bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation in an Independent Cohort of MiR-122, MiR-1271, and MiR-15b as Urinary Biomarkers for the Potential Early Diagnosis of Clear Cell Renal Cell Carcinoma
Authors: Cochetti Giovanni , Cari Luigi , Maulà Vincenza , Cagnani Rosy , Paladini Alessio , Del Zingaro Michele , Nocentini Giuseppe , Mearini Ettore
Published: February 2022

Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cell carcinoma, and the absence of symptoms in the early stages makes metastasis more likely and reduces survival. To aid in the early diagnosis of ccRCC, we recently developed a method based on urinary miR-122-5p, miR-1271-5p, and miR-15b-5p levels and three controls. The study here presented aimed to validate the previously published method through its application on an independent cohort. The expression of miRNAs in urine specimens from 28 ccRCC patients and 28 healthy subjects (HSs) of the same sex and age was evaluated by RT-qPCR. Statistical analyses were performed, including the preparation of receiver operating characteristic (ROC) curves. The mean ccRCC diameter in ccRCC patients was 4.2 ± 2.4 mm. Urinary miRNA levels were higher in patients than in HSs. The data were processed using the previously developed algorithm (7p-urinary score), and the area under the curve (AUC) of the algorithm’s ROC curve was 0.81 (p-value = 0.0003), with a sensitivity of 96% and specificity of 65%. Therefore, the 7p-urinary score is a potential tool for the early diagnosis of ccRCC.
Computer-Assisted Image Processing System for Early Assessment of Lung Nodule Malignancy
Authors: Shaffie Ahmed , Soliman Ahmed , Eledkawy Amr , van Berkel Victor , El-Baz Ayman
Published: February 2022

Lung cancer is one of the most dreadful cancers, and its detection in the early stage is very important and challenging. This manuscript proposes a new computer-aided diagnosis system for lung cancer diagnosis from chest computed tomography scans. The proposed system extracts two different kinds of features, namely, appearance features and shape features. For the appearance features, a Histogram of oriented gradients, a Multi-view analytical Local Binary Pattern, and a Markov Gibbs Random Field are developed to give a good description of the lung nodule texture, which is one of the main distinguishing characteristics between benign and malignant nodules. For the shape features, Multi-view Peripheral Sum Curvature Scale Space, Spherical Harmonics Expansion, and a group of some fundamental morphological features are implemented to describe the outer contour complexity of the nodules, which is main factor in lung nodule diagnosis. Each feature is fed into a stacked auto-encoder followed by a soft-max classifier to generate the initial malignancy probability. Finally, all these probabilities are combined together and fed to the last network to give the final diagnosis. The system is validated using 727 nodules which are subset from the Lung Image Database Consortium (LIDC) dataset. The system shows very high performance measures and achieves 92.55%, 91.70%, and 93.40% for the accuracy, sensitivity, and specificity, respectively. This high performance shows the ability of the system to distinguish between the malignant and benign nodules precisely.
Estrogen Receptor-Beta2 (ERβ2)–Mutant p53–FOXM1 Axis: A Novel Driver of Proliferation, Chemoresistance, and Disease Progression in High Grade Serous Ovarian Cancer (HGSOC)
Authors: Oturkar Chetan C. , Gandhi Nishant , Rao Pramod , Eng Kevin H. , Miller Austin , Singh Prashant K. , Zsiros Emese , Odunsi Kunle O. , Das Gokul M.
Published: February 2022

High grade serous ovarian cancer (HGSOC) is the most common and lethal subtype of epithelial ovarian cancer. Prevalence (~96%) of mutant p53 is a hallmark of HGSOC. Estrogen receptor-beta (ERβ) has been reported to be another important player in HGSOC, although the pro-versus anti-tumorigenic role of its different isoforms remains unsettled. However, whether there is functional interaction between ERβ and mutant p53 in HGSOC is unknown. ERβ1 and ERβ2 mRNA and protein analysis in HGSOC cell lines demonstrated that ERβ2 is the predominant isoform in HGSOC. Specificity of ERβ2 antibody was ascertained using cells depleted of ERβ2 and ERβ1 separately with isoform-specific siRNAs. ERβ2-mutant p53 interaction in cell lines was confirmed by co-immunoprecipitation and in situ proximity ligation assay (PLA). Expression levels of ERβ2, ERα, p53, and FOXM1 proteins and ERβ2-mutant p53 interaction in patient tumors were determined by immunohistochemistry (IHC) and PLA, respectively. ERβ2 levels correlate positively with FOXM1 levels and negatively with progression-free survival (PFS) and overall survival (OS). Quantitative chromatin immunoprecipitation (qChIP) and mRNA expression analysis revealed that ERβ2 and mutant p53 co-dependently regulated FOXM1 gene transcription. The combination of ERβ2-specific siRNA and PRIMA-1MET that converts mutant p53 to wild type conformation increased apoptosis. Our work provides the first evidence for a novel ERβ2-mutant p53-FOXM1 axis that can be exploited for new therapeutic strategies against HGSOC.
Angiogenesis: A Pivotal Therapeutic Target in the Drug Development of Gynecologic Cancers
Authors: Kasherman Lawrence , Liu Shiru (Lucy) , Karakasis Katherine , Lheureux Stephanie
Published: February 2022

Since the discovery of angiogenesis and its relevance to the tumorigenesis of gynecologic malignancies, a number of therapeutic agents have been developed over the last decade, some of which have become standard treatments in combination with other therapies. Limited clinical activity has been demonstrated with anti-angiogenic monotherapies, and ongoing trials are focused on combination strategies with cytotoxic agents, immunotherapies and other targeted treatments. This article reviews the science behind angiogenesis within the context of gynecologic cancers, the evidence supporting the targeting of these pathways and future directions in clinical trials.
Precision Oncology in Lower-Grade Gliomas: Promises and Pitfalls of Therapeutic Strategies Targeting IDH-Mutations
Authors: Persico Pasquale , Lorenzi Elena , Losurdo Agnese , Dipasquale Angelo , Di Muzio Antonio , Navarria Pierina , Pessina Federico , Politi Letterio Salvatore , Lombardi Giuseppe , Santoro Armando , Simonelli Matteo
Published: February 2022

Mutations in isocitrate dehydrogenase (IDH)1 and its homolog IDH2 are considered an earliest “driver” genetic event during gliomagenesis, representing now the molecular hallmark of lower-grade gliomas (LGGs). IDH-mutated genes encode for a neomorphic enzyme that converts α-ketoglutarate to the oncometabolite D-2-hydroxyglutarate (2-HG), which accumulates to high concentrations and alters cellular epigenetics and metabolism. Targeting IDH mutations is the first attempt to apply “precision oncology” in LGGs. Two distinct strategies have been proposed so far and are under intense clinical investigation: (i) reducing the amount of intratumoral 2-HG by directly blocking the function of mutant IDH enzyme; (ii) exploiting the selective epigenetic and metabolic cellular vulnerabilities as a consequence of 2-HG accumulation. The present review describes the physiopathological mechanisms by which IDH mutations lead to tumorigenesis, discussing their prognostic significance and pivotal role in the gliomas diagnostic classification system. We critically review preclinical evidence and available clinical data of first-generation mutant-selective IDH inhibitors and novel IDH-targeted vaccines. Finally, as an alternative and attractive approach, we present the rationale to take advantage of selective 2-HG related epigenetic and metabolic weaknesses. The results of ongoing clinical trials will help us clarify the complex scenario of IDH-targeted therapeutic approaches in gliomas.
Very Late Recurrence in Germ Cell Tumor of the Testis: Lessons and Implications
Authors: Moore Joseph A. , Slack Rebecca S. , Lehner Michael J. , Campbell Matthew T. , Shah Amishi Y. , Zhang Miao , Guo Charles C. , Ward John F. , Karam Jose A. , Wood Christopher G. , Pisters Louis L. , Tu Shi-Ming
Published: February 2022

Background. Very late recurrence (LR), i.e., >5 years after initial presentation, occurs in about 1% of patients with germ cell tumors of the testis (TGCT) and is associated with poor prognosis. Methods. We retrospectively reviewed the records of patients at the M. D. Anderson Cancer Center who developed LR > 5 years after their initial diagnosis of TGCT. Results. We identified 25 patients who developed LR between July 2007 and August 2020. The median age at the time of LR was 46 years (range, 29–61). Pathology of LR: somatic transformation to carcinoma or sarcoma—11, nonseminoma with yolk sac tumor or teratoma—11, nonseminoma without yolk sac tumor or teratoma—2, not available—1. With a median follow-up of 3.5 years, 68% of patients are alive 3 years after LR. Patients with prior post-chemotherapy consolidation surgery do not have statistically significant longer survival compared to patients who did not receive post-chemotherapy consolidation surgery, 83.3% vs. 60.8% at 3 years, respectively, p = 0.50. Conclusions. Patients with LR > 5 years tend to harbor nonseminoma (with yolk sac tumor and or teratoma). Among these patients, a majority who did not undergo surgery to remove residual disease after chemotherapy developed somatic transformation and succumbed to their LR.
NH3 and CO Emissions from Fifteen Euro 6d and Euro 6d-TEMP Gasoline-Fuelled Vehicles
Authors: Selleri Tommaso , Melas Anastasios , Bonnel Pierre , Suarez-Bertoa Ricardo
Published: February 2022

Ammonia (NH3) plays a key role in atmospheric chemistry and largely contributes to the PM2.5 measured in urban areas around the globe. For that reason, the National Emission Ceilings directive, Gothenburg Protocol under the United Nations Convention on Long-Range Transboundary Air Pollution, and International Panel for Climate Change (IPCC) directive required a reduction of the emissions of NH3. Nonetheless, the European Environment Agency (EEA) indicated that road transport emissions of NH3 have increased. Moreover, recent studies reported that, not only vehicle NH3 emissions are greater than agricultural emissions in areas that gather > 40% of the U.S. population, but urban emissions of NH3 for passenger cars are underestimated by a factor of 17 in UK. In this study, fifteen gasoline-fuelled vehicles, meeting the most recent European emission standards, Euro 6d or Euro 6d-TEMP, were investigated in laboratory tests over the type-approval worldwide-harmonized light-duty vehicles test cycle (WLTC), at 23 °C and −7 °C, as well as over the motorway cycle Bundesautobahn (BAB). Results show that all the vehicles tested emitted NH3 over the different duty cycles, and presented emissions level that are comparable to those previously reported for Euro 4–Euro 6b vehicles. Finally, good agreement between the CO and the NH3 emissions was registered during the acceleration events, and, in general, a fair correlation, with R2 > 0.75, was obtained, when comparing the CO and NH3 emissions of the studied vehicles.
Effectiveness of Eggshells as Natural Heterogeneous Catalysts for Transesterification of Rapeseed Oil with Methanol
Authors: Gaide Ieva , Makareviciene Violeta , Sendzikiene Egle
Published: February 2022

Heterogeneous catalysis has an advantage of easy separation of the catalyst after biodiesel is produced. CaO is known to be an efficient heterogeneous catalyst for biodiesel production. Taking into account that CaO is a key component of eggshells, the effectiveness of eggshells as a heterogeneous catalyst for rapeseed oil transesterification with methanol was investigated and optimal conditions of biodiesel production were determined applying RSM methodology. The influence of three independent variables on ester content was analyzed and a quadratic model was created. It was determined that this model is statistically significant. The optimum transesterification conditions when eggshells are used as a heterogeneous catalyst, and the process temperature of 64 °C, were determined as: the methanol-to-oil molar ratio 10.93:1; the catalyst amount 6.80 wt%; the reaction duration 9.48 h. The ester yield of 97.79 wt% was obtained under these conditions.
Photodegradation of Congo Red by Modified P25-Titanium Dioxide with Cobalt-Carbon Supported on SiO2 Matrix, DFT Studies of Chemical Reactivity
Authors: Hammud Hassan H. , Traboulsi Hassan , Karnati Ranjith Kumar , Bakir Esam M.
Published: February 2022

Congo red is a hazardous material in the environment. The present work describes the synthesis of TiO2/CoC@SiO2-bipy (1) and TiO2/CoC@SiO2-phen (2) nanocomposites for the photodegradation of azo-dye Congo red (CR) dye in aqueous solution, by combining pure TiO2 with CoC@SiO2-bipy (s1) and CoC@SiO2-phen (s2) nanoparticles. The prepared nanocomposites were evaluated in term of photocatalytic activity rates in aqueous solution using CR. The nanocomposites TiO2/CoC@SiO2-bipy (1) and TiO2/CoC@SiO2-phen (2) were prepared from TiO2 (75%) and CoC@SiO2-bipy (s1) or CoC@SiO2-phen (s2) (25%) (weight ratio). Ultra-sonication and milling were used to prepare the heterogeneous nano catalysts. The pH, initial dye concentration, and catalyst dosage appeared to have a significant impact on the photocatalytic degradation performance. Molecular oxygen and other active species played a significant role in the photocatalyst degradation of CR with sunlight energy (UV-index 5.0). The chemical reactions were accelerated depending upon electrophilicity (ω) and energy gap (Eg) of azo dye species CR-N=N, CR-N=NH and CR=N-NH species which were calculated by density function theory (DFT). It can be concluded that the rate of electron–hole recombination of the TiO2 catalyst, when adding CoC@SiO2-bipy (s1) or CoC@SiO2-phen (s2), not only enhances the degradation but also effectively removes toxic dye molecules and their by-products. The newly prepared TiO2/CoC@SiO2-bipy (1) nanocomposites showed increased photocatalytic efficiency at low catalyst dose and faster rate of degradation of Congo red compared to TiO2/CoC@SiO2-phen (2) and TiO2 catalysts. The novel catalysts (1) and (2) can be easily separated by centrifugation and filtration, from the reaction mixture compared to TiO2.
The Nature of Active Sites in the Pd/C-Catalyzed Hydrogenation/Hydrodeoxygenation of Benzaldehyde
Authors: Capelli Sofia , Cattaneo Stefano , Stucchi Marta , Vandegehuchte Bart D. , Chieregato Alessandro , Villa Alberto , Prati Laura
Published: February 2022

Hydrogenations and hydrodeoxygenations represent two of the most important reactions in the production of both bulk and fine chemicals. Despite the wide and long use of metal-based catalysts for this reaction, there is still some uncertainty with respect to the properties governing the catalyst activity. Using the hydrogenation of benzaldehyde as a model reaction, in this paper, we disclose the dominant parameters determining catalyst activity of Pd nanoparticles supported on a carbonaceous material (carbon nanoplates, GNP). In particular, several operating parameters of the catalyst synthesis were varied in order to obtain materials with differences in such physico-chemical properties as nanoparticle size, Pd oxidation state and Pd surface exposure. A linear correlation between catalyst activity and the amount of surface Pd(0) atoms was found; this dependence, maintained after catalyst recycling, pointed out the nature of the active site of the Pd/GNP catalyst represented by exposed Pd(0) species.
Sustained Elevated Circulating Activin A Impairs Global Longitudinal Strain in Pregnant Rats: A Potential Mechanism for Preeclampsia-Related Cardiac Dysfunction
Authors: Bakrania Bhavisha A. , Palei Ana C. , Bhattarai Umesh , Chen Yingjie , Granger Joey P. , Shahul Sajid
Published: February 2022

Mediators of cardiac injury in preeclampsia are not well understood. Preeclamptic women have decreased cardiac global longitudinal strain (GLS), a sensitive measure of systolic function that indicates fibrosis and tissue injury. GLS is worse in preeclampsia compared to gestational hypertension, despite comparable blood pressure, suggesting that placental factors may be involved. We previously showed that Activin A, a pro-fibrotic factor produced in excess by the placenta in preeclampsia, predicts impaired GLS postpartum. Here, we hypothesized that chronic excess levels of Activin A during pregnancy induces cardiac dysfunction. Rats were assigned to sham or activin A infusion (1.25–6 µg/day) on a gestational day (GD) 14 (n = 6–10/group). All animals underwent blood pressure measurement and comprehensive echocardiography followed by euthanasia and the collection of tissue samples on GD 19. Increased circulating activin A (sham: 0.59 ± 0.05 ng/mL, 6 µg/day: 2.8 ± 0.41 ng/mL, p < 0.01) was associated with impaired GLS (Sham: −22.1 ± 0.8%, 6 µg/day: −14.7 ± 1.14%, p < 0.01). Activin A infusion (6 µg/day) increased beta-myosin heavy chain expression in heart tissue, indicating cardiac injury. In summary, our findings indicate that increasing levels of activin A during pregnancy induces cardiac dysfunction and supports the concept that activin A may serve as a possible mediator of PE-induced cardiac dysfunction.
Role of Dietary Supplements and Probiotics in Modulating Microbiota and Bone Health: The Gut-Bone Axis
Authors: de Sire Alessandro , de Sire Roberto , Curci Claudio , Castiglione Fabiana , Wahli Walter
Published: February 2022

Osteoporosis is characterized by an alteration of bone microstructure with a decreased bone mineral density, leading to the incidence of fragility fractures. Around 200 million people are affected by osteoporosis, representing a major health burden worldwide. Several factors are involved in the pathogenesis of osteoporosis. Today, altered intestinal homeostasis is being investigated as a potential additional risk factor for reduced bone health and, therefore, as a novel potential therapeutic target. The intestinal microflora influences osteoclasts’ activity by regulating the serum levels of IGF-1, while also acting on the intestinal absorption of calcium. It is therefore not surprising that gut dysbiosis impacts bone health. Microbiota alterations affect the OPG/RANKL pathway in osteoclasts, and are correlated with reduced bone strength and quality. In this context, it has been hypothesized that dietary supplements, prebiotics, and probiotics contribute to the intestinal microecological balance that is important for bone health. The aim of the present comprehensive review is to describe the state of the art on the role of dietary supplements and probiotics as therapeutic agents for bone health regulation and osteoporosis, through gut microbiota modulation.
A Focused Review on Primary Graft Dysfunction after Clinical Lung Transplantation: A Multilevel Syndrome
Authors: Van Slambrouck Jan , Van Raemdonck Dirk , Vos Robin , Vanluyten Cedric , Vanstapel Arno , Prisciandaro Elena , Willems Lynn , Orlitová Michaela , Kaes Janne , Jin Xin , Jansen Yanina , Verleden Geert M. , Neyrinck Arne P. , Vanaudenaerde Bart M. , Ceulemans Laurens J.
Published: February 2022

Primary graft dysfunction (PGD) is the clinical syndrome of acute lung injury after lung transplantation (LTx). However, PGD is an umbrella term that encompasses the ongoing pathophysiological and -biological mechanisms occurring in the lung grafts. Therefore, we aim to provide a focused review on the clinical, physiological, radiological, histological and cellular level of PGD. PGD is graded based on hypoxemia and chest X-ray (CXR) infiltrates. High-grade PGD is associated with inferior outcome after LTx. Lung edema is the main characteristic of PGD and alters pulmonary compliance, gas exchange and circulation. A conventional CXR provides a rough estimate of lung edema, while a chest computed tomography (CT) results in a more in-depth analysis. Macroscopically, interstitial and alveolar edema can be distinguished below the visceral lung surface. On the histological level, PGD correlates to a pattern of diffuse alveolar damage (DAD). At the cellular level, ischemia-reperfusion injury (IRI) is the main trigger for the disruption of the endothelial-epithelial alveolar barrier and inflammatory cascade. The multilevel approach integrating all PGD-related aspects results in a better understanding of acute lung failure after LTx, providing novel insights for future therapies.
Normal and Neoplastic Growth Suppression by the Extended Myc Network
Authors: Prochownik Edward V. , Wang Huabo
Published: February 2022

Among the first discovered and most prominent cellular oncogenes is MYC, which encodes a bHLH-ZIP transcription factor (Myc) that both activates and suppresses numerous genes involved in proliferation, energy production, metabolism and translation. Myc belongs to a small group of bHLH-ZIP transcriptional regulators (the Myc Network) that includes its obligate heterodimerization partner Max and six “Mxd proteins” (Mxd1–4, Mnt and Mga), each of which heterodimerizes with Max and largely opposes Myc’s functions. More recently, a second group of bHLH-ZIP proteins (the Mlx Network) has emerged that bears many parallels with the Myc Network. It is comprised of the Myc-like factors ChREBP and MondoA, which, in association with the Max-like member Mlx, regulate smaller and more functionally restricted repertoires of target genes, some of which are shared with Myc. Opposing ChREBP and MondoA are heterodimers comprised of Mlx and Mxd1, Mxd4 and Mnt, which also structurally and operationally link the two Networks. We discuss here the functions of these “Extended Myc Network” members, with particular emphasis on their roles in suppressing normal and neoplastic growth. These roles are complex due to the temporal- and tissue-restricted expression of Extended Myc Network proteins in normal cells, their regulation of both common and unique target genes and, in some cases, their functional redundancy.
Circulating Serum MiRNA-8074 as a Novel Prognostic Biomarker for Multiple Myeloma
Authors: Szudy-Szczyrek Aneta , Mlak Radosław , Mielnik Michał , Mazurek Marcin , Chocholska Sylwia , Podgajna Martyna , Szczyrek Michał , Homa-Mlak Iwona , Małecka-Massalska Teresa , Hus Marek
Published: February 2022

MiRNA-8074 is a molecule with the potential to regulate the expression of key genes related to the pathogenesis of multiple myeloma (MM), i.e., TP53, MYC, MAPK1, and KIAA. We analyzed the predictive and prognostic value of miRNA-8074 expression in MM patients. In total, 105 newly diagnosed MM patients treated with thalidomide (n = 27), bortezomib (n = 41) and bortezomib with thalidomide (n = 37) were studied. For miRNA analysis, the column method and the Real-Time PCR technique with specific TaqMan Fast Advanced Master Mix and TaqMan probes were used. Factors that were associated with a significant reduction in progression-free survival (PFS) included: ECOG > 1, ISS stage III, low hemoglobin, thrombocytopenia, hypoalbuminemia, abnormal renal function, elevated creatinine, GFR < 60 mL/min/1.73 m2, elevated LDH, del(17p), t(11;14), the use of a single drug regimen (thalidomide or bortezomib) and high miRNA-8074 expression (HR = 2.01, 95% CI: 1.16–3.49; p = 0.0233). In addition to the known prognostic factors, such as ECOG > 1, Durie–Salmon stage III, diagnosis of light chain disease or non-secreting MM, renal failure, hypoalbuminemia, hypercalcemia, high β2-microglobulin, elevated LDH, and t(14;16), a high expression of miRNA-8074 was significantly associated with a higher risk of death (HR = 4.12, 95% CI: 2.20–7.70; p = 0.0009). In summary, miRNA-8074 may be a useful diagnostic tool to assess the prognosis in MM patients.
Ghrelin Acylation—A Post-Translational Tuning Mechanism Regulating Adult Hippocampal Neurogenesis
Authors: Sassi Martina , Morgan Alwena H. , Davies Jeffrey S.
Published: February 2022

Adult hippocampal neurogenesis—the generation of new functional neurones in the adult brain—is impaired in aging and many neurodegenerative disorders. We recently showed that the acylated version of the gut hormone ghrelin (acyl-ghrelin) stimulates adult hippocampal neurogenesis while the unacylated form of ghrelin inhibits it, thus demonstrating a previously unknown function of unacyl-ghrelin in modulating hippocampal plasticity. Analysis of plasma samples from Parkinson’s disease patients with dementia demonstrated a reduced acyl-ghrelin:unacyl-ghrelin ratio compared to both healthy controls and cognitively intact Parkinson’s disease patients. These data, from mouse and human studies, suggest that restoring acyl-ghrelin signalling may promote the activation of pathways to support memory function. In this short review, we discuss the evidence for ghrelin’s role in regulating adult hippocampal neurogenesis and the enzymes involved in ghrelin acylation and de-acylation as targets to treat mood-related disorders and dementia.
Pseudotime Analysis Reveals Exponential Trends in DNA Methylation Aging with Mortality Associated Timescales
Authors: Lapborisuth Kalsuda , Farrell Colin , Pellegrini Matteo
Published: February 2022

The epigenetic trajectory of DNA methylation profiles has a nonlinear relationship with time, reflecting rapid changes in DNA methylation early in life that progressively slow with age. In this study, we use pseudotime analysis to determine the functional form of these trajectories. Unlike epigenetic clocks that constrain the functional form of methylation changes with time, pseudotime analysis orders samples along a path, based on similarities in a latent dimension, to provide an unbiased trajectory. We show that pseudotime analysis can be applied to DNA methylation in human blood and brain tissue and find that it is highly correlated with the epigenetic states described by the Epigenetic Pacemaker. Moreover, we show that the pseudotime trajectory can be modeled with respect to time, using a sum of two exponentials, with coefficients that are close to the timescales of human age-associated mortality. Thus, for the first time, we can identify age-associated molecular changes that appear to track the exponential dynamics of mortality risk.
New Immunometabolic Strategy Based on Cell Type-Specific Metabolic Reprogramming in the Tumor Immune Microenvironment
Authors: Sung Ji-Yong , Cheong Jae-Ho
Published: February 2022

Immunometabolism is an emerging discipline in cancer immunotherapy. Tumor tissues are heterogeneous and influenced by metabolic reprogramming of the tumor immune microenvironment (TIME). In the TIME, multiple cell types interact, and the tumor and immune cells compete for limited nutrients, resulting in altered anticancer immunity. Therefore, metabolic reprogramming of individual cell types may influence the outcomes of immunotherapy. Understanding the metabolic competition for access to limited nutrients between tumor cells and immune cells could reveal the breadth and complexity of the TIME and aid in developing novel therapeutic approaches for cancer. In this review, we highlight that, when cells compete for nutrients, the prevailing cell type gains certain advantages over other cell types; for instance, if tumor cells prevail against immune cells for nutrients, the former gains immune resistance. Thus, a strategy is needed to selectively suppress such resistant tumor cells. Although challenging, the concept of cell type-specific metabolic pathway inhibition is a potent new strategy in anticancer immunotherapy.
Combining HDAC and MEK Inhibitors with Radiation against Glioblastoma-Derived Spheres
Authors: Essien Eno I. , Hofer Thomas P. , Atkinson Michael J. , Anastasov Nataša
Published: February 2022

Glioblastoma stem-like cells (GSLCs) in glioblastoma limit effective treatment and promote therapeutic resistance and tumor recurrence. Using a combined radiation and drug-screening platform, we tested the combination of a histone deacetylase inhibitor (HDACi) and MAPK/ERK kinase inhibitor (MEKi) with radiation to predict the efficacy against GSLCs. To mimic a stem-like phenotype, glioblastoma-derived spheres were used and treated with a combination of HDACi (MS-275) and MEKi (TAK-733 or trametinib) with 4 Gy irradiation. The sphere-forming ability after the combined radiochemotherapy was investigated using a sphere formation assay, while the expression levels of the GSLC markers (CD44, Nestin and SOX2) after treatment were analyzed using Western blotting and flow cytometry. The combined radiochemotherapy treatment inhibited the sphere formation in both glioblastoma-derived spheres, decreased the expression of the GSLC markers in a cell-line dependent manner and increased the dead cell population. Finally, we showed that the combined treatment with radiation was more effective at reducing the GSLC markers compared to the standard treatment of temozolomide and radiation. These results suggest that combining HDAC and MEK inhibition with radiation may offer a new strategy to improve the treatment of glioblastoma.
FT-IR Spectral Signature of Sensitive and Multidrug-Resistant Osteosarcoma Cell-Derived Extracellular Nanovesicles
Authors: Perut Francesca , Graziani Gabriela , Roncuzzi Laura , Zini Nicoletta , Avnet Sofia , Baldini Nicola
Published: February 2022

Osteosarcoma (OS) is the most common primary bone cancer in children and adolescents. Despite aggressive treatment regimens, the outcome is unsatisfactory, and multidrug resistance (MDR) is a pivotal process in OS treatment failure. OS-derived extracellular vesicles (EVs) promote drug resistance to chemotherapy and target therapy through different mechanisms. The aim of this study was to identify subpopulations of osteosarcoma-EVs by Fourier transform infrared spectroscopy (FT-IR) to define a specific spectral signature for sensitive and multidrug-resistant OS-derived EVs. EVs were isolated from sensitive and MDR OS cells as well as from mesenchymal stem cells by differential centrifugation and ultracentrifugation. EVs size, morphology and protein expression were characterized. FT-IR/ATR of EVs spectra were acquired in the region of 400–4000 cm−1 (resolution 4 cm−1, 128 scans). The FT-IR spectra obtained were consistently different in the EVs compared to cells from which they originate. A specific spectral signature, characterized by a shift and a new band (1601 cm−1), permitted to clearly distinguish EVs isolated by sensitive and multidrug-resistant OS cells. Our data suggest that FT-IR spectroscopy allows to characterize and define a specific spectral signature for sensitive and MDR OS-derived EVs.
Maintaining Golgi Homeostasis: A Balancing Act of Two Proteolytic Pathways
Authors: Benyair Ron , Eisenberg-Lerner Avital , Merbl Yifat
Published: February 2022

The Golgi apparatus is a central hub for cellular protein trafficking and signaling. Golgi structure and function is tightly coupled and undergoes dynamic changes in health and disease. A crucial requirement for maintaining Golgi homeostasis is the ability of the Golgi to target aberrant, misfolded, or otherwise unwanted proteins to degradation. Recent studies have revealed that the Golgi apparatus may degrade such proteins through autophagy, retrograde trafficking to the ER for ER-associated degradation (ERAD), and locally, through Golgi apparatus-related degradation (GARD). Here, we review recent discoveries in these mechanisms, highlighting the role of the Golgi in maintaining cellular homeostasis.
Transcriptome Differences in Normal Human Bronchial Epithelial Cells in Response to Influenza A pdmH1N1 or H7N9 Virus Infection
Authors: Hsieh Tzu-Hsuan , Lin Ya-Jhu , Hsioa Mei-Jen , Wang Hsin-Ju , Chen Lu-Ting , Yang Shu-Li , Huang Chung-Guei
Published: February 2022

Avian influenza A (H7N9) virus infections frequently lead to acute respiratory distress syndrome and death in humans. The emergence of H7N9 virus infections is a serious public health threat. To identify virus–host interaction differences between the highly virulent H7N9 and pandemic influenza H1N1 (pdmH1N1), RNA sequencing was performed of normal human bronchial epithelial (NHBE) cells infected with either virus. The transcriptomic analysis of host cellular responses to viral infection enables the identification of potential cellular factors related to infection. Significantly different gene expression patterns were found between pdmH1N1- and H7N9-infected NHBE cells. In addition, the H7N9 virus infection induced strong immune responses, while cellular repair mechanisms were inhibited. The differential expression of specific factors observed between avian H7N9 and pdmH1N1 influenza virus strains can account for variations in disease pathogenicity. These findings provide a framework for future studies examining the molecular mechanisms underlying the pathogenicity of avian H7N9 virus.
Misreporting of Energy Intake Is Related to Specific Food Items in Low-Middle Income Chilean Adolescents
Authors: Martínez-Arroyo Angela , Duarte Batista Lais , Corvalán Aguilar Camila , Fisberg Regina Mara
Published: February 2022

Background: Misreporting of energy intake (EI) in self-reported dietary assessment is inevitable, and even less is known about which food items are misreported by low-middle income adolescents. We evaluated the prevalence of misreporting of energy intake and its relationship with nutrients and food intake. Methods: We analyzed 24 h dietary recalls collected from 576 adolescents (52.08% boys) from southeastern Santiago. Anthropometrics measurements and information about sociodemographic characteristics were obtained during clinical visits. The method proposed by McCrory et al. was used to identify under-reporters (UnRs), over-reporters (OvRs), or plausible reporters (PRs). Food items were collapsed into 28 categories and every food item was expressed as a percentage of total EI. Logistic regression models were performed to investigate the factors associated with misreporting, and a two-part model was used to estimate the difference in the percentage of EI between UnRs versus PRs, and OvRs versus PRs in each food item. Results: Half of the participants were classified as UnRs and 9% were OvRs. UnR was higher among boys (62%) and adolescents with overweight and obesity (72%). OvR was higher among adolescents with normal weight. UnRs had a lower intake of energy from cookies/cake, chocolate/confectionery, and a higher intake of vegetables and eggs than PRs. OvRs had a higher intake of cookies/cake, chocolate/confectionery, and a lower intake of fruit, white milk, and yogurt than PRs. Conclusions: A high frequency of UnR among boys and participants with excess weight was found in this study. Healthy and unhealthy foods are reported differently between UnRs and OvRs of energy intake, indicating that bias is specific for some food items that adolescents commonly eat.
Vesicoscopic Cross-Trigonal Ureteral Reimplantation for Vesicoureteral Reflux: Intermediate Results
Authors: Kruppa Christian , Fitze Guido , Schuchardt Katrin
Published: February 2022

For the treatment of vesicoureteral reflux, the introduction of vesicoscopic procedures offers new perspectives for improving patient comfort and quality. Our aim was to examine whether minimally invasive vesicoscopic cross-trigonal ureteral reimplantation (VCUR) would meet expectations. Between 2012 and 2021, 99 girls and 35 boys with high-grade vesicoureteral reflux (VUR) underwent VCUR. For two boys, we failed to establish the pneumovesicum, leading to conversion to open surgery. The mean age was 4.5 years, ranging from 10 months to 18 years. VCUR was successfully performed in 132 patients, including 75 patients with bilateral VUR and 12 children with double ureters with unilateral or bilateral VUR, corresponding to a total of 229 operated ureters. The mean time of operation was 151 min for all patients. There were no perioperative complications, with the exception of three cases of pneumoperitoneum without consequences. Postoperatively, we recognized three cases of acute hydronephrosis, two of them required transient drainage. Three patients developed extravasation of urine after the postoperative removal of the transurethral catheter, rapidly resolved by new drainage. In two patients, we combined VCUR with laparoscopic heminephrectomy and opposite laparoscopic nephrectomy, respectively. Overall, mean postoperative hospital stay was 4.2 days. We observed recurrent VUR in seven ureters, resulting in a success rate for VCUR of 96.9%. These results demonstrate the feasibility of VCUR and its potential to displace open surgery with high safety and wide applicability.
Mixed Convection Flow of Magnetized Casson Nanofluid over a Cylindrical Surface
Authors: Alwawi Firas A. , Hamarsheh Abdulkareem Saleh , Alkasasbeh Hamzeh T. , Idris Ruwaidiah
Published: February 2022

This work aimed to establish a numerical simulation of kerosene oil as a host Casson fluid flowing around a cylindrical shape with an applied magnetic field crossing through it, under constant wall temperature boundary conditions. Nanoparticles of zinc, aluminum, and titanium oxides were included to reinforce its thermal characteristics. The governing model was established based on the Tiwari and Das model. Graphical and numerical results for correlated physical quantities were gained through the Keller Box method, with the assistance of MATLAB software (9.2). The combined convection (λ>0 & λ<0), magnetic parameter (M>0), Casson parameter (β>0), and nanosolid volume fraction (0.1≤χ≤0.2) were the parameter ranges considered in this study. According to the current findings, the growth of mixed convection parameter or volume fraction of ultrafine particles contributes to boosting the rate of energy transport, skin friction, and velocity distribution. Zinc oxide–kerosene oil has the highest velocity and temperature, whatever the parameters influencing it.
Nondetectable Prostate Carcinoma (pT0) after Radical Prostatectomy: A Narrative Review
Authors: Kalampokis Nikolaos , Grivas Nikolaos , Karavitakis Markos , Leotsakos Ioannis , Katafigiotis Ioannis , Moschovas Marcio Covas , van der Poel Henk ,   European Association of Urology (EAU) Young Academic Urologists (YAU) Robotic Urology Working Group
Published: February 2022

(1) Background: Following radical prostatectomy (RP), the absence of a demonstrable tumor on the specimen of a previously histologically proven malignancy is known as the pT0 stage. The aim of our present study is to perform a narrative review of current literature in order to determine the frequency and oncological outcomes in patients with pT0 disease. (2) Methods: A narrative review of all available literature was performed. (3) Results: The incidence of pT0 ranges between 0.07% and 1.3%. Predictors of the pT0 stage are only a single biopsy core with low-grade cancer, a cancer length not exceeding 2 mm and a high prostate volume. Biochemical recurrence ranges between 0 and 11%. (4) Conclusions: The absence of malignancy in the RP specimen despite a previous positive biopsy is a rare and unpredictable finding. Although the prognosis is considered to be excellent in most of the cases, a continued close follow-up is warranted.
Spatiotemporal Variation in Coral Assemblages and Reef Habitat Complexity among Shallow Fore-Reef Sites in the Florida Keys National Marine Sanctuary
Authors: Simmons Kayelyn R. , Bohnenstiehl DelWayne R. , Eggleston David B.
Published: February 2022

With the unprecedented degradation and loss of coral reefs at multiple scales, the underlying changes in abiotic and biotic features relevant to the three-dimensional architecture of coral reefs are critical to conservation and restoration. This study characterized the spatiotemporal variation of habitat metrics at eight fore-reef sites representing three management zones in the Florida Keys, USA using visual habitat surveys (2017–2018) acquired before and after Hurricane Irma. Post-hurricane, five of those sites were surveyed using structure-from-motion photogrammetry to further investigate coral morphology on structural complexity. Multivariate results for visual surveys identified moderate separation among sites, with fished sites characterized by complex physical features such as depth and vertical hard relief while protected sites generally harbored high abundances of live coral cover. Three-dimensional models of mapped sites showed within site variation as another driver in site separation. Additionally, fine-scale orthoimage analyses identified significant differences in dominant coral morphologies at each mapped site. This study suggests protected reef sites generally harbor higher live coral cover despite some fished sites being structurally similar in seabed topography. Our work provides fine-scale spatial data on several managed sites within a marine sanctuary and highlights the contribution of diverse coral assemblages to the coral reef framework.
Gaps in Monitoring Leave Northern Australian Mammal Fauna with Uncertain Futures
Authors: Preece Noel , Fitzsimons James
Published: February 2022

Northern Australian biomes hold high biodiversity values within largely intact vegetation complexes, yet many species of mammals, and some other taxa, are endangered. Recently, six mammal species were added to the 20 or so already listed in the Australian endangered category. Current predictions suggest that nine species of mammal in northern Australia are in imminent danger of extinction within 20 years. We examine the robustness of the assumptions of status and trends in light of the low levels of monitoring of species and ecosystems across northern Australia, including monitoring the effects of management actions. The causes of the declines include a warming climate, pest species, changed fire regimes, grazing by introduced herbivores, and diseases, and work to help species and ecosystems recover is being conducted across the region. Indigenous custodians who work on the land have the potential and capacity to provide a significant human resource to tackle the challenge of species recovery. By working with non-Indigenous researchers and conservation managers, and with adequate support and incentives, many improvements in species’ downward trajectories could be made. We propose a strategy to establish a network of monitoring sites based on a pragmatic approach by prioritizing particular bioregions. The policies that determine research and monitoring investment need to be re-set and new and modified approaches need to be implemented urgently. The funding needs to be returned to levels that are adequate for the task. At present resourcing levels, species are likely to become extinct through an avoidable attrition process.
A Mixture Hidden Markov Model to Mine Students’ University Curricula
Authors: Bacci Silvia , Bertaccini Bruno
Published: February 2022

In the context of higher education, the wide availability of data gathered by universities for administrative purposes or for recording the evolution of students’ learning processes makes novel data mining techniques particularly useful to tackle critical issues. In Italy, current academic regulations allow students to customize the chronological sequence of courses they have to attend to obtain the final degree. This leads to a variety of sequences of exams, with an average time taken to obtain the degree that may significantly differ from the time established by law. In this contribution, we propose a mixture hidden Markov model to classify students into groups that are homogenous in terms of university paths, with the aim of detecting bottlenecks in the academic career and improving students’ performance.
Virtual Non-Contrast Reconstructions of Photon-Counting Detector CT Angiography Datasets as Substitutes for True Non-Contrast Acquisitions in Patients after EVAR—Performance of a Novel Calcium-Preserving Reconstruction Algorithm
Authors: Decker Josua A. , Bette Stefanie , Scheurig-Muenkler Christian , Jehs Bertram , Risch Franka , Woźnicki Piotr , Braun Franziska M. , Haerting Mark , Wollny Claudia , Kroencke Thomas J. , Schwarz Florian
Published: February 2022

The purpose of this study was to evaluate virtual-non contrast reconstructions of Photon-Counting Detector (PCD) CT-angiography datasets using a novel calcium-preserving algorithm (VNCPC) vs. the standard algorithm (VNCConv) for their potential to replace unenhanced acquisitions (TNC) in patients after endovascular aneurysm repair (EVAR). 20 EVAR patients who had undergone CTA (unenhanced and arterial phase) on a novel PCD-CT were included. VNCConv- and VNCPC-series were derived from CTA-datasets and intraluminal signal and noise compared. Three readers evaluated image quality, contrast removal, and removal of calcifications/stent parts and assessed all VNC-series for their suitability to replace TNC-series. Image noise was higher in VNC- than in TNC-series (18.6 ± 5.3 HU, 16.7 ± 7.1 HU, and 14.9 ± 7.1 HU for VNCConv-, VNCPC-, and TNC-series, p = 0.006). Subjective image quality was substantially higher in VNCPC- than VNCConv-series (4.2 ± 0.9 vs. 2.5 ± 0.6; p < 0.001). Aortic contrast removal was complete in all VNC-series. Unlike in VNCConv-reconstructions, only minuscule parts of stents or calcifications were erroneously subtracted in VNCPC-reconstructions. Readers considered 95% of VNCPC-series fully or mostly suited to replace TNC-series; for VNCConv-reconstructions, however, only 75% were considered mostly (and none fully) suited for TNC-replacement. VNCPC-reconstructions of PCD-CT-angiography datasets have excellent image quality with complete contrast removal and only minimal erroneous subtractions of stent parts/calcifications. They could replace TNC-series in almost all cases.
Comparison of the Amplitude of Accommodation Measured Using a New-Generation Closed-Field Autorefractor with Conventional Subjective Methods
Authors: Kanclerz Piotr , Pluta Karolina , Momeni-Moghaddam Hamed , Khoramnia Ramin
Published: February 2022

Purpose: This study aims to compare and assess the agreement of the objective amplitude of accommodation (AA) measured using a new-generation closed-field autorefractor with conventional subjective methods. Methods: In total, 84 healthy individuals with an age range of 19 to 50 years participated in this cross-sectional study. AA was measured objectively with a Nidek autorefractor (AR-1a; Nidek Co., Ltd., Tokyo, Japan) and subjectively using push-up (PU) and minus-lens (ML) methods in a random order. Comparison between different methods was performed using repeated-measures analysis of variance and the Bonferroni test for pairwise comparisons. In addition to the Pearson correlation, the Bland and Altman method and the intraclass correlation coefficient were used to determine the agreement between the three techniques. Only the right-eye results were used for analysis. Results: AA measured using the Nidek autorefractor (3.43 ± 1.94 D) was significantly lower than that measured with PU (7.67 ± 2.38 D; p < 0.001) and ML (7.60 ± 2.81 D; p < 0.001) methods. The difference between the subjective methods was not significant statistically (p = 1.0). The correlation for Nidek measurements and PU and ML methods was moderate (r = 0.5502 and r = 0.6832, respectively), while it was strong when comparing subjective methods (r = 0.7821). The limits of agreement for Nidek vs. PU, Nidek vs. ML, and PU vs. ML methods were −8.28 to −0.23 D, −8.19 to −0.15 D, and −3.38 to 3.51 D, respectively. Conclusions: There was a moderate agreement between AA obtained with subjective methods and objective Nidek measurements. The objective AA measurements obtained with a new Nidek autorefractor were significantly lower than subjective measurements.