bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of MgCl2 Loading on the Yield and Performance of Cabbage-Based Biochar
Authors: Zhu Cui , Huang Kuncheng , Xue Mengyuan , Zhang Yiming , Wang Jiaquan , Liu Lu
Published: July 2023

Converting more CO2 absorbed by plant photosynthesis into biomass-activated carbon effectively reduces carbon emissions. In this study, we used a one-step preparation of biomass-activated carbon loaded with MgO nanoparticles to investigate the effect of Mg loading on the catalytic pyrolysis process. The influences of magnesium loading on biochar yield and fixed carbon production were assessed. The addition of 1% Mg weakened the carbonyl C=O, inhibited the dehydroxylation reaction, enhanced the C-H signal strength, and the formation of MgO inhibited the weaker- bound substituent breakage. Additionally, the addition of magnesium altered the morphological features and chemical composition of the biochar material. It also increased the activated carbon mesoporosity by 3.94%, biochar yield by 5.55%, and fixed carbon yield by 12.14%. The addition of 1% Mg increased the adsorption capacity of the activated carbon to potassium dichromate, acid magenta, methylene blue, and tetracycline effluents by 8.71 mg, 37.15 mg, 117.68 mg, and 3.53 mg, respectively. The results showed that MgCl2 played a significant role in promoting the thermal degradation of biomass and improving the solid yield and adsorption performance of activated carbon.
Proline Isomerization: From the Chemistry and Biology to Therapeutic Opportunities
Authors: Gurung Deepti , Danielson Jacob A , Tasnim Afsara , Zhang Jian-Ting , Zou Yue , Liu Jing-Yuan
Published: July 2023

Proline isomerization, the process of interconversion between the cis- and trans-forms of proline, is an important and unique post-translational modification that can affect protein folding and conformations, and ultimately regulate protein functions and biological pathways. Although impactful, the importance and prevalence of proline isomerization as a regulation mechanism in biological systems have not been fully understood or recognized. Aiming to fill gaps and bring new awareness, we attempt to provide a wholistic review on proline isomerization that firstly covers what proline isomerization is and the basic chemistry behind it. In this section, we vividly show that the cause of the unique ability of proline to adopt both cis- and trans-conformations in significant abundance is rooted from the steric hindrance of these two forms being similar, which is different from that in linear residues. We then discuss how proline isomerization was discovered historically followed by an introduction to all three types of proline isomerases and how proline isomerization plays a role in various cellular responses, such as cell cycle regulation, DNA damage repair, T-cell activation, and ion channel gating. We then explore various human diseases that have been linked to the dysregulation of proline isomerization. Finally, we wrap up with the current stage of various inhibitors developed to target proline isomerases as a strategy for therapeutic development.
PACAP and VIP Neuropeptides’ and Receptors’ Effects on Appetite, Satiety and Metabolism
Authors: Vu John P. , Luong Leon , Sanford Daniel , Oh Suwan , Kuc Alma , Pisegna Rita , Lewis Michael , Pisegna Joseph R. , Germano Patrizia M.
Published: July 2023

The overwhelming increase in the prevalence of obesity and related disorders in recent years is one of the greatest threats to the global healthcare system since it generates immense healthcare costs. As the prevalence of obesity approaches epidemic proportions, the importance of elucidating the mechanisms regulating appetite, satiety, body metabolism, energy balance and adiposity has garnered significant attention. Currently, gastrointestinal (GI) bariatric surgery remains the only approach capable of achieving successful weight loss. Appetite, satiety, feeding behavior, energy intake and expenditure are regulated by central and peripheral neurohormonal mechanisms that have not been fully elucidated yet. Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) and Vasoactive Intestinal Polypeptide (VIP) are members of a family of regulatory peptides that are widely distributed in parallel with their specific receptors, VPAC1R, VPAC2R and PAC1R, in the central nervous system (CNS) and in the periphery, such as in the gastrointestinal tract and its associated organs and immune cells. PACAP and VIP have been reported to play an important role in the regulation of body phenotype, metabolism and homeostatic functions. The purpose of this review is to present recent data on the effects of PACAP, VIP, VPAC1R, VPAC2R and PAC1R on the modulation of appetite, satiety, metabolism, calorie intake and fat accumulation, to evaluate their potential use as therapeutic targets for the treatment of obesity and metabolic syndrome.
Preclinical Characterization of a Stabilized Gastrin-Releasing Peptide Receptor Antagonist for Targeted Cancer Theranostics
Authors: Abouzayed Ayman , Kanellopoulos Panagiotis , Gorislav Alisa , Tolmachev Vladimir , Maina Theodosia , Nock Berthold A. , Orlova Anna
Published: July 2023

Radiolabeled gastrin-releasing peptide receptor (GRPR) antagonists have shown great promise for the theranostics of prostate cancer; however, their suboptimal metabolic stability leaves room for improvements. It was recently shown that the replacement of Gly11 with Sar11 in the peptidic [D-Phe6,Leu13-NHEt,des-Met14]BBN(6–14) chain stabilized the [99mTc]Tc-DB15 radiotracer against neprilysin (NEP). We herein present DOTAGA-PEG2-(Sar11)RM26 (AU-RM26-M1), after Gly11 to Sar11-replacement. The impact of this replacement on the metabolic stability and overall biological performance of [111In]In-AU-RM26-M1 was studied using a head-to-head comparison with the unmodified reference [111In]In-DOTAGA-PEG2-RM26. In vitro, the cell uptake of [111In]In-AU-RM26-M1 could be significantly reduced in the presence of a high-excess GRPR-blocker that demonstrated its specificity. The cell uptake of both radiolabeled GRPR antagonists increased with time and was superior for [111In]In-AU-RM26-M1. The dissociation constant reflected strong affinities for GRPR (500 pM for [111In]In-AU-RM26-M1). [111In]In-AU-RM26-M1 showed significantly higher stability in peripheral mice blood at 5 min pi (88 ± 8% intact) than unmodified [111In]In-DOTAGA-PEG2-RM26 (69 ± 2% intact; p < 0.0001). The administration of a NEP inhibitor had no significant impact on the Sar11-compound (91 ± 2% intact; p > 0.05). In vivo, [111In]In-AU-RM26-M1 showed high and GRPR-mediated uptake in the PC-3 tumors (7.0 ± 0.7%IA/g vs. 0.9 ± 0.6%IA/g in blocked mice) and pancreas (2.2 ± 0.6%IA/g vs. 0.3 ± 0.2%IA/g in blocked mice) at 1 h pi, with rapid clearance from healthy tissues. The tumor uptake of [111In]In-AU-RM26-M1 was higher than for [111In]In-DOTAGA-PEG2-RM26 (at 4 h pi, 5.7 ± 1.8%IA/g vs. 3 ± 1%IA/g), concordant with its higher stability. The implanted PC-3 tumors were visualized with high contrast in mice using [111In]In-AU-RM26-M1 SPECT/CT. The Gly11 to Sar11-substitution stabilized [111In]In-DOTAGA-PEG2-(Sar11)RM26 against NEP without negatively affecting other important biological features. These results support the further evaluation of AU-RM26-M1 for prostate cancer theranostics after labeling with clinically relevant radionuclides.
Genome-Wide Acetylation Modification of H3K27ac in Bovine Rumen Cell Following Butyrate Exposure
Authors: Kang Xiaolong , Li Chenglong , Liu Shuli , Baldwin Ransom L. , Liu George E. , Li Cong-Jun
Published: July 2023

Butyrate contributes epigenetically to the changes in cellular function and tissue development of the rumen in ruminant animals, which might be achieved by its genetic or epigenetic regulation of gene expression. To explore the role of butyrate on bovine rumen epithelial function and development, this study characterized genome-wide H3K27ac modification changes and super-enhancer profiles in rumen epithelial primary cells (REPC) induced with butyrate by ChIP-seq, and analyzed its effects on gene expression and functional pathways by integrating RNA-seq data. The results showed that genome-wide acetylation modification was observed in the REPC with 94,675 and 48,688 peaks in the butyrate treatment and control group, respectively. A total of 9750 and 5020 genes with increased modification (H3K27ac-gain) and decreased modification (H3K27ac-loss) were detected in the treatment group. The super-enhancer associated genes in the butyrate-induction group were involved in the AMPK signaling pathway, MAPK signaling pathway, and ECM-receptor interaction. Finally, the up-regulated genes (PLCG1, CLEC3B, IGSF23, OTOP3, ADTRP) with H3K27ac gain modification by butyrate were involved in cholesterol metabolism, lysosome, cell adhesion molecules, and the PI3K-Akt signaling pathway. Butyrate treatment has the role of genome-wide H3K27ac acetylation on bovine REPC, and affects the changes in gene expression. The effect of butyrate on gene expression correlates with the acetylation of the H3K27ac level. Identifying genome-wide acetylation modifications and expressed genes of butyrate in bovine REPC cells will expand the understanding of the biological role of butyrate and its acetylation.
Computational Analysis Reveals Unique Binding Patterns of Oxygenated and Deoxygenated Myoglobin to the Outer Mitochondrial Membrane
Authors: Anishkin Andriy , Adepu Kiran Kumar , Bhandari Dipendra , Adams Sean H. , Chintapalli Sree V.
Published: July 2023

Myoglobin (Mb) interaction with the outer mitochondrial membrane (OMM) promotes oxygen (O2) release. However, comprehensive molecular details on specific contact regions of the OMM with oxygenated (oxy-) and deoxygenated (deoxy-)Mb are missing. We used molecular dynamics (MD) simulations to explore the interaction of oxy- and deoxy-Mb with the membrane lipids of the OMM in two lipid compositions: (a) a typical whole membrane on average, and (b) specifically the cardiolipin-enriched cristae region (contact site). Unrestrained relaxations showed that on average, both the oxy- and deoxy-Mb established more stable contacts with the lipids typical of the cristae contact site, then with those of the average OMM. However, in steered detachment simulations, deoxy-Mb clung more tightly to the average OMM, and oxy-Mb strongly preferred the contact sites of the OMM. The MD simulation analysis further indicated that a non-specific binding, mediated by local electrostatic interactions, existed between charged or polar groups of Mb and the membrane, for stable interaction. To the best of our knowledge, this is the first computational study providing the molecular details of the direct Mb–mitochondria interaction that assisted in distinguishing the preferred localization of oxy- and deoxy-Mb on the OMM. Our findings support the existing experimental evidence on Mb–mitochondrial association and shed more insights on Mb-mediated O2 transport for cellular bioenergetics.
H3G34-Mutant Gliomas—A Review of Molecular Pathogenesis and Therapeutic Options
Authors: Nguyen Anthony V. , Soto Jose M. , Gonzalez Sarah-Marie , Murillo Jennifer , Trumble Eric R. , Shan Frank Y. , Huang Jason H.
Published: July 2023

The 2021 World Health Organization Classification of Tumors of the Central Nervous System reflected advances in understanding of the roles of oncohistones in gliomagenesis with the introduction of the H3.3-G34R/V mutant glioma to the already recognized H3-K27M altered glioma, which represent the diagnoses of pediatric-type diffuse hemispheric glioma and diffuse midline glioma, respectively. Despite advances in research regarding these disease entities, the prognosis remains poor. While many studies and clinical trials focus on H3-K27M-altered-glioma patients, those with H3.3-G34R/V mutant gliomas represent a particularly understudied population. Thus, we sought to review the current knowledge regarding the molecular mechanisms underpinning the gliomagenesis of H3.3-G34R/V mutant gliomas and the diagnosis, treatment, long-term outcomes, and possible future therapeutics.
Prognostic Significance of PD-L1 Expression in Gastric Cancer Patients with Peritoneal Metastasis
Authors: Chen Xiao-Jiang , Wei Cheng-Zhi , Lin Jun , Zhang Ruo-Peng , Chen Guo-Ming , Li Yuan-Fang , Nie Run-Cong , Chen Yong-Ming
Published: July 2023

Background: Recently, many studies have explored the relationship between the expression of programmed death ligand 1 (PD-L1) and prognosis in gastric cancer, but there is still controversy. Additionally, few studies have specifically investigated the expression of PD-L1 in patients with peritoneal metastasis. Methods: Immunohistochemistry was used to analyze the expression of PD-L1 in gastric cancer patients with peritoneal metastasis. The combined positive score (CPS) was calculated to evaluate the expression of PD-L1, and the clinicopathological data were analyzed to explore prognostic significance. Results: In total, 147 gastric cancer patients with peritoneal metastasis were enrolled. The negative PD-L1 expression was defined as a CPS < 1, and high PD-L1 expression was defined as a CPS ≥ 10. PD-L1 expression with CPS ≥ 1 and CPS-negative was detected in 67 (45.58%) and 80 (54.42%) patients, respectively. High PD-L1 expression at PD-L1 CPS ≥ 10 was detected in 21(14.29%) patients. The median overall survival (OS) was 18.53 months in the CPS < 10 group and 27.00 months in the CPS ≥ 10 group; the OS difference between the two groups was significant (p = 0.015). Multivariate analysis demonstrated that a poor Eastern Cooperative Oncology Group performance score (ECOG PS) (p = 0.002) and severe peritoneal metastasis (p = 0.033) were significantly associated with poor survival, while palliative chemotherapy (p = 0.002) and high PD-L1 expression (p = 0.008) were independent and significantly favorable prognostic factors. Conclusions: Our study demonstrated that PD-L1 expression was widely presented in gastric cancer patients with peritoneal metastasis, while a CPS no less than 10 predicted better prognosis.
Role of the Renin-Angiotensin System in Long COVID’s Cardiovascular Injuries
Authors: Cojocaru Elena , Cojocaru Cristian , Vlad Cristiana-Elena , Eva Lucian
Published: July 2023

The renin-angiotensin system (RAS) is one of the biggest challenges of cardiovascular medicine. The significance of the RAS in the chronic progression of SARS-CoV-2 infection and its consequences is one of the topics that are currently being mostly discussed. SARS-CoV-2 undermines the balance between beneficial and harmful RAS pathways. The level of soluble ACE2 and membrane-bound ACE2 are both upregulated by the endocytosis of the SARS-CoV-2/ACE2 complex and the tumor necrosis factor (TNF)-α-converting enzyme (ADAM17)-induced cleavage. Through the link between RAS and the processes of proliferation, the processes of fibrous remodelling of the myocardium are initiated from the acute phase of the disease, continuing into the long COVID stage. In the long term, RAS dysfunction may cause an impairment of its beneficial effects leading to thromboembolic processes and a reduction in perfusion of target organs. The main aspects of ACE2—a key pathogenic role in COVID-19 as well as the mechanisms of RAS involvement in COVID cardiovascular injuries are studied. Therapeutic directions that can be currently anticipated in relation to the various pathogenic pathways of progression of cardiovascular damage in patients with longCOVID have also been outlined.
Extracellular Matrix- and Integrin Adhesion Complexes-Related Genes in the Prognosis of Prostate Cancer Patients’ Progression-Free Survival
Authors: Samaržija Ivana , Konjevoda Paško
Published: July 2023

Prostate cancer is a heterogeneous disease, and one of the main obstacles in its management is the inability to foresee its course. Therefore, novel biomarkers are needed that will guide the treatment options. The extracellular matrix (ECM) is an important part of the tumor microenvironment that largely influences cell behavior. ECM components are ligands for integrin receptors which are involved in every step of tumor progression. An underlying characteristic of integrin activation and ligation is the formation of integrin adhesion complexes (IACs), intracellular structures that carry information conveyed by integrins. By using The Cancer Genome Atlas data, we show that the expression of ECM- and IACs-related genes is changed in prostate cancer. Moreover, machine learning methods revealed that they are a source of biomarkers for progression-free survival of patients that are stratified according to the Gleason score. Namely, low expression of FMOD and high expression of PTPN2 genes are associated with worse survival of patients with a Gleason score lower than 9. The FMOD gene encodes protein that may play a role in the assembly of the ECM and the PTPN2 gene product is a protein tyrosine phosphatase activated by integrins. Our results suggest potential biomarkers of prostate cancer progression.
Deep Learning Combinatorial Models for Intelligent Supply Chain Demand Forecasting
Authors: Ma Xiaoya , Li Mengxiu , Tong Jin , Feng Xiaying
Published: July 2023

Low-carbon and environmentally friendly living boosted the market demand for new energy vehicles and promoted the development of the new energy vehicle industry. Accurate demand forecasting can provide an important decision-making basis for new energy vehicle enterprises, which is beneficial to the development of new energy vehicles. From the perspective of an intelligent supply chain, this study explored the demand forecasting of new energy vehicles, and proposed an innovative SARIMA-LSTM-BP combination model for prediction modeling. The data showed that the RMSE, MSE, and MAE values of the SARIMA-LSTM-BP combination model were 2.757, 7.603, and, 1.912, respectively, all of which are lower values than those of the single models. This study therefore, indicated that, compared with traditional econometric forecasting models and deep learning forecasting models, such as the random forest, support vector regression (SVR), long short-term memory (LSTM), and back propagation neural network (BP) models, the SARIMA-LSTM-BP combination model performed outstandingly with higher accuracy and better forecasting performance.
Ultrasensitive Electrochemical Aptasensing of Malathion Based on Hydroxylated Black Phosphorus/Poly-L-Lysine Composite
Authors: Ma Tingting , Zhou Jie , Wei Dan , Peng Hongquan , Liu Xun , Guo Wenfei , Zhang Chuanxiang , Liu Xueying , Li Song , Deng Yan
Published: July 2023

A highly sensitive unlabeled electrochemical aptasensor based on hydroxylated black phosphorus/poly-L-lysine (hBP/PLL) composite is introduced herein for the detection of malathion. Poly-L-lysine (PLL) with adhesion and coating properties adhere to the surface of the nanosheets by noncovalent interactions with underlying hydroxylated black phosphorus nanosheets (hBP) to produce the hBP/PLL composite. The as-synthesized hBP/PLL composite bonded to Au nanoparticles (Au NPs) firmly by assembling and using them as a substrate for the aptamer with high specificity as a probe to fabricate the sensor. Under optimal conditions, the linear range of the electrochemical aptasensor was 0.1 pM~1 μM, and the detection limit was 2.805 fM. The electrochemical aptasensor has great selectivity, a low detection limit, and anti-interference, which has potential application prospects in the field of rapid trace detection of pesticide residues.
Reminders of Mortality: Investigating the Effects of Different Mortality Saliences on Somatosensory Neural Activity
Authors: Gyimes Istvan Laszlo , Valentini Elia
Published: July 2023

The Terror Management Theory (TMT) offered a great deal of generative hypotheses that have been tested in a plethora of studies. However, there is a still substantive lack of clarity about the interpretation of TMT-driven effects and their underlying neurological mechanisms. Here, we aimed to expand upon previous research by introducing two novel methodological manipulations aimed to enhance the effects of mortality salience (MS). We presented participants with the idea of the participants’ romantic partner’s death as well as increased the perceived threat of somatosensory stimuli. Linear mixed modelling disclosed the greater effects of MS directed at one’s romantic partner on pain perception (as opposed to the participant’s own mortality). The theta event-related oscillatory activity measured at the vertex of the scalp was significantly lower compared to the control condition. We suggest that MS aimed at one’s romantic partner can result in increased effects on perceptual experience; however, the underlying neural activities are not reflected by a classical measure of cortical arousal.
Development of a BIM-Enabled Automated Cost Segregation System
Authors: Zhang Chengyi , Kumar Danish , Li Huimin , Zhou Rong , Lv Lelin , Tian Junrui
Published: July 2023

The cost segregation study is a tax planning strategy employed to optimize cash flow by redefining real estate assets as personal property and land improvement, enabling accelerated tax depreciation. However, conventional cost segregation practices suffer from limitations, such as time-consuming procedures and high associated costs, which hinder their effectiveness. To overcome these challenges, this paper presents an innovative strategy that integrates Building Information Modelling (BIM) to develop an automated cost segregation system. The research aims to optimize the workflow by developing a BIM model and using 5D BIM to perform a cost segregation study by categorizing building elements under a Modified Accelerated Cost Recovery System (MACRS). This workflow aims at minimizing the time and financial resources expended with traditional methodologies. The proposed workflow enables precise identification and separate depreciation of building components, resulting in significant tax deductions that would otherwise be unattainable. The results indicate that performing cost segregation with BIM leads to a significant increase in depreciation amounts, particularly during the initial six years, while also raising the net present value of depreciation by 45%. The integration of BIM technology facilitates effective management and sharing of cost segregation data among stakeholders, enhancing collaboration and decision-making throughout the project lifecycle. Owners can optimize cost management and financial planning, identifying tax-saving opportunities and improving cash flow. General Contractors (GCs) can leverage the system during the bidding process, enhancing their competitiveness and project acquisition potential. Future research can explore the integration of cost segregation modules from BIM with asset management tools, enabling improved facility and fiscal management of building components. Such integration holds promise for enhancing the construction and real estate industry’s overall efficiency and performance.
Capacity Spectrum-Based Retrofitting Method and Quick Design for Viscously Damped Structures by Utilizing the Concept of Uniform Damping Ratio
Authors: Hu Xiuyan , Zhao Zhipeng , Zhang Ruifu , Lu Zhaohui , Guo Ming , Guo Liang
Published: July 2023

Viscous dampers have proven to be effective in enhancing the seismic performance of existing structures. Despite this, there is still a need for rapid and simplified design methods and formulae for viscous dampers that can take into account the elastic–plastic performance of structures. This study introduces a retrofit design method for existing structures using viscous dampers, based on the concept of uniform damping ratio (UDR), with the aim of fully utilizing each damper. The UDR concept assumes that each damper in the structure provides the same UDR when subjected to seismic excitations of identical intensity. In this method, the first step involves defining the equivalent damping ratio (EDR) of the damper. Then, based on the capacity spectrum of the structure, the response mitigation ratio can be determined, which helps to determine the additional EDR required from the dampers. Once the UDR and additional EDR from the viscous damper have been determined, the parameters of the dampers at each story can be rapidly obtained. To demonstrate the effectiveness of this method, a six-story reinforced concrete frame was utilized as a benchmark structure. A comparison between this UDR-based approach and a traditional design approach was also conducted. The study findings reveal that the UDR concept enables the maximum utilization of energy dissipation capacity of viscous dampers installed in the structure, leading to a more effective and economical design approach.
Micro RNAs as a Diagnostic Marker between Glioma and Primary CNS Lymphoma: A Systematic Review
Authors: Dabbagh Ohadi Mohammad Amin , Aleyasin Mir Sajjad , Samiee Reza , Bordbar Sanaz , Maroufi Seyed Farzad , Bayan Nikoo , Hanaei Sara , Smith Timothy R.
Published: July 2023

Differentiating glioma from primary central nervous system lymphoma (PCNSL) can be challenging, and current diagnostic measures such as MRI and biopsy are of limited efficacy. Liquid biopsies, which detect circulating biomarkers such as microRNAs (miRs), may provide valuable insights into diagnostic biomarkers for improved discrimination. This review aimed to investigate the role of specific miRs in diagnosing and differentiating glioma from PCNSL. A systematic search was conducted of PubMed, Scopus, Web of Science, and Embase for articles on liquid biopsies as a diagnostic method for glioma and PCNSL. Sixteen dysregulated miRs were identified with significantly different levels in glioma and PCNSL, including miR-21, which was the most prominent miR with higher levels in PCNSL, followed by glioma, including glioblastoma (GBM), and control groups. The lowest levels of miR-16 and miR-205 were observed in glioma, followed by PCNSL and control groups, whereas miR-15b and miR-301 were higher in both tumor groups, with the highest levels observed in glioma patients. The levels of miR-711 were higher in glioma (including GBM) and downregulated in PCNSL compared to the control group. This review suggests that using these six circulating microRNAs as liquid biomarkers with unique changing patterns could aid in better discrimination between glioma, especially GBM, and PCNSL.
Presence of Circulating Tumor Cells Predates Imaging Detection of Relapse in Patients with Stage III Melanoma
Authors: Lucci Anthony , Addanki Sridevi , Chiang Yi-Ju , Meas Salyna , Sarli Vanessa N. , Upshaw Joshua R. , Manchem Mayank , Patel Sapna P. , Wargo Jennifer A. , Gershenwald Jeffrey E. , Ross Merrick I.
Published: July 2023

Stage III melanoma includes nodal metastasis or in-transit disease. Five-year survival rates vary between 32% and 93%. The identification of high-risk patients is important for clinical decision making. We demonstrated previously that ≥1 circulating tumor cells (CTCs) at baseline was associated with recurrence. In this study, we investigated how frequently CTCs were identified prior to radiologically detected recurrence. Stage III patients (n = 325) had imaging at baseline and q 3 months. Baseline and q 6–12 months blood draws (7.5 mL) were performed to identify CTCs up to 3.5 years from diagnosis. CTC assessment was performed using the immunomagnetic capture of CD146-positive cells and anti-MEL-PE. The presence of one or more CTCs was considered positive. We analyzed the cohort of patients with relapse confirmed by radiologic imaging. CTC collection dates were assessed to determine the lead time for CTC detection. CTC-negative patients were significantly less likely to relapse compared to patients positive for CTCs (p-value < 0.001). Within the 325-patient cohort, 143 patients (44%) had recurrence, with a median follow-up of 52 months from diagnosis. The cohort (n = 143) with positive imaging and CTC results revealed 76% of patients (108/143) had CTC+ results before the radiological identification of relapse. The median time between positive CTC and positive imaging was 9 months. CTCs were positive in >75% of patients prior to relapse at a median of 9 months before radiologic detection.
Characterization and Classification of Spatial White Matter Tract Alteration Patterns in Glioma Patients Using Magnetic Resonance Tractography: A Systematic Review and Meta-Analysis
Authors: Mahmoodi Arash L. , Landers Maud J. F. , Rutten Geert-Jan M. , Brouwers H. Bart
Published: July 2023

Introduction: Magnetic resonance (MR) tractography can be used to study the spatial relations between gliomas and white matter (WM) tracts. Various spatial patterns of WM tract alterations have been described in the literature. We reviewed classification systems of these patterns, and investigated whether low-grade gliomas (LGGs) and high-grade gliomas (HGGs) demonstrate distinct spatial WM tract alteration patterns. Methods: We conducted a systematic review and meta-analysis to summarize the evidence regarding MR tractography studies that investigated spatial WM tract alteration patterns in glioma patients. Results: Eleven studies were included. Overall, four spatial WM tract alteration patterns were reported in the current literature: displacement, infiltration, disruption/destruction and edematous. There was a considerable heterogeneity in the operational definitions of these terms. In a subset of studies, sufficient homogeneity in the classification systems was found to analyze pooled results for the displacement and infiltration patterns. Our meta-analyses suggested that LGGs displaced WM tracts significantly more often than HGGs (n = 259 patients, RR: 1.79, 95% CI [1.14, 2.79], I2 = 51%). No significant differences between LGGs and HGGs were found for WM tract infiltration (n = 196 patients, RR: 1.19, 95% CI [0.95, 1.50], I2 = 4%). Conclusions: The low number of included studies and their considerable methodological heterogeneity emphasize the need for a more uniform classification system to study spatial WM tract alteration patterns using MR tractography. This review provides a first step towards such a classification system, by showing that the current literature is inconclusive and that the ability of fractional anisotropy (FA) to define spatial WM tract alteration patterns should be critically evaluated. We found variations in spatial WM tract alteration patterns between LGGs and HGGs, when specifically examining displacement and infiltration in a subset of the included studies.
Automated Detection and Scoring of Tumor-Infiltrating Lymphocytes in Breast Cancer Histopathology Slides
Authors: Yosofvand Mohammad , Khan Sonia Y. , Dhakal Rabin , Nejat Ali , Moustaid-Moussa Naima , Rahman Rakhshanda Layeequr , Moussa Hanna
Published: July 2023

Detection of tumor-infiltrating lymphocytes (TILs) in cancer images has gained significant importance as these lymphocytes can be used as a biomarker in cancer detection and treatment procedures. Our goal was to develop and apply a TILs detection tool that utilizes deep learning models, following two sequential steps. First, based on the guidelines from the International Immuno-Oncology Biomarker Working Group (IIOBWG) on Breast Cancer, we labeled 63 large pathology imaging slides and annotated the TILs in the stroma area to create the dataset required for model development. In the second step, various machine learning models were employed and trained to detect the stroma where U-Net deep learning structure was able to achieve 98% accuracy. After detecting the stroma area, a Mask R-CNN model was employed for the TILs detection task. The R-CNN model detected the TILs in various images and was used as the backbone analysis network for the GUI development of the TILs detection tool. This is the first study to combine two deep learning models for TILs detection at the cellular level in breast tumor histopathology slides. Our novel approach can be applied to scoring TILs in large cancer slides. Statistical analysis showed that the output of the implemented approach had 95% concordance with the scores assigned by the pathologists, with a p-value of 0.045 (n = 63). This demonstrated that the results from the developed software were statistically meaningful and highly accurate. The implemented approach in analyzing whole tumor histology slides and the newly developed TILs detection tool can be used for research purposes in biomedical and pathology applications and it can provide researchers and clinicians with the TIL score for various input images. Future research using additional breast cancer slides from various sources for further training and validation of the developed models is necessary for more inclusive, rigorous, and robust clinical applications.
An Assessment of the Penile Squamous Cell Carcinoma Surfaceome for Biomarker and Therapeutic Target Discovery
Authors: Grass George Daniel , Ercan Dalia , Obermayer Alyssa N. , Shaw Timothy , Stewart Paul A. , Chahoud Jad , Dhillon Jasreman , Lopez Alex , Johnstone Peter A. S. , Rogatto Silvia Regina , Spiess Philippe E. , Eschrich Steven A.
Published: July 2023

Penile squamous cell carcinoma (PSCC) is a rare malignancy in most parts of the world and the underlying mechanisms of this disease have not been fully investigated. About 30–50% of cases are associated with high-risk human papillomavirus (HPV) infection, which may have prognostic value. When PSCC becomes resistant to upfront therapies there are limited options, thus further research is needed in this venue. The extracellular domain-facing protein profile on the cell surface (i.e., the surfaceome) is a key area for biomarker and drug target discovery. This research employs computational methods combined with cell line translatomic (n = 5) and RNA-seq transcriptomic data from patient-derived tumors (n = 18) to characterize the PSCC surfaceome, evaluate the composition dependency on HPV infection, and explore the prognostic impact of identified surfaceome candidates. Immunohistochemistry (IHC) was used to validate the localization of select surfaceome markers. This analysis characterized a diverse surfaceome within patient tumors with 25% and 18% of the surfaceome represented by the functional classes of receptors and transporters, respectively. Significant differences in protein classes were noted by HPV status, with the most change being seen in transporter proteins (25%). IHC confirmed the robust surface expression of select surfaceome targets in the top 85% of expression and a superfamily immunoglobulin protein called BSG/CD147 was prognostic of survival. This study provides the first description of the PSCC surfaceome and its relation to HPV infection and sets a foundation for novel biomarker and drug target discovery in this rare cancer.
Optimization of Indocyanine Green for Intraoperative Fluorescent Image-Guided Localization of Lung Cancer; Analysis Based on Solid Component of Lung Nodule
Authors: Jeon Ok Hwa , Choi Byeong Hyeon , Rho Jiyun , Kim Kyungsu , Lee Jun Hee , Lee Jinhwan , Kim Beop-Min , Kim Hyun Koo
Published: July 2023

ICG fluorescence imaging has been used to detect lung cancer; however, there is no consensus regarding the optimization of the indocyanine green (ICG) injection method. The aim of this study was to determine the optimal dose and timing of ICG for lung cancer detection using animal models and to evaluate the feasibility of ICG fluorescence in lung cancer patients. In a preclinical study, twenty C57BL/6 mice with footpad cancer and thirty-three rabbits with VX2 lung cancer were used. These animals received an intravenous injection of ICG at 0.5, 1, 2, or 5 mg/kg, and the cancers were detected using a fluorescent imaging system after 3, 6, 12, and 24 h. In a clinical study, fifty-one patients diagnosed with lung cancer and scheduled to undergo surgery were included. Fluorescent images of lung cancer were obtained, and the fluorescent signal was quantified. Based on a preclinical study, the optimal injection method for lung cancer detection was 2 mg/kg ICG 12 h before surgery. Among the 51 patients, ICG successfully detected 37 of 39 cases with a consolidation-to-tumor (C/T) ratio of >50% (TNR: 3.3 ± 1.2), while it failed in 12 cases with a C/T ratio ≤ 50% and 2 cases with anthracosis. ICG injection at 2 mg/kg, 12 h before surgery was optimal for lung cancer detection. Lung cancers with the C/T ratio > 50% were successfully detected using ICG with a detection rate of 95%, but not with the C/T ratio ≤ 50%. Therefore, further research is needed to develop fluorescent agents targeting lung cancer.
Pareto-Optimized Non-Negative Matrix Factorization Approach to the Cleaning of Alaryngeal Speech Signals
Authors: Maskeliūnas Rytis , Damaševičius Robertas , Kulikajevas Audrius , Pribuišis Kipras , Ulozaitė-Stanienė Nora , Uloza Virgilijus
Published: July 2023

The problem of cleaning impaired speech is crucial for various applications such as speech recognition, telecommunication, and assistive technologies. In this paper, we propose a novel approach that combines Pareto-optimized deep learning with non-negative matrix factorization (NMF) to effectively reduce noise in impaired speech signals while preserving the quality of the desired speech. Our method begins by calculating the spectrogram of a noisy voice clip and extracting frequency statistics. A threshold is then determined based on the desired noise sensitivity, and a noise-to-signal mask is computed. This mask is smoothed to avoid abrupt transitions in noise levels, and the modified spectrogram is obtained by applying the smoothed mask to the signal spectrogram. We then employ a Pareto-optimized NMF to decompose the modified spectrogram into basis functions and corresponding weights, which are used to reconstruct the clean speech spectrogram. The final noise-reduced waveform is obtained by inverting the clean speech spectrogram. Our proposed method achieves a balance between various objectives, such as noise suppression, speech quality preservation, and computational efficiency, by leveraging Pareto optimization in the deep learning model. The experimental results demonstrate the effectiveness of our approach in cleaning alaryngeal speech signals, making it a promising solution for various real-world applications.
Recent Progress in Nickel and Silica Containing Catalysts for CO2 Hydrogenation to CH4
Authors: Albeladi Nadiyah , Alsulami Qana A. , Narasimharao Katabathini
Published: July 2023

The recent unusual weather changes occurring in different parts of the world are caused by global warming, a consequence of the release of extreme amounts of greenhouse gases into the atmosphere. Carbon dioxide (CO2) is one of these greenhouse gasses, which can be captured and reused to generate fuel through the methanation process. Nickel- and silica-based catalysts have been recognized as promising catalysts due to their efficiency, availability, and low prices. However, these catalysts suffer from metal sintering at high temperatures. Researchers have achieved remarkable improvements through altering conventional synthesis methods, supports, metal loading amounts, and promoters. The modified routes have enhanced stability and activity while the supports offer large surface areas, dispersion, and strong metal–support interactions. Nickel loading affects the formed structure and catalytic activity, whereas doping causes CO2 conversion at low temperatures and forms basic sites. This review aims to discuss the CO2 methanation process over Ni- and SiO2-based catalysts, in particular the silica-supported Ni metal in previously reported research works and point out directions for potential future work.
Recent Advances for the Synthesis of Dihydroquinolin-2(1H)-ones via Catalytic Annulation of α,β-Unsaturated N-Arylamides
Authors: Niu Yan-Ning , Tian Lin-Shuang , Lv Huai-Zhong , Li Ping-Gui
Published: July 2023

Dihydroquinolin-2(1H)-ones (DHQOs) represent a class of valuable bioactive compounds with six-membered nitrogen-containing heterocyclic structures. The development of simple, mild, and efficient synthetic methods has been widely considered by synthetic chemists. In this review, we have summarized a series of different synthetic strategies for the synthesis of DHQOs via the catalytic annulation of α,β-unsaturated N-arylamides in the past decade, including covering electrophilic cyclization, radical initiated cyclization, and photochemical cyclization reactions. Additionally, the substrate scope and mechanistic details are also discussed. This paper provides a useful reference for the development of diverse synthesis methodologies of DHQO.
An Asymmetric Dinuclear Bis(ansa-Zirconocene) Complex: Synthesis and Performance in Olefin (co-)Polymerization
Authors: Jende Lars N. , Roisnel Thierry , Cirriez Virginie , Welle Alexandre , Kirillov Evgueni , Carpentier Jean-Francois
Published: July 2023

A synthetic strategy to access asymmetric dinuclear bis(ansa-metallocene) pre-catalysts is described. As a key step, the Pd-catalyzed Suzuki cross-coupling of 9,9-bis(trimethylsilyl)-fluoren-2-yl-boronic acid with a substituted 2-bromo-9H-fluorene generates an asymmetric 2,2′-bifluorene platform, which can be individually functionalized at the two differentiated 9-positions. Herein, as a first demonstration of this strategy, we report the asymmetric dinuclear bis(ansa-zirconocene) complex 2,2′-[{Me2C(Flu)(Cp)}ZrCl2][{Me2C(7-tBuFlu)(Cp)}ZrCl2], which has been characterized with NMR spectroscopy and high-resolution mass spectrometry. The performance of this bimetallic pre-catalyst when combined with MAO has been evaluated in ethylene, propylene, and ethylene/1-hexene (co-)polymerization. This pre-catalyst is revealed to be less productive than the mononuclear reference pre-catalyst {Me2C(2,7-tBuFlu)(Cp)}ZrCl2, likely because of higher steric hindrance induced by the linkage at the difluorenyl platform. The resulting (co-)polymers featured only slight differences in terms of molecular weights, tacticity, and comonomer incorporation. No bimodal molecular weight distribution was achieved at any produced polymer; this might have originated from the close similarity of the connected Cp/Flu moieties or a rapid chain-transfer phenomenon between the different active sites which were quite close to each other.
Metal–Organic Frameworks for Electrocatalytic CO2 Reduction into Formic Acid
Authors: Xie Wen-Jun , Mulina Olga M. , Terent’ev Alexander O. , He Liang-Nian
Published: July 2023

Metal–organic frameworks (MOFs) are used in catalysis due to their high specific surface area and porous structure. The dispersed active sites and limited reaction space that render MOFs have the potential for highly selective electrocatalytic CO2 reduction reaction (ECO2RR). Meanwhile, formic acid (HCOOH) is attracting attention as a liquid product with high economic benefits. This review summarizes the MOFs and their derivatives applied for ECO2RR into HCOOH products. The preparation methods of MOFs as electrocatalysts and their unique advantages are discussed. A series of MOFs and MOF derivatives obtained by electrochemical reduction or carbonization processes are highlighted, including metal nanomaterials, carbon-based nanocomposites, single-atom catalysts, and bimetallic nanocomposites. Depending on the MOF building units (metal ions and organic linkers) and the reaction conditions of derivatization, MOF-based catalysts exhibit rich diversity and controllable modulation of catalytic performance. Finally, the challenges encountered at this stage and the future research directions of MOF-based catalysts are proposed.
Electrochemical Studies of Inkjet Printed Semi-Transparent NiCo2O4/ITO Supercapacitor Electrodes
Authors: Banti Angeliki , Charalampakis Michalis , Pardalis Paris , Prochaska Charikleia , Sotiropoulos Sotirios , Binas Vassilios
Published: July 2023

Transparent supercapacitors find a large number of applications as components of many electronic devices and circuits. Mixed Ni–Co oxides (NCOs) are among the most promising supercapacitor electrode materials exhibiting high pseudo-capacitance and good electronic conductivity, while inkjet printing is a low cost and versatile technique for electrode printing. Surprisingly, although there have been many studies of NCO supercapacitor films on ITO glass substrates, these have not been prepared by the inkjet technique, and their optical properties were not fully characterized. Hereby, we report the fabrication and characterization of thin (295 and 477 nm thick; 0.017 and 0.035 mg cm−2 NCO loading) semi-transparent NiCo2O4/ITO supercapacitor electrodes, showing transparency to visible light (60–30%, from the thinner to the thicker electrode layers tested), typical mass specific capacitance for NCO-based supercapacitor electrodes (1294–829 Fg−1 at 1 mA cm−2 discharge current density) and high volumetric capacitance (746–608 F cm−3 at 1 mA cm−2). The NCO nanoparticles were prepared by hydrothermal synthesis followed by thermal treatment and ball milling (ZrO2 balls, 0.5 mm diameter), resulting in a cubic nickel–cobalt oxide structure and particle size in the 30–150 nm range, whereas the electrode layers were printed from water-propylene glycol solutions using a Dimatix DMP-2850 drop-on-demand (DoD) inkjet printer. Constant current charge–discharge experiments of the supercapacitor electrode (at ca 0.5 mA cm−2) for 1000 cycles confirmed stability of performance.
ROP16 of Toxoplasma gondii Inhibits Innate Immunity by Triggering cGAS-STING Pathway Inactivity through the Polyubiquitination of STING
Authors: Jin Qi-Wang , Yu Ting , Pan Ming , Fan Yi-Min , Huang Si-Yang
Published: July 2023

cGAS-STING signaling is a major pathway in inducing type Ⅰ IFN, which plays a crucial role in the defense against T. gondii infection. In contrast, T. gondii develops multiple strategies to counteract the host defense, causing serious diseases in a wide range of hosts. Here, we demonstrate that T. gondii rhoptry protein 16 (ROP16) dampens type I interferon signaling via the inhibition of the cGAS (cyclic GMP-AMP synthase) pathway through the polyubiquitination of STING. Mechanistically, ROP16 interacts with STING through the SignalP domain and inhibits the K63-linked ubiquitination of STING in an NLS (nuclear localization signal)-domain-dependent manner. Consequently, knocking out the ROP16 in PRU tachyzoites promotes the STING-mediated production of type I IFNs and limits the replication of T. gondii. Together, these findings describe a distinct pathway where T. gondii exploits the ubiquitination of STING to evade host anti-parasite immunity, revealing new insights into the interaction between the host and parasites.
Policosanol Stimulates Osteoblast Differentiation via Adenosine Monophosphate-Activated Protein Kinase-Mediated Expression of Insulin-Induced Genes 1 and 2
Authors: Kim Kyeong-Min , Lim Young-Ju , Jang Won-Gu
Published: July 2023

Policosanol is known as a hypocholesterolemic compound and is derived from plants such as sugar cane and corn. Policosanol can lower blood pressure or inhibit adipogenesis, but its effect on osteogenic differentiation and the molecular mechanism is unclear. This study aims to investigate the effect of policosanol on osteogenic differentiation in MC3T3-E1 cells and zebrafish models. Administration of policosanol into MC3T3-E1 induced the expression of the osteogenic genes such as distal-less homeobox 5 (Dlx5) and runt-related transcription factor 2 (Runx2). Alkaline phosphatase activity and extracellular mineralization also increased. Policosanol promoted activation of adenosine monophosphate-activated protein kinase (AMPK) and insulin-induced genes (INSIGs) expression and regulation of INSIGs modulated osteoblast differentiation. AMPK activation through transfection of the constitutively active form of AMPK (CA-AMPK) increased INSIGs expression, whereas policosanol-induced INSIGs expression was suppressed by inhibitor of AMPK (Com. C). Furthermore, the osteogenic effects of policosanol were verified in zebrafish. Amputated caudal fin rays were regenerated by policosanol treatment. Taken together, these results show that policosanol increases osteogenic differentiation and contributes to fin regeneration in zebrafish via AMPK-mediated INSIGs expression, suggesting that policosanol has potential as an osteogenic agent.