bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of the Share of Solar Power in China Based on FGM (1,1) Model
Authors: Li Yuhan , Wang Shuya , Dai Wei , Wu Liusan
Published: October 2022

In recent years, fossil energy reserves have decreased year by year, and the development and use of renewable energy has attracted great attention of governments all over the world. China continues to promote the high-quality development of renewable energy such as solar power generation. Accurate prediction of the share of solar power in China is beneficial to implementing the goals of carbon peaking and carbon neutralization. According to the website of China’s National Bureau of statistics, the earliest annual data of China’s solar power generation is 2017, which leads to there being very few data on the share of China’s solar power generation. Therefore, the prediction accuracy of most prediction methods is low, and the advantages of the grey prediction model are shown. Based on the share of solar power in China from 2017 to 2020, this paper constructs an FGM (1,1) model, calculates r using the Particle Swarm Optimization (PSO) algorithm, and predicts the share of solar power in China in the next few years. r = 0.3858 and MAPE = 0.20% were obtained by calculation of the model. The prediction results show that the share of solar power generation in China will increase year by year, and it will reach about 4.2301% by 2030. In addition, it is found that the share of China’s solar power generation in 2021 is 2.1520%, and the predicted value is 2.1906%. It can be seen that the prediction error is small. Finally, the limitations and future research directions are elucidated. The prediction results presented in this paper will help to guide the development of solar power generation in China, and are of great significance in speeding up the pace of energy structural adjustment, accelerating the construction of a clean, low-carbon, safe and efficient energy system, and promoting sustainable development.
Advances in Molecular Biomarkers in Cardiology
Authors: Scicchitano Pietro , Cameli Matteo
Published: October 2022

Cardiovascular diseases (CVD) represent the leading cause of death in the world despite innovations in therapies and advances in the general management of patients [...]
Gerstmann–Sträussler–Scheinker Disease with F198S Mutation Induces Independent Tau and Prion Protein Pathologies in Bank Voles
Authors: Bruno Rosalia , Pirisinu Laura , Riccardi Geraldina , D’Agostino Claudia , De Cecco Elena , Legname Giuseppe , Cardone Franco , Gambetti Pierluigi , Nonno Romolo , Agrimi Umberto , Di Bari Michele Angelo
Published: October 2022

Gerstmann–Sträussler–Scheinker disease (GSS) is a rare genetic prion disease. A large GSS kindred linked to the serine-for-phenylalanine substitution at codon 198 of the prion protein gene (GSS-F198S) is characterized by conspicuous accumulation of prion protein (PrP)-amyloid deposits and neurofibrillary tangles. Recently, we demonstrated the transmissibility of GSS-F198S prions to bank vole carrying isoleucine at 109 PrP codon (BvI). Here we investigated: (i) the transmissibility of GSS-F198S prions to voles carrying methionine at codon 109 (BvM); (ii) the induction of hyperphosphorylated Tau (pTau) in two vole lines, and (iii) compared the phenotype of GSS-F198S-induced pTau with pTau induced in BvM following intracerebral inoculation of a familial Alzheimer’s disease case carrying Presenilin 1 mutation (fAD-PS1). We did not detect prion transmission to BvM, despite the high susceptibility of BvI previously observed. Immunohistochemistry established the presence of induced pTau depositions in vole brains that were not affected by prions. Furthermore, the phenotype of pTau deposits in vole brains was similar in GSS-F198S and fAD-PS1. Overall, results suggest that, regardless of the cause of pTau deposition and its relationship with PrPSc in GSS-F198S human-affected brains, the two components possess their own seeding properties, and that pTau deposition is similarly induced by GSS-F198S and fAD-PS1.
Regulation of CD4 T Cell Responses by the Transcription Factor Eomesodermin
Authors: Dhume Kunal , Kaye Brandon , McKinstry K. Kai
Published: October 2022

Central to the impacts of CD4 T cells, both positive in settings of infectious disease and cancer and negative in the settings of autoimmunity and allergy, is their ability to differentiate into distinct effector subsets with specialized functions. The programming required to support such responses is largely dictated by lineage-specifying transcription factors, often called ‘master regulators’. However, it is increasingly clear that many aspects of CD4 T cell immunobiology that can determine the outcomes of disease states involve a broader transcriptional network. Eomesodermin (Eomes) is emerging as an important member of this class of transcription factors. While best studied in CD8 T cells and NK cells, an increasing body of work has focused on impacts of Eomes expression in CD4 T cell responses in an array of different settings. Here, we focus on the varied impacts reported in these studies that, together, indicate the potential of targeting Eomes expression in CD4 T cells as a strategy to improve a variety of clinical outcomes.
The Characterization of Binding between Aptamer and Bisphenol A and Developing Electrochemical Aptasensors for Bisphenol A with Rationally Engineered Aptamers
Authors: Liu Liying , Yu Hao , Zhao Qiang
Published: October 2022

Bisphenol A (BPA) is widely used in the manufacture of polycarbonate and epoxy-resin-based products, and BPA contamination often happens in a variety of types of environment and food stuffs. BPA can cause many harmful effects to health due to its high toxicity. The rapid detection of BPA is of great significance in environmental monitoring and food safety. Nucleic acid aptamers show advantages in biosensors due to good chemical stability, the ease of labeling functional groups, and target binding that induces conformation change. Here, we performed a thorough characterization of the binding performance of one 60-nt anti-BPA DNA aptamer with isothermal titration calorimetry (ITC). We found the crucial region of the aptamer sequence for affinity binding with BPA, and the aptamer was able to be truncated to 29-nt DNA without losing affinity. We then developed a simple reagent-less electrochemical aptamer-based sensor for rapid BPA detection with this engineered aptamer. The truncated aptamer with a redox tag methylene blue (MB) was immobilized on a gold electrode. BPA-binding induced the conformation change of the MB-labeled aptamer, moving the MB close to the electrode surface and causing a significant current increase in MB in square wave voltammetry (SWV). Under optimized conditions, we achieved the quantitative detection of BPA with a detection limit of BPA at 0.1 μM. This sensor showed quick response to BPA and could be regenerated by washing with deionized water. This sensor was selective, and it allowed detecting BPA in complex samples, showing its potential in practice. This study will help in further applications of the aptamers of BPA.
Dynamic Detection of HbA1c Using a Silicon Nanowire Field Effect Tube Biosensor
Authors: Chen Hang , Deng Lijuan , Sun Jialin , Li Hang , Zhu Xiaoping , Wang Tong , Jiang Yanfeng
Published: October 2022

As an emerging diabetes diagnostic indicator and a dynamic change index, HbA1c can not only reflect the average blood glucose level over a period of time but can also well predict the incidence of related microvascular complications. It is important to develop a detection method that can dynamically characterize HbA1c. Silicon nanowire (SiNW) devices were mass-produced using top-down sputtering technology, and a microdialyzer was installed in a SiNW field effect tube biosensor detection system. Finally, the detection system was used to detect HbA1c levels quantitatively and dynamically in experimental rabbits. Various measurements showed that mass-produced SiNW devices have ideal dimensions, stable structures, and good performance. A series of microscopy results showed that the SiNW surface can be functionalized for intermolecular interactions. The addition of a dialysis device can effectively overcome Debye shielding, making the blood test similar to the pure standard test. Finally, the dynamic detection of HbA1c within 40 h was realized. SiNW biosensors are capable of the dynamic detection of biomolecules, and dynamic observation of the interaction between blood glucose and HbA1c provides new ideas for the diagnosis and treatment of patients with diabetes. Therefore, the SiNW biosensor can reflect the dynamic changes in HbA1c in a shorter time, which has a certain potential value in the clinical treatment of diabetes.
White Blood Cell and Platelet Counts Are Not Suitable as Biomarkers in the Differential Diagnostics of Dementia
Authors: Schröder Sebastian , Heck Johannes , Groh Adrian , Frieling Helge , Bleich Stefan , Kahl Kai G. , Bosch Jacobus J. , Krichevsky Benjamin , Schulze-Westhoff Martin
Published: October 2022

Apart from Alzheimer’s disease (AD), no biomarkers for the differential diagnosis of dementia have been established to date. Inflammatory processes contribute to the pathogenesis of dementia subtypes, e.g., AD or frontotemporal dementia (FTD). In the context of cancer or cardiovascular diseases, white blood cell (WBC) populations and platelet counts, as well as C-reactive protein (CRP), have emerged as biomarkers. Their clinical relevance in dementia, however, is currently only insufficiently investigated. In the present study, hematological and inflammatory parameters were measured in the peripheral blood of 97 patients admitted to the gerontopsychiatric ward of Hannover Medical School, a university hospital in Germany, for dementia assessment. The study population comprised 20 non-demented, depressed patients (control group) and 77 demented patients who were assigned to five different groups based on their underlying dementia etiology: AD, n = 33; vascular dementia, n = 12; mixed dementia, n = 21; FTD, n = 5; and Korsakoff syndrome, n = 6. We observed neither statistically significant differences regarding total WBC populations, platelet counts, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio, nor CRP levels between the control group and the five dementia groups. CRP levels tended to be higher in patients with Korsakoff syndrome than in the control group and in AD patients. Thus, CRP could possibly play a role in the differential diagnosis of dementia. This should be investigated further in future prospective studies with larger sample sizes. WBC and platelet counts, by contrast, do not appear to be suitable biomarkers in the differential diagnosis of dementia.
Eye-Movement Deficits in Seniors with Hearing Aids: Cognitive and Multisensory Implications
Authors: Chavant Martin , Kapoula Zoï
Published: October 2022

In recent years, there has been a growing body of literature highlighting the relationship between presbycusis and consequences in areas other than hearing. In particular, presbycusis is linked to depression, dementia, and cognitive decline. Among this literature, the effect of hearing aids, currently the most common method of treating presbycusis, is also a growing research topic. This pilot study aims to explore the effects of hearing aids on the cognitive and multisensory consequences of presbycusis. To that purpose, saccades and vergences eye movements were studied, towards visual and audiovisual targets, of a presbycusis population wearing hearing aids for an average of two years. These measurements were done whether or not participants were wearing their hearing aids. Eye-movement characteristics, particularly latencies (the reaction time taken to initiate an eye movement), allows one to measure attentional and multisensory characteristics. Previous studies showed that presbycusis was linked with an increase of saccade latencies and an improvement in audiovisual interaction capacities, i.e., latencies for audiovisual targets are shorter than those for visual targets. Eye movements are measured and analyzed with REMOBI and AIDEAL technologies. Results show a shortening, with hearing aids, of right saccade latencies to visual targets, suggesting an increase in attention and/or engagement. Yet, saccade latencies are not shorter for audiovisual vs. visual targets alone, neither when wearing hearing aids, nor without. Moreover, convergence latencies are particularly slow for any type of target and with or without hearing aids. The results suggest deficits for audiovisual interactions and the initiation of convergences in that population. These deficits could be part of the factors triggering the need to wear hearing aids. These results therefore show interesting relationships between hearing-aid wearing in a presbycusis population and oculomotricity and invite further research in this area.
Multiparametric Longitudinal Profiling of RCAS-tva-Induced PDGFB-Driven Experimental Glioma
Authors: Becker Hannes , Castaneda-Vega Salvador , Patzwaldt Kristin , Przystal Justyna M. , Walter Bianca , Michelotti Filippo C. , Canjuga Denis , Tatagiba Marcos , Pichler Bernd , Beck Susanne C. , Holland Eric C. , la Fougère Christian , Tabatabai Ghazaleh
Published: October 2022

Glioblastomas are incurable primary brain tumors harboring a heterogeneous landscape of genetic and metabolic alterations. Longitudinal imaging by MRI and [18F]FET-PET measurements enable us to visualize the features of evolving tumors in a dynamic manner. Yet, close-meshed longitudinal imaging time points for characterizing temporal and spatial metabolic alterations during tumor evolution in patients is not feasible because patients usually present with already established tumors. The replication-competent avian sarcoma-leukosis virus (RCAS)/tumor virus receptor-A (tva) system is a powerful preclinical glioma model offering a high grade of spatial and temporal control of somatic gene delivery in vivo. Consequently, here, we aimed at using MRI and [18F]FET-PET to identify typical neuroimaging characteristics of the platelet-derived growth factor B (PDGFB)-driven glioma model using the RCAS-tva system. Our study showed that this preclinical glioma model displays MRI and [18F]FET-PET features that highly resemble the corresponding established human disease, emphasizing the high translational relevance of this experimental model. Furthermore, our investigations unravel exponential growth dynamics and a model-specific tumor microenvironment, as assessed by histology and immunochemistry. Taken together, our study provides further insights into this preclinical model and advocates for the imaging-stratified design of preclinical therapeutic interventions.
Torsional Improvement of RC Beams Using Various Strengthening Systems
Authors: El-Mandouh Mahmoud A. , Hu Jong Wan , Shim Won Sup , Abdelazeem Fathi , ELsamak Galal
Published: October 2022

Many structural elements are subjected to a significant torsional moment that affects the structural design and may require strengthening. This paper presents different effective strengthening techniques to enhance the torsional capacity of reinforced concrete (RC) beams. An experimental and numerical investigation was undertaken to evaluate the efficacy of utilizing various strengthening systems. The experimental program included six full-scale RC beams with a cross-section dimension of (150 mm × 300 mm) and a length of 1500 mm, split into one beam without strengthening as a control beam, and six beams strengthened with various materials. The various strengthening materials were wrapped aluminum strips with anchorage bolts, wrapped stainless steel strips with anchorage bolts, wrapped glass fiber reinforcement polymer (GFRP), one layer of wrapped steel wire, and two layers of wrapped steel wire meshes along the beam. The results showed that the ultimate torque of the beam strengthened by wrapped aluminum strips and the beam strengthened by wrapped stainless steel strips was larger than the control beam by about 32% and 40%, respectively, because the strips acted as an external reinforcement. In addition to the strengthening systems, using aluminum strips and stainless steel strips is effective in raising the capacity to a similar degree despite the high cost of the stainless steel strips. The ultimate torque of the beams strengthened by GFRP, one-layered wrapped steel wire meshes, and two-layered wrapped steel wire meshes along the beam is larger than the control beam by about 62%, 118%, and 163%, respectively, in addition to the ultimate angle of twist, which was larger than the control beam by about 53%, 93%, and 126%, respectively. This showed that the strengthening using the two-layered wrapped steel wire meshes along the beam would be very significant in increasing the ultimate torque strength. Moreover, the strengthened beam by two-layered fully wrapped steel wire meshes along the beam developed the highest ductility factor compared to all strengthened beams; in contrast, the beam strengthened by GFRP had less ductility. To verify the outcomes of the experimental tests, a finite-element program, ABAQUS, was performed. Finally, an excellent agreement between the experimental and numerical results was obtained.
Eleven-Year Follow-Up on the Effect of Thermoplastic Aggregates’ Addition to Reinforced Concrete
Authors: Gavela Stamatia , Rakanta Eleni , Ntziouni Afroditi , Kasselouri-Rigopoulou Vasilia
Published: October 2022

An experimental investigation was carried out to study the effect of thermoplastics’ addition to reinforcement corrosion and the durability of concrete. A long-term study is necessary for the final decision on the possibility of the utilization of materials, and this study is contributing to this direction. Two types of thermoplastics were used, high-density polyethylene and polypropylene. The percentage of replacement of conventional aggregates was 0% and 12% by volume. After being demolded and cured for 7 days, the specimens were immersed in 3.5 wt% NaCl solution for 240 days. Afterwards, they were left in laboratory ambient air up to 11 years. Carbonation depth and the volume of permeable voids were determined. Optical microscopy, stereoscopy, and electrochemical impedance spectroscopy measurements were performed. Results showed that replacing conventional limestone aggregates with the particular two thermoplastics does not have a negative impact on rebars’ corrosion behavior. Optical microscopy and stereoscopy of rebars’ surface revealed that the corrosion process has initiated and carbonation is observed in all mixes, but corrosion rates are negligible for all the mixes studied.
Associations of Dietary Intakes of Carotenoids and Vitamin A with Lung Cancer Risk in a Low-Income Population in the Southeastern United States
Authors: Sun Yan , Wu Jie , Yoon Hyung-Suk , Buchowski Maciej S. , Cai Hui , Deppen Stephen A. , Steinwandel Mark D. , Zheng Wei , Shu Xiao-Ou , Blot William J. , Cai Qiuyin
Published: October 2022

Observational studies found inverse associations of dietary carotenoids and vitamin A intakes with lung cancer risk. However, interventional trials among high-risk individuals showed that β-carotene supplements increased lung cancer risk. Most of the previous studies were conducted among European descendants or Asians. We prospectively examined the associations of lung cancer risk with dietary intakes of carotenoids and vitamin A in the Southern Community Cohort Study, including 65,550 participants with 1204 incident lung cancer cases. Multivariate Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Lung cancer cases had lower energy-adjusted dietary intakes of all carotenoids and vitamin A than non-cases. However, dietary intakes of carotenoids and vitamin A were not associated with overall lung cancer risk. A significant positive association of dietary vitamin A intake with lung cancer risk was observed among current smokers (HRQ4 vs. Q1 = 1.23; 95% CI: 1.02–1.49; Ptrend = 0.01). In addition, vitamin A intake was associated with an increased risk of adenocarcinoma among African Americans (HRQ4 vs. Q1 = 1.55; 95%CI: 1.08–2.21; Ptrend = 0.03). Dietary lycopene intake was associated with an increased risk of lung cancer among former smokers (HRQ4 vs. Q1 = 1.50; 95% CI: 1.04–2.17; Ptrend = 0.03). There are positive associations of dietary β-cryptoxanthin intake with squamous carcinoma risk (HRQ4 vs. Q1 = 1.49; 95% CI: 1.03–2.15; Ptrend = 0.03). Further studies are warranted to confirm our findings.
Emerging Role of ERBB2 in Targeted Therapy for Metastatic Colorectal Cancer: Signaling Pathways to Therapeutic Strategies
Authors: Wang Nannan , Cao Yuepeng , Si Chengshuai , Shao Peng , Su Guoqing , Wang Ke , Bao Jun , Yang Liu
Published: October 2022

Despite recent improvements in the comprehensive therapy of malignancy, metastatic colorectal cancer (mCRC) continues to have a poor prognosis. Notably, 5% of mCRC cases harbor Erb-B2 receptor tyrosine kinase 2 (ERBB2) alterations. ERBB2, commonly referred to as human epidermal growth factor receptor 2, is a member of the human epidermal growth factor receptor family of protein tyrosine kinases. In addition to being a recognized therapeutic target in the treatment of gastric and breast malignancies, it is considered crucial in the management of CRC. In this review, we describe the molecular biology of ERBB2 from the perspective of biomarkers for mCRC-targeted therapy, including receptor structures, signaling pathways, gene alterations, and their detection methods. We also discuss the relationship between ERBB2 aberrations and the underlying mechanisms of resistance to anti-EGFR therapy and immunotherapy tolerance in these patients with a focus on novel targeted therapeutics and ongoing clinical trials. This may aid the development of a new standard of care in patients with ERBB2-positive mCRC.
Longitudinally Heterogeneous Tumor Dose Optimizes Proton Broadbeam, Interlaced Minibeam, and FLASH Therapy
Authors: Sammer Matthias , Rousseti Aikaterini , Girst Stefanie , Reindl Judith , Dollinger Günther
Published: October 2022

The prerequisite of any radiation therapy modality (X-ray, electron, proton, and heavy ion) is meant to meet at least a minimum prescribed dose at any location in the tumor for the best tumor control. In addition, there is also an upper dose limit within the tumor according to the International Commission on Radiation Units (ICRU) recommendations in order to spare healthy tissue as well as possible. However, healthy tissue may profit from the lower side effects when waving this upper dose limit and allowing a larger heterogeneous dose deposition in the tumor, but maintaining the prescribed minimum dose level, particularly in proton minibeam therapy. Methods: Three different longitudinally heterogeneous proton irradiation modes and a standard spread-out Bragg peak (SOBP) irradiation mode are simulated for their depth-dose curves under the constraint of maintaining a minimum prescribed dose anywhere in the tumor region. Symmetric dose distributions of two opposing directions are overlaid in a 25 cm-thick water phantom containing a 5 cm-thick tumor region. Interlaced planar minibeam dose distributions are compared to those of a broadbeam using the same longitudinal dose profiles. Results and Conclusion: All longitudinally heterogeneous proton irradiation modes show a dose reduction in the healthy tissue compared to the common SOBP mode in the case of broad proton beams. The proton minibeam cases show eventually a much larger mean cell survival and thus a further reduced equivalent uniform dose (EUD) in the healthy tissue than any broadbeam case. In fact, the irradiation mode using only one proton energy from each side shows better sparing capabilities in the healthy tissue than the common spread-out Bragg peak irradiation mode with the option of a better dose fall-off at the tumor edges and an easier technical realization, particularly in view of proton minibeam irradiation at ultra-high dose rates larger than ~10 Gy/s (so-called FLASH irradiation modes).
Neoantigen Vaccines; Clinical Trials, Classes, Indications, Adjuvants and Combinatorial Treatments
Authors: Niemi Jenni Viivi Linnea , Sokolov Aleksandr V. , Schiöth Helgi B.
Published: October 2022

Personalized neoantigen vaccines are a highly specific cancer treatment designed to induce a robust cytotoxic T-cell attack against a patient’s cancer antigens. In this study, we searched ClinicalTrials.gov for neoantigen vaccine clinical trials and systematically analyzed them, a total of 147 trials. Peptide vaccines are the largest neoantigen vaccine type, comprising up to 41% of the clinical trials. However, mRNA vaccines are a growing neoantigen vaccine group, especially in the most recent clinical trials. The most common cancer types in the clinical trials are glioma, lung cancer, and malignant melanoma, being seen in more than half of the clinical trials. Small-cell lung cancer and non-small-cell lung cancer are the largest individual cancer types. According to the results from the clinical trials, neoantigen vaccines work best when combined with other cancer treatments, and popular combination treatments include immune checkpoint inhibitors, chemotherapy, and radiation therapy. Additionally, half of the clinical trials combined neoantigen vaccines with an adjuvant to boost the immune effects, with poly-ICLC being the most recurrent adjuvant choice. This study clarifies the rapid clinical trial development of personalized neoantigen vaccines as an emerging class of cancer treatment with increasingly diversified opportunities in classes, indications, and combinatorial treatments.
Molecular Classification of Colorectal Cancer by microRNA Profiling: Correlation with the Consensus Molecular Subtypes (CMS) and Validation of miR-30b Targets
Authors: Paz-Cabezas Mateo , Calvo-López Tania , Romera-Lopez Alejandro , Tabas-Madrid Daniel , Ogando Jesus , Fernández-Aceñero María-Jesús , Sastre Javier , Pascual-Montano Alberto , Mañes Santos , Díaz-Rubio Eduardo , Perez-Villamil Beatriz
Published: October 2022

Colorectal cancer consensus molecular subtypes (CMSs) are widely accepted and constitutes the basis for patient stratification to improve clinical practice. We aimed to find whether miRNAs could reproduce molecular subtypes, and to identify miRNA targets associated to the High-stroma/CMS4 subtype. The expression of 939 miRNAs was analyzed in tumors classified in CMS. TALASSO was used to find gene-miRNA interactions. A miR-mRNA regulatory network was constructed using Cytoscape. Candidate gene-miR interactions were validated in 293T cells. Hierarchical-Clustering identified three miRNA tumor subtypes (miR-LS; miR-MI; and miR-HS) which were significantly associated (p < 0.001) to the reported mRNA subtypes. miR-LS correlated with the low-stroma/CMS2; miR-MI with the mucinous-MSI/CMS1 and miR-HS with high-stroma/CMS4. MicroRNA tumor subtypes and association to CMSs were validated with TCGA datasets. TALASSO identified 1462 interactions (p < 0.05) out of 21,615 found between 176 miRs and 788 genes. Based on the regulatory network, 88 miR-mRNA interactions were selected as candidates. This network was functionally validated for the pair miR-30b/SLC6A6. We found that miR-30b overexpression silenced 3′-UTR-SLC6A6-driven luciferase expression in 293T-cells; mutation of the target sequence in the 3′-UTR-SLC6A6 prevented the miR-30b inhibitory effect. In conclusion CRC subtype classification using a miR-signature might facilitate a real-time analysis of the disease course and treatment response.
Endogenous Propionibacterium acnes Promotes Ovarian Cancer Progression via Regulating Hedgehog Signalling Pathway
Authors: Huang Qifa , Wei Xin , Li Wenyu , Ma Yanbing , Chen Guanxiang , Zhao Lu , Jiang Ying , Xie Siqi , Chen Qi , Chen Tingtao
Published: October 2022

Background: The oncogenesis and progression of epithelial ovarian cancer (EOC) is a complicated process involving several key molecules and factors, yet whether microbiota are present in EOC, and their role in the development of EOC, remains greatly unknown. Methods: In this study, 30 patients were enrolled to compare the similarities and differences of intratumour microbiota among patients with epithelial benign ovarian tumours (EBOTs) and patients with EOC based on the high-throughput sequencing method. Subsequently, we further isolated the specific EOC-related bacteria and defined Propionibacterium acnes as a key strain in facilitating EOC progression. More importantly, we constructed a mouse EOC model to evaluate the effect of the P. acnes strain on EOC using immunohistochemistry, Western blotting, and RT-qPCR. Results: The high-throughput sequencing showed that the intratumour microbiota in EOC tissues had a higher microbial diversity and richness compared to EBOT tissues. The abundance of previously considered pathogens, Actinomycetales, Acinetobacter, Streptococcus, Ochrobacterium, and Pseudomonadaceae Pseudomonas, was increased in the EOC tissues. Meanwhile, we discovered the facilitating role of the P. acnes strain in the progression of EOC, which may be partially associated with the increased inflammatory response to activate the hedgehog (Hh) signalling pathway. This microbial-induced EOC progression mechanism is further confirmed using the inhibitor GANT61. Conclusions: This study profiled the intratumour microbiota of EBOT and EOC tissues and demonstrated that the diversity and composition of the intratumour microbiota were significantly different. Furthermore, through in vivo and in vitro experiments, we confirmed the molecular mechanism of intratumour microbiota promotion of EOC progression in mice, which induces inflammation to activate the Hh signalling pathway. This could provide us clues for improving EOC treatment.
Spermidine/Spermine N1-Acetyltransferase 1 (SAT1)—A Potential Gene Target for Selective Sensitization of Glioblastoma Cells Using an Ionizable Lipid Nanoparticle to Deliver siRNA
Authors: Yathindranath Vinith , Safa Nura , Sajesh Babu V. , Schwinghamer Kelly , Vanan Magimairajan Issai , Bux Rashid , Sitar Daniel S. , Pitz Marshall , Siahaan Teruna J. , Miller Donald W.
Published: October 2022

Spermidine/spermine N1-acetyltransferase 1 (SAT1) responsible for cell polyamine catabolism is overexpressed in glioblastoma multiforme (GB). Its role in tumor survival and promoting resistance towards radiation therapy has made it an interesting target for therapy. In this study, we prepared a lipid nanoparticle-based siRNA delivery system (LNP-siSAT1) to selectively knockdown (KD) SAT1 enzyme in a human glioblastoma cell line. The LNP-siSAT1 containing ionizable DODAP lipid was prepared following a microfluidics mixing method and the resulting nanoparticles had a hydrodynamic size of around 80 nm and a neutral surface charge. The LNP-siSAT1 effectively knocked down the SAT1 expression in U251, LN229, and 42MGBA GB cells, and other brain-relevant endothelial (hCMEC/D3), astrocyte (HA) and macrophage (ANA-1) cells at the mRNA and protein levels. SAT1 KD in U251 cells resulted in a 40% loss in cell viability. Furthermore, SAT1 KD in U251, LN229 and 42MGBA cells sensitized them towards radiation and chemotherapy treatments. In contrast, despite similar SAT1 KD in other brain-relevant cells no significant effect on cytotoxic response, either alone or in combination, was observed. A major roadblock for brain therapeutics is their ability to cross the highly restrictive blood–brain barrier (BBB) presented by the brain microcapillary endothelial cells. Here, we used the BBB circumventing approach to enhance the delivery of LNP-siSAT1 across a BBB cell culture model. A cadherin binding peptide (ADTC5) was used to transiently open the BBB tight junctions to promote paracellular diffusion of LNP-siSAT1. These results suggest LNP-siSAT1 may provide a safe and effective method for reducing SAT1 and sensitizing GB cells to radiation and chemotherapeutic agents.
Endometrial Cancer in Reproductive Age: Fertility-Sparing Approach and Reproductive Outcomes
Authors: Mutlu Levent , Manavella Diego D. , Gullo Giuseppe , McNamara Blair , Santin Alessandro D. , Patrizio Pasquale
Published: October 2022

Endometrial cancer is the most common gynecologic malignancy in developed countries and approximately 7% of the women with endometrial cancer are below the age of 45. Management of endometrial cancer in young women who desire to maintain fertility presents a unique set of challenges since the standard surgical treatment based on hysterectomy and salpingo-oophorectomy is often not compatible with the patient’s goals. A fertility-preserving approach can be considered in selected patients with early stage and low-grade endometrial cancer. An increasing amount of data suggest that oncologic outcomes are not compromised if a conservative approach is utilized with close monitoring until childbearing is completed. If a fertility-preserving approach is not possible, assisted reproductive technologies can assist patients in achieving their fertility goals.
CD26 and Cancer
Authors: Cordero Oscar J.
Published: October 2022

This Special Issue presents new knowledge on the complex behaviour of dipeptidyl peptidase 4 (DPP4, EC 3 [...]
Interaction of HPV16 and Cutaneous HPV in Head and Neck Cancer
Authors: Al-Soneidar Walid A. , Harper Sam , Alli Babatunde Y. , Nicolau Belinda
Published: October 2022

Objectives: Human papillomavirus 16 (HPV16) is an established risk factor for Head and Neck Cancer (HNC). Recent reports have shown that genotypes from the beta (β) and gamma (γ) genera, also known as cutaneous HPV, can be found in the oral cavity, but their role is largely unidentified. We investigated the interaction between oral HPV16 and cutaneous HPV in HNC. Methods: We use data on incident HNC cases (n = 384) and frequency-matched hospital-based controls (n = 423) from the HeNCe Life study in Montreal, Canada. Participants were tested for alpha HPV and cutaneous genera using oral mouth rinse and brush samples. We used unconditional logistic regression to obtain adjusted odds ratios (aOR) and 95% confidence interval (CI) as a measure of the effect between HPV and HNC and assessed the interaction between HPV genotypes on the multiplicative and additive scales. Results: Prevalence of HPV infection was higher among cases (73%) than controls (63.4%), with cases more likely to be coinfected with more than a single genotype, 52.9% vs. 43.5%, respectively. Infection with HPV16 alone had a strong effect on HNC risk aOR = 18.2 [6.2, 53.2], while infection with any cutaneous HPV, but not HPV16, appeared to have the opposite effect aOR = 0.8 [0.6, 1.1]. The observed effect of joint exposure to HPV16 and any cutaneous HPV (aOR = 20.4 [8.3, 50.1]) was stronger than the expected effect based on an assumption of independent exposures but was measured with considerable imprecision. While the point estimate suggests a positive interaction between HPV16 and cutaneous HPV, results were imprecise with relative excess risk due to interaction (RERI) = 2.4 [−23.3, 28.2]. Conclusion: There could be biologic interaction between HPV16 and genotypes from cutaneous genera, which warrants further investigation. Although cutaneous HPVs are not usually found in tumor tissues, they are cofactors that could interact with HPV16 in the oral cavity and thus strengthen the latter’s carcinogenic effect.
Prognostic Value and Quantitative CT Analysis in RANKL Expression of Spinal GCTB in the Denosumab Era: A Machine Learning Approach
Authors: Wang Qizheng , Chen Yongye , Qin Siyuan , Liu Xiaoming , Liu Ke , Xin Peijin , Zhao Weili , Yuan Huishu , Lang Ning
Published: October 2022

The receptor activator of the nuclear factor kappa B ligand (RANKL) is the therapeutic target of denosumab. In this study, we evaluated whether radiomics signature and machine learning analysis can predict RANKL status in spinal giant cell tumors of bone (GCTB). This retrospective study consisted of 107 patients, including a training set (n = 82) and a validation set (n = 25). Kaplan-Meier survival analysis was used to validate the prognostic value of RANKL status. Radiomic feature extraction of three heterogeneous regions (VOIentire, VOIedge, and VOIcore) from pretreatment CT were performed. Followed by feature selection using Selected K Best and least absolute shrinkage and selection operator (LASSO) analysis, three classifiers (random forest (RF), support vector machine, and logistic regression) were used to build models. The area under the curve (AUC), accuracy, F1 score, recall, precision, sensitivity, and specificity were used to evaluate the models’ performance. Classification of 75 patients with eligible follow-up based on RANKL status resulted in a significant difference in progression-free survival (p = 0.035). VOIcore-based RF classifier performs best. Using this model, the AUCs for the training and validation cohorts were 0.880 and 0.766, respectively. In conclusion, a machine learning approach based on CT radiomic features could discriminate prognostically significant RANKL status in spinal GCTB, which may ultimately aid clinical decision-making.
Role of Immunotherapy in the Treatment of Cancer: A Systematic Review
Authors: Ling Sia Pei , Ming Long Chiau , Dhaliwal Jagjit Singh , Gupta Madhu , Ardianto Chrismawan , Goh Khang Wen , Hussain Zahid , Shafqat Naeem
Published: October 2022

Tremendous progress has been made in cancer research over the years, and, as a result, immunotherapy has emerged as an important therapy for the treatment of cancer, either as a stand-alone treatment or in conjunction with other cancer therapies. Immunotherapy has demonstrated encouraging outcomes and offers a viable strategy for not only enhancing the quality of life but also dramatically boosting the overall survival rate of cancer patients. The objective of this systematic review was to assess the efficacy of immunotherapy in the treatment of cancer. Databases such as PubMed and Science Direct were searched from their inception until September 2021, using the following keywords: cancer immunotherapy, cancer recurrence, cancer treatment options, and cancer therapies. The systematic review was conducted in accordance with the PRISMA protocol. There were a total of 599 articles; however, after applying the inclusion and exclusion criteria, the final review ended up with 34 publications. In conclusion, the studies have demonstrated that immunotherapy is a viable alternative treatment option for patients with recurrent or metastatic cancer, since the overall survival rate and progression-free survival rate were shown to be successful.
Predictors of Survival in Elderly Patients with Metastatic Colon Cancer: A Population-Based Cohort Study
Authors: Badic Bogdan , Bouvier Anne-Marie , Bouvier Véronique , Morvan Marie , Jooste Valérie , Alves Arnaud , Nousbaum Jean-Baptiste , Reboux Noémi
Published: October 2022

Oncological strategies in the elderly population are debated. The objective of this study was to determine the predictive factors of survival in patients aged 80 years and older with metastatic colon cancer. Data from four digestive tumour registry databases were used in this analysis. This population-based retrospective study included 1115 patients aged 80 years and older with stage IV colon adenocarcinoma diagnosed between 2007 and 2016. Cox regression was used to assess the impact of different prognostic factors. Age was significantly correlated with the surgical treatment (p < 0.001) but not with overall survival. Patients with a low comorbidity burden had better survival than patients with higher comorbidities scores (9.4 (0–123) versus 7.9 (0–115) months) (p = 0.03). Surgery was more common for proximal colon cancer (p < 0.001), but the location of the primary lesion was not correlated with improved survival (p = 0.07). Patients with lung metastases had a better prognosis than those with liver metastases (HR 0.56 95% CI 0.40, 0.77 p < 0.001); multiple organ involvement had the worst survival (HR 1.32 95% CI 1.15, 1.51 p < 0.001). Chemotherapy was associated with improved survival for both operated (HR 0.45 95% CI 0.35, 0.58 p < 0.001) and non-operated patients (HR 0.41 95% CI 0.34, 0.50 p < 0.001). The majority of patients receiving adjuvant treatment had a low comorbidity burden. In our study, the location of metastases but not the primary tumor location had an impact on overall survival. Low comorbidity burden, curative surgery, and chemotherapy had a significant advantage for elderly patients with metastatic colon cancer.
Is Lymphocyte C-Reactive Protein Ratio Useful for Predicting Survival in Patients with Non-Metastatic Soft Tissue Sarcoma?
Authors: Nakamura Tomoki , Hagi Tomohito , Asanuma Kunihiro , Sudo Akihiro
Published: October 2022

Background: Recently, the lymphocyte-to-CRP ratio (LCR) was found to have a prognostic role in many cancers. However, the clinical significance of LCR in patients with soft tissue sarcoma (STS) has not yet been established. This study aimed to determine whether LCR can predict disease-specific survival (DSS) and event-free survival (EFS) in patients with STS. Methods: In this study, 132 patients were enrolled. The mean follow-up periods were 76.5 months. Blood examinations were performed prior to treatment for all patients. Results: The 5-year DSS in patients with higher and lower LCR was 86.5% and 52.8%, respectively (p < 0.001). Patients with lower LCR had worse survival than those with higher LCR. The 5-year EFS in patients with higher and lower LCR was 66.2% and 31.2%, respectively (p < 0.001). On Receiver operating characteristic analysis, however, there was no significant difference in the area under curve (AUC) between CRP level (AUC = 0.72) and LCR (AUC = 0.711). Conclusions: LCR may be a prognostic factor for predicting oncological events in multivariate analysis, although ROC analysis could not show the superiority of LCR to CRP for predicting oncological outcomes in patients with STS.
Computational Insights into Ru, Pd and Pt fcc Nano-Catalysts from Density Functional Theory Calculations: The Influence of Long-Range Dispersion Corrections
Authors: Ungerer Marietjie J. , De Leeuw Nora H.
Published: October 2022

Ruthenium, palladium and platinum fall within the group of noble metals that are widely used in catalysis, especially for the electrocatalytic production of hydrogen. The dominant phase of the bulk Ru metal is hexagonal close-packed (hcp), which has been studied extensively. However, significantly less attention has been paid to the face-centred cubic (fcc) phases, which have been observed in nanoparticles. In this study, we have carried out density functional theory calculations with long-range dispersion corrections [DFT-D2, DFT-D3 and DFT-D3-(BJ)] to investigate the lattice parameters, surface energies and work functions of the (001), (011) and (111) surfaces of Ru, Pd and Pt in the fcc phase. When investigating the surface properties of the three metals, we observed that the DFT-D2 method generally underestimated the lattice parameters by up to 2.2% for Pt and 2.8% for Ru. The surface energies followed the observed trend (111) < (001) < (011) for both Ru and Pd with all three methods, which is comparable to experimental data. For Pt the same trend was observed with DFT-D2 and DFT-D3(BJ), but it deviated to Pt (111) < Pt (011) < Pt (001) for the DFT-D3 method. DFT-D2 overestimated the surface energies for all three Miller Indexes by 82%, 73%, and 60%, when compared to experimental values. The best correlation for the surface energies was obtained with the DFT-D3 and DFT-D3(BJ) methods, both of which have deviate by less than 15% deviation for all surfaces with respect to experiment. The work function followed the trend of Φ (111) < Φ (001) < Φ (011) for all three metals and calculated by all three methods. Five different types of Ru, Pd and Pt nanoparticles were considered, including icosahedral, decahedral, cuboctahedral, cubic and spherical particles of different sizes. The bulk, surface and nanoparticle calculations showed that the DFT-D2 method for Pt overestimated the exchange-correlation, leading to higher energy values that can be contributed erroneously to a more stable structure. The calculations showed that as soon as the surface-to-bulk ratio > 1, the energy per atom resembles bulk energy values.
Sustainable Amination of Bio-Based Alcohols by Hydrogen Borrowing Catalysis
Authors: Hameury Sophie , Bensalem Hana , De Oliveira Vigier Karine
Published: October 2022

In this review, we aim to give an overview of the use of the Borrowing Hydrogen (BH) methodology with bio-based alcohols. This methodology only forms water as a by-product, thus providing a sustainable way to amines, which have a large range of applications. This process is of particular interest when related to biomass due to the high abundance of alcohol functions in natural compounds. However, natural compounds often comprise multiple chemical functions that can change the reactivity of the substrate. This comprehensive review, comprising both homogeneous and heterogeneous catalysts, aims at summarizing the recent advancements in biomass amination for every class of substrate, highlighting the key parameters governing their reactivity and the remaining scientific hurdles. Even though most substrates have successfully been converted into the corresponding amines, reaction selectivity and functional group tolerance still need to be improved.
Dysregulated Cell–Cell Communication Characterizes Pulmonary Fibrosis
Authors: Kurche Jonathan S. , Stancil Ian T. , Michalski Jacob E. , Yang Ivana V. , Schwartz David A.
Published: October 2022

Idiopathic pulmonary fibrosis (IPF) is a progressive disease of older adults characterized by fibrotic replacement of functional gas exchange units in the lung. The strongest risk factor for IPF is a genetic variantin the promoter region of the gel-forming mucin, MUC5B. To better understand how the MUC5B variant influences development of fibrosis, we used the NicheNet R package and leveraged publicly available single-cell RNA sequencing data to identify and evaluate how epithelia participating in gas exchange are influenced by ligands expressed in control, MUC5B variant, and fibrotic environments. We observed that loss of type-I alveolar epithelia (AECI) characterizes the single-cell RNA transcriptome in fibrotic lung and validated the pattern of AECI loss using single nuclear RNA sequencing. Examining AECI transcriptomes, we found enrichment of transcriptional signatures for IL6 and AREG, which we have previously shown to mediate aberrant epithelial fluidization in IPF and murine bleomycin models. Moreover, we found that the protease ADAM17, which is upstream of IL6 trans-signaling, was enriched in control MUC5B variant donors. We used immunofluorescence to validate a role for enhanced expression of ADAM17 among MUC5B variants, suggesting involvement in IPF pathogenesis and maintenance.