bluuebunny/crossref_metadata_2025 huggingface dataset:
Artificial Intelligence-Based Robust Hybrid Algorithm Design and Implementation for Real-Time Detection of Plant Diseases in Agricultural Environments
Authors: Yağ İlayda , Altan Aytaç
Published: November 2022

The early detection and prevention of plant diseases that are an important cause of famine and food insecurity worldwide are very important for increasing agricultural product productivity. Not only the early detection of the plant disease but also the determination of its type play a critical role in determining the appropriate treatment. The fact that visual inspection, which is frequently used in determining plant disease and types, is tiring and prone to human error, necessitated the development of algorithms that can automatically classify plant disease with high accuracy and low computational cost. In this study, a new hybrid plant leaf disease classification model with high accuracy and low computational complexity, consisting of the wrapper approach, including the flower pollination algorithm (FPA) and support vector machine (SVM), and a convolutional neural network (CNN) classifier, is developed with a wrapper-based feature selection approach using metaheuristic optimization techniques. The features of the image dataset consisting of apple, grape, and tomato plants have been extracted by a two-dimensional discrete wavelet transform (2D-DWT) using wavelet families such as biorthogonal, Coiflets, Daubechies, Fejer–Korovkin, and symlets. Features that keep classifier performance high for each family are selected by the wrapper approach, consisting of the population-based metaheuristics FPA and SVM. The performance of the proposed optimization algorithm is compared with the particle swarm optimization (PSO) algorithm. Afterwards, the classification performance is obtained by using the lowest number of features that can keep the classification performance high for the CNN classifier. The CNN classifier with a single layer of classification without a feature extraction layer is used to minimize the complexity of the model and to deal with the model hyperparameter problem. The obtained model is embedded in the NVIDIA Jetson Nano developer kit on the unmanned aerial vehicle (UAV), and real-time classification tests are performed on apple, grape, and tomato plants. The experimental results obtained show that the proposed model classifies the specified plant leaf diseases in real time with high accuracy. Moreover, it is concluded that the robust hybrid classification model, which is created by selecting the lowest number of features with the optimization algorithm with low computational complexity, can classify plant leaf diseases in real time with precision.
Commensal Intestinal Protozoa—Underestimated Members of the Gut Microbial Community
Authors: Dubik Magdalena , Pilecki Bartosz , Moeller Jesper Bonnet
Published: November 2022

The human gastrointestinal microbiota contains a diverse consortium of microbes, including bacteria, protozoa, viruses, and fungi. Through millennia of co-evolution, the host–microbiota interactions have shaped the immune system to both tolerate and maintain the symbiotic relationship with commensal microbiota, while exerting protective responses against invading pathogens. Microbiome research is dominated by studies describing the impact of prokaryotic bacteria on gut immunity with a limited understanding of their relationship with other integral microbiota constituents. However, converging evidence shows that eukaryotic organisms, such as commensal protozoa, can play an important role in modulating intestinal immune responses as well as influencing the overall health of the host. The presence of several protozoa species has recently been shown to be a common occurrence in healthy populations worldwide, suggesting that many of these are commensals rather than invading pathogens. This review aims to discuss the most recent, conflicting findings regarding the role of intestinal protozoa in gut homeostasis, interactions between intestinal protozoa and the bacterial microbiota, as well as potential immunological consequences of protozoa colonization.
Leptin and Asthma: What Are the Interactive Correlations?
Authors: Wang Yang , Hu Chengping
Published: November 2022

Leptin is an adipokine directly correlated with the proinflammatory obese-associated phenotype. Leptin has been demonstrated to inhibit adipogenesis, promote fat demarcation, promote a chronic inflammatory state, increase insulin sensitivity, and promote angiogenesis. Leptin, a regulator of the immune response, is implicated in the pathology of asthma. Studies involved in the key cell reaction and animal models of asthma have provided vital insights into the proinflammatory role of leptin in asthma. Many studies described the immune cell and related cellular pathways activated by leptin, which are beneficial in asthma development and increasing exacerbations. Subsequent studies relating to animal models support the role of leptin in increasing inflammatory cell infiltration, airway hyperresponsiveness, and inflammatory responses. However, the conclusive effects of leptin in asthma are not well elaborated. In the present study, we explored the general functions and the clinical cohort study supporting the association between leptin and asthma. The main objective of our review is to address the knowns and unknowns of leptin on asthma. In this perspective, the arguments about the different faces of leptin in asthma are provided to picture the potential directions, thus yielding a better understanding of asthma development.
Impact of Biometric Patient Data, Probiotic Supplementation, and Selected Gut Microorganisms on Calprotectin, Zonulin, and sIgA Concentrations in the Stool of Adults Aged 18–74 Years
Authors: Jendraszak Magdalena , Gałęcka Mirosława , Kotwicka Małgorzata , Schwiertz Andreas , Regdos Aleksandra , Pazgrat-Patan Michalina , Andrusiewicz Mirosław
Published: November 2022

Alterations to the intestinal barrier may be involved in the pathogenesis of various chronic diseases. The diagnosis of mucosal barrier disruption has become a new therapeutic target for disease prevention. The aim of this study was to determine whether various patient demographic and biometric data, often not included in diagnostic analyses, may affect calprotectin, zonulin, and sIgA biomarker values. Stool markers’ levels in 160 samples were measured colorimetrically. The analysis of twenty key bacteria (15 genera and 5 species) was carried out on the basis of diagnostic tests, including cultures and molecular tests. The concentrations of selected markers were within reference ranges for most patients. The sIgA level was significantly lower in participants declaring probiotics supplementation (p = 0.0464). We did not observe differences in gastrointestinal discomfort in participants. We found significant differences in the sIgA level between the 29–55 years and >55 years age-related intervals groups (p = 0.0191), together with a significant decreasing trend (p = 0.0337) in age-dependent sIgA concentration. We observed complex interdependencies and relationships between their microbiota and the analyzed biomarkers. For correct clinical application, standardized values of calprotectin and sIgA should be determined, especially in elderly patients. We observed a correlation between the composition of the gut community and biomarker levels, although it requires further in-depth analysis.
PDX-1: A Promising Therapeutic Target to Reverse Diabetes
Authors: Zhang Yanjiao , Fang Xinyi , Wei Jiahua , Miao Runyu , Wu Haoran , Ma Kaile , Tian Jiaxing
Published: November 2022

The pancreatic duodenum homeobox-1 (PDX-1) is a transcription factor encoded by a Hox-like homeodomain gene that plays a crucial role in pancreatic development, β-cell differentiation, and the maintenance of mature β-cell functions. Research on the relationship between PDX-1 and diabetes has gained much attention because of the increasing prevalence of diabetes melitus (DM). Recent studies have shown that the overexpression of PDX-1 regulates pancreatic development and promotes β-cell differentiation and insulin secretion. It also plays a vital role in cell remodeling, gene editing, and drug development. Conversely, the absence of PDX-1 increases susceptibility to DM. Therefore, in this review, we summarized the role of PDX-1 in pancreatic development and the pathogenesis of DM. A better understanding of PDX-1 will deepen our knowledge of the pathophysiology of DM and provide a scientific basis for exploring PDX-1 as a potential target for treating diabetes.
Refining the Clinical Spectrum of the 17p13.3 Microduplication Syndrome: Case-Report of a Familial Small Microduplication
Authors: Da Silva Jorge Diogo , Gonzaga Diana , Barreta Ana , Correia Hildeberto , Fortuna Ana Maria , Soares Ana Rita , Tkachenko Nataliya
Published: November 2022

The chromosomal region 17p13.3 contains extensive repetitive sequences and is a well-recognized region of genomic instability. The 17p13.3 microduplication syndrome has been associated with a clinical spectrum of moderately non-specific phenotypes, including global developmental delay/intellectual disability, behavioral disorders, autism spectrum disorder and variable dysmorphic features. Depending on the genes involved in the microduplication, it can be categorized in two subtypes with different phenotypes. Here, we report a case of a 7-year-old boy with global developmental delay, speech impairment, hypotonia, behavioral conditions (ADHD and ODD), non-specific dysmorphic features and overgrowth. Genetic testing revealed a small 17p13.3 chromosomal duplication, which included the BHLHA9, CRK and YWHAE genes. Additionally, we observed that this was maternally inherited, and that the mother presented with a milder phenotype including mild learning disabilities, speech impairment and non-specific dysmorphic features, which did not significantly affect her. In conclusion, we present a clinical case of a 17p13.3 duplication that further delineates the clinical spectrum of this syndrome, including its intrafamilial/intergenerational variability.
Lipedema: Insights into Morphology, Pathophysiology, and Challenges
Authors: Poojari Ankita , Dev Kapil , Rabiee Atefeh
Published: November 2022

Lipedema is an adipofascial disorder that almost exclusively affects women. Lipedema leads to chronic pain, swelling, and other discomforts due to the bilateral and asymmetrical expansion of subcutaneous adipose tissue. Although various distinctive morphological characteristics, such as the hyperproliferation of fat cells, fibrosis, and inflammation, have been characterized in the progression of lipedema, the mechanisms underlying these changes have not yet been fully investigated. In addition, it is challenging to reduce the excessive fat in lipedema patients using conventional weight-loss techniques, such as lifestyle (diet and exercise) changes, bariatric surgery, and pharmacological interventions. Therefore, lipedema patients also go through additional psychosocial distress in the absence of permanent treatment. Research to understand the pathology of lipedema is still in its infancy, but promising markers derived from exosome, cytokine, lipidomic, and metabolomic profiling studies suggest a condition distinct from obesity and lymphedema. Although genetics seems to be a substantial cause of lipedema, due to the small number of patients involved in such studies, the extrapolation of data at a broader scale is challenging. With the current lack of etiology-guided treatments for lipedema, the discovery of new promising biomarkers could provide potential solutions to combat this complex disease. This review aims to address the morphological phenotype of lipedema fat, as well as its unclear pathophysiology, with a primary emphasis on excessive interstitial fluid, extracellular matrix remodeling, and lymphatic and vasculature dysfunction. The potential mechanisms, genetic implications, and proposed biomarkers for lipedema are further discussed in detail. Finally, we mention the challenges related to lipedema and emphasize the prospects of technological interventions to benefit the lipedema community in the future.
The Limb Kinetics of Goat Walking on the Slope with Different Angles
Authors: Tian Weijun , Zhang Jinhua , Zhou Kuiyue , Wang Zhirui , Dang Ruina , Jiang Lei , Wang Ju , Cong Qian
Published: November 2022

The study aimed to assess the gait adjustment techniques of limbs on different slopes and investigate the relationship between forelimb and hindlimb kinetics and the center of mass (COM) during the uphill movement of a specific Boer goat using a pressure-sensitive walkway (PSW). During the uphill and downhill movements at a comfortable walking speed, we measured the ground reaction force (GRF) of the forelimbs and hindlimbs on the slope, the change in the included angle of the propulsive force direction of the forelimbs and hindlimbs, and the impulse relationship between GRF and propulsive force. According to the study, since the forelimbs of the goat were nearer the COM, they were primarily adjusted during the movement on the slope. By lowering the initial included angle of the propulsive force and the angle variation range, the forelimbs and hindlimbs could walk steadily. The forelimbs and hindlimbs exhibited completely different adjustment strategies during uphill and downhill movements. In particular, the forelimbs performed braking and the hindlimbs performed driving. In addition, we discovered that the goat altered its adjustment strategy when climbing the steep slope. All findings of this study indicate the need to understand the gait adjustment mode of the Boer goat during movement on the slope to thoroughly comprehend the driving strategy of quadrupeds with the ability to walk on specialized terrains.
Identification of Potential Antimalarial Drug Candidates Targeting Falcipain-2 Protein of Malaria Parasite—A Computational Strategy
Authors: Nema Shrikant , Verma Kanika , Mani Ashutosh , Maurya Neha Shree , Tiwari Archana , Bharti Praveen Kumar
Published: November 2022

Falcipain-2 (FP-2) is one of the main haemoglobinase of P. falciparum which is an important molecular target for the treatment of malaria. In this study, we have screened alkaloids to identify potential inhibitors against FP-2 since alkaloids possess great potential as anti-malarial agents. A total of 340 alkaloids were considered for the study using a series of computational pipelines. Initially, pharmacokinetics and toxicity risk assessment parameters were applied to screen compounds. Subsequently, molecular docking algorithms were utilised to understand the binding efficiency of alkaloids against FP-2. Further, oral toxicity prediction was done using the pkCSM tool, and 3D pharmacophore features were analysed using the PharmaGist server. Finally, MD simulation was performed for Artemisinin and the top 3 drug candidates (Noscapine, Reticuline, Aclidinium) based on docking scores to understand the functional impact of the complexes, followed by a binding site interaction residues study. Overall analysis suggests that Noscapine conceded good pharmacokinetics and oral bioavailability properties. Also, it showed better binding efficiency with FP-2 when compared to Artemisinin. Interestingly, structure alignment analysis with artemisinin revealed that Noscapine, Reticuline, and Aclidinium might possess similar biological action. Molecular dynamics and free energy calculations revealed that Noscapine could be a potent antimalarial agent targeting FP-2 that can be used for the treatment of malaria and need to be studied experimentally in the future.
Effects of Genetics and Sex on Acute Gene Expression Changes in the Hippocampus Following Neonatal Ethanol Exposure in BXD Recombinant Inbred Mouse Strains
Authors: Baker Jessica A. , Brettin Jacob T. , Mulligan Megan K. , Hamre Kristin M.
Published: November 2022

Fetal alcohol spectrum disorders (FASD) are prevalent neurodevelopmental disorders. Genetics have been shown to have a role in the severity of alcohol’s teratogenic effects on the developing brain. We previously identified recombinant inbred BXD mouse strains that show high (HCD) or low cell death (LCD) in the hippocampus following ethanol exposure. The present study aimed to identify gene networks that influence this susceptibility. On postnatal day 7 (3rd-trimester-equivalent), male and female neonates were treated with ethanol (5.0 g/kg) or saline, and hippocampi were collected 7hrs later. Using the Affymetrix microarray platform, ethanol-induced gene expression changes were identified in all strains with divergent expression sets found between sexes. Genes, such as Bcl2l11, Jun, and Tgfb3, showed significant strain-by-treatment interactions and were involved in many apoptosis pathways. Comparison of HCD versus LCD showed twice as many ethanol-induced genes changes in the HCD. Interestingly, these changes were regulated in the same direction suggesting (1) more perturbed effects in HCD compared to LCD and (2) limited gene expression changes that confer resistance to ethanol-induced cell death in LCD. These results demonstrate that genetic background and sex are important factors that affect differential cell death pathways after alcohol exposure during development that could have long-term consequences.
The Split-Half Reliability and Construct Validity of the Virtual Reality-Based Path Integration Task in the Healthy Population
Authors: Fu Xiao , Zhang Zhenglin , Zhou Yanfei , Chen Qi , Yang Li-Zhuang , Li Hai
Published: November 2022

Objective: The virtual reality (VR)-based path integration task shows substantial promise in predicting dementia risk. However, the reliability and validity in healthy populations need further exploration. The present study investigates the relationship between task indicators and brain structures in a healthy population using a VR-based navigation task, particularly the entorhinal cortex (EC) and hippocampus. Methods: Sixty healthy adults were randomly recruited to perform a VR-based path integration task, the digit span task (DST), and an MRI scan. The indicators of the VR-based path integration task were calculated, including the absolute distance error (ADE), degree of angle deviation (DAD), degree of path deviation (DPD), and return time (Time). The reliability of the above indicators was then estimated using the split-half method and Cronbach’s alpha. Correlation and regression analyses were then performed to examine the associations between these indicators and age, general cognitive ability (DST), and brain structural measures. Results: ADE, DAD, and DPD showed reasonable split-half reliability estimates (0.84, 0.81, and 0.72) and nice Cronbach’s alpha estimates (0.90, 0.86, and 0.96). All indicators correlated with age and DST. ADE and DAD were sensitive predictors of hippocampal volume, and return time was a predictor of EC thickness. Conclusion: Our findings demonstrate that the VR-based path integration task exhibits good reliability and validity in the healthy population. The task indicators are age-sensitive, can capture working memory capacity, and are closely related to the integrity of individual EC and hippocampal structures.
Towards Conceptual Clarification of Proactive Inhibitory Control: A Review
Authors: van den Wildenberg Wery P. M. , Ridderinkhof K. Richard , Wylie Scott A.
Published: November 2022

The aim of this selective review paper is to clarify potential confusion when referring to the term proactive inhibitory control. Illustrated by a concise overview of the literature, we propose defining reactive inhibition as the mechanism underlying stopping an action. On a stop trial, the stop signal initiates the stopping process that races against the ongoing action-related process that is triggered by the go signal. Whichever processes finishes first determines the behavioral outcome of the race. That is, stopping is either successful or unsuccessful in that trial. Conversely, we propose using the term proactive inhibition to explicitly indicate preparatory processes engaged to bias the outcome of the race between stopping and going. More specifically, these proactive processes include either pre-amping the reactive inhibition system (biasing the efficiency of the stopping process) or presetting the action system (biasing the efficiency of the go process). We believe that this distinction helps meaningful comparisons between various outcome measures of proactive inhibitory control that are reported in the literature and extends to experimental research paradigms other than the stop task.
CaMKIIα as a Promising Drug Target for Ischemic Grey Matter
Authors: Griem-Krey Nane , Clarkson Andrew N. , Wellendorph Petrine
Published: November 2022

Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a major mediator of Ca2+-dependent signaling pathways in various cell types throughout the body. Its neuronal isoform CaMKIIα (alpha) centrally integrates physiological but also pathological glutamate signals directly downstream of glutamate receptors and has thus emerged as a target for ischemic stroke. Previous studies provided evidence for the involvement of CaMKII activity in ischemic cell death by showing that CaMKII inhibition affords substantial neuroprotection. However, broad inhibition of this central kinase is challenging because various essential physiological processes like synaptic plasticity rely on intact CaMKII regulation. Thus, specific strategies for targeting CaMKII after ischemia are warranted which would ideally only interfere with pathological activity of CaMKII. This review highlights recent advances in the understanding of how ischemia affects CaMKII and how pathospecific pharmacological targeting of CaMKII signaling could be achieved. Specifically, we discuss direct targeting of CaMKII kinase activity with peptide inhibitors versus indirect targeting of the association (hub) domain of CaMKIIα with analogues of γ-hydroxybutyrate (GHB) as a potential way to achieve more specific pharmacological modulation of CaMKII activity after ischemia.
Application of Grey Relational Analysis to Predict Dementia Tendency by Cognitive Function, Sleep Disturbances, and Health Conditions of Diabetic Patients
Authors: Huang Chiung-Yu , Lin Yu-Ching , Lu Yung-Chuan , Chen Chun-I
Published: November 2022

Background: The number of elderly diabetic patients has been increasing recently, and these patients have a higher morbidity of dementia than those without diabetes. Diabetes is associated with an increased risk for the development of dementia in elderly individuals, which is a serious health problem. Objectives: The primary aim was to examine whether diabetes is a risk factor for dementia among elderly individuals. The secondary aim was to apply grey theory to integrate the results and how they relate to cognitive impairments in elderly diabetic patients and to predict which participants are at high risk of developing dementia. Methods: Two hundred and twenty patients aged 50 years or older who were diagnosed with diabetes mellitus were recruited. Information on demographics, disease characteristics, activities of daily living, Mini Mental State Examination, sleep quality, depressive symptoms, and health-related quality of life was collected via questionnaires. The grey relational analysis approach was applied to evaluate the relationship between the results and health outcomes. Results: A total of 13.6% of participants had cognitive disturbances, of whom 1.4% had severe cognitive dysfunction. However, with regard to sleep disorders, 56.4% had sleep disturbances of varying degrees from light to severe. Further investigation is needed to address this problem. A higher prevalence of sleep disturbances among diabetic patients translates to a higher degree of depressive symptoms and a worse physical and mental health-related quality of life. Furthermore, based on the grey relational analysis, the grey relation coefficient varies from 0.6217~0.7540. Among the subjects, Participant 101 had the highest value, suggesting a need for immediate medical care. In this study, we observed that 20% of the total participants, for whom the grey relation coefficient was 0.6730, needed further and immediate medical care.
Negative Impacts of Sleep–Wake Rhythm Disturbances on Attention in Young Adults
Authors: Li Zijun , Fu Shimin , Jiang Fan , Nan Weizhi
Published: November 2022

Sleep–wake rhythm disturbances have a negative impact on attention. However, how it affects attention and whether the restoration of regular rhythms can restore attention are unclear. This study aims to explore the effects of sleep–wake rhythm disturbances on three subfunctions of attention (alertness, orientation, and executive control) and the restoration of regular rhythms on these functions. Twenty-one participants in the experimental group (who experienced sleep–wake rhythm disturbances for at least one month; aged 18–26) were required to sleep regularly following a sleep schedule, whereas 20 participants in the control group (who maintained regular sleep for at least three months; aged 19–22) received no manipulation of their sleep. All participants were assessed using the attention network test three times in six days. All of them wore spectrum activity monitors and kept sleep diaries every day. The results showed that the effects of alertness and executive control in the experimental group were significantly lower than those in the control group. After five days of regular sleep, the difference in the alertness effect between the two groups significantly decreased. These results suggested that under natural conditions, sleep–wake rhythm disturbances could negatively influence alertness and executive control, and a short period of restoring a regular rhythm has a recovery effect on alertness.
Passion for Violently Themed Music and Psychological Well-Being: A Survey Analysis
Authors: Powell Merrick , Olsen Kirk N. , Vallerand Robert J. , Thompson William Forde
Published: November 2022

While the benefits to mood and well-being from passionate engagement with music are well-established, far less is known about the relationship between passion for explicitly violently themed music and psychological well-being. The present study employed the Dualistic Model of Passion to investigate whether harmonious passion (i.e., passionate engagement that is healthily balanced with other life activities) predicts positive music listening experiences and/or psychological well-being in fans of violently themed music. We also investigated whether obsessive passion (i.e., uncontrollable passionate engagement with an activity) predicts negative music listening experiences and/or psychological ill-being. Fans of violently themed music (N = 177) completed the passion scale, scale of positive and negative affective experiences, and various psychological well- and ill-being measures. As hypothesised, harmonious passion for violently themed music significantly predicted positive affective experiences which, in turn, predicted psychological well-being. Obsessive passion for violently themed music significantly predicted negative affective experiences which, in turn, predicted ill-being. Findings support the Dualistic Model of Passion, and suggest that even when music engagement includes violent content, adaptive outcomes are often experienced. We propose that the nature of one’s passion for music is more influential in predicting well-being than the content or valence of the lyrical themes.
Prediction of Blast-Induced Structural Response and Associated Damage Using Machine Learning
Authors: Abd-Elhamed Ayman , Alkhatib Soliman , Abdelfattah Ahmed M. H.
Published: November 2022

Terrorist bombing-induced casualties are not only related to immediate fatalities but also to structural deterioration, damage, or even collapse that might occur and may lead to tremendous loss of life. Efficient assessment of blast-induced structural damage following explosion events is becoming a growing problem in modern societies. An attempt based on machine learning is made in this study to anticipate structures’ responses and the associated structural damage to reinforced concrete (RC) buildings exposed to extremely short-duration explosive loads. A program is developed to generate a set of analytically derived data for nonlinear building models subjected to explosive loads. Common machine learning models and Python libraries were utilized during the development of our program implementation to learn from a dataset. The latter has different features or input parameters, such as the amount of explosive charge, the distance from the building, fundamental period, and the building’s mass and rigidity, as well as the soil type. Our database is thus used, along with our regression-and-classification based implementations, to generate an output index that estimates and categorizes the state of damage based on the several most-important parameters of the explosion exposure. In the input database, the state of damage, based on the values of captured damage indices, is classified into one of four cases. Our code efficiently predicts those cases using a model that learns from the database. The prediction rates of the presented model reach an overall high accuracy. Therefore, the proposed model provides an accurate prediction of the level of structural damage by using the computed damage indices.
Retrofit of Building Façade Using Precast Sandwich Panel: An Integrated Thermal and Environmental Assessment on BIM-Based LCA
Authors: Tushar Quddus , Zhang Guomin , Bhuiyan Muhammed A. , Navaratnam Satheeskumar , Giustozzi Filippo , Hou Lei
Published: November 2022

The study conducts a comprehensive life cycle assessment (LCA) of precast sandwich panels by integrating operational and embodied phases detailing thermal efficiency and environmental impacts. The analytical regression model is developed for climatic diversity and design variables using the energy rating tool FirstRate5 to compare with a conventional brick veneer construction. LCA is performed on the building information modeling (BIM) platform to connect operational energy and express the relative embodied impacts of insulation constituents, compressive strength, reinforcement, and mix design. Monte Carlo simulation shows significant advantages of concrete sandwich panels in reducing operational H/C loads over building service life. LCA reveals a 100 mm thick external precast concrete wall with 50% fly ash reduces CO2 emission and energy demand by 54.7% and 75.9% consecutively against the benchmark. Moreover, it comprises 84.31% of the total building mass, accountable for only 53.27% of total CO2 emission and 27.25% of energy demand, which is comparatively lower than other materials. In the case of selecting lining insulation, a broader benefit is identified for extruded polystyrene (XPS) and expanded polystyrene (EPS) boards due to their relative weight, thickness, and environmental impacts. Representative equations of energy efficiency and impact assessment will assist in adopting sandwich panels for new construction and refurbishment with relative dimensions.
Metastases to Meningiomas: A Comprehensive Literature Review Including Mediating Proteins
Authors: Johnson Mahlon
Published: November 2022

Approximately 5–15% of solid tumors metastasizing to the central nervous system metastasize to the leptomeninges. Less common, is metastasis to leptomeningeal meningiomas. These are primarily carcinomas of the breast and lung. Awareness of this phenomenon is critical to the evaluation of meningiomas, especially since the metastases may be the first indication of an occult tumor elsewhere in the body. Lack of clear demarcation between the metastasis and meningioma parenchyma, as well as histological features similar to the meningioma, may hinder recognition. The mechanisms underlying metastases anchoring and spread along the leptomeninges are not established. However, several cell adhesion molecules are thought to contribute to this phenomenon. E cadherin is a cell adhesion molecule present in meningioma cells. Binding to endothelium by adhesion molecules such as ICAM, B1 integrin, P-selectin, PECAM-1, CXCL12 and SDF-1 have also been proposed as part of the mechanisms underlying breast carcinoma metastases. In addition, the leptomeninges and meningiomas express mesothelin that acts as an anchoring protein coupling with mucin-16. Consequently, metastatic tumor cell mucin and mesothelin may also facilitate the anchoring of metastases to meningiomas.
T-Cell Infiltration and Clonality May Identify Distinct Survival Groups in Colorectal Cancer: Development and Validation of a Prognostic Model Based on The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC)
Authors: Campana Luca G. , Mansoor Wasat , Hill James , Macutkiewicz Christian , Curran Finlay , Donnelly David , Hornung Ben , Charleston Peter , Bristow Robert , Lord Graham M. , Valpione Sara
Published: November 2022

Predicting the survival outcomes of patients with colorectal cancer (CRC) remains challenging. We investigated the prognostic significance of the transcriptome and tumour-infiltrating lymphocyte T-cell receptor (TIL/Tc-TCR) repertoire and analysed TIL/Tc-TCR sequences of The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) CRC cohorts. Using a multivariate Cox regression, we tested whether TIL/Tc-TCR repertoire, patient and tumour characteristics (stage, sidedness, total non-synonymous mutations, microsatellite instability (MSI) and transcriptional signatures) correlated with patient overall survival (OS) and designed a prognostic nomogram. A multivariate analysis (C-index = 0.75) showed that only patient age, disease stage, TIL/Tc degree of infiltration and clonality were independent prognostic factors for OS. The cut-offs for patients’ allocation to TIL/Tc abundance subgroups were determined using a strategy of maximally selected rank statistics with the OptimalCutpoints R package. These were “high”, “low” and “very high” (90 th percentile) TIL/Tc infiltration-stratified OS (median not reached, 67 and 44.3 months; p < 0.001); the results were validated in the CPTAC cohort. TIL/Tc clonality was prognostic (median OS in “high” vs. “low” clonality not reached and 67.3 months; p = 0.041) and independent of TIL/Tc infiltration. Whilst tumour sidedness was not prognostic, the “very highly” infiltrated tumours were prevalent among right-sided CRCs (p = 0.039) and showed distinct immunological features, with lower Th1 signature (p = 0.004), higher PD-L1 expression (p < 0.001) and likely enrichment in highly suppressory IL1R1+ Tregs (FoxP3 and IL1R1 overexpression, p < 0.001). TIL/Tc abundance and clonality are independent prognosticators in CRC and, combined with clinical variables, refine risk stratification. We identified a subset of CRCs with “very high” TIL/Tc infiltration, poor prognosis and distinct genetic and immunologic features, which may benefit from alternative therapeutic approaches. These results need validation in prospective patient cohorts.
Clinical Score to Predict Recurrence in Patients with Stage II and Stage III Colon Cancer
Authors: Viñal David , Martinez-Recio Sergio , Martinez-Perez Daniel , Ruiz-Gutierrez Iciar , Jimenez-Bou Diego , Peña-Lopez Jesús , Alameda-Guijarro Maria , Martin-Montalvo Gema , Rueda-Lara Antonio , Gutierrez-Sainz Laura , Palacios Maria Elena , Custodio Ana Belén , Ghanem Ismael , Feliu Jaime , Rodríguez-Salas Nuria
Published: November 2022

Background: The prognosis of patients with stage II and stage III colon cancer is heterogeneous. Clinical and pathological characteristics, such as tumor budding, may help to further refine the recurrence risk. Methods: We included all the patients with localized colon cancer at Hospital Universitario La Paz from October 2016 to October 2021. We built a prognostic score for recurrence in the training cohort based on multivariate cox regression analysis and categorized the patients into two risk groups. Results: A total of 440 patients were included in the training cohort. After a median follow-up of 45 months, 81 (18%) patients had a first tumor recurrence. T4, N2, and high tumor budding remained with a p value <0.05 at the last step of the multivariate cox regression model for time to recurrence (TTR). We assigned 2 points to T4 and 1 point to N2 and high tumor budding. Forty-five percent of the patients were assigned to the low-risk group (score = 0). Compared to the high-risk group (score 1–4), patients in the low-risk group had a significantly longer TTR (hazard ratio for disease recurrence of 0.14 (95%CI: 0.00 to 0.90; p < 0.045)). The results were confirmed in the validation cohort. Conclusions: In our study, we built a simple score to predict tumor recurrence based on T4, N2, and high tumor budding. Patients in the low-risk group, that comprised 44% of the cohort, had an excellent prognosis.
Gemcitabine: An Alternative Treatment for Oxaliplatin-Resistant Colorectal Cancer
Authors: Chocry Mathieu , Leloup Ludovic , Parat Fabrice , Messé Mélissa , Pagano Alessandra , Kovacic Hervé
Published: November 2022

Resistance to treatments is one of the leading causes of cancer therapy failure. Oxaliplatin is a standard chemotherapy used to treat metastatic colorectal cancer. However, its efficacy is greatly reduced by the development of resistances. In a previous study, we deciphered the mechanisms leading to oxaliplatin resistance and highlighted the roles played by ROS production and the p38 MAPK pathway in this phenomenon. In this report, we studied the effects of different chemotherapy molecules on our oxaliplatin-resistant cells to identify alternative treatments. Among all the studied molecules, gemcitabine was the only one to present a major cytotoxic effect on oxaliplatin-resistant cancer cells both in vivo and in vitro. However, the combination of oxaliplatin and gemcitabine did not present any major interest. Indeed, the study of combination efficiency using Chou and Talalay’s method showed no synergy between oxaliplatin and gemcitabine. Using PamGene technology to decipher gemcitabine’s effects on oxaliplatin-resistant cells, we were able to show that gemcitabine counteracts chemoresistance by strongly inhibiting the Akt and src/p38 MAPK pathways, leading to apoptosis induction and cell death. In view of these results, gemcitabine could be an interesting alternative therapy for patients with colorectal cancer not responding to oxaliplatin-based protocols such as FOLFOX.
Epigenetics in Pancreatic Ductal Adenocarcinoma: Impact on Biology and Utilization in Diagnostics and Treatment
Authors: Elrakaybi Asmaa , Ruess Dietrich A. , Lübbert Michael , Quante Michael , Becker Heiko
Published: November 2022

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies with high potential of metastases and therapeutic resistance. Although genetic mutations drive PDAC initiation, they alone do not explain its aggressive nature. Epigenetic mechanisms, including aberrant DNA methylation and histone modifications, significantly contribute to inter- and intratumoral heterogeneity, disease progression and metastasis. Thus, increased understanding of the epigenetic landscape in PDAC could offer new potential biomarkers and tailored therapeutic approaches. In this review, we shed light on the role of epigenetic modifications in PDAC biology and on the potential clinical applications of epigenetic biomarkers in liquid biopsy. In addition, we provide an overview of clinical trials assessing epigenetically targeted treatments alone or in combination with other anticancer therapies to improve outcomes of patients with PDAC.
Role of the Hypoxic-Secretome in Seed and Soil Metastatic Preparation
Authors: Clemente-González Cynthia , Carnero Amancio
Published: November 2022

During tumor growth, the delivery of oxygen to cells is impaired due to aberrant or absent vasculature. This causes an adaptative response that activates the expression of genes that control several essential processes, such as glycolysis, neovascularization, immune suppression, and the cancer stemness phenotype, leading to increased metastasis and resistance to therapy. Hypoxic tumor cells also respond to an altered hypoxic microenvironment by secreting vesicles, factors, cytokines and nucleic acids that modify not only the immediate microenvironment but also organs at distant sites, allowing or facilitating the attachment and growth of tumor cells and contributing to metastasis. Hypoxia induces the release of molecules of different biochemical natures, either secreted or inside extracellular vesicles, and both tumor cells and stromal cells are involved in this process. The mechanisms by which these signals that can modify the premetastatic niche are sent from the primary tumor site include changes in the extracellular matrix, recruitment and activation of different stromal cells and immune or nonimmune cells, metabolic reprogramming, and molecular signaling network rewiring. In this review, we will discuss how hypoxia might alter the premetastatic niche through different signaling molecules.
Valorization of Recycled Honeycombs from Exhausted TWCs by Means of Their Use as a Support of MnOx Catalysts for Acetone Combustion
Authors: De los Santos Carolina , Gatica José Manuel , Castiglioni Jorge , Vidal Hilario
Published: November 2022

Exhausted TWCs subjected to chemical/thermal treatments were used as a support of MnOx catalysts for the total combustion of acetone. The so-prepared new devices were characterized by using adherence tests, elemental and thermal analyses, XRD, N2 physisorption, and SEM-EDS. Incorporation of only 2.6 wt.% of the active phase (Mn2O3 and Mn3O4) to the recycled honeycomb considerably improved the catalytic response, achieving at 250 °C a 60% increase in acetone conversion with respect to the spent autocatalyst. The following procedure is proposed as a simple way to provide the TWC devoid of noble metals a second life in the VOCs’ oxidation field.
Interfacial Electronic Engineering of NiSe–Anchored Ni–N–C Composite Electrocatalyst for Efficient Hydrogen Evolution
Authors: Che Sai , Ta Na , Yang Fan , Yang Yulong , Li Yongfeng
Published: November 2022

Rational design and construction of cost–effective electrocatalysts for efficient hydrogen production has attracted extensive research attention worldwide. Herein, we report the construction of a transition metal selenide/carbon composite catalyst featuring uniform NiSe nanoparticles anchored to single Ni atom doped porous carbon structure (NiSe/Ni–N–C) via a facile one–pot pyrolysis of low–cost solid mixtures. NiSe/Ni–N–C exhibits remarkable catalytic performance towards hydrogen evolution reaction (HER) in 1.0 M KOH, requiring a low overpotential of 146 mV to reach a current density of 10 mA cm−2. The unique carbon layer encapsulation derived from the enwrapping of fluid catalytic cracking slurry further renders NiSe/Ni–N–C excellent for long–term durability in electrolyte corrosion and nanostructure aggregation. This work paves the way for the design and synthesis of highly efficient composite HER electrocatalysts.
Efficient Visible-Light Driven Photocatalytic Hydrogen Production by Z-Scheme ZnWO4/Mn0.5Cd0.5S Nanocomposite without Precious Metal Cocatalyst
Authors: Ma Tingting , Li Zhen , Wang Gan , Zhang Jinfeng , Wang Zhenghua
Published: November 2022

How to restrain the recombination of photogenerated electrons and holes is still very important for photocatalytic hydrogen production. Herein, Z-scheme ZnWO4/Mn0.5Cd0.5S (ZWMCS) nanocomposites are prepared and are applied as visible-light driven precious metal cocatalyst free photocatalyst for hydrogen generation. The ZnWO4/Mn0.5Cd0.5S nanocomposites with 30 wt% ZnWO4 (ZWMCS-2) can reach a photocatalytic hydrogen evolution rate of 3.36 mmol g−1 h−1, which is much higher than that of single ZnWO4 (trace) and Mn0.5Cd0.5S (1.96 mmol g−1 h−1). Cycling test reveals that the ZMWCS-2 nanocomposite can maintain stable photocatalytic hydrogen evolution for seven cycles (21 h). The type of heterojunction in the ZWMCS-2 nanocomposite can be identified as Z-scheme heterojunction. The Z-scheme heterojunction can effectively separate the electrons and holes, so that the hydrogen generation activity and stability of the ZWMCS-2 nanocomposite can be enhanced. This work provides a highly efficient and stable Z-scheme heterojunction photocatalyst for hydrogen generation.
Liraglutide Improves the Angiogenic Capability of EPC and Promotes Ischemic Angiogenesis in Mice under Diabetic Conditions through an Nrf2-Dependent Mechanism
Authors: Yan Xiaoqing , Su Yue , Fan Xia , Chen Hui , Lu Zixian , Liu Zijuan , Li Yingjian , Yi Mei , Zhang Guigui , Gu Chunjie , Wang Kai , Wu Jiamin , Sun Da , Zhang Yikai , Zhang Chi , Dai Xiaozhen , Zheng Chao
Published: November 2022

The impairment in endothelial progenitor cell (EPC) functions results in dysregulation of vascular homeostasis and dysfunction of the endothelium under diabetic conditions. Improving EPC function has been considered as a promising strategy for ameliorating diabetic vascular complications. Liraglutide has been widely used as a therapeutic agent for diabetes. However, the effects and mechanisms of liraglutide on EPC dysfunction remain unclear. The capability of liraglutide in promoting blood perfusion and angiogenesis under diabetic conditions was evaluated in the hind limb ischemia model of diabetic mice. The effect of liraglutide on the angiogenic function of EPC was evaluated by cell scratch recovery assay, tube formation assay, and nitric oxide production. RNA sequencing was performed to assess the underlying mechanisms. Liraglutide enhanced blood perfusion and angiogenesis in the ischemic hindlimb of db/db mice and streptozotocin-induced type 1 diabetic mice. Additionally, liraglutide improved tube formation, cell migration, and nitric oxide production of high glucose (HG)-treated EPC. Assessment of liraglutide target pathways revealed a network of genes involved in antioxidant activity. Further mechanism study showed that liraglutide decreased the production of reactive oxygen species and increased the activity of nuclear factor erythroid 2-related factor 2 (Nrf2). Nrf2 deficiency attenuated the beneficial effects of liraglutide on improving EPC function and promoting ischemic angiogenesis under diabetic conditions. Moreover, liraglutide activates Nrf2 through an AKT/GSK3β/Fyn pathway, and inhibiting this pathway abolished liraglutide-induced Nrf2 activation and EPC function improvement. Overall, these results suggest that Liraglutide represents therapeutic potential in promoting EPC function and ameliorating ischemic angiogenesis under diabetic conditions, and these beneficial effects relied on Nrf2 activation.
Insights into Regulators of p53 Acetylation
Authors: Nagasaka Mai , Miyajima Chiharu , Aoki Hiromasa , Aoyama Mineyoshi , Morishita Daisuke , Inoue Yasumichi , Hayashi Hidetoshi
Published: November 2022

The tumor suppressor p53 is a transcription factor that regulates the expression of dozens of target genes and diverse physiological processes. To precisely regulate the p53 network, p53 undergoes various post-translational modifications and alters the selectivity of target genes. Acetylation plays an essential role in cell fate determination through the activation of p53. Although the acetylation of p53 has been examined, the underlying regulatory mechanisms remain unclear and, thus, have attracted the interest of researchers. We herein discuss the role of acetylation in the p53 pathway, with a focus on p53 acetyltransferases and deacetylases. We also review recent findings on the regulators of these enzymes to understand the mode of p53 acetylation from a broader perspective.