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Breast cancer is the most common cancer in women, and incidence rates are rising, it is thought in part, due to increasing levels of obesity. Endocrine therapy (ET) remains the cornerstone of systemic therapy for early and advanced oestrogen receptor-positive (ER +) breast cancer, but despite treatment advances, it is becoming more evident that obesity and insulin resistance are associated with worse outcomes. Here, we describe the current understanding of the relationship between both obesity and diabetes and the prevalence and outcomes for ER+ breast cancer. We also discuss the mechanisms associated with resistance to ET and the relationship to treatment toxicity. [ABSTRACT FROM AUTHOR]

The nuclear envelope (NE) separates translation and transcription and is the location of multiple functions, including chromatin organization and nucleocytoplasmic transport. The molecular basis for many of these functions have diverged between eukaryotic lineages. Trypanosoma brucei, a member of the early branching eukaryotic lineage Discoba, highlights many of these, including a distinct lamina and kinetochore composition. Here, we describe a cohort of proteins interacting with both the lamina and NPC, which we term lamina-associated proteins (LAPs). LAPs represent a diverse group of proteins, including two candidate NPC-anchoring pore membrane proteins (POMs) with architecture conserved with S. cerevisiae and H. sapiens, and additional peripheral components of the NPC. While many of the LAPs are Kinetoplastid specific, we also identified broadly conserved proteins, indicating an amalgam of divergence and conservation within the trypanosome NE proteome, highlighting the diversity of nuclear biology across the eukaryotes, increasing our understanding of eukaryotic and NPC evolution. [ABSTRACT FROM AUTHOR]

Concerns around concussion highlight the need for strategies to improve the implementation and translation of concussion guidelines in community sports. This study assessed players' utilisation and compliance with New Zealand Rugby's Concussion Management Pathway (CMP). This pragmatic, mixed methods study comprised of concussion injury surveillance and mapping of players' healthcare touchpoints through the CMP. Semi‐structured interviews were conducted to understand stakeholders' experiences. Over the season, 27 different healthcare pathways were identified with 28% of players progressing through all phases of the CMP (ideal pathway). Of the 206 suspected concussions reported over the season, 70% were logged in the CMP phone App, and 89% of these had an associated valid baseline concussion assessment. Prior to returning to contact training, 64% of players obtained a medical clearance. One theme, 'belief in the value of pathway' was identified as a facilitator across all CMP components. Themes such as 'concussion knowledge and the nature of concussion'; 'communication between stakeholders and sufficient information on the process'; and 'strong relationships and clarity around responsibilities' were identified as facilitators across several pathway components. Other facilitators included 'ease and timing of general practitioner access'; 'the phone App as facilitator to logging'; and 'spotting for concussion as a team'. Additionally, the findings signify baseline testing as a potential pre‐cursor to overall CMP compliance. Strategies that support the facilitators identified in this study may further enhance compliance. Highlights: Many barriers to optimal concussion management exist at the community level rugby. In response, New Zealand Rugby developed and implemented a community concussion management pathway (CMP) to support improved recognition, diagnosis and management of concussion.Not all concussion management barriers are easily surmountable; nonetheless, many success stories also exist. Purposefully identifying and setting strategies in place that support and cultivate facilitators to optimal CMP use may assist in more players following the ideal pathway.The study found that stakeholders who prioritise player welfare and other facilitators like concussion knowledge, communication, strong relationships, role clarity and players attending a baseline assessment contributed to creating a successful journey through the CMP. [ABSTRACT FROM AUTHOR]

The unique properties of the lanthanide (Ln) elements make them critical components of modern technologies, such as lasers, anti‐corrosive films and catalysts. Thus, there is significant interest in establishing structure–property relationships for Ln‐containing materials to advance these technologies. Extended X‐ray absorption fine structure (EXAFS) is an excellent technique for this task considering its ability to determine the average local structure around the Ln atoms for both crystalline and amorphous materials. However, the limited availability of EXAFS reference spectra of the Ln oxides and challenges in the EXAFS analysis have hindered the application of this technique to these elements. The challenges include the limited k‐range available for the analysis due to the superposition of L‐edges on the EXAFS, multielectron excitations (MEEs) creating erroneous peaks in the EXAFS and the presence of inequivalent absorption sites. Herein, we removed MEEs to model the local atomic environment more accurately for light Ln oxides. Further, we investigated the use of cubic and non‐cubic lattice expansion to minimize the fitting parameters needed and connect the fitting parameters to physically meaningful crystal parameters. The cubic expansion reduced the number of fitting parameters but resulted in a statistically worse fit. The non‐cubic expansion resulted in a similar quality fit and showed non‐isotropic expansion in the crystal lattice of Nd2O3. In total, the EXAFS spectra and the fits for the entire set of Ln oxides (excluding promethium) are included. The knowledge developed here can assist in the structural determination of a wide variety of Ln compounds and can further studies on their structure–property relationships. [ABSTRACT FROM AUTHOR]

This study examined whether autistic people with siblings score higher on measures of empathy than those without siblings. Cohorts of autistic children (n = 939; mean age = 7.35 years (SD = 2.15)) and autistic adults (n = 736; mean age = 37 years (SD = 12.39)) from the Cambridge Autism Research Database (CARD) were each divided into two groups: with or without siblings. Empathy was measured using the children version of the Empathy Quotient (EQ) (parent-report) for children. For adults, the EQ (self-report version) and the Reading the Mind in the Eyes Test (RMET) were used. Contrary to the hypothesis, autistic children without siblings scored higher on EQ than those with siblings (t(283.70) = 4.20, p <.001; d = 0.50). In adults, there was no difference between autistic adults with and without siblings on both measures, but there was an interaction effect between sex and group on the RMET (f(1732) = 4.10, p = 0.04): whilst autistic males without siblings on average scored lower than females, autistic males with siblings on average performed similarly to females. Future research should investigate the possible effect of siblings on autistic males' empathy performance in a larger cohort of autistic individuals. Children's empathic abilities may be underestimated by their parents when they have siblings due to a contrast effect. [ABSTRACT FROM AUTHOR]

Objective: To provide detailed guidance on the administration of systemic bevacizumab in patients with recurrent respiratory papillomatosis (RRP) based on a detailed review of the scientific literature and a consensus of experts with real‐world clinical experience. Methods: A bevacizumab consensus working group (N = 10) was composed of adult and pediatric otolaryngologists, adult and pediatric oncologists, and a representative from the RRP Foundation (RRPF), all with experience administering systemic bevacizumab in patients with RRP. After extensive review of the medical literature, a modified Delphi method‐based survey series was utilized to establish consensus on the following key areas: clinical and patient characteristics ideal for treatment candidacy, patient perspective in treatment decisions, treatment access, initial dosing, monitoring, guidelines for tapering and discontinuation, and reintensifying therapy. Results: Seventy‐nine statements were identified across nine critical domains, and 45 reached consensus [clinical benefits of bevacizumab (3), patient and disease characteristics for treatment consideration (7), contraindications for treatment (3), shared decision‐making (incorporating the patient perspective) (5), treatment access (3), initial dosing and administration (8), monitoring (7), tapering and discontinuation (6), and reintensification (3)]. Conclusion: This consensus statement provides the necessary guidance for clinicians to initiate systemic administration of bevacizumab and represents a potential paradigm shift toward nonsurgical treatment options for patients with RRP. Level of Evidence: 5 Laryngoscope, 134:5041–5046, 2024 [ABSTRACT FROM AUTHOR]

Background: This scoping study explored patients' preoperative perspectives of their expectations, their tolerance for risk, and what factors may influence their decision to undergo hallux valgus surgery. Methods: Recently consented patients for hallux valgus surgery at a tertiary public hospital were recruited for this mixed-methods study. Firstly, semi-structured interviews were undertaken to explore attitudes, perceptions, feelings about risk, and expectations of surgery. Following the interview, questionnaires assessing demographics, pain, and health-related quality of life were completed. The data were analysed using NVivo and SPSS. Results: Seven participants (Five women; mean age 63, range 47–79, years) were recruited for this study. Foot pain was rated as moderate to high, but catastrophisation and sensitisation were low. Surgery was viewed a definitive resolution and expectations were high. Participants with higher pain had higher expectations and the experience of others was used to judge the chance of a successful outcome. Conclusion: People with high foot pain and hallux valgus may have higher expectations of a successful operation. Expectations and acceptance of risk in people having surgery for hallux valgus are optimistic. Key points: People use previous experience with non-related surgery as predictor of success of hallux valgus surgery People trust their surgeon and are optimistic about their outcome People with higher pain expect higher levels of improvement with hallux valgus surgery [ABSTRACT FROM AUTHOR]

Supported metal catalysts are essential to a plethora of processes in the chemical industry. The overall performance of these catalysts depends strongly on the interaction of adsorbates at the atomic level, which can be manipulated and controlled by the different constituents of the active material (i.e., support and active metal). The description of catalyst activity and the relationship between active constituent and the support, or metal–support interactions (MSI), in heterogeneous (thermo)catalysts is a complex phenomenon with multivariate (dependent and independent) contributions that are difficult to disentangle, both experimentally and theoretically. So-called "strong metal–support interactions" have been reported for several decades and summarized in excellent review articles. However, in recent years, there has been a proliferation of new findings related to atomically dispersed metal sites, metal oxide defects, and, for example, the generation and evolution of MSI under reaction conditions, which has led to the designation of (sub)classifications of MSI deserving to be critically and systematically evaluated. These include dynamic restructuring under alternating redox and reaction conditions, adsorbate-induced MSI, and evidence of strong interactions in oxide-supported metal oxide catalysts. Here, we review recent literature on MSI in oxide-supported metal particles to provide an up-to-date understanding of the underlying physicochemical principles that dominate the observed effects in supported metal atomic, cluster, and nanoparticle catalysts. Critical evaluation of different subclassifications of MSI is provided, along with discussions on the formation mechanisms, theoretical and characterization advances, and tuning strategies to manipulate catalytic reaction performance. We also provide a perspective on the future of the field, and we discuss the analysis of different MSI effects on catalysis quantitatively. [ABSTRACT FROM AUTHOR]

Experiences of dating violence are widespread among adolescents. Therefore, increasing the understanding on the developmental antecedents is crucial. However, most existing studies involve cross-sectional designs, which poses a challenge in better understanding the developmental precursors of dating violence victimization. To address this, we examine age 13 predictors of age 17 dating violence victimization in a culturally diverse sample of 643 participants (57.3% girls). Negative binomial regression models showed some significant associations between self-reports of anxiety and depression, poly-victimization, endorsement of violence-legitimizing norms of masculinity, and having initiated sexual relationships and dating at age 13 with dating violence victimization at age 17, with variations depending on the gender of the victim and the form of dating violence measured. Findings increase longitudinal evidence in the field with the aim of informing prevention and intervention strategies that address factors associated with dating violence early in adolescence. [ABSTRACT FROM AUTHOR]

Fears of negative evaluation (FNEs) and fears of positive evaluation (FPEs) comprise a bivalent model of evaluation that can explain the aetiology and maintenance of Social Anxiety Disorder (SAD). In this study, we examined an extended version of this model which incorporates two related cognitive processes (concerns about reprisal and discounting of positive outcomes) as partial mediators of the effects of FNEs and FPEs. We built on earlier work by including a broader measure of social anxiety across different social situations and comparing models for groups of participants with and without probable SAD. Structural equation modelling was utilised to test the model in a sample of 890 university students (74.8% female, mean age 29.49). We replicated the findings of Cook et al. in the overall sample and in the group with probable SAD. FNEs and FPEs predicted social anxiety directly and were serially mediated by concerns about reprisal and discounting positive outcomes. The model was also a good fit for those without SAD; however, in the model, FNEs were no longer a direct predictor of social anxiety. The findings confirm the utility of the extended bivalent model and have implications for psychoevolutionary accounts of social anxiety. [ABSTRACT FROM AUTHOR]

Background Most schwannomas are isolated tumours occurring in otherwise healthy people. However, bilateral vestibular schwannomas (BVS) or multiple nonvestibular schwannomas indicate an underlying genetic predisposition. This is most commonly NF2-related schwannomatosis (SWN), but when BVS are absent, this can also indicate SMARCB1-related or LZTR1-related SWN. Methods We assessed the variant detection rates for the three major SWN genes (NF2, LZTR1 and SMARCB1) in 154 people, from 150 families, who had at least one non-vestibular schwannoma, but who did not meet clinical criteria for NF2-related SWN at the time of genetic testing. Results We found that 17 (11%) people from 13 families had a germline SMARCB1 variant and 19 (12%) unrelated individuals had a germline LZTR1 variant. 19 people had an NF2 variant, but 18 of these were mosaic and 17 were only detected when 2 tumours were available for testing. The overall detection rate was 25% using blood alone, but increased to 36% when tumour analysis was included. Another 12 people had a germline variant of uncertain significance (VUS). Conclusions There were similar proportions of LZTR1, SMARCB1 or mosaic NF2. However, since an NF2 variant was detected in tumours from 103 people, it is likely that further cases of mosaicism would be detected if more people had additional tumours available for analysis. In addition, if further evidence becomes available to show that the VUSs are pathogenic, this would significantly increase the proportion of people with a genetic diagnosis. Our results indicate the importance of comprehensive genetic testing and improved variant classification. [ABSTRACT FROM AUTHOR]

DNA metabarcoding andmorphological taxonomic (microscopic) analysis of the gut contents was used to examine diet diversity of seven species of fishes collected from mesopelagic depths (200-1000 m) in the NW Atlantic Ocean Slope Water during Summer 2018 and 2019. Metabarcoding used two gene regions: V9 hypervariable region of nuclear 18S rRNA and mitochondrial cytochrome oxidase I (COI). V9 sequences were classified into 14 invertebrate prey groups, excluding fish due to predator swamping. Ecological network analysis was used to evaluate relative strengths of predator-prey linkages. Multivariate statistical analysis revealed consistently distinct diets of four fish species in 2018 and/or 2019: Argyropelecus aculeatus, Chauliodus sloani, Hygophum hygomii, and Sigmops elongatus. Three other species analyzed (Malacosteus niger, Nemichthys scolopaceus, and Scopelogadus beanii) showed more variability between sampling years. COI sequences were classified into eight invertebrate prey groups, within which prey species were detected and identified. Considering all predator species together, a total of 77 prey species were detected with a minimum of 1,000 COI sequences, including 22 copepods, 18 euphausiids, and 7 amphipods. Morphological prey counts were classified into seven taxonomic groups, including a gelatinous group comprised of soft-bodied organisms. The ocean twilight zone or is home to exceptional diversity and biomass of marine fish, which are key players in deep sea food webs. This study used integrative morphological-molecular analysis to provide new insights into trophic relationships and sources of productivity for mesopelagic fishes, including identification of key prey species, recognition of the importance of gelatinous prey, and characterization of differences in diet among fish predators in the NW Atlantic Slope Water. [ABSTRACT FROM AUTHOR]

The current generation of total-body positron emission tomography (PET) scanners offer significant sensitivity increase with an extended axial imaging extent. With the large volume of lutetium-based scintillation crystals that are used as detector elements in these scanners, there is an increased flux of background radiation originating from 176Lu decay in the crystals and higher sensitivity for detecting it. Combined with the ability of scanning the entire body in a single bed position, this allows more effective utilization of the lutetium background as a transmission source for estimating 511 keV attenuation coefficients. In this study, utilization of the lutetium background radiation for attenuation correction in total-body PET was studied using Monte Carlo simulations of a 3D whole-body XCAT phantom in the uEXPLORER PET scanner, with particular focus on ultralow-dose PET scans that are now made possible with these scanners. Effects of an increased acceptance angle, reduced scan durations, and Compton scattering on PET quantification were studied. Furthermore, quantification accuracy of lutetium-based attenuation correction was compared for a 20-min scan of the whole body on the uEXPLORER, a one-meter-long, and a conventional 24-cm-long scanner. Quantification and lesion contrast were minimally affected in both long axial field-of-view scanners and in a whole-body 20-min scan, the mean bias in all analyzed organs of interest were within a ±10% range compared to ground-truth activity maps. Quantification was affected in certain organs, when scan duration was reduced to 5 min or a reduced acceptance angle of 17 was used. Analysis of the Compton scattered events suggests that implementing a scatter correction method for the transmission data will be required, and increasing the energy threshold from 250 keV to 290 keV can reduce the computational costs and data rates, with negligible effects on PET quantification. Finally, the current results can serve as groundwork for transferring lutetium-based attenuation correction into research and clinical practice. [ABSTRACT FROM AUTHOR]

DNA metabarcoding and morphological taxonomic (microscopic) analysis of the gut contents was used to examine diet diversity of seven species of fishes collected from mesopelagic depths (200-1000 m) in the NW Atlantic Ocean Slope Water during Summer 2018 and 2019. Metabarcoding used two gene regions: V9 hypervariable region of nuclear 18S rRNA and mitochondrial cytochrome oxidase I (COI). V9 sequences were classified into 14 invertebrate prey groups, excluding fish due to predator swamping. Ecological network analysis was used to evaluate relative strengths of predator-prey linkages. Multivariate statistical analysis revealed consistently distinct diets of four fish species in 2018 and/or 2019: Argyropelecus aculeatus, Chauliodus sloani, Hygophum hygomii, and Sigmops elongatus. Three other species analyzed (Malacosteus niger, Nemichthys scolopaceus, and Scopelogadus beanii) showed more variability between sampling years. COI sequences were classified into eight invertebrate prey groups, within which prey species were detected and identified. Considering all predator species together, a total of 77 prey species were detected with a minimum of 1,000 COI sequences, including 22 copepods, 18 euphausiids, and 7 amphipods. Morphological prey counts were classified into seven taxonomic groups, including a gelatinous group comprised of soft-bodied organisms. The ocean twilight zone or is home to exceptional diversity and biomass of marine fish, which are key players in deep sea food webs. This study used integrative morphological-molecular analysis to provide new insights into trophic relationships and sources of productivity for mesopelagic fishes, including identification of key prey species, recognition of the importance of gelatinous prey, and characterization of differences in diet among fish predators in the NW Atlantic Slope Water. [ABSTRACT FROM AUTHOR]

While earlier first-generation epigenetic aging clocks were trained to estimate chronological age as accurately as possible, more recent next-generation clocks incorporate DNA methylation information more pertinent to health, lifestyle, and/or outcomes. Recently, we produced a non-invasive next-generation epigenetic clock trained using Infinium MethylationEPIC data from more than 8,000 diverse adult buccal samples. While this clock correlated with various health, lifestyle, and disease factors, we did not assess its ability to capture mortality. To address this gap, we applied CheekAge to the longitudinal Lothian Birth Cohorts of 1921 and 1936. Despite missing nearly half of its CpG inputs, CheekAge was significantly associated with mortality in this longitudinal blood dataset. Specifically, a change in one standard deviation corresponded to a hazard ratio (HR) of 1.21 (FDR q = 1.66e-6). CheekAge performed better than all first-generation clocks tested and displayed a comparable HR to the next-generation, blood-trained DNAm PhenoAge clock (HR = 1.23, q = 2.45e-9). To better understand the relative importance of each CheekAge input in blood, we iteratively removed each clock CpG and re-calculated the overall mortality association. The most significant effect came from omitting the CpG cg14386193, which is annotated to the gene ALPK2. Excluding this DNA methylation site increased the FDR value by nearly threefold (to 4.92e-06). We additionally performed enrichment analyses of the top annotated CpGs that impact mortality to better understand their associated biology. Taken together, we provide important validation for CheekAge and highlight novel CpGs that underlie a newly identified mortality association. [ABSTRACT FROM AUTHOR]

Multicomponent catalysts can be designed to synergistically combine reaction intermediates at interfacial active sites, but restructuring makes systematic control and understanding of such dynamics challenging. We here unveil how reducibility and mobility of indium oxide species in Ru‐based catalysts crucially control the direct, selective conversion of CO2 to ethanol. When uncontrolled, reduced indium oxide species occupy the Ru surface, leading to deactivation. With the addition of steam as a mild oxidant and using porous polymer layers to control In mobility, Ru−In2O3 interface sites are stabilized, and ethanol can be produced with superior overall selectivity (70 %, rest CO). Our work highlights how engineering of bifunctional active ensembles enables cooperativity and synergy at tailored interfaces, which unlocks unprecedented performance in heterogeneous catalysts. [ABSTRACT FROM AUTHOR]

Multicomponent catalysts can be designed to synergistically combine reaction intermediates at interfacial active sites, but restructuring makes systematic control and understanding of such dynamics challenging. We here unveil how reducibility and mobility of indium oxide species in Ru‐based catalysts crucially control the direct, selective conversion of CO2 to ethanol. When uncontrolled, reduced indium oxide species occupy the Ru surface, leading to deactivation. With the addition of steam as a mild oxidant and using porous polymer layers to control In mobility, Ru−In2O3 interface sites are stabilized, and ethanol can be produced with superior overall selectivity (70 %, rest CO). Our work highlights how engineering of bifunctional active ensembles enables cooperativity and synergy at tailored interfaces, which unlocks unprecedented performance in heterogeneous catalysts. [ABSTRACT FROM AUTHOR]

Sustainability risks in aquaculture are increasingly addressed through forms of assurance that rely on the use of digital technologies. By bringing in new actors and informational processes, these forms of digital sustainability assurance challenge existing notions of how global value chains are governed. Based on in‐depth interviews with experts, we find that the growing use of digital technologies to mediate assurance is shaped by the digital codification of informational processes designed to support sustainability, which in turn increases the complexity of sustainability claims and changes the capabilities needed by value chain actors to comply. Furthermore, we find that digital sustainability assurance represents a new form of value chain coordination by a new set of extra‐transactional "digital lead actors." As these lead actors become more prominent, their control over digital data flows constitutes a new form of value chain governance with the potential to have greater impact on steering toward sustainability. [ABSTRACT FROM AUTHOR]

Objective. Penalty parameters in penalized likelihood positron emission tomography (PET) reconstruction are typically determined empirically. The cross-validation log-likelihood (CVLL) method has been introduced to optimize these parameters by maximizing a CVLL function, which assesses the likelihood of reconstructed images using one subset of a list-mode dataset based on another subset. This study aims to validate the efficacy of the CVLL method in whole-body imaging for cancer patients using a conventional clinical PET scanner. Approach. Fifteen lung cancer patients were injected with 243.7 ± 23.8 MBq of [18F]FDG and underwent a 22 min PET scan on a Biograph mCT PET/CT scanner, starting at 60 ± 5 min post-injection. The PET list-mode data were partitioned by subsampling without replacement, with 20 minutes of data for image reconstruction using an in-house ordered subset expectation maximization algorithm and the remaining 2 minutes of data for cross-validation. Two penalty parameters, penalty strength β and Fair penalty function parameter δ, were subjected to optimization. Whole-body images were reconstructed, and CVLL values were computed across various penalty parameter combinations. The optimal image corresponding to the maximum CVLL value was selected by a grid search for each patient. Main results. The δ value required to maximize the CVLL value was notably small (⩽10−6 in this study). The influences of voxel size and scan duration on image optimization were investigated. A correlation analysis revealed a significant inverse relationship between optimal β and scan count level, with a correlation coefficient of −0.68 (p -value = 3.5 × 10−5). The optimal images selected by the CVLL method were compared with those chosen by two radiologists based on their diagnostic preferences. Differences were observed in the selection of optimal images. Significance. This study demonstrates the feasibility of incorporating the CVLL method into routine imaging protocols, potentially allowing for a wide range of combinations of injected radioactivity amounts and scan durations in modern PET imaging. [ABSTRACT FROM AUTHOR]

Here, we employed the nudged elastic band (NEB) method to simulate the diffusion of ferrocene through vanadyl phosphate (VOPO4), with a focus on understanding the diffusion pathways arising from the complex structure of ferrocene. We systematically evaluated a total of 36 potential diffusion paths, categorizing them into three groups based on their directional orientation: 15 paths between V sites along the [110] direction, 15 paths from V to P sites along the [100] direction, and 6 paths between P sites also along the [110] direction. Our analysis revealed that the energy barriers for diffusion along the [110] direction typically ranged between 0.25 and 0.35 eV, which are notably higher than those observed for pathways along the [100] direction, where the energy barriers ranged from 0.11 to 0.20 eV. To further elucidate the complex deformation of ferrocene during diffusion, we established four key measures to characterize the structural conformation: the angle of the axis of the ferrocene molecule relative to the [010] direction within the (001) plane, the dihedral angle between the two cyclopentadienyl rings, the orientation angle of the -CH bonds with respect to the [001] direction, and the angle between two -CH bonds from the two cyclopentadienyl rings. [ABSTRACT FROM AUTHOR]

Neuro‐imaging data can often be represented as statistical networks, especially for functional magnetic resonance imaging (fMRI) data, where brain regions are defined as nodes and the functional interactions between those regions are taken as edges. Such networks are commonly divided into classes depending on the type of edges, namely binary or weighted. A binary network means edges can either be present or absent. Whereas the edges of a weighted network are associated with weight values, and fMRI networks belong to weighted networks. Statistical methods are often adopted to analyse such networks, among which, the exponential random graph model (ERGM) is an important network analysis approach. Typically ERGMs are applied to binary networks, and weighted networks often need to be binarised by arbitrarily selecting a threshold value to define the presence of the edges, which can lead to non‐robustness and loss of valuable edge weight information representing the strength of fMRI interaction in fMRI networks. While it is therefore important to gain deeper insight in adopting ERGM on weighted networks, there only exists a few different ERGM frameworks for weighted networks; some of these are not directly implementable on fMRI networks based on their original proposal. We systematically review, implement, analyse and compare five such frameworks via a simulation study and provide guidelines on each modelling framework as well as conclude the suitability of them on fMRI networks based on a range of criteria. We concluded that Multi‐Layered ERGM is currently the most suitable framework. [ABSTRACT FROM AUTHOR]

Objectives: To explore the strength of the association between cognitive functioning and depression and anxiety in older people without dementia. Methods: An exploratory, cross‐sectional analysis of Wave 1 (2004–2007) data from the Lothian Birth Cohort 1936 dataset. Three subgroups were based on Hospital Anxiety and Depression Scale (HADS) subscales: no probable anxiety or depression (N = 592), probable anxiety no depression (N = 122), probable depression with/without anxiety (depression) (N = 30). Regression analyses determined relationships between subgroups and identified cognitive test variables. Results: Participants were 744 individuals (male = 385 [51.5%]; mean [M] age = 69.5 years [Standard deviation = 0.83]); characteristics for subgroups were similar. Participants with probable depression had slower simple reaction time scores than those with no anxiety or depression (regression slope [β] on the log10 scale = 0.05, 95% Confidence Interval [0.03, 0.08], p ≤ 0.001). Those with probable anxiety had significantly worse scores on other tests: Spatial span (β = −0.80 [−1.36, −0.25], p ≤ 0.005), Symbol Search (β = −1.67 [−2.90, −0.45], p ≤ 0.01), Matrix Reasoning (β = −1.58 [−2.55, −0.60], p ≤ 0.005) and Block Design (β = −3.33 [−5.29, −1.37], p ≤ 0.001), than those without probable anxiety or depression. Conclusion: Probable depression and anxiety were found to be associated with lower cognitive function in those without evidence of dementia. People with probable anxiety showed poorer performance in tests that concerned making decisions. People with probable depression showed slower processing speed. [ABSTRACT FROM AUTHOR]

The death of dopamine-producing neurons in the substantia nigra in the base of the brain is a defining pathological feature in the development of Parkinson's disease (PD). PD is, however, a multi-systemic disease, also affecting the peripheral nervous system and gastrointestinal tract (GIT) that interact via the gut–brain axis (GBA). Our dual-flow GIT–brain microphysiological system (MPS) was modified to investigate the gut-to-brain translocation of the neurotoxin trigger of PD, 1-methyl-4-phenylpyridinium (MPP+), and its impact on key GIT and brain cells that contribute to the GBA. The modular GIT–brain MPS in combination with quantitative and morphometric image analysis methods reproduces cell specific neurotoxin-induced dopaminergic cytotoxicity and mitochondria-toxicity with the drug having no detrimental impact on the viability or integrity of cellular membranes of GIT-derived colonic epithelial cells. Our findings demonstrate the utility and capability of the GIT-brain MPS for measuring neuronal responses and its suitability for identifying compounds or molecules produced in the GIT that can exacerbate or protect against neuronal inflammation and cell death. [ABSTRACT FROM AUTHOR]

Aims: Impaired awareness of hypoglycaemia (IAH) increases the risk of severe hypoglycaemia in people with type 1 diabetes mellitus (T1DM). IAH can be reversed through meticulous avoidance of hypoglycaemia. Diabetic autonomic neuropathy (DAN) has been proposed as an underlying mechanism contributing to IAH; however, data are inconsistent. The aim of this study was to examine the effects of cardiac autonomic neuropathy (CAN) on IAH reversibility inT1DM. Methods: Participants with T1DM and IAH (Gold score ≥4) recruited to the HypoCOMPaSS (24‐week 2 × 2 factorial randomised controlled) trial were included. All underwent screening for cardiac autonomic function testing at baseline and received comparable education and support aimed at avoiding hypoglycaemia and improving hypoglycaemia awareness. Definite CAN was defined as the presence of ≥2 abnormal cardiac reflex tests. Participants were grouped according to their CAN status, and changes in Gold score were compared. Results: Eighty‐three participants (52 women [62.7%]) were included with mean age (SD) of 48 (12) years and mean HbA1c of 66 (13) mmol/mol (8.2 [3.3] %). The mean duration of T1DM was 29 (13) years. The prevalence of CAN was low with 5/83 (6%) participants having definite autonomic neuropathy with 11 (13%) classified with possible/early neuropathy. All participants, regardless of the autonomic function status, showed a mean improvement in Gold score of ≥1 (mean improvement −1.2 [95% CI −0.8, −1.6]; p < 0.001). Conclusions: IAH can be improved in people with T1DM, and a long duration of disease, with and without cardiac autonomic dysfunction. These data suggest that CAN is not a prime driver for modulating IAH reversibility. [ABSTRACT FROM AUTHOR]

Australia is one of the largest barley exporters in the world, with Western Australia accounting for some 40% of national production. The crop is predominantly grown in the south and south‐west of the state in winter and spring, where temperate conditions and higher rainfall levels are more suited to barley than northern and eastern regions. Between 2007 and 2013, prolonged outbreaks of barley powdery mildew (BPM) occurred. This was brought about by a combination of the extensive use of susceptible cultivars and an over‐reliance on a small number of single mode‐of‐action demethylation inhibitor fungicides, which select for mutations in the C14α‐demethylase (Cyp51A) gene. This review highlights the steps taken to reduce losses to BPM, breeding efforts to introduce resistance into cultivars and the success of pre‐breeding research to find new and durable resistance genes. We also draw comparisons with powdery mildew in Australian wheat, where similar factors are leading to substantial outbreaks. [ABSTRACT FROM AUTHOR]

SUMMARY: Diagnostic systems are not conducive to compassionate health-bringing psychiatric treatment. The systems were built around the fallacy that the politics of biomedicine could be reliably applied to the emergent properties of human psychological suffering and enable diagnosis-specific treatment packages. The resulting industrialised medicine, which reified people, failed to facilitate the compassion needed for healing. This article outlines an approach to psychiatric practice that involves understanding children's suffering and vulnerabilities in terms of their attachment strategies and adaptation to their context and takes a mindful approach to developing compassionate collaborative treatment goals (intelligent kindness). A shift towards mindful psychiatric medicine would encourage politicians to serve the people by addressing the contexts associated with human suffering and what makes people vulnerable, especially social inequalities. Healthy societies in which the psychiatric dis-ease of the population is adequately addressed will not be built with limited biomedical understanding of dis-ease. [ABSTRACT FROM AUTHOR]

Background: Diabetes-specific quality of life (QoL) questionnaires are commonly used to assess the impact of diabetes and its management on an individual's quality of life. While several valid and reliable measures of diabetes-specific QoL exist, there is no consensus on which to use and in what setting. Furthermore, there is limited evidence of their acceptability to people with diabetes. Our aim was to explore perceptions of adults with type 1 diabetes (T1D) toward five diabetes-specific QoL measures. Methods: Adults (aged 18 + years) with T1D living in Australia or the United Kingdom (UK) were eligible to take part in 'YourSAY: QoL', an online cross-sectional survey. Recruitment involved study promotion on diabetes-related websites and social media, as well as direct invitation of people with T1D via a hospital client list (UK only). In random order, participants completed five diabetes-specific QoL measures: Audit of Diabetes-Dependent Quality of Life (ADDQoL-19); Diabetes Care Profile: Social and Personal Factors subscale (DCP); DAWN Impact of Diabetes Profile (DIDP); Diabetes-Specific Quality of Life Scale: Burden Subscale (DSQoLS); Diabetes Quality of Life Questionnaire (Diabetes QOL-Q). They were invited to provide feedback on each questionnaire in the form of a brief free-text response. Responses were analysed using inductive, thematic template analysis. Results: Of the N = 1,946 adults with T1D who completed the survey, 20% (UK: n = 216, Australia: n = 168) provided qualitative responses about ≥ 1 measure. All measures received both positive and negative feedback, across four themes: (1) clarity and ease of completion, e.g., difficulty isolating impact of diabetes, dislike of hypothetical questions, and preference for 'not applicable' response options; (2) relevance and comprehensiveness, e.g., inclusion of a wide range of aspects of life to improve personal relevance; (3) length and repetition, e.g., length to be balanced against respondent burden; (4) framing and tone, e.g., preference for respectful language and avoidance of extremes. Conclusions: These findings suggest opportunities to improve the relevance and acceptability of existing diabetes-specific QoL measures, and offer considerations for developing new measures, which need to be better informed by the preferences of people living with diabetes. [ABSTRACT FROM AUTHOR]

Soil carbon (C) stability is an important consideration for management that aims to increase long-term C storage. The fraction of soil C allocated to physico-chemically protected mineral-associated organic matter (MAOM) is a common soil C stability benchmark. However, the reality of soil C persistence is more complex than MAOM content alone—particularly in ecosystems such as meadows with high rates of belowground C inputs that can stimulate MAOM decomposition. Here, we combined three metrics of soil C persistence to characterize soil C stability across a meadow restoration chronosequence averaging belowground C gains of 330 g C m−2 y−1 for ~20 y. The metrics were: (1) the fraction of soil C in MAOM and particulate organic matter (POM), (2) the susceptibility of soil C to decomposition under varying temperatures, and (3) the utilization of MAOM-C by microbes. Two metrics suggested soil C stability may increase following montane meadow restoration. As soil C concentration increased with restoration, C storage in MAOM, but not POM, increased (metric 1). The susceptibility of MAOM-C to decomposition (microbial respiration relative to MAOM-C) decreased with increasing soil C concentration across temperatures (metric 2). Stable isotope results could not definitively determine the source of carbon dioxide efflux (metric 3) but generate hypotheses for future research to address. We posit that C sequestered following montane meadow restoration could be stable, with implications for regional C storage objectives. Further, our data point toward complex mineral-associated C dynamics including the potential importance of plant inputs for MAOM formation in meadow soils. [ABSTRACT FROM AUTHOR]

The impact of dysfunctional attitudes and unhelpful thinking upon clients presenting with personality-related psychological distress is an important clinical area of investigation as it informs psychological interventions. Despite this, there is limited research in this area. Thus, this study had two main aims: (1) examine the interrelationships between maladaptive personality traits, dysfunctional attitudes, unhelpful thinking, and psychological distress; and (2) explore the potential mediating roles of dysfunctional attitudes and unhelpful thinking on the relationship between maladaptive personality traits and psychological distress. A convenience sample of 728 undergraduate psychology students (mean age: 31.57 years; 76% female) completed an online questionnaire for course credit. The results supported the first hypothesis that after controlling for gender and age, there would be significant positive correlations among maladaptive personality traits, dysfunctional attitudes, and psychological distress. A structural equation model with an excellent fit (CMIN/df = 2.23, p =.063, TLI = 0.98, CFI = 0.99, SRMR, = 0.01, and RMSEA = 0.04) provided partial support for the second hypothesis in that dysfunctional attitudes and unhelpful thoughts mediated the relationship between maladaptive personality traits and psychological distress. Specifically, negative affectivity and detachment's relationship with psychological distress were partially mediated via dysfunction attitudes and unhelpful thoughts, and dysfunctional attitudes respectively. These findings suggest that while dysfunctional attitudes and unhelpful thinking contribute to the relationship between personality traits and psychological distress, identification of other factors are required to improve theoretical understanding and subsequently psychological interventions. [ABSTRACT FROM AUTHOR]

Rationale: Despite evidence demonstrating a prognostic role for computed tomography (CT) scans in idiopathic pulmonary fibrosis (IPF), image-based biomarkers are not routinely used in clinical practice or trials. Objectives: To develop automated imaging biomarkers using deep learning–based segmentation of CT scans. Methods: We developed segmentation processes for four anatomical biomarkers, which were applied to a unique cohort of treatment-naive patients with IPF enrolled in the PROFILE (Prospective Observation of Fibrosis in the Lung Clinical Endpoints) study and tested against a further United Kingdom cohort. The relationships among CT biomarkers, lung function, disease progression, and mortality were assessed. Measurements and Main Results: Data from 446 PROFILE patients were analyzed. Median follow-up duration was 39.1 months (interquartile range, 18.1–66.4 mo), with a cumulative incidence of death of 277 (62.1%) over 5 years. Segmentation was successful on 97.8% of all scans, across multiple imaging vendors, at slice thicknesses of 0.5–5 mm. Of four segmentations, lung volume showed the strongest correlation with FVC (r = 0.82; P < 0.001). Lung, vascular, and fibrosis volumes were consistently associated across cohorts with differential 5-year survival, which persisted after adjustment for baseline gender, age, and physiology score. Lower lung volume (hazard ratio [HR], 0.98 [95% confidence interval (CI), 0.96–0.99]; P = 0.001), increased vascular volume (HR, 1.30 [95% CI, 1.12–1.51]; P = 0.001), and increased fibrosis volume (HR, 1.17 [95% CI, 1.12–1.22]; P < 0.001) were associated with reduced 2-year progression-free survival in the pooled PROFILE cohort. Longitudinally, decreasing lung volume (HR, 3.41 [95% CI, 1.36–8.54]; P = 0.009) and increasing fibrosis volume (HR, 2.23 [95% CI, 1.22–4.08]; P = 0.009) were associated with differential survival. Conclusions: Automated models can rapidly segment IPF CT scans, providing prognostic near and long-term information, which could be used in routine clinical practice or as key trial endpoints. [ABSTRACT FROM AUTHOR]

In situ and operando X‐ray absorption spectroscopy (XAS) provides fundamental insight into the working principles of electrocatalysts and is an important tool for future catalyst development. However, the design of an operando XAS electrocatalytic cell is not facile, and researchers designing cells, whether new cells or modifications to previous cells, often spend many hours on cell design before obtaining high‐quality XAS data. Here, we describe the design, with engineering drawings, and operation of a versatile XAS cell with options for gas flow, electrolyte flow, pH monitoring, temperature monitoring, and the ability to handle many catalyst forms (any catalyst that can be deposited onto a conductive X‐ray transparent substrate). We benchmarked XAS spectra collected using the new experimental cell to a previous cell design showing its ability to produce quality XAS data. We demonstrate the viability of this cell by providing insight into electrocatalysts by studying cation effects and show the tetrabutylammonium cation prevents bulk oxidation of copper. We hope the availability of this cell allows researchers to convert time typically spent on cell design to time spent on breakthroughs in electrocatalysis. [ABSTRACT FROM AUTHOR]

Adolescent development of human brain structural and functional networks is increasingly recognized as fundamental to emergence of typical and atypical adult cognitive and emotional processes. We analysed multimodal magnetic resonance imaging (MRI) data collected from N ~ 300 healthy adolescents (51%; female; 14 to 26 y) each scanned repeatedly in an accelerated longitudinal design, to provide an analyzable dataset of 469 structural scans and 448 functional MRI scans. We estimated the morphometric similarity between each possible pair of 358 cortical areas on a feature vector comprising six macro- and microstructural MRI metrics, resulting in a morphometric similarity network (MSN) for each scan. Over the course of adolescence, we found that morphometric similarity increased in paralimbic cortical areas, e.g., insula and cingulate cortex, but generally decreased in neocortical areas, and these results were replicated in an independent developmental MRI cohort (N~304). Increasing hubness of paralimbic nodes in MSNs was associated with increased strength of coupling between their morphometric similarity and functional connectivity. Decreasing hubness of neocortical nodes in MSNs was associated with reduced strength of structure-function coupling and increasingly diverse functional connections in the corresponding fMRI networks. Neocortical areas became more structurally differentiated and more functionally integrative in a metabolically expensive process linked to cortical thinning and myelination, whereas paralimbic areas specialized for affective and interoceptive functions became less differentiated, as hypothetically predicted by a developmental transition from periallocortical to proisocortical organization of the cortex. Cytoarchitectonically distinct zones of the human cortex undergo distinct neurodevelopmental programs during typical adolescence. [ABSTRACT FROM AUTHOR]

Aim: Experimental hypoglycaemia blunts the counterregulatory hormone and symptom responses to a subsequent episode of hypoglycaemia. In this study, we aimed to assess the associations between antecedent exposure and continuous glucose monitoring (CGM)‐recorded hypoglycaemia during a 1‐week period and the counterregulatory responses to subsequent experimental hypoglycaemia in people with type 1 diabetes. Materials and Methods: Forty‐two people with type 1 diabetes (20 females, mean ± SD glycated haemoglobin 7.8% ± 1.0%, diabetes duration median (interquartile range) 22.0 (10.5‐34.9) years, 29 CGM users, and 19 with impaired awareness of hypoglycaemia) wore an open intermittently scanned CGM for 1 week to detect hypoglycaemic exposure before a standardized hyperinsulinaemic‐hypoglycaemic [2.8 ± 0.1 mmol/L (50.2 ± 2.3 mg/dl)] glucose clamp. Symptom responses and counterregulatory hormones were measured during the clamp. The study is part of the HypoRESOLVE project. Results: CGM‐recorded hypoglycaemia in the week before the clamp was negatively associated with adrenaline response [β −0.09, 95% CI (−0.16, −0.02) nmol/L, p =.014], after adjusting for CGM use, awareness of hypoglycaemia, glycated haemoglobin and total daily insulin dose. This was driven by level 2 hypoglycaemia [<3.0 mmol/L (54 mg/dl)] [β −0.21, 95% CI (−0.41, −0.01) nmol/L, p =.034]. CGM‐recorded hypoglycaemia was negatively associated with total, autonomic, and neuroglycopenic symptom responses, but these associations were lost after adjusting for potential confounders. Conclusions: Recent exposure to CGM‐detected hypoglycaemia was independently associated with an attenuated adrenaline response to experimental hypoglycaemia in people with type 1 diabetes. [ABSTRACT FROM AUTHOR]

Aims: The DAFNEplus programme incorporates behaviour change techniques into a modified educational intervention and was developed to help address the glycaemic drift observed amongst graduates of standard DAFNE programmes. As the programme's success will be contingent on staff buy‐in, we explored healthcare professionals' experiences of, and views about, delivering DAFNEplus during a clinical trial to help inform decision making about rollout post‐trial. Methods: We interviewed n = 18 nurses and dieticians who delivered DAFNEplus during the trial. Data were analysed thematically. Results: While many shared initial reservations, all described how their experiences of DAFNEplus programme delivery had had a positive, transformative impact upon their perceptions and working practices. This transformation was enabled by initial training and supervision sessions, the confidence gained from using scripts to support novel programme content delivery, and experiences of delivering the programme and observing DAFNEplus principles being well received by, and having a positive impact on, attendees. Due to these positive experiences, interviewees described a strongly felt ethical mandate to use some DAFNEplus techniques and curriculum content in routine clinical care. While being supportive of a national rollout, they anticipated a variety of attitudinal and logistical (e.g. workload) challenges. Conclusions: This study provides a vital dimension to the evaluation of the DAFNEplus programme. Interviewees found the intervention to be acceptable and expressed high levels of buy‐in. As well as offering potential endorsement for a national rollout, our findings offer insights which could help inform development and rollout of future behaviour change interventions to support diabetes self‐management. [ABSTRACT FROM AUTHOR]

Aims: As part of a broader process evaluation, we explored participants' experiences of, and engagement with, the DAFNEplus programme's group‐based structured education course. This course, which was informed by behavioural science, provided participants with education and instruction to use flexible intensive insulin therapy (FIIT) together with techniques to identify and address unhelpful cognitive and emotional influences on their type 1 diabetes self‐management. Methods: We interviewed n = 28 DAFNEplus participants. Data were analysed thematically and took account of previous work exploring individuals' experiences of standard DAFNE courses. Results: As well as benefitting from the DAFNEplus course's skills‐based training and educational curriculum, participants' accounts suggested they had experienced cognitive and emotional changes that had positively influenced their confidence and motivation to adopt and sustain the use of FIIT. These benefits were most keenly felt by those who reported negative emotional states and mind‐sets pre‐course which had made their diabetes self‐management challenging. Participants' cognitive and emotional changes were enabled through techniques used during the course to normalise setbacks and imperfect diabetes self‐management, capitalise upon group synergies and encourage the use of social support, including from healthcare professionals. Participants also highlighted motivational gains arising from being reassured that diabetes complications are not common or inevitable if a FIIT regimen is followed. Conclusions: Our findings suggest that offering training in FIIT, in conjunction with behaviour change techniques that target unhelpful mindsets and emotional resilience, may be more effective in promoting diabetes self‐management than offering education and skills training alone. [ABSTRACT FROM AUTHOR]

Bowlby remained attached to his psychoanalytic roots and conceptualised treatment in terms of one-to-one relationships, albeit acknowledging the need for a family formulation. Bowlby's five therapeutic tasks were never adapted to the current understanding of working with the relationships fostering the development and maintenance of children's attachment strategies. This paper goes through each of Bowlby's five tasks and adapts them to our current understanding of development, with consequences for prioritising family approaches, rather than a secure base alone with a therapist. In doing so I will review the process of achieving security, seeing it as more similar to an allostatic process than a state of homeostasis. [ABSTRACT FROM AUTHOR]

Background Longevity, a hallmark of successful aging, is a multifactorial trait with influences from birth onwards. However, limited evidence exists on the pathways linking diverse life-course exposures to longevity, especially within a single cohort. Methods We investigated associations between life-course factors and longevity among community-dwelling adults aged 79 (N = 547) from the Lothian Birth Cohort 1921 with a mortality follow-up of 24 years. Cox proportional hazards and structural equation (path) models were used to explore how factors from early life (social class, childhood intelligence quotient [IQ], education), midlife (social class), and later life (health, lifestyle, psychosocial well-being), as well as sex, personality, and apolipoprotein E e4 status, influence survival time in days. Results During follow-up (1999–2023), 538 participants (98%) died (mean age of death = 89.3 years) and 9 survived (mean age = 101.6 years). Factors associated with lower mortality risk in the multivariable Cox model were higher cognitive function (hazard ratio [HR] = 0.72; 95% confidence interval [CI]: 0.59–0.88), better physical function (HR = 0.61; 95% CI: 0.44–0.85), and greater physical activity (HR = 0.81; 95% CI: 0.71–0.92), while history of cancer was associated with higher mortality risk (HR = 1.84; 95% CI: 1.22–2.77). The life-course path model identified the same direct predictors, with additional contributions from female sex and nonsmoking status, to greater longevity. Early- and midlife factors (IQ, education, social class), and emotional stability, conscientiousness, and female sex, were indirectly and positively associated with survival trajectories via multiple dimensions of adult health. Conclusions In understanding why people live to very old ages it is necessary to consider factors from throughout the life course, and to include demographic, psychosocial, and health variables. [ABSTRACT FROM AUTHOR]

This study investigated preservice teachers' experiences of helping peers with technical support. Considering college-aged students prefer to seek help from relative experts rather than instructors, the rationale for the study was to contribute to the literature on relative expertise by exploring how preservice teachers supported peers. A mixed methods approach was employed using (1) social network analysis to find and identify the preservice teachers who assisted the greatest number of peers and (2) phenomenological interviewing and thematic analysis to understand how they helped their peers with technical support. Findings show that prior to serving as a relative expert around technical support, a preservice teacher explores tools and becomes comfortable with offering support. Findings also show how relative experts are approached by peers, how they offer support, and what changes they exhibit in confidence and comfort as a result of offering support. The findings in this study could be leveraged by teacher education programs to increase outcomes related to technology use and relative expertise. Implications and future research directions are noted including the potential value of peer technical support to help preservice teachers more easily transition to inservice teaching. [ABSTRACT FROM AUTHOR]

Background: Anastomotic leak after esophagectomy is a major contributor to surgery-related morbidity and mortality. The purpose of this systematic review was to evaluate if positive-smoking status is associated with the incidence of this complication. Methods: A systematic search of MEDLINE, EMBASE, Scopus, Web of Science and Cochrane Library was performed on April 4th, 2023. Inclusion criteria comprised human participants undergoing esophagectomy, age ≥ 18, n ≥ 5, and identification of smoking status. The primary outcome was incidence of anastomotic leak. Sub-group analysis by ex- or current smoking status was performed. Meta-analysis was performed with RevMan 5.4.1 using a Mantel–Haenszel random-effects model. Publication bias was evaluated visually with funnel plots and through the Egger test. Results: A total of 220 abstracts were screened, of which 69 full-text studies were assessed for eligibility, with 13 studies selected for final inclusion. This included 16,103 patients, of which 4433 were ex- or current smokers, and 9141 were never smokers. Meta-analysis revealed an increased odds of anastomotic leak in patients with a positive-smoking status (current or ex-smokers) compared to never smokers (OR 1.44, 95% CI 1.18–1.76, I2 = 44%, p < 0.001. Meta-analysis of six studies comparing active smokers alone to never smokers identified a significant increased odds of anastomotic leak (OR 1.80, 95% CI 1.25–2.59, p = 0.002, I2 = 0%). Meta-analysis of five studies comparing ex-smokers to never smokers identified a significant increased odds of anastomotic leak (OR 1.36, 95% CI 1.02–1.82, p = 0.04, I2 = 0%). The odds of anastomotic leak decreased among ex-smokers compared to active smokers. Conclusion: The findings of this systematic review and meta-analysis support the association between positive-smoking status and the risk of anastomotic leak after esophagectomy. Results further emphasize the importance of preoperative smoking cessation to reduce post-operative morbidity. [ABSTRACT FROM AUTHOR]