Correlating Pressure‐Induced Emission Modulation with Linker Rotation in a Photoluminescent MOF

Conformational changes of linker units in metal‐organic frameworks (MOFs) are often responsible for gate‐opening phenomena in selective gas adsorption and stimuli‐responsive optical and electrical sensing behaviour. Herein, we show that pressure‐induced bathochromic shifts in both fluorescence emission and UV‐Vis absorption spectra of a two‐fold interpenetrated Hf MOF, linked by 1,4‐phenylene‐bis(4‐ethynylbenzoate) ligands ( Hf‐peb ), are induced by rotation of the central phenyl ring of the linker, from a coplanar arrangement to a twisted, previously unseen conformer. Single‐crystal X‐ray diffraction, alongside in situ fluorescence and UV‐Vis absorption spectroscopies, measured up to 2.1 GPa in a diamond anvil cell on single crystals, are in excellent agreement, correlating linker rotation with modulation of emission. Topologically isolating the 1,4‐phenylene‐bis(4‐ethynylbenzoate) units within a MOF facilitates concurrent structural and spectroscopic study in the absence of intermolecular perturbation, allowing characterisation of the luminescence properties of a high‐energy, twisted conformation of the previously well‐studied chromophore. We expect the unique environment provided by network solids, and the capability of combining crystallographic and spectroscopic analysis, will greatly enhance understanding of luminescent molecules and lead to the development of novel sensors and adsorbents

Using Intervention Mapping to Develop an Efficacious Multicomponent Systems-Based Intervention to Increase Human Papillomavirus (HPV) Vaccination in a Large Urban Pediatric Clinic Network

Background: The CDC recommends HPV vaccine for all adolescents to prevent cervical, anal, oropharyngeal, vaginal, vulvar, and penile cancers, and genital warts. HPV vaccine rates currently fall short of national vaccination goals. Despite evidence-based strategies with demonstrated efficacy to increase HPV vaccination rates, adoption and implementation of these strategies within clinics is lacking. The Adolescent Vaccination Program (AVP) is a multicomponent systems-based intervention designed to implement five evidence-based strategies within primary care pediatric practices. The AVP has demonstrated efficacy in increasing HPV vaccine initiation and completion among adolescents 10-17 years of age. The purpose of this paper is to describe the application of Intervention Mapping (IM) toward the development, implementation, and formative evaluation of the clinic-based AVP prototype. Methods: Intervention Mapping (IM) guided the development of the Adolescent Vaccination Program (AVP). Deliverables comprised: a logic model of the problem (IM Step 1); matrices of behavior change objectives (IM Step 2); a program planning document comprising scope, sequence, theory-based methods, and practical strategies (IM Step 3); functional AVP component prototypes (IM Step 4); and plans for implementation (IM Step 5) and evaluation (IM Step 6). Results: The AVP consists of six evidence-based strategies implemented in a successful sequenced roll-out that (1) established immunization champions in each clinic, (2) disseminated provider assessment and feedback reports with data-informed vaccination goals, (3) provided continued medical and nursing education (with ethics credit) on HPV, HPV vaccination, message bundling, and responding to parent hesitancy, (4) electronic health record cues to providers on patient eligibility, and (5) patient reminders for HPV vaccine initiation and completion. Conclusions: IM provided a logical and systematic approach to developing and evaluating a multicomponent systems-based intervention to increase HPV vaccination rates among adolescents in pediatric clinics

Uncovering the Structural Diversity of Y(III) Naphthalene-2,6-Dicarboxylate MOFs Through Coordination Modulation

Metal-organic frameworks (MOFs)—network structures built from metal ions or clusters and connecting organic ligands—are typically synthesized by solvothermal self-assembly. For transition metal based MOFs, structural predictability is facilitated by control over coordination geometries and linker connectivity under the principles of isoreticular synthesis. For rare earth (RE) MOFs, coordination behavior is dominated by steric and electronic factors, leading to unpredictable structures, and poor control over self-assembly. Herein we show that coordination modulation—the addition of competing ligands into MOF syntheses—offers programmable access to six different Y(III) MOFs all connected by the same naphthalene-2,6-dicarboxylate ligand, despite controlled synthesis of multiple phases from the same metal-ligand combination often being challenging for rare earth MOFs. Four of the materials are isolable in bulk phase purity, three are amenable to rapid microwave synthesis, and the fluorescence sensing ability of one example toward metal cations is reported. The results show that a huge variety of structurally versatile MOFs can potentially be prepared from simple systems, and that coordination modulation is a powerful tool for systematic control of phase behavior in rare earth MOFs

The Brugia malayi neuropeptide receptor-4 is activated by FMRFamide-like peptides and signals via Gα

Genetic studies undertaken in the model organism Caenorhabditis elegans have demonstrated the importance of neuropeptidergic signalling in nematode physiology. Disruption of this signalling may have deleterious phenotypic consequences, including altered locomotion, feeding behaviour, and reproduction. Neuropeptide G protein-coupled receptors (GPCRs) that transduce many of these signals therefore represent cogent drug targets. Recently published genomic sequencing data for a number of parasitic helminths of medical and veterinary importance has revealed the apparent conservation of a number of neuropeptides, and neuropeptide receptors between parasitic and free-living species, raising the intriguing possibility of developing broad-spectrum anthelmintic therapeutics. Here, we identify and clone a neuropeptide receptor, NPR-4, from the human filarial nematode Brugia malayi and demonstrate its activation in vitro, by FMRFamide-like peptides of the FLP-18 family, and intracellular signalling via G i mediated pathways. These data represent the first example of deorphanisation of a neuropeptide GPCR in any parasitic helminth species.MRC South Africa and the University of Cape Town.http://www.journals.elsevier.com/molecular-and-biochemical-parasitology/hb2014Zoology and EntomologyMammal Research Institut

Loss-of-function mutations in the human luteinizing hormone receptor predominantly cause intracellular retention

This work was supported by the South African Medical Research Council (Award to the MRC/UCT Receptor Biology Research Unit); the Claude Leon Foundation, South Africa (Postdoctoral Research Fellowship: C.L.N.); the University of Cape Town (URC Fellowship: R.C.A.); The University of Pretoria (RDP grants: C.L.N. and R.C.A.); and the National Research Foundation, South Africa (CSUR Grant [94008]: C.L.N.).http://press.endocrine.org/journal/endoam2016ImmunologyPhysiologyZoology and Entomolog

Predicting Responses of Geo-ecological Carbonate Reef Systems to Climate Change: A Conceptual Model and Review

Coral reefs provide critical ecological and geomorphic (e.g. sediment production for reef-fronted shoreline maintenance) services, which interact in complex and dynamic ways. These services are under threat from climate change, requiring dynamic modelling approaches that predict how reef systems will respond to different future climate scenarios. Carbonate budgets, which estimate net reef calcium carbonate production, provide a comprehensive ‘snap-shot’ assessment of reef accretionary potential and reef stability. These budgets, however, were not intended to account for the full suite of processes that maintain coral reef services or to provide predictive capacity on longer timescales (decadal to centennial). To respond to the dual challenges of enhancing carbonate budget assessments and advancing their predictive capacity, we applied a novel model elicitation and review method to create a qualitative geo-ecological carbonate reef system model that links geomorphic, ecological and physical processes. Our approach conceptualizes relationships between net carbonate production, sediment transport and landform stability, and rates knowledge confidence to reveal major knowledge gaps and critical future research pathways. The model provides a blueprint for future coral reef research that aims to quantify net carbonate production and sediment dynamics, improving our capacity to predict responses of reefs and reef-fronted shorelines to future climate change

Performance status: A key factor in predicting mortality in the first wave of COVID-19 in South-East Scotland

BACKGROUND: COVID-19 mortality risk factors have been established in large cohort studies; long-term mortality outcomes are less documented. METHODS: We performed multivariable logistic regression to identify factors associated with in-patient mortality and intensive care unit (ICU) admission in symptomatic COVID-19 patients admitted to hospitals in South-East Scotland from 1st March to 30th June 2020. One-year mortality was reviewed. RESULTS: Of 726 patients (median age 72; interquartile range: 58–83 years, 55% male), 104 (14%) required ICU admission and 199 (27%) died in hospital. A further 64 died between discharge and 30th June 2021 (36% overall 1-year mortality). Stepwise logistic regression identified age >79 (odds ratio (OR), 4.77 (95% confidence interval (CI), 1.96–12.75)), male sex (OR, 1.83 (95% CI, 1.21–2.80)) and higher European Cooperative Oncology Group/World Health Organization performance status as associated with higher mortality risk. DISCUSSION: Poor functional baseline was the predominant independent risk factor for mortality in COVID-19. More than one-third of individuals had died by 1 year following admission

Multimorbidity, polypharmacy, and COVID-19 infection within the UK Biobank cohort

Background: It is now well recognised that the risk of severe COVID-19 increases with some long-term conditions (LTCs). However, prior research primarily focuses on individual LTCs and there is a lack of data on the influence of multimorbidity (≥2 LTCs) on the risk of COVID-19. Given the high prevalence of multimorbidity, more detailed understanding of the associations with multimorbidity and COVID-19 would improve risk stratification and help protect those most vulnerable to severe COVID-19. Here we examine the relationships between multimorbidity, polypharmacy (a proxy of multimorbidity), and COVID-19; and how these differ by sociodemographic, lifestyle, and physiological prognostic factors. Methods and findings: We studied data from UK Biobank (428,199 participants; aged 37–73; recruited 2006–2010) on self-reported LTCs, medications, sociodemographic, lifestyle, and physiological measures which were linked to COVID-19 test data. Poisson regression models examined risk of COVID-19 by multimorbidity/polypharmacy and effect modification by COVID-19 prognostic factors (age/sex/ethnicity/socioeconomic status/smoking/physical activity/BMI/systolic blood pressure/renal function). 4,498 (1.05%) participants were tested; 1,324 (0.31%) tested positive for COVID-19. Compared with no LTCs, relative risk (RR) of COVID-19 in those with 1 LTC was no higher (RR 1.12 (CI 0.96–1.30)), whereas those with ≥2 LTCs had 48% higher risk; RR 1.48 (1.28–1.71). Compared with no cardiometabolic LTCs, having 1 and ≥2 cardiometabolic LTCs had a higher risk of COVID-19; RR 1.28 (1.12–1.46) and 1.77 (1.46–2.15), respectively. Polypharmacy was associated with a dose response higher risk of COVID-19. All prognostic factors were associated with a higher risk of COVID-19 infection in multimorbidity; being non-white, most socioeconomically deprived, BMI ≥40 kg/m2, and reduced renal function were associated with the highest risk of COVID-19 infection: RR 2.81 (2.09–3.78); 2.79 (2.00–3.90); 2.66 (1.88–3.76); 2.13 (1.46–3.12), respectively. No multiplicative interaction between multimorbidity and prognostic factors was identified. Important limitations include the low proportion of UK Biobank participants with COVID-19 test data (1.05%) and UK Biobank participants being more affluent, healthier and less ethnically diverse than the general population. Conclusions: Increasing multimorbidity, especially cardiometabolic multimorbidity, and polypharmacy are associated with a higher risk of developing COVID-19. Those with multimorbidity and additional factors, such as non-white ethnicity, are at heightened risk of COVID-19

Direct three-dimensional printing of polymeric scaffolds with nanofibrous topography

Three-dimensional (3D) printing is a powerful manufacturing tool for making 3D structures with well-defined architectures for a wide range of applications. The field of tissue engineering has also adopted this technology to fabricate scaffolds for tissue regeneration. The ability to control architecture of scaffolds, e.g. matching anatomical shapes and having defined pore size, has since been improved significantly. However, the material surface of these scaffolds is smooth and does not resemble that found in natural extracellular matrix (ECM), in particular, the nanofibrous morphology of collagen. This natural nanoscale morphology plays a critical role in cell behaviour. Here, we have developed a new approach to directly fabricate polymeric scaffolds with an ECM-like nanofibrous topography and defined architectures using extrusion-based 3D printing. 3D printed tall scaffolds with interconnected pores were created with disparate features spanning from nanometres to centimetres. Our approach removes the need for a sacrificial mould and subsequent mould removal compared to previous methods. Moreover, the nanofibrous topography of the 3D printed scaffolds significantly enhanced protein absorption, cell adhesion and differentiation of human mesenchymal stem cells (MSCs) when compared to those with smooth material surfaces. These 3D printed scaffolds with both defined architectures and nanoscale ECM-mimicking morphologies have potential applications in cartilage and bone regeneration