Genes and Pathways Associated with Skeletal Sagittal Malocclusions: A Systematic Review

Skeletal class II and III malocclusions are craniofacial disorders that negatively impact people’s quality of life worldwide. Unfortunately, the growth patterns of skeletal malocclusions and their clinical correction prognoses are difficult to predict largely due to lack of knowledge of their precise etiology. Inspired by the strong inheritance pattern of a specific type of skeletal malocclusion, previous genome-wide association studies (GWAS) were reanalyzed, resulting in the identification of 19 skeletal class II malocclusion-associated and 53 skeletal class III malocclusion-associated genes. Functional enrichment of these genes created a signal pathway atlas in which most of the genes were associated with bone and cartilage growth and development, as expected, while some were characterized by functions related to skeletal muscle maturation and construction. Interestingly, several genes and enriched pathways are involved in both skeletal class II and III malocclusions, indicating the key regulatory effects of these genes and pathways in craniofacial development. There is no doubt that further investigation is necessary to validate these recognized genes’ and pathways’ specific function(s) related to maxillary and mandibular development. In summary, this systematic review provides initial insight on developing novel gene-based treatment strategies for skeletal malocclusions and paves the path for precision medicine where dental care providers can make an accurate prediction of the craniofacial growth of an individual patient based on his/her genetic profile. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Neural EGFL Like 1 as a Potential Pro-Chondrogenic, Anti-Inflammatory Dual-Functional Disease-Modifying Osteoarthritis Drug

Arthritis, an inflammatory condition that causes pain and cartilage destruction in joints, affects over 54.4 million people in the US alone. Here, for the first time, we demonstrated the emerging role of neural EGFL like 1 (NELL-1) in arthritis pathogenesis by showing that Nell-1-haploinsufficient (Nell-1+/6R) mice had accelerated and aggravated osteoarthritis (OA) progression with elevated inflammatory markers in both spontaneous primary OA and chemical-induced secondary OA models. In the chemical-induced OA model, intra-articular injection of interleukin (IL)1β induced more severe inflammation and cartilage degradation in the knee joints of Nell-1+/6R mice than in wildtype animals. Mechanistically, in addition to its pro-chondrogenic potency, NELL-1 also effectively suppressed the expression of inflammatory cytokines and their downstream cartilage catabolic enzymes by upregulating runt-related transcription factor (RUNX)1 in mouse and human articular cartilage chondrocytes. Notably, NELL-1 significantly reduced IL1β-stimulated inflammation and damage to articular cartilage in vivo. In particular, NELL-1 administration markedly reduced the symptoms of antalgic gait observed in IL1β-challenged Nell-1+/6R mice. Therefore, NELL-1 is a promising pro-chondrogenic, anti-inflammatory dual-functional disease-modifying osteoarthritis drug (DMOAD) candidate for preventing and suppressing arthritis-related cartilage damage. © 2019 Elsevier Lt

Neurexin Superfamily Cell Membrane Receptor Contactin-Associated Protein Like-4 (Cntnap4) Is Involved in Neural EGFL-Like 1 (Nell-1)-Responsive Osteogenesis

Contactin-associated protein-like 4 (Cntnap4) is a member of the neurexin superfamily of transmembrane molecules that have critical functions in neuronal cell communication. Cntnap4 knockout mice display decreased presynaptic gamma-aminobutyric acid (GABA) and increased dopamine release that is associated with severe, highly penetrant, repetitive, and perseverative movements commonly found in human autism spectrum disorder patients. However, no known function of Cntnap4 has been revealed besides the nervous system. Meanwhile, secretory protein neural EGFL-like 1 (Nell-1) is known to exert potent osteogenic effects in multiple small and large animal models without the off-target effects commonly found with bone morphogenetic protein 2. In this study, while searching for a Nell-1-specific cell surface receptor during osteogenesis, we identified and validated a ligand/receptor-like interaction between Nell-1 and Cntnap4 by demonstrating: 1) Nell-1 and Cntnap4 colocalization on the surface of osteogenic-committed cells; 2) high-affinity interaction between Nell-1 and Cntnap4; 3) abrogation of Nell-1-responsive Wnt and MAPK signaling transduction, as well as osteogenic effects, via Cntnap4 knockdown; and 4) replication of calvarial cleidocranial dysplasias-like defects observed in Nell-1-deficient mice in Wnt1-Cre-mediated Cntnap4-knockout transgenic mice. In aggregate, these findings indicate that Cntnap4 plays a critical role in Nell-1-responsive osteogenesis. Further, this is the first functional annotation for Cntnap4 in the musculoskeletal system. Intriguingly, Nell-1 and Cntnap4 also colocalize on the surface of human hippocampal interneurons, implicating Nell-1 as a potential novel ligand for Cntnap4 in the nervous system. This unexpected characterization of the ligand/receptor-like interaction between Nell-1 and Cntnap4 indicates a novel biological functional axis for Nell-1 and Cntnap4 in osteogenesis and, potentially, in neural development and function. © 2018 American Society for Bone and Mineral Research. © 2018 American Society for Bone and Mineral Researc

CDKN2B Upregulation Prevents Teratoma Formation in Multipotent Fibromodulin-Reprogrammed Cells

Tumorigenicity is a well-documented risk to overcome for pluripotent or multipotent cell applications in regenerative medicine. To address the emerging demand for safe cell sources in tissue regeneration, we established a novel, protein-based reprogramming method that does not require genome integration or oncogene activation to yield multipotent fibromodulin (FMOD)-reprogrammed (FReP) cells from dermal fibroblasts. When compared with induced pluripotent stem cells (iPSCs), FReP cells exhibited a superior capability for bone and skeletal muscle regeneration with markedly less tumorigenic risk. Moreover, we showed that the decreased tumorigenicity of FReP cells was directly related to an upregulation of cyclin-dependent kinase inhibitor 2B (CDKN2B) expression during the FMOD reprogramming process. Indeed, sustained suppression of CDKN2B resulted in tumorigenic, pluripotent FReP cells that formed teratomas in vivo that were indistinguishable from iPSC-derived teratomas. These results highlight the pivotal role of CDKN2B in cell fate determination and tumorigenic regulation and reveal an alternative pluripotent/multipotent cell reprogramming strategy that solely uses FMOD protein. © 2019, American Society for Clinical Investigation

AGI-P: A Gender Identification Framework for Authorship Analysis Using Customized Fine-Tuning of Multilingual Language Model

In this investigation, we propose a solution for the author’s gender identification task called AGI-P. This task has several real-world applications across different fields, such as marketing and advertising, forensic linguistics, sociology, recommendation systems, language processing, historical analysis, education, and language learning. We created a new dataset to evaluate our proposed method. The dataset is balanced in terms of gender using a random sampling method and consists of 1944 samples in total. We use accuracy as an evaluation measure and compare the performance of the proposed solution (AGI-P) against state-of-the-art machine learning classifiers and fine-tuned pre-trained multilingual language models such as DistilBERT, mBERT, XLM-RoBERTa, and Multilingual DEBERTa. In this regard, we also propose a customized fine-tuning strategy that improves the accuracy of the pre-trained language models for the author gender identification task. Our extensive experimental studies reveal that our solution (AGI-P) outperforms the well-known machine learning classifiers and fine-tuned pre-trained multilingual language models with an accuracy level of 92.03%. Moreover, the pre-trained multilingual language models, fine-tuned with the proposed customized strategy, outperform the fine-tuned pre-trained language models using an out-of-the-box fine-tuning strategy. The codebase and corpus can be accessed on our GitHub page at: https://github.com/mumairhassan/AGI-

On the interplay between Babai and Černý’s conjectures

Motivated by the Babai conjecture and the Černý conjecture, we study the reset thresholds of automata with the transition monoid equal to the full monoid of transformations of the state set. For automata with n states in this class, we prove that the reset thresholds are upperbounded by 2n2 -6n + 5 and can attain the value (Formula presented). In addition, we study diameters of the pair digraphs of permutation automata and construct n-state permutation automata with diameter (formula presented). © Springer International Publishing AG 2017

Comparing Fear of COVID-19 and Preventive COVID-19 Infection Behaviors Between Iranian and Taiwanese Older People: Early Reaction May Be a Key

This study assessed fear of the novel coronavirus-2019 (COVID-19), preventive COVID-19 infection behaviors, and the association between fear of COVID-19 and preventive COVID-19 infection behaviors among older people in Iran and Taiwan. Older people aged over 60 years (n = 144 for Iranians and 139 for Taiwanese) completed the Fear of COVID-19 Scale (FCV-19S) and two items on preventive COVID-19 infection behaviors (i.e., hand washing and mouth covering when sneezing). Iranian older people had a significantly higher level of fear of COVID-19 than did Taiwanese older people. Moreover, Iranian older people had significantly lower frequencies of preventive COVID-19 infection behaviors than did Taiwanese older people. Different timings in implementing COVID-19 infection control policies in Iran and Taiwan may explain why Iranian older people had greater fear of COVID-19 and lower preventive COVID-19 infection behaviors than did Taiwanese older people

An outcome analysis of self-expandable metallic stents in central airway obstruction: a cohort study

<p>Abstract</p> <p>Background</p> <p>Self-expandable metallic stents (SEMSs) have provided satisfactory management of central airway obstruction. However, the long-term benefits and complications of this management modality in patients with benign and malignant obstructing lesions after SEMS placement are unclear. We performed this cohort study to analyze the outcomes of Ultraflex SEMSs in patients with tracheobronchial diseases.</p> <p>Methods</p> <p>Of 149 patients, 72 with benign and 77 with malignant tracheobronchial disease received 211 SEMSs (benign, 116; malignant, 95) and were retrospectively reviewed in a tertiary hospital.</p> <p>Results</p> <p>The baseline characteristics of patients who received SEMS implantation for benign conditions and those who underwent implantation for malignant conditions were significantly different. These characteristics included age (mean, 63.9 vs. 58; <it>p </it>< 0.01), gender (male, 62% vs. 90%; <it>p </it>< 0.0001), smoking (47% vs. 85%; <it>p </it>< 0.0001), forced expiratory volume in 1 second (mean, 0.9 vs. 1.47 L/s; <it>p </it>< 0.0001), follow-up days after SEMS implantation (median; 429 vs. 57; <it>p </it>< 0.0001), and use of covered SEMS (36.2% vs. 94.7%; <it>p </it>< 0.0001). Symptoms improved more after SEMS implantation in patients with benign conditions than in those with malignant conditions (76.7% vs. 51.6%; <it>p </it>< 0.0001). The overall complication rate after SEMS implantation in patients with benign conditions was higher than that in patients with malignancy (42.2% vs. 21.1%; <it>p </it>= 0.001). Successful management of SEMS migration, granulation tissue formation, and SEMS fracture occurred in 100%, 81.25%, and 85% of patients, respectively.</p> <p>Conclusions</p> <p>Patients who received SEMS implantation owing to benign conditions had worse lung function and were older than those who received SEMS for malignancies. There was higher complication rate in patients with benign conditions after a longer follow-up period owing to the nature of the underlying diseases.</p

Overexpression of Arabidopsis FLOWERING LOCUS T (FT) gene improves floral development in cassava (Manihot esculenta, Crantz)

Cassava is a tropical storage-root crop that serves as a worldwide source of staple food for over 800 million people. Flowering is one of the most important breeding challenges in cassava because in most lines flowering is late and non-synchronized, and flower production is sparse. The FLOWERING LOCUS T (FT) gene is pivotal for floral induction in all examined angiosperms. The objective of the current work was to determine the potential roles of the FT signaling system in cassava. The Arabidopsis thaliana FT gene (atFT) was transformed into the cassava cultivar 60444 through Agrobacterium-mediated transformation and was found to be overexpressed constitutively. FT overexpression hastened flower initiation and associated fork-type branching, indicating that cassava has the necessary signaling factors to interact with and respond to the atFT gene product. In addition, overexpression stimulated lateral branching, increased the prolificacy of flower production and extended the longevity of flower development. While FT homologs in some plant species stimulate development of vegetative storage organs, atFT inhibited storage-root development and decreased root harvest index in cassava. These findings collectively contribute to our understanding of flower development in cassava and have the potential for applications in breeding