Refining Field Cancerization: An Institutional Cohort Analysis of Patient Characteristics in a Validation Cohort.

BACKGROUND: Field cancerization is poorly defined in dermatology. The author group previously proposed and applied a classification system in an original cohort to risk-stratify patients with field cancerization. OBJECTIVE: Apply the authors' classification system within a validation cohort. METHODS: Patients with keratinocyte carcinoma history completed a survey regarding demographic information, medical history, and chemoprevention use. Patients were assigned a field cancerization class, and differences between validation and original cohorts were assessed. RESULTS: A total of 363 patients were enrolled (mean age 67.4; 61.7% male). After comparing validation and original cohorts, there were differences in age between class II (p = .02) and class IVb (p = .047), and differences in chemoprevention use in class III (p = .04). Similar to the original cohort, the validation cohort was associated with increases in total number of skin cancers in the last year (p < .001), 5 years (p < .001), lifetime (p < .001), years since first skin cancer (p < .001), and chemoprevention use (p < .001). In the validation cohort, there were increases in age (p = .03) and immunocompromised status (p = .04) with increasing class, which were not observed in the original cohort. CONCLUSION: Differences among field cancerization classes were similar in a validation cohort, further highlighting the importance of class-specific treatment and management.

Sustainable and Biomimetic Methodology for Extraction of High-Value-Added Compounds in Almond Hulls.

Almond trees are the most cultivated nut tree in the world. The production of almonds generates large amounts of by-products, much of which goes unused. Herein, this study aimed to develop a green chemistry approach to identify and extract potentially valuable compounds from almond by-products. Initially, a screening was performed with 10 different Natural Deep Eutectic Solvents (NADESs). The mixture lactic acid/glycerol, with a molar ratio 1:1 (1:50 plant material to NADES (w/v) with 20% v/v of water) was identified as the best extraction solvent for catechin, caffeoylquinic acid, and condensed tannins in almond hulls. Subsequently, a method was optimized by a Design of Experiment (DoE) protocol using a miniaturized extraction technique, Microwave-Assisted Extraction (MAE), in conjunction with the chosen NADESs. The optimal conditions were found to be 70 °C with 15 min irradiation time. The optimal extraction conditions determined by the DoE were confirmed experimentally and compared to methods already established in the literature. With these conditions, the extraction of metabolites was 2.4 times higher, according to the increase in total peak area, than the established literature methods used. Additionally, by applying the multiparameter Analytical Greenness Metric (AGREE) and Green Analytical Process Index (GAPI) metrics, it was possible to conclude that the developed method was greener than the established literature methods as it includes various principles of green analytical chemistry.

Development of a capillary zone electrophoresis method to monitor magnesium ion consumption during in vitro transcription for mRNA production.

Messenger RNA (mRNA) vaccines represent a landmark in vaccinology, especially with their success in COVID-19 vaccines, which have shown great promise for future vaccine development and disease prevention. As a platform technology, synthetic mRNA can be produced with high fidelity using in vitro transcription (IVT). Magnesium plays a vital role in the IVT process, facilitating the phosphodiester bond formation between adjacent nucleotides and ensuring accurate transcription to produce high-quality mRNA. The development of the IVT process has prompted key inquiries about in-process characterization of magnesium ion (Mg++) consumption, relating to the RNA polymerase (RNAP) activation, fed-batch mode production yield, and mRNA quality. Hence, it becomes crucial to monitor the free Mg++ concentration throughout the IVT process. However, no free Mg++ analysis method has been reported for complex IVT reactions. Here we report a robust capillary zone electrophoresis (CZE) method with indirect UV detection. The assay allows accurate quantitation of free Mg++ for the complex IVT reaction where it is essential to preserve IVT samples in their native-like state during analysis to avoid dissociation of bound Mg complexes. By applying this CZE method, the relationships between free Mg++ concentration, the mRNA yield, and dsRNA impurity level were investigated. Such mechanistic understanding facilitates informed decisions regarding the quantity and timing of feeding starting materials to increase the yield. Furthermore, this approach can serve as a platform method for analyzing the free Mg++ in complex sample matrices where preserving the native-like state of Mg++ binding is key for accurate quantitation.

Determining the Oxidation Mechanism through Radical Intermediates in Polysorbates 80 and 20 by Electron Paramagnetic Resonance Spectroscopy.

Polysorbates 20 and 80 (PS20 and PS80) are added to many commercial biologic and vaccine pharmaceuticals. It is commonly known that these polysorbates undergo a radical oxidation mechanism; however, the identity of these radical intermediates has not been clearly determined. Furthermore, PS20 and PS80 differ by the presence of a lauric acid instead of an oleic acid, respectively. The oxidation of PS80 is thought to be centered around the double bond of the oleic acid even though PS20 also undergoes oxidation, making the mechanism of oxidation unclear for PS20. Using commercial stocks of PS20 and PS80 alkyl (R•), alkoxyl (C-O•) and peroxyl (C-OO•) radicals were detected by electron paramagnetic resonance spectroscopy likely originating from radical-initiating species already present in the material. When dissolved in water, the peroxyl radicals (C-OO•) originally in the stocks were not detected but poly(ethylene oxide) radicals were. An oxidative pathway for polysorbates was suggested based on the radical species identified in the polysorbate stock material and solutions.

A case of trichodysplasia spinulosa related to ruxolitinib treated successfully with oral acitretin.

Trichodysplasia spinulosa (TS) is a rare disease that affects immunocompromised patients, characterized by hair-like growths caused by TS-associated polyomavirus infection. Little is known about specific immunosuppressive drugs that can precipitate the condition. We report a case of TS presenting after initiating the oral Janus-associated kinase inhibitor (JAKi) ruxolitinib. A 67-year-old female with a history of allogeneic bone marrow transplant requiring immunosuppression with tacrolimus, prednisone and, more recently, ruxolitinib 5 mg twice daily due to Graft versus Host Disease presented to the clinic with a facial rash. The clinical and histopathological findings in the setting of immunosuppression were consistent with TS. Initial treatments were ineffective, but oral acitretin showed significant improvement after 3 months. Due to the close temporal relationship between the initiation of ruxolitinib and the development of TS, this case suggests that JAKis may contribute to TS development by suppressing the JAK-signal transducer and activator of the transcription pathway's antiviral functions.

Online reading habits can reveal personality traits: towards detecting psychological microtargeting.

Building on big data from Reddit, we generated two computational text models: (i) Predicting the personality of users from the text they have written and (ii) predicting the personality of users based on the text they have consumed. The second model is novel and without precedent in the literature. We recruited active Reddit users (N=1,105) of fiction-writing communities. The participants completed a Big Five personality questionnaire and consented for their Reddit activity to be scraped and used to create a machine learning model. We trained an natural language processing model [Bidirectional Encoder Representations from Transformers (BERT)], predicting personality from produced text (average performance: r=0.33). We then applied this model to a new set of Reddit users (N=10,050), predicted their personality based on their produced text, and trained a second BERT model to predict their predicted-personality scores based on consumed text (average performance: r=0.13). By doing so, we provide the first glimpse into the linguistic markers of personality-congruent consumed content.

Refining the Classification of Field Cancerization.

BACKGROUND: Field cancerization is a commonly encountered but poorly defined entity in dermatology. Lack of a consensus definition makes characterizing and studying this condition difficult. OBJECTIVE: Propose a framework for defining and managing field cancerization patients. METHODS: Clinical experience and available data in the literature was used to develop a proposed field cancerization disease classification system and chemoprevention algorithm. RESULTS: The author group developed a field cancerization classification and treatment algorithm that stratifies patients into 5 different classes based on the extent of their field cancerization. They have started to recruit and study the highest risk cohort (Category 4 or 5) and have recruited 57 patients with 5 or more lifetime keratinocyte carcinomas for a prospective study evaluating chemoprevention strategies and disease burden. In these cohorts, the average number of skin cancers was greater than 12; however, less than 39% of these patients had used any chemoprevention in the prior 6 months. CONCLUSION: A meaningful and clinically relevant disease stratification framework with chemoprevention guidance has the potential to highly impact the specialty and patients.

Postoperative Complications After Interpolated Flap Repair for Mohs Defects of the Nose: A Multicenter Prospective Cohort Study.

BACKGROUND: Dermatologists perform most interpolated flaps after skin cancer resection. Prospective, multicenter data on complications after interpolated flap repair in this setting are limited. OBJECTIVE: To determine the rate of physician-reported complications after interpolated flap repair of the nose. METHODS: Multicenter, prospective cohort study of 169 patients undergoing 2-stage interpolated flap repair of post-Mohs nasal defects. Frequency of bleeding, infection, dehiscence, necrosis, hospitalization, and death in the 30 days after flap placement and flap takedown are reported. RESULTS: Patients experienced 23 complications after flap placement (13.61%) and 6 complications after flap takedown (3.55%) that were related to the surgical procedure. The most frequent complication after flap placement was bleeding (9, 5.33%, 95% confidence interval [CI]: 2.83%-9.82%). The most frequent complication after flap takedown was infection (5, 2.96%, 95% CI: 1.27%-6.74%). There was one hospitalization related to an adverse reaction to antibiotics. There were no deaths. CONCLUSION: Most complications after interpolated flap repair for post-Mohs defects of the nose are minor and are associated with flap placement. Interpolated flap repair for post-Mohs defects can be performed safely in the outpatient setting under local anesthesia.

Extensive Characterization of Polysorbate 80 Oxidative Degradation Under Stainless Steel Conditions.

Polysorbate-80 (PS-80) is a common surfactant used in biologics formulations. However, the tendency of oxidation to PS-80 when exposed to stainless steel surfaces brings various challenges during manufacturing processes, such as inconsistent shelf-life of PS-80 solutions, which can further impact the biologics and vaccines production. In this work, the root causes of PS-80 oxidation when in contact with stainless steel conditions were thoroughly investigated through the use of various complementary analytical techniques including U/HPLC-CAD, LC-MS, ICP-MS, peroxide assay, and EPR spectroscopy. The analytical tool kit used in this work successfully revealed a PS-80 degradation mechanism from the perspective of PS-80 content, PS-80 profile, iron content, peroxide production, and radical species. The combined datasets reveal that PS-80 oxidative degradation occurs in the presence of histidine and iron in addition to being combined with the hydroperoxides in PS-80 material. The oxidative pathway and potential degradants were identified by LC-MS. The PS-80 profile based on the U/HPLC-CAD assay provided an effective way to identify early-signs of PS-80 degradation. The results from a peroxide assay observed increased hydroperoxide along with PS-80 degradation. EPR spectra confirmed the presence of histidine-related radicals during PS-80 oxidation identifying how histidine is involved in the oxidation. All assays and findings introduced in this work will provide insight into how PS-80 oxidative degradation can be avoided, controlled, or detected. It will also provide valuable evaluations on techniques that can be used to identify PS-80 degradation related events that occur during the manufacturing process.