Photocatalytic Functionalization of Dehydroalanine-Derived Peptides in Batch and Flow.

Unnatural amino acids, and their synthesis by the late-stage functionalization (LSF) of peptides, play a crucial role in areas such as drug design and discovery. Historically, the LSF of biomolecules has predominantly utilized traditional synthetic methodologies that exploit nucleophilic residues, such as cysteine, lysine or tyrosine. Herein, we present a photocatalytic hydroarylation process targeting the electrophilic residue dehydroalanine (Dha). This residue possesses an α,ß-unsaturated moiety and can be combined with various arylthianthrenium salts, both in batch and flow reactors. Notably, the flow setup proved instrumental for efficient scale-up, paving the way for the synthesis of unnatural amino acids and peptides in substantial quantities. Our photocatalytic approach, being inherently mild, permits the diversification of peptides even when they contain sensitive functional groups. The readily available arylthianthrenium salts facilitate the seamless integration of Dha-containing peptides with a wide range of arenes, drug blueprints, and natural products, culminating in the creation of unconventional phenylalanine derivatives. The synergistic effect of the high functional group tolerance and the modular characteristic of the aryl electrophile enables efficient peptide conjugation and ligation in both batch and flow conditions.

Impact of Cancer in Patients Undergoing Transcatheter Aortic Valve Replacement: A Single-Center Study.

BACKGROUND: The use of transcatheter aortic valve replacement (TAVR) in cancer survivors and patients with active cancer (AC) in cancer survivors and patients with active cancer (AC) is expanding, suggesting a need to adjust the indications and risk assessment pre-TAVR. OBJECTIVES: The purpose of this study was to determine the impact of cancer on peri-procedural complications and survival in a long-term, single-center cohort of patients treated with TAVR. METHODS: Patients treated with TAVR between January 2006 and December 2018 were grouped as follows: controls (patients without cancer), stable cancer (SC), and AC. The primary endpoints were peri-procedural complications and 30-day survival. A secondary endpoint was 10-year survival. RESULTS: A total of 1,088 patients (age 81 ± 5 years, 46.6% men) treated with transfemoral TAVR were selected: 839 controls, 196 SC, and 53 AC. Predominant malignancies were breast, gastrointestinal, and prostate cancer. No differences were observed between patients with cancer and controls regarding peri-procedural complications. Patients with AC had similar 30-day survival compared with controls and SC (94.3% vs. 93.3% vs. 96.9%, p = 0.161), but as expected, reduced 10-year survival. AC was associated with a 1.47 (95% CI 1.16 to 1.87) fold increased risk of all-cause 10-year mortality in multivariable adjusted models. CONCLUSIONS: TAVR should be performed in patients with cancer when indicated, considering that patients with cancer have similar periprocedural complications and short-term survival compared with control patients. However, patients with AC have worse 10-year survival. Future studies are needed to define cancer-specific determinants of worse long-term survival.

Correction: Prevalence and associated factors of skin cancer in aged nursing home residents: A multicenter prevalence study.

[This corrects the article DOI: 10.1371/journal.pone.0215379.].

Prevalence and associated factors of skin cancer in aged nursing home residents: A multicenter prevalence study.

Non-melanoma-skin cancer is an emerging clinical problem in the elderly, fair skinned population which predominantly affects patients aged older than 70 years. Its steady increase in incidence rates and morbidity is paralleled by related medical costs. Despite the fact that many elderly patients are in need of care and are living in nursing homes, specific data on the prevalence of skin cancer in home care and the institutional long-term care setting is currently lacking. A representative multicenter prevalence study was conducted in a random sample of ten institutional long-term care facilities in the federal state of Berlin, Germany. In total, n = 223 residents were included. Actinic keratoses, the precursor lesions of invasive cutaneous squamous cell carcinoma were the most common epithelial skin lesions (21.1%, 95% CI 16.2 to 26.9). Non-melanoma skin cancer was diagnosed in 16 residents (7.2%, 95% CI 4.5 to 11.3). None of the residents had a malignant melanoma. Only few bivariate associations were detected between non-melanoma skin cancer and demographic, biographic and functional characteristics. Male sex was significantly associated with actinic keratosis whereas female sex was associated with non-melanoma skin cancer. Smoking was associated with an increased occurrence of non-melanoma skin cancer. Regular dermatology check-ups in nursing homes would be needed but already now due to financial limitations, lack of time in daily clinical practice and limited number of practising dermatologists, it is not the current standard. With respect to the worldwide growing aging population new programs and decisions are required. Overall, primary health care professionals should play a more active role in early diagnosis of skin cancer in nursing home residents. Dermoscopy courses, web-based or smartphone-based applications and teledermatology may support health care professionals to provide elderly nursing home residents an early diagnosis of skin cancer.