bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatiotemporal Distribution of Precipitation over the Mongolian Plateau during 1976–2017
Authors: Xia Yingying , Dan Dan , Liu Hongyu , Zhou Haijun , Wan Zhiqiang
Published: December 2022

Located in the interior of Eurasia, the Mongolian Plateau (MP) is extremely sensitive to global warming and become a critical area for studying precipitation patterns. Based on the monthly data of 135 meteorological stations during 1976–2017, we analyze the spatiotemporal change in precipitation and discuss its response to atmospheric circulation. The results show that: (1) Precipitation shows increasing trends in spring, autumn, and winter, but a decreasing trend at a rate of 5.3 mm/decade in summer. The annual precipitation also shows an overall slight decreasing trend. (2) The spatial distribution is uneven, the annual precipitation in the northern Great Khingan Mountains is more, but it gradually decreases at the rate of 10–30 mm/decade, showing a trend of “wet gets dry”; while there is less in the southwest Gobi Desert region, but it gradually increases with the rate of 10–20 mm/decade, showing a trend of “dry gets wet”. (3) Over decades, the East Asian summer monsoon (EASM) and westerly circulation show a seesaw change in MP. Affected by the weakening of the EASM, the area of arid regions has gradually expanded. The results also demonstrate that the EASM has a higher impact on the annual precipitation change pattern, particularly in the southeastern MP. The conclusion indicated that the variation in the position and orientation between EASM and the westerly circulation may be an explanation for the spatiotemporal precipitation pattern, providing a new viewpoint to the question of circulation mechanisms behind climate change in MP in recent 40 years.
Evaluation of Air–Sea Flux Parameterization for Typhoon Mangkhut Simulation during Intensification Period
Authors: Ye Lei , Li Yubin , Gao Zhiqiu
Published: December 2022

Using the Advanced Research Weather Research and Forecasting (WRF) model, a series of numerical experiments are conducted to examine the sensitivity of the Typhoon Mangkhut intensification simulation to different air–sea flux parameterization schemes (isftcflx option), including option 0 (OPT0), option 1 (OPT1), and option 2 (OPT2). The results show that three schemes basically reproduce tropical cyclone (TC) track and intensity of observation, and the simulated exchange coefficient of three schemes is consistent with theoretical results. Using the same upper limit of Cd as OPT0 and OPT2, OPT1 has much larger Ck than the other two options, which leads to larger latent heat (and sensible heat) flux and produces stronger inflow (within boundary layer) and updrafts (around eyewall), and thus stronger TC intensity. Meanwhile, the results that larger Ck/Cd corresponds with stronger TC in the mature stage are consistent with Emanuel’s potential intensity theory. The fact that Ck in OPT1 is evidently larger than the Ck from previous studies leads to produce a better TC intensity simulation. Generally, we should use more reasonable air–sea flux parameterization based on observation to improve TC intensity simulation.
Discrete Single-Factor Extension of the Exponential Distribution: Features and Modeling
Authors: El-Morshedy Mahmoud , Shahen Hend S. , Almohaimeed Bader , Eliwa Mohamed S.
Published: December 2022

The importance of counting data modeling and its applications to real-world phenomena has been highlighted in several research studies. The present study focuses on a one-parameter discrete distribution that can be derived via the survival discretization approach. The proposed model has explicit forms for its statistical properties. It can be applied to discuss asymmetric “right skewed” data with long “heavy” tails. Its failure rate function can be used to discuss the phenomena with a monotonically decreasing or unimodal failure rate shape. Further, it can be utilized as a probability tool to model and discuss over- and under-dispersed data. Various estimation techniques are reported and discussed in detail. A simulation study is performed to test the property of the estimator. Finally, three real data sets are analyzed to prove the notability of the introduced model.
Statistical Inference of the Beta Binomial Exponential 2 Distribution with Application to Environmental Data
Authors: Hassan Osama H. Mahmoud , Elbatal Ibrahim , Al-Nefaie Abdullah H. , El-Saeed Ahmed R.
Published: December 2022

A new four-parameter lifetime distribution called the beta binomial exponential 2 (BBE2) distribution is proposed. Some mathematical features, including quantile function, moments, generating function and characteristic function, of the BBE2 distribution, are computed. When the life test is truncated at a predetermined time, acceptance sampling plans (ASP) are constructed for the BBE2 distribution. The truncation time is supposed to represent the median lifetime of the BBE2 distribution with predetermined factors for the smallest sample size required to guarantee that the prescribed life test is achieved at a given consumer’s risk. Some numerical results for a given consumer’s risk, BBE2 distribution parameters and truncation time are derived. Classical (maximum likelihood and maximum product of spacing estimation methods) and Bayesian estimation approaches are utilized to estimate the model parameters. The performance of the model parameters is examined through the simulation study by using the three different approaches of estimation. Subsequently, we examine real-world data applications to demonstrate the versatility and potential of the BBE2 model. A real-world application demonstrates that the new distribution can offer a better fit than other competitive lifetime models.
The Boundary Homotopy Retract on the Scalar Hairy Charged Black Hole Spacetime
Authors: Abu-Saleem Mohammed , Taani Ali
Published: December 2022

In this paper, we investigate and define the topology of some astrophysical phenomena, like the hairy (scalarized) charged black hole spacetime, to improve our understanding of the kinematics and dynamics of their nature. We use the Lagrangian equation to find different types of geodesic equations. This can be done under some conditions for the variations of the Cosmological constant and Newton’s constant. We show how to induce the two types (null and spacelike) of geodesics as boundary retractions, in order to obtain the boundary homotopy retract of the scalar charged black hole. These types are used the Lagrangian equation in a 4-D scalar charged black hole to explain the event horizon for this black hole.
Direct Constructions of Uniform Designs under the Weighted Discrete Discrepancy
Authors: Wang Jiaqi , Tang Yu
Published: December 2022

Uniform designs are widely used in many fields in view of their ability to reduce experimentalcosts. In a lot of practical cases, different factors may take different numbers of values, so a mixed-level uniform design is needed. Since it is not reasonable to use the uniformity measure with the same weight for factors with different levels, the weighted discrete discrepancy was proposed in the existing literature. This paper discusses the construction method of mixed-level uniform designs under the weighted discrete discrepancy. The underlying method is to utilize some properties of partitioned difference families (PDFs) to obtain an infinite class of uniformly resolvable weighted balanced designs (URWBDs), which can directly produce corresponding uniform designs. Some examples are presented to illustrate the methods.
In Silico Study of Mangostin Compounds and Its Derivatives as Inhibitors of α-Glucosidase Enzymes for Anti-Diabetic Studies
Authors: Maulana Ahmad Fariz , Sriwidodo Sriwidodo , Rukayadi Yaya , Maksum Iman Permana
Published: December 2022

Diabetes is a chronic disease with a high mortality rate worldwide and can cause other diseases such as kidney damage, narrowing of blood vessels, and heart disease. The concomitant use of drugs such as metformin, sulfonylurea, miglitol, and acarbose may cause side effects with long-term administration. Therefore, natural ingredients are the best choice, considering that their long-term side effects are not significant. One of the compounds that can be used as a candidate antidiabetic is mangostin; however, information on the molecular mechanism needs to be further analyzed through molecular docking, simulating molecular dynamics, and testing the in silico antidiabetic potential. This study focused on modeling the protein structure, molecular docking, and molecular dynamics simulations and analyses. This process produces RMSD values, free energies, and intermolecular hydrogen bonding. Based on the analysis results, all molecular dynamics simulations can occur under physiological conditions, and γ-mangostin is the best among the test compounds.
Geographically Disperse, Culturable Seed-Associated Microbiota in Forage Plants of Alfalfa (Medicago sativa L.) and Pitch Clover (Bituminaria bituminosa L.): Characterization of Beneficial Inherited Strains as Plant Stress-Tolerance Enhancers
Authors: Niza-Costa Marla , Rodríguez-dos Santos Ana Sofía , Rebelo-Romão Inês , Ferrer María Victoria , Sequero López Cristina , Vílchez Juan Ignacio
Published: December 2022

Agricultural production is being affected by increasingly harsh conditions caused by climate change. The vast majority of crops suffer growth and yield declines due to a lack of water or intense heat. Hence, commercial legume crops suffer intense losses of production (20–80%). This situation is even more noticeable in plants used as fodder for animals, such as alfalfa and pitch trefoil, since their productivity is linked not only to the number of seeds produced, but also to the vegetative growth of the plant itself. Thus, we decided to study the microbiota associated with their seeds in different locations on the Iberian Peninsula, with the aim of identifying culturable bacteria strains that have adapted to harsh environments and that can be used as biotreatments to improve plant growth and resistance to stress. As potentially inherited microbiota, they may also represent a treatment with medium- and long-term adaptative effects. Hence, isolated strains showed no clear relationship with their geographical sampling location, but had about 50% internal similarity with their model plants. Moreover, out of the 51 strains isolated, about 80% were capable of producing biofilms; around 50% produced mid/high concentrations of auxins and grew notably in ACC medium; only 15% were characterized as xerotolerant, while more than 75% were able to sporulate; and finally, 65% produced siderophores and more than 40% produced compounds to solubilize phosphates. Thus, Paenibacillus amylolyticus BB B2-A, Paenibacillus xylanexedens MS M1-C, Paenibacillus pabuli BB Oeiras A, Stenotrophomonas maltophilia MS M1-B and Enterobacter hormaechei BB B2-C strains were tested as plant bioinoculants in lentil plants (Lens culinaris Medik.), showing promising results as future treatments to improve plant growth under stressful conditions.
Foliar Spray or Soil Drench: Microalgae Application Impacts on Soil Microbiology, Morpho-Physiological and Biochemical Responses, Oil and Fatty Acid Profiles of Chia Plants under Alkaline Stress
Authors: Youssef Samah M. , El-Serafy Rasha S. , Ghanem Kholoud Z. , Elhakem Abeer , Abdel Aal Azza A.
Published: December 2022

Alkaline soil inhibits the growth and productivity of chia plants (Salvia hispanica L.). Microalgae as biofertilizers have been reported to induce alkalinity tolerance and enhance yield and quality. However, limited information is known concerning the influence of microalgae application on medical plants, including chia. Our experiments were performed to evaluate the effect of microalgae strains of Arthrospira platensis, Chlorella vulgaris, Nostoc muscorum, and Anabaena azollae with two application methods, foliar spray and soil drench, on morpho-physiological and biochemical parameters, yield, seed and oil quality, and fatty acid profiles of chia plants cultivated under alkaline soil conditions, as well as the on soil microbial activity. The results obtained reveal that both application methods positively influenced the growth and productivity of chia plants. However, the foliar application showed significant differences in the herb’s fresh and dry weights and leaf pigments, whereas the drenching application caused more effect than the foliar spray application at the reproductive stage. Untreated chia plants showed a slight decline in the growth, productivity, and antioxidant level with an increase in Na content. However, microalgae applications significantly ameliorated these impacts as they induced an enhancement in the growth, leaf pigments, total protein and carbohydrate contents, nutrient content, seed and oil yields, as well as an increase in linolenic and linoleic fatty acids, with a reduction in saturated fatty acids, namely, palmitic and lauric acid. Soil drenching generated an improvement in the soil microbial activity and caused a reduction in the pH. The treatment of A. platensis with drenching application resulted in higher seed and oil yield, with an increase of 124 and 263.3% in seed and oil yield, respectively.
Genome-Wide Association Study Revealed the Effect of rs312715211 in ZNF652 Gene on Abdominal Fat Percentage of Chickens
Authors: Zhu Yuting , Liu Xiaojing , Wang Yongli , Liu Lu , Wang Yidong , Zhao Guiping , Wen Jie , Cui Huanxian
Published: December 2022

Abdominal fat percentage (AFP) is an important economic trait in chickens. Intensive growth selection has led to the over-deposition of abdominal fat in chickens, but the genetic basis of AFP is not yet clear. Using 520 female individuals from selection and control lines of Jingxing yellow chicken, we investigated the genetic basis of AFP using a genome-wide association study (GWAS) and fixation indices (FST). A 0.15 MB region associated with AFP was located on chromosome 27 and included nine significant single nucleotide polymorphisms (SNPs), which could account for 3.34–5.58% of the phenotypic variation. In addition, the π value, genotype frequency, and dual-luciferase results identified SNP rs312715211 in the intron region of ZNF652 as the key variant. The wild genotype was associated with lower AFP and abdominal fat weight (AFW), but higher body weight (BW). Finally, annotated genes based on the top 1% SNPs were used to investigate the physiological function of ZNF652. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that ZNF652 may reduce AFW and BW in broilers through the TGF-β1/SMad2/3 and MAPK/FoxO pathways via EGFR and TGFB1. Our findings elucidated the genetic basis of chicken AFP, rs312715211 on the ZNF652 gene, which can affect BW and AFW and was the key variant associated with AFP. These data provide new insight into the genetic mechanism underlying AF deposition in chickens and could be beneficial in breeding chickens for AF.
Paramecium bursaria as a Potential Tool for Evaluation of Microplastics Toxicity
Authors: Zhang Jianhua , Li Changhong , Chen Xiangrui , Li Yunqian , Fei Chenjie , Chen Jiong
Published: December 2022

Microplastics (MPs) are normally defined as small plastic wastes with a size of 1 μm to 5 mm in diameter. This tiny plastic debris is abundant in aquatic systems and poses a great threat to aquatic biota. To date, toxicological assessment of MPs is predominantly dependent on metazoan animals, although their applications are sometimes limited due to the high cost, narrow ecological niche, or ethical considerations. In this regard, unicellular eukaryotes (i.e., protozoa) that are ubiquitously present in nature represent a promising alternative for evaluating the toxicity of MPs. In this study, we selected Paramecium bursaria (P. bursaria) as a representative of protozoa and further investigated behavioral and molecular changes in MPs-exposed P. bursaria. Our results showed that following MPs uptake, P. bursaria exhibited various changes, including anomalies in swimming patterns, reduction in moving speed, impairment of avoidance behavior, elevation of oxidative stress, and potential disturbance of endosymbiosis. These elicited changes in P. bursaria in response to MPs exposure were pronounced and measurable. Overall, this study demonstrated that P. bursaria could serve as a promising alternative for the toxicological assessment of MPs and may be further applied to evaluate the toxicity of other environmental contaminants.
Influence of Diets Enriched with Flavonoids (Cocoa and Hesperidin) on the Systemic Immunity of Intensively Trained and Exhausted Rats
Authors: Ruiz-Iglesias Patricia , Massot-Cladera Malén , Pérez-Cano Francisco J. , Castell Margarida
Published: December 2022

The aim of this study was to establish the influence of flavonoid-enriched diets on the immune alterations induced by an intensive training and a final exhaustion test in rats. A flavanol-enriched diet (with 10% cocoa, C10 diet) and a flavanol and flavanone-enriched diet (C10 plus 0.5% hesperidin, CH diet) were used. Lewis rats were fed either a standard diet, C10 diet or CH diet while they were submitted to an intensive running training on a treadmill. After 6 weeks, samples were obtained 24 h after performing a regular training (T groups) and after carrying out a final exhaustion test (TE groups). The C10 diet attenuated the increase in plasma cortisol induced by exhaustion, while both the C10 and the CH diets prevented the alterations in the spleen Th cell proportion. The experimental diets also induced an increase in serum immunoglobulin concentration and an enhancement of spleen natural killer cytotoxicity, which may be beneficial in situations with a weakened immunity. Most of the effects observed in the CH groups seem to be due to the cocoa content. Overall, a dietary intervention with flavonoids enhances immune function, partially attenuating the alterations in systemic immunity induced by intensive training or exhausting exercise.
The Effect of Novel Selenopolysaccharide Isolated from Lentinula edodes Mycelium on Human T Lymphocytes Activation, Proliferation, and Cytokines Synthesis
Authors: Roszczyk Aleksander , Zych Michał , Zielniok Katarzyna , Krata Natalia , Turło Jadwiga , Klimaszewska Marzenna , Zagożdżon Radosław , Kaleta Beata
Published: December 2022

Polysaccharides isolated from Lentinula edodes are bioactive compounds with immunomodulatory properties. In our previous studies from L. edodes mycelium, we have isolated a selenium(Se)-enriched fraction (named Se-Le-30), a mixture of linear 1,4-α-glucan and linear 1,3-β- and 1,6-β-glucans. In this study, we analyzed the effects of Se-Le-30 on the activation and proliferation of human T lymphocytes stimulated by anti-CD3 and anti-CD3/CD28 antibodies (Abs) and on the production of cytokines by peripheral blood mononuclear cells (PBMCs). Se-Le-30 had effects on T cell proliferation induced by Abs against CD3 and CD28. It significantly inhibited the proliferation of CD3-stimulated CD4+ and CD8+ T cells and enhanced the proliferation of CD4+ T cells stimulated with anti-CD3/CD28 Ab. Moreover, Se-Le-30 downregulated the number of CD3-stimulated CD4+CD69+ cells, CD4+CD25+ cells, as well as CD8+CD25+ cells, and upregulated the expression of CD25 marker on CD4+ and CD8+ T cells activated with anti-CD3/CD28 Abs. Furthermore, Se-Le-30 enhanced the synthesis of IFN-γ by the unstimulated and anti-CD3/CD28-stimulated PBMCs, inhibited synthesis of IL-2 and IL-4 by CD3-stimulated cells, and augmented the synthesis of IL-6 and IL-10 by unstimulated, CD3-stimulated, and CD3/CD28-stimulated PBMCs. Together, we demonstrated that Se-Le-30 exerts immunomodulatory effects on human T lymphocytes. These observations are of importance for the prospective use of Se-Le-30 in research or as a therapeutic compound.
One-Carbon and Polyamine Metabolism as Cancer Therapy Targets
Authors: Islam Anowarul , Shaukat Zeeshan , Hussain Rashid , Gregory Stephen L.
Published: December 2022

Cancer metabolic reprogramming is essential for maintaining cancer cell survival and rapid replication. A common target of this metabolic reprogramming is one-carbon metabolism which is notable for its function in DNA synthesis, protein and DNA methylation, and antioxidant production. Polyamines are a key output of one-carbon metabolism with widespread effects on gene expression and signaling. As a result of these functions, one-carbon and polyamine metabolism have recently drawn a lot of interest for their part in cancer malignancy. Therapeutic inhibitors that target one-carbon and polyamine metabolism have thus been trialed as anticancer medications. The significance and future possibilities of one-carbon and polyamine metabolism as a target in cancer therapy are discussed in this review.
Oxidative Stress and Phototherapy in Atopic Dermatitis: Mechanisms, Role, and Future Perspectives
Authors: Borgia Francesco , Li Pomi Federica , Vaccaro Mario , Alessandrello Clara , Papa Vincenzo , Gangemi Sebastiano
Published: December 2022

Atopic dermatitis is a chronic inflammatory skin disease in which the overproduction of reactive oxygen species plays a pivotal role in the pathogenesis and persistence of inflammatory lesions. Phototherapy represents one of the most used therapeutic options, with benefits in the clinical picture. Studies have demonstrated the immunomodulatory effect of phototherapy and its role in reducing molecule hallmarks of oxidative stress. In this review, we report the data present in literature dealing with the main signaling molecular pathways involved in oxidative stress after phototherapy to target atopic dermatitis-affected cells. Since oxidative stress plays a pivotal role in the pathogenesis of atopic dermatitis and its flare-up, new research lines could be opened to study new drugs that act on this mechanism, perhaps in concert with phototherapy.
Differential Regulation of MMPs, Apoptosis and Cell Proliferation by the Cannabinoid Receptors CB1 and CB2 in Vascular Smooth Muscle Cells and Cardiac Myocytes
Authors: Greiner Bettina , Sommerfeld Manuela , Kintscher Ulrich , Unger Thomas , Kappert Kai , Kaschina Elena
Published: December 2022

Cannabinoids (CB) are implicated in cardiovascular diseases via the two main receptor subtypes CB1R and CB2R. This study investigated whether cannabinoids regulate the activity of matrix metalloproteases (MMP-2, MMP-9) in vascular smooth muscle cells (VSMCs) and in cells of cardiac origin (H9c2 cell line). The influence of CB1- and CB2 receptor stimulation or inhibition on cell proliferation, apoptosis and glucose uptake was also evaluated. We used four compounds that activate or block CB receptors: arachidonyl-2-chloroethylamide (ACEA)—CB1R agonist, rimonabant—CB1R antagonist, John W. Huffman (JWH133)—CB2R agonist and CB2R antagonist—6-Iodopravadoline (AM630). Treatment of cells with the CB2R agonist JWH133 decreased cytokine activated secretion of proMMP-2, MMP-2 and MMP-9, reduced Fas ligand and caspase-3-mediated apoptosis, normalized the expression of TGF-beta1 and prevented cytokine-induced increase in glucose uptake into the cell. CB1R inhibition with rimonabant showed similar protective properties as the CB2R agonist JWH133, but to a lesser extent. In conclusion, CB1R and CB2R exert opposite effects on cell glucose uptake, proteolysis and apoptosis in both VSMCs and H9c2 cells. The CB2R agonist JWH133 demonstrated the highest protective properties. These findings may pave the way to a new treatment of cardiovascular diseases, especially those associated with extracellular matrix degradation.
Ruminococcaceae_UCG-013 Promotes Obesity Resistance in Mice
Authors: Feng Jinlian , Ma Hongliang , Huang Yiting , Li Jiangchao , Li Weidong
Published: December 2022

Alterations in the gut microbiome have been linked to obesity and type 2 diabetes, in epidemiologic studies and studies of fecal transfer effects in germ-free mice. Here, we aimed to identify the effects of specific gut microbes on the phenotype of mice fed a high-fat diet (HFD). After eight weeks of HFD feeding, male C57BL/6J mice in the HFD group ranking in the upper and lower quartiles for body weight gain were considered obese prone and obese resistant, respectively. 16S rRNA gene sequencing was used to determine the composition of the intestinal microbiota, and fecal transplantation (FMT) was conducted to determine whether the microbiota plays a causal role in phenotypic variation. Ruminococcaceae_UCG-013 was more abundant in the gut microbes of mice with a lean phenotype than in those with an obese phenotype. Ruminococcaceae_UCG-013 was identified as the most significant biomarker for alleviating obesity by random forest analysis. In a correlation analysis of serum parameters and body weight, Ruminococcaceae_UCG-013 was positively associated with serum HDL-C levels and negatively associated with serum TC, TG, and LDL-C levels. To conclude, Ruminococcaceae_UCG-013 was identified as a novel microbiome biomarker for obesity resistance, which may serve as a basis for understanding the critical gut microbes responsible for obesity resistance. Ruminococcaceae_UCG-013 may serve as a target for microbiome-based diagnoses and treatments in the future.
Amyloid Disassembly: What Can We Learn from Chaperones?
Authors: Almeida Zaida L. , Brito Rui M. M.
Published: December 2022

Protein aggregation and subsequent accumulation of insoluble amyloid fibrils with cross-β structure is an intrinsic characteristic of amyloid diseases, i.e., amyloidoses. Amyloid formation involves a series of on-pathway and off-pathway protein aggregation events, leading to mature insoluble fibrils that eventually accumulate in multiple tissues. In this cascade of events, soluble oligomeric species are formed, which are among the most cytotoxic molecular entities along the amyloid cascade. The direct or indirect action of these amyloid soluble oligomers and amyloid protofibrils and fibrils in several tissues and organs lead to cell death in some cases and organ disfunction in general. There are dozens of different proteins and peptides causing multiple amyloid pathologies, chief among them Alzheimer’s, Parkinson’s, Huntington’s, and several other neurodegenerative diseases. Amyloid fibril disassembly is among the disease-modifying therapeutic strategies being pursued to overcome amyloid pathologies. The clearance of preformed amyloids and consequently the arresting of the progression of organ deterioration may increase patient survival and quality of life. In this review, we compiled from the literature many examples of chemical and biochemical agents able to disaggregate preformed amyloids, which have been classified as molecular chaperones, chemical chaperones, and pharmacological chaperones. We focused on their mode of action, chemical structure, interactions with the fibrillar structures, morphology and toxicity of the disaggregation products, and the potential use of disaggregation agents as a treatment option in amyloidosis.
Effectiveness and Safety Profiles of Biological Therapies in Inflammatory Bowel Disease: Real Life Data from an Active Pharmacovigilance Project
Authors: Barbieri Maria Antonietta , Viola Anna , Cicala Giuseppe , Spina Edoardo , Fries Walter
Published: December 2022

Post-marketing surveillance is essential to evaluate the risk/benefit profile of drugs; however, pharmacovigilance studies comparing persistence and safety of biologic therapies in patients with inflammatory bowel disease (IBD) are scant. The aim of this study was to prospectively investigate persistence together with safety profiles of biologics in a cohort of patients diagnosed with Crohn’s Disease (CD) or ulcerative colitis (UC) followed by the IBD unit of Messina and treated with infliximab (IFX), adalimumab (ADA), golimumab (GOL), vedolizumab (VED), and ustekinumab (UST) from 2017 through 2021. Descriptive and treatment persistence analyses with predictors for discontinuation and occurrence of adverse drug reactions (ADRs) were performed. A total of 675 IBD patients were enrolled. A higher persistence rate was noted for UST and ADA in the first year (83.8% and 83.1%, respectively) and for IFX in the fifth year of treatment (58.1%). GOL, VED, and UST—all used as second/third-line therapies—seemed to have a higher risk of non-persistence than IFX (in order HR: 2.19; CI 95%: 1.33–3.61, 1.45; 1.04–2.04, 2.25; 1.25–4.07) as well as switchers and those who had at least one ADR (18.1; 13.22–24.68 and 1.55; 1.20–1.99, respectively). The reported ADRs, which were generally mild–moderate, were largely known. However, real-world data should be implemented to further study undetected safety concerns, including risk of malignancy.
Synbiotic Intervention Ameliorates Oxidative Stress and Gut Permeability in an In Vitro and In Vivo Model of Ethanol-Induced Intestinal Dysbiosis
Authors: Patel Dhara , Desai Chirayu , Singh Deepmala , Soppina Virupakshi , Parwani Kirti , Patel Farhin , Mandal Palash
Published: December 2022

Alcoholic liver disease (ALD) alters gut microbiota and tight junctions, causing bacterial components to enter the portal vein and induce oxidative stress-induced inflammation in the liver. Only corticosteroids and liver transplants are treatment options for severe alcoholic hepatitis. ALD’s pathophysiology is unknown. However, acetaldehyde’s toxic effects cause oxidative stress and intestinal permeability. This study investigates the influence of a synbiotic (a combination of aged garlic extract (AGE) and Lactobacillus rhamnosus MTCC1423) on colonic oxidative stress and inflammation in ALD male Wistar rats and Caco2 cells. MDA measurement by HPLC in CaCo2 cells, blood serum, and colon tissue demonstrated that synbiotic treatment in the ALD model reduces oxidative stress. Further, fecal high-throughput 16S rRNA gene sequencing revealed the microbiome’s shift towards Firmicutes in the synbiotic group compared to ethanol. In addition, DCFDA labeling and H/E staining demonstrate that the synbiotic is beneficial in inhibiting the development of ALD. In the colon, the synbiotic reduces the activation of CYP2E1 and the inflammatory markers TNF-a and IL-6 while elevating the mRNA expression of ZO-1, occludin, and IL-10. Synbiotics colonize Lactobacillus to restore barrier function and microbiota and reduce colon oxidative stress. Thus, a synbiotic combination can be used in ALD treatment.
Hypoxia-Induced Downregulation of miR-29 in Renal Tumor Cells Affects Collagen IV Subunit Expression through Multiple Sites
Authors: Liu Chuncheng , Liu Linan , Bo Jinlai , Lu Xian , Qu Donghui , Liu Gehui , Jiang Zhiyan , Cai Lu
Published: December 2022

Multiple tumor exacerbations and treatment procedures, such as extracellular matrix remodeling, metabolic reprogramming, immunological evasion, and resistance to chemotherapy and radiotherapy, are influenced by intratumoral hypoxia. It is becoming increasingly clear how hypoxia interacts with the extracellular matrix and how this affects the growth of cancer. We analyzed the published sequencing results of hypoxia-stressed mouse kidney tumor cells and found that the expression of miR-29b was significantly downregulated. There are several sites that are complementary to the miR-29 seed sequence in the 3’ non-coding regions (3’UTRs) of various extracellular matrix-related genes, including collagen IV. We analyzed the sequences of the 3’UTRs of different subunits of collagen IV in different species and constructed the corresponding phylogenetic trees. We found that the 3’UTRs of Col4a1 and Col4a4 may have been subjected to particular evolutionary pressures. By cloning the 3’UTRs of collagen IV subunits into the psiCHECKTM-2 vector, we found that seven of the eight sites in the Col4a3–Col4a6 gene complementary to miR-29 were significantly repressed by miR-29a, b (except for the 7774–7781 of Col4a3 gene). The inhibitory efficiency of miR-29a, b on these seven sites was between 27% and 57%. The research on the regulation of miR-29 and extracellular matrix by hypoxia can provide a theoretical basis for tumor and fibrosis research and treatment.
Prognostic and Predictive Biomarkers in Head and Neck Squamous Cell Carcinoma Treated with Radiotherapy—A Systematic Review
Authors: Schanne Daniel H. , Koch Alexander , Elicin Olgun , Giger Roland , Medová Michaela , Zimmer Yitzhak , Aebersold Daniel M.
Published: December 2022

Background: Radiotherapy is a mainstay in head and neck squamous cell carcinoma (HNSCC) treatment but is mostly applied without stratification by molecular diagnostics. Development of reliable biomarkers may have the potential to improve radiotherapy (RT) efficacy and reduce toxicity. We conducted a systematic review to summarize the field of biomarkers in HNSCC treated by RT. Methods: Pubmed and EMBASE were searched independently by two researchers following pre-defined inclusion and exclusion criteria. Z curves were generated to investigate publication bias. OncoKB was used for identification of druggable targets. Results: 134 manuscripts remained for data extraction. 12% of tumors were AJCC/UICC stage I–II and 82% were stage III–IV. The most common biomarkers were proteins (39%), DNA (14%) and mRNA (9%). Limiting analysis to prospective data and statistically significant results, we found three potentially druggable targets: ERCC2, PTCH1 and EGFR. Regarding data quality, AJCC/UICC stage was missing in 32% of manuscripts. 73% of studies were retrospective and only 7% were based on prospective randomized trials. Z-curves indicated the presence of publication bias. Conclusion: An abundance of potential biomarkers in HNSCC is available but data quality is limited by retrospective collection, lack of validation and publication bias. Improved study design and reporting quality might accelerate successful development of personalized treatments in HNSCC.
Cytokine Profiles Differentiate Symptomatic from Asymptomatic PTSD in Service Members and Veterans with Chronic Traumatic Brain Injury
Authors: Smith Ethan G. , Hentig James , Martin Carina , Wagner Chelsea , Guedes Vivian A. , Edwards Katie A. , Devoto Christina , Dunbar Kerri , Roy Michael J. , Gill Jessica M.
Published: December 2022

Traumatic brain injuries (TBI) and posttraumatic stress disorder (PTSD) are commonly observed comorbid occurrences among military service members and veterans (SMVs). In this cross-sectional study, SMVs with a history of TBI were stratified into symptomatic and asymptomatic PTSD groups based on posttraumatic stress checklist-civilian (PCL-C) total scores. Blood-based biomarkers were assessed, and significant differential markers were associated with scores from multiple neurobehavioral self-report assessments. PCL-C cutoffs were total scores >50 (PTSD symptomatic) and <25 (asymptomatic). Cytokines IL6, IL8, TNFα, and IL10 were significantly elevated (p < 0.05–0.001) in the TBI+/PTSD symptomatic group compared to the TBI+/asymptomatic group. Cytokine levels of IL8, TNFα, and IL10 were strongly associated with PCL-C scores (0.356 < r > 0.624 for all, p < 0.01 for all), while TNFα and IL10 were additionally associated with NSI totals (r = 0.285 and r = 0.270, p < 0.05, respectively). This is the first study focused on PTSD symptom severity to report levels of circulating pro-inflammatory IL8, specifically in SMVs with TBI. These data suggest that within the military TBI population, there are unique cytokine profiles that relate to neurobehavioral outcomes associated with TBI and PTSD.
Delphi-Based Consensus on Interstitial Lung Disease Screening in Patients with Connective Tissue Diseases (Croatian National-Based Study)
Authors: Radić Mislav , Novak Srđan , Barešić Marko , Hećimović Ana , Perković Dijana , Tekavec-Trkanjec Jasna , Mayer Miroslav , Prus Višnja , Morović-Vergles Jadranka , Marasović Krstulović Daniela , Cerovec Mislav , Bulat Kardum Ljiljana , Samaržija Miroslav , Anić Branimir
Published: December 2022

The aim of this study was to develop a Croatian Delphi-based expert consensus for screening interstitial lung disease (ILD) associated with connective tissue disease (CTD). A systematic literature review was conducted on risk factors for the development of ILD, prevalence and incidence of ILD, diagnostic and screening methods for ILD, and prognosis of ILD in idiopathic inflammatory myopathy (IIM), mixed connective tissue disease (MCTD), primary Sjögren’s syndrome (pSS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc) were performed. Based on the evidence found, experts developed questionnaires for screening and monitoring ILD in each CTD, which were provided via an online survey. Following the electronic survey, two screening algorithms were developed based on the consensus opinions. The detection strategy for ILD included high-resolution computed tomography (HRCT) in addition to pulmonary function testing for IIM, MCTD, and SSc. and pulmonary function testing for newly diagnosed pSS, RA and SLE. However, in patients with identified risk factors for ILD HRCT, these tests should also be performed. A screening strategy for early identification of patients with various CTD-ILD was first developed by a multidisciplinary team of rheumatologists, pulmonologists, and radiologists to identify early CTD patients at risk of ILD, a severe extra-articular manifestation of CTD.
Arsenic Trioxide Triggers Apoptosis of Metastatic Oral Squamous Cells Carcinoma with Concomitant Downregulation of GLI1 in Hedgehog Signaling
Authors: Nogueira Raphael Luís Rocha , de Araújo Taís Bacelar Sacramento , Valverde Ludmila Faro , Silva Viviane Aline Oliveira , Cavalcante Bruno Raphael Ribeiro , Rossi Erik Aranha , Allahdadi Kyan James , dos Reis Mitermayer Galvão , Pereira Thiago Almeida , Coletta Ricardo D. , Bezerra Daniel Pereira , de Freitas Souza Bruno Solano , Dias Rosane Borges , Rocha Clarissa A. Gurgel
Published: December 2022

Given the lack of advances in Oral Squamous Cell Carcinoma (OSCC) therapy in recent years, pharmacological strategies to block OSCC-related signaling pathways have gained prominence. The present study aimed to evaluate the therapeutic potential of Arsenic Trioxide (ATO) concerning its antitumoral effects and the inhibition of the Hedgehog (HH) pathway in OSCC. Initially, ATO cytotoxicity was assessed in a panel of cell lines. Cell viability, cell cycle, death patterns, and cell morphology were analyzed, as well as the effect of ATO on the expression of HH pathway components. After the cytotoxic assay, HSC3 cells were chosen for all in vitro assays. ATO increased apoptotic cell death and nuclear fragmentation in the sub-G1 cell cycle phase and promoted changes in cell morphology. In addition, the reduced expression of GLI1 indicated that ATO inhibits HH activity. The present study provides evidence of ATO as an effective cytotoxic drug for oral cancer treatment in vitro.
Artificial Intelligence: The Milestone in Modern Biomedical Research
Authors: Athanasopoulou Konstantina , Daneva Glykeria N. , Adamopoulos Panagiotis G. , Scorilas Andreas
Published: December 2022

In recent years, the advent of new experimental methodologies for studying the high complexity of the human genome and proteome has led to the generation of an increasing amount of digital information, hence bioinformatics, which harnesses computer science, biology, and chemistry, playing a mandatory role for the analysis of the produced datasets. The emerging technology of Artificial Intelligence (AI), including Machine Learning (ML) and Artificial Neural Networks (ANNs), is nowadays at the core of biomedical research and has already paved the way for significant breakthroughs in both biological and medical sciences. AI and computer science have transformed traditional medicine into modern biomedicine, thus promising a new era in systems biology that will enhance drug discovery strategies and facilitate clinical practice. The current review defines the main categories of AI and thoroughly describes the fundamental principles of the widely used ML, ANNs and DL approaches. Furthermore, we aim to underline the determinant role of AI-based methods in various biological research fields, such as proteomics and drug design techniques, and finally, investigate the implication of AI in everyday clinical practice and healthcare systems. Finally, this review also highlights the challenges and future directions of AI in Modern Biomedical study.
The Roadmap of Graphene-Based Sensors: Electrochemical Methods for Bioanalytical Applications
Authors: Ashraf Ghazala , Aziz Ayesha , Iftikhar Tayyaba , Zhong Zi-Tao , Asif Muhammad , Chen Wei
Published: December 2022

Graphene (GR) has engrossed immense research attention as an emerging carbon material owing to its enthralling electrochemical (EC) and physical properties. Herein, we debate the role of GR-based nanomaterials (NMs) in refining EC sensing performance toward bioanalytes detection. Following the introduction, we briefly discuss the GR fabrication, properties, application as electrode materials, the principle of EC sensing system, and the importance of bioanalytes detection in early disease diagnosis. Along with the brief description of GR-derivatives, simulation, and doping, classification of GR-based EC sensors such as cancer biomarkers, neurotransmitters, DNA sensors, immunosensors, and various other bioanalytes detection is provided. The working mechanism of topical GR-based EC sensors, advantages, and real-time analysis of these along with details of analytical merit of figures for EC sensors are discussed. Last, we have concluded the review by providing some suggestions to overcome the existing downsides of GR-based sensors and future outlook. The advancement of electrochemistry, nanotechnology, and point-of-care (POC) devices could offer the next generation of precise, sensitive, and reliable EC sensors.
Prolonged Longitudinal Transcutaneous Auricular Vagus Nerve Stimulation Effect on Striatal Functional Connectivity in Patients with Major Depressive Disorder
Authors: Zhang Shuai , He Jia-Kai , Zhong Gang-Liang , Wang Yu , Zhao Ya-Nan , Wang Lei , Li Shao-Yuan , Xiao Xue , Yang Zheng-Yi , Zhao Bin , Zhang Jin-Ling , Jiang Tian-Zi , Fang Ji-Liang , Rong Pei-Jing
Published: December 2022

Background: Transcutaneous auricular vagus nerve stimulation (taVNS) is effective for treating major depressive disorder (MDD). We aimed to explore the modulating effect of prolonged longitudinal taVNS on the striatal subregions’ functional connectivity (FC) in MDD patients. Methods: Sixteen MDD patients were enrolled and treated with taVNS for 8 weeks. Sixteen healthy control subjects (HCs) were recruited without intervention. The resting-state FC (rsFC) based on striatal subregion seed points and the Hamilton Depression Scale (HAMD) were evaluated in the MDD patients and HCs at baseline and after 8 weeks. A two-way ANCOVA test was performed on each rsFC metric to obtain the (group-by-time) interactions. Results: The rsFC values between the left ventral caudate (vCa) and right ventral prefrontal cortex (vPFC), and between the right nucleus accumbens (NAc) and right dorsal medial prefrontal cortex (dmPFC) and ventrolateral prefrontal cortex (vlPFC) are lower in the MDD patients compared to the HCs at baseline, and increase following taVNS; the rsFC values between the left vCa and right, superior occipital gyrus (SOG), and between the left dorsal caudate (dCa) and right cuneus are higher in MDD patients and decrease following taVNS. Conclusions: Prolonged longitudinal taVNS can modulate the striatum rsFC with the prefrontal cortex, occipital cortex, temporal cortex, and intra-striatum, and these changes partly underlie any symptomatic improvements. The results indicate that prolonged longitudinal taVNS may produce beneficial treatment effects by modulating the cortical striatum circuitry in patients with MDD.
Towards a Data-Rich Era: A Bibliometric Analysis of Construction Management from 2000 to 2020
Authors: Zhu Shiyao , Li Dezhi , Zhu Jin , Feng Haibo
Published: December 2022

The rapid development of new technologies has made the acquisition and processing of big data much easier and more accessible to various domains including construction management. This trend has resulted in numerous new technical or management issues in the field, as well as increased research needs. Thus, it is very necessary to invest and assess the past, present, and possible future developments of construction management-related studies. This paper provides a comprehensive bibliometric analysis of the articles published in this field over the previous two decades. The seven most popular research themes were identified and discussed with the data adopted in the related studies, including modern technology, waste management, performance management, risk management, project management, knowledge management, and organization management. Typical research data, research approaches, and future research directions were discussed. Emerging topics such as smart technology, sustainability, resilience, and human factors are suggested to be further explored in the domain. The review conducted in this study can provide some insights into what has been done and what can be achieved in future research in the construction management domain towards a data-rich era.
Individually Designed House in Finland: Perspectives of Architectural Experts and a Design Case Study
Authors: Saarinen Stina , Ilgın Hüseyin Emre , Karjalainen Markku , Hirvilammi Teemu
Published: December 2022

This article provides a comprehensive understanding of small house practices, including the perspective of Finnish architectural experts, by conducting semi-structured in-depth interviews and proposing an individually designed house case study with a particular focus on cost and quality. Key findings based on main themes including the role and qualifications of the architect, architect’s involvement, architect’s fee, reasons to hire an architect, implementation, quality, and cost, highlighted that: (1) architect can assist small house projects in many ways, such as accurately identifying the client’s needs, choosing the most suitable layout, and applications for building permits; (2) allocating sufficient time for planning an average of six months is critical for the thoughts of both the architect and the client to mature in peace; (3) the share of architectural design in the total cost of the project is around 3–5%; (4) it is estimated that the total amount of small houses designed by an architect is between 10–20%; (5) an architect’s typical client is reported to be those who dream of a long-term home and are concerned with aesthetics as well as functional quality; (6) the client is always satisfied with the quality of the house designed by the architect; (7) while an individually designed home may seem more costly than a prefab home, an architect-designed home can be affordable as long as the budget is known from the start of the project. It is believed that this paper will encourage the participation of architects in small house projects that will be expanded and established in the Finnish residential construction industry.