Single-Crystal Cage Framework with High Selectivity and Reversibility in Fullerene Binding.

Host-guest chemistry, a pivotal branch of supramolecular chemistry, plays an essential role in understanding and constructing complex structures through non-covalent interactions. Organic molecular cages, characterized by their intrinsic confined cavities, can selectively bind a variety of guest molecules. Their host-guest chemistry has been well studied in the solution phase, and several attempts have been made to encode well-defined molecular architectures into solid-state polymeric materials. However, only limited studies have explored their potential in the solid state, where their lack of robustness and less ordered networks significantly hinder practical applications. Herein, we report the synthesis of a single-crystal cage framework and a systematic study of its host-guest chemistry, spanning from the solution state to the solid state. Our studies reveal that the host-guest interactions inherent to the cage are successfully maintained in the solid-state polymeric material. Furthermore, the framework's robustness allows for the guest molecules (fullerene) to be released triggered by an organic acid (trifluoracetic acid), with subsequent regeneration of the framework through an organic base (triethylamine) treatment. Our findings represent the first synthesis of a robust, single-crystal cage framework exhibiting highly selective and reversible host-guest chemistry, thus showing great potential towards molecular separation application.

Circulating KRAS G12D but not G12V is associated with survival in metastatic pancreatic ductal adenocarcinoma.

While high circulating tumor DNA (ctDNA) levels are associated with poor survival for multiple cancers, variant-specific differences in the association of ctDNA levels and survival have not been examined. Here we investigate KRAS ctDNA (ctKRAS) variant-specific associations with overall and progression-free survival (OS/PFS) in first-line metastatic pancreatic ductal adenocarcinoma (mPDAC) for patients receiving chemoimmunotherapy ("PRINCE", NCT03214250), and an independent cohort receiving standard of care (SOC) chemotherapy. For PRINCE, higher baseline plasma levels are associated with worse OS for ctKRAS G12D (log-rank p = 0.0010) but not G12V (p = 0.7101), even with adjustment for clinical covariates. Early, on-therapy clearance of G12D (p = 0.0002), but not G12V (p = 0.4058), strongly associates with OS for PRINCE. Similar results are obtained for the SOC cohort, and for PFS in both cohorts. These results suggest ctKRAS G12D but not G12V as a promising prognostic biomarker for mPDAC and that G12D clearance could also serve as an early biomarker of response.

Ionic Covalent Organic Frameworks Consisting of Tetraborate Nodes and Flexible Linkers.

Covalent organic frameworks (COFs) have emerged as versatile materials with many applications, such as carbon capture, molecular separation, catalysis, and energy storage. Traditionally, flexible building blocks have been avoided due to their potential to disrupt ordered structures. Recent studies have demonstrated intriguing properties and enhanced structural diversity achievable with flexible components by judicious selection of building blocks. This study presents a novel series of ionic COFs (ICOFs) consisting of tetraborate nodes and flexible linkers. These ICOFs use borohydrides to irreversibly deprotonate the alcohol monomers to achieve a high polymerization degree. Structural analysis confirms the dia topologies. Reticulation is explored using various monomers and metal counter-ions. Also, these frameworks exhibit excellent stability in alcohols and coordinating solvents. The materials are tested as single-ion conductive solid-state electrolytes. ICOF-203-Li displays one of the lowest activation energies reported for ion conduction. This tetraborate chemistry is anticipated to facilitate further structural diversity and functionality in crystalline polymers.

Molecular recognition with resolution below 0.2 angstroms through thermoregulatory oscillations in covalent organic frameworks.

Crystalline materials with uniform molecular-sized pores are desirable for a broad range of applications, such as sensors, catalysis, and separations. However, it is challenging to tune the pore size of a single material continuously and to reversibly distinguish small molecules (below 4 angstroms). We synthesized a series of ionic covalent organic frameworks using a tetraphenoxyborate linkage that maintains meticulous synergy between structural rigidity and local flexibility to achieve continuous and reversible (100 thermal cycles) tunability of "dynamic pores" between 2.9 and 4.0 angstroms, with resolution below 0.2 angstroms. This results from temperature-regulated, gradual amplitude change of high-frequency linker oscillations. These thermoelastic apertures selectively block larger molecules over marginally smaller ones, demonstrating size-based molecular recognition and the potential for separating challenging gas mixtures such as oxygen/nitrogen and nitrogen/methane.

Oceanic Anoxic Event 2 triggered by Kerguelen volcanism.

Large Igneous Provinces (LIPs) are associated with global warming and carbon cycle perturbations during Oceanic Anoxic Event 2 (OAE2, ~94 Ma) and the Mid-Cenomanian Event (MCE, ~96.5 Ma). However, there is still no consensus on the role volcanism played as a trigger, or its source - previously ascribed to the Caribbean LIP or High Arctic LIP. Here, we use Mentelle Basin sedimentary mercury (Hg) concentrations to determine the timing of volcanism, and neodymium (Nd) and strontium (Sr) isotopes for sedimentary provenance. High Hg concentrations compared to Northern Hemisphere records, and a shift to radiogenic Nd isotopes, indicates Kerguelen LIP volcanic activity and plateau uplift occurred in the lead up to and within OAE2. Whilst we find limited evidence that a volcanic event caused the MCE, pulsed Hg spikes before and during OAE2 imply volcanic emissions were key in driving climate and carbon cycle changes and triggering OAE2.

New Advances in Covalent Network Polymers via Dynamic Covalent Chemistry.

Covalent network polymers, as materials composed of atoms interconnected by covalent bonds in a continuous network, are known for their thermal and chemical stability. Over the past two decades, these materials have undergone significant transformations, gaining properties such as malleability, environmental responsiveness, recyclability, crystallinity, and customizable porosity, enabled by the development and integration of dynamic covalent chemistry (DCvC). In this review, we explore the innovative realm of covalent network polymers by focusing on the recent advances achieved through the application of DCvC. We start by examining the history and fundamental principles of DCvC, detailing its inception and core concepts and noting its key role in reversible covalent bond formation. Then the reprocessability of covalent network polymers enabled by DCvC is thoroughly discussed, starting from the significant milestones that marked the evolution of these polymers and progressing to their current trends and applications. The influence of DCvC on the crystallinity of covalent network polymers is then reviewed, covering their bond diversity, synthesis techniques, and functionalities. In the concluding section, we address the current challenges faced in the field of covalent network polymers and speculates on potential future directions.

Factors predicting long-term weight maintenance in anorexia nervosa: a systematic review.

PURPOSE: Eating disorder recovery is a poorly defined concept, with large variations among researchers' definitions. Weight maintenance is a key aspect of recovery that remains relatively underexplored in the literature. Understanding the role of weight maintenance may help guide the development of treatments. This paper aims to address this by (1) investigating the factors predicting long-term weight maintenance in anorexia nervosa (AN) patients; (2) exploring differences in predictive factors between adolescent and adult populations; and (3) exploring how weight maintenance is conceptualised in the literature. METHODS: We conducted a systematic review following PRISMA guidelines to address our research questions. Five databases were searched and filtered according to our exclusion criteria. RESULTS: From the search, 1059 studies were yielded, and 13 studies were included for review. A range of weight, biological and psychological factors were found to predict weight maintenance among these papers. BMI at admission and discharge from inpatient treatment was the most common predictor among the papers. Few studies investigated biological factors and mixed evidence was found for psychological factors. We found no observable differences between adult and adolescent populations. Finally, weight maintenance was defined and measured differently across studies. CONCLUSION: This review's findings can help contribute to a well-rounded understanding of weight maintenance, and ultimately, of recovery. This can help support clinicians in tailoring interventions to improve long-term outcomes in AN. Future research should aim to replicate studies to better understand the relationship between the factors identified and weight maintenance. LEVEL I: Systematic review.

GWAS-informed data integration and non-coding CRISPRi screen illuminate genetic etiology of bone mineral density.

Over 1,100 independent signals have been identified with genome-wide association studies (GWAS) for bone mineral density (BMD), a key risk factor for mortality-increasing fragility fractures; however, the effector gene(s) for most remain unknown. Informed by a variant-to-gene mapping strategy implicating 89 non-coding elements predicted to regulate osteoblast gene expression at BMD GWAS loci, we executed a single-cell CRISPRi screen in human fetal osteoblast 1.19 cells (hFOBs). The BMD relevance of hFOBs was supported by heritability enrichment from cross-cell type stratified LD-score regression involving 98 cell types grouped into 15 tissues. 24 genes showed perturbation in the screen, with four (ARID5B, CC2D1B, EIF4G2, and NCOA3) exhibiting consistent effects upon siRNA knockdown on three measures of osteoblast maturation and mineralization. Lastly, additional heritability enrichments, genetic correlations, and multi-trait fine-mapping revealed that many BMD GWAS signals are pleiotropic and likely mediate their effects via non-bone tissues that warrant attention in future screens.

The use and misuse of the SCOFF screening measure over two decades: a systematic literature review.

PURPOSE: The SCOFF questionnaire was designed as a simple, memorable screening tool to raise suspicion that a person might have an eating disorder. It is over 20 years since the creation of the SCOFF, during which time it has been widely used. Considering this, we wish to review the use of the SCOFF in peer-reviewed scientific journals, and to assess whether it is being used appropriately in the manner in which it was originally devised and tested. METHODS: The Preferred Reporting Items for a Systematic Review and Meta-analysis (PRISMA) guidelines were followed, and all search strategies and methods were determined before the onset of the study. PubMed and Wiley Online Library were searched using the terms SCOFF and eating. Two reviewers were involved in the reviewing process. Criteria for appropriate use of the SCOFF were formalised with the tool's original authors. RESULTS: 180 articles were included in the final review. 48 articles had used the SCOFF appropriately, 117 articles inappropriately and 15 articles had been mixed in the appropriateness of their use. CONCLUSION: This systematic review highlights the inappropriate use of the SCOFF in diverse languages and settings. When used correctly the SCOFF has made a significant contribution to the understanding of eating disorders and its simplicity has been applauded and led to widespread use. However in over two-thirds of studies, the use of the SCOFF was inappropriate and the paper highlights how and in what way it was misused, Guidelines for the appropriate use of the SCOFF are stated. Future validation and avenues of research are suggested. LEVEL OF EVIDENCE: Level I.

Dynamic Entwined Topology in Helical Covalent Polymers Dictated by Competing Supramolecular Interactions.

Naturally occurring polymeric structures often consist of 1D polymer chains intricately folded and entwined through non-covalent bonds, adopting precise topologies crucial for their functionality. The exploration of crystalline 1D polymers through dynamic covalent chemistry (DCvC) and supramolecular interactions represents a novel approach for developing crystalline polymers. This study shows that sub-angstrom differences in the counter-ion size can lead to various helical covalent polymer (HCP) topologies, including a novel metal-coordination HCP (m-HCP) motif. Single-crystal X-ray diffraction (SCXRD) analysis of HCP-Na revealed that double helical pairs are formed by sodium ions coordinating to spiroborate linkages to form rectangular pores. The double helices are interpenetrated by the unreacted diols coordinating sodium ions. The reticulation of the m-HCP structure was demonstrated by the successful synthesis of HCP-K. Finally, ion-exchange studies were conducted to show the interconversion between HCP structures. This research illustrates how seemingly simple modifications, such as changes in counter-ion size, can significantly influence the polymer topology and determine which supramolecular interactions dominate the crystal lattice.

Clinical pharmacist intervention to ensure safe stimulant prescribing practices at a Veterans Affairs facility.

Introduction: The Psychotropic Drug Safety Initiative (PDSI) is a national Veterans Affairs program that recommends obtaining cardiovascular vital signs semiannually and urine toxicology screening annually for veterans prescribed stimulants. The PDSI also recommends a risk review of concurrent central nervous system (CNS) depressants to ensure the benefits of coadministration with stimulants outweigh the risks. This project's purpose was to evaluate the occurrence of coprescriptions for CNS depressants and stimulants and encourage compliance with the PDSI recommendations to increase safe and appropriate management of veterans prescribed the combination. This study aimed to evaluate the occurrence of coprescriptions for CNS depressants and stimulants, evaluate compliance with stimulant monitoring recommendations, and measure the proportion of pharmacist recommendations implemented by the prescriber. Methods: This quality improvement project identified veterans with an outpatient prescription for a stimulant and any coprescription(s) for benzodiazepines, sedative-hypnotics, and/or opioids. A pharmacy intervention note was generated to request a risk review, provide recommendations for de-escalation, and notify the stimulant prescriber of overdue monitoring parameters. Impact was measured 60 days after intervention. Descriptive statistics and a McNemar test were used to compare preintervention and postintervention data. Results: From the 61 patients included, there were 67 unique prescriptions for benzodiazepines (49.3%), sedative-hypnotics (34.3%), and opioids (16.4%) in combination with a stimulant. Pharmacist intervention resulted in de-escalation of coprescribing for 9 patients (16.1%) and was associated with statistically significant improvement in compliance to stimulant monitoring recommendations. Discussion: Clinical pharmacists can assist in ensuring safe and appropriate monitoring and management of veterans prescribed stimulants.

Specific psychological therapies versus other therapies or no treatment for severe and enduring anorexia nervosa.

BACKGROUND: Anorexia nervosa is a psychological condition characterised by self-starvation and fear or wait gain or other body image disturbance. The first line of treatment is specific psychological therapy; however, there is no consensus on best practice for treating people who develop severe and enduring anorexia nervosa (SEAN). Notably, there is no universal definition of SEAN. OBJECTIVES: To evaluate the benefits and harms of specific psychological therapies for severe and enduring anorexia nervosa compared with other specific therapies, non-specific therapies, no treatment/waiting list, antidepressant medication, dietary counselling alone, or treatment as usual. SEARCH METHODS: We used standard, extensive Cochrane search methods. The last search date was 22 July 2022. SELECTION CRITERIA: We included parallel randomised controlled trials (RCTs) of people (any age) with anorexia nervosa of at least three years' duration. Eligible experimental interventions were any specific psychological therapy for improved physical and psychological health in anorexia nervosa, conducted in any treatment setting with no restrictions in terms of number of sessions, modality, or duration of therapy. Eligible comparator interventions included any other specific psychological therapy for anorexia nervosa, non-specific psychological therapy for mental health disorders, no treatment or waiting list, antipsychotic treatment (with or without psychological therapy), antidepressant treatment (with or without psychological therapy), dietary counselling, and treatment as usual as defined by the individual trials. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Our primary outcomes were clinical improvement (weight restoration to within the normal weight range for participant sample) and treatment non-completion. Results were presented using the GRADE appraisal tool. MAIN RESULTS: We found two eligible studies, but only one study provided usable data. This was a parallel-group RCT of 63 adults with SEAN who had an illness duration of at least seven years. The trial compared outpatient cognitive behaviour therapy for SEAN (CBT-SEAN) with specialist supportive clinical management for SEAN (SSCM-SE) over eight months. It is unclear if there is any difference between the effect of CBT-SEAN versus SSCM-SE on clinical improvement at 12 months (risk ratio (RR) 1.42, 95% confidence interval (CI) 0.66 to 3.05) or treatment non-completion (RR 1.72, 95% CI 0.45 to 6.59). There were no reported data on adverse effects. The trial was at high risk of performance and detection bias. We rated the GRADE level of evidence as very low-certainty for both primary outcomes, downgrading for imprecision and risk of bias concerns. AUTHORS' CONCLUSIONS: This review reports evidence from one trial that evaluated CBT-SEAN versus SSCM-SE. There was very low-certainty evidence of little or no difference in clinical improvement and treatment non-completion between the two therapies. There is a need for larger high-quality trials to determine the benefits of specific psychological therapies for people with SEAN. These should take into account the duration of illness as well as participants' previous experience with evidence-based psychological therapy for anorexia nervosa.

3D Covalent Organic Framework as a Metastable Intermediate in the Formation of a Double-Stranded Helical Covalent Polymer.

The design and development of intricate artificial architectures have been pursued for decades. Helical covalent polymer (HCP) was recently reported as an unexpected topology that consists of chiral 1D polymers assembled through weak hydrogen bonds from achiral building blocks. However, many questions remained about the formation, driving force, and the single-handedness observed in each crystal. In this work, we reveal a metastable, racemic, fully covalently cross-linked, 3D covalent organic framework (COF) as an intermediate in the early stage of polymerization, which slowly converts into single-handed HCP double helices through partial fragmentation and self-sorting with the aid of a series of hydrogen bonding. Our work provides an intriguing example where weak noncovalent bonds serve as the determining factor of the overall product structure and facilitate the formation of a sophisticated polymeric architecture.

Dynamic Covalent Self-sorting in Molecular and Polymeric Architectures Enabled by Spiroborate Bond Exchange.

Self-sorting is commonly observed in complex reaction systems, which has been utilized to guide the formation of single major by-design molecules. However, most studies have been focused on non-covalent systems, and using self-sorting to achieve covalently bonded architectures is still relatively less explored. Herein, we first demonstrated the dynamic nature of spiroborate linkage and systematically studied the self-sorting behavior observed in the transformation between spiroborate-linked well-defined polymeric and molecular architectures, which is enabled by spiroborate bond exchange. The scrambling between a macrocycle and a 1D helical covalent polymer led to the formation of a molecular cage, whose structures are all unambiguously elucidated by single-crystal X-ray diffraction. The results indicate that the molecular cage is the thermodynamically favored product in this multi-component reaction system. This work represents the first example of a 1D polymeric architecture transforming into a shape-persistent molecular cage, driven by dynamic covalent self-sorting. This study will further guide the design of spiroborate-based materials and open the possibilities for the development of novel complex yet responsive dynamic covalent molecular or polymeric systems.

Current and upcoming radionuclide therapies in the direction of precision oncology: A narrative review.

As new molecular tracers are identified to target specific receptors, tissue, and tumor types, opportunities arise for the development of both diagnostic tracers and their therapeutic counterparts, termed "theranostics." While diagnostic tracers utilize positron emitters or gamma-emitting radionuclides, their theranostic counterparts are typically bound to beta and alpha emitters, which can deliver specific and localized radiation to targets with minimal collateral damage to uninvolved surrounding structures. This is an exciting time in molecular imaging and therapy and a step towards personalized and precise medicine in which patients who were either without treatment options or not candidates for other therapies now have expanded options, with tangible data showing improved outcomes. This manuscript explores the current state of theranostics, providing background, treatment specifics, and toxicities, and discusses future potential trends.

Developments in Pb-210 methodologies to provide chronologies for environmental change.

Chronologies generated from core profiles to apply dates to environmental changes commonly use the measurement of the activity of radionuclides deposited and stratified with physical environmental material. The most commonly reported nuclide to define chronologies covering the last 150 years is Pb-210, for which accepted data processing methodologies in the literature have focussed on the constant rate of supply (CRS) model and the more recently published Bayesian Plum model. This short communication describes a validation approach using defined sediment layers referred to as 'varve' counting, which provide known points of reference to account for uncertainty between generated dates from each model using published Pb-210 measurements. A significant improvement in the chronologies was observed when applying reference date corrections to the models. This was shown to be essential in providing confidence in reported datasets and accuracy of predicted chronologies, which will better inform the interpretation of environmental change, e.g. sedimentation rates, climate change, pollution pathways and land degradation. Generated chronologies from both the CRS and Plum methods showed good agreement with the established varve dates (typically < 4-year difference).

Asystole following spinal anaesthesia: the hazards of intrinsic cardiac reflexes.

Unwanted initiation of intrinsic cardiac reflexes can precipitate bradycardia and cardiac arrest after spinal anaesthesia. We report the case of a 40-year-old man who suffered sudden asystolic cardiac arrest following spinal anaesthesia prior to planned abdominal surgery, likely due to the initiation of one or more intrinsic cardiac reflexes including the Bezold-Jarisch reflex, the reverse Bainbridge reflex and the pacemaker stretch reflex. The characteristics of this patient placed him at increased risk of this underappreciated cause of bradycardia and hypotension. We present a summary of the physiology and clinical features relevant to this case and the considerations for avoidance of similar complications after spinal anaesthesia.