Screening Carbon Nano Materials for preventing amyloid protein aggregation by adopting a facile method.

The soluble-to-toxic transformation of intrinsically disordered amyloidogenic proteins such as amyloid beta (Aβ), α-synuclein, mutant Huntingtin Protein (mHTT) and islet amyloid polypeptide (IAPP) among others is associated with disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and Type 2 Diabetes (T2D), respectively. The dissolution of mature fibrils and toxic amyloidogenic intermediates including oligomers continues to be the pinnacle in the treatment of neurodegenerative disorders. Yet, methods to effectively, and quantitatively, report on the interconversion between amyloid monomers, oligomers and mature fibrils fall short.

A focused update to the 2019 NLA scientific statement on use of lipoprotein(a) in clinical practice.

Since the 2019 National Lipid Association (NLA) Scientific Statement on Use of Lipoprotein(a) in Clinical Practice was issued, accumulating epidemiological data have clarified the relationship between lipoprotein(a) [Lp(a)] level and cardiovascular disease risk and risk reduction. Therefore, the NLA developed this focused update to guide clinicians in applying this emerging evidence in clinical practice. We now have sufficient evidence to support the recommendation to measure Lp(a) levels at least once in every adult for risk stratification.

Peptidoglycan-Targeted [F]3,3,3-Trifluoro-d-alanine Tracer for Imaging Bacterial Infection.

Imaging is increasingly used to detect and monitor bacterial infection. Both anatomic (X-rays, computed tomography, ultrasound, and MRI) and nuclear medicine ([In]-WBC SPECT, [F]FDG PET) techniques are used in clinical practice but lack specificity for the causative microorganisms themselves. To meet this challenge, many groups have developed imaging methods that target pathogen-specific metabolism, including PET tracers integrated into the bacterial cell wall.

How can trial designs better serve the needs of children and young people with juvenile idiopathic arthritis?

In juvenile idiopathic arthritis we have seen remarkable progress in the number of available licensed biological and small molecule treatments in the past two decades, leading to improved outcomes for patients. Designing clinical trials for these therapeutics is fraught with ethical, legislative, and practical challenges. However, many aspects of current clinical trial design in juvenile idiopathic arthritis do not meet the needs of patients and clinicians.

Refinements in the use of silicone oil as an intraocular tamponade.

It is over 60 years since Paul Cibis et al. reported the experimental use of liquid silicone in the surgical management of retinal detachment. Initial experiences were complicated by significant side-effects associated with the impurities in the non-medical grade commercial silicone oils deployed at the time.

Implementation, enrollment, and engagement in an opt-out telehealth pharmacist-assisted tobacco treatment program for patients seen in oncology outpatient clinics.

Objective: To describe the workflow, reach, cost, and self-reported quit rates for an opt-out tobacco treatment program (TTP) for patients seen in 43 oncology outpatient clinics.

Methods: Between May 25, 2021, and December 31, 2022, adult patients (≥18 years) visiting clinics affiliated with the Medical University of South Carolina Hollings Cancer Center were screened for smoking status. Those currently smoking were referred to a telehealth pharmacy-assisted TTP.

Evaluating Outcome Prediction via Baseline, End-of-Treatment, and Delta Radiomics on PET-CT Images of Primary Mediastinal Large B-Cell Lymphoma.

Objectives: Accurate outcome prediction is important for making informed clinical decisions in cancer treatment. In this study, we assessed the feasibility of using changes in radiomic features over time (Delta radiomics: absolute and relative) following chemotherapy, to predict relapse/progression and time to progression (TTP) of primary mediastinal large B-cell lymphoma (PMBCL) patients.

Material And Methods: Given the lack of standard staging PET scans until 2011, only 31 out of 103 PMBCL patients in our retrospective study had both pre-treatment and end-of-treatment (EoT) scans.

Diindoles produced from commensal microbiota metabolites function as endogenous CAR/Nr1i3 ligands.

Numerous studies have demonstrated the correlation between human gut bacteria and host physiology, mediated primarily via nuclear receptors (NRs). Despite this body of work, the systematic identification and characterization of microbe-derived ligands that regulate NRs remain a considerable challenge. In this study, we discover a series of diindole molecules produced from commensal bacteria metabolites that act as specific agonists for the orphan constitutive androstane receptor (CAR).

Targeted sampling of natural product space to identify bioactive natural product-like polyketide macrolides.

Polyketide or polyketide-like macrolides (pMLs) continue to serve as a source of inspiration for drug discovery. However, their inherent structural and stereochemical complexity challenges efforts to explore related regions of chemical space more broadly. Here, we report a strategy termed the Targeted Sampling of Natural Product space (TSNaP) that is designed to identify and assess regions of chemical space bounded by this important class of molecules.

Semi-supervised learning towards automated segmentation of PET images with limited annotations: application to lymphoma patients.

Manual segmentation poses a time-consuming challenge for disease quantification, therapy evaluation, treatment planning, and outcome prediction. Convolutional neural networks (CNNs) hold promise in accurately identifying tumor locations and boundaries in PET scans. However, a major hurdle is the extensive amount of supervised and annotated data necessary for training.

Structural analysis of a U-superfamily conotoxin containing a mini-granulin fold: Insights into key features that distinguish between the ICK and granulin folds.

We are entering an exciting time in structural biology where artificial intelligence can be used to predict protein structures with greater accuracy than ever before. Extending this level of accuracy to the predictions of disulfide-rich peptide structures is likely to be more challenging, at least in the short term, given the tight packing of cysteine residues and the numerous ways that the disulfide bonds can potentially be linked. It has been previously shown in many cases that several disulfide bond connectivities can be accommodated by a single set of NMR-derived structural data without significant violations.

The SecM arrest peptide traps a pre-peptide bond formation state of the ribosome.

Nascent polypeptide chains can induce translational stalling to regulate gene expression. This is exemplified by the E. coli secretion monitor (SecM) arrest peptide that induces translational stalling to regulate expression of the downstream encoded SecA, an ATPase that co-operates with the SecYEG translocon to facilitate insertion of proteins into or through the cytoplasmic membrane.

RAPP-containing arrest peptides induce translational stalling by short circuiting the ribosomal peptidyltransferase activity.

Arrest peptides containing RAPP (ArgAlaProPro) motifs have been discovered in both Gram-positive and Gram-negative bacteria, where they are thought to regulate expression of important protein localization machinery components. Here we determine cryo-EM structures of ribosomes stalled on RAPP arrest motifs in both Bacillus subtilis and Escherichia coli. Together with molecular dynamics simulations, our structures reveal that the RAPP motifs allow full accommodation of the A-site tRNA, but prevent the subsequent peptide bond from forming.

Mentally healthy living after pandemic social distancing: a study of older Canadians reveals helpful anxiety reduction strategies.

Background: Throughout the COVID-19 pandemic, older Canadians were the most at risk of severe physical harm, including death, and their return to post-COVID life was expected to be especially anxiety-provoking. A study was conducted to obtain nationally representative evidence of older Canadians' self-perceived anxiety levels and their strategies to manage or mitigate it as public health restrictions were lifting.

Materials And Methods: This study had a cross-sectional descriptive design.

The condition-dependence of male genital size and shape.

The male genitals of internal fertilisers evolve rapidly and divergently, and sexual selection is generally responsible for this. Many sexually selected traits are condition-dependent-with their expression dependent upon the resources available to be allocated to them-as revealed by genetic or environmental manipulations of condition. However, it is not clear whether male genitals are also condition-dependent.

Optimal phase-based control of strongly perturbed limit cycle oscillators using phase reduction techniques.

Phase reduction is a well-established technique for analysis and control of weakly perturbed limit cycle oscillators. However, its accuracy is diminished in a strongly perturbed setting where information about the amplitude dynamics must also be considered. In this paper, we consider phase-based control of general limit cycle oscillators in both weakly and strongly perturbed regimes.

Sex Workers' Experiences of Screening for Intimate Partner Violence.

Objective: To examine experiences of intimate partner violence (IPV) screening among women who sell sex.

Design: A qualitative descriptive study.

Setting: Telephone interviews during the COVID-19 pandemic (June 2020 to October 2020).

Early-life prefrontal cortex inhibition and early-life stress lead to long-lasting behavioral, transcriptional, and physiological impairments.

Early-life stress has been linked to multiple neurodevelopmental and neuropsychiatric deficits. Our previous studies have linked maternal presence/absence from the nest in developing rat pups to changes in prefrontal cortex (PFC) activity. Furthermore, we have shown that these changes are modulated by serotonergic signaling.

Utility of peripheral protein biomarkers for the prediction of incident interstitial features: a multicentre retrospective cohort study.

Introduction/rationale: Protein biomarkers may help enable the prediction of incident interstitial features on chest CT.

Methods: We identified which protein biomarkers in a cohort of smokers (COPDGene) differed between those with and without objectively measured interstitial features at baseline using a univariate screen (t-test false discovery rate, FDR p<0.001), and which of those were associated with interstitial features longitudinally (multivariable mixed effects model FDR p<0.

Enantioselective Total Synthesis of the Marine Macrolides Salarins A and C.

Here we report the first total synthesis of the marine macrolide salarin C, a potent anticancer agent, and demonstrate the biomimetic oxidation-Wasserman rearrangement to access salarin A. This synthesis relies on L-proline catalysis to install a chlorohydrin function that masks the sensitive C16-C17 epoxide and potentially mimics the biosynthesis of these compounds where a related chlorohydrin may yield both THF- and epoxide-containing salarins. Additional and key features of the synthesis include (i) macrocycle formation via ring-closing metathesis, (ii) macrocyclic substrate-controlled epoxidation of the C12-C13 allylic alcohol, and (iii) a late-stage Julia-Kocienski olefination to install the side chain.