bluuebunny/crossref_metadata_2025 huggingface dataset:
Whole Genome Expression Profiling of Semitendinosus Tendons from Children with Diplegic and Tetraplegic Cerebral Palsy
Authors: Nemska Simona , Serio Simone , Larcher Veronica , Beltrame Giulia , Portinaro Nicola Marcello , Bang Marie-Louise
Published: October 2023

Cerebral palsy (CP) is the most common movement disorder in children, with a prevalence ranging from 1.5 to 4 per 1000 live births. CP is caused by a non-progressive lesion of the developing brain, leading to progressive alterations of the musculoskeletal system, including spasticity, often leading to the development of fixed contractures, necessitating tendon lengthening surgery. Total RNA-sequencing analysis was performed on semitendinosus tendons from diplegic and tetraplegic CP patients subjected to tendon lengthening surgery compared to control patients undergoing anterior cruciate ligament reconstructive surgery. Tetraplegic CP patients showed increased expression of genes implicated in collagen synthesis and extracellular matrix (ECM) turnover, while only minor changes were observed in diplegic CP patients. In addition, tendons from tetraplegic CP patients showed an enrichment for upregulated genes involved in vesicle-mediated transport and downregulated genes involved in cytokine and apoptotic signaling. Overall, our results indicate increased ECM turnover with increased net synthesis of collagen in tetraplegic CP patients without activation of inflammatory and apoptotic pathways, similar to observations in athletes where ECM remodeling results in increased tendon stiffness and tensile strength. Nevertheless, the resulting increased tendon stiffness is an important issue in clinical practice, where surgery is often required to restore joint mobility.
Type VI Secretion System Accessory Protein TagAB-5 Promotes Burkholderia pseudomallei Pathogenicity in Human Microglia
Authors: Lohitthai Sanisa , Rungruengkitkun Amporn , Jitprasutwit Niramol , Kong-Ngoen Thida , Duangurai Taksaon , Tandhavanant Sarunporn , Sukphopetch Passanesh , Chantratita Narisara , Indrawattana Nitaya , Pumirat Pornpan
Published: October 2023

Central nervous system (CNS) melioidosis caused by Burkholderia pseudomallei is being increasingly reported. Because of the high mortality associated with CNS melioidosis, understanding the underlying mechanism of B. pseudomallei pathogenesis in the CNS needs to be intensively investigated to develop better therapeutic strategies against this deadly disease. The type VI secretion system (T6SS) is a multiprotein machine that uses a spring-like mechanism to inject effectors into target cells to benefit the infection process. In this study, the role of the T6SS accessory protein TagAB-5 in B. pseudomallei pathogenicity was examined using the human microglial cell line HCM3, a unique resident immune cell of the CNS acting as a primary mediator of inflammation. We constructed B. pseudomallei tagAB-5 mutant and complementary strains by the markerless allele replacement method. The effects of tagAB-5 deletion on the pathogenicity of B. pseudomallei were studied by bacterial infection assays of HCM3 cells. Compared with the wild type, the tagAB-5 mutant exhibited defective pathogenic abilities in intracellular replication, multinucleated giant cell formation, and induction of cell damage. Additionally, infection by the tagAB-5 mutant elicited a decreased production of interleukin 8 (IL-8) in HCM3, suggesting that efficient pathogenicity of B. pseudomallei is required for IL-8 production in microglia. However, no significant differences in virulence in the Galleria mellonella model were observed between the tagAB-5 mutant and the wild type. Taken together, this study indicated that microglia might be an important intracellular niche for B. pseudomallei, particularly in CNS infection, and TagAB-5 confers B. pseudomallei pathogenicity in these cells.
Atheroprotective Effect of Fucoidan in THP-1 Macrophages by Potential Upregulation of ABCA1
Authors: Mirza Zeenat , Al-Saedi Dalal A. , Saddeek Salma , Almowallad Sanaa , AlMassabi Rehab F. , Huwait Etimad
Published: October 2023

Targeting foam cells reduces the risk and pathophysiology of atherosclerosis, of which they are one of its early hallmarks. The precise mechanism of action of fucoidan, a potential anti-atherogenic drug, is still unknown. Our objective was to assess the ability of fucoidan to regulate expression of ATP-binding cassette transporter A1 (ABCA1) in ox-LDL-induced THP-1 macrophages. Molecular docking was used to predict how fucoidan interacts with anti-foam cell markers, and further in vitro experiments were performed to evaluate the protective effect of fucoidan on modulating uptake and efflux of lipids. THP-1 macrophages were protected by 50 µg/mL of fucoidan and were then induced to form foam cells with 25 µg/mL of ox-LDL. Expression levels were assessed using RT-qPCR, and an Oil Red O stain was used to observe lipid accumulation in THP-1 macrophages. In addition, ABCA1 protein was examined by Western blot, and cellular cholesterol efflux was determined using fluorescently labeled cholesterol. Under a light microscope, decreased lipid accumulation in ox-LDL-induced-THP-1 macrophages pre-treated with fucoidan showed a significant effect, although it did not affect the expression of scavenger receptors (SR-AI and CD36). It is interesting to note that fucoidan dramatically increased the gene and protein expression of ABCA1, perhaps via the liver X receptor-α (LXR-α). Moreover, fucoidan’s ability to increase and control the efflux of cholesterol from ox-LDL-induced THP-1 macrophages revealed how it may alter ABCA1’s conformation and have a major effect on how it interacts with apolipoprotein A (ApoA1). In vitro results support a rationale for predicting fucoidan and its interaction with its receptor targets’ predicted data, hence validating its anti-atherogenic properties and suggesting that fucoidan could be promising as an atheroprotective.
Fecal Microbiota Transplantation in Liver Cirrhosis
Authors: Boicean Adrian , Birlutiu Victoria , Ichim Cristian , Brusnic Olga , Onișor Danusia Maria
Published: October 2023

The human gastrointestinal tract houses a diverse array of probiotic and pathogenic bacteria and any alterations in this microbial composition can exert a significant influence on an individual’s well-being. It is well-established that imbalances in the gut microbiota play a pivotal role in the development of liver diseases. In light of this, a new adjuvant therapy for liver diseases could be regulating the intestinal microbiota. Through fecal microbiota transplantation, patients whose microbiomes are compromised are treated with stool from healthy donors in an attempt to restore a normal microbiome and alleviate their symptoms. A review of cross-sectional studies and case reports suggests that fecal microbiota transplants may offer effective treatment for chronic liver diseases. Adding to the potential of this emerging therapy, recent research has indicated that fecal microbiota transplantation holds promise as a therapeutic approach specifically for liver cirrhosis. By introducing a diverse range of beneficial microorganisms into the gut, this innovative treatment aims to address the microbial imbalances often observed in cirrhotic patients. While further validation is still required, these preliminary findings highlight the potential impact of fecal microbiota transplantation as a novel and targeted method for managing liver cirrhosis. We aimed to summarize the current state of understanding regarding this procedure, as a new therapeutic method for liver cirrhosis, as well as to explain its clinical application and future potential.
The Association between Metformin Use and Risk of Developing Severe Dementia among AD Patients with Type 2 Diabetes
Authors: Xue Ying , Xie Xiangqun
Published: October 2023

This study explores the potential impact of metformin on the development of severe dementia in individuals with Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM). With an emerging interest in the role of the APOE genotype in mediating metformin’s effects on cognitive decline in AD patients, we sought to investigate whether metformin usage is associated with a reduced risk of severe dementia. Using data from the National Alzheimer’s Coordinating Center (NACC) database (2005–2021), we identified 1306 participants with both AD and T2DM on diabetes medications. These individuals were categorized based on metformin usage, and a propensity score-matched cohort of 1042 participants was analyzed. Over an average follow-up of 3.6 years, 93 cases of severe dementia were observed. A Kaplan–Meier analysis revealed that metformin users and non-users had similar probabilities of remaining severe dementia-free (log-rank p = 0.56). Cox proportional hazards models adjusted for covariates showed no significant association between metformin usage and a lower risk of severe dementia (HR, 0.96; 95% CI, 0.63–1.46; p = 0.85). A subgroup analysis based on APOE ε4 carrier status demonstrated consistent results, with metformin use not correlating with a reduced severe dementia risk. In conclusion, our findings from a substantial cohort of AD and T2DM patients suggest that metformin usage is not significantly associated with a decreased risk of severe dementia. This observation persists across APOE ε4 carriers and non-carriers, indicating a lack of genotype-mediated effect.
Synergistic Antimicrobial Effects of Ibuprofen Combined with Standard-of-Care Antibiotics against Cystic Fibrosis Pathogens
Authors: Chen Qingquan , Ilanga Marleini , Simbassa Sabona B. , Chirra Bhagath , Shah Kush N. , Cannon Carolyn L.
Published: October 2023

Cystic fibrosis (CF) is a common life-shortening genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Lungs of CF patients are often colonized or infected with microorganisms requiring frequent courses of antibiotics. Antibiotic-resistant bacterial infections have been a growing concern in CF patients. Chronic bacterial infections and concomitant airway inflammation damage the lungs, ultimately leading to respiratory failure. Several clinical trials have demonstrated that high-dose ibuprofen reduces the rate of pulmonary function decline in CF patients. This beneficial effect has been attributed to the anti-inflammatory properties of ibuprofen. Previously, we have confirmed that high-dose ibuprofen demonstrates antimicrobial activity against P. aeruginosa both in vitro and in vivo. However, no study has examined the antimicrobial effect of combining ibuprofen with standard-of-care antimicrobials. Here, we evaluated the possible synergistic activity of combinations of common nonsteroidal anti-inflammatory drugs (NSAIDs), namely, ibuprofen, naproxen, and aspirin, with commonly used antibiotics for CF patients. The drug combinations were screened against different CF clinical isolates. Antibiotics that demonstrated increased efficacy in the presence of ibuprofen were further tested for potential synergistic effects between these NSAIDS and antimicrobials. Finally, a survival analysis of a P. aeruginosa murine infection model was used to demonstrate the efficacy of the most potent combination identified in in vitro screening. Our results suggest that combinations of ibuprofen with commonly used antibiotics demonstrate synergistic antimicrobial activity against drug-resistant, clinical bacterial strains in vitro. The efficacy of the combination of ceftazidime and ibuprofen against resistant P. aeruginosa was demonstrated in an in vivo pneumonia model.
Effective Invasiveness Recognition of Imbalanced Data by Semi-Automated Segmentations of Lung Nodules
Authors: Tung Yu-Cheng , Su Ja-Hwung , Liao Yi-Wen , Lee Yeong-Chyi , Chen Bo-An , Huang Hong-Ming , Jhang Jia-Jhan , Hsieh Hsin-Yi , Tong Yu-Shun , Cheng Yu-Fan , Lai Chien-Hao , Chang Wan-Ching
Published: October 2023

Over the past few decades, recognition of early lung cancers was researched for effective treatments. In early lung cancers, the invasiveness is an important factor for expected survival rates. Hence, how to effectively identify the invasiveness by computed tomography (CT) images became a hot topic in the field of biomedical science. Although a number of previous works were shown to be effective on this topic, there remain some problems unsettled still. First, it needs a large amount of marked data for a better prediction, but the manual cost is high. Second, the accuracy is always limited in imbalance data. To alleviate these problems, in this paper, we propose an effective CT invasiveness recognizer by semi-automated segmentation. In terms of semi-automated segmentation, it is easy for doctors to mark the nodules. Just based on one clicked pixel, a nodule object in a CT image can be marked by fusing two proposed segmentation methods, including thresholding-based morphology and deep learning-based mask region-based convolutional neural network (Mask-RCNN). For thresholding-based morphology, an initial segmentation is derived by adaptive pixel connections. Then, a mathematical morphology is performed to achieve a better segmentation. For deep learning-based mask-RCNN, the anchor is fixed by the clicked pixel to reduce the computational complexity. To incorporate advantages of both, the segmentation is switched between these two sub-methods. After segmenting the nodules, a boosting ensemble classification model with feature selection is executed to identify the invasiveness by equalized down-sampling. The extensive experimental results on a real dataset reveal that the proposed segmentation method performs better than the traditional segmentation ones, which can reach an average dice improvement of 392.3%. Additionally, the proposed ensemble classification model infers better performances than the compared method, which can reach an area under curve (AUC) improvement of 5.3% and a specificity improvement of 14.3%. Moreover, in comparison with the models with imbalance data, the improvements of AUC and specificity can reach 10.4% and 33.3%, respectively.
Textile Types, Number of Layers and Wrapping Types Effect on Shear Strengthening of Reinforced Concrete Beams with Textile-Reinforced Mortar versus Carbon-Fiber-Reinforced Polymer
Authors: Yılmaz Mahmut Cem
Published: October 2023

In the scope of this study, the strengthening of reinforced concrete beams against to shear with different types of composite materials was investigated experimentally. A total of seventeen reinforced concrete beams, one with high shear strength and sixteen with low shear strength, were fabricated. The beam with high shear strength and one of the beams with low shear strength were chosen as reference beams. The remaining fifteen beam specimens were strengthened with textile-reinforced mortar (TRM) and carbon-fiber-reinforced polymer (CFRP). While light and heavy carbon mesh were used for strengthening with TRM, unidirectional carbon textile was used for strengthening with CFRP. Other experimental parameters were the spacing of strips, the number of layers (one or two) and the way of wrapping (strip or full). Simply supported beam specimens were tested under three-point loading. Beam specimens were compared in terms of failure mode, ultimate load capacity, ductility index and energy dissipation capacity.
Prognostic Markers within the Tumour Microenvironment in Classical Hodgkin Lymphoma
Authors: Martynchyk Arina , Chowdhury Rakin , Hawkes Eliza A. , Keane Colm
Published: October 2023

Classical Hodgkin lymphoma (cHL) accounts for 0.4% of all new cancer cases globally. Despite high cure rates with standard treatment, approximately 15% of patients still experience relapsed or refractory (RR) disease, and many of these eventually die from lymphoma-related causes. Exciting new targeted agents such as anti-PD-1 agents and brentuximab vedotin have changed the therapeutic paradigm beyond chemotherapy and radiotherapy alone. Advances in understanding of the molecular biology are providing insights in the context of novel therapies. The signature histology of cHL requires the presence of scant malignant Hodgkin Reed–Sternberg cells (HRSCs) surrounded by a complex immune-rich tumour microenvironment (TME). The TME cellular composition strongly influences outcomes, yet knowledge of the precise characteristics of TME cells and their interactions with HRSCs is evolving. Novel high-throughput technologies and single-cell sequencing allow deeper analyses of the TME and mechanisms elicited by HRSCs to propagate growth and avoid immune response. In this review, we explore the evolution of knowledge on the prognostic role of immune cells within the TME and provide an up-to-date overview of emerging prognostic data on cHL from new technologies that are starting to unwind the complexity of the cHL TME and provide translational insights into how to improve therapy in the clinic.
Engineering of GH11 Xylanases for Optimal pH Shifting for Industrial Applications
Authors: Kim In Jung , Kim Soo Rin , Bornscheuer Uwe T. , Nam Ki Hyun
Published: October 2023

Endo-1,4-β-xylanases belonging to the glycoside hydrolase (GH) 11 family hydrolyze the β-1,4-glycosidic linkages in the xylan backbone to convert polymeric xylan into xylooligosaccharides. GH11 xylanases play an essential role in sugar metabolism and are one of the most widely used enzymes in various industries, such as pulp and paper, food and feed, biorefinery, textile, and pharmaceutical industries. pH is a crucial factor influencing the biochemical properties of GH11 xylanase and its application in bioprocessing. For the optimal pH shifting of GH11 xylanase in industrial applications, various protein engineering studies using directed evolution, rational engineering, and in silico approaches have been adopted. Here, we review the functions, structures, and engineering methods developed for the optimal pH shifting of GH11 xylanases. The various GH11 engineering techniques and key residues involved in pH shifting are discussed based on their crystal and modeled structure. This review provides an overview of recent advancements in the characterization and engineering of GH11 xylanases, providing a guide for future research in this field.
Structure-Sensitive Behavior of Supported Vanadia-Based Catalysts for Combustion of Soot
Authors: Rzadki Tomasz , Legutko Piotr , Adamski Andrzej , Kotarba Andrzej , Trawczyński Janusz
Published: October 2023

Catalytic performance of 3 and 5 wt.% of vanadia, supported on zirconia, zirconia-ceria, and zirconia-yttria, tested in the combustion of soot without and in the presence of NO was described. The catalysts were characterized by structural (XRD, RS) and functional (EPR, TPR) methods. The effect of composition on the catalytic performance of the investigated systems in soot combustion was discussed in detail. Zirconia-supported vanadia was found to be the most active catalyst for soot oxidation characterized by the lowest combustion temperature (~375 °C) attributed to the maximal signal of conversion to the detected products. The relationship between the reducibility of surface oxovanadium species and their catalytic activity was established, revealing the involvement of the lattice oxygen in the combustion process. The importance of thermal treatment conditions and the nature of zirconia-based support determining the stability of specific oxovanadium entities on the catalyst surface was emphasized.
The Post-Translational Role of UFMylation in Physiology and Disease
Authors: Wang Xingde , Xu Xingzhi , Wang Zhifeng
Published: October 2023

Ubiquitin-fold modifier 1 (UFM1) is a newly identified ubiquitin-like protein that has been conserved during the evolution of multicellular organisms. In a similar manner to ubiquitin, UFM1 can become covalently linked to the lysine residue of a substrate via a dedicated enzymatic cascade. Although a limited number of substrates have been identified so far, UFM1 modification (UFMylation) has been demonstrated to play a vital role in a variety of cellular activities, including mammalian development, ribosome biogenesis, the DNA damage response, endoplasmic reticulum stress responses, immune responses, and tumorigenesis. In this review, we summarize what is known about the UFM1 enzymatic cascade and its biological functions, and discuss its recently identified substrates. We also explore the pathological role of UFMylation in human disease and the corresponding potential therapeutic targets and strategies.
Noninvasive Monitoring Strategies for Bronchopulmonary Dysplasia or Post-Prematurity Respiratory Disease: Current Challenges and Future Prospects
Authors: Zini Tommaso , Miselli Francesca , Berardi Alberto
Published: October 2023

Definitions of bronchopulmonary dysplasia (BPD) or post-prematurity respiratory disease (PPRD) aim to stratify the risk of mortality and morbidity, with an emphasis on long-term respiratory outcomes. There is no univocal classification of BPD due to its complex multifactorial nature and the substantial heterogeneity of clinical presentation. Currently, there is no definitive treatment available for extremely premature very-low-birth-weight infants with BPD, and challenges in finding targeted preventive therapies persist. However, innovative stem cell-based postnatal therapies targeting BPD-free survival are emerging, which are likely to be offered in the first few days of life to high-risk premature infants. Hence, we need easy-to-use noninvasive tools for a standardized, precise, and reliable BPD assessment at a very early stage, to support clinical decision-making and to predict the response to treatment. In this non-systematic review, we present an overview of strategies for monitoring preterm infants with early and evolving BPD-PPRD, and we make some remarks on future prospects, with a focus on near-infrared spectroscopy (NIRS).
A School-Based Program for Problematic Internet Use for Adolescents in Japan
Authors: Otsuka Yuichiro , Kaneita Yoshitaka , Itani Osamu , Matsumoto Yuuki
Published: October 2023

Despite the serious influence of problematic Internet use on mental health among Japanese adolescents, no randomized clinical trials have investigated universal school-based interventions for this potential health challenge. Therefore, this study aimed to assess the efficacy of a school-based educational program. This two-armed, parallel, cluster-based randomized clinical trial included 5312 students from 13 high schools situated in a mid-sized Japanese city. The students in the intervention arm received 10 weekly standardized sessions, including a combination of information provision and interactive sessions by schoolteachers. The students in the control group followed a standard school curriculum. A generalized estimating equation model was applied to assess the primary (Korean Scale for Internet Addiction [K-scale] score) and secondary (behavioral change status according to changes in the transtheoretical model smartphone addiction score and Internet usage time) outcomes two months after intervention completion. The intention-to-treat analysis included 2597 (97.2%) and 2504 (94.9%) students in the intervention and control groups, respectively. Nevertheless, a significant discrepancy emerged regarding the behavioral change status. Therefore, this school-based program did not improve the Internet or smartphone addiction scores among Japanese adolescents. Further studies are needed to develop appropriate interventions for adolescents.
Intercultural Differences between Spain and Italy Regarding School Bullying, Gender, and Age
Authors: Ragusa Antonio , Obregón-Cuesta Ana Isabel , Di Petrillo Emma , Moscato Eduardo Maria , Fernández-Solana Jessica , Caggiano Valeria , González-Bernal Jerónimo J.
Published: October 2023

The objectives of this research were to establish the differences between Spain and Italy regarding the presence of bullying in primary and secondary schools, as well as to determine whether there are differences between experiencing or perpetrating bullying and gender and age in the practice of school bullying. To assess the EBIPQ scores in terms of country and gender, the chi-squared test was used, and ANOVA was applied for age. A total of 1536 students from primary and secondary schools in Spain and Italy participated in the study. Their ages ranged from 10 to 19 years (mean = 13.01, standard deviation = 2.19). The results revealed statistically significant differences in terms of bullying categories concerning the country of origin and gender, with a higher number of Italian participants in the role of “no victim aggress” and Spanish participants in the roles of “victim” and “victim and aggress”. Additionally, there were more boys in the role of “victim and aggress” and girls in the role of “no victim aggress”. Regarding age, statistically significant differences were found, with older students taking on the role of “aggress” on average, while younger students assumed the role of “victim”.
Autophagy Modulation and Its Implications on Glioblastoma Treatment
Authors: Chen Johnny , Rodriguez Andrea Salinas , Morales Maximiliano Arath , Fang Xiaoqian
Published: October 2023

Autophagy is a vital cellular process that functions to degrade and recycle damaged organelles into basic metabolites. This allows a cell to adapt to a diverse range of challenging conditions. Autophagy assists in maintaining homeostasis, and it is tightly regulated by the cell. The disruption of autophagy has been associated with many diseases, such as neurodegenerative disorders and cancer. This review will center its discussion on providing an in-depth analysis of the current molecular understanding of autophagy and its relevance to brain tumors. We will delve into the current literature regarding the role of autophagy in glioma pathogenesis by exploring the major pathways of JAK2/STAT3 and PI3K/AKT/mTOR and summarizing the current therapeutic interventions and strategies for glioma treatment. These treatments will be evaluated on their potential for autophagy induction and the challenges associated with their utilization. By understanding the mechanism of autophagy, clinical applications for future therapeutics in treating gliomas can be better targeted.
Altered Blood Molecular Markers of Cardiovascular Function in Rats after Intrauterine Hypoxia and Drug Therapy
Authors: Popazova Olena , Belenichev Igor , Yadlovskyi Oleh , Oksenych Valentyn , Kamyshnyi Aleksandr
Published: October 2023

Many children and adults who have suffered prenatal hypoxia at an early age develop many serious diseases. This disease is an actual problem of pediatric cardiology and little studied. The aim was to analyze the cardioprotective effect of L-arginine, Thiotriazoline, Angioline, and Mildronate on the cardiovascular system of rats after prenatal hypoxia. Methods: The experiments were carried out on 50 female white rats; intraperitoneal sodium nitrite solution was administered daily to pregnant female rats after 16 days at a dose of 50 mg/kg. Control pregnant rats received saline. The offspring were divided into groups: 1—intact; 2—the control group of rat pups after PH, treated daily with physiological saline; 3—six groups of rat pups after PH, treated daily from the 1st to the 30th day after birth. Heat shock protein HSP70 was determined by enzyme immunoassay, ST2 Nitrotyrosine, and eNOS was observed by ELISA. Results: Angiolin showed a high cardioprotective effect even a month after discontinuation of the drug, and after introduction, the highest decrease in ST2 nitrotyrosine was revealed. Thiotriazoline and L-arginine have an antioxidant effect and a positive effect on eNOS expression, increasing the concentration of HSP70. Mildronate increased the expression of eNOS and the concentration of HSP70 in the blood of experimental rats after a course of administration, but did not show an antioxidant effect and did not reduce the concentration of nitrotyrosine. The results obtained indicate the cardioprotective effect of modulators of the NO system with different mechanisms of action of drugs after prenatal hypoxia.
Evaluation of Subseasonal Precipitation Simulations for the Sao Francisco River Basin, Brazil
Authors: Ferreira Nicole C. R. , Chou Sin C. , Dereczynski Claudine
Published: October 2023

Water conflicts have been a significant issue in Brazil, especially in the Sao Francisco River basin. Subseasonal forecasts, up to a 60-day forecast range, can provide information to support decision-makers in managing water resources in the river basin, especially before drought events. This report aims to evaluate 5-year mean subseasonal simulations generated by the Eta regional model for the period from 2011 to 2016 and assess the usefulness of this information to support decision-making in water resource conflicts in the Sao Francisco River basin. The capability of the Eta model to reproduce the drought events that occurred between the years 2011 and 2016 was compared against the Climate Prediction Center Morphing (CMORPH) precipitation data. Two sets of 60-day simulations were produced: one started in September (SO) and the other in January (JF) of each year. These months were chosen to evaluate the model’s capability to reproduce the onset and the middle of the rainy seasons in central Brazil, where the upper Sao Francisco River is located. The SO simulations reproduced the observed spatial distribution of precipitation but underestimated the amounts. Precipitation errors exhibited large variability across the subbasins. The JF simulations also reproduced the observed precipitation distribution but overestimated it in the upper and lower subbasins. The JF simulations better captured the interannual variability in precipitation. The 60-day simulations were discretized into six 10-day accumulations to assess the intramonthly variability. They showed that the simulations captured the onset of the rainy season and the small periods of rainy months that occurred in these severe drought years. This research is a critical step to indicate subbasins where the model simulation needs to be improved and provide initial information to support water allocation in the region.
Ninety-Nine Percent? Re-Examining the Consensus on the Anthropogenic Contribution to Climate Change
Authors: Dentelski David , Damari Ran , Marmor Yanir , Niv Avner , Roses Mor , Dubi Yonatan
Published: October 2023

Anthropogenic activity is considered a central driver of current climate change. A recent paper, studying the consensus regarding the hypothesis that the recent increase in global temperature is predominantly human-made via the emission of greenhouse gasses (see text for reference), argued that the scientific consensus in the peer-reviewed scientific literature pertaining to this hypothesis exceeds 99%. This conclusion was reached after the authors scanned the abstracts and titles of some 3000 papers and mapped them according to their (abstract) statements regarding the above hypothesis. Here, we point out some major flaws in the methodology, analysis, and conclusions of the study. Using the data provided in the study, we show that the 99% consensus, as defined by the authors, is actually an upper limit evaluation because of the large number of “neutral” papers which were counted as pro-consensus in the paper and probably does not reflect the true situation. We further analyze these results by evaluating how so-called “skeptic” papers fit the consensus and find that biases in the literature, which were not accounted for in the aforementioned study, may place the consensus on the low side. Finally, we show that the rating method used in the study suffers from a subjective bias which is reflected in large variations between ratings of the same paper by different raters. All these lead to the conclusion that the conclusions of the study does not follow from the data.
Modeling the Dynamic Effects of Human Mobility and Airborne Particulate Matter on the Spread of COVID-19
Authors: Patanarapeelert Klot , Chandumrong Rossanan , Patanarapeelert Nichaphat
Published: October 2023

Identifying the relationship between human mobility, air pollution, and communicable disease poses a challenge for impact evaluation and public health planning. Specifically, Coronavirus disease 2019 (COVID-19) and air pollution from fine particulates (PM2.5), by which human mobility is mediated in a public health emergency. To describe the interplay between human mobility and PM2.5 during the spread of COVID-19, we proposed a nonlinear model of the time-dependent transmission rate as a function of these factors. A compartmental epidemic model, together with daily confirmed case data in Bangkok, Thailand during 2020–2021, was used to estimate the intrinsic parameters that can determine the impact on the transmission dynamic of the two earlier outbreaks. The results suggested a positive association between mobility and transmission, but this was strongly dependent on the context and the temporal characteristics of the data. For the ascending phase of an epidemic, the estimated coefficient of mobility variable in the second wave was greater than in the first wave, but the value of the mobility component in the transmission rate was smaller. Due to the influence of the baseline value and PM2.5, the estimated basic reproduction number of the second wave was higher than that of the first wave, even though mobility had a greater influence. For the descending phase, the value of the mobility component in the second wave was greater, due to the negative value of the estimated mobility coefficient. Despite this scaling effect, the results suggest a negative association between PM2.5 and the transmission rates. Although this conclusion agrees with some previous studies, the true effect of PM2.5 remains inconclusive and requires further investigation.
Random Number Generators: Principles and Applications
Authors: Bikos Anastasios , Nastou Panagiotis E. , Petroudis Georgios , Stamatiou Yannis C.
Published: October 2023

In this paper, we present approaches to generating random numbers, along with potential applications. Rather than trying to provide extensive coverage of several techniques or algorithms that have appeared in the scientific literature, we focus on some representative approaches, presenting their workings and properties in detail. Our goal is to delineate their strengths and weaknesses, as well as their potential application domains, so that the reader can judge what would be the best approach for the application at hand, possibly a combination of the available approaches. For instance, a physical source of randomness can be used for the initial seed; then, suitable preprocessing can enhance its randomness; then, the output of preprocessing can feed different types of generators, e.g., a linear congruential generator, a cryptographically secure one and one based on the combination of one-way hash functions and shared key cryptoalgorithms in various modes of operation. Then, if desired, the outputs of the different generators can be combined, giving the final random sequence. Moreover, we present a set of practical randomness tests that can be applied to the outputs of random number generators in order to assess their randomness characteristics. In order to demonstrate the importance of unpredictable random sequences, we present an application of cryptographically secure generators in domains where unpredictability is one of the major requirements, i.e., eLotteries and cryptographic key generation.
Unveiling Therapeutic Targets for Esophageal Cancer: A Comprehensive Review
Authors: Acharya Rakesh , Mahapatra Ananya , Verma Henu Kumar , Bhaskar L. V. K. S.
Published: October 2023

Esophageal cancer is a highly aggressive and deadly disease, ranking as the sixth leading cause of cancer-related deaths worldwide. Despite advances in treatment, the prognosis remains poor. A multidisciplinary approach is crucial for achieving complete remission, with treatment options varying based on disease stage. Surgical intervention and endoscopic treatment are used for localized cancer, while systemic treatments like chemoradiotherapy and targeted drug therapy play a crucial role. Molecular markers such as HER2 and EGFR can be targeted with drugs like trastuzumab and cetuximab, and immunotherapy drugs like pembrolizumab and nivolumab show promise by targeting immune checkpoint proteins. Epigenetic modifications offer new avenues for targeted therapy. Treatment selection depends on factors like stage, tumor location, and patient health, with post-operative and rehabilitation care being essential. Early diagnosis, appropriate treatment, and supportive care are key to improving outcomes. Continued research is needed to develop effective targeted drugs with minimal side effects. This review serves as a valuable resource for clinicians and researchers dedicated to enhancing esophageal cancer treatment outcomes.
Mitigating Overheating Risks for Modern Flats in London Due to Climate Change
Authors: Jariwala Mansi , Taki Ahmad
Published: October 2023

With the increase in global temperatures, a significant threat of overheating has been reported due to more frequent and severe heatwaves in the UK housing stock. This research analyzes dwellings’ physical attributes through overheating assessments and their adaptation for modern flats in London in the current (2022) and anticipated (2050) weather. According to preliminary research, Southeast and London in England, mid-terraced, and flats (especially built post 2012), among other archetypes, were discovered to be the most susceptible to overheating in the UK. This study employed a case study of a 2015 modern flat located in a high-risk overheating zone in London to understand the building’s overheating exposure. A range of Dynamic Thermal Simulations (DTS) was conducted using EnergyPlus with reference to case studies in order to assess the performance of passive cooling mitigation strategies (PCMS) on peak summer days (15 July) as well as during the summer against CIBSE Guide A and ASHARE 55. Reduced window area and LoE triple glazing were identified as excellent mitigation prototypes, in which solar gains through exterior glazing were reduced by 85.5% due to triple glazing. Zone sensible cooling was reduced by 52%, which minimized CO2 emissions. It was also identified that the final retrofit model passed CIBSE Guide A by achieving a temperature threshold of 20 °C to 25 °C during the summer months, whereas it failed to accomplish the ASHARE 55 criteria (20–24 °C). The outcome of this study justifies the necessity of tested PCMS and advises UK policymakers on how to foster resilient housing plans to overcome overheating issues.
An Experimental Investigation and Numerical Analysis of the Thermal Behavior of a Clutch System Using the Frictional Facing of Functionally Graded Materials
Authors: Jabbar Nasr A. , Hussain Ihsan Y. , Abdullah Oday I. , Mohammed M. N.
Published: October 2023

The friction clutch design strongly depends upon the frictional heat generated between contact surfaces during slipping at the beginning of the engagement. Firstly, the frictional heat generated reduces the performance of the clutch system and then leads to premature failure for contacting surfaces in some cases. The experimental effort in this work included manufacturing friction facing from functionally graded material (FGM) (aluminum and silicon carbide) for the clutch system. For this purpose, a special test rig was developed to investigate the thermal behavior of FGM and compare it with other frictional materials. The Taguchi L9 orthogonal design was selected to analyze the effect of the three factors (rotational, speed, torque, and the type of the frictional material) with three levels on the surface temperature of the contacting surfaces. A three-dimensional finite element model was built to validate the experimental results where the difference between them did not exceed 5.2%. The experimental results showed that the temperatures grew with the disc radius. Furthermore, the surfaces of the pressure plates and the flywheel were affected by frictional heat flow, and this effect increased when increasing the sliding speed. The lowest temperatures occurred when using FGM, which was lower than the other materials by 10%. This study presented an integrated approach consisting of design, manufacturing, and testing to study the complex frictional materials’ effect on the clutch system’s tribological performance.
Diagnosis of Salivary Gland Tumors Using Transfer Learning with Fine-Tuning and Gradual Unfreezing
Authors: Cheng Ping-Chia , Chiang Hui-Hua Kenny
Published: October 2023

Ultrasound is the primary tool for evaluating salivary gland tumors (SGTs); however, tumor diagnosis currently relies on subjective features. This study aimed to establish an objective ultrasound diagnostic method using deep learning. We collected 446 benign and 223 malignant SGT ultrasound images in the training/validation set and 119 benign and 44 malignant SGT ultrasound images in the testing set. We trained convolutional neural network (CNN) models from scratch and employed transfer learning (TL) with fine-tuning and gradual unfreezing to classify malignant and benign SGTs. The diagnostic performances of these models were compared. By utilizing the pretrained ResNet50V2 with fine-tuning and gradual unfreezing, we achieved a 5-fold average validation accuracy of 0.920. The diagnostic performance on the testing set demonstrated an accuracy of 89.0%, a sensitivity of 81.8%, a specificity of 91.6%, a positive predictive value of 78.3%, and a negative predictive value of 93.2%. This performance surpasses that of other models in our study. The corresponding Grad-CAM visualizations were also presented to provide explanations for the diagnosis. This study presents an effective and objective ultrasound method for distinguishing between malignant and benign SGTs, which could assist in preoperative evaluation.
Perineural Invasion Is a Significant Prognostic Factor in Oral Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis
Authors: Binmadi Nada , Alsharif Maha , Almazrooa Soulafa , Aljohani Suad , Akeel Sara , Osailan Samira , Shahzad Muhammad , Elias Wael , Mair Yasmin
Published: October 2023

(1) Objectives: This systematic review and meta-analysis aimed to summarize current evidence regarding the prognostic role of perineural invasion (PNI) in patients with oral squamous cell carcinoma (OSCC). (2) Methods: We searched Cochrane Central, ProQuest, PubMed, Scopus, Science Direct, and Web of Science, using relevant keywords to identify eligible articles. Two independent reviewers conducted two-stage screening, data extraction, and quality assessment. The risk of bias was assessed using the Newcastle–Ottawa Scale (NOS) criteria. All analyses were performed using comprehensive meta-analysis (CMA; version 3.3.070) software. (3) Results: The study included 101 published articles encompassing 26,062 patients. The pooled analyses showed that PNI was associated with significantly worse overall survival (OS; HR = 1.45, 95% CI: 1.32–1.58; p < 0.001), worse disease-specific survival (DSS; HR = 1.87, 95% CI: 1.65–2.12; p < 0.001), and worse disease-free survival (DFS; HR = 1.87, 95% CI: 1.65–2.12; p < 0.001). Similarly, both local recurrence-free survival (LRFS) and regional recurrence-free survival (RRFS) were worse in patients with PNI (HR = 2.31, 95% CI: 1.72–3.10, p < 0.001; and HR = 2.04, 95% CI: 1.51–2.74, p < 0.001), respectively. The random-effect estimate of three studies demonstrated that the presence of PNI was associated with worse failure-free survival (FFS; HR = 2.59, 95% CI: 1.12–5.98, p < 0.001). (4) Conclusions: The current evidence suggests that PNI can be used as an independent predictor of the prognosis for patients with OSCC. The presence of PNI was associated with worse OS, DFS, DSS, FFS, and with recurrence. Asian patients and patients with extra-tumoral or peripheral PNI invasion were associated with worse prognosis.
The Use of a New Dedicated Electrocautery Lumen-Apposing Metal Stent for Gallbladder Drainage in Patients with Acute Cholecystitis
Authors: Brandaleone Luca , Franchellucci Gianluca , Facciorusso Antonio , Samanta Jayanta , Moon Jong Ho , Vargas-Madrigal Jorge , Robles Medranda Carlos , Barbera Carmelo , Di Matteo Francesco , Bulajic Milutin , Auriemma Francesco , Paduano Danilo , Calabrese Federica , Gentile Carmine , Massidda Marco , Bianchi Marco , De Luca Luca , Polverini Davide , Masoni Benedetta , Poletti Valeria , Marcozzi Giacomo , Hassan Cesare , Repici Alessandro , Mangiavillano Benedetto
Published: October 2023

Aims: Lumen-apposing metal stents (LAMSs) in ultrasonography-guided gallbladder drainage (EUS-GBD) have become increasingly important for high-risk surgical patients. Our study aims to evaluate the technical and clinical success, safety, and feasibility of endoscopic ultrasonography-guided gallbladder drainage using a new dedicated LAMS. Methods: This is a retrospective multicenter study that included all consecutive patients not suitable for surgery who were referred to a tertiary center for EUS-GBD using a new dedicated electrocautery LAMS for acute cholecystitis at eight different centers. Results: Our study included 54 patients with a mean age of 76.48 years (standard deviation: 12.6 years). Out of the 54 endoscopic gallbladder drainages performed, 24 (44.4%) were cholecysto-gastrostomy, and 30 (55.4%) were cholecysto-duodenostomy. The technical success of LAMS placement was 100%, and clinical success was achieved in 23 out of 30 patients (76.67%). Adverse events were observed in two patients (5.6%). Patients were discharged after a median of 5 days post-stenting. Conclusions: EUS-GBD represents a valuable option for high-surgical-risk patients with acute cholecystitis. This new dedicated LAMS has demonstrated a high rate of technical and clinical success, along with a high level of safety.
Diffuse Cardiac Uptake Misdiagnosed as Cardiac Amyloidosis in Bone Scan
Authors: Lee Yeongjoo , Jang Jaehyuk , Na Sae Jung
Published: October 2023

In this presented case, a 77-year-old woman with an implanted prosthesis and ongoing knee pain underwent a bone scan using 99mTc-hydroxydiphosphonate (HDP) in suspicion for bone infection. An incidental finding from this scan revealed diffuse cardiac uptake, necessitating further diagnostic procedures to exclude the possibility of cardiac amyloidosis. In the subsequent 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scan and SPECT images, no perceptible cardiac uptake was observed at all. Upon retrospective review of the patient’s medical records, she received 1000 mg of ferric carboxymaltose for iron-deficient anemia the day before the 99mTc-HDP bone scan. Therefore, it was assumed that the diffuse and temporary cardiac activity was due to the transient iron overload. We present and share these bone scan images in order to avoid possible future misinterpretation of cardiac amyloidosis.