Accurate structure prediction of biomolecular interactions with AlphaFold 3.

The introduction of AlphaFold 21 has spurred a revolution in modelling the structure of proteins and their interactions, enabling a huge range of applications in protein modelling and design2-6. Here we describe our AlphaFold 3 model with a substantially updated diffusion-based architecture that is capable of predicting the joint structure of complexes including proteins, nucleic acids, small molecules, ions and modified residues. The new AlphaFold model demonstrates substantially improved accuracy over many previous specialized tools: far greater accuracy for protein-ligand interactions compared with state-of-the-art docking tools, much higher accuracy for protein-nucleic acid interactions compared with nucleic-acid-specific predictors and substantially higher antibody-antigen prediction accuracy compared with AlphaFold-Multimer v.2.37,8. Together, these results show that high-accuracy modelling across biomolecular space is possible within a single unified deep-learning framework.

Novel Asymmetric Y Design of Fascial Sling for Restoration of Oral Competence and Adequate Mouth Opening in Oral Commissure Defects Post-Malignancy Resection.

Reconstruction of through-and-through defects of cheek and commissure resulting from cancer resection are challenging. The specialized function of oral competence that the oral commissure and lip play is difficult to replicate with flap only reconstruction. Static slings play an important role in improving the functional and aesthetic outcome. The asymmetric "y" fascial sling helps in achieving the goals of oral competence along with adequate mouth opening. A total of 10 patients were operated by this technique. The results were satisfactory in terms of functional and aesthetic outcome postsurgery and were maintained 6 months postradiation.

Sustainable Harnessing of Waste Polycarbonate for Synthesizing Activated Furans to Generate Stenhouse Adducts on Polymer Surface.

Plastics are versatile materials, offering lightweight, durable, and affordable solutions across various industries. However, their non-degradable nature poses challenges by end of their life. This study presented an innovative carbonyl extraction method to utilize waste poly(bisphenol A carbonate) (PC) as reaction precursor to synthesis of activated furan as precursor for photoswitchable Stenhouse adducts. This innovative chemical strategy not only generated N,N'-functionalized barbiturates but also provided an eco-friendly and cost-effective alternative to traditional synthesis methods. The method presented hereby not only promotes sustainability by repurposing waste polycarbonate as carbonyl equivalent under green conditions but also yielded reusable bisphenol A (BPA). Furthermore, the derived activated furans exhibited their functionality by forming colored donor-acceptor Stenhouse adducts (DASAs) on aminated polymer surfaces. This work demonstrated a transition from a linear plastics economy toward a circular one, highlighting the potential of plastic waste as a resource for creating materials with improved properties.

A prospective observational study validating the CET score as a screening tool in suspected DRESS syndrome.

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) is an idiosyncratic severe cutaneous adverse reaction that may be potentially life-threatening. Recently, a simple scoring system for the early screening of DRESS patients was derived by combining hsCRP levels, the eosinophil count, and the total body surface area (CET score). The objectives of this study were validating the CET score, and calculating its lead time advantage and cost-benefits compared to RegiSCAR scoring. METHODS: This is a prospective observational case-control study, where 110 consecutive patients diagnosed with drug-induced maculopapular exanthema (MPE) were recruited during the 18 months of the study period. Patients were classified as cases (DRESS) and controls (MPE) using RegiSCAR score cut-off 2 (possible DRESS). They were also simultaneously screened using the CET score, based on which patients were classified as positive or negative. They were subsequently followed up on Day 15 for a second comparison and assessment of lead time and at 3 and 6 weeks to evaluate clinical response. RESULTS: Seventy cases and 40 controls were recruited. At a cut-off of >2.12, the CET score had a sensitivity of 94.3%, a specificity of 60%, a positive predictive value (PPV) of 80.5%, and a negative predictive value (PPV) of 85.7%. The median delay in diagnosing DRESS using RegiSCAR was around 14.5 hours. There was a median cost benefit of 12.1 USD in favor of the CET score. CONCLUSIONS: The CET score had good diagnostic performance in screening DRESS patients with a lead time of 14.5 hours and fewer costs incurred.

Reverse Koebner phenomenon in erythema nodosum leprosum.

BACKGROUND: Erythema nodosum leprosum (ENL) is an immunologically mediated phenomenon complicating the course of leprosy. Reverse Koebner phenomenon is the term used to describe the sparing of previously injured or diseased skin by new skin lesions of the disease. METHODS: A middle-aged woman with a known case of lepromatous leprosy for the past year presented with an eruption of reddish painful nodules over her body. The lesions were found to characteristically spare the sites of previous scars. RESULTS: This sparing phenomenon of previous scar sites has been termed reverse Koebner phenomenon, a site of the body that offers greater resistance than the rest of the body to the onset of the disease, seen in various diseases, but it has never been described in ENL. CONCLUSION: This sparing of scar sites in ENL can be attributed to reverse Koebner phenomenon.

A preliminary characterization of and call for benchmarking pharmacy alumni engagement.

INTRODUCTION: Alumni are essential but often overlooked stakeholders for pharmacy programs, and engaging alumni in philanthropy, volunteerism, events, and communication may have important implications for the growth and success of pharmacy programs. This research aims to preliminarily characterize pharmacy alumni engagement across four metrics and provide a call to action for standardized tracking and reporting of alumni engagement efforts across the Academy. METHODS: A cross-sectional survey was sent to alumni relations and advancement personnel at United States schools and colleges of pharmacy. The survey gathered information on the accuracy of pharmacy alumni records, alumni engagement within four categories (philanthropy, communication, events, and volunteering), alumni relations personnel, and barriers to alumni engagement efforts. RESULTS: Respondents reported using various database systems to track and measure alumni engagement, and 41% noted having accurate pharmacy alumni records. Opportunities for alumni engagement within the four categories varied across institutions. Fifty percent of respondents indicated that one full-time equivalent position is allocated to pharmacy alumni engagement efforts at their institution. Barriers to alumni engagement efforts included limited budgets, and staff, engaging alumni via in-person events, and maintaining accurate alumni records. CONCLUSIONS: The Academy may benefit from expanding the annual alumni survey and developing a consistent tracking mechanism to capture and report alumni engagement activities. Additionally, education on alumni engagement metrics and potential collaborative efforts with institutional alumni relations personnel would be of value. This is vital in developing and optimizing alumni relations efforts and engaging pharmacy alumni bases.

Learning few-shot imitation as cultural transmission.

Cultural transmission is the domain-general social skill that allows agents to acquire and use information from each other in real-time with high fidelity and recall. It can be thought of as the process that perpetuates fit variants in cultural evolution. In humans, cultural evolution has led to the accumulation and refinement of skills, tools and knowledge across generations. We provide a method for generating cultural transmission in artificially intelligent agents, in the form of few-shot imitation. Our agents succeed at real-time imitation of a human in novel contexts without using any pre-collected human data. We identify a surprisingly simple set of ingredients sufficient for generating cultural transmission and develop an evaluation methodology for rigorously assessing it. This paves the way for cultural evolution to play an algorithmic role in the development of artificial general intelligence.

Papillon Flap-Design Modification of ALT Flap for Circumferential Laryngopharyngeal Defect.

Anterolateral thigh (ALT) free flap is a commonly used flap for reconstruction of circumferential laryngopharyngeal defects. The flap is harvested as an ellipse and tubed along its length. We would like to present a design modification of the ALT flap where the tubing of the flap is done along the width of the flap. This design has advantages as it allows for a two-layered closure without the harvest of additional tissue and provides skin for neck coverage also. After inset, the flap resembles a butterfly, hence the name "Papillon Flap."

Non-COVID-19 Cutaneous Mucormycosis from a Plastic Surgical Perspective.

Background Cutaneous mucormycosis is a rare and fulminant infection associated with high mortality. Plastic surgeons come across this infection in the settings of road traffic accidents, surgical site infections, and as a secondary infection with underlying bacterial soft tissue infections. Due to this infection's rarity and aggressive course, it is essential to initiate prompt multidisciplinary management at the first presentation. With this study, we aim to present a protocol for managing the condition. Methods This is a retrospective observational study of patients with cutaneous mucormycosis managed at a tertiary care hospital from January 1, 2016 to November 30, 2022 excluding patients with mucormycosis who tested positive for coronavirus disease 2019. Results Of 24 patients, 22 were males, and most were in the age group of 41 to 60 years. Sixteen patients survived and five out of eight deceased had comorbidities, six presented primarily without prior debridement, and six had trunk involvement. Conclusion A high index of clinical suspicion is necessary for early diagnosis and management of patients with invasive cutaneous mucormycosis. A multidisciplinary approach with appropriate medical and surgical management can improve outcomes in cases that otherwise carry a high mortality rate.