bluuebunny/crossref_metadata_2025 huggingface dataset:
The Absence of Gasdermin D Reduces Nuclear Autophagy in a Cecal Ligation and Puncture-Induced Sepsis-Associated Encephalopathy Mouse Model
Authors: Su Wei , Xie Zhenxing , Bai Xiangjun , Li Zhanfei , Liu Xinghua
Published: March 2023

Sepsis-associated encephalopathy (SAE) is a common complication of sepsis, which is a life-threatening condition resulting from a dysregulated host response to infection. Pyroptosis, a pro-inflammatory mode of lytic cell death mediated by GSDMD (Gasdermin D), is involved in the pathogenesis of SAE. While autophagy has been extensively studied in SAE, the role of nuclear autophagy is not yet well understood. In this study, we aimed to investigate the involvement of pyroptosis and neural nuclear autophagy in the pathogenesis of SAE. We analyzed a CLP (cecal ligation and puncture)-induced SAE model in wild-type and GSDMD−/− mice to gain insights into the underlying mechanisms. Here, we show that in sepsis, neural nuclear autophagy is extremely activated, and nuclear LaminB decreases and is accompanied by an increase in the ratio of LC3BII/I. These effects can be reversed in GSDMD−/− mice. The behavioral outcomes of septic wild-type mice are impaired by the evidence from the novel object recognition test (NORT) and open field test (OFT), but are improved in septic GSDMD−/− mice. In conclusion, our study demonstrates the activation of neural nuclear autophagy in SAE. The absence of GSDMD inhibits nuclear autophagy and improves the behavioral outcomes of SAE.
Impact of Gender on Insomnia
Authors: Boer Jolijn , Höhle Nadya , Rosenblum Lisa , Fietze Ingo
Published: March 2023

There is a distinct preponderance of female insomniacs when compared to male insomniacs. The aim of this study was to examine possible gender differences in the causes for insomnia, and the phenotypes of insomnia, and to investigate whether gender-specific insomnia diagnosis and treatment could be relevant in clinical practice. Data were collected from 121 insomniac patients by a medical specialist in the framework of normal clinical practice in Germany. The data consist of the patient’s medical history and various sleep-related patient questionnaires. Data from both genders were tested for independence using chi-square tests and Mann–Whitney U tests. We found a correlation between the gender of the patient and insomnia phenotypes in several aspects: concomitant lipometabolic disorders, diabetes mellitus, and high BMIs are more common in male insomniacs (p < 0.05). Frequency of insomnia occurrence in certain age groups, insomnia severity, distribution of SOI (sleep onset insomnia), SMI (sleep maintenance insomnia) and combined SOI + SMI, sleep duration, the time needed to seek medical consultation, trying out sleep-inducing drugs/techniques and the trigger, etiology and familial predisposition of the insomniac disorder were independent of the patient’s gender. We would like to re-evaluate the results with a larger number of patients in a further study.
The Association between COVID-19 Related Anxiety, Stress, Depression, Temporomandibular Disorders, and Headaches from Childhood to Adulthood: A Systematic Review
Authors: Minervini Giuseppe , Franco Rocco , Marrapodi Maria Maddalena , Mehta Vini , Fiorillo Luca , Badnjević Almir , Cervino Gabriele , Cicciù Marco
Published: March 2023

Objective: The coronavirus belongs to the family of Coronaviridae, which are not branched single-stranded RNA viruses. COVID-19 creates respiratory problems and infections ranging from mild to severe. The virus features mechanisms that serve to delay the cellular immune response. The host’s response is responsible for the pathological process that leads to tissue destruction. Temporomandibular disorders are manifested by painful jaw musculature and jaw joint areas, clicks, or creaks when opening or closing the mouth. All these symptoms can be disabling and occur during chewing and when the patient yawns or even speaks. The pandemic situation has exacerbated anxieties and amplified the vulnerability of individuals. Therefore, from this mechanism, how the COVID-19 pandemic may have increased the incidence of temporomandibular disorders is perceived. The purpose of this review is to evaluate whether COVID-19-related anxiety has caused an increase in temporomandibular dysfunction symptoms in adults to children. Methods: PubMed, Web of Science, Lilacs, and Scopus were systematically searched, until 30 July 2022, to identify studies presenting: the connection between COVID-19 with temporomandibular disorders. Results: From 198 papers, 4 studies were included. Literature studies have shown that the state of uncertainty and anxiety has led to an increase in the incidence of this type of disorder, although not all studies agree. Seventy-three studies were identified after viewing all four search engines; at the end of the screening phase, only four were considered that met the PECO, the planned inclusion, and the exclusion criteria. All studies showed a statistically significant correlation between temporomandibular disorders and COVID-19 with a p < 0.05. Conclusions: All studies agreed that there is an association between COVID-19 and increased incidence of temporomandibular disorders.
An Analysis of Deep Learning Models in SSVEP-Based BCI: A Survey
Authors: Xu Dongcen , Tang Fengzhen , Li Yiping , Zhang Qifeng , Feng Xisheng
Published: March 2023

The brain–computer interface (BCI), which provides a new way for humans to directly communicate with robots without the involvement of the peripheral nervous system, has recently attracted much attention. Among all the BCI paradigms, BCIs based on steady-state visual evoked potentials (SSVEPs) have the highest information transfer rate (ITR) and the shortest training time. Meanwhile, deep learning has provided an effective and feasible solution for solving complex classification problems in many fields, and many researchers have started to apply deep learning to classify SSVEP signals. However, the designs of deep learning models vary drastically. There are many hyper-parameters that influence the performance of the model in an unpredictable way. This study surveyed 31 deep learning models (2011–2023) that were used to classify SSVEP signals and analyzed their design aspects including model input, model structure, performance measure, etc. Most of the studies that were surveyed in this paper were published in 2021 and 2022. This survey is an up-to-date design guide for researchers who are interested in using deep learning models to classify SSVEP signals.
Effects of Mindfulness-Based Interventions (MBIs) in Patients with Early-Stage Alzheimer’s Disease: A Pilot Study
Authors: Giulietti M. V. , Spatuzzi R. , Fabbietti P. , Vespa A.
Published: March 2023

Bachground In this study, we hypothesize that mindfulness-based interventions (MBIs) may improve well-being and the related outcomes in Alzheimer’s dementia patients (AD-P) at an early stage. MBIs consist of the practice of consciously observing the psychic contents in the present moment (thoughts, sensations, feelings, and other events). This attention allows one to become aware of the psychic contents and integrate them, thus favoring the quality of life and an increase in the mood of practitioners. Methods The randomized controlled study enrolled 22 AD-P at an early stage (age ≥ 60 years) treated with MBIs and 22 patients without treatment (six months of MBI training). Tests (T0–T1 six months): Mini-Mental State Examination (MMPI); Spiritual Well-Being (SWB); Beck Depression Inventory (BDI); SF36. Test-Caregiver: Everyday Cognition scales (ECOG). Results AD-P with mindfulness: Improvement of ECOG (p = 0.026), quality of life (p < 0.001), spiritual well-being (p < 0.001); decrease in depression BDI (p < 0.001). The MMSE remains unchanged. The control group of untreated patients showed a significant worsening in all these dimensions. Conclusions MBI training is effective in increasing quality of life and preventing worsening in patients with early-stage Alzheimer’s dementia.
Effectiveness of Remote Interventions to Improve Medication Adherence in Patients after Stroke: A Systematic Literature Review and Meta-Analysis
Authors: Choi Yan Yee Cherizza , Fineberg Micah , Kassavou Aikaterini
Published: March 2023

Background: Stroke affects more than 30 million people every year, but only two-thirds of patients comply with prescribed medication, leading to high stroke recurrence rates. Digital technologies can facilitate interventions to support treatment adherence. Purpose: This study evaluates the effectiveness of remote interventions and their mechanisms of action in supporting medication adherence after stroke. Methods: PubMed, MEDLINE via Ovid, Cochrane CENTRAL, the Web of Science, SCOPUS, and PsycINFO were searched, and meta-analysis was performed using the Review Manager Tool. Intervention content analysis was conducted based on the COM-B model. Results: Ten eligible studies were included in the review and meta-analysis. The evidence suggested that patients who received remote interventions had significantly better medication adherence (SMD 0.49, 95% CI [0.04, 0.93], and p = 0.03) compared to those who received the usual care. The adherence ratio also indicated the interventions’ effectiveness (odds ratio 1.30, 95% CI [0.55, 3.10], and p = 0.55). The systolic and diastolic blood pressure (MD −3.73 and 95% CI [−5.35, −2.10])/(MD −2.16 and 95% CI [−3.09, −1.22]) and cholesterol levels (MD −0.36 and 95% CI [−0.52, −0.20]) were significantly improved in the intervention group compared to the control. Further behavioural analysis demonstrated that enhancing the capability within the COM-B model had the largest impact in supporting improvements in adherence behaviour and relevant clinical outcomes. Patients’ satisfaction and the interventions’ usability were both high, suggesting the interventions’ acceptability. Conclusion: Telemedicine and mHealth interventions are effective in improving medication adherence and clinical indicators in stroke patients. Future studies could usefully investigate the effectiveness and cost-effectiveness of theory-based and remotely delivered interventions as an adjunct to stroke rehabilitation programmers.
Examining the Relationship between Adaptive Behavior and Intelligence
Authors: Tassé Marc J. , Kim Minje
Published: March 2023

Adaptive behavior and intelligence are both essential components of defining and diagnosing intellectual disability. The exact relationship between these two constructs still warrants some clarification. Previous studies have examined the correlation between adaptive behavior and intelligence and have reported differing results. Overall, there seems to be agreement that a modest to moderate correlation exists between adaptive behavior and intelligence and that the strength of this relationship may increase as ability level decreases further below the population mean. Using the Diagnostic Adaptive Behavior Scale and a sample of 57 youth aged from 4 to 21 years old, we examined the correlation coefficients between the full-scale IQ scores and their scores obtained on conceptual, social, and practical adaptive skill domain scores, as well as the total adaptive behavior score. The results obtained indicated a modest to moderate correlation between adaptive behavior and intelligence. The strongest statistically significant correlation coefficient was between the full-scale IQ score and the conceptual adaptive skills domain score (r = 0.64). The correlation between the full-scale IQ score and the practical adaptive skills domain (r = 0.39) and social adaptive skills domain (r = 0.28; ns) were more modest. The correlation coefficient between the full-scale IQ score and the total adaptive behavior score also showed a moderate relationship with intelligence (r = 0.46). These findings are consistent with previous research, documenting that adaptive behavior and intelligence are two related but independent constructs. We discuss these findings and their implications.
Reuse of Abandoned Shield Residues Stabilized by a Sustainable Binder: Assessment of Strength, Durability, and Environmental Properties
Authors: Cao Wei , Zhao Jun , Jiang Zhe-Yuan , Li Ying-Zhen , Che Chi
Published: March 2023

The resourceful reuse, construction, and environmental and safety hazards of shield residues in underground construction have received a lot of attention. This paper reports the assessment of shield residues generated with the underground space development through stabilization. The variations of strength, durability, and environmental properties of magnesium oxide (MgO)-activated ground granulated blast furnace slag (GGBS)-fiber material stabilized shield residues are tested by unconfined compressive strength test, direct shear test, pH test, and modified dry and soaking cycle test (acidic sulfate ion condition, pH = 5.0). Portland cement (PC)-stabilized shield residues are selected as the control group. The optimal ratio of MgO-activated GGBS-fiber-stabilized material is recommended. The test results show that the basalt fiber with 12 mm length and 0.1% ratio is designed as the optimal value. The MgO-activated GGBS-fiber-stabilized shield residues specimens with the ratio of MgO to GGBS of 1:7 display higher unconfined compressive strength (qu) and shear strength (τ). After ten dry–soaking cycles, the qu, τ, and pH of the MgO-activated GGBS-fiber-stabilized shield residues specimens decreased by 21%, 8%, and 12%, respectively, compared to those corresponding to the standard curing time. In contrast, the qu, τ, and pH of the control group were reduced by 46%, 39%, and 13%.
Embodied Carbon Minimization for Single-Story Steel Gable Frames
Authors: Salama Abdallah , Atif Farag Assem , Eraky Atef , El-Sisi Alaa A. , Samir Rania
Published: March 2023

As the construction industry, especially steel construction, contributes to a large portion of global greenhouse gas emissions, sustainable structural design has become a necessity to achieve the world vision of reaching net zero emissions by 2050. As steel portal frames are the most used structural system for single-story buildings, the main objective of this study is to determine the optimal steel portal frame configuration using prismatic and/or non-prismatic members to achieve the least embodied carbon. Five different portal frame configurations are considered under the effect of five distinct loading conditions. The results led to developing design charts consisting of contour plots showing the embodied carbon per unit of volume enclosed by the steel frame for different frame configurations, loading conditions, span lengths, and column heights. In addition, by increasing the number of member divisions, design variables, and non-prismatic segments, the average embodied carbon of the steel portal frames can be significantly reduced by about 14.34% up to 26.47% relative to the configuration with only prismatic members.
Mechanical Performance and Physico-Chemical Properties of Limestone Calcined Clay Cement (LC3) in Malawi
Authors: Kafodya Innocent , Basuroy Debojyoti , Marangu Joseph Mwiti , Kululanga Grant , Maddalena Riccardo , Novelli Viviana Iris
Published: March 2023

Malawi is one of the least-developed countries in Sub-Saharan Africa with disaster-prone housing infrastructure characterized by poor construction materials. Therefore, there is a need to provide resilient and cost-effective materials, such as limestone calcined clay cement (LC3). However, the exploitation of LC3 in Malawi is limited due to a lack of mineralogical information about the clays and limestone and related strength and durability when used as a cementitious material. In this study, the strength and physico-chemical properties of LC3 systems with 50% and 40% clinker contents (LC3-50 and LC3-40) were investigated. Cement mortar specimens were prepared at water to cement (w/c) ratios of 0.45, 0.5, and 0.6 with varying calcined clay (CC) to limestone (CC/LS) ratios (1:1, 2:1, and 3:1). The effects of CC/LS ratio on the fresh properties, strength, and durability were investigated. The results showed that specimens with 40% Portland cement replacement levels (LC3-40) exhibited higher standard consistency (up to 45%) than LC3-50, porosity in the range of 8.3–13.3%, and maximum water uptake in the range of 3.8–10.9%. On the other hand, LC3-50 samples offered the highest strength of approximately 40 MPa, complying with requirements for pozzolanic cementitious materials, whereas LC3-40 conforms to the strength requirements for masonry cements. This work shows that LC3 systems can be manufactured with local clays and limestone available in Malawi, and used as a sustainable construction material to mitigate carbon emissions as well as boost the local economy.
Implementation of BIM Virtual Models in Industry for the Graphical Coordination of Engineering and Architecture Projects
Authors: Fernández Rodríguez Juan Francisco
Published: March 2023

Building information modeling (BIM) has traditionally been considered as a tool for the graphical representation of architectural and engineering projects. This technology has become a key instrument for the development of virtual models that simulate the constructive process and facilitate the analysis of the designed solutions to detect incidents linked to traditional bi-dimensional projects. This article focuses on the use of this technology to optimize the design of MEP (mechanical, electrical, plumbing) facilities and architecture by developing virtual BIM models. Therefore, the purpose of this research is to analyze two experiences of complex buildings that have developed a BIM Execution Plan to improve the coordination of all disciplines involved, in order to explore how these real experiences can contribute to the implementation of the use of this technology in the construction industry. The results of the research are divided into two aspects: on the one hand, the improvements that BIM brings to the coordination and optimization of MEP facilities, linked to the typification of design incidents detected to anticipate conflicts between disciplines, facilitate collaborative design between different agents, keep graphic documentation updated and avoid execution problems and additional costs; and on the other hand, the keys to facilitating the extension of the use of this technology in the industry. Therefore, the conclusions of the research point out to the need for improvement in the automation of incident detection and the reduction in design process deadlines, as well as the need to simplify the virtual modeling process to bring it closer to unqualified personnel involved in the workflow and facilitate the implementation of this technology in the construction industry.
Green Evaluation for Building Interior Decoration Based on BIM-BN Technology
Authors: Fan Wenhan , Yan Baofeng , Bao Quanxi , Zhao Yueqin , Zhou Jianliang
Published: March 2023

The popularity of green building and BIM technology has increased globally, with strong government support in China. However, the integration of green requirements into interior decoration poses practical difficulties. Despite the few studies on the combination of green evaluation and BIM in building decoration, current methods largely rely on expert scores after completion. This research proposes a green evaluation index system for building interior decoration, examining the inter-index relationships and contribute to the final green degree of the project. Additionally, a green evaluation method based on BIM technology and the Bayesian network is explored, aimed at evaluating the green degree of design schemes, providing feedback, and supporting the realization of green interior decoration. With a focus on green evaluation, the current methods that rely solely on expert scores after completion will be improved. The results will provide technical support for the realization of green decoration and offer a reference for the improvement of green evaluation methods in the future.
Graphene-like Carbon Structure Synthesis from Biomass Pyrolysis: A Critical Review on Feedstock–Process–Properties Relationship
Authors: Asif Farhan Chowdhury , Saha Gobinda C.
Published: March 2023

Biomass pyrolysis is a promising route for synthesizing graphene-like carbon (GLC) structures, potentially offering a cost-effective and renewable alternative to graphene. This review paper responds to the call for highlighting the state of the art in GLC materials design and synthesis from renewable biomass microwave pyrolysis. This paper includes an introduction of the microwave pyrolysis technology, information on feedstock variability and selection, discussion on the correlation between microwave pyrolysis process conditions and pyrolyzed product characteristics, and, more importantly, a section identifying any differences between pyrolyzing feedstock using the microwave pyrolysis method vs. conventional pyrolysis method. Furthermore, this work concludes by detailing the knowledge currently missing with the recommendation for future research/innovation directions.
Assessment of Fibrinogen Thermal Conductivity and Interaction Energy with Polyarylethersulfone (PAES) Clinical Hemodialysis Membranes at Normal and Elevated Patient Body Temperatures
Authors: Mollahosseini Arash , Abdelrasoul Amira
Published: March 2023

Fibrinogen (FB) can trigger several biological reactions and is one of the critical proteins targeted during hemodialysis (HD). A better understanding of the thermal behavior of FB and its interactions with polymeric membranes during the HD process is needed in both normal and fever temperature conditions. This study calculated the thermal behavior of FB along with its interaction energy with polyarylethersulfone (PAES) clinical HD membranes using molecular dynamics (MD) approaches. The Dreiding force field was used for the MD simulations. The influence of temperature on the thermal conductivity (TC) and the interaction energy of the FB structure was assessed to understand the activation trends in fever conditions. Based on the MD simulation, the TC of FB at normal body temperature was 0.044 and 0.084 W/m·K according to equilibrium and non-equilibrium approaches, respectively. The elevation of temperature from normal to fever conditions increased the thermal conduction of FB to 0.577 and 0.114 W/m·K for equilibrium and non-equilibrium approaches, respectively. In addition, the elevation of patient blood temperature resulted in nearly 32 kcal/mol higher total interaction energy between FB and the PAES model. When end-stage renal disease (ESRD) patients have a HD session and experience fever and elevated temperature as a side effect, the interaction between FB and the membrane increases. More importantly, FB is exposed to more heat passage and accordingly more temperature-induced confirmation and activation compared to other human serum proteins such as albumin.
The Chorioallantoic Membrane Xenograft Assay as a Reliable Model for Investigating the Biology of Breast Cancer
Authors: Ranjan Raphela A. , Muenzner Julienne K. , Kunze Philipp , Geppert Carol I. , Ruebner Matthias , Huebner Hanna , Fasching Peter A. , Beckmann Matthias W. , Bäuerle Tobias , Hartmann Arndt , Walther Wolfgang , Eckstein Markus , Erber Ramona , Schneider-Stock Regine
Published: March 2023

The chorioallantoic membrane (CAM) assay is an alternative in vivo model that allows for minimally invasive research of cancer biology. Using the CAM assay, we investigated phenotypical and functional characteristics (tumor grade, mitosis rate, tumor budding, hormone receptor (HR) and HER2 status, Ki-67 proliferation index) of two breast cancer cell lines, MCF-7 and MDA-MB-231, which resemble the HR+ (luminal) and triple-negative breast cancer (TNBC) subgroups, respectively. Moreover, the CAM results were directly compared with murine MCF-7- and MDA-MB-231-derived xenografts and human patient TNBC tissue. Known phenotypical and biological features of the aggressive triple-negative breast cancer cell line (MDA-MB-231) were confirmed in the CAM assay, and mouse xenografts. Furthermore, the histomorphological and immunohistochemical variables assessed in the CAM model were similar to those in human patient tumor tissue. Given the confirmation of the classical biological and growth properties of breast cancer cell lines in the CAM model, we suggest this in vivo model to be a reliable alternative test system for breast cancer research to reduce murine animal experiments.
Progranulin Oncogenic Network in Solid Tumors
Authors: Ventura Elisa , Ducci Giacomo , Benot Dominguez Reyes , Ruggiero Valentina , Belfiore Antonino , Sacco Elena , Vanoni Marco , Iozzo Renato V. , Giordano Antonio , Morrione Andrea
Published: March 2023

Progranulin is a pleiotropic growth factor with important physiological roles in embryogenesis and maintenance of adult tissue homeostasis. While-progranulin deficiency is associated with a broad range of pathological conditions affecting the brain, such as frontotemporal dementia and neuronal ceroid lipofuscinosis, progranulin upregulation characterizes many tumors, including brain tumors, multiple myeloma, leiomyosarcoma, mesothelioma and epithelial cancers such as ovarian, liver, breast, bladder, adrenal, prostate and kidney carcinomas. The increase of progranulin levels in tumors might have diagnostic and prognostic significance. In cancer, progranulin has a pro-tumorigenic role by promoting cancer cell proliferation, migration, invasiveness, anchorage-independent growth and resistance to chemotherapy. In addition, progranulin regulates the tumor microenvironment, affects the function of cancer-associated fibroblasts, and modulates tumor immune surveillance. However, the molecular mechanisms of progranulin oncogenic function are not fully elucidated. In bladder cancer, progranulin action relies on the activation of its functional signaling receptor EphA2. Notably, more recent data suggest that progranulin can also modulate a functional crosstalk between multiple receptor-tyrosine kinases, demonstrating a more complex and context-dependent role of progranulin in cancer. Here, we will review what is currently known about the function of progranulin in tumors, with a focus on its molecular mechanisms of action and regulation.
MicroRNA-483-5p Inhibits Hepatocellular Carcinoma Cell Proliferation, Cell Steatosis, and Fibrosis by Targeting PPARα and TIMP2
Authors: Niture Suryakant , Gadi Sashi , Qi Qi , Gyamfi Maxwell Afari , Varghese Rency S. , Rios-Colon Leslimar , Chimeh Uchechukwu , Vandana  , Ressom Habtom W. , Kumar Deepak
Published: March 2023

MicroRNAs (miRNAs) are small non-coding RNA molecules that bind with the 3′ untranslated regions (UTRs) of genes to regulate expression. Downregulation of miR-483-5p (miR-483) is associated with the progression of hepatocellular carcinoma (HCC). However, the significant roles of miR-483 in nonalcoholic fatty liver disease (NAFLD), alcoholic fatty liver diseases (AFLD), and HCC remain elusive. In the current study, we investigated the biological significance of miR-483 in NAFLD, AFLD, and HCC in vitro and in vivo. The downregulation of miR-483 expression in HCC patients’ tumor samples was associated with Notch 3 upregulation. Overexpression of miR-483 in a human bipotent progenitor liver cell line HepaRG and HCC cells dysregulated Notch signaling, inhibited cell proliferation/migration, induced apoptosis, and increased sensitivity towards antineoplastic agents sorafenib/regorafenib. Interestingly, the inactivation of miR-483 upregulated cell steatosis and fibrosis signaling by modulation of lipogenic and fibrosis gene expression. Mechanistically, miR-483 targets PPARα and TIMP2 gene expression, which leads to the suppression of cell steatosis and fibrosis. The downregulation of miR-483 was observed in mice liver fed with a high-fat diet (HFD) or a standard Lieber-Decarli liquid diet containing 5% alcohol, leading to increased hepatic steatosis/fibrosis. Our data suggest that miR-483 inhibits cell steatosis and fibrogenic signaling and functions as a tumor suppressor in HCC. Therefore, miR-483 may be a novel therapeutic target for NAFLD/AFLD/HCC management in patients with fatty liver diseases and HCC.
Hyperthermia Treatment Monitoring via Deep Learning Enhanced Microwave Imaging: A Numerical Assessment
Authors: Yago Ruiz Álvaro , Cavagnaro Marta , Crocco Lorenzo
Published: March 2023

The paper deals with the problem of monitoring temperature during hyperthermia treatments in the whole domain of interest. In particular, a physics-assisted deep learning computational framework is proposed to provide an objective assessment of the temperature in the target tissue to be treated and in the healthy one to be preserved, based on the measurements performed by a microwave imaging device. The proposed concept is assessed in-silico for the case of neck tumors achieving an accuracy above 90%. The paper results show the potential of the proposed approach and support further studies aimed at its experimental validation.
Sentinel Lymph Node Biopsy in Breast Cancer Patients Undergoing Neo-Adjuvant Chemotherapy: Clinical Experience with Node-Negative and Node-Positive Disease Prior to Systemic Therapy
Authors: Tinterri Corrado , Sagona Andrea , Barbieri Erika , Di Maria Grimaldi Simone , Caraceni Giulia , Ambrogi Giacomo , Jacobs Flavia , Biondi Ersilia , Scardina Lorenzo , Gentile Damiano
Published: March 2023

Background: Sentinel lymph node biopsy (SLNB) has emerged as the standard procedure to replace axillary lymph node dissection (ALND) in breast cancer (BC) patients undergoing neo-adjuvant chemotherapy (NAC). SLNB is accepted in clinically node-negative (cN0) patients; however, its role in clinically node-positive (cN+) patients is debatable. Methods: We performed a retrospective analysis of BC patients undergoing NAC and SLNB. Our aim was to evaluate the clinical significance of SLNB in the setting of NAC. This was accomplished by comparing the characteristics and oncological outcomes between cN0 and cN+ patients prior to NAC and type of axillary surgery. Results: A total of 291 patients were included in the analysis: 131 were cN0 and 160 were cN+ who became ycN0 after NAC. At a median follow-up of 43 months, axillary recurrence occurred in three cN0 (2.3%) and two cN+ (1.3%) patients. However, there were no statistically significant differences in oncological outcomes (disease-free survival, distant disease-free survival, overall survival, and breast-cancer-specific survival) between cN0 and cN+ patients nor between patients treated with SLNB only or ALND. Conclusions: SLNB in the setting of NAC is an acceptable procedure with a general good prognosis and low axillary failure rates for both cN0 and cN+ patients.
Deep Learning Applied to Raman Spectroscopy for the Detection of Microsatellite Instability/MMR Deficient Colorectal Cancer
Authors: Blake Nathan , Gaifulina Riana , Griffin Lewis D. , Bell Ian M. , Rodriguez-Justo Manuel , Thomas Geraint M. H.
Published: March 2023

Defective DNA mismatch repair is one pathogenic pathway to colorectal cancer. It is characterised by microsatellite instability which provides a molecular biomarker for its detection. Clinical guidelines for universal testing of this biomarker are not met due to resource limitations; thus, there is interest in developing novel methods for its detection. Raman spectroscopy (RS) is an analytical tool able to interrogate the molecular vibrations of a sample to provide a unique biochemical fingerprint. The resulting datasets are complex and high-dimensional, making them an ideal candidate for deep learning, though this may be limited by small sample sizes. This study investigates the potential of using RS to distinguish between normal, microsatellite stable (MSS) and microsatellite unstable (MSI-H) adenocarcinoma in human colorectal samples and whether deep learning provides any benefit to this end over traditional machine learning models. A 1D convolutional neural network (CNN) was developed to discriminate between healthy, MSI-H and MSS in human tissue and compared to a principal component analysis–linear discriminant analysis (PCA–LDA) and a support vector machine (SVM) model. A nested cross-validation strategy was used to train 30 samples, 10 from each group, with a total of 1490 Raman spectra. The CNN achieved a sensitivity and specificity of 83% and 45% compared to PCA–LDA, which achieved a sensitivity and specificity of 82% and 51%, respectively. These are competitive with existing guidelines, despite the low sample size, speaking to the molecular discriminative power of RS combined with deep learning. A number of biochemical antecedents responsible for this discrimination are also explored, with Raman peaks associated with nucleic acids and collagen being implicated.
The Role of Genetic, Metabolic, Inflammatory, and Immunologic Mediators in the Progression of Intraductal Papillary Mucinous Neoplasms to Pancreatic Adenocarcinoma
Authors: Shockley Kylie E. , To Briana , Chen Wei , Lozanski Gerard , Cruz-Monserrate Zobeida , Krishna Somashekar G.
Published: March 2023

Intraductal papillary mucinous neoplasms (IPMN) have the potential to progress to pancreatic ductal adenocarcinoma (PDAC). As with any progression to malignancy, there are a variety of genetic and metabolic changes, as well as other disruptions to the cellular microenvironment including immune alterations and inflammation, that can contribute to tumorigenesis. Previous studies further characterized these alterations, revealing changes in lipid and glucose metabolism, and signaling pathways that mediate the progression of IPMN to PDAC. With the increased diagnosis of IPMNs and pancreatic cysts on imaging, the opportunity to attenuate risk with the removal of high-risk lesions is possible with the understanding of what factors accelerate malignant progression and how they can be clinically utilized to determine the level of dysplasia and stratify the risk of progression. Here, we reviewed the genetic, metabolic, inflammatory, and immunologic pathways regulating the progression of IPMN to PDAC.
Aberrant HMGA2 Expression Sustains Genome Instability That Promotes Metastasis and Therapeutic Resistance in Colorectal Cancer
Authors: Campos Gudiño Rubi , McManus Kirk J. , Hombach-Klonisch Sabine
Published: March 2023

Colorectal cancer (CRC) is one of the most lethal cancers worldwide, accounting for nearly ~10% of all cancer diagnoses and deaths. Current therapeutic approaches have considerably increased survival for patients diagnosed at early stages; however, ~20% of CRC patients are diagnosed with late-stage, metastatic CRC, where 5-year survival rates drop to 6–13% and treatment options are limited. Genome instability is an enabling hallmark of cancer that confers increased acquisition of genetic alterations, mutations, copy number variations and chromosomal rearrangements. In that regard, research has shown a clear association between genome instability and CRC, as the accumulation of aberrations in cancer-related genes provides subpopulations of cells with several advantages, such as increased proliferation rates, metastatic potential and therapeutic resistance. Although numerous genes have been associated with CRC, few have been validated as predictive biomarkers of metastasis or therapeutic resistance. A growing body of evidence suggests a member of the High-Mobility Group A (HMGA) gene family, HMGA2, is a potential biomarker of metastatic spread and therapeutic resistance. HMGA2 is expressed in embryonic tissues and is frequently upregulated in aggressively growing cancers, including CRC. As an architectural, non-histone chromatin binding factor, it initiates chromatin decompaction to facilitate transcriptional regulation. HMGA2 maintains the capacity for stem cell renewal in embryonic and cancer tissues and is a known promoter of epithelial-to-mesenchymal transition in tumor cells. This review will focus on the known molecular mechanisms by which HMGA2 exerts genome protective functions that contribute to cancer cell survival and chemoresistance in CRC.
Periodontitis and Cancer: Beyond the Boundaries of Oral Cavity
Authors: Amato Alessandra
Published: March 2023

Oral squamous cell carcinoma (OSCC) is the 16th most common cancer and the 15th leading cause of death worldwide, with an incidence of 4 cases per 100,000 people [...]
Integrative Analyses Reveal the Anticancer Mechanisms and Sensitivity Markers of the Next-Generation Hypomethylating Agent NTX-301
Authors: Lim Byungho , Yoo Dabin , Chun Younghwa , Go Areum , Kim Ji Yeon , Lee Ha Young , Boohaker Rebecca J. , Cho Kyung-Jin , Ahn Sunjoo , Lee Jin Soo , Jung DooYoung , Choi Gildon
Published: March 2023

Epigenetic dysregulation characterized by aberrant DNA hypermethylation is a hallmark of cancer, and it can be targeted by hypomethylating agents (HMAs). Recently, we described the superior therapeutic efficacy of a novel HMA, namely, NTX-301, when used as a monotherapy and in combination with venetoclax in the treatment of acute myeloid leukemia. Following a previous study, we further explored the therapeutic properties of NTX-301 based on experimental investigations and integrative data analyses. Comprehensive sensitivity profiling revealed that NTX-301 primarily exerted anticancer effects against blood cancers and exhibited improved potency against a wide range of solid cancers. Subsequent assays showed that the superior efficacy of NTX-301 depended on its strong effects on cell cycle arrest, apoptosis, and differentiation. Due to its superior efficacy, low doses of NTX-301 achieved sufficiently substantial tumor regression in vivo. Multiomics analyses revealed the mechanisms of action (MoAs) of NTX-301 and linked these MoAs to markers of sensitivity to NTX-301 and to the demethylation activity of NTX-301 with high concordance. In conclusion, our findings provide a rationale for currently ongoing clinical trials of NTX-301 and will help guide the development of novel therapeutic options for cancer patients.
A Recent Review of Primary Hydrogen Carriers, Hydrogen Production Methods, and Applications
Authors: Li Risheng , Kawanami Hajime
Published: March 2023

Hydrogen is a promising energy carrier, especially for transportation, owing to its unique physical and chemical properties. Moreover, the combustion of hydrogen gas generates only pure water; thus, its wide utilization can positively affect human society to achieve global net zero CO2 emissions by 2050. This review summarizes the characteristics of the primary hydrogen carriers, such as water, methane, methanol, ammonia, and formic acid, and their corresponding hydrogen production methods. Additionally, state-of-the-art studies and hydrogen energy applications in recent years are also included in this review. In addition, in the conclusion section, we summarize the advantages and disadvantages of hydrogen carriers and hydrogen production techniques and suggest the challenging tasks for future research.
Theoretically Predicted CO Adsorption and Activation on the Co-Doped hcp-Fe7C3 Catalyst
Authors: Duan Yajing , Sun Huijuan , Du Hui , Lu Wencai
Published: March 2023

The Hcp-Fe7C3 phase has attracted more attention due to the high catalytic activity in Fischer–Tropsch synthesis (FTS) reactions. In this work, the adsorption and activation of CO on a Co-doped hcp-Fe7C3 catalyst were investigated by density functional theory (DFT) in order to understand the effect of Co doping on the initial step of FTS reactions on iron-based catalysts. Different Co-doped hcp-Fe7C3 001 and 11¯0 surfaces were constructed, and the CO adsorption configurations were studied. The calculated results show that the structure of the 001 surface remains basically unchanged after doping with Co atoms, while the replacement of Fe or C atoms on 11¯0 surfaces with Co atoms has a significant impact on the surface structure. The top sites on the doped Co atoms of hcp-Fe7C3 are disadvantages for the CO adsorption, whereas the T, 2F, or 3F sites around the doped Co atoms are beneficial for promoting the adsorption of CO. The CO direct dissociation pathways on the four types of Co-doped hcp-Fe7C3 001 surfaces are exothermic, while the H-assisted dissociation pathways of CO are endothermic. The H-assisted activation via HCO on the 3F1 site of the 2Co2-doped hcp-Fe7C3 001 surface shows the lowest energy barrier of 1.96 eV. For the Co-doped hcp-Fe7C3 11¯0 surfaces, the H-assisted activation via HCO is the preferred activation pathway for CO on the Co-doped surfaces with the energy barrier of approximately 1.30 eV.
A Molybdenum(VI) Complex of 5-(2-pyridyl-1-oxide)tetrazole: Synthesis, Structure, and Transformation into a MoO3-Based Hybrid Catalyst for the Epoxidation of Bio-Olefins
Authors: Nunes Martinique S. , Gomes Diana M. , Gomes Ana C. , Neves Patrícia , Mendes Ricardo F. , Paz Filipe A. Almeida , Lopes André D. , Pillinger Martyn , Valente Anabela A. , Gonçalves Isabel S.
Published: March 2023

The discovery of heterogeneous catalysts synthesized in easy, sustainable ways for the valorization of olefins derived from renewable biomass is attractive from environmental, sustainability, and economic viewpoints. Here, an organic–inorganic hybrid catalyst formulated as [MoO3(Hpto)]·H2O (2), where Hpto = 5-(2-pyridyl-1-oxide)tetrazole, was prepared by a hydrolysis–condensation reaction of the complex [MoO2Cl2(Hpto)]∙THF (1). The characterization of 1 and 2 by FT-IR and Raman spectroscopies, as well as 13C solid-state NMR, suggests that the bidentate N,O-coordination of Hpto in 1 (forming a six-membered chelate ring, confirmed by X-ray crystallography) is maintained in 2, with the ligand coordinated to a molybdenum oxide substructure. Catalytic studies suggested that 2 is a rare case of a molybdenum oxide/organic hybrid that acts as a stable solid catalyst for olefin epoxidation with tert-butyl hydroperoxide. The catalyst was effective for converting biobased olefins, namely fatty acid methyl esters (methyl oleate, methyl linoleate, methyl linolenate, and methyl ricinoleate) and the terpene limonene, leading predominantly to the corresponding epoxide products with yields in the range of 85–100% after 24 h at 70 °C. The versatility of catalyst 2 was shown by its effectiveness for the oxidation of sulfides into sulfoxides and sulfones, at 35 °C (quantitative yield of sulfoxide plus sulfone, at 24 h; sulfone yields in the range of 77–86%). To the best of our knowledge, 2 is the first molybdenum catalyst reported for methyl linolenate epoxidation, and the first of the family [MoO3(L)x] studied for methyl ricinoleate epoxidation.
CO Oxidation Reaction by Platinum Clusters on the Surface of Multiwalled Carbon Nanotubes: Experimental and Theoretical Study of Kinetics in a Wide Range of O2/CO Ratios
Authors: Lashina Elena , Slavinskaya Elena , Kibis Lidiya , Stadnichenko Andrey , Stonkus Olga , Zhuravlev Daniil , Zadesenets Andrey , Korenev Sergey , Podyacheva Olga , Boronin Andrei
Published: March 2023

This work presents a systematic study of the kinetic aspects of CO oxidation reaction catalyzed by platinum nanoparticles (NPs) supported on the surface of multiwalled carbon nanotubes (MWCNTs). The investigation presented is closely related to the actual practical task of air purification in enclosed spaces. Therefore, the catalytic reaction was carried out in the presence of an excess of oxygen (5 vol.%) and over a wide range of CO concentrations from 50 ppm to 1600 ppm. For the catalyst characterization, transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) were applied. Kinetic modelling based on the Langmuir–Hinshelwood and Mars-van Krevelen mechanisms was taken as a basis, using the results obtained on Pt foil. Simulation of CO oxidation reaction on platinum NPs at temperatures above 90 °C was carried out using a kinetic model describing the reaction mechanism on bulk platinum. The description of the kinetics of CO oxidation reaction on Pt NPs over the entire temperature range, including the low temperatures down to −40 °C, required the introduction of the steps characterizing an additional concerted mechanism related to CO-assisted O2 dissociation. Using the presented model, some predictions of the kinetic behaviour of the system were made.
Astragalus Polysaccharide Promotes Doxorubicin-Induced Apoptosis by Reducing O-GlcNAcylation in Hepatocellular Carcinoma
Authors: Li Mingzhe , Duan Fangfang , Pan Zhiqiang , Liu Xiaomei , Lu Wenli , Liang Chao , Fang Zhaoqin , Peng Peike , Jia Dongwei
Published: March 2023

The toxicity and side effects of chemotherapeutic drugs remain a crucial obstacle to the clinical treatment of hepatocellular carcinoma (HCC). Identifying combination therapy from Chinese herbs to enhance the sensitivity of tumors to chemotherapeutic drugs is of particular interest. Astragalus polysaccharide (APS), one of the natural active components in Astragalus membranaceus, has been reported to exhibit anti-tumor properties in diverse cancer cell lines. The aim of this study was to determine the effect of APS on Doxorubicin (Dox)-induced apoptosis in HCC and the underlying mechanism. The results showed that APS dose-dependently promoted Dox-induced apoptosis and enhanced endoplasmic reticulum (ER) stress. Additionally, APS decreased the mRNA level and protein stability of O-GlcNAc transferase (OGT), and increased the O-GlcNAcase (OGA) expression. Furthermore, OGT lentiviral transfection or PugNAc (OGA inhibitor) treatment reversed the ER stress and apoptosis induced by the combination of Dox and APS. A xenograft tumor mouse model confirmed that the combination of APS and Dox showed an advantage in inhibiting tumor growth in vivo. These findings suggested that APS promoted Dox-induced apoptosis in HCC cells through reducing the O-GlcNAcylation, which led to the exacerbation of ER stress and activation of apoptotic pathways.
Electrical Stimulation Increases the Secretion of Cardioprotective Extracellular Vesicles from Cardiac Mesenchymal Stem Cells
Authors: Zhang Haitao , Shen Yan , Kim Il-man , Liu Yutao , Cai Jingwen , Berman Adam E. , Nilsson Kent R. , Weintraub Neal L. , Tang Yaoliang
Published: March 2023

Clinical trials have shown that electric stimulation (ELSM) using either cardiac resynchronization therapy (CRT) or cardiac contractility modulation (CCM) approaches is an effective treatment for patients with moderate to severe heart failure, but the mechanisms are incompletely understood. Extracellular vesicles (EV) produced by cardiac mesenchymal stem cells (C-MSC) have been reported to be cardioprotective through cell-to-cell communication. In this study, we investigated the effects of ELSM stimulation on EV secretion from C-MSCs (C-MSCELSM). We observed enhanced EV-dependent cardioprotection conferred by conditioned medium (CM) from C-MSCELSM compared to that from non-stimulated control C-MSC (C-MSCCtrl). To investigate the mechanisms of ELSM-stimulated EV secretion, we examined the protein levels of neutral sphingomyelinase 2 (nSMase2), a key enzyme of the endosomal sorting complex required for EV biosynthesis. We detected a time-dependent increase in nSMase2 protein levels in C-MSCELSM compared to C-MSCCtrl. Knockdown of nSMase2 in C-MSC by siRNA significantly reduced EV secretion in C-MSCELSM and attenuated the cardioprotective effect of CM from C-MSCELSM in HL-1 cells. Taken together, our results suggest that ELSM-mediated increases in EV secretion from C-MSC enhance the cardioprotective effects of C-MSC through an EV-dependent mechanism involving nSMase2.