bluuebunny/crossref_metadata_2025 huggingface dataset:
ctDNA Is Useful to Detect Mutations at Codon 641 of Exon 16 of EZH2, a Biomarker for Relapse in Patients with Diffuse Large B-Cell Lymphoma
Authors: Díaz-Chávez José , Gutiérrez-Hernández Olga , Taja-Chayeb Lucia , Gutiérrez-Chavarría Sindy , Avilés-Salas Alejandro , Candelaria Myrna
Published: September 2022

(1) Background: The epigenetic regulator EZH2 is a subunit of the polycomb repressive complex 2 (PRC2), and methylates H3K27, resulting in transcriptional silencing. It has a critical role in lymphocyte differentiation within the lymph node. Therefore, mutations at this level are implicated in lymphomagenesis. In fact, the mutation at the Y641 amino acid in the EZH2 gene is mutated in up to 40% of B-cell lymphomas. (2) Methods: We compared the presence of exon 16 EZH2 mutations in tumor samples and ctDNA in a prospective trial. These mutations were determined by Sanger sequencing and ddPCR. (3) Results: One hundred and thirty-eight cases were included. Ninety-eight were germinal center, and twenty had EZH2 mutations. Mean follow-up (IQR 25–75) was 23 (7–42) months. The tumor samples were considered the standard of reference. Considering the results of the mutation in ctDNA by Sanger sequencing, the sensibility (Se) and specificity (Sp) were 52% and 99%, respectively. After adding the droplet digital PCR (ddPCR) analysis, the Se and Sp increased to 95% and 100%, respectively. After bivariate analysis, only the presence of double-hit lymphoma (p = 0.04) or EZH2 mutations were associated with relapse. The median Progression free survival (PFS) (95% interval confidence) was 27.7 (95% IC: 14–40) vs. 44.1 (95% IC: 40–47.6) months for the mutated vs. wild-type (wt) patients. (4) Conclusions: The ctDNA is useful for analyzing EZH2 mutations, which have an impact on PFS.
Melanoma Management: From Epidemiology to Treatment and Latest Advances
Authors: Lopes Joana , Rodrigues Cecília M. P. , Gaspar Maria Manuela , Reis Catarina Pinto
Published: September 2022

Melanoma is the deadliest skin cancer, whose morbidity and mortality indicators show an increasing trend worldwide. In addition to its great heterogeneity, melanoma has a high metastatic potential, resulting in very limited response to therapies currently available, which were restricted to surgery, radiotherapy and chemotherapy for many years. Advances in knowledge about the pathophysiological mechanisms of the disease have allowed the development of new therapeutic classes, such as immune checkpoint and small molecule kinase inhibitors. However, despite the incontestable progress in the quality of life and survival rates of the patients, effectiveness is still far from desired. Some adverse side effects and resistance mechanisms are the main barriers. Thus, the search for better options has resulted in many clinical trials that are now investigating new drugs and/or combinations. The low water solubility of drugs, low stability and rapid metabolism limit the clinical potential and therapeutic use of some compounds. Thus, the research of nanotechnology-based strategies is being explored as the basis for the broad application of different types of nanosystems in the treatment of melanoma. Future development focus on challenges understanding the mechanisms that make these nanosystems more effective.
Diagnostic Outcomes and Treatment Modalities in Patients with Mycosis Fungoides in West Sweden—A Retrospective Register-Based Study
Authors: Wojewoda Karolina , Gillstedt Martin , Englund Hanna , Ali Shada , Lewerin Catharina , Osmancevic Amra
Published: September 2022

(1) Background: Mycosis fungoides (MF) is a variant of primary cutaneous T-cell lymphoma. The aim of this study was to describe the clinical features and epidemiological and diagnostic findings in addition to the treatment modalities and responses in patients with MF. Furthermore, comparisons between patients in the early stage and the advanced stage were evaluated. (2) Methods: A retrospective register-based study based on data collected from the primary cutaneous lymphoma register and medical records was performed at the Department of Dermatology and Venerology at Sahlgrenska University Hospital, Gothenburg, Sweden. (3) Results: Eighty-four patients with a median age of 55 years with MF were included. Most of the patients (n = 73) were diagnosed at the early stage of the disease (IA–IIA). Overall disease progression was seen in 12.5% (n = 9) of the patients. Nine (10.7%) patients were deceased, out of which four (4.8%) deaths were associated with MF-related causes. (4) Conclusions: This study contributes to the knowledge of the epidemiological and clinical features in addition to the diagnostic findings and treatment responses in patients with MF in Sweden.
Diagnostic Accuracy of Liquid Biomarkers for the Non-Invasive Diagnosis of Endometrial Cancer: A Systematic Review and Meta-Analysis
Authors: Karkia Rebecca , Wali Sarah , Payne Annette , Karteris Emmanouil , Chatterjee Jayanta
Published: September 2022

Endometrial cancer rates are increasing annually due to an aging population and rising rates of obesity. Currently there is no widely available, accurate, non-invasive test that can be used to triage women for diagnostic biopsy whilst safely reassuring healthy women without the need for invasive assessment. The aim of this systematic review and meta-analysis is to evaluate studies assessing blood and urine-based biomarkers as a replacement test for endometrial biopsy or as a triage test in symptomatic women. For each primary study, the diagnostic accuracy of different biomarkers was assessed by sensitivity, specificity, likelihood ratio and area under ROC curve. Forest plots of summary statistics were constructed for biomarkers which were assessed by multiple studies using data from a random-effect models. All but one study was of blood-based biomarkers. In total, 15 studies reported 29 different exosomal biomarkers; 34 studies reported 47 different proteomic biomarkers. Summary statistic meta-analysis was reported for micro-RNAs, cancer antigens, hormones, and other proteomic markers. Metabolites and circulating tumor materials were also summarized. For the majority of biomarkers, no meta-analysis was possible. There was a low number of small, heterogeneous studies for the majority of evaluated index tests. This may undermine the reliability of summary estimates from the meta-analyses. At present there is no liquid biopsy that is ready to be used as a replacement test for endometrial biopsy. However, to the best of our knowledge this is the first study to report and meta-analyze the diagnostic accuracy of different classes of blood and urine biomarkers for detection of endometrial cancer. This review may thus provide a reference guide for those wishing to explore candidate biomarkers for further research.
The Development of a Prediction Model Based on Random Survival Forest for the Postoperative Prognosis of Pancreatic Cancer: A SEER-Based Study
Authors: Lin Jiaxi , Yin Minyue , Liu Lu , Gao Jingwen , Yu Chenyan , Liu Xiaolin , Xu Chunfang , Zhu Jinzhou
Published: September 2022

Accurate prediction for the prognosis of patients with pancreatic cancer (PC) is a emerge task nowadays. We aimed to develop survival models for postoperative PC patients, based on a novel algorithm, random survival forest (RSF), traditional Cox regression and neural networks (Deepsurv), using the Surveillance, Epidemiology, and End Results Program (SEER) database. A total of 3988 patients were included in this study. Eight clinicopathological features were selected using least absolute shrinkage and selection operator (LASSO) regression analysis and were utilized to develop the RSF model. The model was evaluated based on three dimensions: discrimination, calibration, and clinical benefit. It found that the RSF model predicted the cancer-specific survival (CSS) of the postoperative PC patients with a c-index of 0.723, which was higher than the models built by Cox regression (0.670) and Deepsurv (0.700). The Brier scores at 1, 3, and 5 years (0.188, 0.177, and 0.131) of the RSF model demonstrated the model’s favorable calibration and the decision curve analysis illustrated the model’s value of clinical implement. Moreover, the roles of the key variables were visualized in the Shapley Additive Explanations plotting. Lastly, the prediction model demonstrates value in risk stratification and individual prognosis. In this study, a high-performance prediction model for PC postoperative prognosis was developed, based on RSF The model presented significant strengths in the risk stratification and individual prognosis prediction.
Optimizing the Choice for Adjuvant Chemotherapy in Gastric Cancer
Authors: Grassadonia Antonino , De Luca Antonella , Carletti Erminia , Vici Patrizia , Di Lisa Francesca Sofia , Filomeno Lorena , Cicero Giuseppe , De Lellis Laura , Veschi Serena , Florio Rosalba , Brocco Davide , Alberti Saverio , Cama Alessandro , Tinari Nicola
Published: September 2022

Advances in the management of gastric cancer have improved patient survival in the last decade. Nonetheless, the number of patients relapsing and dying after a diagnosis of localized gastric cancer is still too high, even in early stages (10% in stage I). Adjuvant systemic chemotherapy has been proven to significantly improve outcomes. In the present article we have critically reviewed the clinical trials that guide the current clinical practice in the adjuvant treatment of patients affected by resectable gastric cancer, focusing on the different approaches worldwide, i.e., adjuvant chemotherapy, adjuvant chemoradiotherapy, and perioperative chemotherapy. We also delineate the clinical–pathological characteristics that are commonly taken into account to identify patients at a higher risk of recurrence and requiring adjuvant chemotherapy, and also describe novel biomarkers and therapeutic agents that might allow personalization of the treatment.
Cancer Cells Evade Stress-Induced Apoptosis by Promoting HSP70-Dependent Clearance of Stress Granules
Authors: Wang Aifang , Abulaiti Xianmixinuer , Zhang Han , Su Hang , Liu Guangzhi , Gao Shaorong , Li Lingsong
Published: September 2022

The formation of stress granules (SG) is regarded as a cellular mechanism to temporarily limit protein synthesis and prevent the unfolding of proteins in stressed cells. It has been noted that SG formation can promote the survival of stressed cells. Paradoxically, however, persistent SGs could cause cell death. The underlying molecular mechanism that affects the relationship between SG dynamics and cellular states is not fully understood. Here we found that SG dynamics in cancer cells differ significantly from those in normal cells. Specifically, prolonged stress caused the formation of persistent SGs and consequently resulted in apoptosis in the normal cells. By contrast, cancer cells resolved SGs and survived the prolonged stress. Regarding the mechanism, the knockdown of HSP70 or the inhibition of the HSP70s’ ATPase activity caused defective SG clearance, leading to apoptosis in otherwise healthy cancer cells. On the other hand, the knockout of G3BPs to block the formation of SGs allowed cancer cells to escape from the HSP70 inhibition-induced apoptosis. Given the observation that SG dynamics were barely affected by the inhibition of autophagy or proteasome, we propose that SG dynamics are regulated mainly by HSP70-mediated refolding of the unfolded proteins or their removal from SGs. As a result, cancer cells evade stress-induced apoptosis by promoting the HSP70-dependent SG clearance.
Evaluation of the 8th Edition AJCC Staging System for the Clinical Staging of Pancreatic Cancer
Authors: Kang Huapyong , Kim Seung-seob , Sung Min Je , Jo Jung Hyun , Lee Hee Seung , Chung Moon Jae , Park Jeong Youp , Park Seung Woo , Song Si Young , Park Mi-Suk , Bang Seungmin
Published: September 2022

The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for pancreatic cancer (PC) has been validated for pathological staging; however, its significance for clinical staging remains uncertain. We validated the prognostic performance and suitability of the current staging system for the clinical staging of PC. We identified 1043 patients from our PC registry who were staged by imaging according to the 8th edition staging system and conducted analysis, including overall survival (OS) comparison. Gradual prognostic stratification according to stage hierarchy yielded significant OS differences between stage groups, except between stage I and II (p = 0.193). A substage comparison revealed no survival differences between IB (T2N0) and IIA (T3N0), which were divided by the T3 criterion only (p = 0.278). A higher N stage had significantly shorter OS than a lower N stage (all pairwise p < 0.05). However, among the 150 patients who received upfront surgery, the pathological stage was more advanced than the clinical stage in 86 (57.3%), mostly due to a false-negative cN0 (70.9%). Our results suggest that the new definition of T3 and the number-based N criteria in the 8th edition AJCC staging system may be not adequate for clinical staging. Establishing separate criteria more suitable for clinical staging should be considered.
Application of Zn1−xCdxS Photocatalyst for Degradation of 2-CP and TC, Catalytic Mechanism
Authors: Tan Jingxin , Wei Guoqiang , Wang Zhen , Su Hui , Liu Lingtao , Li Chunhu , Bian Junjie
Published: September 2022

Zn1−xCdxS catalysts with Zeolitic Imidazolate Framework-8 (ZIF-8) as the precursor were successfully prepared by ion exchange method, and the ability and electrochemical properties of a series of ZIF-8, ZnS and Zn1−xCdxS catalysts in photocatalytic degradation of 2-CP and TC were investigated. Doping of Cd ions was able to modulate the ZnS band gap width and improve the utilization of visible light by the photocatalyst. The nanocage catalysts with hollow structure of Zn1−xCdxS have better photocatalytic response. The removal of photocatalytic pollutants was up to 90% under optimal conditions. Using a Peroxymonosulfate (PMS)-assisted system to improve the degradation efficiency of 2-chlorophenol and tetracycline hydrochloride under visible light, we present a possible mechanism of Zn1−xCdxS as a photocatalyst for degradation in persistent pollutants and in PMS-assisted photocatalysis. Four active species, O2−, h+, -OH, and SO4•−, can be generated to degrade 2-chlorophenol and tetracycline hydrochloride under PMS-assisted activation. Zn1−xCdxS nanocage with high activity and stability provides a feasible approach to catalytically remove persistent pollutants from aqueous solutions under visible light conditions.
A Review of CeO2 Supported Catalysts for CO2 Reduction to CO through the Reverse Water Gas Shift Reaction
Authors: Ebrahimi Parisa , Kumar Anand , Khraisheh Majeda
Published: September 2022

The catalytic conversion of CO2 to CO by the reverse water gas shift (RWGS) reaction followed by well-established synthesis gas conversion technologies could be a practical technique to convert CO2 to valuable chemicals and fuels in industrial settings. For catalyst developers, prevention of side reactions like methanation, low-temperature activity, and selectivity enhancements for the RWGS reaction are crucial concerns. Cerium oxide (ceria, CeO2) has received considerable attention in recent years due to its exceptional physical and chemical properties. This study reviews the use of ceria-supported active metal catalysts in RWGS reaction along with discussing some basic and fundamental features of ceria. The RWGS reaction mechanism, reaction kinetics on supported catalysts, as well as the importance of oxygen vacancies are also explored. Besides, recent advances in CeO2 supported metal catalyst design strategies for increasing CO2 conversion activity and selectivity towards CO are systematically identified, summarized, and assessed to understand the impacts of physicochemical parameters on catalytic performance such as morphologies, nanosize effects, compositions, promotional abilities, metal-support interactions (MSI) and the role of selected synthesis procedures for forming distinct structural morphologies. This brief review may help with future RWGS catalyst design and optimization.
Decorating Zirconium on Graphene Oxide to Design a Multifunctional Nanozyme for Eco-Friendly Detection of Hydrogen Peroxide
Authors: Siddiqui Ayesha Saleem , Ahmad Muhammad Ashfaq , Nawaz Mian Hasnain , Hayat Akhtar , Nasir Muhammad
Published: September 2022

Peroxidase enzymes are crucial in analytical chemistry owing to significant peroxide analytes and their key role in hydrogen peroxide (H2O2) detection. Therefore, exploiting appropriate catalysts for the peroxidase like reactions has become crucial for achieving desired analytical performance. Zirconium (Zr) has attracted growing interest, as a safe and stable potential eco-friendly catalyst for various organic transformations that address increasing environmental challenges. Hence, aiming at fast, sensitive and selective optical detection of H2O2, a colorimetric platform is presented here, based on the excellent peroxidase enzyme-like activity of Zr decorated on graphene oxide (GO). The synergistic effect achieved due to intimate contact between an enzyme like Zr and the high surface area 0f GO ensures efficient electron transfer that increases the chemical and catalytic activity of the composite and advances the decomposition of H2O2 into hydroxyl radicals. The designed probe, thus, efficiently catalyzes the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB), via hydroxyl radicals, thereby transforming the colorless TMB into blue oxidized TMB within 2 min. The catalytic mechanism of the Zr-GO enzyme mimic is proposed herein and verified using a fluorescent probe terephthalic acid (TA) and other scavenger experiments. The multifunctional optical probe allows sensitive and highly selective recognition of H2O2 in a linear range from 100 to 1000 µM with a low detection limit of 0.57 µM. Essentially, the direct accessibility of Zr prevents having to use the complicated preparation and purification procedures mostly practiced for conventional biozymes and nanozymes. The devised method offers several gains, including being green and an inexpensive catalyst, having lower LOD, being fast, cost-effective and sensitive, and having selective work-up procedures.
Accelerated Photodegradation of Organic Pollutants over BiOBr/Protonated g-C3N4
Authors: Liu Juanjuan , Guo Heng , Yin Haoyong , Nie Qiulin , Zou Shihui
Published: September 2022

Interfacial engineering has emerged as an effective strategy to optimize the photocatalytic activity of heterojunctions. Herein, the interface between graphitic carbon nitride (g-C3N4) and BiOBr was readily regulated by a protonation treatment. The synthesized BiOBr/g-C3N4 heterojunctions were characterized by X-ray diffraction, scanning electron microscopy, X-ray photoelectron spectroscopy, and UV-Vis diffuse reflectance spectroscopy. The results show that pretreating g-C3N4 in diluted HCl solution led to a partial protonation of g-C3N4, which ensured intimate contact and high dispersion of supported BiOBr without changing the surface area, bulk g-C3N4 structure, or visible light absorption. The abundant BiOBr/g-C3N4 interfaces remarkably improved the separation and transfer of photogenerated carriers, which produced more h+ and O2●− to accelerate the photocatalytic degradation of organic pollutants. The photocatalytic activities of the BiOBr/g-C3N4 heterojunctions were evaluated by the degradation of RhB under visible-light irradiation (λ ≥ 420 nm). The apparent reaction (pseudo-first-order) rate constant of BiOBr supported on partially protonated g-C3N4 (Bpg-C3N4-0.75) is ca. 3-fold higher than that of BiOBr supported on pristine g-C3N4 (Bg-C3N4), verifying interfacial engineering as an effective strategy to optimize the catalytic activity of heterojunctions.
Fabrication of TaON/CdS Heterostructures for Enhanced Photocatalytic Hydrogen Evolution under Visible Light Irradiation
Authors: Chen Fu , Fu Haitao , Yang Xiaohong , Xiong Shixian , An Xizhong
Published: September 2022

Developing high-performance photocatalysts for H2 production via fabricating heterojunctions has attracted much attention. Herein, we design a simple strategy to prepare composites that consist of TaON/CdS hybrids via a hydrothermal process. The results show that the pristine CdS nanoparticles loaded with 20 wt% TaON (TC4) could maximize the photocatalytic hydrogen evolution rate to 19.29 mmol g−1 h−1 under visible light irradiation, which was 2.13 times higher than that of the pristine CdS (9.03 mmol g−1 h−1) under the same conditions. The apparent quantum yield (AQY) of the TC4 nanocomposites at 420 nm was calculated to be 18.23%. The outstanding photocatalytic performance of the composites can be ascribed to the formation of heterojunctions. The electrochemical measurements indicate that the decoration facilitates the generation of extra photo-electrons, prolonging the recombination rate of photogenerated charge carriers, offering adequate active sites and improving catalytic stability. This study sheds light on the construction strategy and the deep understanding of the novel CdS-based composites for high-performance photocatalytic H2 production.
Ru/Pd Complex and Its Monometallic Fragments as Catalysts for Norbornene Polymerization via ROMP and Addition
Authors: Cruz Thaís R. , Masson Gustavo H. C. , Amorim Kelly A. E. , Machado Antonio E. H. , Goi Beatriz E. , Carvalho-Jr. Valdemiro P.
Published: September 2022

The [Ru(PPh3)2Cl-piperidine(4-aminomethyl)] complex (mono-Ru) was synthesized from [Ru(PPh3)3Cl2] and 4-(aminomethyl)piperidine, whereas the [(PPh3)PdCl(Shiff-pip)] complex (mono-Pd) was obtained by reacting [Pd(PPh3)2Cl2] with its respective Schiff base ligand, both at a 1:1 molar ratio. The heterobimetallic [RuCl2(PPh3)2](μ-Schiff)Pd(PPh3)Cl] complex (Ru/Pd) was synthesized via a one-pot, three-component reaction of mono-Ru, [(Pd(PPh3)2Cl2] and salicylaldehyde. All complexes were fully characterized by FTIR, UV-Vis, and NMR spectroscopy, as well as elemental analysis, MALDI-TOF mass spectrometry, cyclic voltammetry, and computational studies. Ru/Pd was able to polymerize norbornene (NBE) by two different mechanisms: ROMP and vinyl polymerization. The Ru fragment was active for ROMP of NBE, reaching yields of 68 and 31% for mono-Ru and Ru/Pd, respectively, when the [NBE]/[Ru] = 3000 molar ratio and 5 μL EDA addition were employed at 50 °C. The poly(norbornene) (polyNBE) obtained presented an order of magnitude of 104 g mol−1 and Ð values between 1.48 and 1.79. For the vinyl polymerization of NBE, the Pd fragment was active using MAO as a cocatalyst, reaching a yield of 47.0% for Ru/Pd and quantitative yields for mono-Pd when [Al]/[Pd] = 2500 and [NBE]/[Pd] = 20,000 molar ratios were employed, both at 60 °C.
HIV-1 Infection of Long-Lived Hematopoietic Precursors In Vitro and In Vivo
Authors: Renelt Sebastian , Schult-Dietrich Patrizia , Baldauf Hanna-Mari , Stein Stefan , Kann Gerrit , Bickel Markus , Kielland-Kaisen Ulrikke , Bonig Halvard , Marschalek Rolf , Rieger Michael A. , Dietrich Ursula , Duerr Ralf
Published: September 2022

Latent reservoirs in human-immunodeficiency-virus-1 (HIV-1)-infected individuals represent a major obstacle in finding a cure for HIV-1. Hematopoietic stem and progenitor cells (HSPCs) have been described as potential HIV-1 targets, but their roles as HIV-1 reservoirs remain controversial. Here we provide additional evidence for the susceptibility of several distinct HSPC subpopulations to HIV-1 infection in vitro and in vivo. In vitro infection experiments of HSPCs were performed with different HIV-1 Env-pseudotyped lentiviral particles and with replication-competent HIV-1. Low-level infection/transduction of HSPCs, including hematopoietic stem cells (HSCs) and multipotent progenitors (MPP), was observed, preferentially via CXCR4, but also via CCR5-mediated entry. Multi-lineage colony formation in methylcellulose assays and repetitive replating of transduced cells provided functional proof of susceptibility of primitive HSPCs to HIV-1 infection. Further, the access to bone marrow samples from HIV-positive individuals facilitated the detection of HIV-1 gag cDNA copies in CD34+ cells from eight (out of eleven) individuals, with at least six of them infected with CCR5-tropic HIV-1 strains. In summary, our data confirm that primitive HSPC subpopulations are susceptible to CXCR4- and CCR5-mediated HIV-1 infection in vitro and in vivo, which qualifies these cells to contribute to the HIV-1 reservoir in patients.
Dexras1 Induces Dysdifferentiation of Oligodendrocytes and Myelin Injury by Inhibiting the cAMP-CREB Pathway after Subarachnoid Hemorrhage
Authors: Xin Yuanjun , Chen Jie , Zhang Hongxia , Ostrowski Robert P. , Liang Yidan , Zhao Jun , Xiang Xiang , Liang Fuming , Fu Wenqiao , Huang Hao , Wu Xintong , Su Jun , Deng Jiewen , He Zhaohui
Published: September 2022

White matter damage (WMD), one of the research hotspots of subarachnoid hemorrhage (SAH), mainly manifests itself as myelin injury and oligodendrocyte differentiation disorder after SAH, although the specific mechanism remains unclear. Dexamethasone-induced Ras-related protein 1(Dexras1) has been reported to be involved in nervous system damage in autoimmune encephalitis and multiple sclerosis. However, whether Dexras1 participates in dysdifferentiation of oligodendrocytes and myelin injury after SAH has yet to be examined, which is the reason for creating the research content of this article. Here, intracerebroventricular lentiviral administration was used to modulate Dexras1 levels in order to determine its functional influence on neurological injury after SAH. Immunofluorescence, transmission electron microscopy, and Western blotting methods, were used to investigate the effects of Dexras1 on demyelination, glial cell activation, and differentiation of oligodendrocyte progenitor cells (OPCs) after SAH. Primary rat brain neurons were treated with oxyhemoglobin to verify the association between Dexras1 and cAMP-CREB. The results showed that Dexras1 levels were significantly increased upon in vivo SAH model, accompanied by OPC differentiation disturbances and myelin injury. Dexras1 overexpression significantly worsened OPC dysdifferentiation and myelin injury after SAH. In contrast, Dexras1 knockdown ameliorated myelin injury, OPC dysdifferentiation, and glial cell activation. Further research of the underlying mechanism discovered that the cAMP-CREB pathway was inhibited after Dexras1 overexpression in the in vitro model of SAH. This study is the first to confirm that Dexras1 induced oligodendrocyte dysdifferentiation and myelin injury after SAH by inhibiting the cAMP-CREB pathway. This present research may reveal novel therapeutic targets for the amelioration of brain injury and neurological dysfunction after SAH.
DICAM in the Extracellular Vesicles from Astrocytes Attenuates Microglia Activation and Neuroinflammation
Authors: Han Jin , Cho Hyun-Jung , Park Donghwi , Han Seungwoo
Published: September 2022

Cross-talk between astrocytes and microglia plays an important role in neuroinflammation and central sensitization, but the manner in which glial cells interact remains less well-understood. Herein, we investigated the role of dual immunoglobulin domain-containing cell adhesion molecules (DICAM) in the glial cell interaction during neuroinflammation. DICAM knockout (KO) mice revealed enhanced nociceptive behaviors and glial cell activation of the tibia fracture with a cast immobilization model of complex regional pain syndrome (CRPS). DICAM was selectively secreted in reactive astrocytes, mainly via extracellular vesicles (EVs), and contributed to the regulation of neuroinflammation through the M2 polarization of microglia, which is dependent on the suppression of p38 MAPK signaling. In conclusion, DICAM secreted from reactive astrocytes through EVs was involved in the suppression of microglia activation and subsequent attenuation of neuroinflammation during central sensitization.
Exploration of N6-Methyladenosine Profiles of mRNAs and the Function of METTL3 in Atherosclerosis
Authors: Zhou Yaqing , Jiang Rongli , Jiang Yali , Fu Yahong , Manafhan Yerbolat , Zhu Jinfu , Jia Enzhi
Published: September 2022

Objectives: N6-methylladenosine (m6A) modification has not been fully studied in atherosclerosis. The objectives of this study were to investigate differentially expressed m6A methylated peaks and mRNAs, along with the regulatory role of methyltransferase 3 (METTL3) in pathological processes of atherosclerosis. Methods: The pathological models of human coronary artery smooth muscle cells (HCASMCs) were induced in vitro. The differentially expressed mRNAs and m6A peaks were identified by RNA-Seq and meRIP-Seq. The potential mechanisms were analyzed via bioinformatic assays. Methylases expression was tested by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting (WB) in HCASMCs, and by immunohistochemical assays in 40 human coronary arteries. The knockdown of METTL3 expression in cells was performed by siRNA transfection, and cell proliferation and migration were detected after transfection. Results: We identified 5121 m6A peaks and 883 mRNAs that were expressed differentially in the pathological processes of HCASMCs. Bioinformatic analyses showed that the different m6A peaks were associated with cell growth and cell adhesion, and the 883 genes showed that the extracellular matrix and PI3K/AKT pathway regulate the processes of HCASMCs. Additionally, 10 hub genes and 351 mRNAs with differential methylation and expression levels were found. METTL3 was upregulated in the arteries with atherosclerotic lesions and in the proliferation and migration model of HCASMCs, and pathological processes of HCASMCs could be inhibited by the knockdown of METTL3. The mechanisms behind regulation of migration and proliferation reduced by siMETTL3 are concerned with protein synthesis and energy metabolism. Conclusions: These results revealed a new m6A epigenetic method to regulate the progress of atherosclerosis, which suggest approaches for potential therapeutic interventions that target METTL3 for the prevention and treatment of coronary artery diseases.
The Potential of Moringa oleifera to Ameliorate HAART-Induced Pathophysiological Complications
Authors: Ndlovu Siqiniseko S. , Ghazi Terisha , Chuturgoon Anil A.
Published: September 2022

Highly active antiretroviral therapy (HAART) comprises a combination of two or three antiretroviral (ARV) drugs that are administered together in a single tablet. These drugs target different steps within the human immunodeficiency virus (HIV) life cycle, providing either a synergistic or additive antiviral effect; this enhances the efficiency in which viral replication is suppressed. HIV cannot be completely eliminated, making HAART a lifetime treatment. With long-term HAART usage, an increasing number of patients experience a broadening array of complications, and this significantly affects their quality of life, despite cautious use. The mechanism through which ARV drugs induce toxicity is associated with metabolic complications such as mitochondrial dysfunction, oxidative stress, and inflammation. To address this, it is necessary to improve ARV drug formulation without compromising its efficacy; alternatively, safe supplementary medicine may be a suitable solution. The medicinal plant Moringa oleifera (MO) is considered one of the most important sources of novel nutritionally and pharmacologically active compounds that have been shown to prevent and treat various diseases. MO leaves are rich in polyphenols, vitamins, minerals, and tannins; studies have confirmed the therapeutic properties of MO. MO leaves provide powerful antioxidants, scavenge free radicals, promote carbohydrate metabolism, and repair DNA. MO also induces anti-inflammatory, hepatoprotective, anti-proliferative, and anti-mutagenic effects. Therefore, MO can be a source of affordable and safe supplement therapy for HAART-induced toxicity. This review highlights the potential of MO leaves to protect against HAART-induced toxicity in HIV patients.
Preliminary Development and Testing of C595 Radioimmunoconjugates for Targeting MUC1 Cancer Epitopes in Pancreatic Ductal Adenocarcinoma
Authors: Hull Ashleigh , Li Yanrui , Bartholomeusz Dylan , Hsieh William , Tieu William , Pukala Tara L. , Staudacher Alexander H. , Bezak Eva
Published: September 2022

Mucin 1 is a transmembrane glycoprotein which overexpresses cancer-specific epitopes (MUC1-CE) on pancreatic ductal adenocarcinoma (PDAC) cells. As PDAC is a low survival and highly aggressive malignancy, developing radioimmunoconjugates capable of targeting MUC1-CE could lead to improvements in PDAC outcomes. The aim of this study was to develop and perform preliminary testing of diagnostic and therapeutic radioimmunoconjugates for PDAC using an anti-MUC1 antibody, C595. Firstly, p-SCN-Bn-DOTA was conjugated to the C595 antibody to form a DOTA-C595 immunoconjugate. The stability and binding affinity of the DOTA-C595 conjugate was evaluated using mass spectrometry and ELISA. DOTA-C595 was radiolabelled to Copper-64, Lutetium-177, Gallium-68 and Technetium-99m to form novel radioimmunoconjugates. Cell binding assays were performed in PANC-1 (strong MUC1-CE expression) and AsPC-1 (weak MUC1-CE expression) cell lines using 64Cu-DOTA-C595 and 177Lu-DOTA-C595. An optimal molar ratio of 4:1 DOTA groups per C595 molecule was obtained from the conjugation process. DOTA-C595 labelled to Copper-64, Lutetium-177, and Technetium-99m with high efficiency, although the Gallium-68 labelling was low. 177Lu-DOTA-C595 demonstrated high cellular binding to the PANC-1 cell lines which was significantly greater than AsPC-1 binding at concentrations exceeding 100 nM (p < 0.05). 64Cu-DOTA-C595 showed similar binding to the PANC-1 and AsPC-1 cells with no significant differences observed between cell lines (p > 0.05). The high cellular binding of 177Lu-DOTA-C595 to MUC1-CE positive cell lines suggests promise as a therapeutic radioimmunoconjugate against PDAC while further work is required to harness the potential of 64Cu-DOTA-C595 as a diagnostic radioimmunoconjugate.
Determination of Pb(II) Ions in Water by Fluorescence Spectroscopy Based on Silver Nanoclusters
Authors: Burratti Luca , Maranges Valentin , Sisani Michele , Naryyev Eziz , De Matteis Fabio , Francini Roberto , Prosposito Paolo
Published: September 2022

In this work, a method to determine Pb(II) ions in model water is presented; the method is based on the fluorescence emission of a silver nanoclusters (AgNCs) colloidal solution, which is sensitive to lead ions. The presence of Pb(II) ions causes a photoemission enhancement of the AgNCs solution dependent on the pollutant concentration. The functional dependence is logarithmic in the range from 2.5 to 40 µM, and through the linearization of the calibration points, a linear function is determined and exploited for the extrapolation of the test Pb(II) concentrations with a precision estimated by relative standard deviation (RSD) ranging from 21% to 10% from the highest to the lowest Pb(II) quantity, respectively. Finally, inductively coupled plasma–optical emission spectroscopy (ICP-OES) successfully validated the described method. The accuracy of the method is also studied for intentionally polluted mineral waters, revealing the same trend of the model water: the lower the concentration, the higher the precision of the method.
A Molecularly Imprinted Polymer-Disposable Pipette Tip Extraction-Capillary Electrophoresis (MISPE-DPX-CE) Method for the Preconcentration and Determination of Scopolamine in Synthetic Urine Samples
Authors: Silva Weida Rodrigues , Ribeiro Michelle M. A. C. , Richter Eduardo Mathias , Batista Alex D. , da Silveira Petruci João Flávio
Published: September 2022

Alcoholic beverages contaminated with scopolamine (SCP) are often employed for criminal purposes due to their sedative effect. The determination of the residual levels of SCP in body fluids (e.g., urine) can help to track possible victims of induced ingestions. Biological sample analysis usually requires a preconcentration step to enhance their detectability and to provide sample clean-up. Molecularly imprinted polymers (MIPs) in lieu of conventional solid sorbents represent an enhancement of selectivity, due to their specific recognition sites. Additionally, the adaptation of the solid-phase extraction (SPE) cartridge into a disposable pipette tip extraction (DPX) contributes to the miniaturization of the sample preparation step. Herein, an analytical method for the determination of SCP in synthetic urine samples via the integration of molecularly imprinted solid-phase extraction (MISPE) with DPX as a preconcentration step prior to capillary electrophoresis analysis (also known as MISPE-DPX-CE) is presented. The extraction and elution steps were optimized using a factorial design. Using the optimized conditions, a preconcentration factor of 20 was obtained, leading to a working range of 0.5–6 µM with LOD of 0.04 µM and repeatability of 6.4% (n = 7) and adequate recovery values (84 and 101%) The proposed MISPE-DPX-CE approach was successfully applied to selective extraction, preconcentration, and determination of SCP in synthetic urine samples.
Au/La Co-Modified In2O3 Nanospheres for Highly Sensitive Ethanol Gas Detection
Authors: Liu Hang , Li Peihua , Liu Bing , Zhang Tong , Zhang Yuhong
Published: September 2022

In this paper, the gas-sensitive properties of co-doping the rare earth element La and noble metal Au in In2O3 nanospheres were investigated for ethanol detection. Through XRD and SEM characterization, the grain size of La-In2O3 and Au/La-In2O3 nanoparticles was smaller than that of pure In2O3. As expected, the smaller grain size sample has shown a higher response for ethanol vapor. Compared with the pure In2O3 nanoparticles, the 2 mol%Au/2 mol%La-In2O3 sample has shown better ethanol-sensing properties, including higher sensitivity (S = 381) and lower operating temperature (210 °C) for 100 ppm ethanol vapor. In addition, the Au/La-In2O3 sensor presented a fast response time (1 s). The enhancement mechanism of the ethanol response was discussed for Au/La-In2O3 nanoparticles. The obtained experimental results would provide a new road for designing higher response sensors.
An a Priori Approach to Small Airway Dysfunction in Pediatric Asthmatics
Authors: Hopp Russell , Lee Junghyae , Bohan Heather
Published: September 2022

Small airway dysfunction remains a stepchild in the pediatric asthma care pathway. In brief, elements of the pulmonary function test (PFT) concerning smaller airway data remain less utilized. To further the value of the standard PFT we underwent a prospective Proof of Concept (POC) project, utilizing the outpatient performance of PFT tests in children 6–18 years during a 15-month period. The goal of the study was to determine if a priori the PFT represented a small airway disease pattern or not. Only the pulmonary function was used to make that distinction. Children 6–18 years with asthma who completed a PFT had their PFT as being characterized with or without a small airway dysfunction (SAD) designation, coded in the electronic medical record as an a priori decision using the code J98.4 (other disorders of lung) as a marker for electronic medical records retrieval. Subsequently, the results were analyzed between a group of 136 children designated (a priori) as having no small airway dysfunction in comparison to 91 children a priori designated as having small airway dysfunction. The a priori designation groups were post hoc compared for large and smaller airway function differences. Both large and smaller airway dysfunction were highly significantly different between the 2 groups, based solely on the initial division of the total group based on the decision the PFT represented a small airway pattern. We concluded the baseline pulmonary function test used in the evaluation of pediatric asthma has readily identifiable information regarding the presence of small airway dysfunction, and we characterized what was unique on the PFT based on that SAD classification
Oral Cavity Calprotectin and Lactoferrin Levels in Relation to Radiotherapy
Authors: Keskin Mutlu , Kompuinen Jenna , Harmankaya İlknur , Karaçetin Didem , Nissilä Verneri , Gürsoy Mervi , Sorsa Timo , Gürsoy Ulvi Kahraman
Published: September 2022

Background: Lactoferrin, an iron-binding glycoprotein, and calprotectin, a calcium binding protein, are sensitive markers of inflammation and their fecal levels increase during radiotherapy of prostate cancer patients. With this background, we analyzed mouthrinse calprotectin and lactoferrin levels of head- and neck-cancer patients before, during and after radiotherapy. Methods: Twenty cancer patients (mean age 55.85 ± 15.01, 80% male), who had been planned to undergo radiotherapy to the head and neck area, were included in this study. Mouthrinse samples were collected before radiotherapy, at the 3rd and 6th weeks of radiotherapy and 4 weeks after the radiotherapy. Mouthrinse samples were analyzed for calprotectin and lactoferrin using commercial ELISA kits. Results: Calprotectin levels increased significantly during radiotherapy (p = 0.022). Both markers, lactoferrin (p = 0.011) and calprotectin (p = 0.006), decreased significantly after the treatment. Conclusions: Present study results may suggest that the elevations in calprotectin and lactoferrin levels during radiotherapy reflect the increased and emerging inflammatory environment in the oral cavity, thus may increase the risk of periodontal disease initiation or progression.
Behavior of Reinforcing Bar Connection of Hollow-Core Slabs to Steel Beams under In-Plane Forces
Authors: Brito Susana Hernandez , Mahmoud Karam , El-Salakawy Ehab F.
Published: September 2022

Hollow-core slab (HCS) floors supported on steel beams require the use of steel reinforcement as connections to avoid slab displacement caused by lateral loads. However, current North American design codes offer limited provisions on the design and behavior of such connections. In this study, the results of an experimental investigation conducted on such connections to assess their capacity and mode of failure are presented. Eleven full-scale assemblies of HCS reinforcing bar connections to steel beams were tested to failure under monotonic in-plane loading (compression, tension, or shear). Test results revealed that connections tested under compression failed by bar buckling without yielding. Under tension, the connection bar reached close-to-yielding or yielding strains at the unrestrained portion of the bar, followed by grout splitting in the shear key or the grouted core. Finally, the mechanism of failure of specimens subjected to shear was governed by bar yielding.
Approach to Thromboprophylaxis for Prevention of Venous Thromboembolism in COVID-19: Global Updates and Clinical Insights from India
Authors: Ramakrishnan Nagarajan , Ramasubban Suresh , Hegde Ashit , Govil Deepak
Published: September 2022

Venous thromboembolism (VTE) frequently occurs in patients with coronavirus disease-19 (COVID-19) and is associated with increased mortality. Several global guidelines recommended prophylactic-intensity anticoagulation rather than intermediate-intensity or therapeutic-intensity anticoagulation for patients with COVID-19-related acute or critical illness without suspected or confirmed VTE. Even though standard doses of thromboprophylaxis are received, many cases of thrombotic complications are reported; hence, appropriate and adequate thromboprophylaxis is critical for the prevention of VTE in COVID-19. In spite of an increased prevalence of VTE in Indian patients, sufficient data on patient characteristics, diagnosis, and therapeutic approach for VTE in COVID is lacking. In this article, we review the available global literature (search conducted up to 31 May 2021) and provide clinical insights into our approach towards managing VTE in patients with COVID-19. Furthermore, in this review, we summarize the incidence and risk factors for VTE with emphasis on the thromboprophylaxis approach in hospitalized patients and special populations with COVID-19 and assess clinical implications in the Indian context.
Sol–Gel-Process-Based Molten-Flux Synthesis of Plate-like La2NiO4+δ Particles
Authors: Escobar Cano Giamper , Brinkmann Yannick , Zhao Zhijun , Kißling Patrick A. , Feldhoff Armin
Published: September 2022

La2NiO4+δ particles with a plate-like morphology were prepared from a NaOH melt by molten-flux synthesis. For this purpose, the intermediates from a sol–gel process were used as reactants. Using powder X-ray diffraction, the sol–gel intermediates were identified as a mixture of tetragonal La2O2CO3 and cubic NiO. The existence of NiO was also confirmed by transmission electron microscopy in combination with electron-energy loss spectroscopy. The ultrafine mixed sol–gel intermediates were then mixed with NaOH powder and additional water in a nickel crucible and heated to 673 K for 8 h. The chemical reactions in the air during the molten-flux synthesis and the influence of the salt on the formation of La2NiO4+δ were examined by thermogravimetric analysis. The powder X-ray diffraction indicated a K2NiF4-type tetragonal structure with the I4/mmm space group for the reaction product. The scanning electron microscopy showed plate-like La2NiO4+δ crystals with a length and thickness of approximately 9 µm and 2 µm, respectively, while the energy-dispersive X-ray spectroscopy revealed a homogeneous distribution of lanthanum and nickel in the product powder. The influence of the processing parameters on the product generation, as well as on the size and morphology of the La2NiO4+δ particles, was systematically studied.
Noninvasive Determination of the IDH Status of Gliomas Using MRI and MRI-Based Radiomics: Impact on Diagnosis and Prognosis
Authors: Li Yurong , Qin Qin , Zhang Yumeng , Cao Yuandong
Published: September 2022

Gliomas are the most common primary malignant brain tumors in adults. The fifth edition of the WHO Classification of Tumors of the Central Nervous System, published in 2021, provided molecular and practical approaches to CNS tumor taxonomy. Currently, molecular features are essential for differentiating the histological subtypes of gliomas, and recent studies have emphasized the importance of isocitrate dehydrogenase (IDH) mutations in stratifying biologically distinct subgroups of gliomas. IDH plays a significant role in gliomagenesis, and the association of IDH status with prognosis is very clear. Recently, there has been much progress in conventional MR imaging (cMRI), advanced MR imaging (aMRI), and radiomics, which are widely used in the study of gliomas. These advances have resulted in an improved correlation between MR signs and IDH mutation status, which will complement the prediction of the IDH phenotype. Although imaging cannot currently substitute for genetic tests, imaging findings have shown promising signs of diagnosing glioma subtypes and evaluating the efficacy and prognosis of individualized molecular targeted therapy. This review focuses on the correlation between MRI and MRI-based radiomics and IDH gene-phenotype prediction, discussing the value and application of these techniques in the diagnosis and evaluation of the prognosis of gliomas.