Fluorinated carbohydrates for 18F-positron emission tomography (PET).

Carbohydrate diversity is foundational in the molecular literacy that regulates cellular function and communication. Consequently, delineating and leveraging this structure-function interplay continues to be a core research objective in the development of candidates for biomedical diagnostics. A totemic example is the ubiquity of 2-deoxy-2-[18F]-fluoro-D-glucose (2-[18F]-FDG) as a radiotracer for positron emission tomography (PET), in which metabolic trapping is harnessed. Building on this clinical success, more complex sugars with unique selectivities are gaining momentum in molecular recognition and personalised medicine: this reflects the opportunities that carbohydrate-specific targeting affords in a broader sense. In this Tutorial Review, key milestones in the development of 2-[18F]-FDG and related glycan-based radiotracers for PET are described, with their diagnostic functions, to assist in navigating this rapidly expanding field of interdisciplinary research.

Transformative reproductive futures in Northern Ireland.

A foundation of rights-based solidarity has fostered an environment of cooperation between LGBTQ+ (lesbian, gay, bisexual, transgender and queer) rights and reproductive justice in Northern Ireland (NI) following the introduction of equal marriage and the decriminalization of abortion in 2019. This article provides a grounded look at this reproductive justice organizing in NI as an example of transformative organizing for reproductive futures. The case study considers a conversation with two activists who have been central to this work. Emma Campbell coconvenor of Alliance for Choice and Danielle Roberts the coconvenor of Reclaim the Agenda and former Senior Policy and Development Officer of HERe NI. Reclaim the Agenda is a coalition of feminist, youth, LGBTQ+ and community organizations that connects and mobilizes women to promote feminist activism through education, campaigning and celebration. HERe NI is a community organization and registered charity based in Belfast that supports lesbian and bisexual women and their families across NI. Alliance for Choice campaigns for free, safe legal and local abortion access for everyone who needs it in NI. Together these groups approach reproductive justice using a framework informed by lesbian feminist organizing and an intersectional approach that views access to abortion as part of a broader understanding of gender justice inspired by Black-women led SisterSong through (1) cross-movement organizing (2) centering bodily autonomy and (3) trans affirming feminist approaches to navigating shifting language about gender. The case study will be of interest to those working provide abortion services in a queer-informed way, as well as those navigating the challenges of reforming abortion policy.

Women's experiences of social support during pregnancy: a qualitative systematic review.

BACKGROUND: Social support during pregnancy can alleviate emotional and physical pressures, improving the well-being of mother and child. Understanding women's lived experiences and perceptions of social support during pregnancy is imperative to better support women. This systematic review explores and synthesises the qualitative research on women's experiences of social support during pregnancy. METHODS: Databases PubMed, CINAHL, MEDLINE, APA PsycInfo and Scopus were searched with no year limit. Eligible studies included pregnant women or women who were up to one year postpartum and were assessed on their experiences of social support during pregnancy. The data were synthesised using the thematic synthesis approach. RESULTS: Fourteen studies were included with data from 571 participating women across ten countries; two studies used focus groups, and 12 used interviews to collect their data. Four main themes were developed ('a variety of emotional support', 'tangible and intangible instrumental support', 'traditional rituals and spiritual support', and 'the all-encompassing natal home'), and six sub-themes ('female network connections', 'care and affection from the husband', 'dissatisfaction with relationships', 'financial support from the husband and family', 'practical support from family and friends', 'health information support'). CONCLUSIONS: This systematic review sheds light on women's experiences of social support during pregnancy. The results indicate a broad variety of emotional support experienced and valued by pregnant women from different sources. Additionally, women expressed satisfaction and dissatisfaction with tangible and intangible support forms. It was also highlighted that spirituality played an essential role in reducing stress and offering coping mechanisms for some, whereas spirituality increased stress levels for others.

Evaluation of the psychometric properties of the Youth Psychopathic Traits Inventory-Short Version among young people in South Africa and the relationship of high scale scores to reported offending or similar deviant behaviour.

BACKGROUND: While there is empirical evidence to support associations between psychopathy scale ratings and offending or deviant behaviours, suggested as support for a unified theory of crime, evidence to date has been mainly from countries with high economic ratings and Western philosophies. In countries with a wide range of cultural groups and languages and a complex history of colonisation and apartheid, such scale ratings and correlations may differ. AIMS: To explore the psychometric properties of the Youth Psychopathic Traits Inventory-Short Version (YPI-S) and its applicability and relationship to deviant and actual or potential criminal behaviour among young adults in South Africa. METHODS: 18- to 20-year-olds from poor socio-economic backgrounds were recruited by a fieldworker with an existing relationship with community-based youth centres. Consenting participants completed the Deviant Behaviour Variety Scale, reflecting criminal or similar behaviours in the 12 months prior to rating and the YPI-S. Reliability measurements, principal factor analysis, Spearman's Rho correlations, chi square and multiple regression were used to explore performance of the YPI-S in this sample and relationship of YPI-S scores to deviancy. RESULTS: Of the 213 participants recruited, 176 completed all data points and were entered into analyses. The YPI-S was found to have generally good psychometric properties; however, in factor analysis, while items mapped well into an emotional subscale and quite well into an interpersonal scale, as in the original, behavioural items did not. Emotional, interpersonal and total YPI-S scores were significantly associated with reported deviant behaviour scores. CONCLUSION: The findings of this study suggest value in using the YPI-S with young people in South Africa to help identify those vulnerable to committing criminal acts. Among these disadvantaged young people, however, caution should be used in interpreting scores on its behavioural dimension. It is interesting that the emotional dimension, which incorporates perhaps the most personal features such as 'callous and unemotional traits' (albeit probably better considered as difficulty in recognising emotions in others), seemed most robust, suggesting that there may be core problems in a pathway to crime-or theory of crime-that transcend culture. This possibility, likely to be remediable through personal interventions, would benefit from further investigation.

Evaluating resources required to evaluate child outcomes following indirect services in early childhood education centres: A scoping review.

ISSUE ADDRESSED: Speech-language pathologists (SLPs) may provide indirect services focusing on the promotion of rich communication environments in early childhood education centres. Evaluating children's outcomes following SLP-led professional development in early childhood education centres is challenging. The aim of this scoping review was to identify how child outcomes were measured in studies exploring SLP professional development in early childhood education. METHODS: A systematic search of seven databases was conducted to identify studies that included the provision of an indirect SLP service and measurement of child outcomes. Twelve studies were identified that met all inclusion criteria for the scoping review. Information about the research design, professional development training provided and child outcome measures collected were all extracted from the identified studies. RESULTS: Half of the identified studies relied on the direct assessment of child language and seven studies utilised video-recording of interactions between educators and child/ren in their care. CONCLUSIONS: Evaluating child outcomes following SLP professional development in early childhood education centres is not only challenging but also expensive. Considerations for the allocation of suitable resources to evaluate indirect services are discussed. SO WHAT?: SLPs may need to demonstrate the impact of indirect services focusing on health promotion through the evaluation of child outcomes. The findings of this investigation outline the challenges identifying appropriate tools to capture the outcomes of children.

A High Pressure Operando Spectroscopy Examination of Bimetal Interactions in 'Metal Efficient' Palladium/In2 O3 /Al2 O3 Catalysts for CO2 Hydrogenation.

CO2 hydrogenation to methanol has the potential to serve as a sustainable route to a wide variety of hydrocarbons, fuels and plastics in the quest for net zero. Synergistic Pd/In2 O3 (Palldium on Indium Oxide) catalysts show high CO2 conversion and methanol selectivity, enhancing methanol yield. The identity of the optimal active site for this reaction is unclear, either as a Pd-In alloy, proximate metals, or distinct sites. In this work, we demonstrate that metal-efficient Pd/In2 O3 species dispersed on Al2 O3 can match the performance of pure Pd/In2 O3 systems. Further, we follow the evolution of both Pd and In sites, and surface species, under operando reaction conditions using X-ray Absorption Spectroscpy (XAS) and infrared (IR) spectroscopy. In doing so, we can determine both the nature of the active sites and the influence on the catalytic mechanism.

A Chemo- and Regioselective Tandem [3 + 2]Heteroannulation Strategy for Carbazole Synthesis: Combining Two Mechanistically Distinct Bond-Forming Processes.

A modular approach to prepare tri- and tetracyclic carbazoles by a sequential [3 + 2]heteroannulation is described. First, optimization of Pd-catalyzed Buchwald-Hartwig amination followed by C/N-arylation in a one-pot process is established. Second, mechanistic analyses identified the origins of chemo- and regioselective sequential control of both bond-forming steps. Finally, the substrate scope is demonstrated by the preparation of a range of tri- and tetracyclic carbazoles, including expedient access to several natural products and anti-cancer agents.

Splice-switching small molecules: A new therapeutic approach to modulate gene expression.

Manipulating alternative RNA splicing events with small molecules is emerging as a viable mechanism for the development of therapeutics. A salient challenge in the field is understanding the molecular determinants defining the selectivity of splice-switching events and their mechanisms of action. In this review, the current state-of-the-art in splice-switching small molecules is described. Three examples of splice-switching small molecules are presented, and the differences in their modes of action compared.

Mindfulness induction and cognition: A systematic review and meta-analysis.

Mindfulness meditation might improve a variety of cognitive processes, but the available evidence remains fragmented. This preregistered meta-analysis (PROSPERO-CRD42018100320) aimed to provide insight into this hypothesis by assessing the effects of brief mindful attention induction on cognition. Articles were retrieved from Pubmed, PsycInfo and Web of Science up until August 1, 2018. A total of 34 studies were included. The outcomes were categorized into four cognitive domains: attentional functioning, memory, executive functioning and higher-order function. A small effect was found across all cognitive domains (Hedges' g = 0.18, 95% IC = 0.07-0.29). Separated analyses for each cognitive domain revealed an effect only in higher-order cognitive functions (k = 10, Hedges' g = 0.35, 95% IC = 0.20-0.50). Results suggest that mindfulness induction improves cognitive performance in tasks involving complex higher-order functions. There was no evidence of publication bias, but studies generally presented many methodological flaws.

T-cell modulation by cyclophosphamide for tumour therapy.

The power of T cells for cancer treatment has been demonstrated by the success of co-inhibitory receptor blockade and adoptive T-cell immunotherapies. These treatments are highly successful for certain cancers, but are often personalized, expensive and associated with harmful side effects. Other T-cell-modulating drugs may provide additional means of improving immune responses to tumours without these disadvantages. Conventional chemotherapeutic drugs are traditionally used to target cancers directly; however, it is clear that some also have significant immune-modulating effects that can be harnessed to target tumours. Cyclophosphamide is one such drug; used at lower doses than in mainstream chemotherapy, it can perturb immune homeostasis, tipping the balance towards generation of anti-tumour T-cell responses and control of cancer growth. This review discusses its growing reputation as an immune-modulator whose multiple effects synergize with the microbiota to tip the balance towards tumour immunity offering widespread benefits as a safe, and relatively inexpensive component of cancer immunotherapy.

Open letter to Minister Helen Morton.

This letter was sent to the Honourable Helen Morton by Emma Campbell after the Occupational Therapy Australia National Conference. A number of members of First Australian and Australian OTs online were keen to show their support for Emma's letter and share this with other OT colleagues.

A high-throughput SNP array in the amphidiploid species Brassica napus shows diversity in resistance genes.

Single-nucleotide polymorphisms (SNPs)are molecular markers based on nucleotide variation and can be used for genotyping assays across populations and to track genomic inheritance. SNPs offer a comprehensive genotyping alternative to whole-genome sequencing for both agricultural and research purposes including molecular breeding and diagnostics, genome evolution and genetic diversity analyses, genetic mapping, and trait association studies. Here genomic SNPs were discovered between four cultivars of the important amphidiploid oilseed species Brassica napus and used to develop a B. napus Infinium™ array containing 5,306 SNPs randomly dispersed across the genome. Assay success was high, with >94 % of these producing a reproducible, polymorphic genotype in the 1,070 samples screened. Although the assay was designed to B. napus, successful SNP amplification was achieved in the B. napus progenitor species, Brassica rapa and Brassica oleracea, and to a lesser extent in the related species Brassica nigra. Phylogenetic analysis was consistent with the expected relationships between B. napus individuals. This study presents an efficient custom SNP assay development pipeline in the complex polyploid Brassica genome and demonstrates the utility of the array for high-throughput genotyping in a number of related Brassica species. It also demonstrates the utility of this assay in genotyping resistance genes on chromosome A7, which segregate amongst the 1,070 samples.

Chimeric Protein Switch Biosensors.

Rapid detection of protein and small-molecule analytes is a valuable technique across multiple disciplines, but most in vitro testing of biological or environmental samples requires long, laborious processes and trained personnel in laboratory settings, leading to long wait times for results and high expenses. Fusion of recognition with reporter elements has been introduced to detection methods such as enzyme-linked immunoassays (ELISA), with enzyme-conjugated secondary antibodies removing one of the many incubation and wash steps. Chimeric protein switch biosensors go further and provide a platform for homogenous mix-and-read assays where long wash and incubation steps are eradicated from the process. Chimeric protein switch biosensors consist of an enzyme switch (the reporter) coupled to a recognition element, where binding of the analyte results in switching the activity of the reporter enzyme on or off. Several chimeric protein switch biosensors have successfully been developed for analytes ranging from small molecule drugs to large protein biomarkers. There are two main formats of chimeric protein switch biosensor developed, one-component and multi-component, and these formats exhibit unique advantages and disadvantages. Genetically fusing a recognition protein to the enzyme switch has many advantages in the production and performance of the biosensor. A range of immune and synthetic binding proteins have been developed as alternatives to antibodies, including antibody mimetics or antibody fragments. These are mainly small, easily manipulated proteins and can be genetically fused to a reporter for recombinant expression or manipulated to allow chemical fusion. Here, aspects of chimeric protein switch biosensors will be reviewed with a comparison of different classes of recognition elements and switching mechanisms.

Methanol-to-Olefins Studied by UV Raman Spectroscopy as Compared to Visible Wavelength: Capitalization on Resonance Enhancement.

Resonance Raman spectroscopy can provide insights into complex reaction mechanisms by selectively enhancing the signals of specific molecular species. In this work, we demonstrate that, by changing the excitation wavelength, Raman bands of different intermediates in the methanol-to-hydrocarbons reactions can be identified. We show in particular how UV excitation enhances signals from short-chain olefins and cyclopentadienyl cations during the induction period, while visible excitation better detects later-stage aromatics. However, visible excitation is prone to fluorescence that can obscure Raman signals, and hence, we show how fast fluorescence rejection techniques like Kerr gating are necessary for extracting useful information from visible excitation measurements.

Therapeutic drug monitoring of immunotherapies with novel Affimer-NanoBiT sensor construct.

Concentration-therapeutic efficacy relationships have been observed for several therapeutic monoclonal antibodies (TmAb), where low circulating levels can result in ineffective treatment and high concentrations can cause adverse reactions. Rapid therapeutic drug monitoring (TDM) of TmAb drugs would provide the opportunity to adjust an individual patient's dosing regimen to improve treatment results. However, TDM for immunotherapies is currently limited to centralised testing methods with long sample-collection to result timeframes. Here, we show four point-of-care (PoC) TmAb biosensors by combining anti-idiotypic Affimer proteins and NanoBiT split luciferase technology at a molecular level to provide a platform for rapid quantification (<10 minutes) for four clinically relevant TmAb (rituximab, adalimumab, ipilimumab and trastuzumab). The rituximab sensor performed best with 4 pM limit of detection (LoD) and a quantifiable range between 8 pM-2 nM with neglectable matrix effects in serum up to 1%. After dilution of serum samples, the resulting quantifiable range for all four sensors falls within the clinically relevant range and compares favourably with the sensitivity and/or time-to-result of current ELISA standards. Further development of these sensors into a PoC test may improve treatment outcome and quality of life for patients receiving immunotherapy.

Applications of Surface Plasmon Resonance (SPR) to the Study of Diverse Protein-Ligand Interactions.

Functional characterization of enzymes/proteins requires determination of the binding affinity of small molecules or other biomolecules with the target proteins. Several available techniques, such as proteomics and drug discovery strategies, require a precise and high-throughput assay for rapid and reliable screening of potential candidates for further testing. Surface plasmon resonance (SPR), a well-established label-free technique, directly measures biomolecular affinities. SPR assays require immobilization of one interacting component (ligand) on a conductive metal (mostly gold or silver) and a continuous flow of solution containing potential binding partner (analyte) across the surface. The SPR phenomenon occurs when polarized light excites the electrons at the interface of the metal and the dielectric medium to generate electromagnetic waves that propagate parallel to the surface. Changes in the refractive index due to interaction between the ligand and analyte are measured by detecting the reflected light, providing real-time data on kinetics and specificity. A prominent use of SPR is identifying compounds in crude plant extracts that bind to specific molecules. Procedures that utilize SPR are becoming increasingly applicable outside the laboratory setting, and SPR imaging and localized SPR (LSPR) are cheaper and more portable alternative for in situ detection of plant or mammalian pathogens and drug discovery studies. LSPR, in particular, has the advantage of direct attachment to test tissues in live-plant studies. Here, we describe three protocols utilizing SPR-based assays for precise analysis of protein-ligand interactions. © 2024 Wiley Periodicals LLC. Basic Protocol 1: SPR comparison of binding affinities of viral reverse transcriptase polymorphisms Basic Protocol 2: SPR screening of crude plant extract for protein-binding agents Basic Protocol 3: Localized SPR-based antigen detection using antibody-conjugated gold nanoparticles.

A Critical Assessment on Calculating Vibrational Spectra in Nanostructured Materials.

Vibrational spectroscopy is an omnipresent spectroscopic technique to characterize functional nanostructured materials such as zeolites, metal-organic frameworks (MOFs), and metal-halide perovskites (MHPs). The resulting experimental spectra are usually complex, with both low-frequency framework modes and high-frequency functional group vibrations. Therefore, theoretically calculated spectra are often an essential element to elucidate the vibrational fingerprint. In principle, there are two possible approaches to calculate vibrational spectra: (i) a static approach that approximates the potential energy surface (PES) as a set of independent harmonic oscillators and (ii) a dynamic approach that explicitly samples the PES around equilibrium by integrating Newton's equations of motions. The dynamic approach considers anharmonic and temperature effects and provides a more genuine representation of materials at true operating conditions; however, such simulations come at a substantially increased computational cost. This is certainly true when forces and energy evaluations are performed at the quantum mechanical level. Molecular dynamics (MD) techniques have become more established within the field of computational chemistry. Yet, for the prediction of infrared (IR) and Raman spectra of nanostructured materials, their usage has been less explored and remain restricted to some isolated successes. Therefore, it is currently not a priori clear which methodology should be used to accurately predict vibrational spectra for a given system. A comprehensive comparative study between various theoretical methods and experimental spectra for a broad set of nanostructured materials is so far lacking. To fill this gap, we herein present a concise overview on which methodology is suited to accurately predict vibrational spectra for a broad range of nanostructured materials and formulate a series of theoretical guidelines to this purpose. To this end, four different case studies are considered, each treating a particular material aspect, namely breathing in flexible MOFs, characterization of defects in the rigid MOF UiO-66, anharmonic vibrations in the metal-halide perovskite CsPbBr3, and guest adsorption on the pores of the zeolite H-SSZ-13. For all four materials, in their guest- and defect-free state and at sufficiently low temperatures, both the static and dynamic approach yield qualitatively similar spectra in agreement with experimental results. When the temperature is increased, the harmonic approximation starts to fail for CsPbBr3 due to the presence of anharmonic phonon modes. Also, the spectroscopic fingerprints of defects and guest species are insufficiently well predicted by a simple harmonic model. Both phenomena flatten the potential energy surface (PES), which facilitates the transitions between metastable states, necessitating dynamic sampling. On the basis of the four case studies treated in this Review, we can propose the following theoretical guidelines to simulate accurate vibrational spectra of functional solid-state materials: (i) For nanostructured crystalline framework materials at low temperature, insights into the lattice dynamics can be obtained using a static approach relying on a few points on the PES and an independent set of harmonic oscillators. (ii) When the material is evaluated at higher temperatures or when additional complexity enters the system, e.g., strong anharmonicity, defects, or guest species, the harmonic regime breaks down and dynamic sampling is required for a correct prediction of the phonon spectrum. These guidelines and their illustrations for prototype material classes can help experimental and theoretical researchers to enhance the knowledge obtained from a lattice dynamics study.

Progressive remodeling of structural networks following surgery for operculo-insular epilepsy.

Introduction: Operculo-insular epilepsy (OIE) is a rare condition amenable to surgery in well-selected cases. Despite the high rate of neurological complications associated with OIE surgery, most postoperative deficits recover fully and rapidly. We provide insights into this peculiar pattern of functional recovery by investigating the longitudinal reorganization of structural networks after surgery for OIE in 10 patients. Methods: Structural T1 and diffusion-weighted MRIs were performed before surgery (t0) and at 6 months (t1) and 12 months (t2) postoperatively. These images were processed with an original, comprehensive structural connectivity pipeline. Using our method, we performed comparisons between the t0 and t1 timepoints and between the t1 and t2 timepoints to characterize the progressive structural remodeling. Results: We found a widespread pattern of postoperative changes primarily in the surgical hemisphere, most of which consisted of reductions in connectivity strength (CS) and regional graph theoretic measures (rGTM) that reflect local connectivity. We also observed increases in CS and rGTMs predominantly in regions located near the resection cavity and in the contralateral healthy hemisphere. Finally, most structural changes arose in the first six months following surgery (i.e., between t0 and t1). Discussion: To our knowledge, this study provides the first description of postoperative structural connectivity changes following surgery for OIE. The ipsilateral reductions in connectivity unveiled by our analysis may result from the reversal of seizure-related structural alterations following postoperative seizure control. Moreover, the strengthening of connections in peri-resection areas and in the contralateral hemisphere may be compatible with compensatory structural plasticity, a process that could contribute to the recovery of functions seen following operculo-insular resections for focal epilepsy.

Probing the Origin of Affinity in the GM1-Cholera Toxin Complex through Site-Selective Editing with Fluorine.

Carbohydrates regulate an inimitable spectrum of biological functions, yet successfully leveraging this therapeutic avenue continues to be frustrated by low affinities with glycan-specific proteins. A conspicuous exception is the interaction of monosialotetrahexosylganglioside (GM1) with the carbohydrate-recognition domain of cholera toxin from Vibrio cholerae: this is one of the strongest protein-carbohydrate interactions known. To establish the importance of a long-discussed key hydrogen bond between C2 of the terminal galactose of GM1 and the B subunit pentamer of cholera toxin (CTB5), the total synthesis of a selectively fluorinated GM1 epitope was conducted in 19 steps. This process of molecular editing (Oδ-H → Fδ-) strategically deletes the hydrogen bond donor while retaining the localized partial charge of the substituent. Comparison of the binding affinity of F-GM1/CTB5 with native GM1, the GM1 carbohydrate epitope, and meta-mononitrophenyl-α-galactoside (MNPG) revealed a trend that fully supports the importance of this key interaction. These NMR data suggest that F-GM1 binds in a closely similar conformation as native GM1. Crystallographic analyses of the complex also confirm that the OH → F bioisosteric exchange at C2 of the terminal galactose induces a ring conformation that eliminates key hydrogen bonds: these interactions are compensated for by inter- and intramolecular fluorine-specific interactions.