bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Endogenic and Exogenic Oxidative Stress Triggers on Pregnant Woman, Fetus, and Child
Authors: Osredkar Joško
Published: March 2023

In all living organisms, there is a delicate balance between oxidation caused by reactive species (RS, also called free radicals) and antioxidant defence [...]
HyperCys: A Structure- and Sequence-Based Predictor of Hyper-Reactive Druggable Cysteines
Authors: Gao Mingjie , Günther Stefan
Published: March 2023

The cysteine side chain has a free thiol group, making it the amino acid residue most often covalently modified by small molecules possessing weakly electrophilic warheads, thereby prolonging on-target residence time and reducing the risk of idiosyncratic drug toxicity. However, not all cysteines are equally reactive or accessible. Hence, to identify targetable cysteines, we propose a novel ensemble stacked machine learning (ML) model to predict hyper-reactive druggable cysteines, named HyperCys. First, the pocket, conservation, structural and energy profiles, and physicochemical properties of (non)covalently bound cysteines were collected from both protein sequences and 3D structures of protein–ligand complexes. Then, we established the HyperCys ensemble stacked model by integrating six different ML models, including K-nearest neighbors, support vector machine, light gradient boost machine, multi-layer perceptron classifier, random forest, and the meta-classifier model logistic regression. Finally, based on the hyper-reactive cysteines’ classification accuracy and other metrics, the results for different feature group combinations were compared. The results show that the accuracy, F1 score, recall score, and ROC AUC values of HyperCys are 0.784, 0.754, 0.742, and 0.824, respectively, after performing 10-fold CV with the best window size. Compared to traditional ML models with only sequenced-based features or only 3D structural features, HyperCys is more accurate at predicting hyper-reactive druggable cysteines. It is anticipated that HyperCys will be an effective tool for discovering new potential reactive cysteines in a wide range of nucleophilic proteins and will provide an important contribution to the design of targeted covalent inhibitors with high potency and selectivity.
The Influence of Bacteriophages on the Metabolic Condition of Human Fibroblasts in Light of the Safety of Phage Therapy in Staphylococcal Skin Infections
Authors: Kosznik-Kwaśnicka Katarzyna , Stasiłojć Małgorzata , Stasiłojć Grzegorz , Kaźmierczak Natalia , Piechowicz Lidia
Published: March 2023

Phage therapy has been successfully used as an experimental therapy in the treatment of multidrug-resistant strains of Staphylococcus aureus (MDRSA)-caused skin infections and is seen as the most promising alternative to antibiotics. However, in recent years a number of reports indicating that phages can interact with eukaryotic cells emerged. Therefore, there is a need to re-evaluate phage therapy in light of safety. It is important to analyze not only the cytotoxicity of phages alone but also the impact their lytic activity against bacteria may have on human cells. As progeny virions rupture the cell wall, lipoteichoic acids are released in high quantities. It has been shown that they act as inflammatory agents and their presence could lead to the worsening of the patient’s condition and influence their recovery. In our work, we have tested if the treatment of normal human fibroblasts with staphylococcal phages will influence the metabolic state of the cell and the integrity of cell membranes. We have also analyzed the effectiveness of bacteriophages in reducing the number of MDRSA attached to human fibroblasts and the influence of the lytic activity of phages on cell viability. We observed that, out of three tested anti-Staphylococcal phages—vB_SauM-A, vB_SauM-C and vB_SauM-D—high concentrations (109 PFU/mL) of two, vB_SauM-A and vB_SauM-D, showed a negative impact on the viability of human fibroblasts. However, a dose of 107 PFU/mL had no effect on the metabolic activity or membrane integrity of the cells. We also observed that the addition of phages alleviated the negative effect of the MDRSA infection on fibroblasts’ viability, as phages were able to effectively reduce the number of bacteria in the co-culture. We believe that these results will contribute to a better understanding of the influence of phage therapy on human cells and encourage even more studies on this topic.
Chalcones and Gastrointestinal Cancers: Experimental Evidence
Authors: Michalkova Radka , Kello Martin , Cizmarikova Martina , Bardelcikova Annamaria , Mirossay Ladislav , Mojzis Jan
Published: March 2023

Colorectal (CRC) and gastric cancers (GC) are the most common digestive tract cancers with a high incidence rate worldwide. The current treatment including surgery, chemotherapy or radiotherapy has several limitations such as drug toxicity, cancer recurrence or drug resistance and thus it is a great challenge to discover an effective and safe therapy for CRC and GC. In the last decade, numerous phytochemicals and their synthetic analogs have attracted attention due to their anticancer effect and low organ toxicity. Chalcones, plant-derived polyphenols, received marked attention due to their biological activities as well as for relatively easy structural manipulation and synthesis of new chalcone derivatives. In this study, we discuss the mechanisms by which chalcones in both in vitro and in vivo conditions suppress cancer cell proliferation or cancer formation.
Long Non-Coding RNA Malat1 Increases the Rescuing Effect of Quercetin on TNFα-Impaired Bone Marrow Stem Cell Osteogenesis and Ovariectomy-Induced Osteoporosis
Authors: Feng Lu , Yang Zhengmeng , Hou Nan , Wang Ming , Lu Xuan , Li Yucong , Wang Haixing , Wang Yaofeng , Bai Shanshan , Zhang Xiaoting , Lin Yuejun , Yan Xu , Lin Sien , Tortorella Micky D. , Li Gang
Published: March 2023

Osteoporosis, a common systematic bone homeostasis disorder related disease, still urgently needs innovative treatment methods. Several natural small molecules were found to be effective therapeutics in osteoporosis. In the present study, quercetin was screened out from a library of natural small molecular compounds by a dual luciferase reporter system. Quercetin was found to upregulate Wnt/β-catenin while inhibiting NF-κB signaling activities, and thereby rescuing osteoporosis-induced tumor necrosis factor alpha (TNFα) impaired BMSCs osteogenesis. Furthermore, a putative functional lncRNA, Malat1, was shown to be a key mediator in quercetin regulated signaling activities and TNFα-impaired BMSCs osteogenesis, as mentioned above. In an ovariectomy (OVX)-induced osteoporosis mouse model, quercetin administration could significantly rescue OVX-induced bone loss and structure deterioration. Serum levels of Malat1 were also obviously rescued in the OVX model after quercetin treatment. In conclusion, our study demonstrated that quercetin could rescue TNFα-impaired BMSCs osteogenesis in vitro and osteoporosis-induced bone loss in vivo, in a Malat1-dependent manner, suggesting that quercetin may serve as a therapeutic candidate for osteoporosis treatment.
Clinical and Mechanistic Implications of R-Loops in Human Leukemias
Authors: Lee Seo-Yun , Miller Kyle M. , Kim Jae-Jin
Published: March 2023

Genetic mutations or environmental agents are major contributors to leukemia and are associated with genomic instability. R-loops are three-stranded nucleic acid structures consisting of an RNA–DNA hybrid and a non-template single-stranded DNA. These structures regulate various cellular processes, including transcription, replication, and DSB repair. However, unregulated R-loop formation can cause DNA damage and genomic instability, which are potential drivers of cancer including leukemia. In this review, we discuss the current understanding of aberrant R-loop formation and how it influences genomic instability and leukemia development. We also consider the possibility of R-loops as therapeutic targets for cancer treatment.
GSK3β Inhibition Reduced Vascular Calcification in Ins2Akita/+ Mice
Authors: Boström Kristina I. , Qiao Xiaojing , Zhao Yan , Wu Xiuju , Zhang Li , Ma Jocelyn A. , Ji Jaden , Cai Xinjiang , Yao Yucheng
Published: March 2023

Endothelial–mesenchymal transition (EndMT) drives the endothelium to contribute to vascular calcification in diabetes mellitus. In our previous study, we showed that glycogen synthase kinase-3β (GSK3β) inhibition induces β-catenin and reduces mothers against DPP homolog 1 (SMAD1) to direct osteoblast-like cells toward endothelial lineage, thereby reducing vascular calcification in Matrix Gla Protein (Mgp) deficiency. Here, we report that GSK3β inhibition reduces vascular calcification in diabetic Ins2Akita/wt mice. Cell lineage tracing reveals that GSK3β inhibition redirects endothelial cell (EC)-derived osteoblast-like cells back to endothelial lineage in the diabetic endothelium of Ins2Akita/wt mice. We also find that the alterations in β-catenin and SMAD1 by GSK3β inhibition in the aortic endothelium of diabetic Ins2Akita/wt mice are similar to Mgp−/− mice. Together, our results suggest that GSK3β inhibition reduces vascular calcification in diabetic arteries through a similar mechanism to that in Mgp−/− mice.
Single Nucleotide Polymorphisms in the Vitamin D Metabolic Pathway and Their Relationship with High Blood Pressure Risk
Authors: Rojo-Tolosa Susana , Márquez-Pete Noelia , Gálvez-Navas José María , Pineda-Lancheros Laura Elena , Fernández-Alonso Andrea , Membrive-Jiménez Cristina , Ramírez-Tortosa María Carmen , Pérez-Ramírez Cristina , Jiménez-Morales Alberto
Published: March 2023

High blood pressure (HBP) is the leading risk factor for cardiovascular disease (CVD) and all-cause mortality worldwide. The progression of the disease leads to structural and/or functional alterations in various organs and increases cardiovascular risk. Currently, there are significant deficiencies in its diagnosis, treatment, and control. Vitamin D is characterized by its functional versatility and its involvement in countless physiological processes. This has led to the association of vitamin D with many chronic diseases, including HBP and CVD, due to its involvement in the regulation of the renin–angiotensin–aldosterone system. The aim of this study was to evaluate the effect of 13 single nucleotide polymorphisms (SNPs) related to the vitamin D metabolic pathway on the risk of developing HBP. An observational case-control study was performed, including 250 patients diagnosed with HBP and 500 controls from the south of Spain (Caucasians). Genetic polymorphisms in CYP27B1 (rs4646536, rs3782130, rs703842, and rs10877012), CYP2R1 rs10741657, GC rs7041, CYP24A1 (rs6068816, and rs4809957), and VDR (BsmI, Cdx2, FokI, ApaI, and TaqI) were analyzed by real-time PCR using TaqMan probes. Logistic regression analysis, adjusted for body mass index (BMI), dyslipidemia, and diabetes, showed that in the genotypic model, carriers of the GC rs7041 TT genotype were associated with a lower risk of developing HBP than the GG genotype (odds ratio (OR) = 0.44, 95% confidence interval (CI): 0.41–0.77, p = 0.005, TT vs. GG). In the dominant model, this association was maintained; carriers of the T allele showed a lower risk of developing HBP than carriers of the GG genotype (OR = 0.69, 95% CI: 0.47–1.03; TT + TG vs. GG, p = 0.010). Finally, in the additive model, consistent with previous models, the T allele was associated with a lower risk of developing HBP than the G allele (OR = 0.65, 95% CI: 0.40–0.87, p = 0.003, T vs. G). Haplotype analysis revealed that GACATG haplotypes for SNPs rs1544410, rs7975232, rs731236, rs4646536, rs703842, and rs10877012 were associated with a marginally significant lower risk of developing HBP (OR = 0.35, 95% CI: 0.12–1.02, p = 0.054). Several studies suggest that GC 7041 is associated with a lower active isoform of the vitamin D binding protein. In conclusion, the rs7041 polymorphism located in the GC gene was significantly associated with a lower risk of developing HBP. This polymorphism could therefore act as a substantial predictive biomarker of the disease.
Impaired Autophagy in Krabbe Disease: The Role of BCL2 and Beclin-1 Phosphorylation
Authors: Papini Nadia , Todisco Roberta , Giussani Paola , Dei Cas Michele , Paroni Rita , Giallanza Chiara , Tringali Cristina
Published: March 2023

Autophagic impairment was identified in many lysosomal storage diseases and adult neurodegenerative diseases. It seems that this defect could be directly related to the appearance of a neurodegenerative phenotype and could contribute to worsen metabolite accumulation and lysosomal distress. Thus, autophagy is becoming a promising target for supportive therapies. Autophagy alterations were recently identified also in Krabbe disease. Krabbe disease is characterized by extensive demyelination and dysmyelination and it is due to the genetic loss of function of the lysosomal enzyme galactocerebrosidase (GALC). This enzyme leads to the accumulation of galactosylceramide, psychosine, and secondary substrates such as lactosylceramide. In this paper, we induced autophagy through starvation and examined the cellular response occurring in fibroblasts isolated from patients. We demonstrated that the inhibitory AKT-mediated phosphorylation of beclin-1 and the BCL2-beclin-1 complex concur to reduce autophagosomes formation in response to starvation. These events were not dependent on the accumulation of psychosine, which was previously identified as a possible player in autophagic impairment in Krabbe disease. We believe that these data could better elucidate the capability of response to autophagic stimuli in Krabbe disease, in order to identify possible molecules able to stimulate the process.
Macrophage Migration Inhibitory Factor in Psoroptes ovis: Molecular Characterization and Potential Role in Eosinophil Accumulation of Skin in Rabbit and Its Implication in the Host–Parasite Interaction
Authors: Gu Xiaobin , Ge You , Wang Ya , Huang Cuirui , Yang Guangyou , Xie Yue , Xu Jing , He Ran , Zhong Zhijun , Yang Deying , He Zhi , Peng Xuerong
Published: March 2023

Psoroptes ovis, a common surface-living mite of domestic and wild animals worldwide, results in huge economic losses and serious welfare issues in the animal industry. P. ovis infestation rapidly causes massive eosinophil infiltration in skin lesions, and increasing research revealed that eosinophils might play an important role in the pathogenesis of P. ovis infestation. Intradermal injection of P. ovis antigen invoked massive eosinophil infiltration, suggesting that this mite should contain some relative molecules involved in eosinophil accumulation in the skin. However, these active molecules have not yet been identified. Herein, we identified macrophage migration inhibitor factor (MIF) in P. ovis (PsoMIF) using bioinformatics and molecular biology methods. Sequence analyses revealed that PsoMIF appeared with high similarity to the topology of monomer and trimer formation with host MIF (RMSD = 0.28 angstroms and 2.826 angstroms, respectively) but with differences in tautomerase and thiol-protein oxidoreductase active sites. Reverse transcription PCR analysis (qRT-PCR) results showed that PsoMIF was expressed throughout all the developmental stages of P. ovis, particularly with the highest expression in female mites. Immunolocalization revealed that MIF protein located in the ovary and oviduct of female mites and also localized throughout the stratum spinosum, stratum granulosum, and even basal layers of the epidermis in skin lesions caused by P. ovis. rPsoMIF significantly upregulated eosinophil-related gene expression both in vitro (PBMC: CCL5, CCL11; HaCaT: IL-3, IL-4, IL-5, CCL5, CCL11) and in vivo (rabbit: IL-5, CCL5, CCL11, P-selectin, ICAM-1). Moreover, rPsoMIF could induce cutaneous eosinophil accumulation in a rabbit model and increased the vascular permeability in a mouse model. Our findings indicated that PsoMIF served as one of the key molecules contributing to skin eosinophil accumulation in P. ovis infection of rabbits.
Neuronal Prosurvival Role of Ceramide Synthase 2 by Olidogendrocyte-to-Neuron Extracellular Vesicle Transfer
Authors: Casadomé-Perales Álvaro , Naya Sara , Fernández-Martínez Elisa , Mille Bea G. , Guerrero-Valero Marta , Peinado Héctor , Guix Francesc X. , Dotti Carlos G. , Palomer Ernest
Published: March 2023

Ageing is associated with notorious alterations in neurons, i.e., in gene expression, mitochondrial function, membrane degradation or intercellular communication. However, neurons live for the entire lifespan of the individual. One of the reasons why neurons remain functional in elderly people is survival mechanisms prevail over death mechanisms. While many signals are either pro-survival or pro-death, others can play both roles. Extracellular vesicles (EVs) can signal both pro-toxicity and survival. We used young and old animals, primary neuronal and oligodendrocyte cultures and neuroblastoma and oligodendrocytic lines. We analysed our samples using a combination of proteomics and artificial neural networks, biochemistry and immunofluorescence approaches. We found an age-dependent increase in ceramide synthase 2 (CerS2) in cortical EVs, expressed by oligodendrocytes. In addition, we show that CerS2 is present in neurons via the uptake of oligodendrocyte-derived EVs. Finally, we show that age-associated inflammation and metabolic stress favour CerS2 expression and that oligodendrocyte-derived EVs loaded with CerS2 lead to the expression of the antiapoptotic factor Bcl2 in inflammatory conditions. Our study shows that intercellular communication is altered in the ageing brain, which favours neuronal survival through the transfer of oligodendrocyte-derived EVs containing CerS2.
Heterologous VvDREB2c Expression Improves Heat Tolerance in Arabidopsis by Inducing Photoprotective Responses
Authors: Zha Qian , Yin Xiangjing , Xi Xiaojun , Jiang Aili
Published: March 2023

Extreme temperatures limit grape production and sustainability. Dehydration-responsive element-binding (DREB) transcription factors affect plant responses to temperature related stresses. Therefore, we investigated the role of VvDREB2c, a DREB-coding gene, found in grapes (Vitis vinifera L.). Protein characterization revealed that VvDREB2c is localized to the nucleus and that its AP2/ERF domain contains three β-sheets and one α-helix sheet. Analysis of the VvDREB2c promoter region revealed the presence of light-, hormone-, and stress-related cis-acting elements. Furthermore, we observed that the heterologous expression of VvDREB2c in Arabidopsis improved growth, drought tolerance, and heat tolerance. Furthermore, it improved the leaf quantum yield of regulated energy dissipation [Y(NPQ)], elevated the activities of RuBisCO, and phosphoenolpyruvate carboxylase and reduced the quantum yield of non-regulated energy dissipation [Y(NO)] in plants exposed to high temperatures. VvDREB2c-overexpressing lines also specifically upregulated several photosynthesis-related genes (CSD2, HSP21, and MYB102). In addition, VvDREB2c-overexpressing lines reduced light damage and enhanced photoprotective ability by dissipating excess light energy and converting it into heat, which eventually improves tolerance to high temperature. The contents of abscisic acid, jasmonic acid, and salicylic acid and differentially expressed genes (DEGs) in the mitogen-activated protein kinase (MAPK) signaling pathway were affected by heat stress in VvDREB2c-overexpressing lines, which indicated that VvDREB2c positively regulates heat tolerance via a hormonal pathway in Arabidopsis. VvDREB2c promotes heat tolerance in Arabidopsis by exerting effects on photosynthesis, hormones, and growth conditions. This study may provide useful insights into the enrichment of the heat-tolerance pathways in plants.
Ethylene and Jasmonates Signaling Network Mediating Secondary Metabolites under Abiotic Stress
Authors: Pérez-Llorca Marina , Pollmann Stephan , Müller Maren
Published: March 2023

Plants are sessile organisms that face environmental threats throughout their life cycle, but increasing global warming poses an even more existential threat. Despite these unfavorable circumstances, plants try to adapt by developing a variety of strategies coordinated by plant hormones, resulting in a stress-specific phenotype. In this context, ethylene and jasmonates (JAs) present a fascinating case of synergism and antagonism. Here, Ethylene Insensitive 3/Ethylene Insensitive-Like Protein1 (EIN3/EIL1) and Jasmonate-Zim Domain (JAZs)-MYC2 of the ethylene and JAs signaling pathways, respectively, appear to act as nodes connecting multiple networks to regulate stress responses, including secondary metabolites. Secondary metabolites are multifunctional organic compounds that play crucial roles in stress acclimation of plants. Plants that exhibit high plasticity in their secondary metabolism, which allows them to generate near-infinite chemical diversity through structural and chemical modifications, are likely to have a selective and adaptive advantage, especially in the face of climate change challenges. In contrast, domestication of crop plants has resulted in change or even loss in diversity of phytochemicals, making them significantly more vulnerable to environmental stresses over time. For this reason, there is a need to advance our understanding of the underlying mechanisms by which plant hormones and secondary metabolites respond to abiotic stress. This knowledge may help to improve the adaptability and resilience of plants to changing climatic conditions without compromising yield and productivity. Our aim in this review was to provide a detailed overview of abiotic stress responses mediated by ethylene and JAs and their impact on secondary metabolites.
Kaempferol Suppresses the Activation of Mast Cells by Modulating the Expression of FcεRI and SHIP1
Authors: Nagata Kazuki , Araumi Sanae , Ando Daisuke , Ito Naoto , Ando Miki , Ikeda Yuki , Takahashi Miki , Noguchi Sakura , Yasuda Yayoi , Nakano Nobuhiro , Ando Tomoaki , Hara Mutsuko , Yashiro Takuya , Hachisu Masakazu , Nishiyama Chiharu
Published: March 2023

In the present study, we evaluated the effects of kaempferol on bone marrow-derived mast cells (BMMCs). Kaempferol treatment significantly and dose-dependently inhibited IgE-induced degranulation, and cytokine production of BMMCs under the condition that cell viability was maintained. Kaempferol downregulated the surface expression levels of FcεRI on BMMCs, but the mRNA levels of FcεRIα, β, and γ-chains were not changed by kaempferol treatment. Furthermore, the kaempferol-mediated downregulation of surface FcεRI on BMMCs was still observed when protein synthesis or protein transporter was inhibited. We also found that kaempferol inhibited both LPS- and IL-33-induced IL-6 production from BMMCs, without affecting the expression levels of their receptors, TLR4 and ST2. Although kaempferol treatment increased the protein amount of NF-E2-related factor 2 (NRF2)—a master transcription factor of antioxidant stress—in BMMCs, the inhibition of NRF2 did not alter the suppressive effect of kaempferol on degranulation. Finally, we found that kaempferol treatment increased the levels of mRNA and protein of a phosphatase SHIP1 in BMMCs. The kaempferol-induced upregulation of SHIP1 was also observed in peritoneal MCs. The knockdown of SHIP1 by siRNA significantly enhanced IgE-induced degranulation of BMMCs. A Western blotting analysis showed that IgE-induced phosphorylation of PLCγ was suppressed in kaempferol-treated BMMCs. These results indicate that kaempferol inhibited the IgE-induced activation of BMMCs by downregulating FcεRI and upregulating SHIP1, and the SHIP1 increase is involved in the suppression of various signaling-mediated stimulations of BMMCs, such as those associated with TLR4 and ST2.
A Cone Beam CT Study on the Correlation between Crestal Bone Loss and Periapical Disease
Authors: Mahasneh Sari A. , Al-Hadidi Abeer , Kadim Wahab Fouad , Sawair Faleh A. , AL-Rabab’ah Mohammad Abdalla , Al-Nazer Sarah , Bakain Yara , Nardi Cosimo , Cunliffe Joanne
Published: March 2023

The aim of this study was to determine whether the degree of bone loss around teeth can be linked to the loss of vitality of adjacent teeth and periapical disease, which necessitates root canal treatments. Three hundred and twenty-one full maxilla cone-beam computed tomography scans were examined. The parameters investigated included the degree of crestal bone loss in relation to the cementoenamel junction, the presence/absence of apical periodontitis, and the presence/absence of root canal treatments. Out of the 2001 teeth examined, 696 (34.8%) showed evidence of crestal bone loss. The degree of crestal bone loss was classified as mild, moderate, or severe. A significant association (p < 0.001) was found between the presence of crestal bone loss around a tooth and root canal treatment of that tooth. It was found that it is more likely for teeth with crestal bone loss to be root canal treated compared to teeth with existing root canal treatment and healthy crestal bone levels. Furthermore, teeth with buccal or lingual crestal bone loss were significantly associated with a higher rate of periapical disease than teeth without crestal bone loss (p < 0.001). CBCT identified the severity of bone loss on all surfaces of the teeth, and the most common presentation was bone loss to the mid-root level. Teeth with crestal bone loss were significantly more likely to be associated with a higher rate of periapical disease. Teeth with crestal bone loss were more likely to be root treated than teeth with healthy crestal bone levels.
Up to a 15-Year Survival Rate and Marginal Bone Resorption of 1780 Implants with or without Microthreads: A Multi Center Retrospective Study
Authors: Oh Ji-Hwan , Pyo Se-Wook , Chang Jae-Seung , Kim Sunjai
Published: March 2023

The effect of microthreads at the implant neck on the amount of marginal bone resorption is controversial. This multicenter retrospective study compared the implant survival rate and amount of marginal bone resorption between two platform-switching internal connection implant systems with or without microthreads. Patient-related (age and sex), surgery-related (implant installation site, type, diameter, and length), and prosthesis-related (prosthesis type) data were collected from patient charts from the implant placement surgery to the final recall visit. A total of 1780 implants, including 1379 with microthreads and 401 without microthreads, were placed in 804 patients. For implants with and without microthreads, the longest follow-up period after prosthesis delivery was 15 and 6 years, respectively. Twenty implants failed during the 15-year follow-up period (98.8% survival rate) due to failed osseointegration, peri-implantitis, implant fractures, and non-functioning implants. The mean marginal bone loss was < 0.1 mm for both implant systems at the 1-year follow-up and 0.18 mm and 0.09 mm at the 4-year follow-up for implants with and without microthreads, respectively, without statistical significance. Microthreads did not significantly affect the amount of marginal bone loss or the implant survival rate for implants with an internal connection with a platform-switching design.
Management of Pelvic Fracture Urethral Injury: Is Supracrural Urethral Rerouting (Step 4) Becoming Anecdotical or Does It Remain in Force?
Authors: Yepes Christian , Oszczudlowski Maciej , Bandini Marco , Joshi Pankaj M. , Alrefaey Ahmed , Bhadranavar Shreyas , Martins Francisco E. , Kulkarni Sanjay B.
Published: March 2023

Webster described a step-based perineal approach for repairing the posterior urethra in patients with pelvic fracture urethral injury (PFUI). The higher the complexity of the step, the higher the morbidity for the patient and the lower the surgical outcomes. We evaluated the outcomes of anastomotic urethroplasty (especially Step 4 or higher) or substitution urethroplasty in patients with PFUI at our center. Between 2013 to 2021, we retrospectively collected data on patients with PFUI. Surgical procedures were categorized according to the Webster classification and rates of each step were reported. The success rate was defined as Qmax above 10 mL/s and no need for further treatment. In this period, 737 male patients with PFUI were surgically treated. Notably, 18.8%, 17.6%, 46%, 1.8%, and 5.6% of included patients received steps 1, 2, 3, and 4 and the abdominoperineal approach, respectively. In 68 (9.2%) patients, the substitution of urethroplasty with a pedicled preputial tube (PPT) was needed. The success rate was 69.2% in Step 4, 74.4% in the abdominoperineal approach, and 86.4% in PPT; however, recurrence-free survival was not significantly different between groups (p = 0.22). Step 4 perineal anastomotic urethroplasty represents a surgical option in the armamentarium of PFUI treatment. Indications should be carefully reviewed to improve patient selection and avoid surgical failure, stopping at the step which first gives a tension-free anastomosis.
Increased Access to Immunoglobulin Replacement Therapy for Patients with Primary Immunodeficiency in Poland Based on Clinical Usage Data of Immunoglobulin G over a 5-Year Period
Authors: Więsik-Szewczyk Ewa , Ziętkiewicz Marcin , Radziwilska-Muc Anna , Jahnz-Różyk Karina
Published: March 2023

Owing to the rising popularity and demand for immunoglobulins (IgG), obtaining supplies and rationalizing IgG use have become challenging. Herein, IgG consumption in Poland was analyzed through total IgG use and number of patients reported to the National Health Fund between 1 January 2016 and 31 December 2020. Total IgG used within 5 years increased by 27.48%, IgG use/1000 inhabitants/year was 23.13 g (2016) and 29.61 g (2020). In 2020, 35.5 % of IgG used was for neurological conditions, 25% for primary immunodeficiencies (PID), and 39.3% for all other indications. Within 5 years, 1,121,168.75 g IgG was used in PID; the use increased by 72%, from 783 in 2016 to 1153 patients in 2020. The proportion of patients who received subcutaneous immunoglobulin (SCIG) replacement therapy (IgRT) increased to 78% (2020). Within 5 years, 1,783,534.81 g IgG was used in neurological drug programs (+42.44%) and 2,327,513.88 g (+1.25%) outside neurological indications and outside PID. The annual IgG amount decreased in adult anesthesiology and intensive care (−46%), internal medicine (−55%), pneumonology (−50%), pediatric clinical immunology (−50%), and gynecology and obstetrics (−48%) and increased in dermatology (+178%), rheumatology (+103%), and clinical transplantation (+82%). IgG use significantly increased in Poland, mostly owing to PID. Subcutaneous IgG administration is currently the most common mode of IgRT in PID patients. An increase in SCIG administration may be expected for other indications. Implementing evidence-based clinical guidelines is key to prioritizing and rationalizing IgG use for immunomodulatory indications and secondary immune deficiencies.
The Role and Clinical Relevance of Osteopontin in Allergic Airway Diseases
Authors: Liu Yang , Fu Li , Liu Zheng
Published: March 2023

The airway epithelium is exposed to numerous external irritants including infectious agents, environmental allergens, and atmospheric pollutants, releasing epithelial cytokines including thymic stromal lymphopoietin (TSLP), IL-33, and IL-25 and initiating downstream type 2 (IL-4, IL-13, and IL-5) and IgE-driven pathways. These pathways trigger the initiation and progression of allergic airway diseases, including chronic rhinosinusitis with nasal polyps (CRSwNP), allergic rhinitis (AR), and allergic asthma. However, the use of biological agents that target downstream cytokines, such as IL-5, IL-4, and IL-13 receptors and IgE, might not be sufficient to manage some patients successfully. Instead of blocking downstream cytokines, targeting upstream epithelial cytokines has been proposed to address the complex immunologic networks associated with allergic airway diseases. Osteopontin (OPN), an extracellular matrix glyco-phosphoprotein, is a key mediator involved in Th1-related diseases, including systemic lupus erythematosus, multiple sclerosis, inflammatory bowel disease, and rheumatoid arthritis. Emerging evidence, including ours, indicates that epithelial-cell-derived OPN also plays an essential role in Th2-skewed airway diseases, including CRSwNP, AR, and allergic asthma involving the Th17 response. Therefore, we reviewed the current knowledge of epithelial-cell-derived OPN in the pathogenesis of three type-2-biased airway diseases and provided a direction for its future investigation and clinical relevance.
Donor-Derived Cell-Free DNA for Kidney Allograft Surveillance after Conversion to Belatacept: Prospective Pilot Study
Authors: Osmanodja Bilgin , Akifova Aylin , Oellerich Michael , Beck Julia , Bornemann-Kolatzki Kirsten , Schütz Ekkehard , Budde Klemens
Published: March 2023

Donor-derived cell-free DNA (dd-cfDNA) is used as a biomarker for detection of antibody-mediated rejection (ABMR) and other forms of graft injury. Another potential indication is guidance of immunosuppressive therapy when no therapeutic drug monitoring is available. In such situations, detection of patients with overt or subclinical graft injury is important to personalize immunosuppression. We prospectively measured dd-cfDNA in 22 kidney transplant recipients (KTR) over a period of 6 months after conversion to belatacept for clinical indication and assessed routine clinical parameters. Patient and graft survival was 100% after 6 months, and eGFR remained stable (28.7 vs. 31.1 mL/min/1.73 m2, p = 0.60). Out of 22 patients, 2 (9%) developed biopsy-proven rejection—one episode of low-grade TCMR IA and one episode of caABMR. While both episodes were detected by increase in creatinine, the caABMR episode led to increase in absolute dd-cfDNA (168 copies/mL) above the cut-off of 50 copies/mL, while the TCMR episode did show slightly increased relative dd-cfDNA (0.85%) despite normal absolute dd-cfDNA (22 copies/mL). Dd-cfDNA did not differ before and after conversion in a subgroup of 12 KTR with previous calcineurin inhibitor therapy and no rejection (12.5 vs. 25.3 copies/mL, p = 0.34). In this subgroup, 3/12 (25%) patients showed increase of absolute dd-cfDNA above the prespecified cut-off (50 copies/mL) despite improving eGFR. Increase in dd-cfDNA after conversion to belatacept is common and could point towards subclinical allograft injury. To detect subclinical TCMR changes without vascular lesions, additional biomarkers or urinary dd-cfDNA should complement plasma dd-cfDNA. Resolving CNI toxicity is unlikely to be detected by decreased dd-cfDNA levels. In summary, the sole determination of dd-cfDNA has limited utility in the guidance of patients after late conversion to belatacept. Further studies should focus on patients undergoing early conversion and include protocol biopsies at least for patients with increased dd-cfDNA.
The Associations between Insomnia Severity and Health Outcomes in the United States
Authors: Chalet François-Xavier , Saskin Paul , Ahuja Ajay , Thompson Jeffrey , Olopoenia Abisola , Modi Kushal , Morin Charles M. , Wickwire Emerson M.
Published: March 2023

Little is known about the associations between insomnia severity, insomnia symptoms, and key health outcomes. Using 2020 United States National Health and Wellness Survey (NHWS) data, we conducted a retrospective, cross-sectional analysis to determine the associations between insomnia severity and a number of health outcomes germane to patients (health-related quality of life (HRQoL), employers and government (workplace productivity), and healthcare payers (healthcare resource utilization (HCRU)). The Insomnia Severity Index (ISI) questionnaire was used to evaluate overall insomnia severity. HRQoL was assessed using the physical and mental component summary scores of the Short Form-36v2 (SF-36v2) questionnaire, and health utility status was measured using the Short Form-6D (SF-6D) and EuroQoL-5D (EQ-5D) questionnaires. Workplace productivity was measured using the Work Productivity and Activity Impairment (WPAI) questionnaire. After adjusting for confounders, greater insomnia severity was significantly associated with worsened quality of life, decreased productivity, and increased HCRU in an apparent linear fashion. These findings have important implications for future research, including the need for specific assessment of insomnia symptoms and their impact on key health outcomes.
Distinct Sleep Alterations in Alcohol Use Disorder Patients with and without Korsakoff’s Syndrome: Relationship with Episodic Memory
Authors: Laniepce Alice , Segobin Shailendra , André Claire , Bertran Françoise , Boudehent Céline , Lahbairi Najlaa , Maillard Angéline , Mary Alison , Urso Laurent , Vabret François , Cabé Nicolas , Pitel Anne-Lise , Rauchs Géraldine
Published: March 2023

Alcohol Use Disorder (AUD) results in sleep disturbances that may have deleterious impacts on cognition, especially on memory. However, little is known about the sleep architecture in patients with Korsakoff’s syndrome (KS). This study aims at characterizing sleep disturbances in KS compared to AUD without KS and at specifying the relationships with cognitive impairments. Twenty-nine AUD patients (22 without KS and 7 with KS) and 15 healthy controls underwent a neuropsychological assessment and a polysomnography. The severity of sleep-disordered breathing and sleep fragmentation was similar in AUD and KS patients compared to controls. Sleep architecture differed between both patient groups: the proportion of slow-wave sleep was reduced in AUD patients only, while a lower proportion of rapid-eye movement (REM) sleep was specifically observed in KS patients. The proportion of REM sleep correlated with the severity of episodic memory deficits when AUD and KS were examined together. These data provide evidence for both similarities and specificities regarding sleep alterations in AUD patients with and without KS. They also indicate that altered sleep architecture may contribute to the pathophysiology of alcohol-related memory disorders.
Fluoride Retention in Root Dentin following Surface Coating Material Application
Authors: Okuyama Katsushi , Matsuda Yasuhiro , Yamamoto Hiroko , Suzuki Kohtaku , Shintani Kohei , Saito Takashi , Hayashi Mikako , Tamaki Yukimichi
Published: March 2023

This study aimed to use an in-air micro-particle-induced X-ray/gamma emission (in-air µPIXE/PIGE) system to evaluate tooth-bound fluoride (T-F) in dentin following the application of fluoride-containing tooth-coating materials. Three fluoride-containing coating materials (PRG Barrier Coat, Clinpro XT varnish, and Fuji IX EXTRA) and a control were applied to the root dentin surface of human molars (n = 6, total 48 samples). Samples were stored in a remineralizing solution (pH 7.0) for 7 or 28 days and then sectioned into two adjacent slices. One slice of each sample was immersed in 1M potassium hydroxide (KOH) solution for 24 h and rinsed with water for 5 min for the T-F analysis. The other slice did not undergo KOH treatment and was used to analyze the total fluoride content (W-F). The fluoride and calcium distributions were measured in all the slices using an in-air µPIXE/PIGE. Additionally, the amount of fluoride released from each material was measured. Clinpro XT varnish demonstrated the highest fluoride release among all the materials and tended to show high W-F and T-F and lower T-F/W-F ratios. Our study demonstrates that a high fluoride-releasing material shows high fluoride distribution into the tooth structure and low conversion from fluoride uptake by tooth-bound fluoride.
Preliminary Investigation on Marine Radar Oil Spill Monitoring Method Using YOLO Model
Authors: Li Bo , Xu Jin , Pan Xinxiang , Chen Rong , Ma Long , Yin Jianchuan , Liao Zhiqiang , Chu Lilin , Zhao Zhiqiang , Lian Jingjing , Wang Haixia
Published: March 2023

Due to the recent rapid growth of ocean oil development and transportation, the offshore oil spill risk accident probability has increased unevenly. The marine oil spill poses a great threat to the development of coastal cities. Therefore, effective and reliable technologies must be used to monitor oil spills to minimize disaster losses. Based on YOLO deep learning network, an automatic oil spill detection method was proposed. The experimental data preprocessing operations include noise reduction, gray adjustment, and local contrast enhancement. Then, real and synthetically generated marine radar oil spill images were used to make slice samples for training the model in the YOLOv5 network. The detection model can identify the effective oil spill monitoring region. Finally, an adaptive threshold was applied to extract the oil slicks in the effective oil spill monitoring regions. The YOLOv5 detection model generated had the advantage of high efficiency compared with existing methods. The offshore oil spill detection method proposed can support real-time and effective data for routine patrol inspection and accident emergency response.
Recent Advancements, Challenges, and Future Prospects in Usage of Nanoformulation as Theranostics in Inflammatory Diseases
Authors: Goyal Amit K. , Ramchandani Manish , Basak Trambak
Published: March 2023

As of today, chronic inflammatory diseases are a progressive cause of death worldwide, accounting for more than 50% of all fatalities. These inflammatory conditions are a major concern, ranging from heart disease to cancer, diabetes, to even neurodegenerative conditions. Conventional diagnosis and treatment for these problems are often challenging and limited due to complex pathophysiology. To improve upon current treatment and diagnostic strategies, theranostic nanomaterials have been developed. Theranostics is an amalgamation of diagnostic biomarkers and therapeutic medicines that have a shared target in damaged cells or tissues. Different theranostic nanoparticles generate enhanced imaging results for facilities such as MRI, PET scan, and CT scans depending on the site of inflammation in different organs. Furthermore, they can be treated with radiopharmaceuticals and/or medicine in nanoparticles. Following a brief discussion of conventional inflammatory diagnosis and therapeutic strategies, this review will cover the recent progress made in theranostic nanomaterials and nanomedicine tactics for managing inflammatory disorders, covering the preclinical and clinical stages of these advances from the past five years. Furthermore, present challenges with theranostic nanoparticles for inflammatory detection and treatment are discussed, as well as future research possibilities.
A Feasibility Study on the Recall of Metallophilic Fungi from Fe(III)-Contaminated Soil and Evaluating Their Mycoremediation Capacity: Experimental and Theoretical Study
Authors: Tagyan Aya I. , Yasser Manal M. , Mousa Ahmed M. , Alkhalifah Dalal Hussien M. , Hozzein Wael N. , Marzouk Marym A.
Published: March 2023

Mycoremediation is one of the most attractive, eco-friendly, and sustainable methods to mitigate the toxic effects of heavy metals. This study aimed to determine the mycoremediation capacity of metallophilic fungi isolated from heavy-metal-contaminated soil containing a high Fe(III) concentration (118.40 mg/kg). Four common fungal strains were isolated, including Curvularia lunata, Fusarium equiseti, Penicillium pinophilum, and Trichoderma harzianum. These fungal strains were exposed to gradually increasing concentrations of Fe(III) of 100, 200, 300, 400, 500, 600, 700, 800, 900, and 1000 mg/L. Sophisticated techniques and tests were employed to investigate the mycoremediation capability, including tolerance index (TI), scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), and adsorption isotherm. Furthermore, the impacts of initial concentration, pH, and temperature on the Fe(III) removal (%) and uptake capacity (mg/g) of the studied samples were investigated. The results were validated by statistical analysis using one-way ANOVA. It was found that the Fe(III) uptake with different ratios triggered alterations in the Fe(III) tolerance (TI) morphological (SEM), chemical (FTIR), and adsorption capacity properties. The highest Fe(III) tolerance for all studied fungal strains was achieved at 100 mg/L. Moreover, the optimum conditions of Fe(III) removal (%) for all studied fungal strains were within pH 7 and 28 °C, with similar performance at the initial Fe(III) concentration ranging from 50–200 mg/L. At the same time, the maximum Fe(III) uptake was achieved at pH 7, 20 °C, and 200 mg/L. Compared to other strains, the Fe(III) tolerance of T. harzianum was rise in the Fe(III) concentration. The Fe(III) uptake reaction was corroborated by best fitting with the Langmuir model, achieving optimum adsorption capacities of 61.34, 62.90, 63.30, and 72.46 mg/g for C.lunata, F. equiseti, P. pinophilum, T. harzianum, respectively. It can be deduced that the addressed fungi species can be applied in mycoremediation according to the utilized Fe(III) concentrations with more superiority for live T. harzianum.
Fungal Endophytes Enhance Wheat and Tomato Drought Tolerance in Terms of Plant Growth and Biochemical Parameters
Authors: Miranda Victoria , Silva-Castro Gloria Andrea , Ruiz-Lozano Juan Manuel , Fracchia Sebastian , García-Romera Inmaculada
Published: March 2023

Drought is a major threat to plant growth in many parts of the world. During periods of drought, multiple aspects of plant physiology are negatively affected. For instance, water shortages induce osmotic imbalance, inhibit photosynthesis, decrease nutrient uptake, and increases the production of reactive oxygen species (ROS). In this context, it is necessary to develop sustainable strategies for crops that would help mitigate these conditions. In previous studies, endophytic Zopfiella erostrata strains were found to extensively colonize plant roots, forming a profuse melanized mycelium in the rhizosphere, which could be involved in improving water uptake and nutrient mineralization in plants. The aim of this study is to evaluate the effect of different strains of Z. erostrata on stress mitigation in wheat and tomato plants grown under water deficit conditions. General plant growth variables, as well as physiological and biochemical parameters, related to oxidative status were determined. Our data demonstrate that inoculation with both Zopfiella strains had a very significant effect on plant growth, even under water deficit conditions. However, we observed an even more pronounced impact, depending on the plant and strain involved, suggesting a certain degree of plant/strain compatibility. The biochemical aspects, the accumulation of proline, the oxidative damage to lipids, and the activity of antioxidant enzymes varied considerably depending on the endophyte and the plant evaluated.