bluuebunny/crossref_metadata_2025 huggingface dataset:
miR766-3p and miR124-3p Dictate Drug Resistance and Clinical Outcome in HNSCC
Authors: Shibata Tomohiro , Cao Duo-Yao , Dar Tahir B. , Ahmed Faizan , Bhat Shabir A. , Veiras Luciana C. , Bernstein Ellen A. , Khan Abdul Arif , Chaum Manita , Shiao Stephen L. , Tourtellotte Warren G. , Giani Jorge F. , Bernstein Kenneth E. , Cui Xiaojiang , Vail Eric , Khan Zakir
Published: October 2022

Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive disease with poor prognosis, which is mainly due to drug resistance. The biology determining the response to chemo-radiotherapy in HNSCC is poorly understood. Using clinical samples, we found that miR124-3p and miR766-3p are overexpressed in chemo-radiotherapy-resistant (non-responder) HNSCC, as compared to responder tumors. Our study shows that inhibition of miR124-3p and miR766-3p enhances the sensitivity of HNSCC cell lines, CAL27 and FaDu, to 5-fluorouracil and cisplatin (FP) chemotherapy and radiotherapy. In contrast, overexpression of miR766-3p and miR124-3p confers a resistance phenotype in HNSCC cells. The upregulation of miR124-3p and miR766-3p is associated with increased HNSCC cell invasion and migration. In a xenograft mouse model, inhibition of miR124-3p and miR766-3p enhanced the efficacy of chemo-radiotherapy with reduced growth of resistant HNSCC. For the first time, we identified that miR124-3p and miR766-3p attenuate expression of CREBRF and NR3C2, respectively, in HNSCC, which promotes aggressive tumor behavior by inducing the signaling axes CREB3/ATG5 and β-catenin/c-Myc. Since miR124-3p and miR766-3p affect complementary pathways, combined inhibition of these two miRNAs shows an additive effect on sensitizing cancer cells to chemo-radiotherapy. In conclusion, our study demonstrated a novel miR124-3p- and miR766-3p-based biological mechanism governing treatment-resistant HNSCC, which can be targeted to improve clinical outcomes in HNSCC.
New Insights on the Role of Anti-PD-L1 and Anti-CTLA-4 mAbs on Different Lymphocytes Subpopulations in TNBC
Authors: Lembo Rosa Rapuano , Manna Lorenzo , Froechlich Guendalina , Sasso Emanuele , Passariello Margherita , De Lorenzo Claudia
Published: October 2022

Antibody-based cancer immunotherapy includes monoclonals against immune checkpoints (ICs), to modulate specific T cell responses against cancer. NK cells are a newly emerging target for immune checkpoint receptor inhibition in cancer immunotherapy, as ICs are also expressed on NK cells in various cancers. The latter cells are becoming attractive targets for cancer immunotherapy, as they are effector cells similar to CTLs, exerting natural cytotoxicity against primary tumor cells and metastasis, and they are able to distinguish tumor cells from healthy ones, leading to more specific anti-tumor cytotoxicity and reduced off-target effects. Thus, we decided to test the effects on isolated NK cells and T cell subpopulations of novel immunomodulatory mAbs, recently generated in our lab, in comparison with those in clinical use, such as ipilimumab and atezolizumab. Interestingly, we found that the novel anti-CTLA-4 (ID-1) and anti-PD-L1 (PD-L1_1) antibodies are able to induce NK cell activation and exert anti-tumor effects on TNBC cells co-cultured with NK cells more efficiently than the clinically validated ones, either when used as single agents or in combinatorial treatments. On the other hand, ipilimumab was found to be more effective in activating T cells with respect to ID-1. These findings indicate that antibodies targeting different epitopes can have differential effects on different lymphocytes subpopulations and that novel combinations of mAbs could be suitable for therapeutic approaches aimed at activating not only T cells but also NK cells, especially for tumors lacking MHC.
Hepcidin Upregulation in Colorectal Cancer Associates with Accumulation of Regulatory Macrophages and Epithelial–Mesenchymal Transition and Correlates with Progression of the Disease
Authors: Di Grazia Antonio , Di Fusco Davide , Franzè Eleonora , Colella Marco , Strimpakos Georgios , Salvatori Silvia , Formica Vincenzo , Laudisi Federica , Maresca Claudia , Colantoni Alfredo , Ortenzi Angela , Stolfi Carmine , Monteleone Ivan , Monteleone Giovanni
Published: October 2022

Advanced, metastatic colorectal cancer (CRC) is associated with high rate of mortality because of its poor responsiveness to chemotherapy/immunotherapy. Recent studies have shown that hepcidin, a peptide hormone produced mainly by hepatocytes, is expressed by and enhances the growth of tumor cells. We here assessed whether hepcidin expression helps identify subsets of CRC with advanced and aggressive course. By integrating results of in vitro/ex vivo studies with data of bioinformatics databases, we initially showed that hepcidin RNA and protein expression was more pronounced in tissue samples taken from the tumor area, as compared to the macroscopically unaffected, adjacent, colonic mucosa of CRC patients. The induction of hepcidin in the colonic epithelial cell line HCEC-1ct by interleukin (IL)-6, IL-21 and IL-23 occurred via a Stat3-dependent mechanism and, in primary CRC cells, hepcidin co-localized with active Stat3. In CRC tissue, hepcidin content correlated mainly with macrophage accumulation and IL-10 and CD206 expression, two markers of regulatory macrophages. Consistently, both IL-10 and CD206 were up-regulated by hepcidin in blood mononuclear cells. The highest levels of hepcidin were found in metastatic CRC and survival analysis showed that high expression of hepcidin associated with poor prognosis. Moreover, hepcidin expression correlated with markers of epithelial-to-mesenchymal transition and the silencing of hepcidin in CRC cells reduced epithelial-to-mesenchymal transition markers. These findings indicate that hepcidin is markedly induced in the advanced stages of CRC and suggest that it could serve as a prognostic biomarker in CRC.
The Urothelial Transcriptomic Response to Interferon Gamma: Implications for Bladder Cancer Prognosis and Immunotherapy
Authors: Baker Simon C. , Mason Andrew S. , Slip Raphael G. , Eriksson Pontus , Sjödahl Gottfrid , Trejdosiewicz Ludwik K. , Southgate Jennifer
Published: October 2022

Interferon gamma (IFNγ) is central to the inflammatory immune response, such as that entrained by BCG immunotherapy for bladder cancer. However, immune-mediated tumour cell killing is subject to modulation by immunoinhibitory “checkpoint” receptors such as PD-L1. We investigated the effects of IFNγ on barrier-forming in vitro-differentiated normal human urothelium using mRNA-sequencing, and showed canonical upregulation of MHC class I/II and de novo expression of the T cell tropic CXCL9-11 chemokines. Normal urothelium constitutively expressed immunoinhibitory B7 family member VSIR (VISTA), while CD274 (PD-L1) expression was induced/upregulated by IFNγ. We generated a urothelial IFNγ response gene signature. When applied to the unsupervised clustering of non-muscle-invasive bladder cancers, the IFNγ-signature predicted longer recurrence-free survival. In muscle-invasive cancers, the IFNγ-signature split the basal/squamous consensus subtype, with significantly worse overall survival when weak or absent. This study offers novel insights into strategies to enhance immunotherapy via the IFNγ and VISTA/PD-L1 nexus.
Microwave Catheter Navigation System for the Radiofrequency Liver Ablation
Authors: Kollar Jakub , Drizdal Tomas , Vrba Jan , Vrba David , Pokorny Tomas , Novak Marek , Fiser Ondrej
Published: October 2022

Thermal ablation is a well-known method used in interventional radiology to treat cancer. The treatment success is closely related to the exact catheter location in the treated area. Current navigation methods are based mostly on ultrasound or computed tomography. This work explores the possibility of tracking the catheter position during ablation treatment of hepatocellular carcinomas (HCC) using an ultra-wideband (UWB) antenna array and microwave radar imaging based on the “Delay and Sum” (DAS) algorithm. The feasibility was first numerically studied on a simple homogeneous liver model. A heterogeneous anthropomorphic 3D model of the treated region consisting of the main organs within the treated area was then used. Various standard radiofrequency ablation (RFA) catheters were placed virtually in the heterogeneous model. The location and orientation of the antenna elements of the developed imaging system and the applied frequency band were studied. Subsequently, an experimental setup consisting of a 3D printed homogeneous anthropomorphic model, eight UWB dipole antennas, and catheters was created and used in a series of measurements. The average accuracy determining the catheter position from simulated and experimental data was 3.88 ± 0.19 and 6.13 ± 0.66 mm, which are close to the accuracy of clinical navigation systems.
RET Proto-Oncogene—Not Such an Obvious Starting Point in Cancer Therapy
Authors: Kucharczyk Tomasz , Krawczyk Paweł , Kowalski Dariusz M. , Płużański Adam , Kubiatowski Tomasz , Kalinka Ewa
Published: October 2022

Mutations and fusions of RET (rearranged during transfection) gene are detected in a few common types of tumors including thyroid or non-small cells lung cancers. Multiple kinase inhibitors (MKIs) do not show spectacular effectiveness in patients with RET-altered tumors. Hence, recently, two novel RET-specific inhibitors were registered in the US and in Europe. Selpercatinib and pralsetinib showed high efficacy in clinical trials, with fewer adverse effects, in comparison to previously used MKIs. However, the effectiveness of these new drugs may be reduced by the emergence of resistance mutations in RET gene and activation of different activating signaling pathways. This review presents the function of the normal RET receptor, types of molecular disturbances of the RET gene in patients with various cancers, methods of detecting these abnormalities, and the effectiveness of modern anticancer therapies (ranging from immunotherapies, through MKIs, to RET-specific inhibitors).
In Situ Growth of Self-Supporting MOFs-Derived Ni2P on Hierarchical Doped Carbon for Efficient Overall Water Splitting
Authors: Chen Neng , Che Sai , Liu Hongchen , Ta Na , Li Guohua , Chen Fengjiang , Ma Guang , Yang Fan , Li Yongfeng
Published: October 2022

The in situ growth of metal organic framework (MOF) derivatives on the surface of nickel foam is a novel type of promising self-supporting electrode catalyst. In this paper, this work reports for the first time the strategy of in situ growth of Ni-MOF, where the metal source is purely provided by a nickel foam (NF) substrate without any external metal ions. MOF-derived Ni2P/NPC structure is achieved by the subsequent phosphidation to yield Ni2P on porous N, P-doped carbon (NPC) backbone. Such strategy provides the as-synthesized Ni2P/NPC/NF electrocatalyst an extremely low interfacial steric resistance. Moreover, a unique three-dimensional hierarchical structure is achieved in Ni2P/NPC/NF, providing massive active sites, short ion diffusion path, and high electrical conductivity. Directly applied as the electrode, Ni2P/NPC/NF demonstrates excellent electrocatalytic performance towards both the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER), with low overpotentials of only 58 mV and 208 mV to drive 10 mA cm−2, respectively, in 1 M KOH. Furthermore, Ni2P/NPC/NF acting as the overall water splitting electrodes can generate a current density of 10 mA cm−2 at an ultralow cell voltage of 1.53 V. This simple strategy paves the way for the construction of self-supporting transition metal-based electrocatalysts.
Endogenous Ethanol and Triglyceride Production by Gut Pichia kudriavzevii, Candida albicans and Candida glabrata Yeasts in Non-Alcoholic Steatohepatitis
Authors: Mbaye Babacar , Borentain Patrick , Magdy Wasfy Reham , Alou Maryam Tidjani , Armstrong Nicholas , Mottola Giovanna , Meddeb Line , Ranque Stéphane , Gérolami René , Million Matthieu , Raoult Didier
Published: October 2022

Nonalcoholic steatohepatitis (NASH) increases with fructose consumption and metabolic syndrome and has been recently linked with endogenous ethanol production, notably by high alcohol-producing Klebsiella pneumoniae (HiAlc Kpn). Candida yeasts are the main causes of auto-brewery syndromes but have been neglected in NASH. Here, the fecal ethanol and microbial content of 10 cases and 10 controls were compared. Ethanol was measured by gas chromatography-mass spectrometry. Species identification was performed by MALDI-TOF MS, and triglyceride production was assessed by a colorimetric enzymatic assay. The fecal ethanol concentration was four times higher in patients with NASH (median [interquartile range]: 0.13 [0.05–1.43] vs. 0.034 [0.008–0.57], p = 0.037). Yeasts were isolated from almost all cases but not from controls (9/10 vs. 0/10, p = 0.0001). Pichia kudriavzevii was the most frequent (four patients), while Candida glabrata, Candida albicans, and Galactomyces geotrichum were identified in two cases each. The concentration of ethanol produced by yeasts was 10 times higher than that produced by bacteria (median, 3.36 [0.49–5.60] vs. 0.32 [0.009–0.43], p = 0.0029). Using a 10% D-fructose restricted medium, we showed that NASH-associated yeasts transformed fructose in ethanol. Unexpectedly, yeasts isolated from NASH patients produced a substantial amount of triglycerides. Pichia kudriavzevii strains produced the maximal ethanol and triglyceride levels in vitro. Our preliminary human descriptive and in vitro experimental results suggest that yeasts have been neglected. In addition to K. pneumoniae, gut Pichia and Candida yeasts could be linked with NASH pathophysiology in a species- and strain-specific manner through fructose-dependent endogenous alcohol and triglyceride production.
Aberrant B Cell Signaling in Autoimmune Diseases
Authors: Corneth Odilia B. J. , Neys Stefan F. H. , Hendriks Rudi W.
Published: October 2022

Aberrant B cell signaling plays a critical in role in various systemic and organ-specific autoimmune diseases. This is supported by genetic evidence by many functional studies in B cells from patients or specific animal models and by the observed efficacy of small-molecule inhibitors. In this review, we first discuss key signal transduction pathways downstream of the B cell receptor (BCR) that ensure that autoreactive B cells are removed from the repertoire or functionally silenced. We provide an overview of aberrant BCR signaling that is associated with inappropriate B cell repertoire selection and activation or survival of peripheral B cell populations and plasma cells, finally leading to autoantibody formation. Next to BCR signaling, abnormalities in other signal transduction pathways have been implicated in autoimmune disease. These include reduced activity of several phosphates that are downstream of co-inhibitory receptors on B cells and increased levels of BAFF and APRIL, which support survival of B cells and plasma cells. Importantly, pathogenic synergy of the BCR and Toll-like receptors (TLR), which can be activated by endogenous ligands, such as self-nucleic acids, has been shown to enhance autoimmunity. Finally, we will briefly discuss therapeutic strategies for autoimmune disease based on interfering with signal transduction in B cells.
Exosomes from Human Omental Adipose-Derived Mesenchymal Stem Cells Secreted into Ascites Promote Peritoneal Metastasis of Epithelial Ovarian Cancer
Authors: Qu Qingxi , Liu Linghong , Cui Yuqian , Chen Yu , Wang Yu , Wang Yaodu
Published: October 2022

Epithelial ovarian cancer (EOC) patients frequently develop peritoneal metastasis, especially in the human omentum. However, the mechanism underlying this propensity remains unknown. A previous study found that human omental adipose-derived mesenchymal stem cells are potentially involved in ovarian cancer growth and metastasis, but the results were inconsistent and even contradictory. In addition, the underlying mechanisms of visceral adipose metastasis remain poorly understood. Here, our goal is to clarify the role and mechanism of human omental adipose-derived mesenchymal stem cells (HO-ADSCs) in EOC cancer growth and metastasis. We first found that human omental tissue conditioned medium (HO-CM) enhances EOC cell function. Subsequent coculture studies indicated that HO-ADSCs increase the growth, migratory and invasive capabilities of ovarian cancer cells. Then, we demonstrated that exosomes secreted by HO-ADSCs (HO-ADSC exosomes) enhanced ovarian cancer cell function, and further mechanistic studies showed that the FOXM1, Cyclin F, KIF20A, and MAPK signaling pathways were involved in this process. In addition, subcutaneous tumorigenesis and peritoneal metastatic xenograft experiments provided evidence that HO-ADSC exosomes promote ovarian cancer growth and metastasis in vivo. Finally, our clinical studies provided evidence that ascites from ovarian cancer patients enhance EOC cell line proliferation, migration, and invasion in vitro. The present study indicated that HO-ADSC exosomes are secreted into ascites and exert a tumor-promoting effect on EOC growth and metastasis, providing a new perspective and method to develop future novel therapeutic strategies for the treatment of ovarian cancer.
Whole Transcriptome Sequencing Reveals Cancer-Related, Prognostically Significant Transcripts and Tumor-Infiltrating Immunocytes in Mantle Cell Lymphoma
Authors: Esmeray Sönmez Esra , Hatipoğlu Tevfik , Kurşun Deniz , Hu Xiaozhou , Akman Burcu , Yuan Hongling , Erşen Danyeli Ayça , Alacacıoğlu İnci , Özkal Sermin , Olgun Aybüke , Erdağ Taner Kemal , You Hua , Küçük Can
Published: October 2022

Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma (NHL) subtype characterized by overexpression of CCND1 and SOX11 genes. It is generally associated with clinically poor outcomes despite recent improvements in therapeutic approaches. The genes associated with the development and prognosis of MCL are still largely unknown. Through whole transcriptome sequencing (WTS), we identified mRNAs, lncRNAs, and alternative transcripts differentially expressed in MCL cases compared with reactive tonsil B-cell subsets. CCND1, VCAM1, and VWF mRNAs, as well as MIR100HG and ROR1-AS1 lncRNAs, were among the top 10 most significantly overexpressed, oncogenesis-related transcripts. Survival analyses with each of the top upregulated transcripts showed that MCL cases with high expression of VWF mRNA and low expression of FTX lncRNA were associated with poor overall survival. Similarly, high expression of MSTRG.153013.3, an overexpressed alternative transcript, was associated with shortened MCL survival. Known tumor suppressor candidates (e.g., PI3KIP1, UBXN) were significantly downregulated in MCL cases. Top differentially expressed protein-coding genes were enriched in signaling pathways related to invasion and metastasis. Survival analyses based on the abundance of tumor-infiltrating immunocytes estimated with CIBERSORTx showed that high ratios of CD8+ T-cells or resting NK cells and low ratios of eosinophils are associated with poor overall survival in diagnostic MCL cases. Integrative analysis of tumor-infiltrating CD8+ T-cell abundance and overexpressed oncogene candidates showed that MCL cases with high ratio CD8+ T-cells and low expression of FTX or PCA3 can potentially predict high-risk MCL patients. WTS results were cross-validated with qRT-PCR of selected transcripts as well as linear correlation analyses. In conclusion, expression levels of oncogenesis-associated transcripts and/or the ratios of microenvironmental immunocytes in MCL tumors may be used to improve prognostication, thereby leading to better patient management and outcomes.
Role of SUMOylation in Neurodegenerative Diseases
Authors: Mandel Nicolas , Agarwal Nitin
Published: October 2022

Neurodegenerative diseases (NDDs) are irreversible, progressive diseases with no effective treatment. The hallmark of NDDs is the aggregation of misfolded, modified proteins, which impair neuronal vulnerability and cause brain damage. The loss of synaptic connection and the progressive loss of neurons result in cognitive defects. Several dysregulated proteins and overlapping molecular mechanisms contribute to the pathophysiology of NDDs. Post-translational modifications (PTMs) are essential regulators of protein function, trafficking, and maintaining neuronal hemostasis. The conjugation of a small ubiquitin-like modifier (SUMO) is a reversible, dynamic PTM required for synaptic and cognitive function. The onset and progression of neurodegenerative diseases are associated with aberrant SUMOylation. In this review, we have summarized the role of SUMOylation in regulating critical proteins involved in the onset and progression of several NDDs.
Separase Control and Cohesin Cleavage in Oocytes: Should I Stay or Should I Go?
Authors: Wassmann Katja
Published: October 2022

The key to gametogenesis is the proper execution of a specialized form of cell division named meiosis. Prior to the meiotic divisions, the recombination of maternal and paternal chromosomes creates new genetic combinations necessary for fitness and adaptation to an ever-changing environment. Two rounds of chromosome segregation -meiosis I and II- have to take place without intermediate S-phase and lead to the creation of haploid gametes harboring only half of the genetic material. Importantly, the segregation patterns of the two divisions are fundamentally different and require adaptation of the mitotic cell cycle machinery to the specificities of meiosis. Separase, the enzyme that cleaves Rec8, a subunit of the cohesin complex constituting the physical connection between sister chromatids, has to be activated twice: once in meiosis I and immediately afterwards, in meiosis II. Rec8 is cleaved on chromosome arms in meiosis I and in the centromere region in meiosis II. This step-wise cohesin removal is essential to generate gametes of the correct ploidy and thus, embryo viability. Hence, separase control and Rec8 cleavage must be perfectly controlled in time and space. Focusing on mammalian oocytes, this review lays out what we know and what we still ignore about this fascinating mechanism.
Effective, Long-Term, Neutrophil Depletion Using a Murinized Anti-Ly-6G 1A8 Antibody
Authors: Olofsen Patricia A. , Stip Marjolein C. , Jansen J. H. Marco , Chan Chilam , Nederend Maaike , Tieland Ralph G. , Tsioumpekou Maria , Leusen Jeanette H. W.
Published: October 2022

Neutrophils are crucial innate immune cells but also play key roles in various diseases, such as cancer, where they can perform both pro- and anti-tumorigenic functions. To study the function of neutrophils in vivo, these cells are often depleted using Ly-6G or Gr-1 depleting antibodies or genetic “knockout” models. However, these methods have several limitations, being only partially effective, effective for a short term, and lacking specificity or the ability to conditionally deplete neutrophils. Here, we describe the use of a novel murinized Ly-6G (1A8) antibody. The murinized Ly-6G antibody is of the mouse IgG2a isotype, which is the only isotype that can bind all murine Fcγ receptors and C1q and is, therefore, able to activate antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent phagocytosis (ADCP) and complement-dependent cytotoxicity (CDC) pathways. We show that this mouse-Ly-6G antibody shows efficient, long-term, and near-complete (>90%) neutrophil depletion in the peripheral blood of C57Bl6/J, Balb/c, NXG and SCID mice for up to at least four weeks, using a standardized neutrophil depletion strategy. In addition, we show that neutrophils are efficiently depleted in the blood and tumor tissue of IMR32 tumor-bearing SCID mice, analyzed six weeks after the start of the treatment.
Effectiveness of Bio-Waste-Derived Carbon Doping on De-Icing Performance of an Electrically Resistant Concrete
Authors: Bakbolat Baglan , Daulbayev Chingis , Sultanov Fail , Taurbekov Azamat , Tolynbekov Aidos , Yeleuov Mukhtar , Korobeinyk Alina V. , Mansurov Zulkhair
Published: October 2022

This paper proposes a modified carbon-based concrete filler composition, which can potentially be used as a self-de-icing pavement. Carbon fibers (CNFs), graphene-like porous carbon (GLC), and a CNF/GLC composite were developed to reinforce concrete with the aim to improve its electrical conductivity and mechanical properties. The effect of the CNF and GLC loadings on the electrical conductivity of the filled concrete was evaluated in a climatic chamber at temperatures simulating water-freezing conditions on a concrete road. The results show that even a negligible loading (0.2 wt.%) of concrete with CNF/GLC results in a dramatic decrease in its resistance when compared to the same loadings for CNF and GLC added separately. Depending on the number of fillers, the temperature of the modified concrete samples reached up to +19.8 °C at low voltage (10 V) at −10 °C, demonstrating the perspective of their heat output for anti-icing applications. Additionally, this study shows that adding 2.0 wt.% of the CNF/GLC composite to the concrete improves its compressive strength by 33.93% compared to the unmodified concrete.
A Comparative Study of Chloride Adsorption Ability and Corrosion Protection Effect in Epoxy Coatings of Various Layered Double Hydroxides
Authors: Cao Yanhui , Wang Jingjing , Chen Kaifeng , Zhang Xinyue , Zhang Bing , Fang Shuo , Liang Yu , Huang Congshu , Wang Xinyu
Published: October 2022

The positive influence of chloride adsorption on the enhanced protection effect was always emphasized in the published literature. The concrete contribution of chloride adsorption and physical barrier effect of LDH in coatings still remains unclear at present. This work was aimed at exploring the significance of the chloride adsorption role of LDH in the corrosion protection of epoxy coatings. The synthesized LDH samples were characterized by scanning electronic microscopy (SEM), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) to show the influence of different parameters on its morphology, structure and composition, respectively. The corrosion-electrochemical behavior was investigated using electrochemical impedance spectroscopy (EIS) and salt spray test. It was found that although CaAl-LDH presented a lower chloride adsorption ability in comparison with other samples; it showed effective corrosion protection due to the higher physical barrier effect of CaAl-LDH with typically hexagonal and plate-like morphology due to good compatibility with the epoxy coatings. The results indicated that the corrosion protection effect of the incorporated LDH was more closely related to its physical barrier role rather than the role of the chloride adsorption, which was misunderstood in the previous publications. This work clarified the contribution comparison of the chloride adsorption and physical barrier of LDH in epoxy coating corrosion protection for the first time.
Factors Influencing Acceptance of Hippopotamus at a Large Reservoir in Nigeria
Authors: Baker Lynne R. , Radda Ibrahim A. , Teneke Vastinah N. , Kadala Edward , Sturdivant Rodney X. , Madwatte Gwaha A.
Published: October 2022

In a world increasingly affected by human presence and activities, achieving human–wildlife coexistence has become the goal of many wildlife conservation programs. Coexistence requires an understanding of factors that contribute to human tolerance and acceptance of problematic wildlife. In four communities in Nigeria, we used structured and semi-structured interviews to explore local people’s acceptance of the river hippopotamus (Hippopotamus amphibius) at a large reservoir with high human impact and where other conspicuous, damage-causing species are absent. We collected data two years apart to evaluate whether acceptance changed over time. Acceptance was low among respondents (21%). Logistic-regression results showed that attitudes, beliefs related to benefits and risks, behaviors toward hippos, study period, and income source significantly influenced acceptance of hippos. Results from Woolf tests showed that hippo-caused human fatalities most notably modified the observed decline in acceptance between study years. The potential significant impact of rare, yet severe events (in this case, human fatalities) on acceptance of wildlife and thus human–wildlife coexistence was supported in this study, one of few focused on hippo-human relations. For conservation and development interventions to be effective at this site, they should, at a minimum, improve human safety around hippos, emphasize current and potential benefits of hippos, create avenues for off-farm income, and reduce crop losses owing to hippos.
Experimental Investigation on the Compressive Stress-Sensing Ability of Steel Fiber-Reinforced Cement-Based Composites under Varying Temperature Conditions
Authors: Eiras Jesús N. , Duplan François , Payan Cédric
Published: October 2022

This study investigates the piezoresistive (self-sensing) properties of short stainless-steel fiber-reinforced mortar under varying temperature conditions. Different reinforced mortars were produced by varying fiber and aggregate content. First, Electrical Impedance Spectroscopy (EIS) measurements were used to characterize the electrical properties of the mortar specimens. EIS measurements were performed at temperatures of 24 °C, 35 °C, and 50 °C. Second, to investigate the self-sensing capacity of the different composites, the fractional changes of electrical impedance at 1 kHz were monitored under two conditions: temperature variation alone (cooling down from 35 °C or 50 °C to room temperature), and temperature variation combined with cyclic compressive loading (up to 5 MPa). The results of the former were used to compensate for the effect of temperature variations in the latter. Both temperature and mechanical loading produced meaningful variations in the electrical impedance and piezoresistivity of the investigated composites. Conclusions are drawn with respect to the stress and temperature sensitivity of the composites. The real and imaginary parts of the electrical impedance of the mortar produced with the highest fiber volume fraction (0.01%) and higher aggregate content (volume fraction of 60%) were distinctly sensitive to temperature and stress, which suggests the possibility of using the same composite as a stress and temperature sensor.
Investigation of Fatigue Crack Growth in TA2 Cruciform Specimen with an Inclined Crack, Considering Stress Ratio and Biaxial Load Ratio
Authors: Bao Wen-Jie , Liu Jia-Yu , Tao Zhi-Lin , Zhao Guang-Zhou , Zhou Chang-Yu
Published: October 2022

The biaxial fatigue crack growth behavior of commercial pure titanium TA2 of cruciform specimens with different crack inclination angles (β = 90°, 60°, 45°) under various biaxial load ratios (λ = 0, 0.5, 1) and different stress ratios (R = 0, 0.1, 0.3) is studied by an IPBF-5000 biaxial testing machine. The test results prove that the maximum tangential stress criterion is suitable for predicting the initiation angle of uniaxial and biaxial mixed-mode I–II fatigue cracks. The fatigue crack growth rate of a cruciform specimen with mode I and mixed-mode I–II cracks decreases with the increase of biaxial load ratio and increases with the stress ratio. The Walker model and Kujawski model have better compression effects on fatigue crack growth data than the Paris model.
Growth and Spectral Properties of Er3+ and Yb3+ Co-Doped Bismuth Silicate Single Crystal
Authors: Zhang Yan , Hu Shucheng , Tian Tian , Xiao Xuefeng , Chen Yuanzhi , Zhang Yan , Xu Jiayue
Published: October 2022

Rare-earth-doped bismuth silicate (Bi4Si3O12, BSO) crystal is a multifunctional material for scintillation, LED, and laser applications. In the present study, Er3+ and Yb3+ ions co-doped bismuth silicate crystals were grown by a modified vertical Bridgman method, and their spectral properties were investigated for the first time. Transparent Er/Yb: BSO single crystal up to Φ 25 mm × 30 mm was obtained. The segregation coefficient of the Er/Yb: BSO crystal was measured to be 0.96 for Er3+ ions and 0.91 for Yb3+ ions. Absorption and fluorescence spectra had been recorded in the range of 200–1700 nm. The absorption cross section was calculated to be 6.96 × 10−20 cm2 at 976 nm with the full width at half maximum (FWHM) of 8 nm, and the emission cross section was 0.9771 × 10−20 cm2 at 1543 nm with FWHM of 16 nm. The fluorescence decay curve was measured at 976 nm excitation. By linear fitting, the fluorescence lifetime of the upper 4I13/2 level of Er3+ was 8.464 ms at room temperature. Compared with Er3+ ion-doped bismuth silicate crystal (Er: BSO), the Er/Yb: BSO crystal has a wider FWHM and larger absorption cross section. The results indicate that the Er/Yb: BSO crystal is a potential lasing crystal.
Aquatic Insects in Habitat-Forming Sponges: The Case of the Lower Mekong and Conservation Perspectives in a Global Context
Authors: Ruengsawang Nisit , Sangpradub Narumon , Manconi Renata
Published: October 2022

Shallow water sponges settled on a raft along the Pong River (Lower Mekong Basin, Thailand) were investigated to highlight the taxonomic richness, composition, relative abundance and lifestyle of sponge-dwelling aquatic Insecta. The three-dimensional biogenic structures of the model sponges hosted 4 orders of Insecta, belonging to 10 families and 19 genera/species, able to strictly coexist at the level of the sponges in aquiferous canals and/or at the body surface, and/or dwelling in the extracellular matrix. On the basis of the identified 379 larvae and pupae, Trichoptera and Diptera were found to be the dominant inhabitants of Corvospongilla siamensis (Demospongiae: Spongillida), endemic to Southeast Asia. In the focused lotic ecosystem, dominated by soft bottoms, sponges play a functional role. Insecta use sponges as a substratum, nursery ground, food source, and shelter microhabitat, protecting them from predation and environmental aggression. Moreover, their feeding behavior indicates the insects’ adaptive traits to recycle sponge siliceous spicules as a source of exogenous material to strengthen the larval–pupal cases and the digestive system. The results of the Thai sponge model contribute to the inventory of global engineering species richness, ecosystem types, and biogeographic diversity, thus raising awareness for freshwater biodiversity conservation. In this regard, the present data, along with the worldwide inventory, focus on sponges as (a) key habitat-forming species for aquatic insect assemblages, (b) ecosystem engineers in river/lake/wetland ecosystems, providing water purification, the processing of organic matter, recycling of nutrients, and freshwater–terrestrial coupling, and (c) promising candidates in restoration projects of tropical freshwater ecosystems by bioremediation.
Economic Feasibility, Benefits and Challenges of On-Farm Artisanal Cheese Making in South Africa
Authors: Nyamakwere Faith , Esposito Giulia , Mombo Ozias , Raffrenato Emiliano
Published: October 2022

There is limited information regarding artisanal cheese making that can help entrepreneurs evaluate business opportunities and make realistic business decisions. The objective of this study was to assess the economic feasibility, benefits and challenges of on-farm artisanal cheese making. A model was designed to evaluate the economic feasibility of processing hard pecorino-style cheese and soft fresh ricotta on four different smallholder farms. The study assumed a small-scale family-owned business with an average herd size of 10 lactating cows, using 80 L of raw milk a day to make cheese. Projected Cash Flow Statement was used to determine the economic feasibility of cheese making. Sensitivity analysis was conducted using a factor of 10% to determine the changes in net cash flows by varying the milk volume, cheese selling price and both. The positive projected cash flow after the sensitivity analysis for the four farms ranged from $24,073.84 to $33,783.5. The breakeven quantity for the four farms ranged from 325.82 kg to 357.88 kg per year.Overall, the results show that artisanal cheese making is economically viable under the given model assumptions. However, the major challenge noted is that most farmers lack knowledge in terms of the processing techniques, market opportunities and production costs involved in cheese making. Access to this information by small-scale milk producers is vital in considering cheese making as a business.
In Vitro Major Arterial Cardiovascular Simulator to Generate Benchmark Data Sets for In Silico Model Validation
Authors: Wisotzki Michelle , Mair Alexander , Schlett Paul , Lindner Bernhard , Oberhardt Max , Bernhard Stefan
Published: October 2022

Cardiovascular diseases are commonly caused by atherosclerosis, stenosis and aneurysms. Understanding the influence of these pathological conditions on the circulatory mechanism is required to establish methods for early diagnosis. Different tools have been developed to simulate healthy and pathological conditions of blood flow. These simulations are often based on computational models that allow the generation of large data sets for further investigation. However, because computational models often lack some aspects of real-world data, hardware simulators are used to close this gap and generate data for model validation. The aim of this study is to develop and validate a hardware simulator to generate benchmark data sets of healthy and pathological conditions. The development process was led by specific design criteria to allow flexible and physiological simulations. The in vitro hardware simulator includes the major 33 arteries and is driven by a ventricular assist device generating a parametrised in-flow condition at the heart node. Physiologic flow conditions, including heart rate, systolic/diastolic pressure, peripheral resistance and compliance, are adjustable across a wide range. The pressure and flow waves at 17 + 1 locations are measured by inverted fluid-resistant pressure transducers and one ultrasound flow transducer, supporting a detailed analysis of the measurement data even for in silico modelling applications. The pressure and flow waves are compared to in vivo measurements and show physiological conditions. The influence of the degree and location of the stenoses on blood pressure and flow was also investigated. The results indicate decreasing translesional pressure and flow with an increasing degree of stenosis, as expected. The benchmark data set is made available to the research community for validating and comparing different types of computational models. It is hoped that the validation and improvement of computational simulation models will provide better clinical predictions.
An Automatic Method for Assessing Spiking of Tibial Tubercles Associated with Knee Osteoarthritis
Authors: Patron Anri , Annala Leevi , Lainiala Olli , Paloneva Juha , Äyrämö Sami
Published: October 2022

Efficient and scalable early diagnostic methods for knee osteoarthritis are desired due to the disease’s prevalence. The current automatic methods for detecting osteoarthritis using plain radiographs struggle to identify the subjects with early-stage disease. Tibial spiking has been hypothesized as a feature of early knee osteoarthritis. Previous research has demonstrated an association between knee osteoarthritis and tibial spiking, but the connection to the early-stage disease has not been investigated. We study tibial spiking as a feature of early knee osteoarthritis. Additionally, we develop a deep learning based model for detecting tibial spiking from plain radiographs. We collected and graded 913 knee radiographs for tibial spiking. We conducted two experiments: experiments A and B. In experiment A, we compared the subjects with and without tibial spiking using Mann-Whitney U-test. Experiment B consisted of developing and validating an interpretative deep learning based method for predicting tibial spiking. The subjects with tibial spiking had more severe Kellgren-Lawrence grade, medial joint space narrowing, and osteophyte score in the lateral tibial compartment. The developed method achieved an accuracy of 0.869. We find tibial spiking a promising feature in knee osteoarthritis diagnosis. Furthermore, the detection can be automatized.
Incorporation of Tumor-Free Distance and Other Alternative Ultrasound Biomarkers into a Myometrial Invasion-Based Model Better Predicts Lymph Node Metastasis in Endometrial Cancer: Evidence and Future Prospects
Authors: Liro Marcin , Śniadecki Marcin , Wycinka Ewa , Wojtylak Szymon , Brzeziński Michał , Jastrzębska Joanna , Wydra Dariusz
Published: October 2022

Myometrial invasion (MI) is a parameter currently used in transvaginal ultrasound (TVS) in endometrial cancer (EC) to determine local staging; however, without molecular diagnostics, it is insufficient for the selection of high-risk cases, i.e., those with a high risk of lymph node metastases (LNM). The study’s objective was to answer the question of which TVS markers, or their combination, reflecting the molecular changes in EC, can improve the prediction of LNM. Methods: The TVS examination was performed on 116 consecutive EC patients included in this prospective study. The results from the final histopathology were a reference standard. Univariate and multivariate logistic models of analyzed TVS biomarkers (tumor [T] size, T area [AREA], T volume [SPE-VOL], MI, T-free distance to serosa [TFD], endo-myometrial irregularity, [EMIR], cervical stromal involvement, CSI) were evaluated to assess the relative accuracy of the possible LNM predictors., Spline functions were applied to avoid a potential bias in assuming linear relations between LNM and continuous predictors. Calculations were made in R using libraries splines, glmulti, and pROC. Results: LNM was found in 20 out of the 116 (17%) patients. In univariate analysis, only uMI, EMIR, uCSI and uTFD were significant predictors of LNM. The accuracy was 0.707 (AUC 0.684, 95% CI 0.568–0.801) for uMI (p < 0.01), 0.672 (AUC 0.664, 95% CI 0.547–0.781) for EMIR (p < 0.01), 0.776 (AUC 0.647, 95% CI 0.529–0.765) for uCSI (p < 0.01), and 0.638 (AUC 0.683, 95% CI 0.563–0.803) for uTFD (p < 0.05). The cut-off value for uTFD was 5.2 mm. However, AREA and VOL revealed a significant relationship by nonlinear analysis as well. Among all possible multivariate models, the one comprising interactions of splines of uTFD with uMI and splines of SPE-VOL with uCSI showed the most usefulness. Accuracy was 0.802 (AUC 0.791, 95% CI 0.673–0.91) Conclusions: A combination of uTFD for patients with uMI > 50%, and SPE-VOL for patients with uCSI, allows for the most accurate prediction of LNM in EC, rather than uMI alone.
Vantera Mediated Quantification of Urine Citrate and Creatinine: A New Technology to Assess Risk of Nephrolithiasis
Authors: Matyus Steven P. , Wolak-Dinsmore Justyna , Garcia Erwin , Young Randolph M. , Connelly Margery A.
Published: October 2022

Urine citrate is often used to identify patients at risk of recurrent nephrolithiasis or kidney stones. A high-throughput assay was developed to measure urine citrate and creatinine on the Vantera® Clinical Analyzer, a nuclear magnetic resonance (NMR) instrument designed for the clinical laboratory. Assay performance was evaluated and comparisons between the NMR and chemistry results were conducted. Linearity was demonstrated over a wide range of concentrations for citrate (6 and 2040 mg/L) and creatinine (2.8 and 1308 mg/dL). Intra-and inter-assay precision (%CV) ranged from 0.9 to 3.7% for citrate and 0.4 to 2.1% for creatinine. The correlation coefficients for the comparison between NMR and chemistry results were 0.98 (Y = 1.00X + 5.0) for citrate and 0.96 (Y = 0.968X + 0.97) for creatinine. The reference intervals for both analytes were confirmed. Ten endogenous and exogenous substances were tested and none were found to interfere with the assay results. In conclusion, the newly developed high-throughput NMR assay exhibited robust performance and generated results comparable to the currently utilized chemistry tests, thereby providing an alternative means to simultaneously quantify urine citrate and creatinine for clinical and research use. Furthermore, the NMR assay does not exhibit the same interference limitations as the chemistry tests and it enables multiplexing with other urine metabolite assays which saves time and costs.
Mental Strategies in a P300-BCI: Visuomotor Transformation Is an Option
Authors: Syrov Nikolay , Yakovlev Lev , Nikolaeva Varvara , Kaplan Alexander , Lebedev Mikhail
Published: October 2022

Currently, P300-BCIs are mostly used for spelling tasks, where the number of commands is equal to the number of stimuli that evoke event-related potentials (ERPs). Increasing this number slows down the BCI operation because each stimulus has to be presented several times for better classification. Furthermore, P300 spellers typically do not utilize potentially useful imagery-based approaches, such as the motor imagery successfully practiced in motor rehabilitation. Here, we tested a P300-BCI with a motor-imagery component. In this BCI, the number of commands was increased by adding mental strategies instead of increasing the number of targets. Our BCI had only two stimuli and four commands. The subjects either counted target appearances mentally or imagined hand movements toward the targets. In this design, the motor-imagery paradigm enacted a visuomotor transformation known to engage cortical and subcortical networks participating in motor control. The operation of these networks suffers in neurological conditions such as stroke, so we view this BCI as a potential tool for the rehabilitation of patients. As an initial step toward the development of this clinical method, sixteen healthy participants were tested. Consistent with our expectation that mental strategies would result in distinct EEG activities, ERPs were different depending on whether subjects counted stimuli or imagined movements. These differences were especially clear in the late ERP components localized in the frontal and centro-parietal regions. We conclude that (1) the P300 paradigm is suitable for enacting visuomotor transformations and (2) P300-based BCIs with multiple mental strategies could be used in applications where the number of possible outputs needs to be increased while keeping the number of targets constant. As such, our approach adds to both the development of versatile BCIs and clinical approaches to rehabilitation.
Accuracy of Noninvasive Diagnostic Tests for the Detection of Significant and Advanced Fibrosis Stages in Nonalcoholic Fatty Liver Disease: A Systematic Literature Review of the US Studies
Authors: Gosalia Dhaval , Ratziu Vlad , Stanicic Filip , Vukicevic Djurdja , Zah Vladimir , Gunn Nadege , Halegoua-DeMarzio Dina , Tran Tram
Published: October 2022

Background: The purpose of this systematic literature review (SLR) was to evaluate the accuracy of noninvasive diagnostic tools in detecting significant or advanced (F2/F3) fibrosis among patients with nonalcoholic fatty liver (NAFL) in the US healthcare context. Methods: The SLR was conducted in PubMed and Web of Science, with an additional hand search of public domains and citations, in line with the PRISMA statement. The study included US-based original research on diagnostic test sensitivity, specificity and accuracy. Results: Twenty studies were included in qualitative evidence synthesis. Imaging techniques with the highest diagnostic accuracy in F2/F3 detection and differentiation were magnetic resonance elastography and vibration-controlled transient elastography. The most promising standard blood biomarkers were NAFLD fibrosis score and FIB-4. The novel diagnostic tools showed good overall accuracy, particularly a score composed of body mass index, GGT, 25-OH-vitamin D, and platelet count. The novel approaches in liver fibrosis detection successfully combine imaging techniques and blood biomarkers. Conclusions: While noninvasive techniques could overcome some limitations of liver biopsy, a tool that would provide a sufficiently sensitive and reliable estimate of changes in fibrosis development and regression is still missing.