Modeling and tuning the electronic, mechanical and optical properties of a recently synthesized 2D polyaramid: a first principles study.

This work delves into a methodology of modeling 2D materials and their structural engineering, considering an example of a recently synthesized 2D polyaramid (2DPA-1). A bottom-up approach similar to experimental techniques is implemented for modeling, and then its electronic structures and phonon spectrum and the quadratic nature of flexural phonons are analyzed. Furthermore, boron and nitrogen atoms are substituted for the carbon atom of the amide group of 2DPA-1, and their effects on its electronic properties, phonon spectrum, and mechanical properties are compared with those of pristine 2DPA-1 using density functional theory calculations. The ab initio molecular dynamics (AIMD) simulations validate the thermal stability of our system at high temperatures. The spin-polarized electronic structures reveal the transformation of pristine 2DPA-1 from a semiconductor to a half-metal and its magnetic behaviour upon nitrogen substitution. Constraining the quadratic nature of flexural phonons using the Born-Huang criteria significantly enhances the phonon spectra, leading to more accurate and reliable simulations. For modulated 2DPA-1, the elastic modulus varies between 17 and 27 N m-1, and the absorption peaks shift from ∼5.15 eV to 2.42 eV, enabling the application of polymeric 2D nanomaterials in photocatalysis and sensing, where light absorption in the near-infrared region is important. Finally, validation of our methodology is confirmed, as computed Young's modulus (11.26-11.76 GPa) of 2DPA-1 matches excellently with the experimental value (12.7 ± 3.8 GPa). Overall, this study reveals the modeling of a newly synthesized polymeric 2D material, and tuning its properties results in smaller bandgaps and half-metallic and magnetic behaviours.

Orthodontic Extrusion of Subgingivally Fractured Lateral Incisor and Canine Using Gold Post: A Case Report: 1 Year Follow-Up.

The case report describes a multidisciplinary approach using orthodontic forced eruption to facilitate prosthetic restoration of a maxillary permanent lateral incisor and canine with poor restorability for a young patient. Restoration after orthodontic eruption presents a more conservative treatment choice in young patients compared with prosthetic restoration after extraction. On examination, the patient had root stumps in the region of 22 and 23. We decided to treat the patient by orthodontic extrusion followed by endodontic post and core. The case was treated with the help of 19 gauge wire and gold posts.

Outcomes of single- versus multi-port video-assisted thoracoscopic surgery: Data from a multicenter randomized controlled trial of video-assisted thoracoscopic surgery versus thoracotomy for lung cancer.

Objectives: Surgery through a single port may be less painful because access is supplied by 1 intercostal nerve or more painful because multiple instruments are used in 1 port. We analyzed data collected from the video-assisted thoracoscopic surgery group of a randomized controlled trial to compare differences in pain up to 1 year. Methods: Groups were compared in a prespecified exploratory analysis using direct (regression) and indirect comparison (difference with respect to thoracotomy). In-hospital visual analogue scale pain scores were used, and analgesic ratios were calculated. After discharge, pain was evaluated using European Organization for Research and Treatment of Cancer Quality of Life Questionnaires-Core 30 scores up to 1 year. Results: From July 2015 to February 2019, we randomized 503 participants. After excluding 50 participants who did not receive lobectomy, surgery was performed using a single port in 42 participants (predominately by a single surgeon), multiple ports in 166 participants, and thoracotomy in 245 participants. No differences were observed in-hospital between single- and multiple-port video-assisted thoracoscopic surgery when modeled using a direct comparison, mean difference of -0.24 (95% CI, -1.06 to 0.58) or indirect comparison, mean difference of -0.33 (-1.16 to 0.51). Mean analgesic ratio (single/multiple port) was 0.75 (0.64 to 0.87) for direct comparison and 0.90 (0.64 to 1.25) for indirect comparison. After discharge, pain for single-port video-assisted thoracoscopic surgery was lower than for multiple-port video-assisted thoracoscopic surgery (first 3 months), and corresponding physical function was higher up to 12 months. Conclusions: There were no consistent differences for in-hospital pain when lobectomy was undertaken using 1 or multiple ports. However, better pain scores and physical function were observed for single-port surgery after discharge.

2023 White Paper on Recent Issues in Bioanalysis: Deuterated Drugs; LNP; Tumor/FFPE Biopsy; Targeted Proteomics; Small Molecule Covalent Inhibitors; Chiral Bioanalysis; Remote Regulatory Assessments; Sample Reconciliation/Chain of Custody (PART 1A - Recommendations on Mass Spectrometry, Chromatography, Sample Preparation Latest Developments, Challenges, and Solutions and BMV/Regulated Bioanalysis PART 1B - Regulatory Agencies' Inputs on Regulated Bioanalysis/BMV, Biomarkers/IVD/CDx/BAV, Immunogenicity, Gene & Cell Therapy and Vaccine).

The 17th Workshop on Recent Issues in Bioanalysis (17th WRIB) took place in Orlando, FL, USA on June 19-23, 2023. Over 1000 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 17th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.Moreover, in-depth workshops on "EU IVDR 2017/746 Implementation and impact for the Global Biomarker Community: How to Comply with this NEW Regulation" and on "US FDA/OSIS Remote Regulatory Assessments (RRAs)" were the special features of the 17th edition.As in previous years, WRIB continued to gather a wide diversity of international, industry opinion leaders and regulatory authority experts working on both small and large molecules as well as gene, cell therapies and vaccines to facilitate sharing and discussions focused on improving quality, increasing regulatory compliance, and achieving scientific excellence on bioanalytical issues.This 2023 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2023 edition of this comprehensive White Paper has been divided into three parts for editorial reasons.This publication covers the recommendations on Mass Spectrometry Assays, Regulated Bioanalysis/BMV (Part 1A) and Regulatory Inputs (Part 1B). Part 2 (Biomarkers, IVD/CDx, LBA and Cell-Based Assays) and Part 3 (Gene Therapy, Cell therapy, Vaccines and Biotherapeutics Immunogenicity) are published in volume 16 of Bioanalysis, issues 7 and 8 (2024), respectively.

Novel Selective Quantification of Zinpentraxin Alfa Biotherapeutic in the Presence of Endogenous Isomer in Plasma Samples of Idiopathic Pulmonary Fibrosis Patients Using Immunoaffinity LC-MS.

Idiopathic pulmonary fibrosis (IPF) is a progressive fatal interstitial lung disease that affects three million patients worldwide and currently without an effective cure. Zinpentraxin alfa, a recombinant human pentraxin-2 (rhPTX-2) protein, has been evaluated as a potential drug candidate for the treatment of IPF. Clinical pharmacokinetic analysis of zinpentraxin alfa has been challenging historically due to interference from serum amyloid P component (SAP), an endogenous human pentraxin-2 protein. These molecules share an identical primary amino acid sequence and glycan composition; however, zinpentraxin alfa possesses α2,3-linked terminal sialic acid residues while SAP is an α2,6-linked isomer. By taking advantage of this only structural difference, we developed a novel assay strategy where α2,3-sialidase was used to selectively hydrolyze α2,3-linked sialic acid residues, resulting in desialylated zinpentraxin alfa versus unchanged sialylated SAP, following an immunoaffinity capture step. Subsequent tryptic digestion produced a unique surrogate asialo-glycopeptide from zinpentraxin alfa and allowed specific quantification of the biotherapeutic in human plasma. In addition, a common peptide shared by both molecules was selected as a surrogate to determine total hPTX-2 concentrations, i.e., sum of zinpentraxin alfa and SAP. The quantification methods for both zinpentraxin alfa and total hPTX-2 were validated and used in pharmacokinetic assessment in IPF patients. The preliminary results suggest that endogenous SAP levels remained largely constant in IPF patients throughout the treatment with zinpentraxin alfa. Our novel approach provides a general bioanalytical strategy to selectively quantify α2,3-sialylated glycoproteins in the presence of their corresponding α2,6-linked isomers.