bluuebunny/crossref_metadata_2025 huggingface dataset:
Short-Term Associations of Nitrogen Dioxide (NO2) on Mortality in 18 French Cities, 2010–2014
Authors: Corso Magali , Blanchard Myriam , Medina Sylvia , Wagner Vérène
Published: November 2020

We present an analysis of short-term associations between ambient NO2 and mortality according to cause, age-group, and period (cold and warm) in 18 areas in metropolitan France for the 2010–2014 period. Associations were estimated in each area using a generalized additive Poisson regression model, and effects were summarized in a meta-analysis. The percentage increase in mortality rate was estimated for a 10 µg m−3 increase in the NO2 level in each area for each complete calendar year and for cold (November to April) and warm periods (May to October) in each year. We found that the NO2 increase (lag of 0–1 days) was associated with a 0.75% increase of non-accidental mortality for all age-groups (95% confidence interval (CI): (0.4; 1.10)). During the warm period, this NO2 increase was associated with a 3.07% increase in non-accidental mortality in the ≥75 years old group (95% CI: 1.97; 4.18). This study supports the short-term effects of NO2 as a proxy of urban traffic pollution on mortality, even for concentrations below the maximum guideline of 40 µg m−3 set down by the European Air Quality Standards and the World Health Organization (WHO).
Stage I Squamous Cell Carcinoma of the Anus: Is Radiation Therapy Alone Sufficient Treatment?
Authors: Miller Eric , Nalin Ansel , Diaz Pardo Dayssy , Arnett Andrea , Abushahin Laith , Husain Syed , Jin Ning , Williams Terence , Bazan Jose
Published: November 2020

The optimal treatment for stage I squamous cell carcinoma of the anus (SCCA) remains undefined. Recently, wide local excision alone was found to have comparable survival to those treated with chemoradiation (CRT). Given that local excision may be sufficient for the treatment of stage I SCCA, we hypothesized that radiation therapy (RT) alone, compared to CRT would result in equivalent overall survival (OS) in this population. We identified non-surgically treated patients with stage I SCCA from the National Cancer Database from 2004–2015. We included only patients treated either with CRT (45–59.4 Gy with chemotherapy initiated within 14 days of RT) or RT alone (45–59.4 Gy with no chemotherapy). The primary endpoint was OS between CRT and RT patients. Propensity-score matched (PSM) analysis was performed to determine the effect of concurrent chemotherapy on OS using a Cox proportional hazards model with robust standard error to account for clustering in matched pairs. We identified 3552 stage I patients treated with CRT and 287 treated with RT. Compared to patients treated with CRT, those that received RT were more likely to be ≥70 years old (33.1% vs. 19.7%, p < 0.001) and less likely to be female (63.1% vs. 71.0%, p < 0.001). The proportion of patients with a Charlson-Deyo score of 0 was similar in both groups (80.8% RT vs. 82.7% CRT, p = 0.164). The PSM cohort consisted of 287 pairs of patients with median follow-up 48.3 months (interquartile range, 24.4–85.1 months) and 151 deaths (86 RT, 65 CRT). CRT was associated with a 31% reduction in the risk of death (HR = 0.69, 95% CI 0.50–0.95, p = 0.023). We found that CRT was associated with improved OS, compared to RT alone, in patients with non-surgically treated stage I SCCA. These data suggest that de-intensification of therapy in stage I SCCA must be used with caution. However, given the retrospective nature of the data, prospective trials are required.
Strategies for Isolation and Phenotypic, Genetic, and Functional Characterization of Circulating Tumor Cells
Authors: Serrano Maria José , Lorente Jose A
Published: November 2020

From the medical and scientific point of view, we are witnessing important changes in the way we approach diseases, and consequently in the way we manage patients [...]
Comparison of Dose Distribution in Regional Lymph Nodes in Whole-Breast Radiotherapy vs. Whole-Breast Plus Regional Lymph Node Irradiation: An In Silico Planning Study in Participating Institutions of the Phase III Randomized Trial (KROG 1701)
Authors: Kim Haeyoung , Kim Heejung , Park Won , Baek Jong Yun , Ahn Sung Ja , Kim Mi Young , Park Shin-Hyung , Lee Ik Jae , Ha Inbong , Kim Jin Hee , Kim Tae Hyun , Lee Kyu Chan , Lee Hyung-Sik , Kim Tae Gyu , Kim Jin Ho , Lee Jong Hoon , Jung Jinhong , Cho Oyeon , Chang Jee Suk , Kim Eun Seog , Jo In Young , Koo Taeryool , Kim Kyubo , Park Hae Jin , Shin Young-Joo , Ha Boram , Kwon Jeanny , Lee Ju Hye , Moon Sunrock
Published: November 2020

The purpose of the current in silico planning study is to compare radiation doses of whole-breast irradiation (WBI) and whole-breast plus regional lymph node irradiation (WBI+RNI) administered to the regional lymph nodes (RLN) in pN1 breast cancer. Twenty-four participating institutions were asked to create plans of WBI and WBI+RNI for two dummy cases. To compare target coverage between the participants, an isodose line equal to 90% of the prescribed dose was converted to an isodose contour (contour90% iso). The relative nodal dose (RND) was obtained using the ratio of RLN dose to the target dose. The Fleiss’s kappa values which represent inter-observer agreement of contour90% iso were over 0.68. For RNI, 6 institutions included axillary lymph node (ALN), supraclavicular lymph node (SCN), and internal mammary lymph node (IMN), while 18 hospitals included only ALN and SCN. The median RND between the WBI and WBI+RNI were as follows: 0.64 vs. 1.05 (ALN level I), 0.27 vs. 1.08 (ALN level II), 0.02 vs. 1.12 (ALN level III), 0.01 vs. 1.12 (SCN), and 0.54 vs. 0.82 (IMN). In all nodal regions, the RND was significantly lower in WBI than in WBI+RNI (p < 0.01). In this study, we could identify the nodal dose difference between WBI and WBI+RNI.
Prognostic Role of the Red Blood Cell Distribution Width (RDW) in Hodgkin Lymphoma
Authors: Herraez Ines , Bento Leyre , Del Campo Raquel , Sas Adriana , Ramos Rafael , Ibarra Javier , Mestre Francesc , Alemany Regina , Bargay Joan , Sampol Antonia , Gutierrez Antonio
Published: November 2020

The red blood cell distribution width (RDW) is a parameter available from an automated blood count, which measures the degree of heterogeneity of erythrocyte volume and increases in inflammatory conditions. The prognostic role of RDW has been described in different types of cancers. Hodgkin lymphoma (HL) is a hematological malignancy, known to have a proinflammatory background. We aim to study the prognostic role of RDW in HL. We retrospectively analyzed 264 patients with HL from two hospitals in the Balearic Islands between 1990 and 2018. Higher levels of RDW were independently related to anemia, B-symptoms, and low albumin. In age ≥45 years, the presence of lymphopenia and higher RDW were independently associated with worse event-free survival (EFS) and overall survival (OS). Long-term incidence of secondary malignancies was significantly higher in patients with higher RDW, particularly lung cancer. In conclusion, we report for the first time that RDW is a simple, cheap, and easily available prognostic factor in HL that identifies a group with worse EFS, OS, and a higher potential incidence of secondary malignancies. RDW seems to be related to most adverse prognostic factors in HL, making RDW an excellent candidate to be included in prognostic scores for HL.
Mifepristone Treatment Promotes Testicular Leydig Cell Tumor Progression in Transgenic Mice
Authors: Ponikwicka-Tyszko Donata , Chrusciel Marcin , Pulawska Kamila , Bernaczyk Piotr , Sztachelska Maria , Guo Peilan , Li Xiangdong , Toppari Jorma , Huhtaniemi Ilpo T. , Wołczyński Slawomir , Rahman Nafis A.
Published: November 2020

The selective progesterone receptor modulator mifepristone (MF) may act as a potent antiproliferative agent in different steroid-dependent cancers due to its strong antagonistic effect on the nuclear progesterone receptor (PGR). Hereby, we analyzed the effects of MF treatment on Leydig cell tumor (LCT) progression in a transgenic mouse model (inhibin-α promoter-driven SV40 T-antigen), as well as on LCT (BLTK-1 and mLTC-1) cell proliferation. MF significantly stimulated the proliferation of LCT in vitro. Similarly, a 1-mo MF or P4 treatment stimulated LCT tumor growth in vivo. Traceable/absent classical Pgr or nonclassical membrane PRs α, β, γ and Pgrmc2, but abundant membrane Pgrmc1 expression, was found in LCTs. MF did not activate glucocorticoid or androgen receptors in LCTs. Functional analysis showed that PGRMC1 is required for MF and P4 to stimulate the proliferation and invasiveness of LCTs. Accordingly, MF and P4 induced PGRMC1 translocation into the nucleus and thereby stimulated the release of TGFβ1 in LCT cells. MF and P4 treatments upregulated Tgfbr1, Tgfbr2, and Alk1 expression and stimulated TGFβ1 release in LCT cells. Our findings provide novel mechanistic insights into the action of MF as a membrane PR agonist that promotes LCT growth through PGRMC1 and the alternative TGFβ1 signaling pathway.
Non-Coding RNAs: Uncharted Mediators of Thyroid Cancer Pathogenesis
Authors: Tabatabaeian Hossein , Peiling Yang Samantha , Tay Yvonne
Published: November 2020

Thyroid cancer is the most prevalent malignancy of the endocrine system and the ninth most common cancer globally. Despite the advances in the management of thyroid cancer, there are critical issues with the diagnosis and treatment of thyroid cancer that result in the poor overall survival of undifferentiated and metastatic thyroid cancer patients. Recent studies have revealed the role of different non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) that are dysregulated during thyroid cancer development or the acquisition of resistance to therapeutics, and may play key roles in treatment failure and poor prognosis of the thyroid cancer patients. Here, we systematically review the emerging roles and molecular mechanisms of ncRNAs that regulate thyroid tumorigenesis and drug response. We then propose the potential clinical implications of ncRNAs as novel diagnostic and prognostic biomarkers for thyroid cancer.
Patient-Reported Outcomes of Palbociclib Plus Exemestane with GnRH Agonist versus Capecitabine in Premenopausal Women with Hormone Receptor-Positive Metastatic Breast Cancer: A Prospective, Open-Label, Randomized Phase ll Trial (KCSG-BR 15-10)
Authors: Lee Soohyeon , Im Seock-Ah , Kim Gun Min , Jung Kyung Hae , Kang Seok Yun , Park In Hae , Kim Jee Hyun , Lee Kyoung Eun , Ahn Hee Kyung , Lee Moon Hee , Kim Hee-Jun , Kim Han Jo , Lee Jong In , Koh Su-Jin , Park Yeon Hee
Published: November 2020

In the era of CDK4/6 inhibitors in hormone receptor (HR)-positive, HER2-negative metastatic breast cancer, few trials have been specifically studied to compare quality of life between palbociclib plus endocrine therapy (ET) and cytotoxic chemotherapy exclusively in premenopausal women. We aimed to evaluate differences of patient report outcomes (PROs) between palbociclib plus ET and capecitabine. PROs were assessed using EORTC QLQ-C30 at baseline, every 6 weeks, and the end of treatment. All EORTC QLQ-30 scores were maintained from baseline to the end of treatment. Patients treated palbociclib plus ET arm experienced delay in time-to-deterioration of physical functioning (HR = 0.58, 95% CI, 0.36 to 0.84, p = 0.0058), nausea and vomiting (HR = 0.48; 95% CI, 0.32 to 0.73, p = 0.0005), and diarrhea (HR = 0.42; 95% CI, 0.27 to 0.65, p = 0.001). There was a numeric trend for worsening of insomnia (HR = 1.43; 95% CI, 0.96 to 2.16, p = 0.079) and favoring of appetite loss (HR = 0.69, 95% CI, 0.44 to 1.07, p = 0.09) in the palbociclib plus ET arm. Premenopausal patients with palbociclib plus ET maintained QoL without compromising treatment efficacy.
SARS-CoV-2 Infection in Cancer Patients: Effects on Disease Outcomes and Patient Prognosis
Authors: Seth Gaurav , Sethi Saira , Bhattarai Shristi , Saini Geetanjali , Singh Chandra , Aneja Ritu
Published: November 2020

The severity of coronavirus disease 2019 (COVID-19) symptoms and outcomes vary immensely among patients. Predicting disease progression and managing disease symptoms is even more challenging in cancer patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cancer therapies, including chemotherapy, radiotherapy, and immunotherapy, often suppress the immune system, rendering cancer patients more susceptible to SARS-CoV-2 infection and the development of severe complications. However, data on the effects of immunosuppression on COVID-19 outcomes in cancer patients remain limited. Further investigations are warranted to better understand the implications of SARS-CoV-2 infection in cancer patients, particularly those that are immunocompromised. In this review, we outline the current knowledge of the effects of SARS-CoV-2 infection in cancer patients.
Myeloma Cells Deplete Bone Marrow Glutamine and Inhibit Osteoblast Differentiation Limiting Asparagine Availability
Authors: Chiu Martina , Toscani Denise , Marchica Valentina , Taurino Giuseppe , Costa Federica , Bianchi Massimiliano G. , Andreoli Roberta , Franceschi Valentina , Storti Paola , Burroughs-Garcia Jessica , Eufemiese Rosa Alba , Dalla Palma Benedetta , Campanini Nicoletta , Martella Eugenia , Mancini Cristina , Shan Jixiu , Kilberg Michael S. , D’Amico Giovanna , Dander Erica , Agnelli Luca , Pruneri Giancarlo , Donofrio Gaetano , Bussolati Ovidio , Giuliani Nicola
Published: November 2020

Multiple myeloma (MM) cells consume huge amounts of glutamine and, as a consequence, the amino acid concentration is lower-than-normal in the bone marrow (BM) of MM patients. Here we show that MM-dependent glutamine depletion induces glutamine synthetase in stromal cells, as demonstrated in BM biopsies of MM patients, and reproduced in vitro by co-culturing human mesenchymal stromal cells (MSCs) with MM cells. Moreover, glutamine depletion hinders osteoblast differentiation of MSCs, which is also severely blunted by the spent, low-glutamine medium of MM cells, and rescued by glutamine restitution. Glutaminase and the concentrative glutamine transporter SNAT2 are induced during osteoblastogenesis in vivo and in vitro, and both needed for MSCs differentiation, pointing to enhanced the requirement for the amino acid. Osteoblastogenesis also triggers the induction of glutamine-dependent asparagine synthetase (ASNS), and, among non-essential amino acids, asparagine rescues differentiation of glutamine-starved MSCs, by restoring the transcriptional profiles of differentiating MSCs altered by glutamine starvation. Thus, reduced asparagine availability provides a mechanistic link between MM-dependent Gln depletion in BM and impairment of osteoblast differentiation. Inhibition of Gln metabolism in MM cells and supplementation of asparagine to stromal cells may, therefore, constitute novel approaches to prevent osteolytic lesions in MM.
Integration and Comparison of Transcriptomic and Proteomic Data for Meningioma
Authors: Dunn Jemma , Lenis Vasileios P. , Hilton David A. , Warta Rolf , Herold-Mende Christel , Hanemann C. Oliver , Futschik Matthias E.
Published: November 2020

Meningioma are the most frequent primary intracranial tumour. Management of aggressive meningioma is complex, and development of effective biomarkers or pharmacological interventions is hampered by an incomplete knowledge of molecular landscape. Here, we present an integrated analysis of two complementary omics studies to investigate alterations in the “transcriptome–proteome” profile of high-grade (III) compared to low-grade (I) meningiomas. We identified 3598 common transcripts/proteins and revealed concordant up- and downregulation in grade III vs. grade I meningiomas. Concordantly upregulated genes included FABP7, a fatty acid binding protein and the monoamine oxidase MAOB, the latter of which we validated at the protein level and established an association with Food and Drug Administration (FDA)-approved drugs. Notably, we derived a plasma signature of 21 discordantly expressed genes showing positive changes in protein but negative in transcript levels of high-grade meningiomas, including the validated genes CST3, LAMP2, PACS1 and HTRA1, suggesting the acquisition of these proteins by tumour from plasma. Aggressive meningiomas were enriched in processes such as oxidative phosphorylation and RNA metabolism, whilst concordantly downregulated genes were related to reduced cellular adhesion. Overall, our study provides the first transcriptome–proteome characterisation of meningioma, identifying several novel and previously described transcripts/proteins with potential grade III biomarker and therapeutic significance.
iNOS Expression by Tumor-Infiltrating Lymphocytes, PD-L1 and Prognosis in Non-Small-Cell Lung Cancer
Authors: Giatromanolaki Alexandra , Tsolou Avgi , Daridou Eleftheria , Kouroupi Maria , Chlichlia Katerina , Koukourakis Michael I.
Published: November 2020

Background: Inducible Nitric Oxygen Synthase (iNOS) promotes the generation of NO in tissues. Its role in tumor progression and immune response is unclear. Methods: The immunohistochemical expression patterns of iNOS were studied in a series of 98 tissue samples of non-small-cell lung carcinoma (NSCLC), in parallel with the expression of hypoxia and anaerobic metabolism markers, PD-L1 and tumor-infiltrating lymphocytes (TILs). Results: iNOS is expressed by cancer cells in 19/98 (19.4%), while extensive expression by cancer-associated fibroblasts occurs in 8/98 (8.2%) cases. None of these patterns relate to stage or prognosis. Extensive infiltration of the tumor stroma by iNOS-expressing TILs (iNOS+TILs) occurs in 47/98 (48%) cases. This is related to low Hypoxia-Inducible Factor 1α (HIF1α), high PD-L1 expression and a better overall survival (p = 0.002). Expression of PD-L1, however, mitigates the beneficial effect of the presence of iNOS+TIL. Conclusions: Extensive expression of iNOS by TILs occurs in approximately 50% of NSCLCs, and this is significantly related to an improved overall survival. This brings forward the role of iNOS in anti-neoplastic lymphocyte biology, supporting iNOS+TILs as a putative marker of immune response. The value of this biomarker as a predictive and treatment-guiding tool for tumor immunotherapy demands further investigation.
Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome in Spain: Clinical and Genetic Characterization
Authors: Sánchez-Heras A. Beatriz , Castillejo Adela , García-Díaz Juan D. , Robledo Mercedes , Teulé Alexandre , Sánchez Rosario , Zúñiga Ángel , Lastra Enrique , Durán Mercedes , Llort Gemma , Yagüe Carmen , Ramon y Cajal Teresa , López San Martin Consol , López-Fernández Adrià , Balmaña Judith , Robles Luis , Mesa-Latorre José M. , Chirivella Isabel , Fonfria María , Perea Ibañez Raquel , Castillejo M. Isabel , Escandell Inés , Gomez Luis , Berbel Pere , Soto Jose Luis
Published: November 2020

Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC) is a very rare hereditary disorder characterized by cutaneous leiomyomas (CLMs), uterine leiomyomas (ULMs), renal cysts (RCys) and renal cell cancers (RCCs). We aimed to describe the genetics, clinical features and potential genotype-phenotype associations in the largest cohort of fumarate hydratase enzyme mutation carriers known from Spain using a multicentre, retrospective study of individuals with a genetic or clinical diagnosis of HLRCC. We collected clinical information from medical records, analysed genetic variants and looked for genotype-phenotype associations. Analyses were performed using R 3.6.0. software. We included 197 individuals: 74 index cases and 123 relatives. CLMs were diagnosed in 65% of patients, ULMs in 90% of women, RCys in 37% and RCC in 10.9%. Twenty-seven different pathogenic variants were detected, 12 (44%) of them not reported previously. Patients with missense pathogenic variants showed higher frequencies of CLMs, ULMs and RCys, than those with loss-of-function variants (p = 0.0380, p = 0.0015 and p = 0.024, respectively). This is the first report of patients with HLRCC from Spain. The frequency of RCCs was lower than those reported in the previously published series. Individuals with missense pathogenic variants had higher frequencies of CLMs, ULMs and RCys.
Signal Transduction Pathways Activated by Innate Immunity in Mast Cells: Translating Sensing of Changes into Specific Responses
Authors: Espinosa-Riquer Zyanya P. , Segura-Villalobos Deisy , Ramírez-Moreno Itzel G. , Pérez Rodríguez Marian Jesabel , Lamas Mónica , Gonzalez-Espinosa Claudia
Published: November 2020

Mast cells (MCs) constitute an essential cell lineage that participates in innate and adaptive immune responses and whose phenotype and function are influenced by tissue-specific conditions. Their mechanisms of activation in type I hypersensitivity reactions have been the subject of multiple studies, but the signaling pathways behind their activation by innate immunity stimuli are not so well described. Here, we review the recent evidence regarding the main molecular elements and signaling pathways connecting the innate immune receptors and hypoxic microenvironment to cytokine synthesis and the secretion of soluble or exosome-contained mediators in this cell type. When known, the positive and negative control mechanisms of those pathways are presented, together with their possible implications for the understanding of mast cell-driven chronic inflammation. Finally, we discuss the relevance of the knowledge about signaling in this cell type in the recognition of MCs as central elements on innate immunity, whose remarkable plasticity converts them in sensors of micro-environmental discontinuities and controllers of tissue homeostasis.
Cardiac and Vascular α1-Adrenoceptors in Congestive Heart Failure: A Systematic Review
Authors: Kaykı-Mutlu Gizem , Papazisi Olga , Palmen Meindert , Danser A. H. Jan , Michel Martin C. , Arioglu-Inan Ebru
Published: November 2020

As heart failure (HF) is a devastating health problem worldwide, a better understanding and the development of more effective therapeutic approaches are required. HF is characterized by sympathetic system activation which stimulates α- and β-adrenoceptors (ARs). The exposure of the cardiovascular system to the increased locally released and circulating levels of catecholamines leads to a well-described downregulation and desensitization of β-ARs. However, information on the role of α-AR is limited. We have performed a systematic literature review examining the role of both cardiac and vascular α1-ARs in HF using 5 databases for our search. All three α1-AR subtypes (α1A, α1B and α1D) are expressed in human and animal hearts and blood vessels in a tissue-dependent manner. We summarize the changes observed in HF regarding the density, signaling and responses of α1-ARs. Conflicting findings arise from different studies concerning the influence that HF has on α1-AR expression and function; in contrast to β-ARs there is no consistent evidence for down-regulation or desensitization of cardiac or vascular α1-ARs. Whether α1-ARs are a therapeutic target in HF remains a matter of debate.
Hyaluronic Acid Injection Laryngoplasty for Unilateral Vocal Fold Paralysis—A Systematic Review and Meta-Analysis
Authors: Wang Chen-Chi , Wu Shang-Heng , Tu Yu-Kang , Lin Wen-Jiun , Liu Shih-An
Published: November 2020

Unilateral vocal fold paralysis (UVFP) is a common disorder that may cause glottal closure insufficiency and then hoarseness of voice and aspiration during swallowing. We conducted a systematic review and meta-analysis to evaluate whether hyaluronic acid (HA) injection laryngoplasty (IL) is an effective treatment for patients with UVFP. Comprehensive systematic searches were undertaken using PubMed, EBSCO Medline, and Cochrane Library databases. We appraised the quality of studies according to preset inclusion and exclusion criteria. The lengths of follow-up were divided into “short-term” (3 months or shorter), “medium-term” (6 months), and “long-term” (12 months or longer). We performed random-effect meta-analysis to estimate the changes in voice-related quality of life, perceptual evaluation by grading systems, voice lab analysis of maximal phonation time, and normalized glottal gap area, before and after HA IL. Fourteen studies were eligible for the final analysis. The results showed that patients’ glottal closure insufficiency could be improved; maximal phonation time could be prolonged; perceptual evaluations of the voice and quality of life were better after HA IL, but the duration of treatment effect varied among different studies. In conclusion, HA IL is an effective treatment for UVFP, which may achieve a long-term effect and therefore reduce the likelihood of requiring permanent medialization thyroplasty.
Human Adipose Tissue-Derived Stromal Cells Suppress Human, but Not Murine Lymphocyte Proliferation, via Indoleamine 2,3-Dioxygenase Activity
Authors: Torres Crigna Adriana , Uhlig Stefanie , Elvers-Hornung Susanne , Klüter Harald , Bieback Karen
Published: November 2020

Over recent years, mesenchymal stromal cells (MSC) have gained immense attraction in immunotherapy, regenerative medicine and tissue engineering. MSC microenvironment modulation occurs through synergy of direct cell–cell contact, and secreted soluble factors and extracellular vesicles (EV). MSC-derived EV have been suggested as cell-free immunomodulatory alternative to MSC; however, previous findings have challenged this. Furthermore, recent data suggest that evaluating the mechanism of action of human MSC (hMSC) in animal models might promote adverse immune reactions or lack of functionality due to xeno-incompatibilities. In this study, we first assessed the immunomodulatory strength of different human MSC sources on in vitro stimulated T cells and compared this to interferon-gamma (IFNγ) primed MSC conditioned medium (CM) and EV. Second, we addressed the main molecular mechanisms, and third, we assessed the MSC in vitro immunosuppressive effect across interspecies barriers. We identified human adipose tissue-derived stromal cells (ASC) with strongest immunomodulatory strength, followed by bone marrow (BM) and cord blood-derived MSC (CB). Whilst CM from primed ASC managed to exert analogous effects as their cellular counterpart, EV derived thereof did not, reproducing previous findings. IFNγ-induced indoleamine 2,3-dioxygenase (IDO) activity was identified as key mechanism to suppress human lymphocyte proliferation, as in the presence of the IDO inhibitor epacadostat (Epac) a stimulation of proliferation was seen. In addition, we revealed MSC immunosuppressive effects to be species-specific, because human cells failed to suppress murine lymphocyte proliferation. In summary, ASC were the strongest immunomodulators with the IDO-kynurenine pathway being key within the human system. Importantly, the in vitro lack of interspecies immunomodulatory strength suggests that preclinical data need to be carefully interpreted especially when considering a possible translation to clinical field.
Multiple Equilibria and Buckling of Functionally Graded Graphene Nanoplatelet-Reinforced Composite Arches with Pinned-Fixed End
Authors: Yang Zhicheng , Xu Jiamian , Lu Hanwen , Lv Jiangen , Liu Airong , Fu Jiyang
Published: November 2020

This paper presents an analytical study on the multiple equilibria and buckling of pinned-fixed functionally graded graphene nanoplatelet-reinforced composite (FG-GPLRC) arches under central point load. It is assumed that graphene nanoplatelets (GPLs) in each GPLRC layer are uniformly distributed and randomly oriented with its concentration varying layer-wise along the thickness direction. The Halpin–Tsai micromechanics-based model is used to estimate the effective elastic modulus of GPLRC. The non-linear equilibrium path and buckling load of the pinned-fixed FG-GPLRC arch are subsequently derived by employing the principle of virtual work. The effects of GPLs distribution, weight fraction, size and geometry on the buckling load are examined comprehensively. It is found that the buckling performances of FG-GPLRC arches can be significantly improved by using GPLs as reinforcing nanofillers. It is also found that the non-linear equilibrium path of the pinned-fixed FG-GPLRC arch have multiple limit points and non-linear equilibrium branches when the arch is with a special geometric parameter.
Gallate-Based Metal–Organic Frameworks, a New Family of Hybrid Materials and Their Applications: A Review
Authors: Ismail Marhaina , Bustam Mohamad Azmi , Yeong Yin Fong
Published: November 2020

Within three decades of fundamental findings in research on metal–organic frameworks (MOFs), a new family of hybrid materials known as gallate-based MOFs, consisting of metal salt and gallic acid, have been of great interest. Due to the fact that gallic acid is acknowledged to display a range of bioactivities, gallate-based MOFs have been initially expended in biomedical applications. Recently, gallate-based MOFs have been gradually acting as new alternative materials in chemical industrial applications, in which they were first reported for the adsorptive separation of light hydrocarbon separations. However, to date, none of them have been related to CO2/CH4 separation. These porous materials have a bright future and can be kept in development for variety of applications in order to be applied in real industrial practices. Therefore, this circumstance creates a new opportunity to concentrate more on studies in CO2/CH4 applications by using porous material gallate-based MOFs. This review includes the description of recent gallate-based MOFs that presented remarkable properties in biomedical areas and gas adsorption and separation, as well as their future potential application.
A Gliriform Tooth from the Eocene of the Erlian Basin (Nei Mongol, China) and the Premolar Morphology of Anagalidan Mammals at a Crossroads
Authors: Fostowicz-Frelik Łucja , Li Qian , Saha Anwesha
Published: November 2020

The middle Eocene in Nei Mongol (China) was an interval of profound faunal changes as regards the basal Glires and gliriform mammals in general. A major diversification of rodent lineages (ctenodactyloids) and more modern small-sized lagomorphs was accompanied by a decline of mimotonids (Gomphos and Mimolagus) and anagalids. The latter was an enigmatic group of basal Euarchontoglires endemic to China and Mongolia. Here, we describe the first anagalid tooth (a P4) from the Huheboerhe classic site in the Erlian Basin. The tooth, characterized by its unique morphology intermediate between mimotonids and anagalids is semihypsodont, has a single buccal root typical of mimotonids, a large paracone located anteriorly, and a nascent hypocone, characteristic of advanced anagalids. The new finding of neither an abundant nor speciose group suggests a greater diversity of anagalids in the Eocene of China. This discovery is important because it demonstrates the convergent adaptations in anagalids, possibly of ecological significance.
Analysis of Blind Reconstruction of BCH Codes
Authors: Kwon Soonhee , Shin Dong-Joon
Published: November 2020

In this paper, the theoretical lower-bound on the success probability of blind reconstruction of Bose–Chaudhuri–Hocquenghem (BCH) codes is derived. In particular, the blind reconstruction method of BCH codes based on the consecutive roots of generator polynomials is mainly analyzed because this method shows the best blind reconstruction performance. In order to derive a performance lower-bound, the theoretical analysis of BCH codes on the aspects of blind reconstruction is performed. Furthermore, the analysis results can be applied not only to the binary BCH codes but also to the non-binary BCH codes including Reed–Solomon (RS) codes. By comparing the derived lower-bound with the simulation results, it is confirmed that the success probability of the blind reconstruction of BCH codes based on the consecutive roots of generator polynomials is well bounded by the proposed lower-bound.
Multidimensional Analysis of Meat and Bone Meal (MBM) Incineration Process
Authors: Bujak Janusz , Sitarz Piotr , Nakielska Magdalena
Published: November 2020

This paper presents test results of thermal treatment (combustion) of meat and bone meal (MBM) within the context of an animal waste utilization plant. The test facility was equipped with a rotating combustion chamber. The energy and ecological aspects of the operation of this facility were analyzed. This article assesses the impact of the tested system on the natural environment with regard to the emission of pollutants into the atmosphere. In accordance with the chemical composition of the incinerated waste, the following compounds were analyzed: CO, NOx (nitrogen oxides), SO2, HCl, HF, TOC (total organic carbon) and dust. The concentrations recorded in periods of 0.5 and 24 h were in compliance with the admissible levels defined by European Union directives. An analysis of the energy efficiency of the energy recovery system used, which produces saturated steam for the technological needs of the utilization plant, was also carried out. The conditions for the achieved ecological and energy parameters were analyzed and presented synthetically using the multicriteria assessment method, with a simultaneous Pareto principle determination of the process optimum. The results of the research and the analyses of ecological and performance parameters presented in the paper may prove helpful in the design and operation of systems for thermal treatment of waste equipped with a rotating combustion chamber and other types of furnaces.
Simplified Assessment on the Wind Farm Noise Impact of the E2O Experimental Offshore Station in the Asturian Coast
Authors: Argüelles Díaz Katia María , Velarde-Suárez Sandra , Fernández Oro Jesús Manuel , González Pérez José
Published: November 2020

This paper presents a preliminary evaluation of the acoustic impact of an offshore experimental wind farm (E2O), conceived and planned to be installed in Asturias on Spain’s northwest coast. A simplified assessment of the wind turbines’ noise impact at an offshore platform was performed numerically, adapting commercial software for room acoustics to this particular application. As a result, the sound levels at specific receiver sites on the coastline were estimated to select the most convenient level between the two possible locations. Parameters from acoustic emission data of the selected wind turbines were introduced as inputs to the simulation, and the noise propagation in the analyzed domains (for different values of their basic parameters) was simulated. Complementarily, the numerical results were compared to calculations following the ISO 9613-2 standard on sound propagation outdoors for validation purposes, showing good overall agreement. The results revealed that both projected areas under consideration follow the current normative concerning the prescribed acoustic limits, according to the predicted low sound pressure values at the specific considered receiver sites.
Trends in Power Quality, Harmonic Mitigation and Standards for Light and Heavy Industries: A Review
Authors: Lumbreras David , Gálvez Eduardo , Collado Alfonso , Zaragoza Jordi
Published: November 2020

The power quality of electrical grids is becoming an important issue worldwide. The electrical grid has to deliver sinusoidal voltages and currents without frequency or amplitude variations. However, the connection of non-linear loads generates harmonics that degrade the grid quality. The presence of harmonics in the load currents has many negative consequences and can distort the voltage waveform at the point of common coupling (PCC). Thus, it is essential to mitigate the harmonics in order to maintain a suitable grid quality. This is a shared responsibility between energy suppliers, manufacturers of electric and electronic equipment, and users. In this context, this work presents, for each stakeholder, a comprehensive analysis of their responsibilities and the standards that they should meet. Additionally, this paper reviews the most common types of filters used to comply with the applicable standards in industrial applications. Finally, in order to prove that active power filters allow maintaining good power quality in all types of grid, commercially available active power filters were installed in three different grids contexts: an office building, a factory, and a stadium with a large number of LEDs. The experimental results obtained were used to evaluate the impact of active filters on grid quality. This review would help users to overcome their grid distortion problems.
Experimental and Numerical Analysis of the Gas Flow in the Axisymmetric Radial Clearance
Authors: Joachimiak Damian , Frąckowiak Andrzej
Published: November 2020

This paper focuses on the analysis of the gas flow in the axisymmetric mini gap bounded by the surface of the top of the labyrinth seal tooth and the surface of the body. It includes the results of experimental research and numerical calculations. Experimental research focused on the analysis of gas flow for six clearance heights in a wide range of pressure drops. Based on this research, we determined the mass flow in the clearance. Using the Saint-Venant equation, we determined the flow coefficient versus the pressure ratio upstream and downstream from the seal. Flow coefficients for various clearance heights obtained from the experiment can be divided into two data groups, the values of which differ significantly. To explain changes in the value of the gas flow coefficient for selected clearance heights, numerical analysis of the said gas flow was performed using the Fluent software. This analysis allowed us to explain the reason for the variability of the flow coefficient. This research can be the basis for determining the change of seal integrity during operation for staggered and stepped seals.
Smart Energy in a Smart City: Utopia or Reality? Evidence from Poland
Authors: Lewandowska Aleksandra , Chodkowska-Miszczuk Justyna , Rogatka Krzysztof , Starczewski Tomasz
Published: November 2020

The main principles of the smart city concept rely on modern, environmentally friendly technologies. One manifestation of the smart city concept is investments in renewable energy sources (RES), which are currently a popular direction in urban transformation. It makes sense, therefore, to analyse how Polish cities are coping with this challenge and whether they are including the implementation of RES facilities in their development strategies. The aim of the article is to analyze and assess the level at which renewable energy facilities are being implemented or developed in the urban space of cities in Poland as a pillar of the implementation of the smart city concept. This goal is realized on two levels: the theoretical (analysis of strategic documents) and the practical (analysis of the capacity of RES installations, questionnaire studies). The study shows that renewable energy installations are an important part of the development strategies of Polish cities, and especially of those that aspire to be termed “smart cities”. Moreover, it is shown that the predominant RES facilities are those based on solar energy.
Nitrate Respiration in Thermus thermophilus NAR1: from Horizontal Gene Transfer to Internal Evolution
Authors: Sánchez-Costa Mercedes , Blesa Alba , Berenguer José
Published: November 2020

Genes coding for enzymes of the denitrification pathway appear randomly distributed among isolates of the ancestral genus Thermus, but only in few strains of the species Thermus thermophilus has the pathway been studied to a certain detail. Here, we review the enzymes involved in this pathway present in T. thermophilus NAR1, a strain extensively employed as a model for nitrate respiration, in the light of its full sequence recently assembled through a combination of PacBio and Illumina technologies in order to counteract the systematic errors introduced by the former technique. The genome of this strain is divided in four replicons, a chromosome of 2,021,843 bp, two megaplasmids of 370,865 and 77,135 bp and a small plasmid of 9799 pb. Nitrate respiration is encoded in the largest megaplasmid, pTTHNP4, within a region that includes operons for O2 and nitrate sensory systems, a nitrate reductase, nitrate and nitrite transporters and a nitrate specific NADH dehydrogenase, in addition to multiple insertion sequences (IS), suggesting its mobility-prone nature. Despite nitrite is the final product of nitrate respiration in this strain, the megaplasmid encodes two putative nitrite reductases of the cd1 and Cu-containing types, apparently inactivated by IS. No nitric oxide reductase genes have been found within this region, although the NorR sensory gene, needed for its expression, is found near the inactive nitrite respiration system. These data clearly support that partial denitrification in this strain is the consequence of recent deletions and IS insertions in genes involved in nitrite respiration. Based on these data, the capability of this strain to transfer or acquire denitrification clusters by horizontal gene transfer is discussed.
Application of CRISPR/Cas9 Nuclease in Amphioxus Genome Editing
Authors: Su Liuru , Shi Chenggang , Huang Xin , Wang Yiquan , Li Guang
Published: November 2020

The cephalochordate amphioxus is a promising animal model for studying the origin of vertebrates due to its key phylogenetic position among chordates. Although transcription activator-like effector nucleases (TALENs) have been adopted in amphioxus genome editing, its labor-intensive construction of TALEN proteins limits its usage in many laboratories. Here we reported an application of the CRISPR/Cas9 system, a more amenable genome editing method, in this group of animals. Our data showed that while co-injection of Cas9 mRNAs and sgRNAs into amphioxus unfertilized eggs caused no detectable mutations at targeted loci, injections of Cas9 mRNAs and sgRNAs at the two-cell stage, or of Cas9 protein and sgRNAs before fertilization, can execute efficient disruptions of targeted genes. Among the nine tested sgRNAs (targeting five genes) co-injected with Cas9 protein, seven introduced mutations with efficiency ranging from 18.4% to 90% and four caused specific phenotypes in the injected embryos. We also demonstrated that monomerization of sgRNAs via thermal treatment or modifying the sgRNA structure could increase mutation efficacies. Our study will not only promote application of genome editing method in amphioxus research, but also provide valuable experiences for other organisms in which the CRISPR/Cas9 system has not been successfully applied.
Identification of Genetic Susceptibility Factors Associated with Canine Gastric Dilatation-Volvulus
Authors: Piras Ignazio S. , Perdigones Nieves , Zismann Victoria , Briones Natalia , Facista Salvatore , Rivera José Luis , Rozanski Elizabeth , London Cheryl A. , Hendricks William P. D.
Published: November 2020

Canine gastric dilatation-volvulus (GDV) is a common life-threatening condition occurring primarily in large and giant breeds with a 3.9% to 36.7% lifetime risk. The genetic correlates of GDV have not previously been systematically explored. We undertook an inter-breed genome-wide association analysis (GWAS) of 253 dogs from ten breeds including 106 healthy dogs and 147 dogs with at least one GDV episode. SNP array genotyping followed by imputation was conducted on 241 samples to identify GDV-associated single-nucleotide polymorphisms (SNPs) and copy number variations (CNVs). A subset of 33 dogs (15 healthy dogs and 18 GDV patients from the three most represented breeds) was characterized by whole genome sequencing (WGS). After genome-wide Bonferroni correction, we identified a significant putatively protective intergenic SNP (rs851737064) across all breeds. The signal was most significant in Collies, German Shorthaired Pointers, and Great Danes. Subsequent focused analysis across these three breeds identified 12 significant additional putatively protective or deleterious SNPs. Notable significant SNPs included those occurring in genes involved in gastric tone and motility including VHL, NALCN, and PRKCZ. These data provide important new clues to canine GDV risk factors and facilitate generation of hypotheses regarding the genetic and molecular underpinnings this syndrome.
Ischemia–Reperfusion Intervention: From Enhancements in Exercise Performance to Accelerated Performance Recovery—A Systematic Review and Meta-Analysis
Authors: Arriel Rhaí André , Rodrigues Jéssica Ferreira , Souza Hiago Leandro Rodrigues de , Meireles Anderson , Leitão Luís Filipe Moutinho , Crisafulli Antonio , Marocolo Moacir
Published: November 2020

It has been demonstrated that brief cycles of ischemia followed by reperfusion (IR) applied before exercise can improve performance and, IR intervention, applied immediately after exercise (post-exercise ischemic conditioning—PEIC) exerts a potential ergogenic effect to accelerate recovery. Thus, the purpose of this systematic review with meta-analysis was to identify the effects of PEIC on exercise performance, recovery and the responses of associated physiological parameters, such as creatine kinase, perceived recovery and muscle soreness, over 24 h after its application. From 3281 studies, six involving 106 subjects fulfilled the inclusion criteria. Compared to sham (cuff administration with low pressure) and control interventions (no cuff administration), PEIC led to faster performance recovery (p = 0.004; ES = −0.49) and lower increase in creatine kinase (p < 0.001; effect size (ES) = −0.74) and muscle soreness (p < 0.001; ES = −0.88) over 24 h. The effectiveness of this intervention is more pronounced in subjects with low/moderate fitness level and at least a total time of 10 min of ischemia (e.g., two cycles of 5 min) is necessary to promote positive effects.
Alcohol Control Policy in Europe: Overview and Exemplary Countries
Authors: Berdzuli Nino , Ferreira-Borges Carina , Gual Antoni , Rehm Jürgen
Published: November 2020

Alcohol is a major risk factor for burden of disease. However, there are known effective and cost-effective alcohol control policies that could reduce this burden. Based on reviews, international documents, and contributions to this special issue of International Journal of Environmental Research and Public Health (IJERPH), this article gives an overview of the implementation of such policies in the World Health Organization (WHO) European Region, and of best practices. Overall, there is a great deal of variability in the policies implemented between countries, but two countries, the Russian Federation and Lithuania, have both recently implemented significant increases in alcohol taxation, imposed restrictions on alcohol availability, and imposed bans on the marketing and advertising of alcohol within short time spans. Both countries subsequently saw significant decreases in consumption and all-cause mortality. Adopting the alcohol control policies of these best-practice countries should be considered by other countries. Current challenges for all countries include cross-border shopping, the impact from recent internet-based marketing practices, and international treaties.