bluuebunny/crossref_metadata_2025 huggingface dataset:
Tumor Temperature: Friend or Foe of Virus-Based Cancer Immunotherapy
Authors: Knapp Jason P. , Kakish Julia E. , Bridle Byram W. , Speicher David J.
Published: August 2022

The temperature of a solid tumor is often dissimilar to baseline body temperature and, compared to healthy tissues, may be elevated, reduced, or a mix of both. The temperature of a tumor is dependent on metabolic activity and vascularization and can change due to tumor progression, treatment, or cancer type. Despite the need to function optimally within temperature-variable tumors, oncolytic viruses (OVs) are primarily tested at 37 °C in vitro. Furthermore, animal species utilized to test oncolytic viruses, such as mice, dogs, cats, and non-human primates, poorly recapitulate the temperature profile of humans. In this review, we discuss the importance of temperature as a variable for OV immunotherapy of solid tumors. Accumulating evidence supports that the temperature sensitivity of OVs lies on a spectrum, with some OVs likely hindered but others enhanced by elevated temperatures. We suggest that in vitro temperature sensitivity screening be performed for all OVs destined for the clinic to identify potential hinderances or benefits with regard to elevated temperature. Furthermore, we provide recommendations for the clinical use of temperature and OVs.
TERT and TET2 Genetic Variants Affect Leukocyte Telomere Length and Clinical Outcome in Coronary Artery Disease Patients—A Possible Link to Clonal Hematopoiesis
Authors: Opstad Trine B. , Solheim Svein , Pettersen Alf-Åge R. , Kalstad Are A. , Arnesen Harald , Seljeflot Ingebjørg
Published: August 2022

Inherited and acquired mutations in hematopoietic stem cells can cause clonal expansion with increased risk of cardiovascular disease (CVD), a condition known for the clonal hematopoiesis of indeterminate potential (CHIP). Inherited genetic variants in two CHIP-associated genome loci, the telomerase gene telomerase enzyme reverse transcriptase (TERT) (rs7705526) and the epigenetic regulator ten–eleven translocation 2 (TET2) (rs2454206), were investigated in 1001 patients with stable coronary artery disease (CAD) (mean age 62 years, 22% women), with regards to cardiovascular outcome, comorbidities, and leukocyte telomere length. Over 2 years, mutated TERT increased the risk two-fold for major clinical events (MACEs) in all patients (p = 0.004), acute myocardial infarction (AMI) in male patients (p = 0.011), and stroke in female patients (p < 0.001). Mutated TET2 correlated with type 2 diabetes (p < 0.001), the metabolic syndrome (p = 0.002), as well as fasting glucose, HbA1c, and shorter telomeres (p = 0.032, p = 0.003, and p = 0.016, respectively). In conclusion, our results from stable CAD patients highlight TERTs’ role in CVD, and underline TET2s’ role in the epigenetic regulation of lifestyle-related diseases.
Biomarkers in Anal Cancer: Current Status in Diagnosis, Disease Progression and Therapeutic Strategies
Authors: Mathias-Machado Maria Cecília , Peixoto Renata D’Alpino , Moniz Camila Motta Venchiarutti , Jácome Alexandre A.
Published: August 2022

Squamous cell carcinoma of the anal canal (SCCA) is a rare neoplasm, but with rising incidence rates in the past few decades; it is etiologically linked with the human papillomavirus (HPV) infection and is especially prevalent in immunocompromised patients, mainly those infected with HIV. Fluoropyrimidine-based chemoradiotherapy remains the cornerstone of the treatment of non-metastatic disease, but the locally advanced disease still presents high rates of disease recurrence and systemic therapy of SCCA is an unmet clinical need. Despite sharing common molecular aspects with other HPV-related malignancies, such as cervical and head and neck cancers, SCCA presents specific epigenomic, genomic, and transcriptomic abnormalities, which suggest that genome-guided personalized therapies should be specifically designed for this disease. Actionable mutations are rare in SCCA and immune checkpoint inhibition has not yet been proven useful in an unselected population of patients. Therefore, advances in systemic therapy of SCCA will only be possible with the identification of predictive biomarkers and the subsequent development of targeted therapies or immunotherapeutic approaches that consider the unique tumor microenvironment and the intra- and inter-tumoral heterogeneity. In the present review, we address the molecular characterization of SCCA and discuss potential diagnostic, predictive and prognostic biomarkers of this complex and challenging disease.
MGMT Promoter Methylation as a Prognostic Factor in Primary Glioblastoma: A Single-Institution Observational Study
Authors: Szylberg Mateusz , Sokal Paweł , Śledzińska Paulina , Bebyn Marek , Krajewski Stanisław , Szylberg Łukasz , Szylberg Aneta , Szylberg Tadeusz , Krystkiewicz Kamil , Birski Marcin , Harat Marek , Włodarski Robert , Furtak Jacek
Published: August 2022

Glioblastoma is the most malignant central nervous system tumor, which represents 50% of all glial tumors. The understanding of glioma genesis, prognostic evaluation, and treatment planning has been significantly enhanced by the discovery of molecular genetic biomarkers. This study aimed to evaluate survival in patients with primary glioblastoma concerning O6-methylguanine–DNA methyltransferase (MGMT) promoter methylation and other clinical factors. The study included 41 newly diagnosed glioblastoma patients treated from 2011 to 2014 in the 10th Military Research Hospital and Polyclinic, Poland. All patients underwent surgical resection followed by radiation and chemotherapy with alkylating agents. The MGMT promoter methylation was evaluated in all patients, and 43% were found to be methylated. In 26 and 15 cases, gross total resection and subtotal resection were conducted, respectively. Patients with a methylated MGMT promoter had a median survival of 504 days, while those without methylation had a median survival of 329 days. The group that was examined had a median age of 53. In a patient group younger than 53 years, those with methylation had significantly longer overall survival (639 days), compared to 433.5 days for patients without methylation. The most prolonged survival (551 days) was in patients with MGMT promoter methylation after gross total resection. The value of MGMT promoter methylation as a predictive biomarker is widely acknowledged. However, its prognostic significance remains unclear. Our findings proved that MGMT promoter methylation is also an essential positive prognostic biomarker.
Mechanism and Therapeutic Targets of c-Jun-N-Terminal Kinases Activation in Nonalcoholic Fatty Liver Disease
Authors: Min Robert W. M. , Aung Filbert W. M. , Liu Bryant , Arya Aliza , Win Sanda
Published: August 2022

Non-alcoholic fatty liver (NAFL) is the most common chronic liver disease. Activation of mitogen-activated kinases (MAPK) cascade, which leads to c-Jun N-terminal kinase (JNK) activation occurs in the liver in response to the nutritional and metabolic stress. The aberrant activation of MAPKs, especially c-Jun-N-terminal kinases (JNKs), leads to unwanted genetic and epi-genetic modifications in addition to the metabolic stress adaptation in hepatocytes. A mechanism of sustained P-JNK activation was identified in acute and chronic liver diseases, suggesting an important role of aberrant JNK activation in NASH. Therefore, modulation of JNK activation, rather than targeting JNK protein levels, is a plausible therapeutic application for the treatment of chronic liver disease.
Prevention of Anti-HMGCR Immune-Mediated Necrotising Myopathy by C5 Complement Inhibition in a Humanised Mouse Model
Authors: Julien Sarah , Vadysirisack Douangsone , Sayegh Camil , Ragunathan Sharan , Tang Yalan , Briand Emma , Carrette Marion , Jean Laetitia , Zoubairi Rachid , Gondé Henri , Benveniste Olivier , Allenbach Yves , Drouot Laurent , Boyer Olivier
Published: August 2022

Introduction: immune-mediated necrotising myopathy (IMNM) is associated with pathogenic anti-signal recognition particle (SRP) or 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) antibodies, at least partly through activation of the classical pathway of the complement. We evaluated zilucoplan, an investigational drug, and a macrocyclic peptide inhibitor of complement component 5 (C5), in humanized mouse models of IMNM. Methods: purified immunoglobulin G (IgG) from an anti-HMGCR+ IMNM patient was co-injected intraperitoneally with human complement in C57BL/6, C5-deficient B10 (C5def) and Rag2 deficient (Rag2−/−) mice. Zilucoplan was administered subcutaneously in a preventive or interventional paradigm, either injected daily throughout the duration of the experiment in C57BL/6 and C5def mice or 8 days after disease induction in Rag2−/− mice. Results: prophylactic administration of zilucoplan prevented muscle strength loss in C5def mice (anti-HMGCR+ vs. anti-HMGCR+ + zilucoplan: p = 0.0289; control vs. anti-HMGCR+ + zilucoplan: p = 0.4634) and wild-type C57BL/6 (anti-HMGCR+ vs. anti-HMGCR+ + zilucoplan: p = 0.0002; control vs. anti-HMGCR+ + zilucoplan: p = 0.0939) with corresponding reduction in C5b-9 deposits on myofibres and number of regenerated myofibres. Interventional treatment of zilucoplan after disease induction reduced the complement deposits and number of regenerated myofibres in muscles of Rag2−/− mice, although to a lesser extent. In this latter setting, C5 inhibition did not significantly ameliorate muscle strength. Conclusion: Early administration of zilucoplan prevents the onset of myopathy at the clinical and histological level in a humanized mouse model of IMNM.
Peptide-Based Drug Development
Authors: Lubell William D.
Published: August 2022

The celebration of one hundred years of insulin therapy in 2021 marked a milestone for the application of peptide-based therapeutics [...]
Genomic Aberrations Generate Fusion Gene FOXK2::TP63 and Activate NFKB1 in Cutaneous T-Cell Lymphoma
Authors: Nagel Stefan , Pommerenke Claudia , Quentmeier Hilmar , Meyer Corinna , Kaufmann Maren , MacLeod Roderick A. F.
Published: August 2022

Cutaneous T-cell lymphoma (CTCL) is a severe lymphoid malignancy with a worse prognosis lacking curative treatment regimens. Several gene mutations and deregulated pathways, including NFkB signaling, have been implicated in its pathogenesis. Accordingly, CTCL cell line HUT-78 reportedly contains mutated NFKB2, which is constitutively activated via partial gene deletion, also demonstrating that genomic rearrangements cause driving mutations in this malignancy. Here, along with HUT-78, we analyzed CTCL cell line HH to identify additional aberrations underlying gene deregulation. Karyotyping and genomic profiling of HH showed several rearrangements worthy of detailed investigation. Corresponding to the established karyotype, RNA-seq data and PCR analysis confirmed the presence of t(3;17)(q28;q25), generating a novel fusion gene, FOXK2::TP63. Furthermore, chromosomal rearrangement t(1;4)(p32;q25) was connected to amplification at 4q24–26, affecting aberrant NFKB1 overexpression thereat. Transcription factor binding-site analysis and knockdown experiments demonstrated that IRF4 contributed to NFKB1 expression. Within the same amplicon, we identified amplification and overexpression of NFkB signaling activator CAMK2D (4q26) and p53-inhibitor UBE2D3 (4q24). Genomic profiling data for HUT-78 detailed a deletion at 10q25 underlying reported NFKB2 activation. Moreover, amplifications of ID1 (20q11) and IKZF2 (2q34) in this cell line drove overexpression of these NK cell differentiation factors and possibly thus formed corresponding lineage characteristics. Target gene analysis for NFKB1 via siRNA-mediated knockdown in HH revealed activation of TP63, MIR155, and NOTCH pathway component RBPJ. Finally, treatment of HH with NFkB inhibitor demonstrated a role for NFkB in supporting proliferation, while usage of inhibitor DAPT showed significant survival effects via the NOTCH pathway. Collectively, our data suggest that NFkB and/or NOTCH inhibitors may represent reasonable treatment options for subsets of CTCL patients.
The Role of the NRF2 Pathway in Maintaining and Improving Cognitive Function
Authors: Gray Nora E. , Farina Marcelo , Tucci Paolo , Saso Luciano
Published: August 2022

Nuclear factor (erythroid-derived 2)-like 2 (NRF2) is a redox-sensitive transcription factor that binds to the antioxidant response element consensus sequence, decreasing reactive oxygen species and regulating the transcription of a wide array of genes, including antioxidant and detoxifying enzymes, regulating genes involved in mitochondrial function and biogenesis. Moreover, NRF2 has been shown to directly regulate the expression of anti-inflammatory mediators reducing the expression of pro-inflammatory cytokines. In recent years, attention has turned to the role NRF2 plays in the brain in different diseases such Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and others. This review focused on the evidence, derived in vitro, in vivo and from clinical trials, supporting a role for NRF2 activation in maintaining and improving cognitive function and how its activation can be used to elicit neuroprotection and lead to cognitive enhancement. The review also brings a critical discussion concerning the possible prophylactic and/or therapeutic use of NRF2 activators in treating cognitive impairment-related conditions.
Systematic Review on the Use of Biosimilars of Trastuzumab in HER2+ Breast Cancer
Authors: Triantafyllidi Eleni , Triantafillidis John K.
Published: August 2022

Trastuzumab is a monoclonal antibody used in the treatment of breast cancer in cases where the tumor overexpresses the HER2 receptor, a cell membrane receptor activated by the epidermal growth factor. Intravenous and subcutaneous administration of trastuzumab have comparable clinical and pharmacological characteristics, but trastuzumab biosimilars are currently only available in intravenous form. Trastuzumab biosimilars are ultimately preferred by a proportion of patients, especially in cases where co-administration of other chemotherapeutic agents, such as trastuzumab and tucatinib, a small molecule of tyrosine kinase inhibitor, is required in patients with HER-positive metastatic breast cancer. Oncologists should be well-aware of the advantages of intravenously administered trastuzumab biosimilars over subcutaneous administration, certainly also taking into account the patient’s preferences. Further cost-effectiveness analyses will be very important, along with expectations regarding successful concomitant subcutaneous administration of trastuzumab with other anticancer drugs, such as pertuzumab. This systematic review describes and analyzes the so-far published studies concerning the use of the available trastuzumab biosimilars in HER-positive early and metastatic breast cancer in terms of efficacy, safety, and cost–benefit ratio. An attempt was also made to draw some conclusions and to comment on future needs and perspectives.
Sensitive Electrochemical Biosensor for Rapid Screening of Tumor Biomarker TP53 Gene Mutation Hotspot
Authors: Sun Pengcheng , Niu Kai , Du Haiying , Li Ruixin , Chen Jiping , Lu Xianbo
Published: August 2022

Rapid and sensitive detection of cancer biomarkers is crucial for cancer screening, early detection, and improving patient survival rate. The present study proposes an electrochemical gene-sensor capable of detecting tumor related TP53 gene mutation hotspots by self-assembly of sulfhydryl ended hairpin DNA probes tagged with methylene blue (MB) onto a gold electrode. By performing a hybridization reaction with the target DNA sequence, the gene-sensor can rearrange the probe’s structure, resulting in significant electrochemical signal differences by differential pulse voltammetry. When the DNA biosensor is hybridized with 1 μM target DNA, the peak current response signal can decrease more than 60%, displaying high sensitivity and specificity for the TP53 gene. The biosensor achieved rapid and sensitive detection of the TP53 gene with a detection limit of 10 nmol L−1, and showed good specific recognition ability for single nucleotide polymorphism (SNP) and base sequence mismatches in the TP53 gene affecting residue 248 of the P53 protein. Moreover, the biosensor demonstrated good reproducibility, repeatability, operational stability, and anti-interference ability for target DNA molecule in the complex system of 50% fetal bovine serum. The proposed biosensor provides a powerful tool for the sensitive and specific detection of TP53 gene mutation hotspot sequences and could be used in clinical samples for early diagnosis and detection of cancer.
A Flexible and Attachable Colorimetric Film Sensor for the Detection of Gaseous Ammonia
Authors: Lee Sangwon , Lee Eun-Hee , Lee Seung-Woo
Published: August 2022

A cost-effective, simple, flexible, and disposable colorimetric film sensor was constructed for the rapid detection of gaseous ammonia. The sensor was designed to consist of three layers, namely top, middle, and bottom layers of a polymeric elastomer. The bromocresol (BCG) indicator embedded in the middle layer of the film facilitated a change in color of the sensor from yellow-orange to blue upon exposure to gaseous ammonia. The color change was visually observed by the naked eye. The sensitivity of the sensor was verified by a successful detection of gaseous ammonia at concentrations from 4 to 235 ppm within 3 min, and the corresponding visual detection of ammonia gas was at a concentration as low as 11 ppm. The sensor also achieved a selective detection of gaseous ammonia over a variety of alkaline chemicals. The color of the sensor exposed to ammonia reverted from blue to the original yellow-orange upon subsequent exposure to the fume of acetic acid or aeration for 48 h, and it showed reliable performance for the detection of gaseous ammonia even after five repeated uses. The applicability of the sensor was validated by attaching it onto a safety helmet for a simulation of an industrial ammonia gas leak. The results indicated that our colorimetric film sensor is affordable, disposable, and reproducible, and can serve as an effective alternative for simple and rapid recognition of gaseous ammonia in environmental and air quality monitoring as well as in industrial applications.
Integrating Human Waste with Microbial Fuel Cells to Elevate the Production of Bioelectricity
Authors: Pandit Chetan , Thapa Bhim Sen , Srivastava Bhagyashree , Mathuriya Abhilasha Singh , Toor Umair-Ali , Pant Manu , Pandit Soumya , Jadhav Deepak-A.
Published: August 2022

Due to the continuous depletion of natural resources currently used for electricity generation, it is imperative to develop alternative energy sources. Human waste is nowadays being explored as an efficient source to produce bio-energy. Human waste is renewable and can be used as a source for an uninterrupted energy supply in bioelectricity or biofuel. Annually, human waste such as urine is produced in trillions of liters globally. Hence, utilizing the waste to produce bioenergy is bio-economically suitable and ecologically balanced. Microbial fuel cells (MFCs) play a crucial role in providing an effective mode of bioelectricity production by implementing the role of transducers. MFCs convert organic matter into energy using bio-electro-oxidation of material to produce electricity. Over the years, MFCs have been explored prominently in various fields to find a backup for providing bioenergy and biofuel. MFCs involve the role of exoelectrogens which work as transducers to convert the material into electricity by catalyzing redox reactions. This review paper demonstrates how human waste is useful for producing electricity and how this innovation would be beneficial in the long term, considering the current scenario of increasing demand for the supply of products and shortages of natural resources used to produce biofuel and bioelectricity.
High-Level Visual Encoding Model Framework with Hierarchical Ventral Stream-Optimized Neural Networks
Authors: Xiao Wulue , Li Jingwei , Zhang Chi , Wang Linyuan , Chen Panpan , Yu Ziya , Tong Li , Yan Bin
Published: August 2022

Visual encoding models based on deep neural networks (DNN) show good performance in predicting brain activity in low-level visual areas. However, due to the amount of neural data limitation, DNN-based visual encoding models are difficult to fit for high-level visual areas, resulting in insufficient encoding performance. The ventral stream suggests that higher visual areas receive information from lower visual areas, which is not fully reflected in the current encoding models. In the present study, we propose a novel visual encoding model framework which uses the hierarchy of representations in the ventral stream to improve the model’s performance in high-level visual areas. Under the framework, we propose two categories of hierarchical encoding models from the voxel and the feature perspectives to realize the hierarchical representations. From the voxel perspective, we first constructed an encoding model for the low-level visual area (V1 or V2) and extracted the voxel space predicted by the model. Then we use the extracted voxel space of the low-level visual area to predict the voxel space of the high-level visual area (V4 or LO) via constructing a voxel-to-voxel model. From the feature perspective, the feature space of the first model is extracted to predict the voxel space of the high-level visual area. The experimental results show that two categories of hierarchical encoding models effectively improve the encoding performance in V4 and LO. In addition, the proportion of the best-encoded voxels for different models in V4 and LO show that our proposed models have obvious advantages in prediction accuracy. We find that the hierarchy of representations in the ventral stream has a positive effect on improving the performance of the existing model in high-level visual areas.
Dynamic Functional Connectivity of Emotion Processing in Beta Band with Naturalistic Emotion Stimuli
Authors: Mishra Sudhakar , Srinivasan Narayanan , Tiwary Uma Shanker
Published: August 2022

While naturalistic stimuli, such as movies, better represent the complexity of the real world and are perhaps crucial to understanding the dynamics of emotion processing, there is limited research on emotions with naturalistic stimuli. There is a need to understand the temporal dynamics of emotion processing and their relationship to different dimensions of emotion experience. In addition, there is a need to understand the dynamics of functional connectivity underlying different emotional experiences that occur during or prior to such experiences. To address these questions, we recorded the EEG of participants and asked them to mark the temporal location of their emotional experience as they watched a video. We also obtained self-assessment ratings for emotional multimedia stimuli. We calculated dynamic functional the connectivity (DFC) patterns in all the frequency bands, including information about hubs in the network. The change in functional networks was quantified in terms of temporal variability, which was then used in regression analysis to evaluate whether temporal variability in DFC (tvDFC) could predict different dimensions of emotional experience. We observed that the connectivity patterns in the upper beta band could differentiate emotion categories better during or prior to the reported emotional experience. The temporal variability in functional connectivity dynamics is primarily related to emotional arousal followed by dominance. The hubs in the functional networks were found across the right frontal and bilateral parietal lobes, which have been reported to facilitate affect, interoception, action, and memory-related processing. Since our study was performed with naturalistic real-life resembling emotional videos, the study contributes significantly to understanding the dynamics of emotion processing. The results support constructivist theories of emotional experience and show that changes in dynamic functional connectivity can predict aspects of our emotional experience.
Correction: Zhang et al. The Effect of Non-Invasive Brain Stimulation on the Downregulation of Negative Emotions: A Meta-Analysis. Brain Sci. 2022, 12, 786
Authors: Zhang Qingqing , Li Xiaoming , Liu Xinying , Liu Shanshan , Zhang Mengzhu , Liu Yueling , Zhu Chunyan , Wang Kai
Published: August 2022

In the original article [...]
Spatial Olfactory Memory and Spatial Olfactory Navigation, Assessed with a Variant of Corsi Test, Is Modulated by Gender and Sporty Activity
Authors: Invitto Sara , Accogli Giuseppe , Leucci Mariangela , Salonna Marika , Serio Tonia , Fancello Francesca , Ciccarese Vincenzo , Lankford Dion
Published: August 2022

Many studies have focused on navigation, spatial skills, and the olfactory system in comparative models, including those concerning the relationship between them and physical activity. Although the results are often in contrast with each other, it is assumed that physical activity can affect cognition in different ways—both indirectly and through a certain influence on some brain structures. In contrast, there is little research that focuses on the relationship between spatial abilities and olfactory abilities in humans. This research aimed to evaluate and compare the performance in working memory tasks of athletes and non-athletes who require good visual–spatial navigation, olfactory–spatial navigation, and olfactory–semantic skills. The study involved 236 participants (83 athletes) between the ages of 18 and 40. All subjects were matched by age or sex. The standard Corsi Block Tapping Test (CBTT) was administrated to investigate the visual-spatial memory. Olfactory–spatial navigation and olfactory–semantic skills were assessed with two modified versions of CBTT: Olfactory CBTT (OCBTT) and Semantic–Olfactory CBTT (SOCBTT) respectively. The results show differences between the CORSI conditions in direction of a poor performance for athletes. A gender effect in favor of men was also found, particularly in the classic version of the CBTT. Both groups performed better in the classic version of the CBTT than OCBTT and SOCBTT. The mean of SOCBTT results is markedly lower, perhaps due to the different information processing systems needed to perform this kind of task. It is possible to explain how sports practice can affect tasks that require spatial skills and olfactory perception differently, thus supporting new hypotheses and opening new scientific horizons.
Changes in Oral Microbial Diversity in a Piglet Model of Traumatic Brain Injury
Authors: Jeon Julie Heejin , Lourenco Jeferson M. , Fagan Madison M. , Welch Christina B. , Sneed Sydney E. , Dubrof Stephanie , Duberstein Kylee J. , Callaway Todd R. , West Franklin D. , Park Hea Jin
Published: August 2022

Dynamic changes in the oral microbiome have gained attention due to their potential diagnostic role in neurological diseases such as Alzheimer’s disease and Parkinson’s disease. Traumatic brain injury (TBI) is a leading cause of death and disability in the United States, but no studies have examined the changes in oral microbiome during the acute stage of TBI using a clinically translational pig model. Crossbred piglets (4–5 weeks old, male) underwent either a controlled cortical impact (TBI, n = 6) or sham surgery (sham, n = 6). The oral microbiome parameters were quantified from the upper and lower gingiva, both buccal mucosa, and floor of the mouth pre-surgery and 1, 3, and 7 days post-surgery (PS) using the 16S rRNA gene. Faith’s phylogenetic diversity was significantly lower in the TBI piglets at 7 days PS compared to those of sham, and beta diversity at 1, 3, and 7 days PS was significantly different between TBI and sham piglets. However, no significant changes in the taxonomic composition of the oral microbiome were observed following TBI compared to sham. Further studies are needed to investigate the potential diagnostic role of the oral microbiome during the chronic stage of TBI with a larger number of subjects.
Re-Examining Labels in Neurocognitive Research: Evidence from Bilingualism and Autism as Spectrum-Trait Cases
Authors: Andreou Maria , Skrimpa Vasileia
Published: August 2022

Despite the fact that the urge to investigate bilingualism and neurodevelopmental disorders as continuous indices rather than categorical ones has been well-voiced among researchers with respect to research methodological approaches, in the recent literature, when it comes to examining language, cognitive skills and neurodivergent characteristics, it is still the case that the most prevalent view is the categorisation of adults or children into groups. In other words, there is a categorisation of individuals, e.g., monolingual vs. bilingual children or children with typical and atypical/non-typical/non-neurotypical development. We believe that this labelling is responsible for the conflicting results that we often come across in studies. The aim of this review is to bring to the surface the importance of individual differences through the study of relevant articles conducted in bilingual children and children with autism, who are ideal for this study. We concur with researchers who already do so, and we further suggest moving away from labels and instead shift towards the view that not everything is either white or black. We provide suggestions as to how this shift could be implemented in research, while mostly aiming at starting a discourse rather than offering a definite path.
Platform Development of BIM-Based Fire Safety Management System Considering the Construction Site
Authors: Yang Yapin , Sun Ying , Chen Mingsi , Zhou Yuekuan , Wang Ran , Liu Zhengxuan
Published: August 2022

Fire at a construction site usually results in serious accidents. Therefore, fire management at the construction site is critical to decreasing possible accidents. However, conventional fire safety management can be problematic in many aspects, such as visualization, multi-stage alarm systems, and dynamic escape route optimization. To solve these issues, this paper develops a platform for a BIM-based fire safety management system that considers the construction site. The developed platform contains four subsystems: a remote monitoring subsystem, a fire visualization subsystem, a multi-stage fire alarm subsystem, and an escape route optimization subsystem. It detects the fire hazard in the early stage of the fire by the remote monitoring subsystem and transmits this information to the fire visualization subsystem for displaying. Furthermore, the multi-stage fire alarm subsystem sends warnings or alarms based on the fire’s severity. Moreover, the escape route optimization subsystem dynamically optimizes the evacuation routes by considering the actual number of people at the construction site and the potential crowding as people pass through the escapeway. Results show that this system can provide informative and on-time fire protection measures to different participants at the construction site. This study can also serve as a solution to improve fire safety management at the construction site.
An Air Conditioning Design Strategy of the Stepped Hall Based on Building Performance Simulation
Authors: Chen Ruijun , Liu Yu-Tung , Tsay Yaw-Shyan
Published: August 2022

This study proposed an improved air conditioning design strategy based on building performance simulation for a stepped hall. The air velocity and air change rate of the case were measured on-site, which were compared with the simulation data to verify the reliability of the building simulation model. Then, the fully mixing ventilation scheme and the design schemes proposed in this study were simulated. Finally, the building simulation results were summarized to confirm the applicability of the air conditioning design strategy. The building performance results showed that the air distribution performance index (ADPI) value was 76.95% in the original case. Nevertheless, the effective draft temperature (EDT) in the middle seat area exceeded the standard value, indicating that a local cold shock would occur. Moreover, its scale for ventilation efficiency (SVE6) in the residential area was 2.54. However, the SVE6s in the other schemes were between 0.89 and 0.92. It means that the proposed schemes only needed to take one-third of the time to exhaust air. These three indicators’ visualization results can analyze the advantages and disadvantages of each scheme. Therefore, the improved building performance simulation strategy could inspect the design effect and give suggestions quickly for air conditioning design.
Evaluating Life-Cycle Energy Costs of Heritage Buildings
Authors: Al-Sakkaf Abobakr , Bagchi Ashutosh , Zayed Tarek
Published: August 2022

After the sustainability of heritage buildings (HBs) has been evaluated and it is determined that rehabilitation is needed, then the life-cycle cost (LCC) of energy for HBs can be analyzed. The objective of this research was to evaluate the LCC of energy for HBs and develop a comprehensive life-cycle model that will aid in expenditure planning and budget allocation. This study was validated through the weighted sums method and two case studies—Murabba Palace (MP), Saudi Arabia; and Grey Nuns Building (GN), Canada—were evaluated. For any HB, the project life cycle includes planning, manufacturing, transportation, construction, operation, and maintenance phases. Saudi Arabian and Canadian experts completed questionnaires to attribute a percentage of importance of each of the aforementioned phases with respect to energy consumption. The findings from this study will enable facility managers to make effective rehabilitation decisions. The operation phase has the highest impact on the energy consumption, gas consumption, and cost of the building in both case studies. Moreover, the findings from this study can be used to establish cost-effective intervention strategies. Their responses were employed in the development of a life-cycle model. Excel® and Minitab® were used to calculate Cronbach’s alpha values for data reliability, and the project LCC of energy for the two case studies was studied. The operation phase appeared to be the most energy-consuming phase in both case studies, contributing the most to the cost of the building.
Bearing Capacity of UHPC-Filled High-Strength Elliptical Steel Tube Composite Columns with Encased High-Strength H-Shape Steel Subjected to Eccentrical Load
Authors: Ji Jing , Wang Weichen , Jiang Liangqin , Ren Hongguo , Wang Qingqin , Xuan Wenyu , Liu Yingchun
Published: August 2022

In order to investigate the bearing capacity of composite columns composed of ultra-high performance concrete, (UHPC)-filled high-strength elliptical steel tube with encased high-strength H-shape steel (HUCFESTCs) were subjected to eccentric load. Forty-four HUCFESTCs were designed with varying parameters: yield strength of the steel tube (fy), yield strength of the H-shape steel (fy1), concrete-cube compressive strength (fcu), steel tube thickness (t), eccentricity (e), slenderness ratio (λ), the section area of the H-shape steel (AHS), and long–short axis ratio (ψ). Based on a bilinear elastic–plastic constitutive model of steel that considered stress hardening and a nonlinear constitutive model of UHPC, 44 HUCFESTCs models were established by ABAQUS software. The influence of different parameters on the ultimate bearing capacity of the HUCFESTCs was analyzed. The whole process of HUCFESTCs under eccentric load was studied, and the typical failure modes of HUCFESTCs are described. The results show that the main failure mode of the HUCFESTCs subjected to eccentrical load is bulging outward of the steel tube, the buckling of the H-shape steel, and crushing of the concrete in the middle part of the column and the inner part of the H-shape steel. The stiffness of HUCFESTCs increases gradually with the increase in fy, t, and e. The ultimate eccentrical compression bearing capacity of HUCFESTCs improves gradually with increases in fy, t, fy1, AHS, ψ, and fcu, but it decreases gradually with increases in λ and e. By using statistical regression and introducing the reduction coefficient of eccentricity, the calculation formula for the eccentric bearing capacity of HUCFEST columns is developed, which can provide a basis for the application of HUCFESTCs in practical engineering.
Impact of a Warming Climate on Hospital Energy Use and Decarbonization: An Australian Building Simulation Study
Authors: Ma Yunlong , Zedan Sherif , Liu Aaron , Miller Wendy
Published: August 2022

The high energy use of hospitals and healthcare facilities globally contributes to greenhouse gas emissions. At the same time, a large percentage of this energy use is attributed to space heating, cooling and ventilation, and is hence correlated to the climate. While the energy performance of Australian hospitals at the design stage is evaluated using historical weather data, the impact of the warming climate on Australian hospitals into the future remains unknown. The research question addressed is: What is the impact of future climates on the energy use of Australian hospitals built with the current design conditions? Two archetype hospital models were developed (a small single-story healthcare facility and a large multi-story hospital). DesignBuilder was used to simulate the performance of these models in 10 locations, ranging from the tropics to cool temperate regions in Australia. Current (1990–2015) and future climate files (2030, 2050, 2070 and 2090) were used. The results show that with the warming climate, the heating demand decreased, while the cooling demand increased for both hospital models for all sites. Cooling dominated climates, such as Darwin and Brisbane, were significantly impacted by the changing climates due to a substantial increase in cooling energy use. Heating based climates, such as Hobart and Canberra, resulted in an overall small reduction in total building energy use. In addition, the single-story facility was more impacted by the change in climate (in terms of energy use intensity) than the multi-story facility. The study highlights the importance of future climate files in building simulation and decarbonization planning.
International Survey of the Usage of Whole Building Life Cycle Assessment Software
Authors: Sartori Thais , Drogemuller Robin , Omrani Sara , Lamari Fiona
Published: August 2022

The pressure to reduce the environmental impacts of buildings over their lifetime has driven certification bodies and the government to require a Life Cycle Assessment (LCA). However, LCA is a data-intensive and time-consuming process which complicates design activities, especially when performing a Whole Building LCA (WBLCA). Software tools can simplify the assessment by providing information more aligned with the users’ needs. This research surveyed 178 building designers who utilise WBLCA software as a decision-making tool. The aim was to identify patterns in the usage of the software and provide guidance to WBLCA software developers. For this purpose, statistical analyses identified the software preferences within each group of users, e.g., the users’ geographical location, professional background and years of WBLCA experience, among others. The results identified challenges faced by the construction industry, such as the need for more efficient communication among stakeholders. Therefore, attributes that allow designers to share information were rated as the most valuable. Two main groups of users were identified, and guidelines were drawn based on the profiles of the groups. Improving software support to designers will enable WBLCA to be integrated more efficiently with BPP by improving the users’ experience and their ability to make more informed decisions.
Long-Term Settlement Prediction of Ground Reinforcement Foundation Using a Deep Cement Mixing Method in Reclaimed Land
Authors: Lee Haksung , Kim Seok-Jae , Kang Bang-Hun , Lee Kwang-Seung
Published: August 2022

The greenhouse foundation method requires a lower allowable bearing capacity compared to general buildings, but the high-spec and expensive prestressed high-strength concrete (PHC) pile reinforcement method is mainly applied. Therefore, the deep cement mixing (DCM) method, which is one of the ground reinforcement foundations that replaces the PHC piles and secures structural safety suitable for the greenhouse foundation, was considered. To verify the structural safety of the DCM method, a geotechnical survey and soil test were conducted, and a long-term settlement monitoring system was established. The specifications of the DCM foundation were designed to be 0.8 m in diameter, 3 m × 3 m in width and length, and 3 m in depth. Based on the settlement monitoring data, long-term settlement was predicted considering the greenhouse durability of 15 years. For long-term settlement prediction, the Log S–T, hyperbolic, Asaoka method, Schmertmann theory, and the finite element method (FEM) analysis were performed. In the case of the Log S–T, hyperbolic, and Asaoka method based on actual measurement data, the settlement amount was predicted to be 12.18~20.43 mm, and in the case of the Schmertmann empirical formula, it was predicted to be 19.66 m. The FEM analysis result was 8.89 mm. As the most conservative result, the DCM foundation method designed in this paper had an allowable bearing capacity of 310 kN/m2 and a long-term settlement of 20.43 mm. This is the result of satisfying both the allowable bearing capacity of 100 kN/m2 and the allowable settlement range of 25.4 mm as a foundation. Through this study, it was proven that long-term structural safety can be sufficiently secured when the DCM foundation is constructed on a soft ground through a design that considers the required service life and allowable bearing capacity of the structure. In addition, it was confirmed that the Hyperbolic, Asaoka, and FEM analysis method adopted in this paper can be applied to the long-term settlement behavior analysis of the DCM foundation method.
An Evolutionary Neuro-Fuzzy-Based Approach to Estimate the Compressive Strength of Eco-Friendly Concrete Containing Recycled Construction Wastes
Authors: Ashrafian Ali , Hamzehkolaei Naser Safaeian , Dwijendra Ngakan Ketut Acwin , Yazdani Maziar
Published: August 2022

There has been a significant increase in construction and demolition (C&D) waste due to the growth of cities and the need for new construction, raising concerns about the impact on the environment of these wastes. By utilising recycled C&D waste, especially in concretes used in construction, further environmental damage can be prevented. By using these concretes, energy consumption and environmental impacts of concrete production can be reduced. The behaviour of these types of concrete in laboratories has been extensively studied, but reliable methods for estimating their behaviour based on the available data are required. Consequently, this research proposes a hybrid intelligent system, Fuzzy Group Method of Data Handling (GMDH)–Horse herd Optimisation Algorithm (HOA), for predicting one of the most important parameters in concrete structure design, compressive strength. In order to avoid uncertainty in the modelling process, crisp input values were converted to Fuzzy values (Fuzzification). Next, using Fuzzy input variables, the group method of data handling is used to predict the compressive strength of recycled aggregate concrete. The HOA algorithm is one of the newest metaheuristic algorithms being used to optimise the Fuzzy GMDH structure. Several databases containing experimental mix design records containing mixture components are gathered from published documents for compressive strength to assess the accuracy and reliability of the proposed hybrid Fuzzy-based model. Compared to other original approaches, the proposed Fuzzy GMDH model with the HOA optimiser outperformed them in terms of accuracy. A Monte Carlo simulation is also employed for uncertainty analysis of the empirical, standalone, and hybridised models in order to demonstrate that the evolutionary Fuzzy-based approach has less uncertainty than the standalone methods when simulating compressive strength.
Building Energy Prediction Models and Related Uncertainties: A Review
Authors: Yu Jiaqi , Chang Wen-Shao , Dong Yu
Published: August 2022

Building energy usage has been an important issue in recent decades, and energy prediction models are important tools for analysing this problem. This study provides a comprehensive review of building energy prediction models and uncertainties in the models. First, this paper introduces three types of prediction methods: white-box models, black-box models, and grey-box models. The principles, strengths, shortcomings, and applications of every model are discussed systematically. Second, this paper analyses prediction model uncertainties in terms of human, building, and weather factors. Finally, the research gaps in predicting building energy consumption are summarised in order to guide the optimisation of building energy prediction methods.
Detection and Yield of Colorectal Cancer Surveillance in Adults with PTEN Hamartoma Tumour Syndrome
Authors: Drissen Meggie M. C. M. , Vos Janet R. , van der Biessen-van Beek Dorien T. J. , van der Post Rachel S. , Nagtegaal Iris D. , van Kouwen Mariëtte C. A. , Bisseling Tanya M. , Hoogerbrugge Nicoline
Published: August 2022

Colorectal cancer surveillance (CCS) with colonoscopy every five years is advised for PTEN Hamartoma Tumour Syndrome (PHTS) patients aged ≥40 due to an increased colorectal cancer (CRC) risk. However, data to support CCS guidelines are scarce and available CRC risks are low (0–5% at age 50) and likely overestimated. We aimed to assess the detection and yield of CCS for PHTS patients without a CRC history. A retrospective cohort study including PHTS patients aged ≥40 with CCS at a PHTS expertise centre between 2011 and 2022. Adenomas with a ≥10 mm size, (tubulo)villous histology, or high-grade dysplasia were considered advanced. During 67 follow-up years, 37 patients (median age 47 years) underwent 61 colonoscopies. CCS yielded no CRCs. Adenomas were diagnosed in 13/37 (35%) patients during 23/100 colonoscopies (95% CI: 14–36), including one advanced adenoma. Baseline adenoma detection rates were similar to follow-up and higher in patients aged above 50 (50/100, 95% CI: 24–76) vs. age 50 or below (11/100, 95% CI: 3–30; p = 0.021). The low CRC and advanced adenoma yield allow for a more personalised surveillance program. Following our findings combined with literature on CRC risk and progression, we suggest starting CCS at age 40 with variable follow-up intervals between 1 and 10 years depending on previous colonoscopy findings.
Matched Paired Primary and Recurrent Meningiomas Points to Cell-Death Program Contributions to Genomic and Epigenomic Instability along Tumor Progression
Authors: San-Miguel Teresa , Megías Javier , Monleón Daniel , Navarro Lara , Muñoz-Hidalgo Lisandra , Montoliu Carmina , Meri Marina , Roldán Pedro , Cerdá-Nicolás Miguel , López-Ginés Concha
Published: August 2022

Meningioma (MN) is an important cause of disability, and predictive tools for estimating the risk of recurrence are still scarce. The need for objective and cost-effective techniques addressed to this purpose is well known. In this study, we present methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) as a friendly method for deepening the understanding of the mechanisms underlying meningioma progression. A large follow-up allowed us to obtain 50 samples, which included the primary tumor of 20 patients in which half of them are suffering one recurrence and the other half are suffering more than one. We histologically characterized the samples and performed MS-MLPA assays validated by FISH to assess their copy number alterations (CNA) and epigenetic status. Interestingly, we determined the increase in tumor instability with higher values of CNA during the progression accompanied by an increase in epigenetic damage. We also found a loss of HIC1 and the hypermethylation of CDKN2B and PTEN as independent prognostic markers. Comparison between grade 1 and higher primary MN’s self-evolution pointed to a central role of GSTP1 in the first stages of the disease. Finally, a high rate of alterations in genes that are related to apoptosis and autophagy, such as DAPK1, PARK2, BCL2, FHIT, or VHL, underlines an important influence on cell-death programs through different pathways.