Protein–protein interactions (PPIs), many of which are dominated by α‐helical recognition domains, play key roles in many essential cellular processes, and the dysregulation of these interactions can cause detrimental effects. For instance, aberrant PPIs involving the Bcl‐2 protein family can lead to several diseases including cancer, neurodegenerative diseases, and diabetes. Interactions between Bcl‐2 pro‐life proteins, such as Mcl‐1, and pro‐death proteins, such as Bim, regulate the intrinsic pathway of apoptosis. p53, a tumor‐suppressor protein, also has a pivotal role in apoptosis and is negatively regulated by its E3 ubiquitin ligase HDM2. Both Mcl‐1 and HDM2 are upregulated in numerous cancers, and, interestingly, there is crosstalk between both protein pathways. Recently, synergy has been observed between Mcl‐1 and HDM2 inhibitors. Towards the development of new anticancer drugs, we herein describe a polypharmacology approach for the dual inhibition of Mcl‐1 and HDM2 by employing three densely functionalized isoxazoles, pyrazoles, and thiazoles as mimetics of key α‐helical domains of their partner proteins.

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Background RARS is a challenging clinical phenomenon that affects many patients, and diagnostic criteria for this condition are not fully characterized in the literature. Objective To examine diagnostic criteria for recurrent acute rhinosinusitis (RARS). Study Design Systematic review. Methods Cochrane, PubMed (MEDLINE), clinicaltrials.gov, EMBASE, Google Scholar, and Web of Science databases were queried for articles related to RARS dating from 1990 to present, according to PRISMA statement guidelines. Full text articles pertinent to the diagnostic criteria of RARS were included in this review. Inclusion criteria included articles specifically addressing RARS; studies with 3 or more patients; and articles in English. Results A total of 1022 titles/abstracts potentially related to RARS were identified. Of these, sixty-nine full texts were selected for review, and 22 of these ultimately met inclusion criteria. The level of evidence was generally low. Studies and guidelines have used many different definitions for RARS diagnosis over the years based on symptomatology, physical examination, nasal endoscopy, imaging, and laboratory domains. Clinically important RARS has been defined most commonly as 4 or more discrete episodes of ARS per year, but this frequency is typically based on expert opinion. Additionally, radiologic anatomic associations such as concha bullosa, accessory maxillary os, and narrowed infundibular distance may be associated with RARS. Endoscopic visualization and imaging are sometimes used to confirm the presence of sinus disease during exacerbations of RARS, but there is variability in this practice. Conclusion The diagnostic definition for RARS has developed over time and is currently based on low level 4 and 5 evidence. Because of the migratory definition of RARS, comparing inter-study results of RARS management remains difficult, and future studies should aim to follow current expert guidelines on diagnostic criteria of RARS.

Background Objective Study Design RARS is a challenging clinical problem that impacts many patients. This article seeks to systematically review the literature on RARS management. Methods Cochrane, PubMed, EMBASE, and other databases were queried for articles related to RARS dating from 1990 to present, according to PRISMA guidelines. Inclusion criteria included articles specifically addressing RARS management; studies with 3 or more patients; and articles in English. Results A total of 1022 titles/abstracts potentially related to RARS were identified. Of these, sixty-nine full texts were selected for review, and 10 met inclusion criteria (five with level 4 evidence, four with level 3 evidence, one with level 2 evidence). The studies included a total of 890 patients (Age range 5.8 to 53.5 years), with follow up ranging from 1 to 19 months. Endpoints were primarily based on symptomatic improvement, although some articles also reported post-treatment endoscopic and radiographic findings. Management options included medical therapy (intranasal steroids, antibiotics, nasal saline irrigations, N-acetylcysteine, allergy treatment, and decongestants), balloon sinus dilation (BSD), and endoscopic sinus surgery (ESS). Surgical patients (BSD and ESS) had a trend towards greater symptom control than medically-treated patients, but meta-analysis was not possible. Conclusion Despite increasing interest in the treatment of RARS, there remains a lack of consensus regarding optimal management. The literature thus far, largely based on expert opinion, suggests that surgical management, either through balloon sinus dilation or endoscopic sinus surgery, may be helpful in improving symptoms and quality of life in those who do not respond to initial trials of medical management.

Objective: Facial recognition software (FRS) is becoming pervasive in society for commercial use, security systems, and entertainment. Alteration of the facial appearance with surgery poses a challenge to these algorithms, but several methods are being studied to overcome this issue. This study systematically reviews methods used in facial recognition of surgically altered faces. Materials and Methods: A systematic review was performed by searching PubMed and Institute of Electrical and Electronics Engineers (IEEE) databases to identify studies addressing FRS and surgery. On initial review, 178 manuscripts were identified relating to FRS and surgery and allowed division into multiple subgroups. The decision was made to focus on the recognition of surgically altered faces. Results: Eligible studies included those reports in English on FRS of surgically altered faces, and 39 papers were included. Surgical procedures range from affecting skin surface, such as skin peeling, to altering facial features, such as rhinoplasty, mentoplasty, malar augmentation, brow lift, facelift, orthognathic surgery, facial reanimation, and facial feminization. Methods were classified into appearance-based, feature-based, and texture-based. Descriptive versus experimental protocols were characterized by different reporting outcomes and controls. Accuracy ranged from 19.1% to 85.35% using various analysis methods. Conclusions: Knowledge of available limitations and advantages can aid in counseling patients regarding personal technology use, security, and quell fears about surgery to evade authorities. Surgical knowledge can be utilized to improve FRS algorithms for postsurgical recognition.