University of Missouri

Background Mohs micrographic surgery (MMS) is used for the treatment of high-risk cutaneous squamous cell carcinoma (cSCC). MMS examines the surgical margins in real time and does not commonly examine the central component of the tumor. Objective To determine if debulk specimens provide additional details relevant to tumor staging not gained from routine MMS. Methods A retrospective chart review of debulk specimens taken during MMS for cSCC was performed. Dermatopathology reports were analyzed and tumors were staged using Brigham and Women’s Hospital and American Joint Committee on Cancer’s 8th edition staging systems. Results Permanent section evaluation of debulk specimens did not result in clinically meaningful information for staging that could not be gained from MMS layers or initial biopsy analysis. Limitations A single institution, and a small sample size of 39 tumors. Conclusions Evaluation of debulk specimens during MMS may not always be an effective use of time or health care resources.

In the last chapter, we discussed the near resonance continuation theory for periodic orbits of periodically perturbed oscillators. For the case where the unperturbed oscillator has a regular period annulus, we found that there is generally an infinite number of resonances at which a first-order perturbation theory can be used to prove the existence of perturbed periodic orbits. But, as mentioned previously, we cannot conclude from the results of our analysis that the perturbed oscillator has infinitely many periodic orbits. To do so would seem to require a condition that might be impossible to satisfy. Indeed, the nonzero amplitude of the perturbation would have to be made sufficiently small for each of an infinite sequence of continuations corresponding to an infinite sequence of resonant unperturbed periodic orbits that approaches the boundary of a period annulus.

The subject of this chapter is linear systems of the form

Theorem 3.1 states that the zero solution of a constant coefficient homogeneous linear system is asymptotically stable if the spectrum of the coefficient matrix lies in the left half of the complex plane.

Is the subject of ordinary differential equations important? The ultimate answer to this question is certainly beyond the scope of this book.

This chapter is about the most basic concepts of the theory of differential equations. We will answer some fundamental questions: What is a differential equation? Do differential equations always have solutions? Are solutions of differential equations unique? But, the most important goal of this chapter is to introduce a geometric interpretation for the space of solutions of a differential equation.

This chapter is an introduction to the method of averaging—a far-reaching and rich mathematical subject that has many important applications. Our approach to the subject is through perturbation theory; for example, we will discuss the existence of periodic orbits for periodically forced oscillators.

A fundamental engineering problem is to determine the response of a physical system to an applied force. In this chapter some mathematical ideas are introduced that can be used to address a classic case of this problem where the physical system is an oscillator that is modeled by a differential equation with periodic orbits and the applied force is modeled as a small periodic perturbation. Partial answers to several important questions will be given.

The main objectives of this chapter are formulations and proofs of basic results related to the principle of linearized stability. Recall that a linear homogeneous differential equation has a rest point at the origin. For the special case of constant coefficient homogeneous linear differential equations, the stability of this rest point is directly related to the eigenvalues of the system matrix.

Consider the family of differential equations \( \dot{u} = f(u, \lambda ), \;\; u\in {{\mathbb {R}}}^n,\;\; \lambda \in {{\mathbb {R}}}.\) In case \(f(u_0, \lambda _0) = 0\), the differential equation with parameter value \(\lambda =\lambda _0\) has a rest point at \(u_0\) and the linearized system at this point is given by \( \dot{W} = f_u(u_0, \lambda _0) W.\) If the eigenvalues of the linear transformation \(f_u(u_0, \lambda _0):{\mathbb {R}}^n\mapsto {\mathbb {R}}^n\) are all nonzero, then the transformation is invertible, and by an application of the implicit function theorem there is a curve \(\lambda \mapsto \beta (\lambda )\) in \({\mathbb {R}}^n\) such that \(\beta (\lambda _0) = u_0\) and \(f(\beta (\lambda ), \lambda ) \equiv 0\). In other words, for each \(\lambda \) in the domain of \(\beta \), the point \(\beta (\lambda )\in {\mathbb {R}}^n\) corresponds to a rest point for the member of the family (11.1) at the parameter value \(\lambda \).

In the important special case where \(t\mapsto A(t) \) is a constant function, the solution of \(\dot{x} =Ax\) is reduced to a problem in linear algebra. Also, by defining the matrix exponential, the flow of this autonomous system is associated with a one-parameter linear group with generator A.

This chapter is an introduction to the theory of hyperbolic structures in differential equations. The basic idea that is discussed might be called the principle of hyperbolic linearization: If the system matrix of the linearized flow of a differential equation has no eigenvalue with zero real part, then the nonlinear flow behaves locally like the linear flow.

Introduction Shifting sociopolitical landscapes may create doubts, questions, or concerns for individuals, especially those who hold a disenfranchised identity or are in marginalized relationships (Meyer in Psychology of Sexualities Review 7:81–90, 2016). As a result of political and societal opposition following the Supreme Court Obergefell v. Hodges (2015) decision, for example, legal and social uncertainties may lead to distress for same-sex couples. Methods Guided by the Contextual Relational Uncertainty (CRU) model (Monk & Ogolsky in Journal of Family Theory & Review, 11(2):243–261, 2019), we test the association between sociopolitical uncertainties (i.e., uncertainty about legal recognition, social acceptance, and norms or scripts) and relational uncertainty (i.e., self, partner, and relationship uncertainty) among people in same-sex (n = 180) and different-sex (n = 180) relationships 1 year after the Obergefell ruling. Results We found that most sources of sociopolitical uncertainty were positively associated with the sources of relational uncertainty. Using thematic analysis, we also analyzed responses to open-ended questions about concerns and experiences related to the Obergefell v. Hodges decision. We identified primary themes including increased (a) social certainty and (b) relational security, but also increased uncertainty related to (c) the breadth and permanence of legal recognition, (d) family norms and roles, and (e) potential backlash. Conclusions Overall, these findings provide more evidence of the positive and negative consequences of precarious societal transitions on the lives of individuals, particularly people in marginalized relationships. Policy Implications Policymakers and court system officials should be conscious of the full import of legislation. Even when producing legislation that is perceived to benefit a population, policies and educational resources should be considered that further support these communities across the transition.

Objectives Examining loneliness and social isolation during population-wide historical events may shed light on important theoretical questions about age differences, including whether these differences hold across different regions and the timecourse of the unfolding event. We used a systematic, preregistered approach of coordinated data analysis (CDA) of four studies (total N = 1,307; total observations = 18,492) that varied in design (intensive repeated-measures and cross-sectional), region, timing, and timescale during the first year of the COVID-19 pandemic. Method We harmonized our datasets to a common period within 2020-2021 and created a common set of variables. We used a combination of ordinary least squares regression and multilevel modeling to address the extent to which there was within- and between-person variation in the associations between social isolation and loneliness, and whether these associations varied as a function of age. Results Within- and between-person effects of social interactions were negatively associated with loneliness in one study; in follow-up sensitivity analyses, these patterns held across early and later pandemic periods. Across all datasets, there was no evidence of age differences in the within-person or between-person associations of social interactions and loneliness. Discussion Applying the CDA methodological framework allowed us to detect common and divergent patterns of social interactions and loneliness across samples, ages, regions, periods, and study designs.

An 82-year-old woman with COPD presented to the emergency department with cough, increasing sputum production, wheezing, and worsening shortness of breath for two weeks. On imaging studies, the patient was found to have a right upper lobe spiculated nodule and an endobronchial lesion with near total occlusion of the right lower lobe bronchus with sub-segmental atelectasis. Bronchoscopy with EBUS-TBNA of subcarinal and right hilar lymph nodes revealed lung cancer with clear cell phenotype. Given the predominance of clear cell morphology, the diagnosis of metastatic renal or ovarian cancer was entertained. However, there was no evidence of renal or ovarian lesions on the PET-CT scan, ruling out the possibility. Salivary gland type lung cancer (STLC), which is responsible for less than 1% of all lung cancer cases in adults, was also considered. The two distinct STLCs that may have similar morphologic appearances are hyalinizing clear cell carcinoma (HCCC) and mucoepidermoid carcinoma (MEC). The other type of tumour in the lung that demonstrates a clear cell phenotype is perivascular epithelioid cell neoplasms or PEComa, which are mesenchymal in origin. Immunohistochemical staining was strongly positive for p63, CK5/6, CK7, CK-LMW, and negative for TTF-1, Napsin A, p16, and CK20. Additional staining, including HMB-45, S-100, and mucicarmine, were also negative. Next-generation sequencing for the salivary gland fusion panel, including EWSR1-ATF1 fusion and < EWSR1 gene rearrangement for HCCC and MAML2 gene rearrangements for MEC, was negative. She was diagnosed with non-small cell lung cancer favouring squamous cell carcinoma with clear cell phenotype, a rare entity.

Identifying drug-target interactions (DTIs) holds significant importance in drug discovery and development, playing a crucial role in various areas such as virtual screening, drug repurposing and identification of potential drug side effects. However, existing methods commonly exploit only a single type of feature from drugs and targets, suffering from miscellaneous challenges such as high sparsity and cold-start problems. We propose a novel framework called MSI-DTI (Multi-Source Information-based Drug-Target Interaction Prediction) to enhance prediction performance, which obtains feature representations from different views by integrating biometric features and knowledge graph representations from multi-source information. Our approach involves constructing a Drug-Target Knowledge Graph (DTKG), obtaining multiple feature representations from diverse information sources for SMILES sequences and amino acid sequences, incorporating network features from DTKG and performing an effective multi-source information fusion. Subsequently, we employ a multi-head self-attention mechanism coupled with residual connections to capture higher-order interaction information between sparse features while preserving lower-order information. Experimental results on DTKG and two benchmark datasets demonstrate that our MSI-DTI outperforms several state-of-the-art DTIs prediction methods, yielding more accurate and robust predictions. The source codes and datasets are publicly accessible at https://github.com/KEAML-JLU/MSI-DTI.

Ilex kudingcha C.J. Tseng is a nootropic used throughout Asia that shares a number of metabolites with Ilex paraguariensis used throughout South America. Our previous study using a Drosophila melanogaster rugose model of autism spectrum disorders (ASD) showed that consumption of an Ilex kudingcha extract (IKE) mitigates phenotypic characteristics of ASD and in normal mice, alters gene expression involved in cognition, metabolism, and protein synthesis. This study investigated the effects of IKE on prenatal sodium valproate (VPA) treatment-induced ASD core behavioral deficits and ASD associated behaviors, neurochemical markers and histological changes. IKE administration significantly mitigated these behavioral deficits and damaged Purkinje cells, PTEN expression and oxidative stress and resembled treatment with methylphenidate in its effect upon social behavior. These findings extend our previous study with D. melanogaster and together, indicate that IKE consumption ameliorates ASD-like properties in two animal models of ASD with different etiologies. Potential mechanisms involve reduction of oxidative stress, increased PTEN expression and cerebral Purkinje cell health. These data support further studies of IKE and related species for treatment of ASD.

Destructive periodontitis destroys alveolar bone and eventually leads to tooth loss. While guided bone regeneration, which is based on creating a physical barrier to hinder the infiltration of epithelial and connective tissues into defect sites, has been widely used for alveolar bone regeneration, its outcomes remain variable. In this work, a multifunctional nanofibrous hollow microsphere (NFHMS) is developed for enhanced alveolar bone regeneration. The NFHMS is first prepared via combining a double emulsification and a thermally induced phase separation process. Next, E7, a short peptide with high specific affinity to bone marrow‐derived stem cells (BMSCs), is conjugated onto the surface of NFHMS. After that, bone forming peptide (BFP), a short peptide derived from bone morphology protein 7 is loaded in calcium phosphate (CaP) nanoparticles, which are further encapsulated in the hollow space of the NFHMS‐E7 to form NFHMS‐E7‐CaP/BFP. The NFHMS‐E7‐CaP/BFP selectively promoted the adhesion of BMSCs and expelled the adhesion of fibroblasts and epithelial cells. In addition, the BFP is sustainedly released from the NFHMS‐E7‐CaP/BFP to enhance the osteogenesis of BMSCs. A rat challenging fenestration defect model showed that the NFHMS‐E7‐CaP/BFP significantly enhanced alveolar bone tissue regeneration. This work provides a novel bioengineering approach for guided bone regeneration.

Understanding patient non-adherence to prescribed antibiotics can inform clinical practices, patient counseling, and antibiotic efficacy study design in dermatology. The primary objective was to determine the rate of and reasons for antibiotic non-adherence in the dermatologic surgery setting. The secondary objective was to test the applicability of previously studied survey questions for antibiotic non-adherence screening in the dermatologic surgery setting. Five academic outpatient dermatologic surgery centers across the United States conducted one multicenter prospective cohort study. Dermatologic surgery patients ≥ 18 years of age who were prescribed an antibiotic were included as part of this study. 15.2% (42/276) of patients did not adhere to their antibiotic regimen after dermatologic surgery. Most common reasons for incomplete antibiotic courses included forgotten antibiotics (42.9%,18/42) and side effects (28.6%, 12/42). Previously evaluated questions to identify and predict non-adherence had modest performance in the dermatologic surgery setting (Area under the curve of 0.669 [95% CI (0.583–0.754)]). Antibiotic non-adherence after skin surgery is prevalent and commonly due to reasons that physicians can address with patients.

Purpose The purpose of this concept delineation was to differentiate similar concepts impacting nurse well-being during the COVID-19 pandemic, including: compassion fatigue, burnout, moral injury, secondary traumatic stress, and second victim. Methods A total of 63 articles were reviewed for concept delineation. Morse’s (1995) approach to concept delineation was utilized to analyse the articles. Results Concepts were described interchangeably but were found to present themselves in a sequence. A nurse may experience moral injury, leading to a second victim experience, synonymous with secondary traumatic stress, then compassion fatigue and/or burnout that can be acute or chronic in nature. An Occupational Trauma Conceptual Model was created to depict how these concepts interact based on concept delineation findings. Conclusion Nurses are experiencing long-lasting occupational trauma and future intervention research should centre on optimizing nurse well-being to ensure the sustainability of nursing profession.