterns using credibility indicators. Moreover, a new Twitter bot detection algorithm is proposed to classify tweets generated by Twitter bots and real users. The results of conducted experiments showed that the proposed model generates a positive impact on improving classification accuracy and quality of discovered patterns.
A whole-of-nation approach to COVID-19: Taiwan’s National Epidemic Prevention Team
Authors: Hsieh Chih-Wei , Wang Mao , Wong Natalie WM , Ho Lawrence Ka-ki
Published: June 2021

This article analyzes Taiwan’s National Epidemic Prevention Team, a collective synergy between government and society in fighting COVID-19. We draw on a model of collaborative governance to dissect the collaboration between National Epidemic Prevention Team members; that is, central government, local governments, private enterprises and citizens. We argue that the 2003 severe acute respiratory syndrome (SARS) outbreak, democratic deepening and continual diplomatic isolation despite the global health crisis contributed to Taiwan’s National Epidemic Prevention Team capacity and cohesiveness. Our analysis contributes to the heated discourse on democratic resilience in these turbulent times, suggesting that outbreak control can succeed only if there is an integrated system of interdepartmental, central–local, intersectoral and citizen–state collaboration. Overall, this article shows how liberal democracies can control and counteract COVID-19 without resorting to authoritarian methods of containment.