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Objective: Peptide YY(3-36) (PYY(3-36)), a Y2 receptor agonist, and oxyntomodulin, a glucagon-like peptide 1 (GLP-1) receptor agonist, are cosecreted by intestinal L-cells after each meal. Separately each hormone acts as an endogenous satiety signal and reduces appetite in humans when infused intravenously. The aim of the current study was to investigate whether the anorectic effects of PYY(3-36) and oxyntomodulin can be additive.Research Design and Methods: Twelve overweight or obese human volunteers underwent a randomized, double-blinded, placebo-controlled study. An ad libitum test meal was used to measure energy intake during intravenous infusions of either PYY(3-36) or oxyntomodulin or combined PYY(3-36)/oxyntomodulin.Results: Energy intake during coadministration of PYY(3-36) and oxyntomodulin was reduced by 42.7% in comparison with the saline control and was significantly lower than that during infusions of either hormone alone.Conclusions: The anorectic effects of PYY(3-36) and oxyntomodulin can be additive in overweight and obese humans. Coadministration of Y2 receptor agonists and GLP-1 receptor agonists may be a useful treatment strategy for obesity. [ABSTRACT FROM AUTHOR]

Background: Patients with a gastrinoma are treated with proton pump inhibitors (PPI) and histamine type-2 receptor antagonists (H2). In order to diagnose a gastrinoma these drugs must be discontinued, but this increases the risk of gastrointestinal perforation. We aimed to determine if a gastrinoma could be diagnosed without cessation of PPI/H2 therapy. Methods: In all, 90 patients (controls and patients diagnosed with a gastrinoma both on and off PPI/H2 therapy) were recruited, and plasma gastrin measured. Results: Patients with a gastrinoma on PPI/H2 medication had a significantly higher fasting plasma gastrin concentration than control patients on PPI/H2 medication (298±33 versus 204±30 pmol/L, P = 0.01). However, there was substantial overlap between gastrin levels in these two groups. Conclusion: This study confirms that a gastrinoma cannot be diagnosed on the basis of a fasting plasma gastrin assay while patients remain on PPI/H2 therapy. [ABSTRACT FROM AUTHOR]

Competing Interests: Conflicts of interest: None declared.

Background: Staff burnout in higher education may affect nursing department functionality. There is limited literature regarding staff burnout and its manifestations in nursing colleges and schools., Purpose: This study evaluated academic nurse leaders' perceptions of burnout and mitigation strategies in colleges and schools of nursing., Methods: A descriptive, cross-sectional survey examined burnout and mitigation strategies among associate deans, business officers, and members of the Organizational Leadership Network (n = 105)., Results: Among academic leaders, 57.14% noted that staff burnout was either a notable or a major challenge. Resignations (56.86%) and difficulties in backfilling staff positions (54.90%) were the 2 most common manifestations of staff burnout. However, only a small percentage had an active burnout mitigation strategy for faculty (13.33%) and staff (6.67%)., Conclusion: There is a disconnect between acknowledging burnout as a pressing concern and implementing effective mitigation strategies. By creating a supportive work environment and encouraging professional development, leaders can significantly reduce burnout and enhance overall employee well-being., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc.)

Cyclin-CDKs are master regulators of cell division. In addition to directly activating the CDK, the cyclin subunit regulates CDK specificity by binding short peptide "docking" motifs in CDK substrates. Here, we measure the relative binding strength of ~100,000 peptides to 11 human cyclins from five cyclin families (D, E, A, B and F). Using a quantitative intracellular binding assay and large-scale tiled peptide screening, we identified a range of non-canonical binders that unveil a broader than anticipated repertoire of cyclin docking motif types. Structural and saturation mutagenesis studies revealed distinct binding modes and sequence features that govern motif recognition, binding strength, and cyclin preference. Docking motifs vary from highly selective to pan-cyclin, thereby fine-tuning the timing of CDK phosphorylation during cell cycle progression. Overall, these findings provide an unprecedented depth of understanding about the rules encoding specificity and affinity within a group of related but distinct protein domains., Competing Interests: Declaration of Interests The authors declare no competing interests

Caring for newborn offspring hampers resource acquisition of mammalian females, curbing their ability to meet the high energy expenditure of early lactation. Newborns are particularly vulnerable, and, among the large herbivores, ungulates have evolved a continuum of neonatal antipredator tactics, ranging from immobile hider (such as roe deer fawns or impala calves) to highly mobile follower offspring (such as reindeer calves or chamois kids). How these tactics constrain female movements around parturition is unknown, particularly within the current context of increasing habitat fragmentation and earlier plant phenology caused by global warming. Here, using a comparative analysis across 54 populations of 23 species of large herbivores from 5 ungulate families (Bovidae, Cervidae, Equidae, Antilocapridae and Giraffidae), we show that mothers adjust their movements to variation in resource productivity and heterogeneity according to their offspring's neonatal tactic. Mothers with hider offspring are unable to exploit environments where the variability of resources occurs at a broad scale, which might alter resource allocation compared with mothers with follower offspring. Our findings reveal that the overlooked neonatal tactic plays a key role for predicting how species are coping with environmental variation., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The emergence of SARS-CoV-2 variants presents challenges to vaccine effectiveness, underlining the necessity for next-generation vaccines with multiple antigens beyond the spike protein. Here, we investigated a multiantigenic booster containing spike and a chimeric construct composed of nucleoprotein (N) and membrane (M) proteins, comparing its efficacy to a spike-only booster against Omicron BA.5 in K18-hACE2 mice. Initially, mice were primed and boosted with Beta (B.1.351) spike-only mRNA, showing strong spike-specific T cell responses and neutralizing antibodies, albeit with limited cross-neutralization to Omicron variants. Subsequently, a spike-NM multiantigenic vaccine was then examined as a second booster dose for protection in hACE2-transgenic mice. Mice receiving either homologous spike-only or heterologous spike-NM booster had nearly complete inhibition of infectious virus shedding in oral swabs and reduced viral burdens in both lung and nasal tissues following BA.5 challenge. Examination of lung pathology further revealed that both spike-only and spike-NM boosters provided comparable protection against inflammatory infiltrates and fibrosis. Moreover, the spike-NM booster demonstrated neutralization efficacy in a pseudovirus assay against Wuhan-Hu-1, Beta, and Omicron variants akin to the spike-only booster. These findings indicate that supplementing spike with additional SARS-CoV-2 targets in a booster immunization confers equivalent immunity and protection against Omicron BA.5. This work highlights a promising strategy for individuals previously vaccinated with spike-only vaccines, potentially offering enhanced protection against emerging coronaviruses., Competing Interests: Providence Therapeutics provided minimal input in the study design limited to issues related to vaccine assessment, storage, dosage and delivery. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Hurst et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Our rationale was to investigate whether 18 F-FDG PET/MRI in addition to (guideline-recommended) conventional staging leads to changes in therapeutic management in patients with newly diagnosed breast cancer and compare the diagnostic accuracy of 18 F-FDG PET/MRI with that of conventional staging for determining the Union for International Cancer Control (UICC) stage. Methods: In this prospective, double-center study, 208 women with newly diagnosed, therapy-naïve invasive breast cancer were enrolled in accordance with the inclusion criteria. All patients underwent guideline-recommended conventional staging and whole-body 18 F-FDG PET/MRI with a dedicated breast examination. A multidisciplinary tumor board served to determine 2 different therapy recommendations for each patient, one based on conventional staging alone and another based on combined assessment of conventional staging and 18 F-FDG PET/MRI examinations. Major changes in therapy recommendations and differences between the conventional staging algorithm and 18 F-FDG PET/MRI for determining the correct UICC stage were reported and evaluated. Results: Major changes in therapeutic management based on combined assessment of conventional staging and 18 F-FDG PET/MRI were detected in 5 of 208 patients, amounting to changes in therapeutic management in 2.4% (95% CI, 0.78%-5.2%) of the study population. In determining the UICC stage, the guideline-based staging algorithm and 18 F-FDG PET/MRI were concordant in 135 of 208 (64.9%; 95% CI, 58%-71.4%) patients. The conventional guideline algorithm correctly determined the UICC stage in 130 of 208 (62.5%; 95% CI, 55.5%-69.1%) patients, and 18 F-FDG PET/MRI correctly determined the UICC stage in 170 of 208 (81.9%; 95% CI, 75.8%-86.7%) patients. Conclusion: Despite the diagnostic superiority of 18 F-FDG PET/MRI over conventional staging in determining the correct UICC stage, the current (guideline-recommended) conventional staging algorithm is sufficient for adequate therapeutic management of patients with newly diagnosed breast cancer, and 18 F-FDG PET/MRI does not have an impact on patient management., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: This study aimed to assess the perceptions of nurses who self-identify as Black or African American regarding their workplace health and safety and to explore how these perceptions are associated with their perceived personal health., Background: Nurses practicing in unhealthy work environments can experience poorer physical and mental health. Recent civil unrest and ongoing dialogue about structural and systemic racism have prompted calls for greater efforts to understand the workplace perceptions and experiences of ethnic minority nurses, and how these influence nurses' personal well-being. But there is a dearth of relevant evidence concerning these nurses, including Black nurses., Methods: This cross-sectional, descriptive study involved analysis of secondary data collected from May 1, 2017, through December 31, 2019, by the American Nurses Association's HealthyNurse Survey (N = 19,131). We employed descriptive, bivariate, and multivariate analyses to examine the data for the 1,143 respondents who both self-identified as Black or African American and responded to all items concerning the major variable of personal health., Results: Overall, respondents reported a slight tendency to agree or strongly agree that their practice environments were safe. When looking at various factors explaining personal health, the perception of workplace health and safety was found to be a significant contributing factor., Conclusions: The study findings suggest that, among Black nurses, perceptions about workplace health and safety are associated with perceived personal health. These findings underscore the importance of fostering healthy work environments., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Several COVID-19 outbreaks have been reported in meat processing plants in different countries. The aim of this study was to assess the environmental and socio-economic risk factors favouring the transmission of SARS-CoV-2 in meat processing plants and to describe the prevention measures implemented., Methods: Data from epidemiological investigations of COVID-19 clusters in France, the scientific literature, structured interviews and site visits were collected and summarised to investigate the main risk factors for SARS-CoV-2 infection in meat processing plants, including determinants within and outside the workplace., Results: An increased risk of infection was identified among workers with unfavourable socio-economic status (temporary/non-permanent workers, migrants, ethnic minorities, etc.), possibly related to community activities (house-sharing, car-sharing, social activities). Working conditions (proximity between workers) and environmental factors (low temperatures and inadequate ventilation) also appear to be important risk factors. These environmental conditions are particularly prevalent in cutting and boning plants, where the majority of reported cases are concentrated. Preventive measures applied included screening for COVID-19 symptoms, testing, wearing masks, increased hygiene and sanitation, physical and temporal distancing, control of ventilation. Certain food safety hygiene measures were compatible with protecting workers from SARS-CoV-2. The hygiene culture of agri-food workers made it easier to implement preventive measures after adaptation., Conclusion: This study made it possible to identify the environmental and socio-economic factors conducive to the transmission of SARS-CoV-2 in meat processing plants. The knowledge gained from this work was used in simulations to understand the transmission of the virus in the plants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kooh, Guillois, Federighi, Pivette, Maillard, Luong and Chaix.)

Importance: Observational studies have demonstrated consistent protective effects of higher educational attainment (EA) on the risk of suffering mental health conditions (MHC). Determining whether these beneficial effects are causal is challenging given the potential role of dynastic effects and demographic factors (assortative mating and population structure) in this association., Objective: To evaluate to what extent the relationship between EA and various MHC is independent from dynastic effects and demographic factors., Design: Within-sibship Mendelian randomization (MR) study., Setting: One-sample MR analyses included participants' data from the Trøndelag Health Study (HUNT, Norway) and UK Biobank (United Kingdom). For two-sample MR analyses we used summary statistics from publicly available genome-wide-association-studies., Participants: 61 880 siblings (27 507 sibships)., Exposure: Years of education., Main Outcomes: Scores for symptoms of anxiety, depression and neuroticism using the Hospital Anxiety Depression Scale (HADS), the 7-item Generalized Anxiety Disorder Scale (GAD-7), the 9-item Patient Health Questionnaire (PHQ-9), and the Eysenck Personality Questionnaire, as well as self-reported consumption of psychotropic medication., Results: One standard deviation (SD) unit increase in years of education was associated with a lower symptom score of anxiety (-0.20 SD [95%CI: -0.26, -0.14]), depression (-0.11 SD [-0.43, 0.22]), neuroticism (-0.30 SD [-0.53, -0.06]), and lower odds of psychotropic medication consumption (OR: 0.60 [0.52, 0.69]). Estimates from the within-sibship MR analyses showed some attenuation, which however were suggestive of a causal association (anxiety: -0.17 SD [-0.33, -0.00]; depression: -0.18 SD [-1.26, 0.89]; neuroticism: -0.29 SD [-0.43, -0.15]); psychotropic medication consumption: OR, 0.52 [0.34, 0.82])., Conclusions and Relevance: Associations between EA and MHC in adulthood, although to some extend explained by dynastic effects and demographic factors, overall remain robust, indicative of a causal effect. However, larger studies are warranted to improve statistical power and further validate our conclusions., Competing Interests: ØEN reports having received funding from the Norwegian University of Science and Technology for a review assignment. GDS reports a Scientific Advisory Board Membership for Relation Therapeutics and Insitro. MFVV, LB, PRJ, MT, NMD and BMB declare no conflict of interest to disclose.

Fungi are among the most diverse and ecologically important kingdoms in life. However, the distributional ranges of fungi remain largely unknown as do the ecological mechanisms that shape their distributions 1,2 . To provide an integrated view of the spatial and seasonal dynamics of fungi, we implemented a globally distributed standardized aerial sampling of fungal spores 3 . The vast majority of operational taxonomic units were detected within only one climatic zone, and the spatiotemporal patterns of species richness and community composition were mostly explained by annual mean air temperature. Tropical regions hosted the highest fungal diversity except for lichenized, ericoid mycorrhizal and ectomycorrhizal fungi, which reached their peak diversity in temperate regions. The sensitivity in climatic responses was associated with phylogenetic relatedness, suggesting that large-scale distributions of some fungal groups are partially constrained by their ancestral niche. There was a strong phylogenetic signal in seasonal sensitivity, suggesting that some groups of fungi have retained their ancestral trait of sporulating for only a short period. Overall, our results show that the hyperdiverse kingdom of fungi follows globally highly predictable spatial and temporal dynamics, with seasonality in both species richness and community composition increasing with latitude. Our study reports patterns resembling those described for other major groups of organisms, thus making a major contribution to the long-standing debate on whether organisms with a microbial lifestyle follow the global biodiversity paradigms known for macroorganisms 4,5 ., (© 2024. The Author(s).)

Objectives: To investigate the specific strengths of MRI and PET components in 68 Ga-PSMA-11 PET/MRI for staging of patients with biochemically recurrent prostate cancer (PCa)., Methods: Patients with biochemical recurrence of PCa and contrast-enhanced whole-body 68 Ga-PSMA-11 PET/MRI including a dedicated pelvic multiparametric MRI were included in this retrospective study. Imaging datasets of MRI and PET were evaluated separately regarding local PCa recurrence (Tr), pelvic lymph node metastases (N1), distant lymph node metastases (M1a), bone metastases (M1b), and soft tissue metastases (M1c) according to PROMISE version 1. Data evaluation was performed patient- and region-/lesion-based. Cox regression revealed a PSA of 1.69 ng/mL as a cut-off for subgroup analysis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were evaluated for each image component. Differences in staging accuracy were assessed using the Wilcoxon and McNemar test., Results: Altogether 102 patients (mean aged 68 ± 8 years, median PSA 1.33 ng/mL) were included. PCa was found in 70/102 (68%) patients. Accuracy of MRI in the detection of Tr, N1, M + , M1a, and M1b was 100%, 79%, 90%, 97%, and 95% for PSA < 1.69 ng/mL and 100%, 87%, 87%, 91%, and 96% for PSA > 1.69 ng/mL. Accuracy of 68 Ga-PSMA-11 PET was 93%, 97%, 93%, 98%, and 100% for PSA < 1.69 ng/mL and 87%, 91%, 96%, 100%, and 96% for PSA > 1.69 ng/mL., Conclusions: Combined assessment of 68 Ga-PSMA-11 PET/MRI improves tumor localization in men with biochemical recurrence. The MRI detected local recurrence of PCa more often whereas 68  Ga-PSMA-11 PET detected lymph node metastases more often, especially for PSA < 1.69 ng/mL., Clinical Relevance Statement: This study gives a scientific baseline to improve the understanding and reading of 68 Ga-PSMA-11 PET/MRI imaging in patients with biochemically recurrent PCa by showing the specific strength of each imaging component., Key Points: • Combining the individual modality strengths of 68 Ga-PSMA-11 PET/MRI improves tumor localization in men with biochemical recurrence of prostate cancer. • MRI component of 68  Ga-PSMA-11 PET/MRI shows its strength in detecting local recurrence of prostate cancer, especially at PSA < 1.69 ng/mL. • 68  Ga-PSMA-11 PET component shows its strength in detecting local and distant lymph node metastases, especially at PSA < 1.69 ng/mL., (© 2023. The Author(s).)

Seasonally abundant arthropods are a crucial food source for many migratory birds that breed in the Arctic. In cold environments, the growth and emergence of arthropods are particularly tied to temperature. Thus, the phenology of arthropods is anticipated to undergo a rapid change in response to a warming climate, potentially leading to a trophic mismatch between migratory insectivorous birds and their prey. Using data from 19 sites spanning a wide temperature gradient from the Subarctic to the High Arctic, we investigated the effects of temperature on the phenology and biomass of arthropods available to shorebirds during their short breeding season at high latitudes. We hypothesized that prolonged exposure to warmer summer temperatures would generate earlier peaks in arthropod biomass, as well as higher peak and seasonal biomass. Across the temperature gradient encompassed by our study sites (>10°C in average summer temperatures), we found a 3-day shift in average peak date for every increment of 80 cumulative thawing degree-days. Interestingly, we found a linear relationship between temperature and arthropod biomass only below temperature thresholds. Higher temperatures were associated with higher peak and seasonal biomass below 106 and 177 cumulative thawing degree-days, respectively, between June 5 and July 15. Beyond these thresholds, no relationship was observed between temperature and arthropod biomass. Our results suggest that prolonged exposure to elevated temperatures can positively influence prey availability for some arctic birds. This positive effect could, in part, stem from changes in arthropod assemblages and may reduce the risk of trophic mismatch., (© 2024 His Majesty the King in Right of Canada and The Authors. Global Change Biology published by John Wiley & Sons Ltd. Reproduced with the permission of the Minister of Environment and Climate Change Canada. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

There are many studies on central catheter related thrombosis (CCRT), however, there are significantly fewer studies focusing on the incidence and evolution of CCRT in the adult critical care population. This article reviews data collected from observational studies that have performed bedside duplex ultrasound for surveillance of CCRT and discuss if we should routinely screen for CCRT. The reported CCRT incidence is 17-38%, with most thrombus being detectable on ultrasound within seven days of line placement. Nearly all CCRT are designated as asymptomatic (no associated pulmonary embolism (PE) or deep vein thrombosis (DVT)) and no significant changes in mortality rates amongst patients that develop CCRT were reported. Based on the evidence reviewed, we do not recommend screening routinely for CCRT in the adult critical care population.

Novel methods for sampling and characterizing biodiversity hold great promise for re-evaluating patterns of life across the planet. The sampling of airborne spores with a cyclone sampler, and the sequencing of their DNA, have been suggested as an efficient and well-calibrated tool for surveying fungal diversity across various environments. Here we present data originating from the Global Spore Sampling Project, comprising 2,768 samples collected during two years at 47 outdoor locations across the world. Each sample represents fungal DNA extracted from 24 m 3 of air. We applied a conservative bioinformatics pipeline that filtered out sequences that did not show strong evidence of representing a fungal species. The pipeline yielded 27,954 species-level operational taxonomic units (OTUs). Each OTU is accompanied by a probabilistic taxonomic classification, validated through comparison with expert evaluations. To examine the potential of the data for ecological analyses, we partitioned the variation in species distributions into spatial and seasonal components, showing a strong effect of the annual mean temperature on community composition., (© 2024. The Author(s).)

Objectives: Immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs), of which endocrinopathies are common. We characterized endocrine and non-endocrine irAEs in cancer patients receiving ICIs, identified risk factors for their development and established whether endocrine and non-endocrine irAEs were differentially associated with improved cancer prognosis., Design and Methods: Single-center, retrospective cohort study of patients with advanced or metastatic solid tumors receiving at least one ICI treatment cycle (242 men, 151 women, median age 65 years). Main outcome measures were incidence of any irAE during the study period, overall survival and time to treatment failure., Results: Non-endocrine irAEs occurred in 32% and endocrine irAEs in 12% of patients. Primary thyroid dysfunction was the most common endocrine irAE (9.5%) and the majority of endocrinopathies required permanent hormone replacement. Women had an increased risk of developing endocrine irAEs (p = 0.017). The biggest survival advantage occurred in patients who developed both endocrine and non-endocrine irAEs (overall survival: HR 0.16, CI 0.09-0.28). Time to treatment failure was also significantly improved in patients who developed endocrine irAEs (HR 0.49, CI 0.34 - 0.71) or both (HR 0.41, CI 0.25 - 0.64) but not in those who only developed non-endocrine irAEs., Conclusions: Women may have increased risk of endocrine irAEs secondary to ICI treatment. This is the first study to compare the effects of endocrine irAEs with non-endocrine irAEs on survival. Development of endocrine irAEs may confer survival benefit in ICI treatment and future, prospective studies are needed to elucidate this., Competing Interests: AC declares grants for consultancies/advisory boards from BMS, MSD, OncoC4, IQVIA, AstraZeneca. He also declares speaker fees from AstraZeneca, EISAI and Pierre-Fabre. DJP reports grants from GSK, BMS, and MSD (institutions) for supporting academic trials in oncology; personal payment from Wiley for Editor in Chief role unrelated to the topic of this manuscript; consulting fees from Mina Therapeutics, EISAI, H3B, Astra Zeneca, DaVolterra, Avamune, BMS, Roche for supporting research in oncology unrelated to topic of the manuscript; speaker's fees from Roche, BMS, EISAI, and Ewopharma unrelated to the topic of the manuscript; travel support from MSD and Bayer; and participation on advisory board for Astra Zeneca, EISAI, H3B. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Murthy, Cortellini, Lim, Gonzalez, Pinato, Abdel-Malek, Mahmoud and Martin.)

Granulomatosis with polyangiitis (GPA) rarely involves the pituitary gland. Pituitary involvement has been reported in ~ 1% of all cases of GPA. Most commonly, pituitary swelling and inflammation results in symptoms due to pituitary mass effect and arginine vasopressin deficiency. To date, there are no pituitary-specific treatment guidelines for this rare condition. We present three patients with GPA-related hypophysitis highlighting the spectrum of pituitary involvement. All three patients were successfully treated with immunosuppressive regimens that included rituximab (RTX). Following remission induction with high-dose glucocorticoids, patients received 6 monthly RTX for remission maintenance. RTX was well tolerated without significant side effects., (© 2024. The Author(s).)

Purpose: To evaluate if a machine learning prediction model based on clinical and easily assessable imaging features derived from baseline breast [ 18 F]FDG-PET/MRI staging can predict pathologic complete response (pCR) in patients with newly diagnosed breast cancer prior to neoadjuvant system therapy (NAST)., Methods: Altogether 143 women with newly diagnosed breast cancer (54 ± 12 years) were retrospectively enrolled. All women underwent a breast [ 18 F]FDG-PET/MRI, a histopathological workup of their breast cancer lesions and evaluation of clinical data. Fifty-six features derived from positron emission tomography (PET), magnetic resonance imaging (MRI), sociodemographic / anthropometric, histopathologic as well as clinical data were generated and used as input for an extreme Gradient Boosting model (XGBoost) to predict pCR. The model was evaluated in a five-fold nested-cross-validation incorporating independent hyper-parameter tuning within the inner loops to reduce the risk of overoptimistic estimations. Diagnostic model-performance was assessed by determining the area under the curve of the receiver operating characteristics curve (ROC-AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy. Furthermore, feature importances of the XGBoost model were evaluated to assess which features contributed most to distinguish between pCR and non-pCR., Results: Nested-cross-validation yielded a mean ROC-AUC of 80.4 ± 6.0% for prediction of pCR. Mean sensitivity, specificity, PPV, and NPV of 54.5 ± 21.3%, 83.6 ± 4.2%, 63.6 ± 8.5%, and 77.6 ± 8.1% could be achieved. Histopathological data were the most important features for classification of the XGBoost model followed by PET, MRI, and sociodemographic/anthropometric features., Conclusion: The evaluated multi-source XGBoost model shows promising results for reliably predicting pathological complete response in breast cancer patients prior to NAST. However, yielded performance is yet insufficient to be implemented in the clinical decision-making process., (© 2023. The Author(s).)

Shifts in phenology are among the key responses of organisms to climate change. When rates of phenological change differ between interacting species they may result in phenological asynchrony. Studies have found conflicting patterns concerning the direction and magnitude of changes in synchrony, which have been attributed to biological factors. A hitherto overlooked additional explanation are differences in the currency used to quantify resource phenology, such as abundance and biomass. Studying an insectivorous bird (the sanderling) and its prey, we show that the median date of cumulative arthropod biomass occurred, on average, 6.9 days after the median date of cumulative arthropod abundance. In some years this difference could be as large as 21 days. For 23 years, hatch dates of sanderlings became less synchronized with the median date of arthropod abundance, but more synchronized with the median date of arthropod biomass. The currency-specific trends can be explained by our finding that mean biomass per arthropod specimen increased with date. Using a conceptual simulation, we show that estimated rates of phenological change for abundance and biomass can differ depending on temporal shifts in the size distribution of resources. We conclude that studies of trophic mismatch based on different currencies for resource phenology can be incompatible with each other.

The differentiation of resident intestinal macrophages from blood monocytes depends upon signals from the macrophage colony-stimulating factor receptor (CSF1R). Analysis of genome-wide association studies (GWAS) indicates that dysregulation of macrophage differentiation and response to microorganisms contributes to susceptibility to chronic inflammatory bowel disease (IBD). Here, we analyzed transcriptomic variation in monocyte-derived macrophages (MDM) from affected and unaffected sib pairs/trios from 22 IBD families and 6 healthy controls. Transcriptional network analysis of the data revealed no overall or inter-sib distinction between affected and unaffected individuals in basal gene expression or the temporal response to lipopolysaccharide (LPS). However, the basal or LPS-inducible expression of individual genes varied independently by as much as 100-fold between subjects. Extreme independent variation in the expression of pairs of HLA-associated transcripts (HLA-B/C, HLA-A/F and HLA-DRB1/DRB5) in macrophages was associated with HLA genotype. Correlation analysis indicated the downstream impacts of variation in the immediate early response to LPS. For example, variation in early expression of IL1B was significantly associated with local SNV genotype and with subsequent peak expression of target genes including IL23A, CXCL1, CXCL3, CXCL8 and NLRP3. Similarly, variation in early IFNB1 expression was correlated with subsequent expression of IFN target genes. Our results support the view that gene-specific dysregulation in macrophage adaptation to the intestinal milieu is associated with genetic susceptibility to IBD., (© 2024. The Author(s).)

Aim: This study aimed to quantitatively summarise risk factors associated with surgical site infection (SSI) following surgically managed tibial fractures., Method: We searched the Embase/Medline, Cochrane Library, and Scopus databases for relevant studies in October 2023. We included original studies investigating risk factors for SSI following surgically managed traumatic tibial fractures that included ≥10 adult patients with SSIs. Meta-analysis was performed when >5 studies investigated the same risk factor. The risk of bias was assessed using the critical appraisal checklist from Joanna Briggs Institute for cohort studies., Results: This study included 42 studies comprising 24,610 patients with surgically managed tibial fractures and 2,418 SSI cases. The following were identified as significant risk factors for SSI (p < 0.05): compartment syndrome (odds ratio [OR] = 3.8, 95% confidence interval [CI]: 2.4-6.0), blood transfusion (OR = 3.8, 95% CI: 2.1-6.6), open fracture (OR = 3.6, 95% CI: 2.5-5.1), Gustilo-Anderson classification >2 (OR = 3.1, 95% CI: 2.1-4.6), external fixation (OR = 2.9, 95% CI: 2.3-3.8), American Society of Anesthesiologists classification >2 (OR = 2.5, 95% CI: 1.5-4.1), polytrauma (OR = 2.4, 95% CI: 1.5-4.0), dual incision approach (OR = 2.1, 95% CI: 1.5-3.0), smoking (OR = 1.8, 95% CI: 1.5-2.1), male sex (OR = 1.6, 95% CI: 1.3-1.8), high energy trauma (OR = 1.5, 95% CI: 1.1-2.1), and prolonged surgery time (OR = 0.62, 0.43-0.82). Other factors, including diabetes, hypertension, and time to surgery, were not identified as risk factors for SSI. However, the included studies were generally of poor quality and at risk of bias., Conclusions: The review provides a basis for preoperatively assessing a patient's risk of developing an SSI, which could be used to initiate adjusted antibiotic regimes and more frequent postoperative controls. Furthermore, it indicates the risk factors future research should include when adjusting for confounding factors., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The pivotal impact of Social Determinants of Health (SDoH) on people's health and well-being has been widely recognized and researched. However, the effect of Commercial Determinants of Health (CDoH) is only now garnering increased attention. Developing an ontology for CDoH can offer a systematic approach to identifying and categorizing the diverse commercial factors affecting health. These factors, including the production, distribution, and marketing of goods and services, may exert a substantial influence on health outcomes. The objectives of this research are 1) to develop an ontology for CDoH by utilizing PubMed articles and ChatGPT; 2) to foster ontology reuse by integrating CDoH with an existing SDoH ontology into a unified structure; 3) to devise an overarching conception for all nonclinical determinants of health (N-CDoH) and to create an initial ontology for N-CDoH; 4) and to validate the degree of correspondence between concepts provided by ChatGPT with the existing SDoH ontology., (©2023 AMIA - All rights reserved.)

Genomic studies of species threatened by extinction are providing crucial information about evolutionary mechanisms and genetic consequences of population declines and bottlenecks. However, to understand how species avoid the extinction vortex, insights can be drawn by studying species that thrive despite past declines. Here, we studied the population genomics of the muskox (Ovibos moschatus), an Ice Age relict that was at the brink of extinction for thousands of years at the end of the Pleistocene yet appears to be thriving today. We analysed 108 whole genomes, including present-day individuals representing the current native range of both muskox subspecies, the white-faced and the barren-ground muskox (O. moschatus wardi and O. moschatus moschatus) and a ~21,000-year-old ancient individual from Siberia. We found that the muskox' demographic history was profoundly shaped by past climate changes and post-glacial re-colonizations. In particular, the white-faced muskox has the lowest genome-wide heterozygosity recorded in an ungulate. Yet, there is no evidence of inbreeding depression in native muskox populations. We hypothesize that this can be explained by the effect of long-term gradual population declines that allowed for purging of strongly deleterious mutations. This study provides insights into how species with a history of population bottlenecks, small population sizes and low genetic diversity survive against all odds., (© 2023 John Wiley & Sons Ltd.)

Background: Prenatal exposures to endocrine disrupting chemicals (EDCs) are correlated with adverse behavioral outcomes, but the effects of combinations of these chemicals are unclear. The aim of this study was to determine the dose-dependent effects of prenatal exposure to EDCs on male and female behavior. Methods: Pregnant Sprague-Dawley rats were orally dosed with vehicle, bisphenol A (BPA) (5 μg/kg body weight (BW)/day), low-dose (LD) diethylhexyl phthalate (DEHP) (5 μg/kg BW/day), high-dose (HD) DEHP (7.5 mg/kg BW/day), a combination of BPA and LD-DEHP (B + D (LD)), or a combination of BPA and HD-DEHP (B + D (HD)) on gestational days 6-21. Adult offspring were subjected to the Open Field Test (OFT), Elevated Plus Maze (EPM), and Shock Probe Defensive Burying test (SPDB) in adulthood. Body, adrenal gland, and pituitary gland weights were collected at sacrifice. Corticosterone (CORT) was measured in the serum. Results: Female EDC-exposed offspring showed anxiolytic effects in the OFT, while male offspring were unaffected. DEHP (HD) male offspring demonstrated a feminization of behavior in the EPM. Most EDC-exposed male offspring buried less in the SPDB, while their female counterparts showed reduced shock reactivity, indicating sex-specific maladaptive alterations in defensive behaviors. Additionally, DEHP (LD) males and females and B + D (LD) females displayed increased immobility in this test. DEHP (LD) alone and in combination with BPA led to lower adrenal gland weights, but only in male offspring. Finally, females treated with a mixture of B + D (HD) had elevated CORT levels. Conclusion: Prenatal exposure to BPA, DEHP, or a mixture of the two, affects behavior, CORT levels, and adrenal gland weights in a sex- and dose-dependent manner., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Kaimal, Hooversmith, Cherry, Garrity, Al Mansi, Martin, Buechter, Holmes, MohanKumar and MohanKumar.)

The bioavailability of essential and non-essential elements in vegetation is expected to influence the performance of free-ranging terrestrial herbivores. However, attempts to relate the use of geochemical landscapes by animal populations directly to reproductive output are currently lacking. Here we measured concentrations of 14 essential and non-essential elements in soil and vegetation samples collected in the Zackenberg valley, northeast Greenland, and linked these to environmental conditions to spatially predict and map geochemical landscapes. We then used long-term (1996-2021) survey data of muskoxen (Ovibos moschatus) to quantify annual variation in the relative use of essential and non-essential elements in vegetated sites and their relationship to calf recruitment the following year. Results showed that the relative use of the geochemical landscape by muskoxen varied substantially between years and differed among elements. Selection for vegetated sites with higher levels of the essential elements N, Cu, Se, and Mo was positively linked to annual calf recruitment. In contrast, selection for vegetated sites with higher concentrations of the non-essential elements As and Pb was negatively correlated to annual calf recruitment. Based on the concentrations measured in our study, we found no apparent associations between annual calf recruitment and levels of C, Mn, Co, Zn, Cd, Ba, Hg, and C:N ratio in the vegetation. We conclude that the spatial distribution and access to essential and non-essential elements are important drivers of reproductive output in muskoxen, which may also apply to other wildlife populations. The value of geochemical landscapes to assess habitat-performance relationships is likely to increase under future environmental change., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Under-resourced urban minority communities in the United States are characterized by food environments with low access to healthy foods, high food insecurity, and high rates of diet-related chronic disease. In Baltimore, Maryland, low access to healthy food largely results from a distribution gap between small food sources (retailers) and their suppliers. Digital interventions have the potential to address this gap, while keeping costs low., Methods: In this paper, we describe the technical (I) front-end design and (II) back-end development process of the Baltimore Urban food Distribution (BUD) application (app). We identify and detail four main phases of the process: (I) information architecture; (II) low and high-fidelity wireframes; (III) prototype; and (IV) back-end components, while considering formative research and a pre-pilot test of a preliminary version of the BUD app., Results: Our lessons learned provide valuable insight into developing a stable app with a user-friendly experience and interface, and accessible cloud computing services for advanced technical features., Conclusions: Next steps will involve a pilot trial of the app in Baltimore, and eventually, other urban and rural settings nationwide. Once iterative feedback is incorporated into the app, all code will be made publicly available via an open source repository to encourage adaptation for desired communities., Trial Registration: ClinicalTrials.gov NCT05010018., Competing Interests: Conflicts of Interest: The authors have completed the ICMJE uniform disclosure form (available at https://mhealth.amegroups.com/article/view/10.21037/mhealth-23-30/coif). The authors report that this article was supported by National Heart, Lung, and Blood Institute of the National Institutes of Health under award number R34HL145368. The authors have no other conflicts of interest to declare., (2024 mHealth. All rights reserved.)

At the beginning of the COVID-19 pandemic, several contamination clusters were reported in food-processing plants in France and several countries worldwide. Therefore, a need arose to better understand viral transmission in such occupational environments from multiple perspectives: the protection of workers in hotspots of viral circulation; the prevention of supply disruption due to the closure of plants; and the prevention of cluster expansion due to exports of food products contaminated by the virus to other locations. This paper outlines a simulation-based approach (using agent-based models) to study the effects of measures taken to prevent the contamination of workers, surfaces, and food products. The model includes user-defined parameters to integrate characteristics relating to SARS-CoV-2 (variant of concern to be considered, symptom onset…), food-processing plants (dimensions, ventilation…), and other sociodemographic transmission factors based on laboratory experiments as well as industrial and epidemiological investigations. Simulations were performed for a typical meat-processing plant in different scenarios for illustration purposes. The results suggested that increasing the mask-wearing ratio led to great reductions in the probability of observing clusters of more than 25 infections. In the case of clusters, masks being worn by all workers limited the presence of contamination (defined as levels of at least 5 log 10 viral RNA copies) on meat cuts at less than 0.05 % and maintained the production capacity of the plant at optimal levels. Increasing the average distance between two workers from less than 1 m to more than 2 m decreased the cluster-occurrence probability by up to 15 % as well as contamination of food products during cluster situations. The developed approach can open up several perspectives in terms of potential communication-support tools for the agri-food sector and further reuses or adaptations for other hazards and occupational environments., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: Residual glandular tissue (RGT) after risk reducing mastectomy (RRME) is associated with a risk of developing breast cancer for women with a familial predisposition. We aim to examine various surgery-related variables to make risk more easily assessable and to aid in decision-making., Materials and Methods: Pre- and postoperative breast MRI scans from 2006 to 2021 of patients with proven pathogenic mutation were included. The postoperative remaining skin flap was recorded using distance measurements at 8 equally distributed clockwise points and retromamillary. Each breast was volumetrized, as well as existing RGT. Patient-related covariates were further recorded and their influence on RGT was investigated uni- and multivariately., Results: 81 patients (49 with BRCA1, 24 with BRCA2, 9 with other mutations), who were on average 39 years old, had 117 breasts analyzed. The mean follow-up was 71 months. In multivariate analysis, the independent variable skin flap thickness had a positive effect (p ≤ 0.01), while surgeon experience negatively affected RGT (p ≤ 0.05). The incision type was found to impact RGT as well, with nipple-sparing mastectomy (NSM) with inframammary fold incision leading to more RGT (p ≤ 0.01 - p ≤ 0.05), and skin-sparing mastectomy (SSM) with an inverted T incision leading to less (p ≤ 0.01)., Conclusion: Different surgical variables have an impact on postoperative RGT, which is an important tool to quantify the risk of developing breast cancer after RRME. In order to effectively consider these variables in future preoperative/intraoperative management, they must be carefully taken into account., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (© 2023 Published by Elsevier Ltd.)

Objectives: Evaluate the influence of an MRI contrast agent application on primary and follow-up staging in pediatric patients with newly diagnosed lymphoma using [ 18 F]FDG PET/MRI to avoid adverse effects and save time and costs during examination., Methods: A total of 105 [ 18 F]FDG PET/MRI datasets were included for data evaluation. Two different reading protocols were analyzed by two experienced readers in consensus, including for PET/MRI-1 reading protocol unenhanced T2w and/or T1w imaging, diffusion-weighted imaging (DWI), and [ 18 F]FDG PET imaging and for PET/MRI-2 reading protocol an additional T1w post contrast imaging. Patient-based and region-based evaluation according to the revised International Pediatric Non-Hodgkin's Lymphoma (NHL) Staging System (IPNHLSS) was performed, and a modified standard of reference was applied comprising histopathology and previous and follow-up cross-sectional imaging. Differences in staging accuracy were assessed using the Wilcoxon and McNemar tests., Results: In patient-based analysis, PET/MRI-1 and PET/MRI-2 both determined a correct IPNHLSS tumor stage in 90/105 (86%) exams. Region-based analysis correctly identified 119/127 (94%) lymphoma-affected regions. Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for PET/MRI-1 and PET/MRI-2 were 94%, 97%, 90%, 99%, 97%, respectively. There were no significant differences between PET/MRI-1 and PET/MRI-2., Conclusions: The use of MRI contrast agents in [ 18 F]FDG PET/MRI examinations has no beneficial effect in primary and follow-up staging of pediatric lymphoma patients. Therefore, switching to a contrast agent-free [ 18 F]FDG PET/MRI protocol should be considered in all pediatric lymphoma patients., Clinical Relevance Statement: This study gives a scientific baseline switching to a contrast agent-free [ 18 F]FDG PET/MRI staging in pediatric lymphoma patients. This could avoid side effects of contrast agents and saves time and costs by a faster staging protocol for pediatric patients., Key Points: • No additional diagnostic benefit of MRI contrast agents at [ 18 F]FDG PET/MRI examinations of pediatric lymphoma primary and follow-up staging • Highly accurate primary and follow-up staging of pediatric lymphoma patients at MRI contrast-free [ 18 F]FDG PET/MRI., (© 2023. The Author(s).)

Background: The use of omics data for monitoring the microbial flow of fresh meat products along a production line and the development of spoilage prediction tools from these data is a promising but challenging task. In this context, we produced a large multivariate dataset (over 600 samples) obtained on the production lines of two similar types of fresh meat products (poultry and raw pork sausages). We describe a full analysis of this dataset in order to decipher how the spoilage microbial ecology of these two similar products may be shaped differently depending on production parameter characteristics., Methods: Our strategy involved a holistic approach to integrate unsupervised and supervised statistical methods on multivariate data (OTU-based microbial diversity; metabolomic data of volatile organic compounds; sensory measurements; growth parameters), and a specific selection of potential uncontrolled (initial microbiota composition) or controlled (packaging type; lactate concentration) drivers., Results: Our results demonstrate that the initial microbiota, which is shown to be very different between poultry and pork sausages, has a major impact on the spoilage scenarios and on the effect that a downstream parameter such as packaging type has on the overall evolution of the microbial community. Depending on the process, we also show that specific actions on the pork meat (such as deboning and defatting) elicit specific food spoilers such as Dellaglioa algida, which becomes dominant during storage. Finally, ecological network reconstruction allowed us to map six different metabolic pathways involved in the production of volatile organic compounds involved in spoilage. We were able connect them to the different bacterial actors and to the influence of packaging type in an overall view. For instance, our results demonstrate a new role of Vibrionaceae in isopropanol production, and of Latilactobacillus fuchuensis and Lactococcus piscium in methanethiol/disylphide production. We also highlight a possible commensal behavior between Leuconostoc carnosum and Latilactobacillus curvatus around 2,3-butanediol metabolism., Conclusion: We conclude that our holistic approach combined with large-scale multi-omic data was a powerful strategy to prioritize the role of production parameters, already known in the literature, that shape the evolution and/or the implementation of different meat spoilage scenarios., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Poirier, Coeuret, Champomier-Vergès, Desmonts, Werner, Feurer, Frémaux, Guillou, Luong, Rué, Loux, Zagorec, Chaillou and on the behalf of the ANR Redlosses Consortium Group.)

Aim: To explore the experiences of residents, families and staff in the establishment of a new small-scale home model of care for people living with dementia., Background: New and innovative small-scale models of care have the potential to improve outcomes for older people, especially those with dementia, who experience high rates of cognitive impairment in traditional residential aged care homes in Australia., Design: A qualitative descriptive study., Methods: Semi-structured interviews with 14 guests, family and staff of a new small-scale dementia home named 'Kambera House' in the Australian Capital Territory were conducted between July 2021 when the home opened and August 2022. Data were analysed using reflexive thematic analysis and reported according to the COREQ guidelines., Results: Two guests with mild-to-moderate dementia, five family and seven staff members participated in the study. The data revealed high satisfaction with Kambera House, generating five themes. Falls detection technology in the home provided a sense of safety, enabling more time for person-centred care. Free, everyday technology connected the home with families as part of an overall community of care where staff were empowered to maximize choice and dignity of risk of guests living in the home. This contributed to the sense of community, rather than an institution, where the conditions of work supported the conditions of care, and were embedded in a culture of responsiveness, change and flexibility., Conclusion: Kambera House represents a successful example of a new small-scale dementia home. Technology played an important background role in improving overall safety and flexibility as part of a model of care which demonstrated positive experiences for guests and families by being responsive to their individual needs., Impacts: Small-scale homes for people with dementia offer an alternative model that may provide more individualized, person-centred care compared with the traditional institutionalized care., Patient or Public Contribution: No patient or public contribution., (© 2023 The Authors. Journal of Advanced Nursing published by John Wiley & Sons Ltd.)

Objectives: To investigate the diagnostic feasibility of a shortened breast PET/MRI protocol in breast cancer patients., Methods: Altogether 90 women with newly diagnosed T1 tumor-staged (T1 ts ) and T2 tumor-staged (T2 ts ) breast cancer were included in this retrospective study. All underwent a dedicated comprehensive breast [ 18 F]FDG-PET/MRI. List-mode PET data were retrospectively reconstructed with 20, 15, 10, and 5 min for each patient to simulate the effect of reduced PET acquisition times. The SUV max/mean of all malign breast lesions was measured. Furthermore, breast PET data reconstructions were analyzed regarding image quality, lesion detectability, signal-to-noise ratio (SNR), and image noise (IN). The simultaneously acquired comprehensive MRI protocol was then shortened by retrospectively removing sequences from the protocol. Differences in malignant breast lesion detectability between the original and the fast breast MRI protocol were evaluated lesion-based. The 20-min PET reconstructions and the original MRI protocol served as reference., Results: In all PET reconstructions, 127 congruent breast lesions could be detected. Group comparison and T1 ts vs. T2 ts subgroup comparison revealed no significant difference of subjective image quality between 20, 15, 10, and 5 min acquisition times. SNR of qualitative image evaluation revealed no significant difference between different PET acquisition times. A slight but significant increase of IN with decreasing PET acquisition times could be detected. Lesion SUV max group comparison between all PET acquisition times revealed no significant differences. Lesion-based evaluation revealed no significant difference in breast lesion detectability between original and fast breast MRI protocols., Conclusions: Breast [ 18 F]FDG-PET/MRI protocols can be shortened from 20 to below 10 min without losing essential diagnostic information., Key Points: • A highly accurate breast cancer evaluation is possible by the shortened breast [ 18 F]FDG-PET/MRI examination protocol. • Significant time saving at breast [ 18 F]FDG-PET/MRI protocol could increase patient satisfaction and patient throughput for breast cancer patients at PET/MRI., (© 2023. The Author(s).)

With the global change in climate, the Arctic has been pinpointed as the region experiencing the fastest rates of change. As a result, Arctic biological responses-such as shifts in phenology-are expected to outpace those at lower latitudes. 15 years ago, a decade-long dataset from Zackenberg in High Arctic Greenland revealed rapid rates of phenological change. 1 To explore how the timing of spring phenology has developed since, we revisit the Zackenberg time series on flowering plants, arthropods, and birds. Drawing on the full 25-year period of 1996-2020, we find little directional change in the timing of events despite ongoing climatic change. We attribute this finding to a shift in the temporal patterns of climate conditions, from previous directional change to current high inter-annual variability. Additionally, some taxa appear to have reached the limits of their phenological responses, resulting in a leveling off in their phenological responses in warm years. Our findings demonstrate the importance of long-term monitoring of taxa from across trophic levels within the community, allowing for detecting shifts in sensitivities and responses and thus for updated inference in the light of added information., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: To compare the incidence of perioperative thromboembolic events in femoral neck fracture (FNF) patients treated with hybrid total hip arthroplasty (THA) with intraoperative unfractionated heparin (UFH) versus a control group without intraoperative UFH before femoral component cementation., Methods: We compared 139 cases without UFH (group A) versus 134 who received 10 UI/kg UFH (group B). Indication of UFH before cementation depended on the preferences of the anaesthesiologists in each case. We assessed intraoperative bone cement implantation syndrome (BCIS) and 30-day thromboembolic events, and 90-day and 1-year mortality. BCIS was classified as per Donaldson et al.'s classification according to the degree of hypotension, arterial desaturation or loss of consciousness., Results: BCIS was observed in 51 (18%) cases, including 37 (13%) grade 1 and 14 (5%) grade 2. Forty-seven BCISs (35%) were observed in group B and 4 (3%) in group A (p < 0.001). Multivariate regression showed that intraoperative UFH (OR = 18, CI 95% 6-52) and consumption of oral anticoagulants (OR = 3.3, CI 95% 1-10) increased the risk of BCIS. Five patients further developed a 30-day pulmonary embolism in group B, while 2 presented this complication in group A (p = 0.231). No association between BCIS and 30-day thromboembolic events was found (p = 0.62). 90-day (1% each, p = 0.98) and 1-year (2% vs. 3%, p = 0.38) mortality were similar., Conclusions: BCIS was a frequent finding in FNF patients treated with hybrid THA. We found a paradoxically significant increase in BCIS with the use of UFH. Heparin did not seem to prevent BCIS, other thromboembolic events and mortality in this group of patients., (© 2023. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Introduction: Suboptimal iron status is an issue for women joining the military because of its association with impaired aerobic performance, yet no studies have investigated dietary and non-dietary determinants of iron status simultaneously in this population. The purpose of this study was to explore associations between iron stores, dietary patterns (DPs), and potential non-dietary determinants of iron status in premenopausal women at the commencement of basic military training (BMT) in the New Zealand Army., Methods: During week 1 of BMT, demographic, body composition, lifestyle, medical history, and dietary data were measured as potential determinants of serum ferritin (SF) in 101 participants. Following univariate analysis, age, body fat percentage, previous blood donation, at least 6 h of exercise per week that raised the heart rate, and a vegetarian DP were analyzed using a multiple linear regression model., Results: An increase in body fat percentage was associated with increased SF (P < .009), although blood donation in the past year decreased SF (P < .011) compared to those participants who did not donate blood. There was no association between SF and a vegetarian DP or hours of exercise per week. The model explained 17.5% of the variance in SF at the commencement of BMT., Conclusion: Body fat percentage and blood donation in the past year were the strongest determinants of iron stores in healthy premenopausal women commencing BMT. It is recommended that women joining the New Zealand Army are provided information to maintain or improve their iron status based on these findings. This includes clinical screening of iron status, advice for women considering blood donation, and dietary advice regarding total energy requirements and iron bioavailability., (© The Association of Military Surgeons of the United States 2023.)

Background: This study compares the diagnostic potential of conventional staging (computed tomography (CT), axillary sonography and bone scintigraphy), whole-body magnetic resonance imaging (MRI) and whole-body 18 F-fluorodeoxyglucose positron emission tomography ( 18 F-FDG PET/)MRI for N and M staging in newly diagnosed breast cancer. Methods: A total of 208 patients with newly diagnosed breast cancer were prospectively included in this study and underwent contrast-enhanced thoracoabdominal CT, bone scintigraphy and axillary sonography as well as contrast-enhanced whole-body 18 F-FDG PET/MRI. The datasets were analyzed with respect to lesion localization and characterization. Histopathology and follow-up imaging served as the reference standard. A McNemar test was used to compare the diagnostic performance of conventional staging, MRI and 18 F-FDG PET/MRI and a Wilcoxon test was used to compare differences in true positive findings for nodal staging. Results: Conventional staging determined the N stage with a sensitivity of 80.9%, a specificity of 99.2%, a PPV (positive predictive value) of 98.6% and a NPV (negative predictive value) of 87.4%. The corresponding results for MRI were 79.6%, 100%, 100% and 87.0%, and were 86.5%, 94.1%, 91.7% and 90.3% for 18 F-FDG PET/MRI. 18 F-FDG PET/MRI was significantly more sensitive in determining malignant lymph nodes than conventional imaging and MRI ( p < 0.0001 and p = 0.0005). Furthermore, 18 F-FDG PET/MRI accurately estimated the clinical lymph node stage in significantly more cases than conventional imaging and MRI (each p < 0.05). Sensitivity, specificity, PPV and NPV for the M stage in conventional staging were 83.3%, 98.5%, 76.9% and 98.9%, respectively. The corresponding results for both MRI and 18 F-FDG PET/MRI were 100.0%, 98.5%, 80.0% and 100.0%. No significant differences between the imaging modalities were seen for the staging of distant metastases. Conclusions: 18 F-FDG PET/MRI detects lymph node metastases in significantly more patients and estimates clinical lymph node stage more accurately than conventional imaging and MRI. No significant differences were found between imaging modalities with respect to the detection of distant metastases.

Background: Adverse pregnancy outcomes in women with primary Sjögren's syndrome have only been evaluated retrospectively using heterogeneous methods and with contradictory results. We aimed to describe adverse pregnancy, delivery, and birth outcome risks in pregnant women with primary Sjögren's syndrome compared with those of a matched general population in France, and to identify factors predictive of disease flares or adverse pregnancy outcomes., Methods: We conducted a multicentre, prospective, cohort study in France using the GR2 (Groupe de Recherche sur la Grossesse et les Maladies Rares) registry. Women from the GR2 study were eligible if they had conceived before March, 2021, had primary Sjögren's syndrome according to the American College of Rheumatology and European Alliance of Associations for Rheumatology (EULAR) 2016 classification criteria, and had an ongoing pregnancy at 12 weeks of gestation. In women who entered in the registry with pregnancies before 18 weeks of gestation, we sought to identify factors associated with primary Sjögren's syndrome flare (≥3-point increase in EULAR Sjögren's Syndrome Disease Activity Index [ESSDAI] score) or adverse pregnancy outcomes (fetal or neonatal death, placental insufficiency leading to a preterm delivery [<37 weeks of gestation], or small-for-gestational-age birthweight). A matched controlled study compared adverse pregnancy, delivery, and birth outcome rates between pregnant women with primary Sjögren's syndrome from the GR2 registry and matched controls from the general population included in the last French perinatal survey (Enquête Nationale Périnatale 2016)., Findings: 1944 pregnancies were identified in the GR2 cohort, of which 106 pregnancies in 96 women with primary Sjögren's syndrome were included in this analysis. The median age at pregnancy onset was 33 years (IQR 31-36). 87 (83%) of 105 pregnancies (with ethnicity data) were in White women, 18 (17%) were in Black women; 92 (90%) of 102 had previous systemic activity (ESSDAI score of ≥1; data missing in four pregnancies), and 48 (45%) of 106 had systemic activity at inclusion. Of 93 pregnancies included at week 18 of gestation or earlier, primary Sjögren's syndrome flares occurred in 12 (13%). No baseline parameters were associated with primary Sjögren's syndrome flare. Four twin pregnancies and one medical termination were excluded from the adverse pregnancy outcome analysis; of the remaining 88, adverse pregnancy outcomes occurred in six (7%). Among pregnancies in women with data for antiphospholipid antibodies (n=55), antiphospholipid antibody positivity was more frequent among pregnancies with adverse outcomes (two [50%] of four pregnancies) compared with those without adverse outcomes (two [4%] of 51 pregnancies; p=0·023). Anti-RNP antibody positivity was also more frequent among pregnancies with adverse outcomes than those without, although this was not statistically significant. In the matched controlled study, adverse pregnancy outcomes occurred in nine (9%) of 105 pregnancies in women with primary Sjögren's syndrome and 28 (7%) of the 420 matched control pregnancies; adverse pregnancy outcomes were not significantly associated with primary Sjögren's syndrome (odds ratio 1·31, 95% CI 0·53-2·98; p=0·52)., Interpretation: Pregnancies in women with primary Sjögren's syndrome had very good prognoses for mothers and fetuses, with no overall increase in adverse pregnancy outcome risk compared with the general population. Women with antiphospholipid antibodies or anti-RNP antibodies require close monitoring, because these factors might be associated with a higher risk of adverse pregnancy outcomes., Funding: Lupus France, Association des Sclérodermiques de France, Association Gougerot Sjögren, Association Francophone Contre la Polychondrite Chronique Atrophiante, AFM-Telethon, Société Nationale Française de Médecine Interne, Société Française de Rhumatologie, Cochin Hospital, French Health Ministry, Fondation for Research in Rheumatology, Association Prix Véronique Roualet, Union Chimique Belge., Competing Interests: Declaration of interests NC-C reports an unrestricted research grant from UCB to her institution. GN reports grants from la Société Française de Rhumatologie and Arthritis Foundation; consulting fees from Biogen, Pfizer, Novartis, Lilly, and Amgen; support for attending meetings and travel from Amgen; and is an advisory board member for Boehringer Ingelheim. AM reports an unrestricted research grant from Pfizer to her institution; consulting fees from Janssen and Gilead; and honoraria for presentations or speaker bureaus from AbbVie, Bristol Myers Squibb, Biogen, Pfizer, UCB, and Lilly; support from AbbVie, Janssen, Bristol Myers Squibb, and Pfizer for attending meetings or travel; and is an advisory board member for Janssen and UCB. CR reports consulting fees from Novartis and UCB. MM received grants from GSK and received support for travel and attending meetings from Novartis and LFB. LR reports support for attending meetings from Novartis and Otsuka. XM reports consulting fees from AstraZeneca, Bristol Myers Squibb, Galapagos, GlaxoSmithKline, Novartis, and Pfizer. VLG reports honoraria for presentations or speaker bureaus from Bristol Myers Squibb; consulting fees from Novartis; and support from AstraZeneca–MedImmune for attending meetings and travel. RS reports consulting fees from GlaxoSmithKline, Bristol Myers Squibb, Boehringer Ingelheim, and Janssen; honoraria for presentations or speaker bureaus from GlaxoSmithKline, Bristol Myers Squibb, Fresenius Kabi, Boehringer Ingelheim, Janssen, Pfizer, and Roche; and support for attending meetings and travel from Amgen and GlaxoSmithKline. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: To assess the indications, efficiency and tolerance profiles of methotrexate (MTX) in patients with giant cell arteritis (GCA) in a real-life setting., Methods: From a monocentric database of >500 GCA patients, we retrospectively selected 49 patients who received MTX between 2010 and 2020. Cumulative glucocorticoid (GC) doses, the number of relapses and GC-related adverse events were recorded before, during and after MTX. We separately analyzed the 3 main indications of MTX, i.e., disease relapse, GC-sparing strategy, and GCA presentation., Results: With a median follow-up of 84 [10-255] months, 25 (51%) and 18/41 (44%) patients relapsed during MTX treatment and after its discontinuation, respectively. Among the 40 patients who relapsed before MTX, 26 (65%) experienced a new relapse after MTX introduction. Once MTX was introduced, 24 (49%) patients were able to discontinue GC after 20.5 [7-64] months. No significant difference in cumulative GC doses were noted before and after MTX introduction with a total GC dose of 14.7 [1.05-69.4] grams. At the last follow-up, MTX was discontinued in 41 patients, including 13 (32%) due to clinicobiological remission, 12 (30%) due to treatment failure and 15 (36%) due to side effects., Conclusion: Our real-life study showed a modest beneficial effect of MTX on relapse in patients with GCA. However, we did not observe any GC-sparing effect in this study. Other studies are needed to assess the GC-sparing effect in patients in whom GC management is adapted from recent recommendations., Competing Interests: Declarations of Competing Interest None., (Copyright © 2023. Published by Elsevier Inc.)

Atom fruit ( Dacryodes macrophylla ) is a Non-timber Forest Product (NTFP) that comprises a large seed, thick pulp, and a thin hard outer covering. The structural component of its cell wall and thick pulp make it difficult in extracting the juice. Also, Dacryodes macrophylla fruit is greatly underutilized, therefore the need to process and transform it into other value-added products. This work aims to enzymatically extract juice from Dacryodes macrophylla fruit with the aid of pectinase, ferment and test the acceptability of wine produced from this extract. The enzyme and non-enzyme treatments were carried out under the same conditions and their physicochemical properties such as pH, juice yield, total soluble solids, and Vitamin C were compared. A central composite design was used for the optimization of the processing factors for the enzyme extraction process. Enzyme treatment had a great impact on the juice yield (%) and Total soluble solids (TSS) ( 0 Brix) of samples as it was as high as 81 ± 0.7% and 10.6 ± 0.02 0 Brix whereas, that of the non-enzyme treatments were 46 ± 0.7% and 9.5 ± 0.02 0 Brix respectively. However, the Vitamin C content of enzyme-treated juice decreased to 11.32 ± 0.13 mg/ml as compared to that of the non-enzyme-treated juice sample (15.7 ± 0.04 mg/ml). The optimum processing condition in the extraction of juice from the atom fruit was 1.84% enzyme concentration, 49.02 ֯C Incubation temperature, and 43.58 min Incubation time. During wine processing within 14 days of primary fermentation, the pH of the must decreased from 3.42 ± 0.07 to 3.26 ± 0.07 whereas the Titratable acidity (TA) increased from 0.16 ± 0.05 to 0.51 ± 0.0. The wine produced from Dacryodes macrophylla fruit showed promising results as its sensorial scores for all attributes including color, clarity, flavor, mouthfeel, alcoholic burn after taste and overall acceptability were all above 5. Thus, enzymes can be used to improve the juice yield of Dacryodes macrophylla fruit and hence, can be a potential bioresource for wine production., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (© 2023 The Authors.)

In this research, scallops ( Argopecten purpuratus ) visceral meal (SVM) and defatted meal (SVMD) were analysed for their proximal composition, protein solubility, and amino acid profile. Hydrolysed proteins isolated from the scallop's viscera (SPH) were optimised and characterised using response surface methodology with a Box-Behnken design. The effects of three independent variables were examined: temperature (30-70 °C), time (40-80 min), and enzyme concentration (0.1-0.5 AU/g protein) on the degree of hydrolysis (DH %) as a response variable. The optimised protein hydrolysates were analysed for their proximal composition, yield, DH %, protein solubility, amino acid composition, and molecular profile. This research showed that defatted and isolation protein stages are not necessaries to obtain the hydrolysate protein. The conditions of the optimization process were 57 °C, 62 min and 0.38 AU/g protein. The amino acid composition showed a balanced profile since it conforms to the Food and Agriculture Organisation/World Health Organisation recommendations for healthy nutrition. The predominant amino acids were aspartic acid + asparagine, glutamic acid + Glutamate, Glycine, and Arginine. The protein hydrolysates' yield and DH % were higher than 90% and close to 20%, respectively, with molecular weight between 1-5 kDa. The results indicate that the protein hydrolysates of scallops ( Argopecten purpuratus ) visceral by product optimised and characterised was suitable a lab-scale. Further research is necessary to study the bioactivity properties with biologic activity of these hydrolysates.

Background: Instrumental variables (IVs) can be used to provide evidence as to whether a treatment has a causal effect on an outcome . Even if the instrument satisfies the three core IV assumptions of relevance, independence, and exclusion restriction, further assumptions are required to identify the average causal effect (ACE) of on . Sufficient assumptions for this include homogeneity in the causal effect of on ; homogeneity in the association of with ; and no effect modification., Methods: We describe the no simultaneous heterogeneity assumption, which requires the heterogeneity in the - causal effect to be mean independent of (i.e., uncorrelated with) both and heterogeneity in the - association. This happens, for example, if there are no common modifiers of the - effect and the - association, and the - effect is additive linear. We illustrate the assumption of no simultaneous heterogeneity using simulations and by re-examining selected published studies., Results: Under no simultaneous heterogeneity, the Wald estimand equals the ACE even if both homogeneity assumptions and no effect modification (which we demonstrate to be special cases of-and therefore stronger than-no simultaneous heterogeneity) are violated., Conclusions: The assumption of no simultaneous heterogeneity is sufficient for identifying the ACE using IVs. Since this assumption is weaker than existing assumptions for ACE identification, doing so may be more plausible than previously anticipated., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Mechanical ventilation has side effects such as ventilator-induced diaphragm dysfunction, resulting in prolonged intensive care unit length of stays. Artificially evoked diaphragmatic muscle contraction may potentially maintain diaphragmatic muscle function and thereby ameliorate or counteract ventilator-induced diaphragm dysfunction. We hypothesized that bilateral non-invasive electromagnetic phrenic nerve stimulation (NEPNS) results in adequate diaphragm contractions and consecutively in effective tidal volumes., Results: This single-centre proof-of-concept study was performed in five patients who were 30 [IQR 21-33] years old, 60% (n = 3) females and undergoing elective surgery with general anaesthesia. Following anaesthesia and reversal of muscle relaxation, patients received bilateral NEPNS with different magnetic field intensities (10%, 20%, 30%, 40%); the stimulation was performed bilaterally with dual coils (connected to one standard clinical magnetic stimulator), specifically designed for bilateral non-invasive electromagnetic nerve stimulation. The stimulator with a maximal output of 2400 Volt, 160 Joule, pulse length 160 µs at 100% intensity was limited to 50% intensity, i.e. each single coil had a maximal output of 0.55 Tesla and 1200 Volt. There was a linear relationship between dosage (magnetic field intensity) and effect (tidal volume, primary endpoint, p < 0.001). Mean tidal volume was 0.00, 1.81 ± 0.99, 4.55 ± 2.23 and 7.43 ± 3.06 ml/kg ideal body weight applying 10%, 20%, 30% and 40% stimulation intensity, respectively. Mean time to find an initial adequate stimulation point was 89 (range 15-441) seconds., Conclusions: Bilateral non-invasive electromagnetic phrenic nerve stimulation generated a tidal volume of 3-6 ml/kg ideal body weight due to diaphragmatic contraction in lung-healthy anaesthetized patients. Further perspectives in critically ill patients should include assessment of clinical outcomes to confirm whether diaphragm contraction through non-invasive electromagnetic phrenic nerve stimulation potentially ameliorates or prevents diaphragm atrophy., (© 2023. The Author(s).)

Locoregional therapy options for CCA are used, in particular, for non-resectable tumors and aim to reduce tumor viability or delay tumor growth and ultimately prolong overall survival. In addition to local ablative procedures such as radiofrequency- or microwave-ablation, transarterial procedures such as transarterial embolization (TAE), transarterial chemoembolization (TACE), or selective internal radiotherapy (SIRT) play a major role. In particular, in combination with advances in molecular medicine and immunotherapy, there has been a further development in the therapy of primary malignant liver tumors in recent years. In this review, we analyze data from recent studies and examine the implications for therapy of CCA, particularly with regard to the combination of locoregional therapies with modern systemic therapies.

Rationale: Analysis of stable isotopes in tissue and excreta may provide information about animal diets and their nutritional state. As body condition may have a major influence on reproduction, linking stable isotope values to animal demographic rates may help unravel the drivers behind animal population dynamics., Methods: We performed sequential analysis of δ 15 N values in guard hair from 21 muskoxen (Ovibos moschatus) from Zackenberg in high arctic Greenland. We were able to reconstruct the dietary history for the population over a 5-year period with contrasting environmental conditions. We examined the linkage between guard hair δ 15 N values in 12 three-month periods and muskox calf recruitment to detect critical periods for muskox reproduction. Finally, we conducted similar analyses of the correlation between environmental conditions (snow depth and air temperature) and calf recruitment., Results: δ 15 N values exhibited a clear seasonal pattern with high levels in summer and low levels in winter. However, large inter-annual variation was found in winter values, suggesting varying levels of catabolism depending on snow conditions. In particular δ 15 N values during January-March were linked to muskox recruitment rates, with higher values coinciding with lower calf recruitment. δ 15 N values were a better predictor of muskox recruitment rates than environmental conditions., Conclusions: Although environmental conditions may ultimately determine the dietary δ 15 N signal in muskox guard hairs, muskox calf recruitment was more strongly correlated with δ 15 N values than ambient snow and temperature. The period January-March, corresponding to late gestation, appears particularly critical for muskox reproduction., (© 2023 The Authors. Rapid Communications in Mass Spectrometry published by John Wiley & Sons Ltd.)