bluuebunny/crossref_metadata_2025 huggingface dataset:
Bayesian and Non-Bayesian Analysis of Exponentiated Exponential Stress–Strength Model Based on Generalized Progressive Hybrid Censoring Process
Authors: Yousef Manal M. , Hassan Amal S. , Alshanbari Huda M. , El-Bagoury Abdal-Aziz H. , Almetwally Ehab M.
Published: September 2022

In many real-life scenarios, systems frequently perform badly in difficult operating situations. The multiple failures that take place when systems reach their lower, higher, or extreme functioning states typically receive little attention from researchers. This study uses generalized progressive hybrid censoring to discuss the inference of R=P(X<Y<Z) for a component when it is exposed to two stresses, Y,Z, and it has one strength X that is regarded. We assume that both the stresses and strength variables follow an exponentiated exponential distribution with a common scale parameter. We obtain R’s maximum likelihood estimator and approximate confidence intervals. In addition, the Bayesian estimators for symmetric, such as squared error, and asymmetric loss functions, such as linear exponential, are developed. Credible intervals with the highest posterior densities are established. Monte Carlo simulations are used to evaluate and compare the effectiveness of the many proposed estimators. The process is then precisely described using an analysis of real data.
Political Signed Temporal Networks: A Deep Learning Approach
Authors: Manrique de Lara Alejandro Chinea , Korutcheva Elka
Published: September 2022

The evolution analysis of networks whose links are either positive or negative, representing opposite relationships such as friendship and enmity, has been revealed to be particularly useful in sociological contexts. Using a large relational dataset containing the last two centuries of state-wise geopolitical information (the correlates of war–alliance conflicts), a machine learning approach is presented to predict network dynamics. The combination of geometric as well as information–theoretic measures to characterize the resulting discrete time series together with the power of deep learning machines is used to generate a model whose predictions are even accurate on the few days in two centuries of international relations when the typical value (i.e., Alliance or Neutral) changed to a war or a conflict. In other words, the model can predict the next state of the network with a probability of error close to zero.
Design of Species-Specific PCR Primers That Target the aac(6′)-Ii Gene for the Rapid Detection of Enterococcus faecium
Authors: Peykov Slavil , Strateva Tanya , Dimov Svetoslav
Published: September 2022

In this study, we used the sequence of the aac(6′)-Ii gene, which is responsible for the intrinsic low-level aminoglycoside resistance of Enterococcus faecium, to design novel species-specific primers. Two oligonucleotide pairs named EF_200 and EF_120 were designed, generating amplification products with sizes of 200 bp and 120 bp, respectively. They were successfully applied for the identification of various isolates of clinical or environmental origins in both pure cultures and complex food samples. The obtained results indicated that both primer pairs permitted the highly specific, simple, fast and inexpensive detection of E. faecium isolates.
Hierarchical Co-Attention Selection Network for Interpretable Fake News Detection
Authors: Ge Xiaoyi , Hao Shuai , Li Yuxiao , Wei Bin , Zhang Mingshu
Published: September 2022

Social media fake news has become a pervasive and problematic issue today with the development of the internet. Recent studies have utilized different artificial intelligence technologies to verify the truth of the news and provide explanations for the results, which have shown remarkable success in interpretable fake news detection. However, individuals’ judgments of news are usually hierarchical, prioritizing valuable words above essential sentences, which is neglected by existing fake news detection models. In this paper, we propose an interpretable novel neural network-based model, the hierarchical co-attention selection network (HCSN), to predict whether the source post is fake, as well as an explanation that emphasizes important comments and particular words. The key insight of the HCSN model is to incorporate the Gumbel–Max trick in the hierarchical co-attention selection mechanism that captures sentence-level and word-level information from the source post and comments following the sequence of words–sentences–words–event. In addition, HCSN enjoys the additional benefit of interpretability—it provides a conscious explanation of how it reaches certain results by selecting comments and highlighting words. According to the experiments conducted on real-world datasets, our model outperformed state-of-the-art methods and generated reasonable explanations.
Polymorphisms of the IL-17A Gene Influence Milk Production Traits and Somatic Cell Score in Chinese Holstein Cows
Authors: Ghulam Mohyuddin Sahar , Liang Yan , Ni Wei , Adam Idriss Arbab Abdelaziz , Zhang Huiming , Li Mingxun , Yang Zhangping , Karrow Niel A. , Mao Yongjiang
Published: September 2022

The cow’s milk production characteristics are a significant economic indicator in the livestock industry. Serum cytokines such as interleukin-17 (IL-17) may be potential indicators for bovine mastitis concerning the milk somatic cell count (SCC) and somatic cell score (SCS). The current study aims to find previously undiscovered single nucleotide polymorphisms in the bovine (IL-17A) gene and further investigates their associations with milk production traits in Chinese Holstein cows. Twenty Chinese Holstein cows were randomly chosen from six farms in Jiangsu Province, China. The DNA was extracted from selected samples of bloods for PCR amplification Sequence analyses were used to find SNPs in the bovine (IL-17A) gene. The discovered five SNPs are g-1578A>G, g-1835G>A, and g-398T>A in the 5′UTR; g3164T>C and g3409G>C in the exon region. The genotyping of Holstein cows (n = 992) was performed based on Sequenom Mass ARRAY and SNP data. The connection between SNPs, milk production variables, and the somatic cell score was investigated using the least-squares method. Based on the results, SNP g-398T>A had a significant linkage disequilibrium with g3164T>C. SNPs were found to have significant (p < 0.05) correlations with the test-day milk yield. In conclusion, IL-17A affects cow’s milk production traits significantly.
Engineering Smooth Muscle to Understand Extracellular Matrix Remodeling and Vascular Disease
Authors: Yarbrough Danielle , Gerecht Sharon
Published: September 2022

The vascular smooth muscle is vital for regulating blood pressure and maintaining cardiovascular health, and the resident smooth muscle cells (SMCs) in blood vessel walls rely on specific mechanical and biochemical signals to carry out these functions. Any slight change in their surrounding environment causes swift changes in their phenotype and secretory profile, leading to changes in the structure and functionality of vessel walls that cause pathological conditions. To adequately treat vascular diseases, it is essential to understand how SMCs crosstalk with their surrounding extracellular matrix (ECM). Here, we summarize in vivo and traditional in vitro studies of pathological vessel wall remodeling due to the SMC phenotype and, conversely, the SMC behavior in response to key ECM properties. We then analyze how three-dimensional tissue engineering approaches provide opportunities to model SMCs’ response to specific stimuli in the human body. Additionally, we review how applying biomechanical forces and biochemical stimulation, such as pulsatile fluid flow and secreted factors from other cell types, allows us to study disease mechanisms. Overall, we propose that in vitro tissue engineering of human vascular smooth muscle can facilitate a better understanding of relevant cardiovascular diseases using high throughput experiments, thus potentially leading to therapeutics or treatments to be tested in the future.
Substantially Improved Electrofusion Efficiency of Hybridoma Cells: Based on the Combination of Nanosecond and Microsecond Pulses
Authors: Wu Meng , Ke Qiang , Bi Jinhao , Li Xinhao , Huang Shuheng , Liu Zuohua , Ge Liangpeng
Published: September 2022

As the initial antibody technology, the preparation of hybridoma cells has been widely used in discovering antibody drugs and is still in use. Various antibody drugs obtained through this technology have been approved for treating human diseases. However, the key to producing hybridoma cells is efficient cell fusion. High-voltage microsecond pulsed electric fields (μsHVPEFs) are currently one of the most common methods used for cell electrofusion. Nevertheless, the membrane potential induced by the external microsecond pulse is proportional to the diameter of the cell, making it difficult to fuse cells of different sizes. Although nanosecond pulsed electric fields (nsPEFs) can achieve the fusion of cells of different sizes, due to the limitation of pore size, deoxyribonucleic acid (DNA) cannot efficiently pass through the cell pores produced by nsPEFs. This directly causes the significant loss of the target gene and reduces the proportion of positive cells after fusion. To achieve an electric field environment independent of cell size and enable efficient cell fusion, we propose a combination of nanosecond pulsed electric fields and low-voltage microsecond pulsed electric fields (ns/μsLVPEFs) to balance the advantages and disadvantages of the two techniques. The results of fluorescence experiments and hybridoma culture experiments showed that after lymphocytes and myeloma cells were stimulated by a pulse (ns/μsLVPEF, μsHVPEF, and control), compared with μsHVPEF, applying ns/μsLVPEF at the same energy could increase the cell fusion efficiency by 1.5–3.0 times. Thus far, we have combined nanosecond and microsecond pulses and provided a practical solution that can significantly increase cell fusion efficiency. This efficient cell fusion method may contribute to the further development of hybridoma technology in electrofusion.
Green Synthesis and Antibacterial Activity of Ag/Fe2O3 Nanocomposite Using Buddleja lindleyana Extract
Authors: Al-Zahrani Fatimah A. M. , Salem Salem S. , Al-Ghamdi Huda A. , Nhari Laila M. , Lin Long , El-Shishtawy Reda M.
Published: September 2022

In the study reported in this manuscript, silver/iron oxide nanocomposites (Ag/Fe2O3) were phytosynthesized using the extract of Buddleja lindleyana via a green, economical and eco-friendly strategy. The biosynthesized Ag/Fe2O3 nanocomposites were characterized using UV-Vis spectrophotometry, FTIR, XRD, TEM, DLS and SEM-EDX analyses. The particulates showed a triangular and spherical morphology having sizes between 25 and 174 nm. FTIR studies on the nanoparticles showed functional groups corresponding to organic metabolites, which reduce and stabilize the Ag/Fe2O3 nanocomposite. The antimicrobial efficacy of the phytosynthesized Ag/Fe2O3 against bacterial pathogens was assessed. In addition, Ag/Fe2O3 exhibited broad spectrum activities against B. subtilis, S. aureus, E. coli, and P. aeruginosa with inhibition zones of 23.4 ± 0.75, 22.3 ± 0.57, 20.8 ± 1.6, and 19.5 ± 0.5 mm, respectively. The Ag/Fe2O3 composites obtained showed promising antibacterial action against human bacterial pathogens (S. aureus, E. coli, B. subtilis and P. aeruginosa), making them candidates for medical applications.
Using Macro- and Microscale Preservation in Vertebrate Fossils as Predictors for Molecular Preservation in Fluvial Environments
Authors: Colleary Caitlin , O’Reilly Shane , Dolocan Andrei , Toyoda Jason G. , Chu Rosalie K. , Tfaily Malak M. , Hochella Michael F. , Nesbitt Sterling J.
Published: September 2022

Exceptionally preserved fossils retain soft tissues and often the biomolecules that were present in an animal during its life. The majority of terrestrial vertebrate fossils are not traditionally considered exceptionally preserved, with fossils falling on a spectrum ranging from very well-preserved to poorly preserved when considering completeness, morphology and the presence of microstructures. Within this variability of anatomical preservation, high-quality macro-scale preservation (e.g., articulated skeletons) may not be reflected in molecular-scale preservation (i.e., biomolecules). Excavation of the Hayden Quarry (HQ; Chinle Formation, Ghost Ranch, NM, USA) has resulted in the recovery of thousands of fossilized vertebrate specimens. This has contributed greatly to our knowledge of early dinosaur evolution and paleoenvironmental conditions during the Late Triassic Period (~212 Ma). The number of specimens, completeness of skeletons and fidelity of osteohistological microstructures preserved in the bone all demonstrate the remarkable quality of the fossils preserved at this locality. Because the Hayden Quarry is an excellent example of good preservation in a fluvial environment, we have tested different fossil types (i.e., bone, tooth, coprolite) to examine the molecular preservation and overall taphonomy of the HQ to determine how different scales of preservation vary within a single locality. We used multiple high-resolution mass spectrometry techniques (TOF-SIMS, GC-MS, FT-ICR MS) to compare the fossils to unaltered bone from extant vertebrates, experimentally matured bone, and younger dinosaurian skeletal material from other fluvial environments. FT-ICR MS provides detailed molecular information about complex mixtures, and TOF-SIMS has high elemental spatial sensitivity. Using these techniques, we did not find convincing evidence of a molecular signal that can be confidently interpreted as endogenous, indicating that very good macro- and microscale preservation are not necessarily good predictors of molecular preservation.
Biotechnology of Microorganisms from Coal Environments: From Environmental Remediation to Energy Production
Authors: Akimbekov Nuraly S. , Digel Ilya , Tastambek Kuanysh T. , Marat Adel K. , Turaliyeva Moldir A. , Kaiyrmanova Gulzhan K.
Published: September 2022

It was generally believed that coal sources are not favorable as live-in habitats for microorganisms due to their recalcitrant chemical nature and negligible decomposition. However, accumulating evidence has revealed the presence of diverse microbial groups in coal environments and their significant metabolic role in coal biogeochemical dynamics and ecosystem functioning. The high oxygen content, organic fractions, and lignin-like structures of lower-rank coals may provide effective means for microbial attack, still representing a greatly unexplored frontier in microbiology. Coal degradation/conversion technology by native bacterial and fungal species has great potential in agricultural development, chemical industry production, and environmental rehabilitation. Furthermore, native microalgal species can offer a sustainable energy source and an excellent bioremediation strategy applicable to coal spill/seam waters. Additionally, the measures of the fate of the microbial community would serve as an indicator of restoration progress on post-coal-mining sites. This review puts forward a comprehensive vision of coal biodegradation and bioprocessing by microorganisms native to coal environments for determining their biotechnological potential and possible applications.
Gut Microbial Composition and Liver Metabolite Changes Induced by Ammonia Stress in Juveniles of an Invasive Freshwater Turtle
Authors: Li Han , Meng Qinyuan , Wang Wanling , Mo Dongmei , Dang Wei , Lu Hongliang
Published: September 2022

As the most common pollutant in aquaculture systems, the toxic effects of ammonia have been extensively explored in cultured fish, molluscs, and crustaceans, but have rarely been considered in turtle species. In this study, juveniles of the invasive turtle, Trachemys scripta elegans, were exposed to different ammonia levels (0, 0.3, 3.0, and 20.0 mg/L) for 30 days to evaluate the physiological, gut microbiomic, and liver metabolomic responses to ammonia in this turtle species. Except for a relatively low growth rate of turtles exposed to the highest concentration, ammonia exposure had no significant impact on the locomotor ability and gut microbial diversity of turtles. However, the composition of the microbial community could be altered, with some pathogenic bacteria being increased in ammonia-exposed turtles, which might indicate the change in their health status. Furthermore, hepatic metabolite profiles via liquid chromatography–mass spectrometry revealed extensive metabolic perturbations, despite being primarily involved in amino acid biosynthesis and metabolism. Overall, our results show that ammonia exposure causes gut dysbacteriosis and disturbs various metabolic pathways in aquatic turtle species. Considering discrepant defense mechanisms, the toxic impacts of ammonia at environmentally relevant concentrations on physiological performance might be less pronounced in turtles compared with fish and other invertebrates.
Cancer and Chaos and the Complex Network Model of a Multicellular Organism
Authors: Gecow Andrzej , Iantovics Laszlo Barna , Tez Mesut
Published: September 2022

In the search of theoretical models describing cancer, one of promising directions is chaos. It is connected to ideas of “genome chaos” and “life on the edge of chaos”, but they profoundly differ in the meaning of the term “chaos”. To build any coherent models, notions used by both ideas should be firstly brought closer. The hypothesis “life on the edge of chaos” using deterministic chaos has been radically deepened developed in recent years by the discovery of half-chaos. This new view requires a deeper interpretation within the range of the cell and the organism. It has impacts on understanding “chaos” in the term “genome chaos”. This study intends to present such an interpretation on the basis of which such searches will be easier and closer to intuition. We interpret genome chaos as deterministic chaos in a large module of half-chaotic network modeling the cell. We observed such chaotic modules in simulations of evolution controlled by weaker variant of natural selection. We also discuss differences between free and somatic cells in modeling their disturbance using half-chaotic networks.
Bioactive Molecules: Structures, Functions, and Potential Uses for Cancer Prevention and Targeted Therapies
Authors: Dou Qingping
Published: September 2022

Cancer continues to be an increasingly pervasive and destructive disease worldwide [...]
Role of Reactive Oxygen Species in Glucose Metabolism Disorder in Diabetic Pancreatic β-Cells
Authors: Mukai Eri , Fujimoto Shimpei , Inagaki Nobuya
Published: September 2022

The dysfunction of pancreatic β-cells plays a central role in the onset and progression of type 2 diabetes mellitus (T2DM). Insulin secretory defects in β-cells are characterized by a selective impairment of glucose stimulation, and a reduction in glucose-induced ATP production, which is essential for insulin secretion. High glucose metabolism for insulin secretion generates reactive oxygen species (ROS) in mitochondria. In addition, the expression of antioxidant enzymes is very low in β-cells. Therefore, β-cells are easily exposed to oxidative stress. In islet studies using a nonobese T2DM animal model that exhibits selective impairment of glucose-induced insulin secretion (GSIS), quenching ROS generated by glucose stimulation and accumulated under glucose toxicity can improve impaired GSIS. Acute ROS generation and toxicity cause glucose metabolism disorders through different molecular mechanisms. Nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor, is a master regulator of antioxidant defense and a potential therapeutic target in oxidative stress-related diseases, suggesting the possible involvement of Nrf2 in β-cell dysfunction caused by ROS. In this review, we describe the mechanisms of insulin secretory defects induced by oxidative stress in diabetic β-cells.
The Metabolomic Approach for the Screening of Endometrial Cancer: Validation from a Large Cohort of Women Scheduled for Gynecological Surgery
Authors: Troisi Jacopo , Mollo Antonio , Lombardi Martina , Scala Giovanni , Richards Sean M. , Symes Steven J. K. , Travaglino Antonio , Neola Daniele , de Laurentiis Umberto , Insabato Luigi , Di Spiezio Sardo Attilio , Raffone Antonio , Guida Maurizio
Published: September 2022

Endometrial cancer (EC) is the most common gynecological neoplasm in high-income countries. Five-year survival rates are related to stage at diagnosis, but currently, no validated screening tests are available in clinical practice. The metabolome offers an unprecedented overview of the molecules underlying EC. In this study, we aimed to validate a metabolomics signature as a screening test for EC on a large study population of symptomatic women. Serum samples collected from women scheduled for gynecological surgery (n = 691) were separated into training (n = 90), test (n = 38), and validation (n = 563) sets. The training set was used to train seven classification models. The best classification performance during the training phase was the PLS-DA model (96% accuracy). The subsequent screening test was based on an ensemble machine learning algorithm that summed all the voting results of the seven classification models, statistically weighted by each models’ classification accuracy and confidence. The efficiency and accuracy of these models were evaluated using serum samples taken from 871 women who underwent endometrial biopsies. The EC serum metabolomes were characterized by lower levels of serine, glutamic acid, phenylalanine, and glyceraldehyde 3-phosphate. Our results illustrate that the serum metabolome can be an inexpensive, non-invasive, and accurate EC screening test.
4-OI Protects MIN6 Cells from Oxidative Stress Injury by Reducing LDHA-Mediated ROS Generation
Authors: Wu Jianmin , Gu Xingshi , Zhang Juan , Mi Ze , He Zhenhu , Dong Yuqian , Ge Wu , Ghimire Kedar , Rong Pengfei , Wang Wei , Ma Xiaoqian
Published: September 2022

Pancreatic beta cells are highly susceptible to oxidative stress, which plays a crucial role in diabetes outcomes. Progress has been slow to identify molecules that could be utilized to enhance cell survival and function under oxidative stress. Itaconate, a byproduct of the tricarboxylic acid cycle, has both anti-inflammatory and antioxidant properties. The effects of itaconate on beta cells under oxidative stress are relatively unknown. We explored the effects of 4-octyl itaconate—a cell-permeable derivative of itaconate—on MIN6 (a beta cell model) under oxidative stress conditions caused by hypoxia, along with its mechanism of action. Treatment with 4-OI reversed hypoxia-induced cell death, reduced ROS production, and inhibited cell death pathway activation and inflammatory cytokine secretion in MIN6 cells. The 4-OI treatment also suppressed lactate dehydrogenase A (LDHA)activity, which increases under hypoxia. Treatment of cells with the ROS scavenger NAC and LDHA-specific inhibitor FX-11 reproduced the beneficial effects of 4-OI on MIN6 cell viability under oxidative stress conditions, confirming its role in regulating ROS production. Conversely, overexpression of LDHA reduced the beneficial effects exerted by 4-OI on cells. Our findings provide a strong rationale for using 4-OI to prevent the death of MIN6 cells under oxidative stress.
Three Grand Challenges in High Throughput Omics Technologies
Authors: Suravajhala Prashanth , Goltsov Alexey
Published: September 2022

Over the years, next-generation sequencing (NGS) and advanced bioinformatics approaches have allowed the transition of genomic assays into translational practices [...]
Application of Metal–Organic Framework in Diagnosis and Treatment of Diabetes
Authors: Gao Qian , Bai Que , Zheng Caiyun , Sun Na , Liu Jinxi , Chen Wenting , Hu Fangfang , Lu Tingli
Published: September 2022

Diabetes-related chronic wounds are often accompanied by a poor wound-healing environment such as high glucose, recurrent infections, and inflammation, and standard wound treatments are fairly limited in their ability to heal these wounds. Metal–organic frameworks (MOFs) have been developed to improve therapeutic outcomes due to their ease of engineering, surface functionalization, and therapeutic properties. In this review, we summarize the different synthesis methods of MOFs and conduct a comprehensive review of the latest research progress of MOFs in the treatment of diabetes and its wounds. State-of-the-art in vivo oral hypoglycemic strategies and the in vitro diagnosis of diabetes are enumerated and different antimicrobial strategies (including physical contact, oxidative stress, photothermal, and related ions or ligands) and provascular strategies for the treatment of diabetic wounds are compared. It focuses on the connections and differences between different applications of MOFs as well as possible directions for improvement. Finally, the potential toxicity of MOFs is also an issue that we cannot ignore.
De Novo Self-Assembling Peptides Mediate the Conversion of Temozolomide and Delivery of a Model Drug into Glioblastoma Multiforme Cells
Authors: Pitz Megan , Elpers Margaret , Nukovic Alexandra , Wilde Sarah , Gregory Arica Jordan , Alexander-Bryant Angela
Published: September 2022

Glioblastoma multiforme (GBM) is the most aggressive central nervous system tumor, and standard treatment, including surgical resection, radiation, and chemotherapy, has not significantly improved patient outcomes over the last 20 years. Temozolomide (TMZ), the prodrug most commonly used to treat GBM, must pass the blood–brain barrier and requires a basic pH to convert to its active form. Due to these barriers, less than 30% of orally delivered TMZ reaches the central nervous system and becomes bioactive. In this work, we have developed a novel biomaterial delivery system to convert TMZ to its active form and that shows promise for intracellular TMZ delivery. Self-assembling peptides were characterized under several different assembly conditions and evaluated for TMZ loading and conversion. Both solvent and method of assembly were found to affect the supramolecular and secondary structure of peptide assemblies. Additionally, as peptides degraded in phosphate-buffered saline, TMZ was rapidly converted to its active form. This work demonstrates that peptide-based drug delivery systems can effectively create a local stimulus during drug delivery while remaining biocompatible. This principle could be used in many future biomedical applications in addition to cancer treatment, such as wound healing and regenerative medicine.
Lipid Nanoparticles as Delivery Vehicles for Inhaled Therapeutics
Authors: Leong Ellenmae W. X. , Ge Ruowen
Published: September 2022

Lipid nanoparticles (LNPs) have emerged as a powerful non-viral carrier for drug delivery. With the prevalence of respiratory diseases, particularly highlighted by the current COVID-19 pandemic, investigations into applying LNPs to deliver inhaled therapeutics directly to the lungs are underway. The progress in LNP development as well as the recent pre-clinical studies in three main classes of inhaled encapsulated drugs: small molecules, nucleic acids and proteins/peptides will be discussed. The advantages of the pulmonary drug delivery system such as reducing systemic toxicity and enabling higher local drug concentration in the lungs are evaluated together with the challenges and design considerations for improved formulations. This review provides a perspective on the future prospects of LNP-mediated delivery of inhaled therapeutics for respiratory diseases.
J-Shaped Relationship of Serum Uric Acid with Unfavorable Short-Term Outcomes among Patients with Acute Ischemic Stroke
Authors: Liu Chih-Yang , Hsiao Cheng-Lun , Chen Pei-Ya , Tsou Adam , Tzeng I-Shiang , Lin Shinn-Kuang
Published: September 2022

(1) Background: The role of uric acid in stroke outcomes remains inconclusive. (2) Methods: We retrospectively enrolled 3370 patients with acute ischemic stroke. (3) Results: Uric acid level was higher in men than in women. Univariate analyses revealed that the rates of hyperuricemia were higher in all patients and in women for unfavorable outcomes. For death, the hyperuricemia rates were higher in all patients including men and women, and the uric acid levels were also higher in all patients and in women. A J-shaped curve was observed between uric acid and the discharge-modified Rankin Scale score. Patients within Quartiles 1 (<4.1 mg/dL) and 4 (>6.5 mg/dL) of uric acid had higher rates of unfavorable outcomes and death than patients within Quartiles 2 (4.1–5.1 mg/dL) and 3 (5.1–6.2 mg/dL). Multivariable analyses for unfavorable outcomes revealed that Quartile 1 of uric acid was a significant factor in all patients and in men. In men, a significant factor for death was being in Quartile 1 of uric acid. In women, higher levels of uric acid or hyperuricemia (>6.6 mg/dL) were significant factors for death. (4) Conclusions: Lower uric acid levels are a predictor for unfavorable outcomes and death in men, and higher uric acid levels are a predictor for death in women.
Prognostic Significance of Initial Absolute Lymphocyte Count in Adjuvant Radiotherapy for Pancreatic Adenocarcinoma
Authors: Heo Jaesung , Noh O Kyu
Published: September 2022

Background: This study aimed to investigate the impact of absolute lymphocyte count (ALC) on clinical outcomes in patients treated with adjuvant RT with or without chemotherapy for pancreatic adenocarcinoma. Methods: From 2001 to 2015, 68 patients underwent curative surgery followed by adjuvant RT. Chemotherapy was administered concurrently or sequentially with RT. We analyzed the clinical impact of the initial ALC level on locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), and overall survival (OS). Results: With a median follow-up of 13.7 months (range: 3.1–61.3), the 3 year OS, LRRFS, and DMFS are 25.4%, 40.0%, and 26.6%, respectively. The OS and LRRFS of the high initial ALC group (≥ 1540 × 106/L) are significantly higher than that of the group with lower initial ALC (3 year OS: 32.6% vs. 18.6%, p = 0.036; 3 year LRRFS: 53.5% vs. 27.0%, p = 0.031). In multivariable analyses, initial ALC level is the significant prognostic factor affecting LRRFS (HR = 0.457, p = 0.028) and OS (HR = 0.473, p = 0.026). Conclusions: Initial ALC could have potential prognostic significance in patients with pancreatic adenocarcinoma receiving adjuvant RT with or without chemotherapy. Further studies are warranted to investigate the role of adjuvant RT, considering the initial ALC.
Clinical Usefulness of Non-Invasive Metabolic-Associated Fatty Liver Disease Risk Assessment Methods in Patients with Full-Blown Polycystic Ovary Syndrome in Relation to the MRI Examination with the Ideal IQ Sequence
Authors: Blukacz Łukasz , Nowak Artur , Wójtowicz Mariusz , Krawczyk Angelika , Franik Grzegorz , Madej Paweł , Pluta Dagmara , Kowalczyk Karolina , Żorniak Michał
Published: September 2022

The coexistence of polycystic ovary syndrome (PCOS) and liver steatosis has been studied for years. The gold standards for the diagnosis of liver steatosis are liver biopsy and magnetic resonance imaging (MRI), which are invasive and expensive methods. The main aim of this study is to check the usefulness of lipid accumulation product (LAP) and free androgen index (FAI) in the diagnosis of liver steatosis. The Ideal IQ MRI was performed in 49 women with PCOS phenotype A to assess the degree of liver steatosis, which was expressed with the proton density fat fraction (PDFF). Anthropometric examination and laboratory tests were performed, and the LAP and FAI were calculated. The correlation between MRI results and LAP, FAI, and one of the FAI components, sex hormone binding globulin (SHBG), was checked using statistical tests. There is a statistically significant correlation between PDFF and LAP and also between PDFF and FAI. LAP = 70.25 and FAI = 5.05 were established as cut-offs to diagnose liver steatosis. The SHBG is not a statistically significant parameter to predict liver steatosis. The study showed that especially LAP, but also FAI, can be used to predict liver steatosis with high specificity and sensitivity.
Higher Dose Anticoagulation Cannot Prevent Disease Progression in COVID-19 Patients: A Systematic Review and Meta-Analysis
Authors: Kovács Emőke Henrietta , Tánczos Krisztián , Szabó László , Turan Caner , Dembrovszky Fanni , Ocskay Klementina , Lee Bo-Young , Hegyi Péter , Molnár Zsolt
Published: September 2022

Implementation of higher dose (HD) thromboprophylaxis has been considered in patients infected with coronavirus disease 2019 (COVID-19). Our aim was to compare HD to standard dose (SD) thromboprophylaxis in COVID-19 patients. The protocol is registered on PROSPERO (CRD42021284808). We searched for randomised controlled studies (CENTRAL, Embase, Medline and medRxviv) that compared HD to SD anticoagulation in COVID-19 and analysed outcomes such as mortality, thrombotic events, bleedings, and disease progression. The statistical analyses were made using the random effects model. Fourteen articles were included (6253 patients). HD compared with SD showed no difference in mortality (OR 0.83 [95% CI 0.54–1.28]). The use of HD was associated with a decreased risk of thrombosis (OR 0.58 [95% CI 0.44–0.76]), although with an increased risk of major bleeding (OR 1.64 [95% CI 1.25–2.16]). The cohort with D-dimer < 1 mg/mL showed no effect (OR 1.19 [95% CI 0.67–2.11]), but in the case of D-dimer > 1 mg/mL, a tendency of lower risk in the HD group was observed (OR 0.56 [95% CI 0.31–1.00]). The need for intubation in moderately ill patients showed a nonsignificant lower likelihood in the HD group (OR 0.82 [95% CI 0.63–1.08]). We cannot advocate for HD in all COVID-19 patients, although it shows some nonsignificant benefits on disease progression in those with elevated D-dimer who do not need ICU admission.
A Robust Deep Model for Classification of Peptic Ulcer and Other Digestive Tract Disorders Using Endoscopic Images
Authors: Mahmood Saqib , Fareed Mian Muhammad Sadiq , Ahmed Gulnaz , Dawood Farhan , Zikria Shahid , Mostafa Ahmad , Jilani Syeda Fizzah , Asad Muhammad , Aslam Muhammad
Published: September 2022

Accurate patient disease classification and detection through deep-learning (DL) models are increasingly contributing to the area of biomedical imaging. The most frequent gastrointestinal (GI) tract ailments are peptic ulcers and stomach cancer. Conventional endoscopy is a painful and hectic procedure for the patient while Wireless Capsule Endoscopy (WCE) is a useful technology for diagnosing GI problems and doing painless gut imaging. However, there is still a challenge to investigate thousands of images captured during the WCE procedure accurately and efficiently because existing deep models are not scored with significant accuracy on WCE image analysis. So, to prevent emergency conditions among patients, we need an efficient and accurate DL model for real-time analysis. In this study, we propose a reliable and efficient approach for classifying GI tract abnormalities using WCE images by applying a deep Convolutional Neural Network (CNN). For this purpose, we propose a custom CNN architecture named GI Disease-Detection Network (GIDD-Net) that is designed from scratch with relatively few parameters to detect GI tract disorders more accurately and efficiently at a low computational cost. Moreover, our model successfully distinguishes GI disorders by visualizing class activation patterns in the stomach bowls as a heat map. The Kvasir-Capsule image dataset has a significant class imbalance problem, we exploited a synthetic oversampling technique BORDERLINE SMOTE (BL-SMOTE) to evenly distribute the image among the classes to prevent the problem of class imbalance. The proposed model is evaluated against various metrics and achieved the following values for evaluation metrics: 98.9%, 99.8%, 98.9%, 98.9%, 98.8%, and 0.0474 for accuracy, AUC, F1-score, precision, recall, and loss, respectively. From the simulation results, it is noted that the proposed model outperforms other state-of-the-art models in all the evaluation metrics.
Isolation of Hepatocytes from Liver Tissue by a Novel, Semi-Automated Perfusion Technology
Authors: Poggel Carsten , Adams Timo , Janzen Ronald , Hofmann Alexander , Hardt Olaf , Roeb Elke , Schröder Sarah K. , Tag Carmen G. , Roderfeld Martin , Weiskirchen Ralf
Published: September 2022

Primary hepatocytes are a major tool in biomedical research. However, obtaining high yields of variable hepatocytes is technically challenging. Most protocols rely on the two-step collagenase perfusion protocol introduced by Per Ottar Seglen in 1976. In this procedure, the liver is perfused in situ with a recirculating, constant volume of calcium-free buffer, which is maintained at 37 °C and continuously oxygenated. In a second step, the liver is removed from the carcass and perfused with a collagenase solution in order to dissociate the extracellular matrix of the liver and liberate individual cells. Finally, the dissected hepatocytes are further purified and concentrated by density-based centrifugation. However, failure in proper cannulation, incomplete enzymatic digestion or over-digestion can result in low cell yield and viability. Here we present a novel semi-automated perfusion device, which allows gentle, rapid and efficient generation of a single-cell suspension from rodent livers. In combination with prefabricated buffers, the system allows reliable and highly reproducible isolation of primary hepatocytes.
Trace Immunosensing of Multiple Neonicotinoid Insecticides by a Novel Broad-Specific Antibody Obtained from a Rational Screening Strategy
Authors: Jiao Shasha , Wang Yan , Chang Yunyun , Liu Pengyan , Chen Yang , Liu Yihua , Zhu Guonian , Guo Yirong
Published: September 2022

Residues of neonicotinoid pesticides have potential risks to food, environmental and biological safety. In this study, the hapten toward imidacloprid was adopted to gain antibodies. After molecular modeling, the electrostatic potentials of eight commonly-used neonicotinoid pesticides were individually calculated to analyze the structural similarity. Two representative compounds (imidacloprid and acetamiprid) with moderate similarity were rationally selected for hybridoma screening. Using this strategy, four clones of broad-specific monoclonal antibodies (mAbs) against multiple neonicotinoids were obtained, and the clone 6F11 exhibited the broadest spectrum to six neonicotinoid pesticides and two metabolites, with half-maximal inhibitory concentrations (IC50) ranging from 0.20 to 5.92 ng/mL. Then, the novel antibody gene was sequenced and successfully expressed in full-length IgG form using mammalian cells. Based on the sensitive recombinant antibody, a gold lateral-flow immunosensing strip assay was developed and it was qualified for rapid detection of imidacloprid, clothianidin or imidaclothiz residues in food samples.
Biosensing Dopamine and L-Epinephrine with Laccase (Trametes pubescens) Immobilized on a Gold Modified Electrode
Authors: Pimpilova Mariya , Kamarska Kalina , Dimcheva Nina
Published: September 2022

Engineering electrode surfaces through the electrodeposition of gold may provide a range of advantages in the context of biosensor development, such as greatly enhanced surface area, improved conductivity and versatile functionalization. In this work we report on the development of an electrochemical biosensor for the laccase-catalyzed assay of two catecholamines—dopamine and L-epinephrine. Variety of electrochemical techniques—cyclic voltammetry, differential pulse voltammetry, electrochemical impedance spectroscopy and constant potential amperometry have been used in its characterization. It has been demonstrated that the laccase electrode is capable of sensing dopamine using two distinct techniques—differential pulse voltammetry and constant potential amperometry, the latter being suitable for the assay of L-epinephrine as well. The biosensor response to both catecholamines, examined by constant potential chronoamperometry over the potential range from 0.2 to −0.1 V (vs. Ag|AgCl, sat KCl) showed the highest electrode sensitivity at 0 and −0.1 V. The dependencies of the current density on either catecholamine’s concentration was found to follow the Michaelis—Menten kinetics with apparent constants KMapp = 0.116 ± 0.015 mM for dopamine and KMapp = 0.245 ± 0.031 mM for L-epinephrine and linear dynamic ranges spanning up to 0.10 mM and 0.20 mM, respectively. Calculated limits of detection for both analytes were found to be within the sub-micromolar concentration range. The biosensor applicability to the assay of dopamine concentration in a pharmaceutical product was demonstrated (with recovery rates between 99% and 106%, n = 3).
Challenges in the Detection of SARS-CoV-2: Evolution of the Lateral Flow Immunoassay as a Valuable Tool for Viral Diagnosis
Authors: Castrejón-Jiménez Nayeli Shantal , García-Pérez Blanca Estela , Reyes-Rodríguez Nydia Edith , Vega-Sánchez Vicente , Martínez-Juárez Víctor Manuel , Hernández-González Juan Carlos
Published: September 2022

SARS-CoV-2 is an emerging infectious disease of zoonotic origin that caused the coronavirus disease in late 2019 and triggered a pandemic that has severely affected human health and caused millions of deaths. Early and massive diagnosis of SARS-CoV-2 infected patients is the key to preventing the spread of the virus and controlling the outbreak. Lateral flow immunoassays (LFIA) are the simplest biosensors. These devices are clinical diagnostic tools that can detect various analytes, including viruses and antibodies, with high sensitivity and specificity. This review summarizes the advantages, limitations, and evolution of LFIA during the SARS-CoV-2 pandemic and the challenges of improving these diagnostic devices.
Investigating Topic Modeling Techniques to Extract Meaningful Insights in Italian Long COVID Narration
Authors: Scarpino Ileana , Zucco Chiara , Vallelunga Rosarina , Luzza Francesco , Cannataro Mario
Published: September 2022

Through an adequate survey of the history of the disease, Narrative Medicine (NM) aims to allow the definition and implementation of an effective, appropriate, and shared treatment path. In the present study different topic modeling techniques are compared, as Latent Dirichlet Allocation (LDA) and topic modeling based on BERT transformer, to extract meaningful insights in the Italian narration of COVID-19 pandemic. In particular, the main focus was the characterization of Post-acute Sequelae of COVID-19, (i.e., PASC) writings as opposed to writings by health professionals and general reflections on COVID-19, (i.e., non-PASC) writings, modeled as a semi-supervised task. The results show that the BERTopic-based approach outperforms the LDA-base approach by grouping in the same cluster the 97.26% of analyzed documents, and reaching an overall accuracy of 91.97%.
MR Angiography in Assessment of Collaterals in Patients with Acute Ischemic Stroke: A Comparative Analysis with Digital Subtraction Angiography
Authors: Tsui Brian , Nour May , Chen Iris , Qiao Joe X. , Salehi Banafsheh , Yoo Bryan , Colby Geoffrey P. , Salamon Noriko , Villablanca Pablo , Jahan Reza , Duckwiler Gary , Saver Jeffrey L. , Liebeskind David S. , Nael Kambiz
Published: September 2022

Collateral status has prognostic and treatment implications in acute ischemic stroke (AIS) patients. Unlike CTA, grading collaterals on MRA is not well studied. We aimed to evaluate the accuracy of assessing collaterals on pretreatment MRA in AIS patients against DSA. AIS patients with anterior circulation proximal arterial occlusion with baseline MRA and subsequent endovascular treatment were included. MRA collaterals were evaluated by two neuroradiologists independently using the Tan and Maas scoring systems. DSA collaterals were evaluated by using the American Society of Interventional and Therapeutic Neuroradiology grading system and were used as the reference for comparative analysis against MRA. A total of 104 patients met the inclusion criteria (59 female, age (mean ± SD): 70.8 ± 18.1). The inter-rater agreement (k) for collateral scoring was 0.49, 95% CI 0.37–0.61 for the Tan score and 0.44, 95% CI 0.26–0.62 for the Maas score. Total number (%) of sufficient vs. insufficient collaterals based on DSA was 49 (47%) and 55 (53%) respectively. Using the Tan score, 45% of patients with sufficient collaterals and 64% with insufficient collaterals were correctly identified in comparison to DSA, resulting in a poor agreement (0.09, 95% CI 0.1–0.28). Using the Maas score, only 4% of patients with sufficient collaterals and 93% with insufficient collaterals were correctly identified against DSA, resulting in poor agreement (0.03, 95% CI 0.06–0.13). Pretreatment MRA in AIS patients has limited concordance with DSA when grading collaterals using the Tan and Maas scoring systems.
Impact of Rural vs. Urban Residence on Survival Rates of Patients with Glioblastoma: A Tertiary Care Center Experience
Authors: Alwadei Ali , Alnaami Ibrahim , Alenazy Kawthar , Marei Amal , BaHammam Leenh O. , Nasser Sameh , Alswilem Abdullah Mansour , Maklad Ahmed , Shehata Shehata F. , Alqahtani Mohammad Salem , Al-Shahrani Abdulelah , Balbaid Ali
Published: September 2022

Purpose: Although the association between residential location and survival in patients with different cancer types has been established, the conclusions are contentious, and the underlying mechanisms remain unknown. Here, we reviewed the impact of residence on the survival of patients with glioblastoma (GBM). Methods: We conducted a retrospective study to compare the impact of rural and urban residence on the survival rates of patients with GBM diagnosed in Riyadh City and outside Riyadh. All patients in this study were treated in a tertiary care hospital, and their survival rates were analyzed in relation to their residence and other related factors, namely radiotherapy timing. Results: Overall, 125 patients were included: 61 from Riyadh City and 64 from outside. The majority of patients in both groups were aged >50 years (p = 0.814). There was no statistically significant difference between the groups in the Eastern Cooperative Oncology Group Performance Status (p = 0.430), seizure (p = 0.858), or initiation timing of radiotherapy (p = 0.781). Furthermore, the median survival rate in the Riyadh group versus the other group was 14.4 months and 12.2 months, respectively, with no statistical significance (p = 0.187). Conclusions: Our study showed that residential location had no significant effect on GBM prognosis. However, further studies with a larger sample size are required to delineate the other factors of referral within the healthcare system to facilitate the management of these patients within a specific timeframe.