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Abstract Although stapled α-helical peptides can address challenging targets, their advancement is impeded by poor understandings for making them cell permeable while avoiding off-target toxicities. By synthesizing >350 molecules, we present workflows for identifying stapled peptides against Mdm2(X) with in vivo activity and no off-target effects. Key insights include a clear correlation between lipophilicity and permeability, removal of positive charge to avoid off-target toxicities, judicious anionic residue placement to enhance solubility/behavior, optimization of C-terminal length/helicity to enhance potency, and optimization of staple type/number to avoid polypharmacology. Workflow application gives peptides with >292x improved cell proliferation potencies and no off-target cell proliferation effects ( > 3800x on-target index). Application of these ‘design rules’ to a distinct Mdm2(X) peptide series improves ( > 150x) cellular potencies and removes off-target toxicities. The outlined workflow should facilitate therapeutic impacts, especially for those targets such as Mdm2(X) that have hydrophobic interfaces and are targetable with a helical motif.

The article focuses on the diagnosis and clinical presentation of basal cell carcinoma (BCC) in a 68-year-old female patient. Topics include the typical characteristics of BCC, its association with sun exposure and other risk factors, and the importance of biopsy for diagnosis and distinguishing it from other skin cancers.

Over the past decade, with the support of Erasmus Mundus, the number of joint degree programmes in Europe has increased rapidly. In Asia, joint degree programmes have also gained popularity due to the growth of transnational higher education in the region since 2000. However, a joint degree programme is a highly complex and coordinated activity for the university partners involved. Cooperation and coordination are crucial for the quality of any joint degree programme. This study primarily explores QA approaches to European joint degree programmes and their current development in Asia.

Scant research has explored how the emotions of gift‐givers influence their gift selection, particularly negative emotions. Addressing this gap, this research examines how guilt impacts gift‐giving, capitalizing on the conceptual link between guilt, power, and size. Through four experiments, we demonstrate that, compared with gift‐givers in a control condition, guilty gift‐givers are more likely to choose conspicuously branded gifts—items with highly noticeable, large brand logos. We observe this effect using different scenarios and the autobiographical recall procedure to elicit guilt, as well as a variety of operationalizations of brand conspicuousness. We find that the sense of power and power restoration provided by the gift account for the results. Moreover, the preference for a conspicuously branded gift diminishes when guilty gift‐givers engage in reparative actions to alleviate their guilt prior to gift‐giving. This research contributes to the literature on guilt, power, and conspicuous consumption by revealing a novel consequence of guilt on consumer choice in gift‐giving contexts and expanding our understanding of conspicuous brand usage. The findings have practical implications for marketers, particularly in using guilt appeals and promoting conspicuously branded gifts. Finally, we suggest future research directions related to positive emotions and other outcomes of interest in gift‐giving. [ABSTRACT FROM AUTHOR]

The calcified chondroid mesenchymal neoplasm (CCMN) represents a recently recognized tumor type with only 50 well-documented cases in the English-language literature. Herein we report an additional case of CCMN presenting as a large mass in the temporomandibular joint region of a 41-year-old female. A review of previously reported cases and the current case of CCMN shows the following features: 1) average age 52 years (range 14–87 years) and an approximately even sex distribution; 2) most frequently involved sites: distal extremities (including foot, hand, wrist, forearm) (n=41) and temporomandibular joint/temporal/parotid region (n=9); 3) multilobular soft tissue tumor with chondroid to cartilaginous matrix, often grungy or lace-like calcifications, and variable cytologic atypia; 4) frequently detected FN1 rearrangement (n=15), including FN1 fusion with FGFR2 (n=7) or other receptor tyrosine kinases; 5) 2 reported local recurrences (after incomplete excision); 6) no reports of malignant biologic behavior. [ABSTRACT FROM AUTHOR]

Background: Odontogenic carcinosarcoma (OCS) is a rare odontogenic malignancy with limited characterization and unexplored molecular features. We report clinicopathologic and molecular findings in 3 additional OCS and review the literature. Methods: 3 OCS (5.1%) were identified among 59 malignant odontogenic tumors (in our archives from 1992 to 2022). Clinical, radiologic, histopathologic, immunophenotypic, and molecular findings were reviewed. Data from prior case reports and systematic or non-systematic reviews were extracted for analysis. Results: Three mandibular OCS (age range: 66 to 72 years; 1 male, 2 females) were identified. Case 1 had novel clear-cell morphology, multiple recurrences, and a lethal outcome 28 months after resection. EWSR1 rearrangements were negative, but the tumor showed focal nuclear β-catenin and strong LEF-1 immunoreactivity. Case 2 demonstrated ameloblastic and sclerosing features and encased the inferior alveolar nerve; the patient was disease-free 22 months after resection with adjuvant chemoradiation therapy. LEF-1 was again strongly positive, and next-generation sequencing demonstrated 9p region-(CDKN2A, CDKN2B) copy number loss, and 12q region-(MDM2, CDK4) copy number gain. Case 3 showed clear-cell and markedly sclerosing features; no follow-up information was available. Literature review along with the current cases yielded 20 cases. OCS showed a male predilection (1.5:1), mandibular predominance (80%, typically posterior), and a bimodal age distribution (modes: 27.7 years, 62.7 years). OCS presented as masses (100%), often with pain (55%), and paresthesia (45%). Tumors were typically radiolucent (88.9%), with bone destruction (61.1%), and/or tooth effacement (27.8%). Preoperative biopsy was sensitive for malignancy (85.7%). At least 45% show evidence for a precursor lesion. 3-year DSS and DFS were 58% and 35%, respectively. Regional and distant (usually lung) metastatic rates were 25% and 31.3%, respectively. Increased mitotic rates and presence of tumor necrosis trended toward worse DSS and DFS. Conclusion: OCS is a rare but aggressive malignancy, often arising from precursor tumors and may represent a terminal phenotype rather than a distinct entity. We describe novel clear-cell and sclerosing morphologies. Wnt pathway alterations appear important. Mitotic rates and necrosis may be adverse prognosticators. In keeping with nomenclature trends in other sites, OCS may be more appropriately designated as "biphasic sarcomatoid odontogenic carcinomas." [ABSTRACT FROM AUTHOR]

The article presents a case study of commissural lip pits in a 24-year old female during a routine oral examination. Topics include the clinical history, diagnosis, and discussion of commissural lip pits, their hypothesized developmental origin, and their association with congenital conditions, highlighting the need for distinguishing them from other oral anomalies.

Rationale, Aims, and Objectives: This study aims to investigate how reported comprehension of the Medicare programme and its prescription drug benefits is associated with cost‐related medication nonadherence (CRN) among Medicare beneficiaries with cardiovascular disease (CVD) risk factors. Methods: This cross‐sectional study used the 2017 Medicare Current Beneficiary Survey Public Use File data and included Medicare beneficiaries aged ≥65 years who reported having at least one CVD risk factor (i.e., hypertension, hyperlipidemia, diabetes, smoking and obesity) (n = 2821). A survey‐weighted logistic model was used to examine associations between perceived difficulty of understanding the Medicare programme and its prescription drug benefits and CRN, controlling for beneficiaries' demographic (e.g., age) and clinical characteristics (e.g, comorbidities). This study further analyzed five subgroups based on the type of CVD risk factors involved. Results: Among Medicare beneficiaries with CVD risk factors, 14.4% reported CRN. Medicare beneficiaries with CVD risk factors who reported difficulty understanding the overall Medicare programme and its prescription drug benefits were more likely to report CRN, compared to those who reported easy understanding of the overall Medicare programme (OR = 1.50; 95% CI = 1.11−2.04; p = 0.009) and its prescription drug benefits (OR = 2.01; 95% CI = 1.52−2.66; p < 0.001). Similar results were obtained for the subgroups with obesity, hypertension or hyperlipidemia. Conclusions: Perceived difficulty of understanding the Medicare Programme and its prescription drug benefits is associated with CRN among Medicare beneficiaries with CVD risk factors, especially those with obesity, hypertension or hyperlipidemia. Monitoring and enhancing Medicare beneficiaries' overall understanding of the Medicare programme may reduce CRN. [ABSTRACT FROM AUTHOR]

Using content analysis and in-depth interviews, this research has examined three best-practice hospitals in terms of their approaches to implementing interactive e-health tools on their Web sites. The study has demonstrated hospital administrations' visions of and insights into developing e-health. It concludes that the implementation of interactive e-heath tools can be area- and hospital-size-indiscriminative; such implementation accomplishes multiple goals, including service, communication, and education, and serves as an important differentiator in a competitive industry; by understanding the best practice, decision-making, planning processes, and outcomes of implementing e-health online, as well as potential obstacles to such implementation, hospitals can take the lessons learned and design effective interactive e-health tools on their Web sites. Keywords: healthcare new media marketing, healthcare IT, e-health, hospital Web sites, interactive., INTRODUCTION AND BACKGROUND Over the past decade or so, thousands of U.S. hospitals shifted some of their business online (Huang, 2009; Huang & Chang, 2012; Shepherd, 2003). This shift is [...]

The article presents a case study involving a 24-year-old female who presented with jaw pain attributed to an impacted wisdom tooth, revealing distinct radiographic features of associated lesions. Topics include the surgeon's diagnoses of calcifying epithelial odontogenic tumor and lateral periodontal cyst, microscopic characteristics of the lesions, and the successful outcome of surgical intervention, leading to an uneventful 19-month postoperative follow-up without recurrence.

The article focuses on a case study involving a 69-year-old male experiencing right cheek pain and sinonasal congestion, ultimately diagnosed with a low-grade sinonasal adenocarcinoma. It discusses the clinical presentation, histopathological findings, and the diagnostic and therapeutic considerations, highlighting the rarity and distinctions of non-salivary sinonasal adenocarcinomas in terms of diagnosis, management, and prognosis.

Purpose: Oral potentially malignant disorders (OPMDs) may have varying degrees of oral epithelial dysplasia (OED). Traditional grading schemes separate OED into three-tiers (mild, moderate, and severe). Alternatively, a binary grading system has been previously proposed that stratifies OED into low-risk and high-risk categories based on a quantitative threshold of dysplastic pathologic characteristics. This systematic review evaluates the predictive value of a binary OED grading system and examines agreement between pathologists. Methods: This meta-analysis queried 4 databases (PubMed, Ovid-MEDLINE, Cochrane, and SCOPUS) and includes 4 studies evaluating binary OED grading systems. Meta-analysis of proportions and correlations was performed to pool malignant transformation rates (MTR), risk of malignant transformation between OED categories, and measures of interobserver agreement. Results: Pooled analysis of 629 lesions from 4 different studies found a six-time increased odds of malignant transformation in high-risk lesions over low-risk lesions [odds ratio (OR) 6.14, 95% 1.18–15.38]. Reported ORs ranged from 2.8 to 22.4. The overall MTR was 26.8%, with the high-risk and low-risk lesions having MTRs of 57.9% (95% CI 0.386–0.723) and 12.7% (95% CI − 0.210 to 0.438), respectively. Pooled unweighted interobserver kappa values for the binary grading system and three-tiered system were 0.693 (95% CI 0.640–0.740) and 0.388 (95% CI 0.195–0.552), respectively. Conclusion: Binary grading of OED into low-risk and high-risk categories may effectively determine malignant potential, with improved interobserver agreement over three-tiered grading. Improved grading schemes of OED may help guide management (watchful waiting vs. excision) of these OPMDs. [ABSTRACT FROM AUTHOR]

The results from three studies suggest that consumers' perceptions of product effectiveness are critical in determining the amount of a product they choose to use in a given instance. In general, consumers consider green, or environmentally friendly, products to be less effective than regular products; therefore, consumers increase the amount of the green product they use to make up for the perceived inferiority. Notably, this pattern of green versus regular product usage is more pronounced among consumers who are environmentally conscious. When the perceived effectiveness of a green product is boosted by a credible endorsement, the discrepancy between green and regular product usage disappears. [ABSTRACT FROM AUTHOR]

Electronic cigarettes are a type of electronic nicotine delivery system. In the United States, electronic cigarettes have surged in popularity since their introduction to the market in 2007. Health and safety concerns primarily have focused on e-liquid/aerosol composition and whether these devices represent a gateway versus lower risk alternative to conventional cigarettes. Furthermore, recent incidents have demonstrated the potential for significant orofacial injury caused by device explosion while in use. Herein we report a case of a 20-year-old male who sustained oral burns, lacerations, and tooth loss when an electronic cigarette exploded in his mouth shortly after he charged the battery. Only seven other cases of trauma from intraoral electronic cigarette explosions have been reported in the scientific literature to date, although several similar incidents also have been reported by the news media. Treatment of such patients often requires a multidisciplinary approach. Design/manufacturing issues and improper handling may cause an increase in internal battery temperature. An investigation by the United States Fire Administration concluded that user education may aid in preventing some electronic cigarette explosions, and safety design improvements also could help. Although some studies and authorities support the use of electronic cigarettes for tobacco cessation and harm reduction, recent reports of electronic cigarette explosions raise important safety concerns and point to the need for further studies. [ABSTRACT FROM AUTHOR]

Oral cavity squamous cell carcinoma (OC-SCC) is the most common malignancy of the head and neck (excluding nonmelanoma skin cancer). Recent trends have shown a dramatic rise in the incidence of oropharyngeal squamous cell carcinoma (OP-SCC), with a marked increase in lesions related to human papillomavirus infection. This update presents the latest evidence regarding OC-SCC and OP-SCC. In particular, the authors compare and contrast tumors at these two sites with respect to epidemiology, etiopathogenesis, clinicopathologic presentation, clinical assessment, imaging, management, and prognosis. It is important for clinicians to be aware of differences between OC-SCC and OP-SCC so that appropriate patient education and multidisciplinary care can be provided to optimize outcomes. CA Cancer J Clin 2015;65:401-421. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

Nucleolin (NCL) is a major nucleolar phosphoprotein that has pleiotropic effects on cell proliferation and is elevated in a variety of tumors. NCL is highly phosphorylated at the N-terminus by two major kinases: interphase casein kinase 2 (CK2) and mitotic cyclin-dependent kinase 1 (CDK1). Earlier we demonstrated that a NCL-mutant that is partly defective in undergoing phosphorylation by CK2 inhibits chromosomal replication through its interactions with Replication Protein A, mimicking the cellular response to DNA damage. We further delineated that the N-terminus of NCL associates with Hdm2, the most common E3 ubiquitin ligase of p53. We reported that NCL antagonizes Hdm2 to stabilize p53 and stimulates p53 transcriptional activity. Although NCL-phosphorylation by CK2 and ribosomal DNA transcription are closely coordinated during interphase, the role of NCL phosphorylation in regulating cell proliferation remains unexplored. We have therefore engineered unique human cells that specifically induce expression of NCL-wild type (WT) or a phosphorylation-deficient NCL-mutant, 6/S*A where all the six CK2 consensus serine sites residing in the N-terminus NCL were mutated to alanine. Here we show that this NCL-mutant is defective in undergoing phosphorylation by CK2. We also demonstrate that NCL-phosphorylation by CK2 is required through the S-phase progression in cell cycle and hence proliferation. Induced expression of NCL with mutated CK2 phosphorylation sites stabilizes p53, results in higher expression of Bcl2 (B-cell lymphoma 2) homology 3 (BH3)-only apoptotic markers and causes a dominant-negative effect on cell viability. Our unique cellular system thus provides the first evidential support to delineate phospho-specific functions of NCL on cell proliferation. [ABSTRACT FROM AUTHOR]