bluuebunny/crossref_metadata_2025 huggingface dataset:
Ambient Air Quality in the Czech Republic
Authors: Hůnová Iva
Published: June 2021

Ambient air quality in the present-day Czech Republic (CR), one of the two succession countries of Czechoslovakia post-1993, was perceived as a major problem with severe human health and environmental consequences, particularly between the 1970s and 1990s [...]
Bird Taxonomic and Functional Diversity in Three Habitats in Buenos Aires City, Argentina
Authors: Curzel Florencia E. , Leveau Lucas M.
Published: June 2021

Urban green spaces (UGS), such as parks and wooded streets, are open areas with vegetation that provide sustainability to urban areas. However, their role in conserving bird diversity in neotropical cities has scarcely been analyzed. The aim of this study was to analyze the variation of bird assemblages in non-wooded streets, wooded streets, and parks in Buenos Aires City, Argentina. We compared the taxonomic and functional diversity between these habitat types. We selected five non-wooded streets, five wooded streets, and five parks in the city. Bird surveys were performed in 100 m long and 50 m wide transects. We found that taxonomic diversity had the greatest value in the parks, followed by wooded streets, and then the non-wooded streets. Functional diversity was similar between habitats. The taxonomic and functional composition changed between habitats. Non-wooded streets were dominated by the Rock Dove (Columba livia) and the Eared Dove (Zenaida auriculata), whereas parks had the highest abundance of the Picazuro Pigeon (Patagioenas picazuro) and the Rufous-bellied Thrush (Turdus rufiventris). Non-wooded streets were dominated by omnivorous and granivorous species, whereas parks had a higher abundance of herbivorous and frugivorous species. The positive association between UGS and bird diversity highlights the role of UGS as biodiversity conservation sites in neotropical cities.
Carbamazepine Reduces Sharp Wave-Ripple Complexes and Exerts Synapse-Specific Inhibition of Neurotransmission in Ex Vivo Hippocampal Slices
Authors: Simeone Timothy A. , Heruye Segewkal H. , Kostansek Joseph A. , Yeh Mary Y. , Matthews Stephanie A. , Samson Kaeli K. , Simeone Kristina A.
Published: June 2021

Higher therapeutic concentrations of the antiseizure medication carbamazepine (CBZ) are associated with cognitive side effects. Hippocampal sharp wave-ripple complexes (SPW-Rs) are proposed to participate in memory consolidation during periods of quiet and slow-wave sleep. SPW-Rs are generated in the CA3 region and are regulated by multiple synaptic inputs. Here, we used a multi-electrode array to determine the effects of CBZ on SPW-Rs and synaptic transmission at multiple hippocampal synapses. Our results demonstrate that CBZ reduced SPW-Rs at therapeutically relevant concentrations (IC50 = 37 μM) and altered the core characteristics of ripples, important for information processing and consolidation. Moreover, CBZ inhibited neurotransmission in a synapse-specific manner. CBZ inhibition was most potent at the medial-perforant-path-to-CA3 and mossy-fiber-to-CA3 synapses (IC50s ~ 30 and 60 μM, respectively) and least potent at medial-perforant-path-to-dentate granule cell synapses (IC50 ~ 120 μM). These results suggest that the synapse-specific CBZ inhibition of neurotransmission reduces SPW-Rs and that the CBZ inhibition of SPW-Rs may underlie the cognitive impairments observed with therapeutic doses of CBZ.
Lyme Neuroborreliosis: Mechanisms of B. burgdorferi Infection of the Nervous System
Authors: Ford Lenzie , Tufts Danielle M.
Published: June 2021

Lyme borreliosis is the most prevalent tick-borne disease in the United States, infecting ~476,000 people annually. Borrelia spp. spirochetal bacteria are the causative agents of Lyme disease in humans and are transmitted by Ixodes spp ticks. Clinical manifestations vary depending on which Borrelia genospecies infects the patient and may be a consequence of distinct organotropism between species. In the US, B. burgdorferi sensu stricto is the most commonly reported genospecies and infection can manifest as mild to severe symptoms. Different genotypes of B. burgdorferi sensu stricto may be responsible for causing varying degrees of clinical manifestations. While the majority of Lyme borreliae-infected patients fully recover with antibiotic treatment, approximately 15% of infected individuals experience long-term neurological and psychological symptoms that are unresponsive to antibiotics. Currently, long-term antibiotic treatment remains the only FDA-approved option for those suffering from these chronic effects. Here, we discuss the current knowledge pertaining to B. burgdorferi sensu stricto infection in the central nervous system (CNS), termed Lyme neuroborreliosis (LNB), within North America and specifically the United States. We explore the molecular mechanisms of spirochete entry into the brain and the role B. burgdorferi sensu stricto genotypes play in CNS infectivity. Understanding infectivity can provide therapeutic targets for LNB treatment and offer public health understanding of the B. burgdorferi sensu stricto genotypes that cause long-lasting symptoms.
A Comparison between Severe Suicidality and Nonsuicidal Self-Injury Behaviors in Bipolar Adolescents Referred to a Psychiatric Emergency Unit
Authors: Masi Gabriele , Lupetti Ilaria , D’Acunto Giulia , Milone Annarita , Fabiani Deborah , Madonia Ursula , Berloffa Stefano , Lenzi Francesca , Mucci Maria
Published: June 2021

Background: Severe suicide ideation or attempts and non-suicidal self-injury (NSSI) present both differences and relevant overlaps, including frequent co-occurrence and shared risk factors. Specific categorical diagnoses, namely bipolar disorder (BD), may affect clinical features and natural histories of suicidal or not suicidal self-harm behaviour. Our study aimed to compare suicidality (severe suicidal ideation or suicidal attempts) and NSSI in referred bipolar adolescents. Methods: The sample included 95 bipolar adolescents (32 males, 63 females) aged 11 to 18 years. Thirty adolescents with suicide attempts/suicidal ideation and BD (SASIB) were compared with structured measures to 35 adolescents with NSSI and BD, without suicidal ideation or attempts (NSSIB), and to 30 adolescents with BD, without suicidal ideation or attempts or NSSI (CB). Results: Compared to CB, suicidality and NSSI were both associated with female sex, borderline personality disorder and self-reported internalizing disorders, anxiety/depression and thought disorders. The NSSI were specifically associated with somatic problems. Severe suicidal ideation and suicide attempts were associated with adverse life events, immigration, bullying, eating disorders, social problems, depressive feelings, performance and social anxiety, and feelings of rejection. Conclusions: Both shared and differential features between suicidal and not suicidal adolescents may represent possible targets for diagnostic and preventative interventions.
miRNA Clusters with Up-Regulated Expression in Colorectal Cancer
Authors: Pidíková Paulína , Herichová Iveta
Published: June 2021

Colorectal cancer (CRC) is one of the most common malignancies in Europe and North America. Early diagnosis is a key feature of efficient CRC treatment. As miRNAs can be used as CRC biomarkers, the aim of the present study was to analyse experimentally validated data on frequently up-regulated miRNA clusters in CRC tissue and investigate their members with respect to clinicopathological characteristics of patients. Based on available data, 15 up-regulated clusters, miR-106a/363, miR-106b/93/25, miR-17/92a-1, miR-181a-1/181b-1, miR-181a-2/181b-2, miR-181c/181d, miR-183/96/182, miR-191/425, miR-200c/141, miR-203a/203b, miR-222/221, mir-23a/27a/24-2, mir-29b-1/29a, mir-301b/130b and mir-452/224, were selected. The positions of such clusters in the genome can be intronic or intergenic. Most clusters are regulated by several transcription factors, and miRNAs are also sponged by specific long non-coding RNAs. In some cases, co-expression of miRNA with other cluster members or host gene has been proven. miRNA expression patterns in cancer tissue, blood and faeces were compared. Based on experimental evidence, 181 target genes of selected clusters were identified. Panther analysis was used to reveal the functions of the target genes and their corresponding pathways. Clusters miR-17/92a-1, miR-106a/363, miR-106b/93/25 and miR-183/96/182 showed the strongest association with metastasis occurrence and poor patient survival, implicating them as the most promising targets of translational research.
Efficacy and Safety of Hypofractionated Preoperative Radiotherapy for Primary Locally Advanced Soft Tissue Sarcomas of Limbs or Trunk Wall
Authors: Koseła-Paterczyk Hanna , Teterycz Paweł , Spałek Mateusz , Borkowska Aneta , Zawadzka Anna , Wągrodzki Michał , Szumera-Ciećkiewicz Anna , Morysiński Tadeusz , Świtaj Tomasz , Ługowska Iwona , Castaneda-Wysocka Patrycja , Zdzienicki Marcin , Goryń Tomasz , Rutkowski Piotr
Published: June 2021

Background: The use of adjuvant radiotherapy (RT) shows a significantly decreased incidence of local recurrence (LR) in soft tissue sarcomas (STS). This study aimed to assess the treatment scheme’s effect in patients with primary STS treated at one institution. Methods: In this phase 2 trial, 311 patients aged ≥18 years with primary, locally advanced STS of the extremity or trunk wall were assigned to multimodal therapy conducted at one institution. The preoperative RT scheme consisted of 5 Gy per fraction for a total dose of 25 Gy. Surgery was performed within 2–4 days from the last day of RT. The primary endpoint was LR-free survival (LRFS). Adverse events of the treatment were assessed. Results: We included 311 patients with primary locally advanced STS. The median tumor size was 11 cm. In total, 258 patients (83%) had high-grade tumors. In 260 patients (83.6%), clear surgical margins (R0) were obtained. Ninety-six patients (30.8%) had at least one type of treatment adverse event. LR was observed in 13.8% patients. The 5-year overall survival was 63%. Conclusion: In this group, with a significant percentage of patients with extensive, high-grade STS, hypofractionated preoperative RT was associated with good local control and tolerance.
Nucleolin Targeting by N6L Inhibits Wnt/β-Catenin Pathway Activation in Pancreatic Ductal Adenocarcinoma
Authors: Raineri Fabio , Bourgoin-Voillard Sandrine , Cossutta Mélissande , Habert Damien , Ponzo Matteo , Houppe Claire , Vallée Benoît , Boniotto Michele , Chalabi-Dchar Mounira , Bouvet Philippe , Couvelard Anne , Cros Jerome , Debesset Anais , Cohen José L. , Courty José , Cascone Ilaria
Published: June 2021

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and resistant cancer with no available effective therapy. We have previously demonstrated that nucleolin targeting by N6L impairs tumor growth and normalizes tumor vessels in PDAC mouse models. Here, we investigated new pathways that are regulated by nucleolin in PDAC. We found that N6L and nucleolin interact with β-catenin. We found that the Wnt/β-catenin pathway is activated in PDAC and is necessary for tumor-derived 3D growth. N6L and nucleolin loss of function induced by siRNA inhibited Wnt pathway activation by preventing β-catenin stabilization in PDAC cells. N6L also inhibited the growth and the activation of the Wnt/β-catenin pathway in vivo in mice and in 3D cultures derived from MIA PaCa2 tumors. On the other hand, nucleolin overexpression increased β-catenin stabilization. In conclusion, in this study, we identified β-catenin as a new nucleolin interactor and suggest that the Wnt/β-catenin pathway could be a new target of the nucleolin antagonist N6L in PDAC.
Diagnostic Value of Galectin-3 in Distinguishing Invasive Encapsulated Carcinoma from Noninvasive Follicular Thyroid Neoplasms with Papillary-Like Nuclear Features (NIFTP)
Authors: Fu Guodong , Polyakova Olena , Chazen Ronald S. , Freeman Jeremy L. , Witterick Ian J.
Published: June 2021

Background: non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP), which is considered as low-risk cancer, should be distinguished from the malignant invasive encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC). Improved discrimination of NIFTPs from invasive EFVPTCs using a molecular biomarker test could provide useful insights into pre- and post-surgical management of the indeterminate thyroid nodule. Galectin-3 (Gal-3), a β-galactosyl-binding molecule in the lectin group, is involved in different biological functions in well differentiated thyroid carcinomas. The aim of this study was to determine whether Gal-3 expression as a diagnostic marker could distinguish indolent NIFTP from invasive EFVPTC on tissue specimens from surgical thyroid nodules. Methods: immunohistochemical (IHC) analysis of cytoplasmic and nuclear Gal-3 expression was performed in formalin-fixed paraffin-embedded (FFPE) surgical tissues in four specific diagnostic subgroups- benign nodules, NIFTPs, EFVPTCs and lymphocytic/Hashimoto’s thyroiditis (LTs). Results: cytoplasmic Gal-3 expression (mean ± SD) was significantly increased in invasive EFVPTCs (4.80 ± 1.60) compared to NIFTPs (2.75 ± 1.58, p < 0.001) and benign neoplasms (2.09 ± 1.19, p < 0.001) with no significant difference between NIFTPs and benign lesions (p = 0.064). The presence of LT enhanced cytoplasmic Gal-3 expression (3.80 ± 1.32) compared to NIFTPs (p = 0.016) and benign nodules (p < 0.001). Nuclear Gal-3 expression in invasive EFVPTCs (1.84 ± 1.30) was significantly higher than in NIFTPs (1.00 ± 0.72, p = 0.001), but similar to benign nodules (1.44 ± 1.77, p = 0.215), thereby obviating its potential clinical application. Conclusions: our observations have indicated that increased cytoplasmic Gal-3 expression shows diagnostic potential in distinguishing NIFTP among encapsulated follicular variant nodules thereby serving as a possible ancillary test to H&E histopathological diagnostic criteria when LT interference is absent, to assist in the detection of the invasive EFVPTC among such nodules.
Genetic Characterization and Clinical Features of Helicobacter pylori Negative Gastric Mucosa-Associated Lymphoid Tissue Lymphoma
Authors: Kiesewetter Barbara , Copie-Bergman Christiane , Levy Michael , Wu Fangtian , Dupuis Jehan , Barau Caroline , Arcaini Luca , Paulli Marco , Lucioni Marco , Bonometti Arturo , Salar Antonio , Fernández-Rodriguez Concepción , Piris Miguel A. , Cucco Francesco , Dobson Rachel , Li Yan , Chen Zi , Robe Cyrielle , Simonitsch-Klupp Ingrid , Wotherspoon Andrew , Raderer Markus , Du Ming Qing
Published: June 2021

Background: In Western countries, the prevalence of gastric mucosa-associated lymphoid tissue (MALT) lymphoma has declined over the last three decades. Contemporaneously, H. pylori negative gastric MALT lymphoma is increasingly encountered, and their genetic basis and clinical features remain elusive. Methods: A total of 57 cases of H. pylori negative gastric MALT lymphoma were reviewed and investigated for chromosome translocation by fluorescence in-situ hybridization and for somatic mutations by the targeted sequencing of 93 genes. Results: MALT1 translocation, most likely t(11;18)(q21;q21)/BIRC3-MALT1, was detected in 39% (22/57) cases, and IGH translocation was further seen in 12 MALT1-negative cases, together accounting for 60% of the cohort. Targeted sequencing was successful in 35 cases, and showed frequent mutations in NF-κB signaling pathways (TNFAIP3 = 23%, CARD11 = 9%, MAP3K14 = 9%), together affecting 14 cases (40%). The NF-κB pathway mutations were mutually exclusive from MALT1, albeit not IGH translocation, altogether occurring in 86% of cases. There was no significant correlation between the genetic changes and clinicopathological parameters. The patients showed a median of progression-free survival (PFS) of 66.3 months, and a significant superior PFS when treated with systemic versus antibiotic therapy (p = 0.004). Conclusion: H. pylori negative gastric MALT lymphoma is characterized by highly frequent genetic changes in the NF-κB signaling pathways.
The RAD51-FFPE Test; Calibration of a Functional Homologous Recombination Deficiency Test on Diagnostic Endometrial and Ovarian Tumor Blocks
Authors: van Wijk Lise M. , Kramer Claire J. H. , Vermeulen Sylvia , ter Haar Natalja T. , de Jonge Marthe M. , Kroep Judith R. , de Kroon Cor D. , Gaarenstroom Katja N. , Vrieling Harry , Bosse Tjalling , Vreeswijk Maaike P. G.
Published: June 2021

PARP inhibitor (PARPi) sensitivity is related to tumor-specific defects in homologous recombination (HR). Therefore, there is great clinical interest in tests that can rapidly and reliably identify HR deficiency (HRD). Functional HRD tests determine the actual HR status by using the (dis)ability to accumulate RAD51 protein at sites of DNA damage as read-out. In this study, we further improved and calibrated a previously described RAD51-based functional HRD test on 74 diagnostic formalin-fixed paraffin-embedded (FFPE) specimens (RAD51-FFPE test) from endometrial cancer (EC n = 25) and epithelial ovarian cancer (OC n = 49) patients. We established optimal parameters with regard to RAD51 foci cut-off (≥2) and HRD threshold (15%) using matched endometrial and ovarian carcinoma specimens for which HR status had been established using a RAD51-based test that required ex vivo irradiation of fresh tissue (RECAP test). The RAD51-FFPE test detected BRCA deficient tumors with 90% sensitivity and RECAP-HRD tumors with 87% sensitivity, indicating that it is an attractive alternative to DNA-based tests with the potential to be applied in routine diagnostic pathology.
Interactions between Cancer-Associated Fibroblasts and T Cells in the Pancreatic Tumor Microenvironment and the Role of Chemokines
Authors: Gorchs Laia , Kaipe Helen
Published: June 2021

Less than 10% of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) survive 5 years or more, making it one of the most fatal cancers. Accumulation of T cells in pancreatic tumors is associated with better prognosis, but immunotherapies to enhance the anti-tumor activity of infiltrating T cells are failing in this devastating disease. Pancreatic tumors are characterized by a desmoplastic stroma, which mainly consists of activated cancer-associated fibroblasts (CAFs). Pancreatic CAFs have emerged as important regulators of the tumor microenvironment by contributing to immune evasion through the release of chemokines, cytokines, and growth factors, which alters T-cell migration, differentiation and cytotoxic activity. However, recent discoveries have also revealed that subsets of CAFs with diverse functions can either restrain or promote tumor progression. Here, we discuss our current knowledge about the interactions between CAFs and T cells in PDAC and summarize different therapy strategies targeting the CAF–T cell axis with focus on CAF-derived soluble immunosuppressive factors and chemokines. Identifying the functions of different CAF subsets and understanding their roles in T-cell trafficking within the tumor may be fundamental for the development of an effective combinational treatment for PDAC.
Lung Cancer Stem Cells—Origin, Diagnostic Techniques and Perspective for Therapies
Authors: Raniszewska Agata , Kwiecień Iwona , Rutkowska Elżbieta , Rzepecki Piotr , Domagała-Kulawik Joanna
Published: June 2021

Lung cancer remains one of the most aggressive solid tumors with an overall poor prognosis. Molecular studies carried out on lung tumors during treatment have shown the phenomenon of clonal evolution, thereby promoting the occurrence of a temporal heterogeneity of the tumor. Therefore, the biology of lung cancer is interesting. Cancer stem cells (CSCs) are involved in tumor initiation and metastasis. Aging is still the most important risk factor for lung cancer development. Spontaneously occurring mutations accumulate in normal stem cells or/and progenitor cells by human life resulting in the formation of CSCs. Deepening knowledge of these complex processes and improving early recognition and markers of predictive value are of utmost importance. In this paper, we discuss the CSC hypothesis with an emphasis on age-related changes that initiate carcinogenesis. We analyze the current literature in the field, describe our own experience in CSC investigation and discuss the technical challenges with special emphasis on liquid biopsy.
Impact of Hypoxia on Relative Biological Effectiveness and Oxygen Enhancement Ratio for a 62-MeV Therapeutic Proton Beam
Authors: Chan Chun-Chieh , Chen Fang-Hsin , Hsiao Ya-Yun
Published: June 2021

This study uses the yields of double-strand breaks (DSBs) to determine the relative biological effectiveness (RBE) of proton beams, using cell survival as a biological endpoint. DSB induction is determined when cells locate at different depths (6 positions) along the track of 62 MeV proton beams. The DNA damage yields are estimated using Monte Carlo Damage Simulation (MCDS) software. The repair outcomes are estimated using Monte Carlo excision repair (MCER) simulations. The RBE for cell survival at different oxygen concentrations is calculated using the repair-misrepair-fixation (RMF) model. Using 60Co γ-rays (linear energy transfer (LET) = 2.4 keV/μm) as the reference radiation, the RBE for DSB induction and enzymatic DSB under aerobic condition (21% O2) are in the range 1.0–1.5 and 1.0–1.6 along the track depth, respectively. In accord with RBE obtained from experimental data, RMF model-derived RBE values for cell survival are in the range of 1.0–3.0. The oxygen enhancement ratio (OER) for cell survival (10%) decreases from 3.0 to 2.5 as LET increases from 1.1 to 22.6 keV/μm. The RBE values for severe hypoxia (0.1% O2) are in the range of 1.1–4.4 as LET increases, indicating greater contributions of direct effects for protons. Compared with photon therapy, the overall effect of 62 MeV proton beams results in greater cell death and is further intensified under hypoxic conditions.
NLRP7 Promotes Choriocarcinoma Growth and Progression through the Establishment of an Immunosuppressive Microenvironment
Authors: Reynaud Deborah , Abi Nahed Roland , Lemaitre Nicolas , Bolze Pierre-Adrien , Traboulsi Wael , Sergent Frederic , Battail Christophe , Filhol Odile , Sapin Vincent , Boufettal Houssine , Hoffmann Pascale , Aboussaouira Touria , Murthi Padma , Slim Rima , Benharouga Mohamed , Alfaidy Nadia
Published: June 2021

The inflammatory gene NLRP7 is the major gene responsible for recurrent complete hydatidiform moles (CHM), an abnormal pregnancy that can develop into gestational choriocarcinoma (CC). However, the role of NLRP7 in the development and immune tolerance of CC has not been investigated. Three approaches were employed to define the role of NLRP7 in CC development: (i) a clinical study that analyzed human placenta and sera collected from women with normal pregnancies, CHM or CC; (ii) an in vitro study that investigated the impact of NLRP7 knockdown on tumor growth and organization; and (iii) an in vivo study that used two CC mouse models, including an orthotopic model. NLRP7 and circulating inflammatory cytokines were upregulated in tumor cells and in CHM and CC. In tumor cells, NLRP7 functions in an inflammasome-independent manner and promoted their proliferation and 3D organization. Gravid mice placentas injected with CC cells invalidated for NLRP7, exhibited higher maternal immune response, developed smaller tumors, and displayed less metastases. Our data characterized the critical role of NLRP7 in CC and provided evidence of its contribution to the development of an immunosuppressive maternal microenvironment that not only downregulates the maternal immune response but also fosters the growth and progression of CC.
Impact of Preprocessing and Harmonization Methods on the Removal of Scanner Effects in Brain MRI Radiomic Features
Authors: Li Yingping , Ammari Samy , Balleyguier Corinne , Lassau Nathalie , Chouzenoux Emilie
Published: June 2021

In brain MRI radiomics studies, the non-biological variations introduced by different image acquisition settings, namely scanner effects, affect the reliability and reproducibility of the radiomics results. This paper assesses how the preprocessing methods (including N4 bias field correction and image resampling) and the harmonization methods (either the six intensity normalization methods working on brain MRI images or the ComBat method working on radiomic features) help to remove the scanner effects and improve the radiomic feature reproducibility in brain MRI radiomics. The analyses were based on in vitro datasets (homogeneous and heterogeneous phantom data) and in vivo datasets (brain MRI images collected from healthy volunteers and clinical patients with brain tumors). The results show that the ComBat method is essential and vital to remove scanner effects in brain MRI radiomic studies. Moreover, the intensity normalization methods, while not able to remove scanner effects at the radiomic feature level, still yield more comparable MRI images and improve the robustness of the harmonized features to the choice among ComBat implementations.
The Anti-Tumor Effect of Lactococcus lactis Bacteria-Secreting Human Soluble TRAIL Can Be Enhanced by Metformin Both In Vitro and In Vivo in a Mouse Model of Human Colorectal Cancer
Authors: Kaczmarek Katarzyna , Więckiewicz Jerzy , Węglarczyk Kazimierz , Siedlar Maciej , Baran Jarek
Published: June 2021

Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) induces apoptosis of many cancer cells, including CRC cells, being non-harmful for normal ones. However, recombinant form of human TRAIL failed in clinical trial when administered intravenously. To assess the importance of TRAIL in CRC patients, new form of TRAIL delivery would be required. Here we used genetically modified, non-pathogenic Lactococcus lactis bacteria as a vehicle for local delivery of human soluble TRAIL (hsTRAIL) in CRC. Operating under the Nisin Controlled Gene Expression System (NICE), the modified bacteria (L. lactis(hsTRAIL+)) were able to induce cell death of HCT116 and SW480 human cancer cells and reduce the growth of HCT116-tumor spheres in vitro. This effect was cancer cell specific as the cells of normal colon epithelium (FHC cells) were not affected by hsTRAIL-producing bacteria. Metformin (MetF), 5-fluorouracil (5-FU) and irinotecan (CPT-11) enhanced the anti-tumor actions of hsTRAIL in vitro. In the NOD-SCID mouse model, treatment of subcutaneous HCT116-tumors with L. lactis(hsTRAIL+) bacteria given intratumorally, significantly reduced the tumor growth. This anti-tumor activity of hsTRAIL in vivo was further enhanced by oral administration of MetF. These findings indicate that L. lactis bacteria could be suitable for local delivery of biologically active human proteins. At the same time, we documented that anti-tumor activity of hsTRAIL in experimental therapy of CRC can be further enhanced by MetF given orally, opening a venue for alternative CRC-treatment strategies.
Passivation of Co/Al2O3 Catalyst by Atomic Layer Deposition to Reduce Deactivation in the Fischer–Tropsch Synthesis
Authors: Díaz-López José Antonio , Guilera Jordi , Biset-Peiró Martí , Enache Dan , Kelly Gordon , Andreu Teresa
Published: June 2021

The present work explores the technical feasibility of passivating a Co/γ-Al2O3 catalyst by atomic layer deposition (ALD) to reduce deactivation rate during Fischer–Tropsch synthesis (FTS). Three samples of the reference catalyst were passivated using different numbers of ALD cycles (3, 6 and 10). Characterization results revealed that a shell of the passivating agent (Al2O3) grew around catalyst particles. This shell did not affect the properties of passivated samples below 10 cycles, in which catalyst reduction was hindered. Catalytic tests at 50% CO conversion evidenced that 3 and 6 ALD cycles increased catalyst stability without significantly affecting the catalytic performance, whereas 10 cycles caused blockage of the active phase that led to a strong decrease of catalytic activity. Catalyst deactivation modelling and tests at 60% CO conversion served to conclude that 3 to 6 ALD cycles reduced Co/γ-Al2O3 deactivation, so that the technical feasibility of this technique was proven in FTS.
Food Limitation but Not Enhanced Rates of Ejaculate Production Imposes Reproductive and Survival Costs to Male Crickets
Authors: McMahon Saoirse , Matzke Magdalena , Tuni Cristina
Published: June 2021

Estimating costs of ejaculate production is challenging. Metabolic investment in ejaculates may come at the expense of other physiological functions and may negatively affect future reproduction and/or survival. These trade-offs are especially likely to occur under constrained resource pools (e.g., poor nutrition). Here, we investigated costs of ejaculate production via trade-offs in the field cricket Gryllus bimaculatus. We experimentally increased rates of ejaculate production, while keeping an unmanipulated group, in adult males kept at high and low feeding regimes and tested the effects of our treatments on (i) somatic maintenance (i.e., changes in male body mass), (ii) future reproduction (i.e., the likelihood of producing a spermatophore and the viability of its sperm), and (iii) lifetime survival and longevity. We predicted investment in ejaculates to impinge upon all measured responses, especially in low-fed individuals. Instead, we only found negative effects of food limitation, suggesting low or undetectable costs of spermatophore production. High mating rates may select for males to maximize their capacity of ejaculate production, making ejaculate traits less prone to trade-offs with other fitness-related life history traits. Nevertheless, males were impaired due to nutrient deficiency in producing viable ejaculates, suggesting condition-dependent costs for ejaculate production.
Neurogenesis after Spinal Cord Injury: State of the Art
Authors: Rodríguez-Barrera Roxana , Rivas-González Monserrat , García-Sánchez Julián , Mojica-Torres Daniel , Ibarra Antonio
Published: June 2021

Neurogenesis in the adult state is the process of new neuron formation. This relatively infrequent phenomenon comprises four stages: cell proliferation, cell migration, differentiation, and the integration of these cells into an existing circuit. Recent reports suggest that neurogenesis can be found in different regions of the Central Nervous System (CNS), including the spinal cord (SC). This process can be observed in physiological settings; however, it is more evident in pathological conditions. After spinal cord injury (SCI), the activation of microglial cells and certain cytokines have shown to exert different modulatory effects depending on the presence of inflammation and on the specific region of the injury site. In these conditions, microglial cells and cytokines are considered to play an important role in the regulation of neurogenesis after SCI. The purpose of this article is to present an overview on neural progenitor cells and neurogenic and non-neurogenic zones as well as the cellular and molecular regulation of neurogenesis. Additionally, we will briefly describe the recent advances in the knowledge of neurogenesis after SCI.
Vimentin Promotes the Aggressiveness of Triple Negative Breast Cancer Cells Surviving Chemotherapeutic Treatment
Authors: Winter Marie , Meignan Samuel , Völkel Pamela , Angrand Pierre-Olivier , Chopin Valérie , Bidan Nadège , Toillon Robert-Alain , Adriaenssens Eric , Lagadec Chann , Le Bourhis Xuefen
Published: June 2021

Tremendous data have been accumulated in the effort to understand chemoresistance of triple negative breast cancer (TNBC). However, modifications in cancer cells surviving combined and sequential treatment still remain poorly described. In order to mimic clinical neoadjuvant treatment, we first treated MDA-MB-231 and SUM159-PT TNBC cell lines with epirubicin and cyclophosphamide for 2 days, and then with paclitaxel for another 2 days. After 4 days of recovery, persistent cells surviving the treatment were characterized at both cellular and molecular level. Persistent cells exhibited increased growth and were more invasive in vitro and in zebrafish model. Persistent cells were enriched for vimentinhigh sub-population, vimentin knockdown using siRNA approach decreased the invasive and sphere forming capacities as well as Akt phosphorylation in persistent cells, indicating that vimentin is involved in chemotherapeutic treatment-induced enhancement of TNBC aggressiveness. Interestingly, ectopic vimentin overexpression in native cells increased cell invasion and sphere formation as well as Akt phosphorylation. Furthermore, vimentin overexpression alone rendered the native cells resistant to the drugs, while vimentin knockdown rendered them more sensitive to the drugs. Together, our data suggest that vimentin could be considered as a new targetable player in the ever-elusive status of drug resistance and recurrence of TNBC.
A Novel Model for Nephrotic Syndrome Reveals Associated Dysbiosis of the Gut Microbiome and Extramedullary Hematopoiesis
Authors: Maier Jasmin I. , Rogg Manuel , Helmstädter Martin , Sammarco Alena , Walz Gerd , Werner Martin , Schell Christoph
Published: June 2021

Glomerular kidney disease causing nephrotic syndrome is a complex systemic disorder and is associated with significant morbidity in affected patient populations. Despite its clinical relevance, well-established models are largely missing to further elucidate the implications of uncontrolled urinary protein loss. To overcome this limitation, we generated a novel, inducible, podocyte-specific transgenic mouse model (Epb41l5fl/fl*Nphs1-rtTA-3G*tetOCre), developing nephrotic syndrome in adult mice. Animals were comprehensively characterized, including microbiome analysis and multiplexed immunofluorescence imaging. Induced knockout mice developed a phenotype consistent with focal segmental glomerular sclerosis (FSGS). Although these mice showed hallmark features of severe nephrotic syndrome (including proteinuria, hypoalbuminemia and dyslipidemia), they did not exhibit overt chronic kidney disease (CKD) phenotypes. Analysis of the gut microbiome demonstrated distinct dysbiosis and highly significant enrichment of the Alistipes genus. Moreover, Epb41l5-deficient mice developed marked organ pathologies, including extramedullary hematopoiesis of the spleen. Multiplex immunofluorescence imaging demonstrated red pulp macrophage proliferation and mTOR activation as driving factors of hematopoietic niche expansion. Thus, this novel mouse model for adult-onset nephrotic syndrome reveals the significant impact of proteinuria on extra-renal manifestations, demonstrating the versatility of this model for nephrotic syndrome-related research.
Three Novel EPCAM Variants Causing Tufting Enteropathy in Three Families
Authors: Ayyıldız Civan Hasret , Leitner Coleen , Östreicher Iris , Schneider Anna-Maria , Cremer Malte , Mayr Johannes A. , Rossi Rainer , Müller Thomas , Janecke Andreas R.
Published: June 2021

Tufting enteropathy (TE) is caused by recessive EPCAM mutations, and is characterized by intractable diarrhea of congenital onset and disorganization of enterocytes. TE generally requires parenteral nutrition (PN) during childhood or intestinal bowel transplantation. We report three unrelated families with six children with TE. We highlight the high rate of disease-related mortality. We observe adequate weight gain with PN, but low to normal and stunted body length, supporting the recent notion that a short stature might be intrinsic to TE. The diagnosis of TE in the index patients from each family was delayed for months to years, even when clinical data, duodenal biopsies, or exome sequencing data were obtained early on. We identified three novel pathogenic EPCAM variants: a deletion of exon 1 that removes the ATG initiation codon, a missense variant c.326A > G (p.Gln109Arg), and nonsense mutation c.429G > A (p.Trp143*) in a compound heterozygous state with the Mediterranean splice site variant c.556-14A > G (Tyr186Phefs*6). Homozygosity for p.Gln109Arg was associated with absent EPCAM staining, and compound heterozygosity for p.Trp143*/Tyr186Phefs*6 was associated with reduced EPCAM staining in duodenal biopsies; such observations might contribute to a genotype–phenotype correlation in larger cohorts of TE patients. This study extends the clinical and molecular spectrum of TE.
Multi-Validity Process and Factor-Invariance. Perceived Self-Efficacy-Scale for the Prevention of Obesity in Preteens
Authors: Gómez-Peresmitré Gilda , Platas Acevedo Romana Silvia , Pineda-García Gisela , Guzmán-Saldaña Rebeca , León-Hernández Rodrigo Cesar , Calleja Nazira
Published: June 2021

Given the lack of scales with a robust psychometric assessment of self-efficacy related to obesity in early adolescence, we aimed to obtain an instrument with high-quality validity and reliability items. Nonrandom samples (N = 2371) classified boys (1174, M = 12.83, SD = 0.84) and girls (1197, M = 12.68, SD = 0.78) from Mexico City and some cities of the Mexican Republic with obesity rates near to the national level mean. A multi-validity process and structural invariance analysis using the Perceived Self-efficacy Scale for Obesity Prevention were performed. A two-factor—physical activity and healthy eating—model with high effect-sized values—girls R2 (0.88, p < 0.01) and boys R2 (0.87, p < 0.01)—were obtained. Each factor explained more than half of the variance with high-reliability coefficients in each group and acceptable adjustment rates. The self-efficacy scale proved to have only girls, an invariant factor structure, or a psychometric equivalence between the groups. The obtained scale showed that a two-factor structure is feasible and appropriate, according to the highest quality of validity and reliability.
Inflammatory Myofibroblastic Tumor of the Upper Airways Harboring a New TRAF3-ALK Fusion Transcript
Authors: Di Ruscio Valentina , Mastronuzzi Angela , Russo Ida , Neri Marianna , Stracuzzi Alessandra , Giovannoni Isabella , Tropiano Maria Luisa , De Ioris Maria Antonietta , Milano Giuseppe Maria
Published: June 2021

Inflammatory myofibroblastic tumor (IMT) is a rare disease that mainly involves the lung and the abdomen with an intermediate clinical course but a recurrence rate between 15–30%. Radical surgery represents the gold standard of treatment, while chemotherapy and radiotherapy are considered for unresectable lesions. The identification of ALK translocations in IMT opened the option for the use of target therapies. Indeed, the ALK inhibitors have changed the treatment approach for aggressive lesions, improving the prognosis. Intraluminal upper-way IMT is extremely rare and represents a medical challenge. We reported an endotracheal IMT case presenting a previously unknown TRAF3-ALK fusion transcript.
Finite Element Analysis of Heavy Duty Riveted Steel Grating Bridge Deck
Authors: Abdulla Warda , Menzemer Craig
Published: June 2021

Heavy duty riveted gratings are a good alternative for applications that often employ other deck systems, if they are carefully analyzed under static and fatigue loads. Understanding the static behavior of a riveted steel deck under tire patch loads will aid in establishing a design model based on an effective beam width. In addition, use of a riveted system avoids welded details that may lead to fatigue cracking, thereby improving design life. In this study, analysis of a typical riveted steel deck under a standard AASHTO fatigue truck with a 15% impact factor was conducted. Hand calculations were compared with the results of a finite element model using SAP2000 v19.2.1. Bending moments and stresses were evaluated and compared. Stresses at the rivet hole for the most highly loaded bearing bar were evaluated. A model for fatigue cracking around a rivet hole is discussed.
Silver-Releasing Micro-/Nanoporous Coating on Additively Manufactured Macroporous Ti-Ta-Nb-Zr Scaffolds with High Osseointegration and Antibacterial Properties
Authors: Wu Zhenhuan , Luo Junsi , Zhang Jianying , Huang Haokun , Xie Zongyu , Xie Xiaoli
Published: June 2021

The two major problems of titanium alloy surface of bone/dental implants were the lack of native tissue integration and associated infection. To solve these problems, the development of self-defending implants with intrinsic osteogenic properties has been highlighted, in which titanium alloy surfaces of bone/dental implants are endowed with antibacterial property by silver (Ag) incorporated in biomaterials. In this study, we biofunctionalized the surface of selective laser melting (SLM) manufactured volume-porous Ti-Ta-Nb-Zr scaffolds by using plasma electrolytic oxidation (PEO) as a way to eliminate the peri-operative bacterial load and promote osseointegration. In the experiment, the PEO process operated with three different concentration (1, 1, and 2 g/L) of a AgNO3 solution. As a result, a titanium oxide coating embedded with calcium and phosphorous and Ag was formed by one-step PEO treatment, and a presence of HAp was detected by X-ray diffraction (XRD) and XPS. In addition, Ag ions were found to be released from the scaffolds for at least 28 days, resulting in an effective prevention of bacterial adhesion and a decrease of the number of planktonic bacteria, with no sign of cytotoxicity shown simultaneously. Highly porosity micropores were formed on the surface of scaffolds after oxidation, and the mechanical properties did not show any signs of change. Besides, a strong calcium deposition and osteoconductive effect were found on the surface of PEO-treated Ag scaffolds. To sum up, this study reveals the potential of PEO coatings to biofunctionalize SLM Ti-Ta-Nb-Zr scaffolds with antibacterial agents. The biomaterials developed here, therefore, exploit the biofunctionalized behavior of Ag to offer strong antibacterial behavior and osteogenic promotion without cytotoxicity of Ag against mammalian cells.
Gap-Size-Dependent Effective Phase Transition in Metasurfaces of Closed-Ring Resonators
Authors: Lee Seojoo , Kang Ji-Hun
Published: June 2021

We theoretically investigate a metal-to-insulator transition in artificial two-dimensional (2D) crystals (i.e., metasurfaces) of tightly coupled closed-ring resonators. Strong interaction between unit resonators in the metasurfaces yields the effective permittivity highly dependent on the lattice spacing of unit resonators. Through our rigorous theory, we provide a closed form of effective permittivity of the metasurface and reveal that the permittivity possesses a Lorentzian-type resonant behavior, implying that the transition of the effective permittivity can arise when the lattice spacing passes a critical value.
Wafer-Scale Semipolar Micro-Pyramid Lighting-Emitting Diode Array
Authors: Zhang Shuo , Yan Yan , Feng Tao , Yin Yue , Ren Fang , Liang Meng , Wu Chaoxing , Yi Xiaoyan , Wang Junxi , Li Jinmin , Liu Zhiqiang
Published: June 2021

InGaN-based micro-structured light-emitting diodes (µLEDs) play a critical role in the field of full-color display. In this work, selected area growth (SAG) of a micro-pyramid LED array was performed on a 2-inch wafer-scale patterned SiO2 template (periodicity: 4 µm diameter), by which a uniform periodic µLED array was achieved. The single-element pyramid-shaped LED exhibited 6 equivalent semipolar {1-101} planes and a size of about 5 µm, revealing a good crystalline quality with screw and edge dislocation densities of 8.27 × 107 and 4.49 × 108 cm−2. Due to the stress–relaxation out of the SAG, the as-built compressive strain was reduced to 0.59 GPa. The µLED array demonstrated a stable emission, confirmed by a small variation of electroluminescence (EL) peak wavelength over a wide range of current density up to 44.89 A/cm2, as well as tiny fluctuations (within 1.9 nm) in the EL full width at half maximum. The photoluminescence peak wavelength exhibits a good uniformity throughout the whole wafer with a discrete probability of only 0.25%.
“What We Want Is More Access…”: Experiences of Supportive Cancer Care and Strategies for Advancement in a Canadian Provincial Cancer Care Organization
Authors: Avery Jonathan , Schulte Hannah K. , Campbell Kristin L. , Bates Alan , McCune Lisa , Howard Amanda Fuchsia
Published: June 2021

Objectives: Despite calls for better supportive care, patients and families still commonly bear significant responsibility for managing the physical and mental health and social challenges of being diagnosed with and treated for cancer. As such, there is increased advocacy for integrated supportive care to ease the burden of this responsibility. The purpose of this study was to understand patient and caregiver experiences with supportive care to advance its delivery at a large provincial cancer care organization in Canada. Method: We used a qualitative descriptive approach to analyze focus groups with patients and caregivers from seven sites across the large provincial cancer care organization. Results: Focus group participants (n = 69) included cancer patients (n = 57) and caregivers (n = 12). Participants highlighted positive and negative aspects of their experience and strategies for improvement. These are depicted in three themes: (1) improving patient and provider awareness of services; (2) increasing access; (3) enhancing coordination and integration. Participants’ specific suggestions included centralizing relevant information about services, implementing a coach or navigator to help advocate for access, and delivering care virtually. Conclusions: Participants highlighted barriers to access and made suggestions for improving supportive care that they believed would reduce the burden associated with trying to manage their cancer journey.
Assessment of Water Quality, Eutrophication, and Zooplankton Community in Lake Burullus, Egypt
Authors: Alprol Ahmed E. , Heneash Ahmed M. M. , Soliman Asgad M. , Ashour Mohamed , Alsanie Walaa F. , Gaber Ahmed , Mansour Abdallah Tageldein
Published: June 2021

Burullus Lake is Egypt’s second most important coastal lagoon. The present study aimed to shed light on the different types of polluted waters entering the lake from various drains, as well as to evaluate the zooplankton community, determine the physical and chemical characteristics of the waters, and study the eutrophication state based on three years of seasonal monitoring from 2017 to 2019 at 12 stations. The results revealed that Rotifera, Copepoda, Protozoa, and Cladocera dominated the zooplankton population across the three-year study period, with a total of 98 taxa from 59 genera and 10 groups detected in the whole-body lake in 2018 and 2019, compared to 93 species from 52 genera in 2017. Twelve representative surface water samples were collected from the lake to determine physicochemical parameters, i.e., temperature, pH, salinity, dissolved oxygen, biological oxygen demand, chemical oxygen demand, ammonia-N, nitrate–N, nitrate-N, total nitrogen, total phosphorus, dissolved reactive phosphorus, and chlorophyll-a, as well as Fe, Cu, Zn, Cr, Ni, Cd, and Pb ions. Based on the calculations of the water quality index (WQI), the lake was classified as having good water quality. However, the trophic state is ranked as hyper-eutrophic and high trophic conditions.