Deriving and validating a risk prediction model for long COVID: a population-based, retrospective cohort study in Scotland.

Objectives: Using electronic health records, we derived and internally validated a prediction model to estimate risk factors for long COVID and predict individual risk of developing long COVID.

Design: Population-based, retrospective cohort study.

Setting: Scotland.

Single-cell AI-based detection and prognostic and predictive value of DNA mismatch repair deficiency in colorectal cancer.

Testing for DNA mismatch repair deficiency (MMRd) is recommended for all colorectal cancers (CRCs). Automating this would enable precision medicine, particularly if providing information on etiology not captured by deep learning (DL) methods. We present AIMMeR, an AI-based method for determination of mismatch repair (MMR) protein expression at a single-cell level in routine pathology samples.

Assessment of the Addition of Oxaliplatin to Fluoropyrimidine-Based Adjuvant Chemotherapy in Patients With High-Risk Stage II Colon Cancer: An ACCENT Pooled Analysis.

Purpose: The adjuvant treatment for stage III colon cancer (CC) is chemotherapy combining fluoropyrimidine (FP) and oxaliplatin (OX). FP regimen plus OX (FPOX) may benefit in high-risk stage II CC. We performed a pooled analysis of pivotal MOSAIC and C-07 studies evaluating FPOX for the treatment of high-risk stage II CC according to prognostic factors, number of high-risk factors, and current clinicopathologic risk classification on the basis of T stage, tumor perforation, and number of lymph nodes examined.

Cyclic ether and anhydride ring opening copolymerisation delivering new ABB sequences in poly(ester--ethers).

Poly(ester--ethers) are interesting as they combine the ester linkage rigidity and potential for hydrolysis with ether linkage flexibility. This work describes a generally applicable route to their synthesis applying commercial monomers and yielding poly(ester--ethers) with variable compositions and structures. The ring-opening copolymerisation of anhydrides (A), epoxides (B) and cyclic ethers (C), using a Zr(iv) catalyst, produces either ABB or ABC type poly(ester--ethers).

Discovery of the Lipopeptides Albubactins A-H from RKJM0023 via Chemical Elicitation with Rhamnolipids and Synthesis of Albubactin A.

The marine tunicate-derived RKJM0023 was cultured in the presence of a rhamnolipid mixture in an effort to elicit the production of silent natural products. MS/MS-based molecular networking analysis enhanced with nonparametric statistics highlighted the upregulation of a molecular cluster (Kruskal-Wallis = 1.6 e for ) in which no MS/MS features had library matches.

Ultrasonic Shears Decrease Postoperative Hematomas in Head and Neck Microvascular Reconstruction.

Objective: To evaluate postoperative hematoma and takeback rates in a large series of microvascular reconstructions. We sought to determine whether the use of ultrasonic shears reduced these rates.

Study Design: Retrospective cohort study.

Fine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes.

Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV.

Discovery of Acyl-Surugamide A2 from Marine RKJM-0023-A New Cyclic Nonribosomal Peptide Containing an N-ε-acetyl-L-lysine Residue.

We report the discovery of a novel cyclic nonribosomal peptide (NRP), acyl-surugamide A2, from a marine-derived RKJM-0023 (CP133227). The structure of acyl-surugamide A2 was elucidated using a combination of NMR spectroscopy, MS2 fragmentation analysis, and comparative analysis of the biosynthetic gene cluster. Acyl-surugamide A2 contains all eight core amino acids of surugamide A, with a modified N-ε-acetyl-L-lysine residue.

Assessment of monoclonal antibody glycosylation: a comparative study using HRMS, NMR, and HILIC-FLD.

Monoclonal antibodies (mAbs) represent the largest class of therapeutic protein drug products. mAb glycosylation produces a heterogeneous, analytically challenging distribution of glycoforms that typically should be adequately characterized because glycosylation-based product quality attributes (PQAs) can impact product quality, immunogenicity, and efficacy. In this study, two products were compared using a panel of analytical methods.

Oxaliplatin-Based Adjuvant Chemotherapy in Older Patients With Stage III Colon Cancer: An ACCENT/IDEA Pooled Analysis of 12 Trials.

Purpose: A number of studies suggest that older patients may have reduced or no benefit from the addition of oxaliplatin to fluoropyrimidines as adjuvant chemotherapy for stage III colon cancer (CC).

Materials And Methods: We studied the prognostic impact of age, as well as treatment adherence/toxicity patterns according to age, in patients with stage III CC who received 3 or 6 months of infusional fluorouracil, leucovorin, and oxaliplatin/capecitabine and oxaliplatin (CAPOX) on the basis of data collected from trials from the ACCENT and IDEA databases. Associations between age and time to recurrence (TTR), disease-free survival (DFS), overall survival (OS), survival after recurrence (SAR), and cancer-specific survival (CSS) were assessed by a Cox model or a competing risk model, stratified by studies and adjusted for sex, performance status, T and N stage, and year of enrollment.

Prognostic and Predictive Value of Immunoscore in Stage III Colorectal Cancer: Pooled Analysis of Cases From the SCOT and IDEA-HORG Studies.

Purpose: Immunoscore (IS) is prognostic in stage III colorectal cancer (CRC) and may predict benefit of duration (6 3 months) of adjuvant infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy. We sought to determine IS prognostic and predictive value in stage-III CRC treated with adjuvant FOLFOX or oral capecitabine and infusional oxaliplatin (CAPOX) in the SCOT and IDEA-HORG trials.

Methods: Three thousand sixty-one cases had tumor samples, of which 2,643 (1,792 CAPOX) were eligible for IS testing.

High Molar Mass Polycarbonates as Closed-Loop Recyclable Thermoplastics.

Using carbon dioxide (CO) to make recyclable thermoplastics could reduce greenhouse gas emissions associated with polymer manufacturing. CO/cyclic epoxide ring-opening copolymerization (ROCOP) allows for >30 wt % of the polycarbonate to derive from CO; so far, the field has largely focused on oligocarbonates. In contrast, efficient catalysts for high molar mass polycarbonates are underinvestigated, and the resulting thermoplastic structure-property relationships, processing, and recycling need to be elucidated.

Multiplex analysis of intratumoural immune infiltrate and prognosis in patients with stage II-III colorectal cancer from the SCOT and QUASAR 2 trials: a retrospective analysis.

Background: Tumour-infiltrating CD8 cytotoxic T cells confer favourable prognosis in colorectal cancer. The added prognostic value of other infiltrating immune cells is unclear and so we sought to investigate their prognostic value in two large clinical trial cohorts.

Methods: We used multiplex immunofluorescent staining of tissue microarrays to assess the densities of CD8, CD20, FoxP3, and CD68 cells in the intraepithelial and intrastromal compartments from tumour samples of patients with stage II-III colorectal cancer from the SCOT trial (ISRCTN59757862), which examined 3 months versus 6 months of adjuvant oxaliplatin-based chemotherapy, and from the QUASAR 2 trial (ISRCTN45133151), which compared adjuvant capecitabine with or without bevacizumab.

Designing a circular carbon and plastics economy for a sustainable future.

The linear production and consumption of plastics today is unsustainable. It creates large amounts of unnecessary and mismanaged waste, pollution and carbon dioxide emissions, undermining global climate targets and the Sustainable Development Goals. This Perspective provides an integrated technological, economic and legal view on how to deliver a circular carbon and plastics economy that minimizes carbon dioxide emissions.

Mutation profiling in South African patients with Cornelia de Lange syndrome phenotype.

Background: Cornelia de Lange Syndrome (CdLS) presents with a variable multi-systemic phenotype and pathogenic variants have been identified in five main genes. This condition has been understudied in African populations with little phenotypic and molecular information available.

Methods And Results: We present a cohort of 14 patients with clinical features suggestive of CdLS.

Mechanism of action of pseudopteroxazole and pseudopterosin G: Diterpenes from marine origin.

Pseudopteroxazole (Ptx) and the pseudopterosins are marine natural products with promising antibacterial potential. While Ptx has attracted interest for its antimycobacterial activity, pseudopterosins are active against several clinically relevant pathogens. Both compound classes exhibit low cytotoxicity and accessibility to targeted synthesis, yet their antibacterial mechanisms remain elusive.

A feasible molecular diagnostic strategy for rare genetic disorders within resource-constrained environments.

Timely and accurate diagnosis of rare genetic disorders is critical, as it enables improved patient management and prognosis. In a resource-constrained environment such as the South African State healthcare system, the challenge is to design appropriate and cost-effective assays that will enable accurate genetic diagnostic services in patients of African ancestry across a broad disease spectrum. Next-generation sequencing (NGS) has transformed testing approaches for many Mendelian disorders, but this technology is still relatively new in our setting and requires cost-effective ways to implement.

Antiaging Effects of Topical Defensins.

Topical defensins have recently gained attention as agents to improve skin composition. This study aimed to aggregate and synthesize studies in the literature assessing the effects of topical defensins on skin composition in the context of its ability to combat signs of aging.

The Implant-borne Articulation Splint in Fibula Free Flap Mandibular Reconstruction: A Technical Note.

Computer-aided design and computer-aided manufacturing and digitally simulated surgeries have revolutionized maxillomandibular reconstruction. In particular, this technology has increased the accuracy and facilitated the process of dental implantation in fibula free flaps. Despite the efficacy of virtual planning, there is a minor degree of translational difference between digital and intraoperative measurements, which may affect the precision of implant and fibula orientations.

Accounting for intensity variation in image analysis of large-scale multiplexed clinical trial datasets.

Multiplex immunofluorescence (mIF) imaging can provide comprehensive quantitative and spatial information for multiple immune markers for tumour immunoprofiling. However, application at scale to clinical trial samples sourced from multiple institutions is challenging due to pre-analytical heterogeneity. This study reports an analytical approach to the largest multi-parameter immunoprofiling study of clinical trial samples to date.

Different prognostic values of KRAS exon 2 submutations and BRAF V600E mutation in microsatellite stable (MSS) and unstable (MSI) stage III colon cancer: an ACCENT/IDEA pooled analysis of seven trials.

Background: The prognostic value of KRAS and BRAF mutations in stage III colon cancer (CC) remains controversial and has never been clearly analyzed in patients with microsatellite instability-high (MSI-H) tumors due to sample size limitations. Data are also lacking for KRAS submutations and prognosis.

Patients And Methods: We examined clinicopathological variables and prognosis in patients with surgically resected stage III CC who participated in seven clinical trials from the ACCENT/IDEA databases.