bluuebunny/crossref_metadata_2025 huggingface dataset:
Taxonomic Composition of Protist Communities in the Coastal Stratified Lake Kislo-Sladkoe (Kandalaksha Bay, White Sea) Revealed by Microscopy
Authors: Mindolina Yulia V. , Selivanova Elena A. , Ignatenko Marina E. , Krasnova Elena D. , Voronov Dmitry A. , Plotnikov Andrey O.
Published: December 2022

Lake Kislo-Sladkoe is a stratified water body partly isolated from the White Sea. Perennial meromixis in the lake irregularly alternates with mixing events. Taking into account that the protists of Arctic coastal stratified water bodies are understudied, we evaluated for the first time the vertical structure, species richness, and diversity of protists assigned to different taxonomic groups in Lake Kislo-Sladkoe using light, luminescent, and scanning electron microscopy. To test the research hypothesis that a mixing event affects the vertical stratification and species composition of protists in a stratified lake, we compared the protist communities of Lake Kislo-Sladkoe in two extremely different states: strong meromixis vs. full vertical mixing. A total of 97 morphologically distinct phototrophic, heterotrophic, and mixotrophic protists were revealed with the most diverse supertaxa SAR (59), Obazoa (9), and Excavates (14). The hidden diversity of protists (43 species) was a bit less than the active diversity (54 species). A taxonomic list and micrographs of cells for the observed protists are provided. The majority of species revealed are cosmopolitan or widespread in the northern sea waters. The vertical patterns of protist communities were absolutely different in 2018 and 2021. In July 2018, clearly distinct protist communities inhabited different layers of the lake. Bloom of cryptophyte Rhodomonas cf. baltica was detected in chemocline, whereas the maximum density of its grazers was observed in adjacent layers, mainly dinoflagellates Gymnodinium sp. and Scrippsiella trochoidea, as well as a ciliate Prorodon sp. In 2021 due to the recent mixing of lake and seawater, there were no distinct communities in the water column except the superficial 0–1 m layer of fresh water.
D2BOF-COVIDNet: A Framework of Deep Bayesian Optimization and Fusion-Assisted Optimal Deep Features for COVID-19 Classification Using Chest X-ray and MRI Scans
Authors: Hamza Ameer , Khan Muhammad Attique , Alhaisoni Majed , Al Hejaili Abdullah , Shaban Khalid Adel , Alsubai Shtwai , Alasiry Areej , Marzougui Mehrez
Published: December 2022

Background and Objective: In 2019, a corona virus disease (COVID-19) was detected in China that affected millions of people around the world. On 11 March 2020, the WHO declared this disease a pandemic. Currently, more than 200 countries in the world have been affected by this disease. The manual diagnosis of this disease using chest X-ray (CXR) images and magnetic resonance imaging (MRI) is time consuming and always requires an expert person; therefore, researchers introduced several computerized techniques using computer vision methods. The recent computerized techniques face some challenges, such as low contrast CTX images, the manual initialization of hyperparameters, and redundant features that mislead the classification accuracy. Methods: In this paper, we proposed a novel framework for COVID-19 classification using deep Bayesian optimization and improved canonical correlation analysis (ICCA). In this proposed framework, we initially performed data augmentation for better training of the selected deep models. After that, two pre-trained deep models were employed (ResNet50 and InceptionV3) and trained using transfer learning. The hyperparameters of both models were initialized through Bayesian optimization. Both trained models were utilized for feature extractions and fused using an ICCA-based approach. The fused features were further optimized using an improved tree growth optimization algorithm that finally was classified using a neural network classifier. Results: The experimental process was conducted on five publically available datasets and achieved an accuracy of 99.6, 98.5, 99.9, 99.5, and 100%. Conclusion: The comparison with recent methods and t-test-based analysis showed the significance of this proposed framework.
Comparison between Conventional Modality Versus Cone-Beam Computer Tomography on the Assessment of Vertical Furcation in Molars
Authors: Lam Jack , Yeung Andy Wai Kan , Acharya Aneesha , Fok Chris , Fok Melissa , Pelekos Georgios
Published: December 2022

This study aimed to assess the accuracy of diagnosis of vertical furcation subclass in molars using periapical radiographs (PAs) and clinical chartings compared against cone-beam computer tomography (CBCT) as the gold standard. The protocol involved examiners with different levels of experience. This retrospective radiographic study retrieved 40 molar teeth with full periodontal chartings, PAs, and CBCT records. Fifteen examiners with different levels of experience evaluated the PAs and periodontal chartings to assess the vertical depth of furcation and, thus, the vertical subclassification. CBCT was used as the gold standard for comparison. The accuracy of vertical furcal depth measured was assessed together with the accuracy of vertical subclassification assignment. The reliability of the conventional diagnostic modality among the examiners was also evaluated. A linear mixed model adjusted for the CBCT vertical furcal depth measurement was constructed to determine if tooth position, horizontal furcation distribution, and examiner experience level affect the bias in the vertical depth of furcation measurement. The reliability of the conventional periodontal diagnostic method in measuring vertical furcal depth was found to be fair, while vertical subclass assignment was moderate. Significantly better reliability during subclass assignment was found with mandibular molars (p < 0.001) and in maxillary molars with isolated buccal class II furcation. Within the study’s limitations, conventional periodontal diagnostics based on periapical radiographs and clinical periodontal chartings appear to be in poor to fair agreement with CBCT (gold standard) when measuring the vertical depth of furcation. Examiners with the least experience were more prone to bias when estimating the vertical furcal depth.
Current Applications of Deep Learning and Radiomics on CT and CBCT for Maxillofacial Diseases
Authors: Hung Kuo Feng , Ai Qi Yong H. , Wong Lun M. , Yeung Andy Wai Kan , Li Dion Tik Shun , Leung Yiu Yan
Published: December 2022

The increasing use of computed tomography (CT) and cone beam computed tomography (CBCT) in oral and maxillofacial imaging has driven the development of deep learning and radiomics applications to assist clinicians in early diagnosis, accurate prognosis prediction, and efficient treatment planning of maxillofacial diseases. This narrative review aimed to provide an up-to-date overview of the current applications of deep learning and radiomics on CT and CBCT for the diagnosis and management of maxillofacial diseases. Based on current evidence, a wide range of deep learning models on CT/CBCT images have been developed for automatic diagnosis, segmentation, and classification of jaw cysts and tumors, cervical lymph node metastasis, salivary gland diseases, temporomandibular (TMJ) disorders, maxillary sinus pathologies, mandibular fractures, and dentomaxillofacial deformities, while CT-/CBCT-derived radiomics applications mainly focused on occult lymph node metastasis in patients with oral cancer, malignant salivary gland tumors, and TMJ osteoarthritis. Most of these models showed high performance, and some of them even outperformed human experts. The models with performance on par with human experts have the potential to serve as clinically practicable tools to achieve the earliest possible diagnosis and treatment, leading to a more precise and personalized approach for the management of maxillofacial diseases. Challenges and issues, including the lack of the generalizability and explainability of deep learning models and the uncertainty in the reproducibility and stability of radiomic features, should be overcome to gain the trust of patients, providers, and healthcare organizers for daily clinical use of these models.
Small Bowel Endoscopic Features of Eosinophilic Gastroenteritis
Authors: Sasaki Yu , Abe Yasuhiko , Mizumoto Naoko , Nomura Eiki , Ueno Yoshiyuki
Published: December 2022

Eosinophilic gastroenteritis (EoGE) is a rare digestive disorder characterized by eosinophilic infiltration of the stomach and intestines. In the diagnosis of EoE, it is extremely important to recognize distinctive endoscopic findings and accurately detect increased eosinophilia in gastrointestinal tissues. However, endoscopic findings of EoGE in the small intestine remain poorly understood. Therefore, we conducted a literature review of 16 eligible papers. Redness or erythema was the most common endoscopic finding in the small bowel, followed by villous atrophy, erosion, ulceration, and edema. In some cases, stenosis due to circumferential ulceration was observed, which led to retention of the capsule during small bowel capsule endoscopy. Although many aspects of small bowel endoscopic findings in EoGE remain elusive, the findings presented in this review are expected to contribute to the further development of EoGE practice.
Comparison of Diagnostic Performance in Mammography Assessment: Radiologist with Reference to Clinical Information Versus Standalone Artificial Intelligence Detection
Authors: Choi Won Jae , An Jin Kyung , Woo Jeong Joo , Kwak Hee Yong
Published: December 2022

We compared diagnostic performances between radiologists with reference to clinical information and standalone artificial intelligence (AI) detection of breast cancer on digital mammography. This study included 392 women (average age: 57.3 ± 12.1 years, range: 30–94 years) diagnosed with malignancy between January 2010 and June 2021 who underwent digital mammography prior to biopsy. Two radiologists assessed mammographic findings based on clinical symptoms and prior mammography. All mammographies were analyzed via AI. Breast cancer detection performance was compared between radiologists and AI based on how the lesion location was concordant between each analysis method (radiologists or AI) and pathological results. Kappa coefficient was used to measure the concordance between radiologists or AI analysis and pathology results. Binominal logistic regression analysis was performed to identify factors influencing the concordance between radiologists’ analysis and pathology results. Overall, the concordance was higher in radiologists’ diagnosis than on AI analysis (kappa coefficient: 0.819 vs. 0.698). Impact of prior mammography (odds ratio (OR): 8.55, p < 0.001), clinical symptom (OR: 5.49, p < 0.001), and fatty breast density (OR: 5.18, p = 0.008) were important factors contributing to the concordance of lesion location between radiologists’ diagnosis and pathology results.
Passive Microwave Radiometry and microRNA Detection for Breast Cancer Diagnostics
Authors: Fisher Leonid , Fisher Olga , Chebanov Dmitry , Vesnin Sergey , Goltsov Alexey , Turnbull Arran , Dixon Mike , Kudaibergenova Indira , Osmonov Batyr , Karbainov Sergey , Popov Larion , Losev Alexander , Goryanin Igor
Published: December 2022

Breast cancer prevention is an important health issue for women worldwide. In this study, we compared the conventional breast cancer screening exams of mammography and ultrasound with the novel approaches of passive microwave radiometry (MWR) and microRNA (miRNA) analysis. While mammography screening dynamics could be completed in 3–6 months, MWR provided a prediction in a matter of weeks or even days. Moreover, MWR has the potential of being complemented with miRNA diagnostics to further improve its predictive quality. These novel techniques can be used alone or in conjunction with more established techniques to improve early breast cancer diagnosis.
E-Learning Course Recommender System Using Collaborative Filtering Models
Authors: Jena Kalyan Kumar , Bhoi Sourav Kumar , Malik Tushar Kanta , Sahoo Kshira Sagar , Jhanjhi N Z , Bhatia Sajal , Amsaad Fathi
Published: December 2022

e-Learning is a sought-after option for learners during pandemic situations. In e-Learning platforms, there are many courses available, and the user needs to select the best option for them. Thus, recommender systems play an important role to provide better automation services to users in making course choices. It makes recommendations for users in selecting the desired option based on their preferences. This system can use machine intelligence (MI)-based techniques to carry out the recommendation mechanism. Based on the preferences and history, this system is able to know what the users like most. In this work, a recommender system is proposed using the collaborative filtering mechanism for e-Learning course recommendation. This work is focused on MI-based models such as K-nearest neighbor (KNN), Singular Value Decomposition (SVD) and neural network–based collaborative filtering (NCF) models. Here, one lakh of Coursera’s course review dataset is taken from Kaggle for analysis. The proposed work can help learners to select the e-Learning courses as per their preferences. This work is implemented using Python language. The performance of these models is evaluated using performance metrics such as hit rate (HR), average reciprocal hit ranking (ARHR) and mean absolute error (MAE). From the results, it is observed that KNN is able to perform better in terms of higher HR and ARHR and lower MAE values as compared to other models.
A New Unusual Subgenus of the Genus Chrysolina (Coleoptera: Chrysomelidae: Chrysomelinae) from the Highland Forests of China, Yunnan Province
Authors: Bieńkowski Andrzej
Published: December 2022

A new subgenus of the genus Chrysolina Motschulsky, 1860, endemic to Yunnan Province of China, Ch. (Volosatik subgen. nov.) is described. All species inhabit highland forests. Seven species, including four species new to science, are recognized: Chrysolina fascinatrix Lopatin, 1998, Ch. liqingzhaoae Daccordi et Ge, 2011, Ch. wangi Lopatin, 2005, Ch. igori sp. nov., Ch. marinae sp. nov., Ch. genriki sp. nov., and Ch. ilyakabaki sp. nov. The representatives of this new subgenus are characterised by a small, broadly oval, convex, shining body with metallic dorsum, with maxillary palpus narrow, similar in both sexes, with pronotal lateral impressions wide and shallow or obsolete, without numerous large punctures, with elytral puncture rows paired, mostly regular, intervals flat, with tarsomeres 1–3 with entire sole, rather narrow in both sexes, with aedeagus bearing sensilla of different types ventro-laterally near apex, flagellum narrow. Photographs of habitus and male aedeagus are presented.
Opportunistic Survey Analyses Reveal a Recent Decline of Skate (Rajiformes) Biomass in Falkland Islands Waters
Authors: Winter Andreas , Arkhipkin Alexander
Published: December 2022

Data were combined from surveys in 2013, 2018, 2019 and 2021 to examine biomass changes of the skate (Rajiformes) stock in waters around the Falkland Islands. The 2013 and 2019 surveys were research surveys for skate abundance and used 90 mm trawl mesh to capture species and size compositions. The 2018 survey was a mesh size trial, and the 2021 survey was a commercial exploration; both used 400 mm trawl mesh to target skates. All four surveys were compared for biomass by deselecting the proportions of skates per size interval caught in 90 mm mesh that would not have been caught in 400 mm mesh, calculated with the SELECT method. Estimated commercial-size skate biomass decreased for most species individually and approximately 61% overall. Estimated commercial-size skate biomass also decreased by as much south of 51° latitude, the area that was closed to skate target fishing since 1996, as north of 51° latitude, which has been maintained open to skate target fishing. The outcome is correlated with continuing skate bycatch in finfish trawls.
MYC Causes Multiple Myeloma Progression via Attenuating TP53-Induced MicroRNA-34 Expression
Authors: Murakami Yuki , Kimura-Masuda Kei , Oda Tsukasa , Matsumura Ikuko , Masuda Yuta , Ishihara Rei , Watanabe Saki , Kuroda Yuko , Kasamatsu Tetsuhiro , Gotoh Nanami , Takei Hisashi , Kobayashi Nobuhiko , Saitoh Takayuki , Murakami Hirokazu , Handa Hiroshi
Published: December 2022

MicroRNAs (miRNAs and miRs) are small (19–25 base pairs) non-coding RNAs with the ability to modulate gene expression. Previously, we showed that the miR-34 family is downregulated in multiple myeloma (MM) as the cancer progressed. In this study, we aimed to clarify the mechanism of miRNA dysregulation in MM. We focused particularly on the interaction between MYC and the TP53-miR34 axis because there is a discrepancy between increased TP53 and decreased miR-34 expressions in MM. Using the nutlin-3 or Tet-on systems, we caused wild-type (WT) p53 protein accumulation in human MM cell lines (HMCLs) and observed upregulated miR-34 expression. Next, we found that treatment with an Myc inhibitor alone did not affect miR-34 expression levels, but when it was coupled with p53 accumulation, miR-34 expression increased. In contrast, forced MYC activation by the MYC-ER system reduced nutlin-3-induced miR-34 expression. We also observed that TP53 and MYC were negatively correlated with mature miR-34 expressions in the plasma cells of patients with MM. Our results suggest that MYC participates in the suppression of p53-dependent miRNA expressions. Because miRNA expression suppresses tumors, its inhibition leads to MM development and malignant transformation.
Improving the Utilization of STRmix™ Variance Parameters as Semi-Quantitative Profile Modeling Metrics
Authors: Duke Kyle , Myers Steven , Cuenca Daniela , Wallin Jeanette
Published: December 2022

Distributions of the variance parameter values developed during the validation process. Comparisons of these prior distributions to the run-specific average are one measure used by analysts to assess the reliability of a STRmix deconvolution. This study examined the behavior of three different STRmix variance parameters under standard amplification and interpretation conditions, as well as under a variety of challenging conditions, with the goal of making comparisons to the prior distributions more practical and meaningful. Using information found in STRmix v2.8 Interpretation Reports, we plotted the log10 of each variance parameter against the log10 of the template amount of the highest-level contributor (Tc) for a large set of mixture data amplified under standard conditions. We observed nonlinear trends in these plots, which we regressed to fourth-order polynomials, and used the regression data to establish typical ranges for the variance parameters over the Tc range. We then compared the typical variance parameter ranges to log10(variance parameter) v log10(Tc) plots for mixtures amplified and interpreted under a variety of challenging conditions. We observed several distinct patterns to variance parameter shifts in the challenged data interpretations in comparison to the unchallenged data interpretations, as well as distinct shifts in the unchallenged variance parameters away from their prior gamma distribution modes over specific ranges of Tc. These findings suggest that employing empirically determined working ranges for variance parameters may be an improved means of detecting whether aberrations in the interpretation were meaningful enough to trigger greater scrutiny of the electropherogram and genotype interpretation.
Estimation of Linkage Disequilibrium, Effective Population Size, and Genetic Parameters of Phenotypic Traits in Dabieshan Cattle
Authors: Jin Hai , Zhao Shuanping , Jia Yutang , Xu Lei
Published: December 2022

Dabieshan cattle (DBSC) are a valuable genetic resource for indigenous cattle breeds in China. It is a small to medium-sized breed with slower growth, but with good meat quality and fat deposition. Genetic markers could be used for the estimation of population genetic structure and genetic parameters. In this work, we genotyped the DBSC breeding population (n = 235) with the GeneSeek Genomic Profiler (GGP) 100 k density genomic chip. Genotype data of 222 individuals and 81,579 SNPs were retained after quality control. The average minor allele frequency (MAF) was 0.20 and the average linkage disequilibrium (LD) level (r2) was 0.67 at a distance of 0–50 Kb. The estimated relationship coefficient and effective population size (Ne) were 0.023 and 86 for the current generation. In addition, we used genotype data to estimate the genetic parameters of the population’s phenotypic traits. Among them, height at hip cross (HHC) and shin circumference (SC) were rather high heritability traits, with heritability of 0.41 and 0.54, respectively. The results reflected the current cattle population’s extent of inbreeding and history. Through the principal breeding parameters, genomic breeding would significantly improve the genetic progress of breeding.
Digital PCR as a New Method for Minimal Residual Disease Monitoring and Treatment Free Remission Management in Chronic Myeloid Leukemia Patients: Is It Reliable?
Authors: Bernardi Simona , Malagola Michele , Farina Mirko , Polverelli Nicola , Re Federica , Russo Domenico
Published: December 2022

The effective and sensitive monitoring of Minimal Residual Disease or Measurable Residual Disease (MRD) is a very important aspect in the management of patients affected by hematologic malignancies. The recent availability of new technologies has opened to the improvement of MRD monitoring. It is particularly relevant in patients affected by Chronic Myeloid Leukemia (CML). MRD monitoring is key in the management of CML patients thanks to the efficacy of TKIs therapy. Moreover, the policies of TKIs discontinuation aimed at treatment free remission are strongly based on the good selection of patients eligible for stopping TKIs therapy. The recently described application of digital PCR in CML patients monitoring seems to improve the accuracy and precision in the identification of optimal responders. The present review reports an overview on the application of digital PCR in the monitoring of MRD in CML and its impact on TKIs discontinuation trials and, consequently, on TFR success.
Adjustable Thermo-Responsive, Cell-Adhesive Tissue Engineering Scaffolds for Cell Stimulation through Periodic Changes in Culture Temperature
Authors: Vejjasilpa Ketpat , Maqsood Iram , Schulz-Siegmund Michaela , Hacker Michael C.
Published: December 2022

A three-dimensional (3D) scaffold ideally provides hierarchical complexity and imitates the chemistry and mechanical properties of the natural cell environment. Here, we report on a stimuli-responsive photo-cross-linkable resin formulation for the fabrication of scaffolds by continuous digital light processing (cDLP), which allows for the mechano-stimulation of adherent cells. The resin comprises a network-forming trifunctional acrylate ester monomer (trimethylolpropane triacrylate, or TMPTA), N-isopropyl acrylamide (NiPAAm), cationic dimethylaminoethyl acrylate (DMAEA) for enhanced cell interaction, and 4-acryloyl morpholine (AMO) to adjust the phase transition temperature (Ttrans) of the equilibrium swollen cross-polymerized scaffold. With glycofurol as a biocompatible solvent, controlled three-dimensional structures were fabricated and the transition temperatures were adjusted by resin composition. The effects of the thermally induced mechano-stimulation were investigated with mouse fibroblasts (L929) and myoblasts (C2C12) on printed constructs. Periodic changes in the culture temperature stimulated the myoblast proliferation.
Novel Antidepressant Mechanism of Ginsenoside Rg1 in Regulating the Dysfunction of the Glutamatergic System in Astrocytes
Authors: Zhang Ningning , Jiang Hong , Wang Huiqin , Wang Yating , Peng Ye , Liu Yangbo , Xia Congyuan , Yan Xu , Chu Shifeng , Zhang Yi , Wang Zhenzhen , Chen Naihong
Published: December 2022

Ginsenoside Rg1, a traditional Chinese medicine monomer, has been shown to have antidepressant effects. We previously found that Rg1 exerts antidepressant effects by improving the gap junction channels (GJCs) dysfunction; however, the downstream mechanisms through which Rg1 ameliorates GJC dysfunction remain unclear. Since hemichannels directly release glutamate, GJC dysfunction decreases the expression levels of glutamate transporters in astrocytes, and glutamatergic system dysfunction plays an essential role in the pathogenesis of depression. The glutamatergic system may be a potential downstream target of Rg1 that exerts antidepressant effects. Therefore, in this study, we aimed to determine the downstream mechanisms by which Rg1 ameliorated GJC dysfunction and exerted its antidepressant effects. Corticosterone (CORT) is used to mimic high glucocorticoid levels in patients with depression in vitro. Primary cortical astrocytes were isolated and phosphorylation of connexin43 (Cx43) as well as the functions of hemichannels, GJCs, and the glutamatergic system were evaluated after drug treatment. Rg1 pretreatment reversed the anomalous activation of Cx43 phosphorylation as well as the dysfunction of hemichannels, GJCs, and the glutamatergic system induced by CORT. These results suggest that Rg1 can ameliorate CORT-induced dysfunction of the glutamatergic system in astrocytes by potentially reducing Cx43 phosphorylation and inhibiting opening of hemichannels, thereby improving GJC dysfunction.
MicroRNAs as Biomarkers for Coronary Artery Disease Related to Type 2 Diabetes Mellitus—From Pathogenesis to Potential Clinical Application
Authors: Szydełko Joanna , Matyjaszek-Matuszek Beata
Published: December 2022

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease with still growing incidence among adults and young people worldwide. Patients with T2DM are more susceptible to developing coronary artery disease (CAD) than non-diabetic individuals. The currently used diagnostic methods do not ensure the detection of CAD at an early stage. Thus, extensive research on non-invasive, blood-based biomarkers is necessary to avoid life-threatening events. MicroRNAs (miRNAs) are small, endogenous, non-coding RNAs that are stable in human body fluids and easily detectable. A number of reports have highlighted that the aberrant expression of miRNAs may impair the diversity of signaling pathways underlying the pathophysiology of atherosclerosis, which is a key player linking T2DM with CAD. The preclinical evidence suggests the atheroprotective and atherogenic influence of miRNAs on every step of T2DM-induced atherogenesis, including endothelial dysfunction, endothelial to mesenchymal transition, macrophage activation, vascular smooth muscle cells proliferation/migration, platelet hyperactivity, and calcification. Among the 122 analyzed miRNAs, 14 top miRNAs appear to be the most consistently dysregulated in T2DM and CAD, whereas 10 miRNAs are altered in T2DM, CAD, and T2DM-CAD patients. This up-to-date overview aims to discuss the role of miRNAs in the development of diabetic CAD, emphasizing their potential clinical usefulness as novel, non-invasive biomarkers and therapeutic targets for T2DM individuals with a predisposition to undergo CAD.
Ribosomal Stress Couples with the Hypoxia Response in Dec1-Dependent Orthodontic Tooth Movement
Authors: Nakamura Shigeru , Tanimoto Keiji , Bhawal Ujjal K.
Published: December 2022

This study characterized the effects of a deficiency of the hypoxia-responsive gene, differentiated embryonic chondrocyte gene 1 (Dec1), in attenuating the biological function of orthodontic tooth movement (OTM) and examined the roles of ribosomal proteins in the hypoxic environment during OTM. HIF-1α transgenic mice and control mice were used for hypoxic regulation of periodontal ligament (PDL) fibroblasts. Dec1 knockout (Dec1KO) and wild-type (WT) littermate C57BL/6 mice were used as in vivo models of OTM. The unstimulated contralateral side served as a control. In vitro, human PDL fibroblasts were exposed to compression forces for 2, 4, 6, 24, and 48 h. HIF-1α transgenic mice had high expression levels of Dec1, HSP105, and ribosomal proteins compared to control mice. The WT OTM mice displayed increased Dec1 expression in the PDL fibroblasts. Micro-CT analysis showed slower OTM in Dec1KO mice compared to WT mice. Increased immunostaining of ribosomal proteins was observed in WT OTM mice compared to Dec1KO OTM mice. Under hypoxia, Dec1 knockdown caused a significant suppression of ribosomal protein expression in PDL fibroblasts. These results reveal that the hypoxic environment in OTM could have implications for the functions of Dec1 and ribosomal proteins to rejuvenate periodontal tissue homeostasis.
Fermented Perilla frutescens Ameliorates Depression-like Behavior in Sleep-Deprivation-Induced Stress Model
Authors: Jee Hye Jin , Ryu Dajung , Kim Suyeon , Yeon Sung Hum , Son Rak Ho , Hwang Seung Hwan , Jung Yi-Sook
Published: December 2022

Excessive stress plays a critical role in the pathogenesis of mood disorders such as depression. Fermented natural products have recently attracted attention because of their health benefits. We evaluated the antidepressant-like efficacy of fermented Perilla frutescens (FPF), and its underlying mechanisms, in sleep deprivation (SD)-induced stress mice. SD-stressed mice revealed a remarkable increase in the immobility time in both forced swimming test and tail suspension test; this increase was ameliorated by treatment with FPF at doses of 100 and 150 mg/kg. FPF treatment also reduced the level of stress hormones such as corticosterone and adrenocorticotropic hormone. Additionally, FPF increased the levels of serotonin and dopamine which were significantly decreased in the brain tissues of SD-stressed mice. The increased expression of proinflammatory cytokines, such as TNF-α and IL1β, and the decreased expression of brain-derived neurotrophic factor (BDNF) in the stressed mice were significantly reversed by FPF treatment. Furthermore, FPF also increased phosphorylation of tropomyosin receptor kinase B (TrkB), extracellular regulated protein kinase (ERK), and cAMP response element binding protein (CREB). Among the six components isolated from FPF, protocatechuic acid and luteolin-7-O-glucuronide exhibited significant antidepressant-like effects, suggesting that they are major active components. These findings suggest that FPF has therapeutic potential for SD-induced stress, by correcting dysfunction of hypothalamic-pituitary-adrenal axis and modulating the BDNF/TrkB/ERK/CREB signaling pathway.
Structural Studies of Expressed tIK, Anti-Inflammatory Peptide
Authors: Kim Minseon , Kim Yongae
Published: December 2022

Cytokine imbalance is one of the causes of inflammation. Inflammation has yet to be adequately treated without side effects. Therefore, we tried to develop a peptide drug with minimal side effects. Peptide drugs have the advantage of being bio-friendly and bio-specific. In a previous study, three peptides with anti-inflammatory activity were derived based on a truncated IK (tIK) protein, which was a fragment of the IK protein with anti-inflammatory effects. The objective of this study was to optimize the process of expressing, isolating, and purifying the three peptides using bacterial strains and describe the process. Circular dichroism and solution state nuclear magnetic resonance spectroscopy were performed on the final purified high-purity peptide and its secondary structure was also identified.
Acute Inflammation in Tissue Healing
Authors: Soliman Amro M. , Barreda Daniel R.
Published: December 2022

There are well-established links between acute inflammation and successful tissue repair across evolution. Innate immune reactions contribute significantly to pathogen clearance and activation of subsequent reparative events. A network of molecular and cellular regulators supports antimicrobial and tissue repair functions throughout the healing process. A delicate balance must be achieved between protection and the potential for collateral tissue damage associated with overt inflammation. In this review, we summarize the contributions of key cellular and molecular components to the acute inflammatory process and the effective and timely transition toward activation of tissue repair mechanisms. We further discuss how the disruption of inflammatory responses ultimately results in chronic non-healing injuries.
Endoglin Is an Important Mediator in the Final Common Pathway of Chronic Kidney Disease to End-Stage Renal Disease
Authors: Gerrits Tessa , Brouwer Isabella J. , Dijkstra Kyra L. , Wolterbeek Ron , Bruijn Jan A. , Scharpfenecker Marion , Baelde Hans J.
Published: December 2022

Chronic kidney disease (CKD) is a slow-developing, progressive deterioration of renal function. The final common pathway in the pathophysiology of CKD involves glomerular sclerosis, tubular atrophy and interstitial fibrosis. Transforming growth factor-beta (TGF-β) stimulates the differentiation of fibroblasts towards myofibroblasts and the production of extracellular matrix (ECM) molecules, and thereby interstitial fibrosis. It has been shown that endoglin (ENG, CD105), primarily expressed in endothelial cells and fibroblasts, can function as a co-receptor of TGF signaling. In several human organs, endoglin tends to be upregulated when chronic damage and fibrosis is present. We hypothesize that endoglin is upregulated in renal interstitial fibrosis and plays a role in the progression of CKD. We first measured renal endoglin expression in biopsy samples obtained from patients with different types of CKD, i.e., IgA nephropathy, focal segmental glomerulosclerosis (FSGS), diabetic nephropathy (DN) and patients with chronic allograft dysfunction (CAD). We showed that endoglin is upregulated in CAD patients (p < 0.001) and patients with DN (p < 0.05), compared to control kidneys. Furthermore, the amount of interstitial endoglin expression correlated with eGFR (p < 0.001) and the amount of interstitial fibrosis (p < 0.001), independent of the diagnosis of the biopsies. Finally, we investigated in vitro the effect of endoglin overexpression in TGF-β stimulated human kidney fibroblasts. Overexpression of endoglin resulted in an enhanced ACTA2, CCN2 and SERPINE1 mRNA response (p < 0.05). It also increased the mRNA and protein upregulation of the ECM components collagen type I (COL1A1) and fibronectin (FN1) (p < 0.05). Our results suggest that endoglin is an important mediator in the final common pathway of CKD and could be used as a possible new therapeutic target to counteract the progression towards end-stage renal disease (ESRD).
Spatial Distribution of Pyrethroid Resistance and kdr Mutations in Aedes aegypti from La Guajira, Colombia
Authors: Maestre-Serrano Ronald , Flórez-Rivadeneira Zulibeth , Castro-Camacho Juan M. , Soto-Arenilla Eva , Gómez-Camargo Doris , Pareja-Loaiza Paula , Ponce-Garcia Gustavo , Juache-Villagrana Alan E. , Flores Adriana E.
Published: December 2022

Dengue, chikungunya, and Zika are of great concern to the public health of Colombia. One of the main control strategies for these diseases is the application of insecticides directed at the Aedes aegypti vector. However, insecticide resistance has been increasingly recorded in the country, making control measures difficult. Here, we evaluated the resistance profiles for pyrethroids in populations of Ae. aegypti from La Guajira, Colombia. The frequency (diagnostic dose, DD) and intensity (2×, 5×, and 10× DD) of resistance to permethrin, deltamethrin, and lambda-cyhalothrin were determined in 15 populations of Ae. aegypti from La Guajira, Colombia, using the bottle bioassay. The kdr mutations V1016I, F1534C, and V410L, were identified, and their allele and genotype frequencies were calculated. Finally, the mortality values for the analyzed pyrethroids were interpolated following the IDW method for predicting pyrethroid resistance. The populations of Ae. aegypti showed a high frequency of resistance to permethrin with a low to moderate intensity, which was associated with the triple-resistant haplotype LL410/II1016/CC1534. They remain susceptible to deltamethrin and, in some populations, expressed the risk of developing resistance to lambda-cyhalothrin.
Mid-Term Results following Traumatic Knee Joint Dislocation
Authors: Watrinet Julius , von Rüden Christian , Regenbogen Stephan , Brand Andreas , Bormann Markus , Stuby Fabian M. , Fürmetz Julian
Published: December 2022

Purpose: Although treatment strategies of knee joint dislocations have evolved, there is still no consensus on the best method and timing. New therapeutic concepts suggest that early one-stage treatment, including suturing and bracing of the cruciate ligaments in acute knee joint dislocation, are leading to improved functional results. This study aimed to evaluate the midterm functional outcome following traumatic knee joint dislocation and to determine whether the outcome is influenced by the surgical management, patient habitus or concomitant injuries. Methods: In this retrospective single center study, 38 patients with acute Schenck type II to IV knee dislocations were treated over an eight-year period in a level I trauma center. At follow-up, various clinical scores, such as the International Knee Documentation Committee (IKDC) Score, Lysholm Score, and Tegner Activity Scale (TAS), and individual questions about rehabilitation and activity levels of 38 patients were evaluated. Results: Mean follow-up was 5.5 ± 2.7 years. The mean IKDC Score was 65.6 ± 15.7 points, the average Lysholm Score was 70.5 ± 16.4 points and the median TAS was 4 (0–7), resulting in a loss of activity of 2 (range 0–6) points. There was no significant difference between a one-stage treatment compared to a two-stage approach. Ligament reconstruction of the ACL in a two-stage approach was required in only 33.3%. Further operations (early and late) were performed in 37% of cases. Being overweight was associated with more complications and worse outcomes, and external fixation with arthrofibrosis. Conclusions: Knee dislocation is a severe trauma that often leads to a prolonged loss of function and increased knee pain over years, affecting the patient’s activity. Clinical outcome is influenced significantly by concomitant injuries. Severe cases with initial external fixation are associated with a higher risk of knee stiffness and should be considered during rehabilitation. Obese patients present a challenge due to higher complication rates and lower postoperative knee function. Level of evidence: Retrospective single center study, level III.
Effects of Posterior Spinal Correction and Fusion on Postural Stability in Patients with Adolescent Idiopathic Scoliosis
Authors: Osuka Satoshi , Sudo Hideki , Yamada Katsuhisa , Tachi Hiroyuki , Watanabe Kentaro , Sentoku Fuma , Chiba Takeshi , Iwasaki Norimasa , Mukaino Masahiko , Tohyama Harukazu
Published: December 2022

The present study aimed to assess the effects of posterior spinal correction and fusion on postural stability in patients with adolescent idiopathic scoliosis (AIS). The study included 41 female patients with AIS at our institution. All patients performed three 10 s single-leg standing trials on a force plate. The center of pressure (COP) was measured preoperatively, and at 1 week and 6 months postoperatively. The postural stability parameters were absolute minimum time-to-boundary (TTB), mean of the minimum TTB, mean COP velocity, standard deviation, range, and 95% confidence ellipse area. One-way repeated analysis of variance or Friedman test was applied to the postural stability parameters. Multiple comparisons were performed using the Bonferroni correction. The absolute minimum TTB and the mean minimum TTB showed a significant increase 6 months post-operation as compared to preoperatively and 1 week postoperatively. The COP velocity significantly decreased at 6 months post-operation compared to preoperatively and 1 week postoperatively. These changes in postural stability indicate that spinal correction and fusion can be considered to improve postural stability during single-leg standing tests in the postoperative period.
Uteroplacental–Cerebral Ratio: A Doppler Parameter for Prognostic Prediction of Late-Onset Fetal Growth Restriction: Single Center Prospective Cohort Study
Authors: Yang Ziling , Lv Wenjie , Zhao Baojing , Yao Jie , Yang Yuanyuan , Yin Zongzhi
Published: December 2022

Purpose: This study aimed to elucidate the accuracy of Doppler parameters in predicting the prognosis of late-onset fetal growth restriction (FGR). Methods: This was a prospective study of 114 pregnancies. Doppler parameters, including the cerebroplacental ratio and pulsatility index (PI) in the middle cerebral, umbilical, uterine artery, were recorded. The new uteroplacental–cerebro ratio (UPCR) was constructed as the ratio of (umbilical artery + mean of the left and right uterine artery) to middle cerebral artery PI. Logistic regression analyses and receiver operating characteristic curves were performed. Results: Adverse outcomes occurred in 37 (32%) neonates. The z values of the middle cerebral artery PI and cerebroplacental ratio were lower (p < 0.001), while the z values of the umbilical artery PI, mean uterine artery PI, and UPCR (p < 0.001) were higher in late-onset FGR in those with compared to those without adverse outcomes. Multivariate logistic regression revealed that only UPCR was independently associated with adverse outcomes (p < 0.001). For predicting the prognosis of late-onset FGR, UPCR showed a fair degree of accuracy (area under the curve [AUC], 0.824). Conclusion: The new UPCR, reflecting the impact of placental impedance from both fetal and maternal sides on fetal well-being, improves the accuracy of prognostic prediction for late-onset FGR.
Prognostic Value of Pre-Treatment [18F]FDG PET/CT Texture Analysis in Undifferentiated Soft-Tissue Sarcoma
Authors: Annovazzi Alessio , Ferraresi Virginia , Covello Renato , Ascione Andrea , Vari Sabrina , Petrongari Maria , Baldi Jacopo , Biagini Roberto , Sciuto Rosa
Published: December 2022

Background: Undifferentiated soft-tissue sarcomas (USTS) are one of the most common sarcoma histotypes in adults. The standard of care is surgical excision plus adjuvant radiotherapy, while the use of perioperative chemotherapy is still controversial. The aim of this study was to investigate the value of pre-treatment [18F]FDG PET/CT conventional metrics and textural features in predicting disease-free survival (DFS) and overall survival (OS) in patients with USTS of the limbs and trunk. Methods: [18F]FDG PET/CT scans of 51 consecutive patients with locally advanced USTS were retrospectively evaluated. Conventional and textural PET parameters were analysed and tested as predictive factors for DFS and OS. Results: During a median follow up of 50.7 months, 23 (45.1%) and 29 (56.9%) patients had death or disease progression, respectively. Univariate analysis revealed a significant association for perioperative treatment, PET volumetric parameters and the textural feature GLCM_correlation with DFS and OS. In multivariate analysis, perioperative treatment and GLCM_correlation were the only independent factors, allowing stratification of the population into three different prognostic classes. Conclusion: GLCM_correlation can identify USTS at high risk of relapse and death, thus helping to optimize the perioperative treatment of patients.
Effects of Ambient Air Pollution on Precocious Puberty: A Case-Crossover Analysis in Nanjing, China
Authors: Yang Haibo , Ge Aichen , Xie Hang , Li Wei , Qin Yizhou , Yang Wentao , Wang Dandan , Gu Wei , Wang Xu
Published: December 2022

Background: Ambient air pollution is closely related to a variety of health outcomes. Few studies have focused on the correlations between air pollution exposure and children’s sexual development. In this study, we investigated the potential effects of exposure to air pollution on precocious puberty among children using real-world evidence. Methods: We conducted a case-crossover study (n = 2201) to investigate the effect of ambient air pollution exposure on precocious puberty from January 2016 to December 2021. Average exposure levels of PM2.5, PM10, SO2, NO2, CO, and O3 before diagnosis were calculated by using the inverse distance weighting (IDW) method. Distributed lag nonlinear model (DLNM) was used to assess the effect of air pollutants exposure on precocious puberty. Results: The mean age of the children who were diagnosed with precocious puberty was 7.47 ± 1.24 years. The average concentration of PM2.5 and PM10 were 38.81 ± 26.36 μg/m3 and 69.77 ± 41.07 μg/m3, respectively. We found that exposure to high concentrations of PM2.5 and PM10 might increase the risk of precocious puberty using the DLNM model adjusted for the age, SO2, NO2, CO, and O3 levels. The strongest effects of the PM2.5 and PM10 on precocious puberty were observed in lag 27 (OR = 1.72, 95% CI: 1.01–2.92) and lag 16 (OR = 1.95, 95% CI: 1.33–2.85), respectively. Conclusion: Our findings supported that short-term exposure to air pollution was the risk factor for precocious puberty. Every effort should be made to protect children from air pollution.
Upregulation of miRNA-200c during Disease Progression in COVID-19 Patients
Authors: van de Sand Lukas , Braß Peer , Gregorius Jonas , Pattberg Kevin , Engler Andrea , Dittmer Ulf , Taube Christian , Brock Stephan , Berger Marc Moritz , Brenner Thorsten , Witzke Oliver , Krawczyk Adalbert
Published: December 2022

The COVID-19 pandemic has caused more than 6 million deaths worldwide since its first outbreak in December 2019 and continues to be a major health problem. Several studies have established that the infection by SARS-CoV-2 can be categorized in a viremic, acute and recovery or severe phase. Hyperinflammation during the acute pneumonia phase is a major cause of severe disease progression and death. Treatment of COVID-19 with directly acting antivirals is limited within a narrow window of time between first clinical symptoms and the hyperinflammatory response. Therefore, early initiation of treatment is crucial to assure optimal health care for patients. Molecular diagnostic biomarkers represent a potent tool to predict the course of disease and thus to assess the optimal treatment regimen and time point. Here, we investigated miRNA-200c as a potential marker for the prediction of the severity of COVID-19 to preventively initiate and personalize therapeutic interventions in the future. We found that miRNA-200c correlates with the severity of disease. With retrospective analysis, however, there is no correlation with prognosis at the time of hospitalization. Our study provides the basis for further evaluation of miRNA-200c as a predictive biomarker for the progress of COVID-19.
Comparison of Biological Agent Monotherapy and Associations Including Disease-Modifying Antirheumatic Drugs for Rheumatoid Arthritis: Literature Review and Meta-Analysis of Randomized Trials
Authors: Delpech Célia , Laborne François-Xavier , Hilliquin Pascal
Published: December 2022

Objective: Update the available evidence comparing biologic disease-modifying antirheumatic drugs (bDMARDs) in combination with conventional synthetic disease-modifying antirheumatic drugs (CsDMARDs) to bDMARDs in monotherapy in patients with rheumatoid arthritis. Methods: Research was limited to randomized controlled trials. Major outcome: ACR 20 response criteria at 24 weeks. Secondary outcomes: clinical and radiographic criteria at week 24, 52 and 104. Results: 23 trials (6358 patients), including seven bDMARDs and one other molecule: Anbainuo (anti-TNF-R). No study satisfied our search criteria for anakinra, certolizumab and infliximab. Compared to bDMARD monotherapy, combination therapy gives a better ACR 20 at 24 weeks (RR: 0.88 (0.84–0.94)) in fixed and random effect models, and this result is sustained at 52 and 104 weeks. The results were mostly similar for all other outcomes without increasing the risk of adverse effects. Conclusion: This meta-analysis confirms the superiority of combination therapy over monotherapy in rheumatoid arthritis, in accordance to the usual guidelines.