bluuebunny/crossref_metadata_2025 huggingface dataset:
Generalized Summation Formulas for the Kampé de Fériet Function
Authors: Choi Junesang , Milovanović Gradimir V. , Rathie Arjun K.
Published: November 2021

By employing two well-known Euler’s transformations for the hypergeometric function 2F1, Liu and Wang established numerous general transformation and reduction formulas for the Kampé de Fériet function and deduced many new summation formulas for the Kampé de Fériet function with the aid of classical summation theorems for the 2F1 due to Kummer, Gauss and Bailey. Here, by making a fundamental use of the above-mentioned reduction formulas, we aim to establish 32 general summation formulas for the Kampé de Fériet function with the help of generalizations of the above-referred summation formulas for the 2F1 due to Kummer, Gauss and Bailey. Relevant connections of some particular cases of our main identities, among numerous ones, with those known formulas are explicitly indicated.
Changes in Transcriptomic Profiles in Different Reproductive Periods in Yaks
Authors: Guo Shaoke , Cao Mengli , Wang Xingdong , Xiong Lin , Wu Xiaoyun , Bao Pengjia , Chu Min , Liang Chunnian , Yan Ping , Pei Jie , Guo Xian
Published: November 2021

Yak reproductive characteristics have received extensive attention, though the molecular regulation mechanism of its ovarian activity remains to be explored. Therefore, this study initially conducted a comparative analysis of yak ovarian activities in anestrus, estrus, and pregnancy regarding their morphology and histology, followed by implementing RNA sequencing (RNA-seq) technology to detect the overall gene expression and biological mechanism in different reproductive stages. H&E staining showed that there were more growing follicles and mature follicles in ovarian tissue sections during estrus than ovarian tissues during non-estrus. The RNA-seq analysis of yak ovary tissues in three periods showed that DEGs related to follicular development and hormone metabolism were screened in the three comparison groups, such as COL1A2, NR4A1, THBS2, PTGS2, SCARB1, STAR, and WNT2B. Bioinformatics analysis showed that these DEGs are involved in ion binding, cell development, metabolic processes, enriched in ECM–receptor interactions, steroid biosynthesis, together with aldosterone generation/discharge and Wnt/PI3K-Akt signaling pathways. In addition, we speculate alternate splice development events to have important role/s in regulating ovarian functional genomic expression profiles. These results provide essential knowledge aimed at scrutinizing pivotal biomarkers for yak ovarian activity, together with paving the way for enhancing researchers’ focus on improving yak reproductive performance.
Rapid and Direct Action of Lipopolysaccharide (LPS) on Skeletal Muscle of Larval Drosophila
Authors: Potter Rachel , Meade Alexis , Potter Samuel , Cooper Robin L.
Published: November 2021

The endotoxin lipopolysaccharide (LPS) from Gram-negative bacteria exerts a direct and rapid effect on tissues. While most attention is given to the downstream actions of the immune system in response to LPS, this study focuses on the direct actions of LPS on skeletal muscle in Drosophila melanogaster. It was noted in earlier studies that the membrane potential rapidly hyperpolarizes in a dose-dependent manner with exposure to LPS from Pseudomonas aeruginosa and Serratia marcescens. The response is transitory while exposed to LPS, and the effect does not appear to be due to calcium-activated potassium channels, activated nitric oxide synthase (NOS), or the opening of Cl− channels. The purpose of this study was to further investigate the mechanism of the hyperpolarization of the larval Drosophila muscle due to exposure of LPS using several different experimental paradigms. It appears this response is unlikely related to activation of the Na-K pump or Ca2+ influx. The unknown activation of a K+ efflux could be responsible. This will be an important factor to consider in treatments of bacterial septicemia and cellular energy demands.
Effect of Olive Cake and Cactus Cladodes Incorporation in Goat Kids’ Diet on the Rumen Microbial Community Profile and Meat Fatty Acid Composition
Authors: El Otmani Samira , Chebli Youssef , Taminiau Bernard , Chentouf Mouad , Hornick Jean-Luc , Cabaraux Jean-François
Published: November 2021

The olive cake (OC) and the cactus cladodes (CC) are two alternative feed resources widely available in the southern Mediterranean region that could be used in ruminants’ diet. Their impact on the rumen bacterial ecosystem is unknown. This work aims to evaluate their effects on the microbial community and meat fatty acids of goat’s kids. Forty-four goat kids were divided into four groups receiving diets with conventional concentrate, or 35% OC, or 30% CC, or 15% OC, and 15% CC. After 3 months, these animals were slaughtered, and the rumen liquor and longissimus dorsi and semimembranosus muscles samples were collected. Animals receiving a control diet had rumen liquor with high acidity than test groups (p < 0.001). Test rumen liquor was more adapted to digest efficiently their matching diet than control liquor (p < 0.05). These feedstuffs did not affect rumen bacteria abundance and alpha diversity (richness, evenness, and reciprocal Simpson indexes), and these results were confirmed by beta-diversity tests (NMDS plot, HOMOVA, PERMANOVA). The test diets slightly affected the individual fatty acids of meat (p < 0.05) without effect on fatty acids summaries, indexes, and ratios. Thus, these alternative feed resources could take place in goat kids’ diet to diversify their feed and to reduce feed costs.
Morphological, Morphometrical and Molecular Characterization of Oscheius siddiqii Tabassum and Shahina, 2010 (Rhabditida, Rhabditidae) from India with Its Taxonomic Consequences for the Subgenus Oscheius Andrássy, 1976
Authors: Bhat Aashaq Hussain , Gautum Swati , Rana Aasha , Chaubey Ashok Kumar , Abolafia Joaquín , Půža Vladimír
Published: November 2021

An insect parasitic nematode belonging to the genus Oscheius was recovered from the agricultural soils from the Hapur district in western Uttar Pradesh, India. Morphological studies on this species exhibited its high resemblance with two Pakistani species: Oscheius siddiqii and O. niazii. No molecular data are available for these taxa but, morphologically, both species do not differ significantly from our strains and each other. Hence, these nematodes can be considered conspecific, and the correct name for this taxon is O. siddiqii, the first described species. The phylogenetic analyses of the ITS-, 18S-, and the 28S rDNA sequences showed that O. siddiqii is a sister taxon to the group formed by Oscheius microvilli, O. myriophilus, O. safricanus, and several unidentified Oscheius species. Additionally, our analyses show that based on molecular and morphological data, the species Oscheius rugaoensis and O. microvilli cannot be distinguished from O. chongmingensis and O. myriophilus, respectively, and are thus considered junior synonyms of these taxa. Furthermore, the available data are not sufficient to evaluate the status of Oscheius basothovii and O. safricanus, which are, in consequence, considered species inquirendae. These findings highlight the necessity of the proper morphological and molecular characterisation of the described Oscheius species.
Computational Insights into the Unfolding of a Destabilized Superoxide Dismutase 1 Mutant
Authors: Timr Stepan , Sterpone Fabio
Published: November 2021

In this work, we investigate the β-barrel of superoxide dismutase 1 (SOD1) in a mutated form, the isoleucine 35 to alanine (I35A) mutant, commonly used as a model system to decipher the role of the full-length apoSOD1 protein in amyotrophic lateral sclerosis (ALS). It is known from experiments that the mutation reduces the stability of the SOD1 barrel and makes it largely unfolded in the cell at 37 degrees Celsius. We deploy state-of-the-art computational machinery to examine the thermal destabilization of the I35A mutant by comparing two widely used force fields, Amber a99SB-disp and CHARMM36m. We find that only the latter force field, when combined with the Replica Exchange with Solute Scaling (REST2) approach, reproduces semi-quantitatively the experimentally observed shift in the melting between the original and the mutated SOD1 barrel. In addition, we analyze the unfolding process and the conformational landscape of the mutant, finding these largely similar to those of the wildtype. Nevertheless, we detect an increased presence of partially misfolded states at ambient temperatures. These states, featuring conformational changes in the region of the β-strands β4−β6, might provide a pathway for nonnative aggregation.
Termitophily Documented in Earwigs (Dermaptera)
Authors: Kočárek Petr , Wahab Rodzay Abdul
Published: November 2021

Based on behavioral observations, we report termitophily by the earwig Spirolabia kaja Kočárek, sp. nov. (Spongiphoridae: Labiinae). The new species was found in association with the wood-boring termite Schedorhinotermes sarawakensis (Holmgren, 1913) in a dipterocarp rain forest in Borneo; in addition to being observed in the galleries, termite–earwig interactions were subsequently documented in the laboratory. We found that earwigs and termites communicate by antennation, and we observed no form of targeted mutual or unilateral aggressive behavior. The earwigs responded to the proximity of an experimentally irritated termite soldier by conflict-avoidance behavior based on thanatosis, which seems to be a defensive reaction that may reduce the chance of being attacked by an irritated termite. Based on the analysis of gastrointestinal tract contents, we conclude that S. kaja sp. nov. is an omnivorous species that feeds mainly on plant tissues and fungi but occasionally on arthropod remains. The occurrence of S. kaja sp. nov. adults together with the nymphs (2nd to 4th instars) in the galleries of S. sarawakensis strongly suggests that the earwig can reproduce inside the termite colony. Spirolabia kaja Kočárek, sp. nov. is the first earwig species for which termitophily has been demonstrated.
Kinetics of Parasite-Specific Antibody and B-Cell-Associated Gene Expression in Brown Trout, Salmo trutta during Proliferative Kidney Disease
Authors: Shivam Saloni , El-Matbouli Mansour , Kumar Gokhlesh
Published: November 2021

Tetracapsuloides bryosalmonae, a myxozoan endoparasite often causes chronic infection in brown trout. Antiparasite immunity mediated by antibodies and B cells is known as an important determinant of host survival and parasite proliferation during chronic infections. Accordingly, studying their time course during proliferative kidney disease (PKD) might be helpful in improving our understanding of its chronic nature. Therefore, we conducted this study to examine parasite specific serum antibody and B-cell-mediated response in laboratory-infected brown trout at different time points. Brown trout were exposed to the spores of T. bryosalmonae, derived from infected bryozoans. Samples were collected at different time points and processed for indirect ELISA, histopathology, and qRT-PCR. T. bryosalmonae specific antibody was detected at 4 weeks post exposure (wpe) and it persisted until 17 wpe. Additionally, the expressions of C4A, CD34, CD79A, BLNK, CD74, BCL7, and CD22 were differentially regulated in the important immune organs, kidney and spleen. To our knowledge, this is the first study addressing anti-T. bryosalmonae antibody response in brown trout at different time points. The results from this study provide valuable insights into the processes leading to changes in B cell development, inflammation and antibody production during the course of PKD in brown trout.
CRISPR/dCas9 Transcriptional Activation of Endogenous Apolipoprotein AI and Paraoxonase 1 in Enterocytes Alleviates Endothelial Cell Dysfunction
Authors: Toma Laura , Barbălată Teodora , Sanda Gabriela M. , Niculescu Loredan S. , Sima Anca V. , Stancu Camelia S.
Published: November 2021

Atherosclerosis is the main cause of cardiovascular diseases with high prevalence worldwide. A promising therapeutic strategy to reverse atherosclerotic process is to improve the athero-protective potential of high-density lipoproteins (HDL). Since the small intestine is a source of HDL, we aimed to activate transcription of the endogenous HDL major proteins, apolipoprotein AI (ApoAI) and paraoxonase 1 (PON1), in enterocytes, and to evaluate their potential to correct the pro-inflammatory status of endothelial cells (EC). Caco-2 enterocytes were transfected with CRISPR activation plasmids targeting ApoAI or PON1, and their gene and protein expression were measured in cells and conditioned medium (CM). ATP binding cassette A1 and G8 transporters (ABCA1, ABCG8), scavenger receptor BI (SR-BI), and transcription regulators peroxisome proliferator-activated receptor γ (PPARγ), liver X receptors (LXRs), and sirtuin-1 (SIRT1) were assessed. Anti-inflammatory effects of CM from transfected enterocytes were estimated through its ability to inhibit tumor necrosis factor α (TNFα) activation of EC. Transcriptional activation of ApoAI or PON1 in enterocytes induces: (i) increase of their gene and protein expression, and secretion in CM; (ii) stimulation of ABCA1/G8 and SR-BI; (iii) upregulation of PPARγ, LXRs, and SIRT1. CM from transfected enterocytes attenuated the TNFα-induced inflammatory and oxidative stress in EC, by decreasing TNF receptor 1, monocyte chemoattractant protein-1, and p22phox. In conclusion, transcriptional activation of endogenous ApoAI or PON1 in enterocytes by CRISPR/dCas9 system is a realistic approach to stimulate biogenesis and function of major HDL proteins which can regulate cholesterol efflux transporters and reduce the inflammatory stress in activated EC.
Three-Dimensional Graph Matching to Identify Secondary Structure Correspondence of Medium-Resolution Cryo-EM Density Maps
Authors: Behkamal Bahareh , Naghibzadeh Mahmoud , Saberi Mohammad Reza , Tehranizadeh Zeinab Amiri , Pagnani Andrea , Al Nasr Kamal
Published: November 2021

Cryo-electron microscopy (cryo-EM) is a structural technique that has played a significant role in protein structure determination in recent years. Compared to the traditional methods of X-ray crystallography and NMR spectroscopy, cryo-EM is capable of producing images of much larger protein complexes. However, cryo-EM reconstructions are limited to medium-resolution (~4–10 Å) for some cases. At this resolution range, a cryo-EM density map can hardly be used to directly determine the structure of proteins at atomic level resolutions, or even at their amino acid residue backbones. At such a resolution, only the position and orientation of secondary structure elements (SSEs) such as α-helices and β-sheets are observable. Consequently, finding the mapping of the secondary structures of the modeled structure (SSEs-A) to the cryo-EM map (SSEs-C) is one of the primary concerns in cryo-EM modeling. To address this issue, this study proposes a novel automatic computational method to identify SSEs correspondence in three-dimensional (3D) space. Initially, through a modeling of the target sequence with the aid of extracting highly reliable features from a generated 3D model and map, the SSEs matching problem is formulated as a 3D vector matching problem. Afterward, the 3D vector matching problem is transformed into a 3D graph matching problem. Finally, a similarity-based voting algorithm combined with the principle of least conflict (PLC) concept is developed to obtain the SSEs correspondence. To evaluate the accuracy of the method, a testing set of 25 experimental and simulated maps with a maximum of 65 SSEs is selected. Comparative studies are also conducted to demonstrate the superiority of the proposed method over some state-of-the-art techniques. The results demonstrate that the method is efficient, robust, and works well in the presence of errors in the predicted secondary structures of the cryo-EM images.
Quantitative Trait Locus Mapping Combined with RNA Sequencing Reveals the Molecular Basis of Seed Germination in Oilseed Rape
Authors: Yu Kunjiang , He Yuqi , Li Yuanhong , Li Zhenhua , Zhang Jiefu , Wang Xiaodong , Tian Entang
Published: November 2021

Rapid and uniform seed germination improves mechanized oilseed rape production in modern agricultural cultivation practices. However, the molecular basis of seed germination is still unclear in Brassica napus. A population of recombined inbred lines of B. napus from a cross between the lower germination rate variety ‘APL01’ and the higher germination rate variety ‘Holly’ was used to study the genetics of seed germination using quantitative trait locus (QTL) mapping. A total of five QTLs for germination energy (GE) and six QTLs for germination percentage (GP) were detected across three seed lots, respectively. In addition, six epistatic interactions between the QTLs for GE and nine epistatic interactions between the QTLs for GP were detected. qGE.C3 for GE and qGP.C3 for GP were co-mapped to the 28.5–30.5 cM interval on C3, which was considered to be a novel major QTL regulating seed germination. Transcriptome analysis revealed that the differences in sugar, protein, lipid, amino acid, and DNA metabolism and the TCA cycle, electron transfer, and signal transduction potentially determined the higher germination rate of ‘Holly’ seeds. These results contribute to our knowledge about the molecular basis of seed germination in rapeseed.
Serum-Derived Neuronal Exosomal microRNAs as Stress-Related Biomarkers in an Atopic Dermatitis Model
Authors: Sung Minkyoung , Sung Soo-Eun , Kang Kyung-Ku , Choi Joo-Hee , Lee Sijoon , Kim KilSoo , Lim Ju-Hyeon , Lee Gun Woo , Rim Hyo-Deog , Won Seunghee , Kim Byung-Soo , Kim Kyungmin , Jang Seoyoung , Kwak Sang Gyu , Woo Jungmin , Seo Min-Soo
Published: November 2021

Chronic allergic inflammatory skin disease—atopic dermatitis (AD)—is characterized by eczema, pruritus, xeroderma, and lichenification. Psychological stress is one cause of this disease; however, psychological stress will also result from the presence of AD symptoms. Previous studies have shown that psychological stress triggers neuroinflammation in the brain, where microRNAs (miRNAs) in the neuronal exosomes (nEVs) were analyzed to identify the composition of the miRNAs in the nEVs and how they were altered by AD. In this study, the AD model was induced by treatment with 2,4-dinitrochlorobenzene (DNCB). The expression patterns of neuroinflammation markers, such as brain-derived neurotrophic factor, cyclooxygenase-2, and glial fibrillary acidic protein, were subsequently evaluated over time. Among these groups, there was a significant difference in DNCB 14 days expression compared with the control; therefore, nEVs were isolated from serum and next-generation sequencing was performed. The results demonstrate that 9 miRNAs were upregulated and 16 were downregulated in the DNCB 14 days compared with the control. Previous studies have shown that some of these miRNAs are associated with stress and stress-induced depression, which suggests that the miRNAs in nEVs may also be stress-related biomarkers.
Intravesical High Dose BCG Tokyo and Low Dose BCG Tokyo with GMCSF+IFN α Induce Systemic Immunity in a Murine Orthotopic Bladder Cancer Model
Authors: Tham Sin Mun , Rahmat Juwita N. , Chiong Edmund , Wu Qinghui , Esuvaranathan Kesavan , Mahendran Ratha
Published: November 2021

This study evaluates a short therapy schedule for bladder cancer using BCG Tokyo. BCG Tokyo was evaluated in vitro using bone marrow derived dendritic cells, neutrophils, RAW macrophages and the murine bladder cancer cell line, MB49PSA, and compared to other BCG strains. BCG Tokyo > BCG TICE at inducing cytokine production. In vivo, high dose (1 × 107 colony forming units (cfu)) and low dose (1 × 106 cfu) BCG Tokyo with and without cytokine genes (GMCSF + IFNα) were evaluated in C57BL/6J mice (n = 12–16 per group) with orthotopically implanted MB49PSA cells. Mice were treated with four instillations of cytokine gene therapy and BCG therapy. Both high dose BCG alone and low dose BCG combined with cytokine gene therapy were similarly effective. In the second part the responsive groups, mice (n = 27) were monitored by urinary PSA analysis for a further 7 weeks after therapy cessation. More mice were cured at day 84 than at day 42 confirming activation of the immune system. Cured mice resisted the re-challenge with subcutaneous tumors unlike naïve, age matched mice. Antigen specific T cells recognizing BCG, HY and PSA were identified. Thus, fewer intravesical instillations, with high dose BCG Tokyo or low dose BCG Tokyo with GMCSF + IFNα gene therapy, can induce effective systemic immunity.
Special Issue: Hypoxia-Inducible Factors: Regulation and Therapeutic Potential
Authors: Hirota Kiichi
Published: November 2021

Oxygen (O2) is an essential molecule [...]
Cytogenomic Profile of Uterine Leiomyoma: In Vivo vs. In Vitro Comparison
Authors: Koltsova Alla S. , Efimova Olga A. , Malysheva Olga V. , Osinovskaya Natalia S. , Liehr Thomas , Al-Rikabi Ahmed , Shved Natalia Yu. , Sultanov Iskender Yu. , Chiryaeva Olga G. , Yarmolinskaya Maria I. , Polenov Nikolai I. , Kunitsa Vladislava V. , Kakhiani Maka I. , Tral Tatyana G. , Tolibova Gulrukhsor Kh. , Bespalova Olesya N. , Kogan Igor Yu. , Glotov Andrey S. , Baranov Vladislav S. , Pendina Anna A.
Published: November 2021

We performed a comparative cytogenomic analysis of cultured and uncultured uterine leiomyoma (UL) samples. The experimental approach included karyotyping, aCGH, verification of the detected chromosomal abnormalities by metaphase and interphase FISH, MED12 mutation analysis and telomere measurement by Q-FISH. An abnormal karyotype was detected in 12 out of 32 cultured UL samples. In five karyotypically abnormal ULs, MED12 mutations were found. The chromosomal abnormalities in ULs were present mostly by complex rearrangements, including chromothripsis. In both karyotypically normal and abnormal ULs, telomeres were ~40% shorter than in the corresponding myometrium, being possibly prerequisite to chromosomal rearrangements. The uncultured samples of six karyotypically abnormal ULs were checked for the detected chromosomal abnormalities through interphase FISH with individually designed DNA probe sets. All chromosomal abnormalities detected in cultured ULs were found in corresponding uncultured samples. In all tumors, clonal spectra were present by the karyotypically abnormal cell clone/clones which coexisted with karyotypically normal ones, suggesting that chromosomal abnormalities acted as drivers, rather than triggers, of the neoplastic process. In vitro propagation did not cause any changes in the spectrum of the cell clones, but altered their ratio compared to uncultured sample. The alterations were unique for every UL. Compared to its uncultured counterpart, the frequency of chromosomally abnormal cells in the cultured sample was higher in some ULs and lower in others. To summarize, ULs are characterized by both inter- and intratumor genetic heterogeneity. Regardless of its MED12 status, a tumor may be comprised of clones with and without chromosomal abnormalities. In contrast to the clonal spectrum, which is unique and constant for each UL, the clonal frequency demonstrates up or down shifts under in vitro conditions, most probably determined by the unequal ability of cells with different genetic aberrations to exist outside the body.
Inflammatory, Oxidative Stress, and Apoptosis Effects in Zebrafish Larvae after Rapid Exposure to a Commercial Glyphosate Formulation
Authors: Lanzarin Germano , Venâncio Carlos , Félix Luís M. , Monteiro Sandra
Published: November 2021

Glyphosate-based herbicides (GBH) are the most used herbicides in the world, carrying potentially adverse consequences to the environment and non-target species due to their massive and inadequate use. This study aimed to evaluate the effects of acute exposure to a commercial formulation of glyphosate, Roundup® Flex (RF), at environmentally relevant and higher concentrations in zebrafish larvae through the assessment of the inflammatory, oxidative stress and cell death response. Transgenic Tg(mpxGFP)i114 and wild-type (WT) zebrafish larvae (72 h post-fertilisation) were exposed to 1, 5, and 10 µg mL−1 of RF (based on the active ingredient concentration) for 4 h 30 min. A concentration of 2.5 µg mL−1 CuSO4 was used as a positive control. Copper sulphate exposure showed effectiveness in enhancing the inflammatory profile by increasing the number of neutrophils, nitric oxide (NO) levels, reactive oxygen species (ROS), and cell death. None of the RF concentrations tested showed changes in the number of neutrophils and NO. However, the concentration of 10 µg a.i. mL−1 was able to induce an increase in ROS levels and cell death. The activity of antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)), the biotransformation activity, the levels of reduced (GSH) and oxidised (GSSG) glutathione, lipid peroxidation (LPO), lactate dehydrogenase (LDH), and acetylcholinesterase (AChE) were similar among groups. Overall, the evidence may suggest toxicological effects are dependent on the concentration of RF, although at concentrations that are not routinely detected in the environment. Additional studies are needed to better understand the underlying molecular mechanisms of this formulation.
A Rapid and Easy-to-Perform Method of Nucleic-Acid Based Dengue Virus Diagnosis Using Fluorescence-Based Molecular Beacons
Authors: Sukla Soumi , Mondal Prasenjit , Biswas Subhajit , Ghosh Surajit
Published: November 2021

Detecting dengue virus (DENV) infection in patients as early as possible makes the disease management convenient. Conventionally, DENV infection is diagnosed by ELISA-based methods, but sensitivity and specificity are major concerns. Reverse-transcription-PCR (RT-PCR)-based detection confirms the presence of DENV RNA; however, it is expensive, time-consuming, and skilled personnel are required. A fluorescence-based detection system that detects DENV RNA in patient’s serum directly, without any nucleic acid amplification step, has been developed. The method uses target-specific complementary sequence in the molecular beacon, which would specifically bind to the DENV RNA. The molecular beacons are approximately 40 bases long hairpin structures, with a fluorophore-quencher system attached at the terminal ends of the stem. These probes are biotinylated in the stem region, so that they can be immobilized on the streptavidin-tagged magnetic beads. These magnetic beads, coupled with biotinylated molecular beacons, are used for the detection of the target RNA in the serum by incubating the mixture. After incubation, beads are separated and re-suspended in a buffer. The measurement of fluorescence is taken in fluorometer after 15 min incubation at 50 °C. The whole work is carried out in a single tube. This rapid method can precisely detect dengue RNA within two hours, confirming ongoing DENV replication in the patient.
RFID-Based Microwave Biosensor for Non-Contact Detection of Glucose Solution
Authors: Gao Minjia , Qiang Tian , Ma Yangchuan , Liang Junge , Jiang Yanfeng
Published: November 2021

Due to the increasing number of diabetic patients, early monitoring of glucose levels is particularly important; therefore, glucose biosensors have attracted enormous attention from researchers. In this paper, we propose a glucose microwave biosensor based on RFID and achieve a non-contact measurement of the concentration of glucose solutions. The Reader is a complementary split-ring resonator (CSRR), and the Tag is comprised of a squared spiral capacitor (SSC). A polydimethylsiloxane microfluidic quantitative cavity with a volume of 1.56 μL is integrated on the Tag to ensure that the glucose solution can be accurately set to the sensitive area and fully contacted with the electromagnetic flux. Because the SSC exhibits different capacitances when it contacts glucose solutions of different concentrations, changing the resonant frequency of the CSRR, we can use the relationship to characterize the biosensing response. Measurement results show that bare CSRR and RFID-based biosensors have achieved sensitivities of 0.31 MHz/mg·dL−1 and 10.27 kHz/mg·dL−1, and detection limits of 13.79 mg/dL and 1.19 mg/dL, respectively, and both realize a response time of less than 1 s. Linear regression analysis of the abovementioned biosensors showed an excellent linear relationship. The proposed design provides a feasible solution for microwave biosensors aiming for the non-contact measurement of glucose concentration.
Seismic Vulnerability Assessment for Masonry Churches: An Overview on Existing Methodologies
Authors: Zizi Mattia , Rouhi Jafar , Chisari Corrado , Cacace Daniela , De Matteis Gianfranco
Published: November 2021

The present manuscript deals with the seismic vulnerability assessment of existing masonry churches, which is a fundamental process for risk and consequent prioritization analyses, as well as application of effective retrofitting strategies. In the past, different approaches with various levels of accuracy and application ranges have been developed to assess the vulnerability to damage of such structures in case of seismic events. Based on the classification provided in the Italian Guidelines for the Cultural Heritage, in this paper a review of seismic vulnerability assessment methodologies for existing masonry churches is presented. The main goal of the current study is to provide a critical comparative overview about these procedures, highlighting the main issues related to the application of each detail level. Moreover, particular attention is focused on the applications present in literature, allowing for the definition of a potential systematic procedure for smart management policy aimed at preserving cultural, architectural and historical heritage.
In Vivo Targeting of CXCR4—New Horizons
Authors: Schottelius Margret , Herrmann Ken , Lapa Constantin
Published: November 2021

Given its pre-eminent role in the context of tumor cell growth as well as metastasis, the C-X-C motif chemokine receptor 4 (CXCR4) has attracted a lot of interest in the field of nuclear oncology, and clinical evidence on the high potential of CXCR4-targeted theranostics is constantly accumulating. Additionally, since CXCR4 also represents a key player in the orchestration of inflammatory responses to inflammatory stimuli, based on its expression on a variety of pro- and anti-inflammatory immune cells (e.g., macrophages and T-cells), CXCR4-targeted inflammation imaging has recently gained considerable attention. Therefore, after briefly summarizing the current clinical status quo of CXCR4-targeted theranostics in cancer, this review primarily focuses on imaging of a broad spectrum of inflammatory diseases via the quantification of tissue infiltration with CXCR4-expressing immune cells. An up-to-date overview of the ongoing preclinical and clinical efforts to visualize inflammation and its resolution over time is provided, and the predictive value of the CXCR4-associated imaging signal for disease outcome is discussed. Since the sensitivity and specificity of CXCR4-targeted immune cell imaging greatly relies on the availability of suitable, tailored imaging probes, recent developments in the field of CXCR4-targeted imaging agents for various applications are also addressed.
Current and Future Tools for Diagnosis of Kaposi’s Sarcoma
Authors: Dupin Nicolas , Jary Aude , Boussouar Samia , Syrykh Charlotte , Gandjbakhche Amir , Bergeret Sébastien , Palich Romain
Published: November 2021

Kaposi’s sarcoma (KS) is a rare, atypical malignancy associated with immunosuppression and can be qualified as an opportunistic tumor, which responds to immune modulation or restoration. Four different epidemiological forms have been individualized (AIDS-related, iatrogenic, endemic or classic KS). Although clinical examination is sufficient to diagnose cutaneous lesions of KS, additional explorations are necessary in order to detect lesions involving other organs. New histological markers have been developed in recent years concerning the detection of HHV-8 latent or lytic proteins in the lesions, helping to confirm the diagnosis when it is clinically doubtful. More recently, the evaluation of the local immune response has also been shown to provide some guidance in choosing the appropriate therapeutic option when necessary. We also review the indication and the results of conventional radiological imaging and of non-invasive imaging tools such as 18F-fluoro-deoxy-glucose positron emission tomography, thermography and laser Doppler imaging for the diagnosis of KS and for the follow-up of therapeutic response in patients requiring systemic treatment.
Radiodermatitis and Fibrosis in the Context of Breast Radiation Therapy: A Critical Review
Authors: Allali Sofiane , Kirova Youlia
Published: November 2021

Background: Radiation therapy has been progressively improved in order to maintain a satisfactory tumour response, while reducing toxicity. We will review the incidence of radiodermatitis and fibrosis according to the various radiation and fractionation techniques. We will then focus on the various methods used to manage, prevent, and quantify this toxicity. Method: More than 1753 articles were identified using the various search terms. We selected 53 articles to answer the questions addressed in this study according to criteria set in advance. Result: The literature reports lower acute toxicity with IMRT compared to 3DCRT, but no significant differences in terms of late toxicities. Partial breast irradiation appears to be less effective in terms of local control with a higher rate of late toxicity. Intra operative radiation therapy appears to provide good results in terms of both local control and late toxicity. The hypofractionation has equivalent efficacy and safety to the normofractionated regimen, but with lower rates of radiodermatitis and fibrosis. The adddition of a boost, particularly a sequential boost, increases the risk of fibrosis and radiodermatitis during treatment. Conclusion: The development of IMRT has significantly reduced acute toxicity and has improved tolerability during treatment. Modified fractionation has reduced treatment time, as well as adverse effects.
Immune-Checkpoint Inhibition in the Treatment of Gastro-Esophageal Cancer: A Closer Look at the Emerging Evidence
Authors: Paydary Koosha , Reizine Natalie , Catenacci Daniel V. T.
Published: November 2021

To date, several trials have evaluated the safety and efficacy of immune-checkpoint inhibitors (ICI) for the treatment of gastroesophageal cancers (GEC). In the US, ICIs have established indications for second-line treatment of microsatellite unstable tumors, while their use in third-line settings was recently withdrawn. Notably, the use of ICIs for first-line therapy of GEC is rapidly evolving, which currently includes high PD-L1 expressing tumors, irrespective of HER2 status, and in the adjuvant setting after neoadjuvant chemoradiotherapy in select patients. In this article, we review the results of studies that have evaluated the utility of ICI in the third-line, second-line, first-line, and peri-operative treatment settings of GECs. Considerations should be made before making any cross-trial comparisons since these trials vary in chemotherapy backbone, anatomical and histological eligibility, biomarker assessment, PD-L1 diagnostic antibodies, and definition of PD-L1 positivity. Regardless, the totality of the data suggest that first-line ICI use may most benefit GEC patients with high PD-L1 combined positivity score (CPS) ≥5 or ≥10, irrespective of histology or anatomy. Moreover, although PD-L1 by CPS has a good negative predictive value for significant benefit from ICIs, it has a low positive predictive value. Therefore, there is a pressing need to identify better biomarkers to predict benefit from ICIs among these patients.
Local Treatments in the Unresectable Patient with Colorectal Cancer Metastasis: A Review from the Point of View of the Medical Oncologist
Authors: Torres-Jiménez Javier , Esteban-Villarrubia Jorge , Ferreiro-Monteagudo Reyes , Carrato Alfredo
Published: November 2021

For patients with isolated liver metastases from colorectal cancer who are not candidates for potentially curative resections, non-surgical local treatments may be useful. Non-surgical local treatments are classified according to how the treatment is administered. Local treatments are applied directly on hepatic parenchyma, such as radiofrequency, microwave hyperthermia and cryotherapy. Locoregional therapies are delivered through the hepatic artery, such as chemoinfusion, chemoembolization or selective internal radiation with Yttrium 90 radioembolization. The purpose of this review is to describe the different interventional therapies that are available for these patients in routine clinical practice, the most important clinical trials that have tried to demonstrate the effectiveness of each therapy and recommendations from principal medical oncologic societies.
Evaluation of the Hamburg-Glasgow Classification in Pancreatic Cancer: Preoperative Staging by Combining Disseminated Tumor Load and Systemic Inflammation
Authors: Abdalla Thaer S. A. , Almanfalouti Valeria , Effenberger Katharina , Uzunoglu Faik G. , Ghadban Tarik , Dupreé Anna , Izbicki Jakob R. , Pantel Klaus , Reeh Matthias
Published: November 2021

This study aims to compare the Hamburg Glasgow Classification (HGC) to Union for International Cancer Control (UICC) classification in patients with pancreatic ductal adenocarcinoma (PDAC). As adequate tumor classification is only possible after tumor resection and histological evaluation, only 20% of patients with PDAC receive accurate tumor staging. Thus, an accurate preoperative staging system is still missing but urgently needed. Systemic inflammation and tumor dissemination are important factors regarding the oncological outcome. HGC integrates both into a preoperative staging system, by combining C-reactive protein (CRP), albumin, and disseminated tumor cells (DTC) in the bone marrow. In this prospective study, 109 patients underwent surgical exploration for suspected PDAC. All patients underwent a preoperative bone marrow aspiration for DTC detection. HGC showed significant preoperative risk stratification for overall survival (OS) (p-value < 0.001) and progression-free survival (PFS) (p-value < 0.001). These results were comparable to the UICC survival stratification for OS and PFS (p-value = 0.001 and 0.006). Additionally, in non-metastatic PDAC, HGC III-IV was associated with shorter OS and PFS (p-value < 0.001, respectively) when compared to HGC I-II. Therefore, the HGC is a promising preoperative prognostic staging classification for accurate and simple outcome stratification in patients with PDAC.
CARMA3 Promotes Colorectal Cancer Cell Motility and Cancer Stemness via YAP-Mediated NF-κB Activation
Authors: Chang Ting-Yu , Wu Cheng-Tien , Sheu Meei-Ling , Yang Rong-Sen , Liu Shing-Hwa
Published: November 2021

CARD-recruited membrane-associated protein 3 (CARMA3) is overexpressed in various cancers and is associated with cancer cell proliferation, metastasis, and tumor progression; however, the underlying mechanisms of CARMA3 in colorectal cancer (CRC) metastasis remain unclear. Here, we found that higher CARMA3 expression was correlated with poor overall survival and metastasis in CRC patients from the TNMplot database and Human Tissue Microarray staining. Elevating CARMA3 expression promoted cell proliferation, epithelial-mesenchymal transition (EMT) induction, migration/invasion abilities, sphere formation, and cancer stem cell markers expression. Knockdown of CARMA3 decreased these processes via the EMT-related transcription factor Slug. Moreover, CARMA3 depletion significantly reduced tumor growth in mice that were consistent with the in vitro results. CRC migration/invasion could be regulated by CARMA3/YAP/Slug signaling axis using genetic inhibition of Yes-associated protein (YAP). Interestingly, CARMA3 induced activation of nuclear factor (NF)-κB through YAP expression, contributing to upregulation of Slug. YAP expression positively correlated with CARMA3, NF-κB, and Slug gene expression and poor clinical outcomes in CRC patients. Our findings demonstrate for the first time that CARMA3 plays an important role in CRC progression, which may serve as a potential diagnostic biomarker and candidate therapeutic target for CRC treatment.
What Are the Place and Modalities of Surgical Management for Pancreatic Neuroendocrine Neoplasms? A Narrative Review
Authors: Frey Samuel , Mirallié Eric , Le Bras Maëlle , Regenet Nicolas
Published: November 2021

Pancreatic neuroendocrine neoplasms (panNENs) are a heterogeneous group of tumors derived from cells with neuroendocrine differentiation. They are considered malignant by default. However, their outcomes are variable depending on their presentation in the onset of hereditary syndromes, hormonal secretion, grading, and extension. Therefore, although surgical treatment has long been suggested as the only treatment of pancreatic neuroendocrine neoplasms, its modalities are an evolving landscape. For selected patients (small, localized, non-functional panNENs), a “wait and see” strategy is suggested, as it is in the setting of multiple neuroendocrine neoplasia type 1, but the accurate size cut-off remains to be established. Parenchyma-sparring pancreatectomy, aiming to limit pancreatic insufficiency, are also emerging procedures, which place beyond the treatment of insulinomas and small non-functional panNENs (in association with lymph node picking) remains to be clarified. Furthermore, giving the fact that the liver is generally the only metastatic site, surgery keeps a place of choice alongside medical therapies in the treatment of metastatic disease, but its modalities and extensions are still a matter of debate. This narrative review aims to describe the current recommended surgical management for pancreatic NENs and controversies in light of the actual recommendations and recent literature.
Organ Specific Copy Number Variations in Visceral Metastases of Human Melanoma
Authors: Papp Orsolya , Doma Viktória , Gil Jeovanis , Markó-Varga György , Kárpáti Sarolta , Tímár József , Vízkeleti Laura
Published: November 2021

Malignant melanoma is one of the most aggressive skin cancers with high potential of visceral dissemination. Since the information about melanoma genomics is mainly based on primary tumors and lymphatic or skin metastases, an autopsy-based visceral metastasis biobank was established. We used copy number variation arrays (N = 38 samples) to reveal organ specific alterations. Results were partly completed by proteomic analysis. A significant increase of high-copy number gains was found in an organ-specific manner, whereas copy number losses were predominant in brain metastases, including the loss of numerous DNA damage response genes. Amplification of many immune genes was also observed, several of them are novel in melanoma, suggesting that their ectopic expression is possibly underestimated. This “immunogenic mimicry” was exclusive for lung metastasis. We also provided evidence for the possible autocrine activation of c-MET, especially in brain and lung metastases. Furthermore, frequent loss of 9p21 locus in brain metastases may predict higher metastatic potential to this organ. Finally, a significant correlation was observed between BRAF gene copy number and mutant allele frequency, mainly in lung metastases. All of these events may influence therapy efficacy in an organ specific manner, which knowledge may help in alleviating difficulties caused by resistance.
Comparison of Clinical Outcomes of Radical Prostatectomy versus IMRT with Long-Term Hormone Therapy for Relatively Young Patients with High- to Very High-Risk Localized Prostate Cancer
Authors: Shih Hung-Jen , Chang Shyh-Chyi , Hsu Chia-Hao , Lin Yi-Chu , Hung Chu-Hsuan , Wu Szu-Yuan
Published: November 2021

That intensity-modulated radiotherapy (IMRT) plus antiandrogen therapy (IMRT-ADT) and radical prostatectomy (RP) are the definitive optimal treatments for relatively young patients (aged ≤ 65 years) with high- or very high-risk localized prostate cancer (HR/VHR-LPC), but remains controversial. We conducted a national population-based cohort study by using propensity score matching (PSM) to evaluate the clinical outcomes of RP and IMRT-ADT in relatively young patients with HR/VHR-LPC. Methods: We used the Taiwan Cancer Registry database to evaluate clinical outcomes in relatively young (aged ≤ 65 years) patients with HR/VHR-LPC, as defined by the National Comprehensive Cancer Network risk strata. The patients had received RP or IMRT-ADT (high-dose, ≥72 Gy plus long-term, 1.5–3 years, ADT). Head-to-head PSM was used to balance potential confounders. A Cox proportional hazards regression model was used to analyze oncologic outcomes. Results: High-dose IMRT-ADT had a higher risk of biochemical failure (adjusted hazard ratio [aHR] = 2.03, 95% confidence interval [CI] 1.56–2.65, p < 0.0001) compared with RP; IMRT-ADT did not have an increased risk of all-cause death (aHR = 1.2, 95% CI 0.65–2.24, p = 0.564), locoregional recurrence (aHR = 0.88, 95% CI 0.67–1.06, p = 0.3524), or distant metastasis (aHR = 1.03, 95% CI 0.56–1.9, p = 0.9176) compared with RP. Conclusion: In relatively young patients with HR/VHR-LPC, RP and IMRT-ADT yielded similar oncologic outcomes and RP reduced the risk of biochemical failure compared with IMRT-ADT.
Analysis of Circulating Tumour Cells in Early-Stage Uveal Melanoma: Evaluation of Tumour Marker Expression to Increase Capture
Authors: Beasley Aaron B. , Isaacs Timothy W. , Vermeulen Tersia , Freeman James , DeSousa Jean-Louis , Bhikoo Riyaz , Hennessy Doireann , Reid Anna , Chen Fred K. , Bentel Jacqueline , McKay Daniel , Conway R. Max , Pereira Michelle R. , Mirzai Bob , Calapre Leslie , Erber Wendy N. , Ziman Melanie R. , Gray Elin S.
Published: November 2021

(1) Background: The stratification of uveal melanoma (UM) patients into prognostic groups is critical for patient management and for directing patients towards clinical trials. Current classification is based on clinicopathological and molecular features of the tumour. Analysis of circulating tumour cells (CTCs) has been proposed as a tool to avoid invasive biopsy of the primary tumour. However, the clinical utility of such liquid biopsy depends on the detection rate of CTCs. (2) Methods: The expression of melanoma, melanocyte, and stem cell markers was tested in a primary tissue microarray (TMA) and UM cell lines. Markers found to be highly expressed in primary UM were used to either immunomagnetically isolate or immunostain UM CTCs prior to treatment of the primary lesion. (3) Results: TMA and cell lines had heterogeneous expression of common melanoma, melanocyte, and stem cell markers. A multi-marker panel of immunomagnetic beads enabled isolation of CTCs in 37/43 (86%) patients with UM. Detection of three or more CTCs using the multi-marker panel, but not MCSP alone, was a significant predictor of shorter progression free (p = 0.040) and overall (p = 0.022) survival. (4) Conclusions: The multi-marker immunomagnetic isolation protocol enabled the detection of CTCs in most primary UM patients. Overall, our results suggest that a multi-marker approach could be a powerful tool for CTC separation for non-invasive prognostication of UM.