bluuebunny/crossref_metadata_2025 huggingface dataset:
Microbiome Analysis from Paired Mucosal and Fecal Samples of a Colorectal Cancer Biobank
Authors: Wirth Ulrich , Garzetti Debora , Jochum Lara M. , Spriewald Stefanie , Kühn Florian , Ilmer Matthias , Lee Serene M. L. , Niess Hanno , Bazhin Alexandr V. , Andrassy Joachim , Werner Jens , Stecher Barbara , Schiergens Tobias S.
Published: December 2020

The role of gut microbiota in colorectal cancer is subject to extensive research. Before usage of biorepositories for microbiome studies, it is crucial to evaluate technical feasibility of microbiome profiling from various biospecimens. The aim of this study was to assess the feasibility of DNA-extraction and microbiome profiling of samples from different sample sites, tissue sites and storage duration of a colorectal cancer biobank. Mucosa samples, mucosal scrapings and feces as well as different tissue sites (tumor, normal mucosa) were analyzed. 16S rRNA gene-based microbiome profiling with taxonomic assignment was performed on the Illumina MiSeq (Illumina, San Diego, USA) platform from stored snap frozen samples. For statistical analysis, α- and β-diversity measures, PCoA, permutational multivariate analysis of variance and graphical representation were performed. Microbiome analysis could be successfully performed in most of the samples (overall 93.3%) with sufficient numbers of high-quality reads. There were no differences between sample sites, while in some measures significant differences were found between tumor and normal mucosa (α-diversity, Shannon/Simpson Indices p = 0.028/0.027, respectively). Samples stored for up to eight years were used and storage conditions had no significant influence on the results. Tumor and tissue samples of a biobank stored long term can be successfully used for microbiome analysis. As large sample sizes are needed for association studies to evaluate microbial impact on tumorigenesis or progression of colorectal cancer, an already established biorepository may be a useful alternative to prospective clinical studies.
The Emerging Role of miRNAs for the Radiation Treatment of Pancreatic Cancer
Authors: Nguyen Lily , Schilling Daniela , Dobiasch Sophie , Raulefs Susanne , Santiago Franco Marina , Buschmann Dominik , Pfaffl Michael W. , Schmid Thomas E. , Combs Stephanie E.
Published: December 2020

Today, pancreatic cancer is the seventh leading cause of cancer-related deaths worldwide with a five-year overall survival rate of less than 7%. Only 15–20% of patients are eligible for curative intent surgery at the time of diagnosis. Therefore, neoadjuvant treatment regimens have been introduced in order to downsize the tumor by chemotherapy and radiotherapy. To further increase the efficacy of radiotherapy, novel molecular biomarkers are urgently needed to define the subgroup of pancreatic cancer patients who would benefit most from radiotherapy. MicroRNAs (miRNAs) could have the potential to serve as novel predictive and prognostic biomarkers in patients with pancreatic cancer. In the present article, the role of miRNAs as blood biomarkers, which are associated with either radioresistance or radiation-induced changes of miRNAs in pancreatic cancer, is discussed. Furthermore, the manuscript provides own data of miRNAs identified in a pancreatic cancer mouse model as well as radiation-induced miRNA changes in the plasma of tumor-bearing mice.
Circulating Cell-Free Tumour DNA for Early Detection of Pancreatic Cancer
Authors: Jaworski Jedrzej J. , Morgan Robert D. , Sivakumar Shivan
Published: December 2020

Pancreatic cancer is a lethal disease, with mortality rates negatively associated with the stage at which the disease is detected. Early detection is therefore critical to improving survival outcomes. A recent focus of research for early detection is the use of circulating cell-free tumour DNA (ctDNA). The detection of ctDNA offers potential as a relatively non-invasive method of diagnosing pancreatic cancer by using genetic sequencing technology to detect tumour-specific mutational signatures in blood samples before symptoms manifest. These technologies are limited by a number of factors that lower sensitivity and specificity, including low levels of detectable ctDNA in early stage disease and contamination with non-cancer circulating cell-free DNA. However, genetic and epigenetic analysis of ctDNA in combination with other standard diagnostic tests may improve early detection rates. In this review, we evaluate the genetic and epigenetic methods under investigation in diagnosing pancreatic cancer and provide a perspective for future developments.
Role of the Main Non HLA-Specific Activating NK Receptors in Pancreatic, Colorectal and Gastric Tumors Surveillance
Authors: Ferretti Elisa , Carlomagno Simona , Pesce Silvia , Muccio Letizia , Obino Valentina , Greppi Marco , Solari Agnese , Setti Chiara , Marcenaro Emanuela , Della Chiesa Mariella , Sivori Simona
Published: December 2020

Human NK cells can control tumor growth and metastatic spread thanks to their powerful cytolytic activity which relies on the expression of an array of activating receptors. Natural cytotoxicity receptors (NCRs) NKG2D and DNAM-1 are those non-HLA-specific activating NK receptors that are mainly involved in sensing tumor transformation by the recognition of different ligands, often stress-induced molecules, on the surface of cancer cells. Tumors display several mechanisms aimed at dampening/evading NK-mediated responses, a relevant fraction of which is based on the downregulation of the expression of activating receptors and/or their ligands. In this review, we summarize the role of the main non-HLA-specific activating NK receptors, NCRs, NKG2D and DNAM-1, in controlling tumor growth and metastatic spread in solid malignancies affecting the gastrointestinal tract with high incidence in the world population, i.e., pancreatic ductal adenocarcinoma (PDAC), colorectal cancer (CRC), and gastric cancer (GC), also describing the phenotypic and functional alterations induced on NK cells by their tumor microenvironment.
Unusual Faces of Bladder Cancer
Authors: Manini Claudia , López José I.
Published: December 2020

The overwhelming majority of bladder cancers are transitional cell carcinomas. Albeit mostly monotonous, carcinomas in the bladder may occasionally display a broad spectrum of histological features that should be recognized by pathologists because some of them represent a diagnostic problem and/or lead prognostic implications. Sometimes these features are focal in the context of conventional transitional cell carcinomas, but some others are generalized across the tumor making its recognition a challenge. For practical purposes, the review distributes the morphologic spectrum of changes in architecture and cytology. Thus, nested and large nested, micropapillary, myxoid stroma, small tubules and adenoma nephrogenic-like, microcystic, verrucous, and diffuse lymphoepithelioma-like, on one hand, and plasmacytoid, signet ring, basaloid-squamous, yolk-sac, trophoblastic, rhabdoid, lipid/lipoblastic, giant, clear, eosinophilic (oncocytoid), and sarcomatoid, on the other, are revisited. Key histological and immunohistochemical features useful in the differential diagnosis are mentioned. In selected cases, molecular data associated with the diagnosis, prognosis, and/or treatment are also included.
Blockage of Squamous Cancer Cell Collective Invasion by FAK Inhibition Is Released by CAFs and MMP-2
Authors: Sáenz-de-Santa-María Inés , Celada Lucía , San José Martínez Andrés , Cubiella Tamara , Chiara María-Dolores
Published: December 2020

Metastasis remains a clinically unsolved issue in cancer that is initiated by the acquisition of collective migratory properties of cancer cells. Phenotypic and functional heterogeneity that arise among cancer cells within the same tumor increase cellular plasticity and promote metastasis, however, their impact on collective cell migration is incompletely understood. Here, we show that in vitro collective cancer cell migration depends on FAK and MMP-2 and on the presence of cancer-associated fibroblasts (CAFs). The absence of functional FAK rendered cancer cells incapable of invading the surrounding stroma. However, CAFs and cancer cells over-expressing MMP-2 released FAK-deficient cells from this constraint by taking the leader positions in the invasive tracks, pushing FAK-deficient squamous cell carcinoma (SCC) cells towards the stroma and leading to the transformation of non-invasive cells into invasive cells. Our cell-based studies and the RNAseq data from the TCGA cohort of patients with head and neck squamous cell carcinomas reveal that, although both FAK and MMP-2 over-expression are associated with epithelial–mesenchymal transition, it is only MMP-2, not FAK, that functions as an independent prognostic factor. Given the significant role of MMP-2 in cancer dissemination, targeting of this molecule, better than FAK, presents a more promising opportunity to block metastasis.
Regulators at Every Step—How microRNAs Drive Tumor Cell Invasiveness and Metastasis
Authors: Grzywa Tomasz M. , Klicka Klaudia , Włodarski Paweł K.
Published: December 2020

Tumor cell invasiveness and metastasis are the main causes of mortality in cancer. Tumor progression is composed of many steps, including primary tumor growth, local invasion, intravasation, survival in the circulation, pre-metastatic niche formation, and metastasis. All these steps are strictly controlled by microRNAs (miRNAs), small non-coding RNA that regulate gene expression at the post-transcriptional level. miRNAs can act as oncomiRs that promote tumor cell invasion and metastasis or as tumor suppressor miRNAs that inhibit tumor progression. These miRNAs regulate the actin cytoskeleton, the expression of extracellular matrix (ECM) receptors including integrins and ECM-remodeling enzymes comprising matrix metalloproteinases (MMPs), and regulate epithelial–mesenchymal transition (EMT), hence modulating cell migration and invasiveness. Moreover, miRNAs regulate angiogenesis, the formation of a pre-metastatic niche, and metastasis. Thus, miRNAs are biomarkers of metastases as well as promising targets of therapy. In this review, we comprehensively describe the role of various miRNAs in tumor cell migration, invasion, and metastasis.
Functional Dependency Analysis Identifies Potential Druggable Targets in Acute Myeloid Leukemia
Authors: Zhou Yujia , Takacs Gregory P. , Lamba Jatinder K. , Vulpe Christopher , Cogle Christopher R.
Published: December 2020

Refractory disease is a major challenge in treating patients with acute myeloid leukemia (AML). Whereas the armamentarium has expanded in the past few years for treating AML, long-term survival outcomes have yet to be proven. To further expand the arsenal for treating AML, we searched for druggable gene targets in AML by analyzing screening data from a lentiviral-based genome-wide pooled CRISPR-Cas9 library and gene knockout (KO) dependency scores in 15 AML cell lines (HEL, MV411, OCIAML2, THP1, NOMO1, EOL1, KASUMI1, NB4, OCIAML3, MOLM13, TF1, U937, F36P, AML193, P31FUJ). Ninety-four gene KOs met the criteria of (A) specifically essential to AML cell survival, (B) non-essential in non-AML cells, and (C) druggable according to three-dimensional (3D) modeling or ligand-based druggability scoring. Forty-four of 94 gene-KOs (47%) had an already-approved drug match and comprised a drug development list termed “deKO.” Fifty of 94 gene-KOs (53%) had no drug in development and comprised a drug discovery list termed “disKO.” STRING analysis and gene ontology categorization of the disKO targets preferentially cluster in the metabolic processes of UMP biosynthesis, IMP biosynthesis, dihydrofolate metabolism, pyrimidine nucleobase biosynthesis, vitellogenesis, and regulation of T cell differentiation and hematopoiesis. Results from this study serve as a testable compendium of AML drug targets that, after validation, may be translated into new therapeutics.
NDRG1 Expression Is an Independent Prognostic Factor in Inflammatory Breast Cancer
Authors: Villodre Emilly S. , Gong Yun , Hu Xiaoding , Huo Lei , Yoon Esther C. , Ueno Naoto T. , Woodward Wendy A. , Tripathy Debu , Song Juhee , Debeb Bisrat G.
Published: December 2020

NDRG1 is widely described as a metastasis suppressor in breast cancer. However, we found that NDRG1 is critical in promoting tumorigenesis and brain metastasis in mouse models of inflammatory breast cancer (IBC), a rare but highly aggressive form of breast cancer. We hypothesized that NDRG1 is a prognostic marker associated with poor outcome in patients with IBC. NDRG1 levels in tissue microarrays from 64 IBC patients were evaluated by immunohistochemical staining with NDRG1 (32 NDRG1-low (≤median), 32 NDRG1-high (>median)). Overall and disease-free survival (OS and DSS) were analyzed with Kaplan–Meier curves and log-rank test. Univariate analysis showed NDRG1 expression, tumor grade, disease stage, estrogen receptor (ER) status, and receipt of adjuvant radiation to be associated with OS and DSS. NDRG1-high patients had poorer 10-year OS and DSS than NDRG1-low patients (OS, 19% vs. 45%, p = 0.0278; DSS, 22% vs. 52%, p = 0.0139). On multivariable analysis, NDRG1 independently predicted OS (hazard ratio (HR) = 2.034, p = 0.0274) and DSS (HR = 2.287, p = 0.0174). NDRG1-high ER-negative tumors had worse outcomes OS, p = 0.0003; DSS, p = 0.0003; and NDRG1-high tumors that received adjuvant radiation treatment had poor outcomes (OS, p = 0.0088; DSS, p = 0.0093). NDRG1 was a significant independent prognostic factor for OS and DSS in IBC patients. Targeting NDRG1 may represent a novel strategy for improving clinical outcomes for patients with IBC.
Preclinical Rationale for Targeting the PD-1/PD-L1 Axis in Combination with a CD38 Antibody in Multiple Myeloma and Other CD38-Positive Malignancies
Authors: Verkleij Christie P. M. , Jhatakia Amy , Broekmans Marloes E. C. , Frerichs Kristine A. , Zweegman Sonja , Mutis Tuna , Bezman Natalie A. , van de Donk Niels W. C. J.
Published: December 2020

The CD38-targeting antibody daratumumab mediates its anti-myeloma activities not only through Fc-receptor-dependent effector mechanisms, but also by its effects on T-cell immunity through depletion of CD38+ regulatory T-cells, regulatory B-cells, and myeloid-derived suppressor cells. Therefore, combining daratumumab with modulators of other potent immune inhibitory pathways, such as the PD-1/PD-L1 axis, may further improve its efficacy. We show that multiple myeloma (MM) cells from relapsed/refractory patients have increased expression of PD-L1, compared to newly diagnosed patients. Furthermore, PD-1 is upregulated on T-cells from both newly diagnosed and relapsed/refractory MM patients, compared to healthy controls. In short-term experiments with bone marrow samples from MM patients, daratumumab-mediated lysis was mainly associated with the MM cells’ CD38 expression levels and the effector (NK-cells/monocytes/T-cells)-to-target ratio, but not with the PD-L1 expression levels or PD-1+ T-cell frequencies. Although PD-1 blockade with nivolumab did not affect MM cell viability or enhanced daratumumab-mediated lysis in short-term ex vivo experiments, nivolumab resulted in a mild but clear increase in T-cell numbers. Moreover, with a longer treatment duration, PD-1 blockade markedly improved anti-CD38 antibody-mediated cytotoxicity in vivo in murine CD38+ tumor models. In conclusion, dual targeting of CD38 and PD-1 may represent a promising strategy for treating MM and other CD38-positive malignancies.
Predicting and Quantifying Antagonistic Effects of Natural Compounds Given with Chemotherapeutic Agents: Applications for High-Throughput Screening
Authors: Hackman G. Lavender , Collins Meghan , Lu Xiyuan , Lodi Alessia , DiGiovanni John , Tiziani Stefano
Published: December 2020

Natural products have been used for centuries to treat various human ailments. In recent decades, multi-drug combinations that utilize natural products to synergistically enhance the therapeutic effects of cancer drugs have been identified and have shown success in improving treatment outcomes. While drug synergy research is a burgeoning field, there are disagreements on the definitions and mathematical parameters that prevent the standardization and proper usage of the terms synergy, antagonism, and additivity. This contributes to the relatively small amount of data on the antagonistic effects of natural products on cancer drugs that can diminish their therapeutic efficacy and prevent cancer regression. The ability of natural products to potentially degrade or reverse the molecular activity of cancer therapeutics represents an important but highly under-emphasized area of research that is often overlooked in both pre-clinical and clinical studies. This review aims to evaluate the body of work surrounding the antagonistic interactions between natural products and cancer therapeutics and highlight applications for high-throughput screening (HTS) and deep learning techniques for the identification of natural products that antagonize cancer drug efficacy.
Selective Oxofunctionalization of Cyclohexene over Titanium Dioxide-Based and Bismuth Oxyhalide Photocatalysts by Visible Light Irradiation
Authors: Henríquez Adolfo , Mansilla Héctor D. , Martínez-de la Cruz Azael , Cornejo-Ponce Lorena , Schott Eduardo , Contreras David
Published: December 2020

Photocatalysis driven under visible light allows us to carry out hydrocarbon oxofunctionalization under ambient conditions, using molecular oxygen as a sacrificial reagent, with the absence of hazardous subproducts and the potential use of the Sun as a clean and low-cost source of light. In this work, eight materials—five based on titanium dioxide and three based on bismuth oxyhalides—were used as photocatalysts in the selective oxofunctionalization of cyclohexene. The cyclohexane oxofunctionalization reactions were performed inside of a homemade photoreactor equipped with a 400 W metal halide lamp and injected air as a source of molecular oxygen. In all assayed systems, the main oxygenated products, identified by mass spectrometry, were 1,2-epoxycyclohexane, 2-cyclohexen-1-ol, and 2-cyclohexen-1-one. Titanium dioxide-based materials exhibited higher selectivities for 1,2-epoxycyclohexane than bismuth oxyhalide-based materials. In addition to this, titanium dioxide doped with iron exhibited the best selectivity for 1,2-epoxycyclohexane, demonstrating that iron plays a relevant role in the cyclohexene epoxidation process.
U2AF65-Dependent SF3B1 Function in SMN Alternative Splicing
Authors: Choi Namjeong , Liu Yongchao , Oh Jagyeong , Ha Jiyeon , Zheng Xuexiu , Shen Haihong
Published: December 2020

Splicing factor 3b subunit 1 (SF3B1) is an essential protein in spliceosomes and mutated frequently in many cancers. While roles of SF3B1 in single intron splicing and roles of its cancer-linked mutant in aberrant splicing have been identified to some extent, regulatory functions of wild-type SF3B1 in alternative splicing (AS) are not well-understood yet. Here, we applied RNA sequencing (RNA-seq) to analyze genome-wide AS in SF3B1 knockdown (KD) cells and to identify a large number of skipped exons (SEs), with a considerable number of alternative 5′ splice-site selection, alternative 3′ splice-site selection, mutually exclusive exons (MXE), and retention of introns (RI). Among altered SEs by SF3B1 KD, survival motor neuron 2 (SMN2) pre-mRNA exon 7 splicing was a regulatory target of SF3B1. RT-PCR analysis of SMN exon 7 splicing in SF3B1 KD or overexpressed HCT116, SH-SY5Y, HEK293T, and spinal muscular atrophy (SMA) patient cells validated the results. A deletion mutation demonstrated that the U2 snRNP auxiliary factor 65 kDa (U2AF65) interaction domain of SF3B1 was required for its function in SMN exon 7 splicing. In addition, mutations to lower the score of the polypyrimidine tract (PPT) of exon 7, resulting in lower affinity for U2AF65, were not able to support SF3B1 function, suggesting the importance of U2AF65 in SF3B1 function. Furthermore, the PPT of exon 7 with higher affinity to U2AF65 than exon 8 showed significantly stronger interactions with SF3B1. Collectively, our results revealed SF3B1 function in SMN alternative splicing.
Current and Future Perspectives of the Use of Organoids in Radiobiology
Authors: Nagle Peter W. , Coppes Robert P.
Published: December 2020

The majority of cancer patients will be treated with radiotherapy, either alone or together with chemotherapy and/or surgery. Optimising the balance between tumour control and the probability of normal tissue side effects is the primary goal of radiation treatment. Therefore, it is imperative to understand the effects that irradiation will have on both normal and cancer tissue. The more classical lab models of immortal cell lines and in vivo animal models have been fundamental to radiobiological studies to date. However, each of these comes with their own limitations and new complementary models are required to fill the gaps left by these traditional models. In this review, we discuss how organoids, three-dimensional tissue-resembling structures derived from tissue-resident, embryonic or induced pluripotent stem cells, overcome the limitations of these models and thus have a growing importance in the field of radiation biology research. The roles of organoids in understanding radiation-induced tissue responses and in moving towards precision medicine are examined. Finally, the limitations of organoids in radiobiology and the steps being made to overcome these limitations are considered.
Involvement of Bradykinin Receptor 2 in Nerve Growth Factor Neuroprotective Activity
Authors: Petrella Carla , Ciotti Maria Teresa , Nisticò Robert , Piccinin Sonia , Calissano Pietro , Capsoni Simona , Mercanti Delio , Cavallaro Sebastiano , Possenti Roberta , Severini Cinzia
Published: December 2020

Neurotrophin nerve growth factor (NGF) has been demonstrated to upregulate the gene expression of bradykinin receptor 2 (B2R) on sensory neurons, thus facilitating nociceptive signals. The aim of the present study is to investigate the involvement of B2R in the NGF mechanism of action in nonsensory neurons in vitro by using rat mixed cortical primary cultures (CNs) and mouse hippocampal slices, and in vivo in Alzheimer’s disease (AD) transgenic mice (5xFAD) chronically treated with NGF. A significant NGF-mediated upregulation of B2R was demonstrated by microarray, Western blot, and immunofluorescence analysis in CNs, indicating microglial cells as the target of this modulation. The B2R involvement in the NGF mechanism of action was also demonstrated by using a selective B2R antagonist which was able to reverse the neuroprotective effect of NGF in CNs, as revealed by viability assay, and the NGF-induced long-term potentiation (LTP) in hippocampal slices. To confirm in vitro observations, B2R upregulation was observed in 5xFAD mouse brain following chronic intranasal NGF treatment. This study demonstrates for the first time that B2R is a key element in the neuroprotective activity and synaptic plasticity mediated by NGF in brain cells.
The Interplay of WNT and PPARγ Signaling in Vascular Calcification
Authors: Reinhold Stefan , Blankesteijn W. Matthijs , Foulquier Sébastien
Published: December 2020

Vascular calcification (VC), the ectopic deposition of calcium phosphate crystals in the vessel wall, is one of the primary contributors to cardiovascular death. The pathology of VC is determined by vascular topography, pre-existing diseases, and our genetic heritage. VC evolves from inflammation, mediated by macrophages, and from the osteochondrogenic transition of vascular smooth muscle cells (VSMC) in the atherosclerotic plaque. This pathologic transition partly resembles endochondral ossification, involving the chronologically ordered activation of the β-catenin-independent and -dependent Wingless and Int-1 (WNT) pathways and the termination of peroxisome proliferator-activated receptor γ (PPARγ) signal transduction. Several atherosclerotic plaque studies confirmed the differential activity of PPARγ and the WNT signaling pathways in VC. Notably, the actively regulated β-catenin-dependent and -independent WNT signals increase the osteochondrogenic transformation of VSMC through the up-regulation of the osteochondrogenic transcription factors SRY-box transcription factor 9 (SOX9) and runt-related transcription factor 2 (RUNX2). In addition, we have reported studies showing that WNT signaling pathways may be antagonized by PPARγ activation via the expression of different families of WNT inhibitors and through its direct interaction with β-catenin. In this review, we summarize the existing knowledge on WNT and PPARγ signaling and their interplay during the osteochondrogenic differentiation of VSMC in VC. Finally, we discuss knowledge gaps on this interplay and its possible clinical impact.
Nano-Based Theranostic Tools for the Detection and Elimination of Senescent Cells
Authors: Adamczyk-Grochala Jagoda , Lewinska Anna
Published: December 2020

The progressive accumulation of apoptosis-resistant and secretory active senescent cells (SCs) in animal and human aged tissues may limit lifespan and healthspan and lead to age-related diseases such as cancer, neurodegenerative disorders, and metabolic syndrome. Thus, SCs are suggested targets in anti-aging therapy. In the last two decades, a number of nanomaterials have gained much attention as innovative tools in theranostic applications due to their unique properties improving target visualization, drug and gene delivery, controlled drug release, effective diagnosis, and successful therapy. Although the healthcare industry has focused on a plethora of applications of nanomaterials, it remains elusive how nanomaterials may modulate cellular senescence, a hallmark of aging. In this review paper, we consider novel nanotechnology-based strategies for healthspan promotion and the prevention of age-related dysfunctions that are based on the delivery of therapeutic compounds capable to preferentially killing SCs (nano-senolytics) and/or modulating a proinflammatory secretome (nano-senomorphics/nano-senostatics). Recent examples of SC-targeted nanomaterials and the mechanisms underlying different aspects of the nanomaterial-mediated senolysis are presented and discussed.
Genomic Screening Reveals That the Endangered Eucalyptus paludicola (Myrtaceae) Is a Hybrid
Authors: van Dijk Kor-jent , Waycott Michelle , Quarmby Joe , Bickerton Doug , Thornhill Andrew H. , Cross Hugh , Biffin Edward
Published: December 2020

A hybrid origin for a conservation listed taxon will influence its status and management options. Here, we investigate the genetic origins of a nationally endangered listed taxon—Eucalyptus paludicola—a tree that is restricted to the Fleurieu Peninsula and Kangaroo Island of South Australia. Since its description in 1995, there have been suggestions that this taxon may potentially be a stable hybrid species. Using a high throughput sequencing approach, we developed a panel of polymorphic loci that were screened across E. paludicola and its putative parental species E. cosmophylla and E. ovata. Bayesian clustering of the genotype data identified separate groups comprising E. ovata and E. cosmophylla while E. paludicola individuals were admixed between these two, consistent with a hybrid origin. Hybrid class assignment tests indicate that the majority of E. paludicola individuals (~70%) are F1 hybrids with a low incidence of backcrossing. Most of the post-F1 hybrids were associated with revegetation sites suggesting they may be maladapted and rarely reach maturity under natural conditions. These data support the hypothesis that E. paludicola is a transient hybrid entity rather than a distinct hybrid species. We briefly discuss the conservation implications of our findings.
Diagnostic Performance of Different Simulated Low-Dose Levels in Patients with Suspected Cervical Abscess Using a Third-Generation Dual-Source CT Scanner
Authors: Winkelmann Moritz T. , Afat Saif , Walter Sven S. , Stock Eva , Schwarze Vincent , Brendlin Andreas , Kolb Manuel , Artzner Christoph P. , Othman Ahmed E.
Published: December 2020

The aim of this study was to investigate the effects of dose reduction on diagnostic accuracy and image quality of cervical computed tomography (CT) in patients with suspected cervical abscess. Forty-eight patients (mean age 45.5 years) received a CT for suspected cervical abscess. Low-dose CT (LDCT) datasets with 25%, 50%, and 75% of the original dose were generated with a realistic simulation. The image data were reconstructed with filtered back projection (FBP) and with advanced modeled iterative reconstruction (ADMIRE) (strengths 3 and 5). A five-point Likert scale was used to assess subjective image quality and diagnostic confidence. The signal-to-noise ratio (SNR) of the sternocleidomastoid muscle and submandibular gland and the contrast-to-noise ratio (CNR) of the sternocleidomastoid muscle and submandibular glandular fat were calculated to assess the objective image quality. Diagnostic accuracy was calculated for LDCT using the original dose as the reference standard. The prevalence of cervical abscesses was high (72.9%) in the cohort; the mean effective dose for all 48 scans was 1.8 ± 0.8 mSv. Sternocleidomastoid and submandibular SNR and sternocleidomastoid muscle fat and submandibular gland fat CNR increased with higher doses and were significantly higher for ADMIRE compared to FBP, with the best results in ADMIRE 5 (all p < 0.001). Subjective image quality was highest for ADMIRE 5 at 75% and lowest for FBP at 25% of the original dose (p < 0.001). Diagnostic confidence was highest for ADMIRE 5 at 75% and lowest for FBP at 25% (p < 0.001). Patient-based diagnostic accuracy was high for all LDCT datasets, down to 25% for ADMIRE 3 and 5 (sensitivity: 100%; specificity: 100%) and lower for FBP at 25% dose reduction (sensitivity: 88.6–94.3%; specificity: 92.3–100%). The use of a modern dual-source CT of the third generation and iterative reconstruction allows a reduction in the radiation dose to 25% (0.5 mSv) of the original dose with the same diagnostic accuracy for the assessment of neck abscesses.
Research on the Influence of Abrupt Climate Changes on the Analysis of Typical Meteorological Year in China
Authors: Fan Xinying , Chen Bin , Fu Changfeng , Li Lingyun
Published: December 2020

The conventional typical meteorological year (TMY) based on continuous-year original meteorological records without considering abrupt climate changes (ACC) may not be able to represent a real “typical” climate properly. Consequently, building performance analyses and simulations based on TMY may be not accurate. Current research rarely tackles this issue in TMY development. This paper presents an innovative TMY development with the consideration of ACC in the original meteorological records. It is based on the Chinese standard weather database method (CSWD) with the meteorological records of six Chinese cities in different climate zones. It applies the Moving t-test method to identify and exclude ACC points and to refine the timescales for TMY development. It also depicts the development of individual typical meteorological months again with the ACC impact to improve the accuracy of TMY. The method has been verified in several building energy consumption and thermal comfort analyses. The results demonstrate that the analysis based on the new TMY climate datasets when considering ACC will end up with less energy consumption and better thermal performance compared to the analyses based on the conversion dataset without considering ACC. This experimental research will refine TMY development, and further improve building energy performance analysis and design.
How Are Green Spaces Distributed among Different Social Groups in Urban China? A National Level Study
Authors: Wu Longfeng , Kim Seung Kyum
Published: December 2020

The study analyzes the distributional equity of urban green space (UGS) among different social groups across all urban areas in China. Urban green space is measured in two ways: Park area per capita and vegetation coverage ratio within 1.6 km and 3.2 km featuring different ecosystem services they provide. Multiple regression analyses are conducted to assess relationships between different groups (children, the elderly, and migrant populations) and distributed UGS. Largely consistent to other national level studies, the nationwide analytical results indicate emerging social inequality of UGS during the urbanization of China, with a few nuances. A bi-fold pattern is observed in our case: Whilst areas with higher portions of children and senior people have less parks and high vegetation coverage, a marginalized group—internal migrant people, have more parks and low vegetation coverage in their vicinities. The results of regression analyses in different regions further shed light on revealing disparities of UGS in areas with varying socioeconomic development levels, geographical features, and urbanization paces. The implication of the study informs the decision makers to incorporate spatial patterns of social groups into green space guidance and evaluation for the purpose of promoting more equal development of UGS.
Physical and Chemical Effects of Different Working Gases in Coffee Brewing: A Case Study of Caffè Firenze
Authors: Angeloni Giulia , Masella Piernicola , Guerrini Lorenzo , Spadi Agnese , Bellumori Maria , Innocenti Marzia , Parenti Alessandro
Published: December 2020

(1) Background: Recently, a new espresso extraction method, Caffè Firenze, has been developed, which uses gas at operating pressures of 20 bar to obtain abundant, persistent foam. The experiment aimed to evaluate the effect of using six gases (air, argon, nitrogen, carbon dioxide, carbon/nitrogen mix, and nitrous oxide) on the foam and liquid coffee. (2) Methods: Foam volume, persistence, sugar retention time, color, and rheological properties were measured. Volatile organic compounds were also evaluated. Analyses were also carried out on the liquid coffee to determine caffeine and chlorogenic acid concentrations. (3) Results: The analysis of variance revealed significant differences between the gases for all parameters. Multivariate analysis identified three groups of gases: the first comprised air, N2, and Ar; the second CO2 and N2O; and the third comprised samples extracted with CO2/N2 mix. (4) Conclusions: The choice of gas significantly influences the drink’s chemical-physical characteristics and is fundamental for product diversification.
In Vitro Gastrointestinal Digestion and Colonic Catabolism of Mango (Mangifera indica L.) Pulp Polyphenols
Authors: Ordoñez-Díaz José Luis , Moreno-Ortega Alicia , Roldán-Guerra Francisco Javier , Ortíz-Somovilla Victor , Moreno-Rojas José Manuel , Pereira-Caro Gema
Published: December 2020

Mango (Mangifera indica L.), a fruit with sensorial attractiveness and extraordinary nutritional and phytochemical composition, is one of the most consumed tropical varieties in the world. A growing body of evidence suggests that their bioactive composition differentiates them from other fruits, with mango pulp being an especially rich and diverse source of polyphenols. In this study, mango pulp polyphenols were submitted to in vitro gastrointestinal digestion and colonic fermentation, and aliquots were analyzed by HPLC-HRMS. The main phenolic compounds identified in the mango pulp were hydroxybenzoic acid-hexoside, two mono-galloyl-glucoside isomers and vanillic acid. The release of total polyphenols increased after the in vitro digestion, with an overall bioaccessibility of 206.3%. Specifically, the most bioaccessible mango polyphenols were gallic acid, 3-O-methylgallic acid, two hydroxybenzoic acid hexosides, methyl gallate, 3,4-dihydroxybenzoic acid and benzoic acid, which potentially cross the small intestine reaching the colon for fermentation by the resident microbiota. After 48 h of fecal fermentation, the main resultant mango catabolites were pyrogallol, gallic and 3,4-dihydroxybenzoic acids. This highlighted the extensive transformation of mango pulp polyphenols through the gastrointestinal tract and by the resident gut microbiota, with the resultant formation of mainly simple phenolics, which can be considered as biomarkers of the colonic metabolism of mango.
Dynamics of Volatile Compounds in Triticale Bread with Sourdough: From Flour to Bread
Authors: Galoburda Ruta , Straumite Evita , Sabovics Martins , Kruma Zanda
Published: December 2020

Triticale has been suggested for human consumption due to its valuable nutritional composition. The aim of this study was to evaluate volatile compound dynamics in the technological processes of triticale bread and triticale bread with sourdough prepared using Lactobacillus sanfranciscensis based cultures. Two types of sourdough ready-to-use sourdough and two-stage sourdough were used for bread making. Triticale bread without sourdough was used as a control. Volatile compounds from a headspace of flour blend, sourdough, as well as mixed dough, fermented dough, bread crumb and crust were extracted using solid-phase microextraction (SPME) in combination with gas chromatography/mass spectrometry. Alcohols, mainly 1-hexanol, were the main volatiles in the triticale flour blend, whereas in the headspace of sourdough samples ethyl-acetate, ethanol and acetic acid dominated. Two-stage sourdough after 30 min fermentation showed the highest sum of peak areas formed by 14 volatile compounds, resulting in substrates for further aroma development in bread. A total of 29 compounds were identified in the bread: in the crumb the dominant volatile compounds were alcohols, ketones, acids, but in the crust—alcohols, aldehydes, furans dominated. The use of two-stage sourdough provided a more diverse spectrum of volatile compounds. Such volatile compounds as ethanol, 3-methyl-1-butanol, 2-methyl-1-propanol, 2-hydroxy-2-butanone, 2-methylpropanoic acid, and acetic acid were identified in all the analysed samples in all stages of bread making.
Distribution of Important Probiotic Genes and Identification of the Biogenic Amines Produced by Lactobacillus acidophilus PNW3
Authors: Alayande Kazeem Adekunle , Aiyegoro Olayinka Ayobami , Ateba Collins Njie
Published: December 2020

The genome of Lactobacillus acidophilus PNW3 was assessed for probiotic and safety potentials. The genome was completely sequenced, assembled using SPAdes, and thereafter annotated with NCBI prokaryotic genome annotation pipeline (PGAP) and rapid annotation using subsystem technology (RAST). Further downstream assessment was determined using appropriate bioinformatics tools. The production of biogenic amines was confirmed through HPLC analysis and the evolutionary trend of the strain was determined through the Codon Tree pipeline. The strain was predicted as a non-human pathogen. A plethora of encoding genes for lactic acids and bioactive peptides production, adhesion molecules, resistance to the harsh gut environmental conditions, and improvement of the host metabolism, which are putative for important probiotic functionalities, were located at different loci within the genome. A bacteriocin predicted to be helveticin J was identified as one of the secondary metabolites. The maximum zone of inhibition exhibited by the crude bacteriocin against STEC E. coli O177 was 21.7 ± 0.58 mm and 24.3 ± 1.15 mm after partial purification (250 µg/mL). Three coding sequences were identified for insertion sequences and one for the CRISPR-Cas fragment. The protein-encoding sequence for Ornithine decarboxylase was found within the genome. L. acidophilus PNW3 presents important features categorizing it as a viable and safe probiotic candidate, though further safety investigations are necessary. The application of probiotics in livestock-keeping would ensure improved public health and food security.
Games with Adaptation and Mitigation
Authors: Hritonenko Natali , Hritonenko Victoria , Yatsenko Yuri
Published: December 2020

We formulate and study a nonlinear game of n symmetric countries that produce, pollute, and spend part of their revenue on pollution mitigation and environmental adaptation. The optimal emission, adaptation, and mitigation investments are analyzed in both Nash equilibrium and cooperative cases. Modeling assumptions and outcomes are compared to other publications in this fast-developing area of environmental economics. In particular, our analysis implies that: (a) mitigation is more effective than adaptation in a crowded multi-country world; (b) mitigation increases the effectiveness of adaptation; (c) the optimal ratio between mitigation and adaptation investments in the competitive case is larger for more productive countries and is smaller when more countries are involved in the game.
Decisions on Extending Group Membership—Evidence from a Public Good Experiment
Authors: Grund Christian , Harbring Christine , Thommes Kirsten , Tilkes Katja Rebecca
Published: December 2020

We experimentally compare the consequences for group cooperation of two decision mechanisms involving the extension of group membership. We analyze an exogenous decision (random draw) and an endogenous decision (made by a particular group member) mechanism to extend a temporary agent’s group membership. Our results reveal that the prospect of group membership extension affects not only the temporary but also the permanent group members’ contributions with an endogenous mechanism.
The Hunt for Environmental Noise in Virgo during the Third Observing Run
Authors: Fiori Irene , Paoletti Federico , Tringali Maria Concetta , Janssens Kamiel , Karathanasis Christos , Menéndez-Vázquez Alexis , Romero-Rodríguez Alba , Sugimoto Ryosuke , Washimi Tatsuki , Boschi Valerio , Chiummo Antonino , Cieślar Marek , De Rosa Rosario , De Rossi Camilla , Di Renzo Francesco , Nardecchia Ilaria , Pasqualetti Antonio , Patricelli Barbara , Ruggi Paolo , Singh Neha
Published: December 2020

The first twenty years of operation of gravitational-wave interferometers have shown that these detectors are affected by physical disturbances from the surrounding environment. These are seismic, acoustic, or electromagnetic disturbances that are mainly produced by the experiment infrastructure itself. Ambient noise can limit the interferometer sensitivity or potentially generate transients of non-astrophysical origin. Between 1 April 2019 and 27 March 2020, the network of second generation interferometers—LIGO, Virgo and GEO—performed the third joined observing run, named O3, searching for gravitational signals from the deep universe. A thorough investigation has been done on each detector before and during data taking in order to optimize its sensitivity and duty cycle. In this paper, we first revisit typical sources of environmental noise and their coupling paths, and we then describe investigation methods and tools. Finally, we illustrate applications of these methods in the hunt for environmental noise at the Virgo interferometer during the O3 run and its preparation phase. In particular, we highlight investigation techniques that might be useful for the next observing runs and the future generation of terrestrial interferometers.
Advanced LIGO Laser Systems for O3 and Future Observation Runs
Authors: Bode Nina , Briggs Joseph , Chen Xu , Frede Maik , Fritschel Peter , Fyffe Michael , Gustafson Eric , Heintze Matthew , King Peter , Liu Jian , Oberling Jason , Savage Richard L. , Spencer Andrew , Willke Benno
Published: December 2020

The advanced LIGO gravitational wave detectors need high power laser sources with excellent beam quality and low-noise behavior. We present a pre-stabilized laser system with 70 W of output power that was used in the third observing run of the advanced LIGO detectors. Furthermore, the prototype of a 140 W pre-stabilized laser system for future use in the LIGO observatories is described and characterized.
46,XY,r(8)/45,XY,−8 Mosaicism as a Possible Mechanism of the Imprinted Birk-Barel Syndrome: A Case Study
Authors: Kashevarova Anna A. , Nikitina Tatyana V. , Mikhailik Larisa I. , Belyaeva Elena O. , Vasilyev Stanislav A. , Lopatkina Mariya E. , Fedotov Dmitry A. , Fonova Elizaveta A. , Zarubin Aleksei A. , Sivtsev Aleksei A. , Skryabin Nikolay A. , Nazarenko Lyudmila P. , Lebedev Igor N.
Published: December 2020

Ring chromosome 8 (r(8)) is one of the least frequent ring chromosomes. Usually, maternal chromosome 8 forms a ring, which can be lost from cells due to mitotic instability. The 8q24 region contains the imprinted KCNK9 gene, which is expressed from the maternal allele. Heterozygous KCNK9 mutations are associated with the imprinting disorder Birk-Barel syndrome. Here, we report a 2.5-year-old boy with developmental delay, microcephaly, dysmorphic features, diffuse muscle hypotonia, feeding problems, motor alalia and noncoarse neurogenic type of disturbance of muscle electrogenesis, partially overlapping with Birk-Barel syndrome phenotype. Cytogenetic analysis of lymphocytes revealed his karyotype to be 46,XY,r(8)(p23q24.3)[27]/45,XY,−8[3]. A de novo 7.9 Mb terminal 8p23.3p23.1 deletion, a 27.1 Mb 8p23.1p11.22 duplication, and a 4.4 Mb intact segment with a normal copy number located between them, as well as a 154-kb maternal LINGO2 gene deletion (9p21.2) with unknown clinical significance were identified by aCGH + SNP array. These aberrations were confirmed by real-time PCR. According to FISH analysis, the 8p23.1-p11.22 duplication was inverted. The ring chromosome originated from maternal chromosome 8. Targeted massive parallel sequencing did not reveal the KCNK9 mutations associated with Birk-Barel syndrome. Our data allow to assume that autosomal monosomy with inactive allele of imprinted gene arising from the loss of a ring chromosome in some somatic cells may be an etiological mechanism of mosaic imprinting disorders, presumably with less severe phenotype.
Genome-Wide Analysis Revealed Homozygosity and Demographic History of Five Chinese Sheep Breeds Adapted to Different Environments
Authors: Abied Adam , Xu Lei , Sahlu Bahlibi W. , Xing Feng , Ahbara Abulgasim , Pu Yabin , Lin Jiang , Berihulay Haile , Islam Rabiul , He Xiaohong , Mwacharo Joram M. , Zhao Qianjun , Ma Yuehui
Published: December 2020

Homozygosity of long sequence genotypes are a result of parents transmitting identical haplotypes, which can be used to estimate their auto-zygosity. Therefore, we used high-density SNP Chip data to characterize the auto-zygosity of each breed according to the occurrence and distribution of runs of homozygosity (ROH). Subsequently, we identified the genomic regions with high runs of homozygosity frequencies within individuals of each breed. We selected 96 sheep samples from five local Chinese sheep breeds belonging to different geographical locations. We identified 3046 ROHs within the study breed individuals, among which the longer segments (>1–5 Mb) were dominant. On average, ROH segments covered about 12% of the genomes; the coverage rate of OAR20 was the lowest and that of OAR2 was the highest. The distribution analysis of runs of homozygosity showed that the detected ROH mainly distributed between >26 and 28 Mb. The Hetian and Hu sheep showed the lowest ROH distribution. The estimation of homozygosity level reflects the history of modern and ancient inbreeding, which may affect the genomes of Chinese indigenous sheep breeds and indicate that some animals have experienced recent self-pollination events (Yabuyi, Karakul and Wadi). In these sheep breeds, the genomic regions were assumed to be under selection signatures frequently in line with long ROH. These regions included candidate genes associated with disease resistance traits (5S_rRNA), the innate and adaptive immune response (HERC2 and CYFIP1), digestion and metabolism (CENPJ), growth (SPP1), body size and developments (GJB2 and GJA3). This study highlighted new insights into the ROH patterns and provides a basis for future breeding and conservation strategies of Chinese sheep breeds.