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Purpose: Tumoral heterogeneity poses a challenge for personalized cancer treatments. Especially in metastasized cancer, it remains a major limitation for successful targeted therapy, often leading to drug resistance due to tumoral escape mechanisms. This work explores a non-invasive radiomics-based approach to capture textural heterogeneity in liver lesions and compare it between colorectal cancer (CRC) and pancreatic cancer (PDAC). Materials and methods: In this retrospective single-center study 73 subjects (42 CRC, 31 PDAC) with 1291 liver metastases (430 CRC, 861 PDAC) were segmented fully automated on contrast-enhanced CT images by a UNet for medical images. Radiomics features were extracted using the Python package Pyradiomics. The mean coefficient of variation (CV) was calculated patient-wise for each feature to quantify the heterogeneity. An unpaired t-test identified features with significant differences in feature variability between CRC and PDAC metastases. Results: In both colorectal and pancreatic liver metastases, interlesional heterogeneity in imaging can be observed using quantitative imaging features. 75 second-order features were extracted to compare the varying textural characteristics. In total, 18 radiomics features showed a significant difference (p < 0.05) in their expression between the two malignancies. Out of these, 16 features showed higher levels of variability within the cohort of pancreatic metastases, which, as illustrated in a radar plot, suggests greater textural heterogeneity for this entity. Conclusions: Radiomics has the potential to identify the interlesional heterogeneity of CT texture among individual liver metastases. In this proof-of-concept study for the quantification and comparison of imaging-related heterogeneity in liver metastases a variation in the extent of heterogeneity levels in CRC and PDAC liver metastases was shown. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate gyroscope-assisted CT-guided needle puncture (GAP) compared to free hand puncture (FHP) in a phantom. Material and Methods: A simple, low-cost gyroscope was equipped with a magnetic rail to attach it to common puncture needles. 18 radiologists with different levels of training and experience in CT-guided punctures first punctured three targets in free hand technique in a special biopsy phantom with different difficulty levels of the puncture path (T1: not angulated, needle path 7.3 cm, size 15 mm in diameter, T2: single angulated 41°, needle path 11.3 cm, size 9 mm in diameter, T3: double angulated 38°/26°, needle path 7 cm, size 8 mm in diameter). Without knowing the result of the puncture, a second puncture was performed directly afterwards with the aid of the gyroscope. Punctures were performed in a continuous procedure without intermediate control. The hit rate and the distance between the needle tip and the center of the lesion were evaluated. Additionally, the time needed for the procedure was measured. Results: Thirty-three of 54 insertions (61.1%) hit the target in GAP compared to 20 of 54 (37%) in FHP (p = 0.002). The mean distance of the needle tip to the lesion center was 7.49 ± 5.31 mm in GAP compared to 13.37 ± 10.24 mm in FHP (p < 0.001). Puncture time was not significantly different between GAP (36.72 ± 20.38 s) and FHP (37.83 ± 20.53 s) (p = 0.362). Conclusion: Needle guidance with a gyroscope enables an improved hit rate and puncture accuracy in CT-guided punctures without prolonging the puncture time. The needle guidance by gyroscope is inexpensive and easy to establish. [ABSTRACT FROM AUTHOR]

Glass fiber reinforced plastics (GFRP) are essential for lightweight design and are manufactured in high quantities. Since there is no suitable method for recycling, the GFRP are mostly grinded and used as filler at end of life. In this work, the well-known principle of debonding on demand is considered to enable feasible and value-retaining separation of glass fibers from the polymeric matrix. To this end, gas-releasing thermo-responsive substances (TRS) like carboxylic or amino acids are introduced to the composite to investigate their potential for causing delamination after heating. To promote sufficient fiber/matrix adhesion, the TRS are encapsulated with silica or immobilized on magnetite particles. Furthermore, the immobilization synthesis is scaled up by using a custom-made continuous flow reactor. Finally, a new sizing mixed for glass fiber spinning, containing the particles, is formulated. The experiments reveal that a maximum of 0.5 wt.% particles can be used in the sizing to coat the fibers. Although all tested samples show a significant organic functionalization, the particles functionalized with TRS do not trigger sufficient delamination at the current state of development. [ABSTRACT FROM AUTHOR]

Background: The risk for recurrence in patients with distal gastric cancer can be reduced by surgical radicality. However, dispute exists about the value of the proposed minimum proximal margin distance (PMD). Here, we assess the prognostic value of the safety distance between the proximal resection margin and the tumor. Patients and Methods: This is a single-center cohort study of patients undergoing distal gastrectomy for gastric adenocarcinoma (2001–2021). Cohorts were defined by adequacy of the PMD according to the European Society for Medical Oncology (ESMO) guidelines (≥ 5 cm for intestinal and ≥ 8 cm for diffuse Laurén's subtypes). Overall survival (OS) and time to progression (TTP) were assessed by log-rank and multivariable Cox-regression analyses. Results: Of 176 patients, 70 (39.8%) had a sufficient PMD. An adequate PMD was associated with cancer of the intestinal subtype (67% vs. 45%, p = 0.010). Estimated 5-year survival was 63% [95% confidence interval (CI) 51–78] and 62% (95% CI 53–73) for adequate and inadequate PMD, respectively. Overall, an adequate PMD was not prognostic for OS (HR 0.81, 95% CI 0.48–1.38) in the multivariable analysis. However, in patients with diffuse subtype, an adequate PMD was associated with improved oncological outcomes (median OS not reached versus 131 months, p = 0.038, median TTP not reached versus 88.0 months, p = 0.003). Conclusion: Patients with diffuse gastric cancer are at greater risk to undergo resection with an inadequate PMD, which in those patients is associated with worse oncological outcomes. For the intestinal subtype, there was no prognostic association with PMD, indicating that a distal gastrectomy with partial preservation of the gastric function may also be feasible in the setting where an extensive PMD is not achievable. [ABSTRACT FROM AUTHOR]

Purpose: Even today, it remains a challenge for healthcare professionals to decide whether a clinically stable patient who is recovering from uncomplicated medium or major surgery would benefit from a postoperative intensive care unit (ICU) admission, or whether they would be at least as adequately cared for by a few hours of monitoring in the post-operative care unit (PACU). Methods: In this monocentric retrospective observational study, all adult patients who (Deutsche Gesellschaft für Anästhesiologie und Intensivmedizin (DGAI) in Anästh Intensivmed (50):S486–S489, 2009) underwent medium or major surgery between 1 January 1 2014 and 31 December 2018 at the Heidelberg University Surgical Center, and (Vimlati et al. in Eur J Anaesthesiol September 26(9):715–721, 2009) were monitored for 1–12 h in the PACU, and then (De Pietri et al. in World J Gastroenterol 20(9):2304–23207, 2014) transferred to a normal ward (NW) immediately thereafter were included. At the end of the PACU stay, each patient was cleared by both a surgeon and an anesthesiologist to be transferred to a NW. The first objective of this study was to determine the prevalence of relevant early complications (RECs) within the first 24 h on a normal ward. The secondary objective was to determine the prevalence of RECs in the subgroup of included patients who underwent partial pancreaticoduodenectomy. Results: A total of 10,273 patients were included in this study. The prevalence of RECs was 0.50% (confidence interval [CI] 0.40–0.60%), with the median length of stay in the PACU before the patient's first transfer to a NW being 285 min (interquartile range 210–360 min). In the subgroup of patients who underwent partial pancreaticoduodenectomy (n = 740), REC prevalence was 1.1% (CI = 0.55–2.12%). Conclusion: Based on a medical case-by-case assessment, it is possible to select patients who after a PACU stay of only up to 12 h have a low risk of emergency readmission to an ICU within the 24 h following the transfer to the NW. Continued research will be needed to further improve transfer decisions in such low-risk subgroups. [ABSTRACT FROM AUTHOR]

Considerable attention has been devoted to the concept of flexible emotion regulation, which de-emphasizes the importance of any specific regulatory strategy in favor of the flexible deployment of strategies in response to specific situational challenges. The bulk of research in this area has been conducted on adult samples. Research on emotion regulation flexibility (ERF) in youth has been documented in only a limited number of studies and using various definitions. This systematic review aims to gather and summarize different conceptualizations and methodological approaches of adolescent ERF. We incorporate these findings into a general framework to understand ERF and its role in adolescents' emotional, behavioral and social functioning. Adhering to the PRISMA guidelines, 11 studies were included in the review. While ERF has been defined in various and inconsistent ways, the included studies utilized conceptualizations from two overarching domains: the regulation of expressed emotion and the repertoire of emotion regulation strategies. Promising approaches and future directions will be highlighted. [ABSTRACT FROM AUTHOR]

Purpose: Uterine serous carcinoma (USC) is a highly aggressive and frequently recurring subtype of endometrial cancer with limited treatment options for advanced or recurrent stages. Sulindac, a classic non-steroidal anti-inflammatory drug, has demonstrated anti-tumor activity in several pre-clinical tumor models. This study aims to evaluate the effect of sulindac on cell proliferation and invasion in USC cells. Methods: Human USC cell lines ARK-1 and SPEC2 were treated with different concentrations of sulindac. Cell proliferation was assessed using MTT and colony formation assays. ELISA assays measured cellular stress, cleaved caspase 3 activity, antioxidant ability, and adhesion. Cell cycle arrest was evaluated by Cellometer. The invasive capability was detected by wound healing assay. Western blotting was used to analyze the changes in protein expression induced by sulindac. Results: Exposure to sulindac decreased cellular viability in a dose-dependent manner in ARK-1 and SPEC2 cells. Sulindac effectively inhibited cell cycle progression, increased cellular stress, caused apoptosis, and reduced cell adhesion and invasion in USC cells. Additionally, sulindac decreased the expression of COX-2 and blocked phosphorylation of NF-κB induced by TNF-α. Conclusion: Sulindac is a potential therapeutic agent for USC that deserves further exploration in pre-clinical studies and potentially future clinical trials. [ABSTRACT FROM AUTHOR]

Wearable sensor technologies are becoming increasingly relevant in health research, particularly in the context of chronic disease management. They generate real-time health data that can be translated into digital biomarkers, which can provide insights into our health and well-being. Scientific methods to collect, interpret, analyze, and translate health data from wearables to digital biomarkers vary, and systematic approaches to guide these processes are currently lacking. This paper is based on an observational, longitudinal cohort study, BarKA-MS, which collected wearable sensor data on the physical rehabilitation of people living with multiple sclerosis (MS). Based on our experience with BarKA-MS, we provide and discuss ten lessons we learned in relation to digital biomarker development across key study phases. We then summarize these lessons into a guiding framework (DACIA) that aims to informs the use of wearable sensor data for digital biomarker development and chronic disease management for future research and teaching. [ABSTRACT FROM AUTHOR]

Increasing rates of autoimmune and inflammatory disease present a burgeoning threat to human health1. This is compounded by the limited efficacy of available treatments1 and high failure rates during drug development2, highlighting an urgent need to better understand disease mechanisms. Here we show how functional genomics could address this challenge. By investigating an intergenic haplotype on chr21q22—which has been independently linked to inflammatory bowel disease, ankylosing spondylitis, primary sclerosing cholangitis and Takayasu’s arteritis3–6—we identify that the causal gene, ETS2, is a central regulator of human inflammatory macrophages and delineate the shared disease mechanism that amplifies ETS2 expression. Genes regulated by ETS2 were prominently expressed in diseased tissues and more enriched for inflammatory bowel disease GWAS hits than most previously described pathways. Overexpressing ETS2 in resting macrophages reproduced the inflammatory state observed in chr21q22-associated diseases, with upregulation of multiple drug targets, including TNF and IL-23. Using a database of cellular signatures7, we identified drugs that might modulate this pathway and validated the potent anti-inflammatory activity of one class of small molecules in vitro and ex vivo. Together, this illustrates the power of functional genomics, applied directly in primary human cells, to identify immune-mediated disease mechanisms and potential therapeutic opportunities.ETS2—which is associated with inflammatory bowel disease, ankylosing spondylitis, primary sclerosing cholangitis and Takayasu’s arteritis—is a central regulator of human inflammatory macrophages. [ABSTRACT FROM AUTHOR]

Opinion statement: Dysphagia, difficulty in eating and drinking, remains the most common side effect of radiotherapy treatment for head and neck cancer (HNC) with devastating consequences for function and quality of life (QOL). Over the past decade, 5-year survival has improved due to multiple factors including treatment advances, reduction in smoking, introduction of the human papillomavirus (HPV) vaccine and more favourable prognosis of HPV-related cancers. Increased prevalence of HPV-positive disease, which tends to affect younger individuals, has led to an elevated number of people living for longer with the sequelae of cancer and its treatment. Symptoms are compounded by late effects of radiotherapy which may lead to worsening of dysphagia for some long-term survivors or new-onset dysphagia for others. Speech-language pathology (SLP) input remains core to the assessment and management of dysphagia following HNC treatment. In this article, we present current SLP management of dysphagia post-radiotherapy. We discuss conventional treatment approaches, the emergence of therapy adjuncts and current service delivery models. The impact of adherence on therapy outcomes is highlighted. Despite treatment advancements, patients continue to present with dysphagia which is resistant to existing intervention approaches. There is wide variation in treatment programmes, with a paucity of evidence to support optimal type, timing and intensity of treatment. We discuss the need for further research, including exploration of the impact of radiotherapy on the central nervous system (CNS), the link between sarcopenia and radiotherapy-induced dysphagia and the benefits of visual biofeedback in rehabilitation. [ABSTRACT FROM AUTHOR]

Contrast enhanced pulmonary vein magnetic resonance angiography (PV CE-MRA) has value in atrial ablation pre-procedural planning. We aimed to provide high fidelity, ECG gated PV CE-MRA accelerated by variable density Cartesian sampling (VD-CASPR) with image navigator (iNAV) respiratory motion correction acquired in under 4 min. We describe its use in part during the global iodinated contrast shortage. VD-CASPR/iNAV framework was applied to ECG-gated inversion and saturation recovery gradient recalled echo PV CE-MRA in 65 patients (66 exams) using.15 mmol/kg Gadobutrol. Image quality was assessed by three physicians, and anatomical segmentation quality by two technologists. Left atrial SNR and left atrial/myocardial CNR were measured. 12 patients had CTA within 6 months of MRA. Two readers assessed PV ostial measurements versus CTA for intermodality/interobserver agreement. Inter-rater/intermodality reliability, reproducibility of ostial measurements, SNR/CNR, image, and anatomical segmentation quality was compared. The mean acquisition time was 3.58 ± 0.60 min. Of 35 PV pre-ablation datasets (34 patients), mean anatomical segmentation quality score was 3.66 ± 0.54 and 3.63 ± 0.55 as rated by technologists 1 and 2, respectively (p = 0.7113). Good/excellent anatomical segmentation quality (grade 3/4) was seen in 97% of exams. Each rated one exam as moderate quality (grade 2). 95% received a majority image quality score of good/excellent by three physicians. Ostial PV measurements correlated moderate to excellently with CTA (ICCs range 0.52–0.86). No difference in SNR was observed between IR and SR. High quality PV CE-MRA is possible in under 4 min using iNAV bolus timing/motion correction and VD-CASPR. [ABSTRACT FROM AUTHOR]

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The word sarcopenia derives from the Greek terms "sarx" for meat and "penia" for loss, thus being used to define reductions in muscle mass, muscle strength, and lower physical performance that compromise, mainly, the elderly population. Its high negative impact on patients' quality of life encourages the production and publication of new studies that seek to find methods to prevent and reverse cases of loss of muscle mass and strength. Furthermore, the high prevalence of sarcopenia in patients with chronic kidney disease (CKD) is closely related to its pathophysiology, which consists of a state of increased protein catabolism and decreased muscle tissue synthesis. Also considering the inflammatory nature of CKD and sarcopenia, the purinergic system has been an important target of studies, which seek to relate it to the two previous conditions. This system achieves anti-inflammatory action by inhibiting, through adenosine, pro-inflammatory factors such as interleukin-12 (IL-12), tumor necrosis factor alpha (TNF-α), and nitric oxide (NO), as well as by releasing anti-inflammatory substances such as interleukin-10 (IL-10). Simultaneously, the purinergic system presents pro-inflammatory activity, signaled by adenosine triphosphate (ATP), which occurs through the activation of T cells and the release of pro-inflammatory factors such as those mentioned above. Therefore, the ability of this system to act on inflammatory processes can promote positive and negative changes in the clinical aspect of patients with CKD and/or sarcopenia. Furthermore, it appears that there is a correlation between the practice of repeated physical exercise with the clinical improvement and in the quality of life of these patients, presenting a decrease in the levels of C-reactive protein (CRP), NTPDase, and the pro-inflammatory cytokine IL-6, such as increases in IL-10 resulting from modulation of the purinergic system. In this way, the present article seeks to evaluate the effect of physical exercise as a modulator of the purinergic system in the control of sarcopenia in patients with CKD on hemodialysis, in order to trace a relationship that can bring benefits both for biological markers and for quality of life of these patients. [ABSTRACT FROM AUTHOR]

Designing materials capable of disinfecting water without releasing harmful by-products is an ongoing challenge. Here, we report a novel polycationic sponge material synthesized from chitosan derivatives and cellulose fibers, exhibiting antibacterial properties. The design of such material is based on three key principles. First, the formation of a highly porous structure through cryogelation for an extensive surface area. Second, the incorporation of cationic quaternary ammonium moieties onto chitosan to enhance bacterial adsorption and antibacterial activity. Lastly, the reinforcement of mechanical properties through integration of cellulose fibers. The presented sponge materials exhibit up to a 4-log (99.99%) reduction within 6 h against both gram-positive B. subtilis and gram-negative E. coli. Notably, QCHI90/Cell, with the highest surface charge, exhibits a 2–4.5 log reduction within 1 h of incubation time. The eco-friendly synthesis from water and readily available biomaterials, along with cost-effectiveness and simplicity, underscores its versatility and feasibility of upscaling. Together with its outstanding antibacterial activity, this macroporous biomaterial emerges as a promising candidate for water disinfection applications. [ABSTRACT FROM AUTHOR]

Despite tremendous efforts in the past decades, relationships among main avian lineages remain heavily debated without a clear resolution. Discrepancies have been attributed to diversity of species sampled, phylogenetic method and the choice of genomic regions1–3. Here we address these issues by analysing the genomes of 363 bird species4 (218 taxonomic families, 92% of total). Using intergenic regions and coalescent methods, we present a well-supported tree but also a marked degree of discordance. The tree confirms that Neoaves experienced rapid radiation at or near the Cretaceous–Palaeogene boundary. Sufficient loci rather than extensive taxon sampling were more effective in resolving difficult nodes. Remaining recalcitrant nodes involve species that are a challenge to model due to either extreme DNA composition, variable substitution rates, incomplete lineage sorting or complex evolutionary events such as ancient hybridization. Assessment of the effects of different genomic partitions showed high heterogeneity across the genome. We discovered sharp increases in effective population size, substitution rates and relative brain size following the Cretaceous–Palaeogene extinction event, supporting the hypothesis that emerging ecological opportunities catalysed the diversification of modern birds. The resulting phylogenetic estimate offers fresh insights into the rapid radiation of modern birds and provides a taxon-rich backbone tree for future comparative studies.Using intergenic regions and coalescent methods to analyse the genomes of 363 bird species, the authors present a well-supported tree confirming that Neoaves experienced rapid radiation at or near the Cretaceous–Palaeogene boundary. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "QEPro: An ability measure of emotional intelligence for managers in a French cultural environment" published in Current Psychology. The correction states that there was a text error in the original article, where the QEPro questionnaire was mistakenly referred to as having 36 items instead of 35 items. Additionally, the wrong figure and table were included in the article, and the correct versions are provided in the correction notice. The correction was reported by Christophe Haag, Lisa Bellinghausen, and Mariya Jilinskaya-Pandey. [Extracted from the article]

Coastal elevation data are essential for a wide variety of applications, such as coastal management, flood modelling, and adaptation planning. Low-lying coastal areas (found below 10 m +Mean Sea Level (MSL)) are at risk of future extreme water levels, subsidence and changing extreme weather patterns. However, current freely available elevation datasets are not sufficiently accurate to model these risks. We present DeltaDTM, a global coastal Digital Terrain Model (DTM) available in the public domain, with a horizontal spatial resolution of 1 arcsecond (∼30 m) and a vertical mean absolute error (MAE) of 0.45 m overall. DeltaDTM corrects CopernicusDEM with spaceborne lidar from the ICESat-2 and GEDI missions. Specifically, we correct the elevation bias in CopernicusDEM, apply filters to remove non-terrain cells, and fill the gaps using interpolation. Notably, our classification approach produces more accurate results than regression methods recently used by others to correct DEMs, that achieve an overall MAE of 0.72 m at best. We conclude that DeltaDTM will be a valuable resource for coastal flood impact modelling and other applications. [ABSTRACT FROM AUTHOR]

The aim was to investigate whether the "Big Five" personality traits modify the association between household income and life satisfaction (LF); and to evaluate the interaction and main effects of personality traits and income on LF. Data from the Dental Care and Oral Health Study (DCOHS, 2015–2016) was used for the cross-sectional study (n = 3,475). Multivariable Poisson regression models (adjusted for demographics and health behaviours) assessed the effect of personality traits (measured using the Ten-Item Personality Inventory) on the association between income and LF (measured by the Satisfaction With Life Scale) using prevalence ratios (PRs). The Relative Excess Risk due to Interaction (RERI) was calculated to assess the direction of effect modification. Among low-income respondents, low LF was less prevalent in those with high personality trait scores than those with low scores. The difference in the prevalence of low LF by personality traits was greater between low versus high income for openness (11.4% vs 7.7%), agreeableness (12.3% vs 9.4%) and emotional stability (26.1% vs 20.2%) categories. The combined effects of low income and low scores for these traits on LF also exceeded the sum of their individual effects, as shown by their positive RERIs. The association between low income and low LF was modified by high openness, agreeableness and emotional stability scores. Findings suggest that psychological interventions for improving LF would be most beneficial in low-income groups. [ABSTRACT FROM AUTHOR]

Synchrotron based nuclear forward scattering (NFS) experiments using the 193Ir nucleus have been performed for the first time on a dinuclear iridium(I) complex, [IrCl(COD)]2 with COD being cycloocta-1,5-diene. This complex serves as a catalyst for hydrogenation and other chemical reactions. Both, the obtained absolute values of the isomer shift δ = 0.87 mm s - 1 and the quadrupole splitting Δ E Q = 3.82 mm s - 1 agree within the experimental error with values obtained via conventional 193Ir Mössbauer spectroscopy reported earlier (Gál M. et al. J. Radioanal. Nucl. Chem., 260 (1) 2004, 133). In addition, we present density functional theory (DFT) calculations of the complex yielding its electronic structure and related Mössbauer parameters. [ABSTRACT FROM AUTHOR]

The present study elucidates heterogeneity in post-traumatic stress symptoms (PTSS) across adolescence in a sample of youth who have experienced myriad types and combinations of potentially traumatic events (PTEs), including substantiated physical abuse, sexual abuse, neglect and/or at least one other self-reported PTE. A machine learning technique was used to assess a multivariate set of variables (e.g., PTEs, individual risk and protective factors, social risk and protective factors, and racial and ethnic minority status) as predictors of PTSS trajectory group membership. The sample included 498 maltreated (n = 275) and comparison (n = 223) 14-19-year-old female adolescents (M = 15.27, SD = 1.06 at Time 1) assessed annually until age 19. 45.7% of participants were White, 45.3% Black, 0.4% Native American, 0.8% Hispanic, and 7.7% other. Growth mixture modeling identified three distinct trajectories of PTSS: (1) recovery (56%); (2) moderate, chronic (25%); and (3) high, chronic (19%). An elastic net model was used to test predictors of membership in the recovery versus the high, chronic PTSS trajectory groups. Results demonstrated that the recovery trajectory was characterized by the absence of sexual abuse, physical abuse, and other traumas, higher self-esteem, less affective dysregulation, less risky peers, lower levels of parent depression, and being of racial/ethnic minority status. Findings help to characterize individual variation in trajectories of PTSS following PTEs by underscoring the unique trauma responses of racial and ethnic minority youth and offering possible targets of interventions to promote recovery from PTSS. [ABSTRACT FROM AUTHOR]

Water-based acrylic pressure-sensitive adhesives (PSA) are a common component of disposable products such as tapes, labels, and packaging. Such adhesives are generated from fossil-derived monomers and additives and persist in the environment due to their low biodegradability. Furthermore, they can interfere with the recycling and remediation of products they interact with, such as plastic and paper products. Although touted as a promising remedy to these issues, adhesive polymers generated using renewable and degradable monomers tend to fall short regarding performance and cost. This study reports on the fungal degradation behaviors of hybrid PSAs copolymerized mainly from traditional acrylics and lactide-based macromonomers. These structures provide high performance at a reasonable cost and represent an alternative approach to addressing environmental concerns. Evaluating the biodegradability of these hybrid PSAs involved solid and liquid cultures using 53 unique fungal species. Nearly 50% (n = 23) of the screened species showed PSA-degrading capacities of varying degrees, including Trametes versicolor and Pestalotiopsis microspora, providing roughly complete (> 96%) polymer removal in liquid cultures. Fungal degradation of cast adhesive films was monitored using evolved CO2 and mass loss and confirmed through scanning electron microscopy and spectral analysis (FTIR). Enzyme assays, namely laccases, lipases, and proteases, showed a high correlation with the observed biodegradation rates, suggesting that hydrolytic and oxidative enzymes were likely factors driving latex degradation. These results demonstrate that the high-performing hybrid formulation is degradable by fungi. While a portion of the studied adhesive was synthesized using petroleum-derived monomers, this could serve as a bridge technology, helping to usher in more sustainable disposable consumer products until a time comes when all components are renewably sourced. [ABSTRACT FROM AUTHOR]

We consider the class of inclusive hadron collider processes in which one or more energetic jets are produced, possibly accompanied by colourless particles. We provide a general formulation of a slicing scheme for this class of processes, by identifying the various contributions that need to be computed up to next-to-leading order (NLO) in QCD perturbation theory. We focus on two novel observables, the one-jet resolution variable ∆Et and the n-jet resolution variable k T ness , and explicitly compute all the ingredients needed to carry out NLO computations using these variables. We contrast the behaviour of these variables when the slicing parameter becomes small. In the case of k T ness we also present results for the hadroproduction of multiple jets. [ABSTRACT FROM AUTHOR]

The MDM2 proto-oncogene (MDM2) is a primary negative regulator of p53. The latter is frequently mutated in gastric cancer (GC). In the present study, we aimed to validate gene amplification, protein expression, and the putative tumor biological function of MDM2 in a well-characterized Western GC cohort. MDM2 amplification and protein expression were studied in a cohort of 327 GCs by fluorescence in situ hybridization (FISH) and immunohistochemistry. Gene amplification and protein expression were correlated with diverse clinicopathological patient characteristics including patient outcome. Immunohistochemically, 97 GCs (29.7%) were categorized as MDM2 positive and 230 GCs (70.3%) as negative. An amplification of MDM2 was found in 11 (3.4%) cases without evidence of intratumoral heterogeneity. Nine of these eleven (81.8%) cases showed MDM2 protein expression. MDM2 amplification correlated significantly with MDM2 protein expression (p < 0.001). On a case-by-case analysis, MDM2-amplified cases showed varied histological phenotypes and were most commonly microsatellite stable; EBV, HER2, and MET negative; and FGFR2 positive. A single case harbored both, MDM2 amplification and TP53 mutation. MDM2 amplification and MDM2 expression, respectively, did not correlate with overall or tumor-specific survival. Our targeted analysis of MDM2 in a well-characterized cohort of GC patients showed that MDM2 amplification is rare, of no specific histological phenotype, and may not be always mutually exclusive with TP53 mutations. Given the low number of cases, currently, no diagnostic or therapeutic recommendation related to MDM2 amplification can be given for GC of Western origin. [ABSTRACT FROM AUTHOR]

Purpose: Despite improvements in multimodal treatment of locally advanced esophagogastric adenocarcinoma, the majority of patients still relapses. The impact of structured follow-up for early detection of recurrence is unclear and controversially discussed. Methods: Patients with locally advanced esophagogastric adenocarcinoma having received neoadjuvant/perioperative chemotherapy followed by tumor resection between 2009 and 2021, underwent a structured follow-up including three-monthly imaging during the first 2 years, followed by semiannual and annual examinations in year 3–4 and 5, respectively. Clinical outcome including pattern and time point of relapse was analyzed. Results: Two hundred fifty-seven patients were included in this analysis. In 50.2% (n = 129) of patients, recurrent disease was diagnosed, with the majority (94.6%) relapsing within the first 2 years. The most common site of relapse were lymph node metastases followed by peritoneal carcinomatosis and hepatic and pulmonary metastases. 52.7% of patients presented with symptoms at the time of relapse. Cumulative risk and time point of relapse differed significantly between patient with a node-positive tumor (ypN+) after neoadjuvant treatment (high-risk group) and patients with node-negative primary tumor (ypN0) (low-risk group). High-risk patients had a significantly inferior disease-free survival (DFS) and overall survival (OS) with 11.1 and 29.0 months, respectively, whereas median DFS and OS were not reached for the low-risk group. Conclusions: The risk of relapse differs significantly between high- and low-risk patients. Only a part of relapses is associated with clinical symptoms. An individualized follow-up strategy is recommended for high- and low-risk patients considering the individual risk of relapse. [ABSTRACT FROM AUTHOR]

Mouse models are a critical tool for studying human diseases, particularly developmental disorders1. However, conventional approaches for phenotyping may fail to detect subtle defects throughout the developing mouse2. Here we set out to establish single-cell RNA sequencing of the whole embryo as a scalable platform for the systematic phenotyping of mouse genetic models. We applied combinatorial indexing-based single-cell RNA sequencing3 to profile 101 embryos of 22 mutant and 4 wild-type genotypes at embryonic day 13.5, altogether profiling more than 1.6 million nuclei. The 22 mutants represent a range of anticipated phenotypic severities, from established multisystem disorders to deletions of individual regulatory regions4,5. We developed and applied several analytical frameworks for detecting differences in composition and/or gene expression across 52 cell types or trajectories. Some mutants exhibit changes in dozens of trajectories whereas others exhibit changes in only a few cell types. We also identify differences between widely used wild-type strains, compare phenotyping of gain- versus loss-of-function mutants and characterize deletions of topological associating domain boundaries. Notably, some changes are shared among mutants, suggesting that developmental pleiotropy might be ‘decomposable’ through further scaling of this approach. Overall, our findings show how single-cell profiling of whole embryos can enable the systematic molecular and cellular phenotypic characterization of mouse mutants with unprecedented breadth and resolution.A study reports single-cell RNA-sequencing profiles for more than 1.6 million cell nuclei from 101 whole mouse embryos including 22 mutant and 4 wild-type genotypes, from one experiment. [ABSTRACT FROM AUTHOR]

The major sources of macronutrients (nitrate, ammonium, phosphate, and silicic acid) in Jakolof Bay, Alaska are submarine groundwater discharge (SGD), rivers, and offshore water. We estimated SGD using natural geochemical tracers (radon and radium), a salt mass balance, and a two-component salinity mixing equation based on the change in groundwater salinity on falling lower low tide. Previous studies have hypothesized that the major macronutrient input into Jakolof Bay is offshore water. This study challenges that assumption by determining the relative contribution of macronutrients from SGD relative to offshore water and rivers. Here, SGD is tidally driven and, as the Northern Gulf of Alaska experiences some of the largest tidal ranges in the world, the SGD fluxes from this region are high relative to the global average regardless of local sediment type. The fluxes ranged from 596 ± 85 cm day−1 at low tide to 97 ± 83 cm day−1 at high tide and are predominantly composed of recirculated seawater (89%) rather than freshwater (11%). The major macronutrients in seawater had different input mechanisms into the semi-enclosed bay. SGD and offshore waters contend as the primary sources of nitrate, which is shown to be the limiting nutrient in this coastal area, while SGD dominates the input of silicic acid. Conversely, the aquifer is found to be a sink for phosphate, indicating that the nutrient is primarily sourced from offshore water. [ABSTRACT FROM AUTHOR]

Bacteriophages (phages) are the most abundant biological entities on Earth, exerting a significant influence on the dissemination of bacterial virulence, pathogenicity, and antimicrobial resistance. Temperate phages integrate into the bacterial chromosome in a dormant state through intricate regulatory mechanisms. These mechanisms repress lytic genes while facilitating the expression of integrase and the CI master repressor. Upon bacterial SOS response activation, the CI repressor undergoes auto-cleavage, producing two fragments with the N-terminal domain (NTD) retaining significant DNA-binding ability. The process of relieving CI NTD repression, essential for prophage induction, remains unknown. Here we show a specific interaction between the ClpX protease and CI NTD repressor fragment of phages Ф11 and 80α in Staphylococcus aureus. This interaction is necessary and sufficient for prophage activation after SOS-mediated CI auto-cleavage, defining the final stage in the prophage induction cascade. Our findings unveil unexpected roles of bacterial protease ClpX in phage biology. Prophage induction is a fundamental process in the phage life cycle. Here the authors show that the final stage of prophage induction in Staphylococcus aureus is controlled by the ClpX protease, unveiling and unexpected role for ClpX in phage biology. [ABSTRACT FROM AUTHOR]

Background: Sedentary lifestyle habits are directly related to the increase in the production of reactive oxygen species, to provide a chronic state of oxidative stress. Furthermore, the purinergic system is involved in extracellular signaling and thus influences pathological and physiological processes. Thus, physical exercise is responsible for triggering molecular and tissue changes, to condition the body's pathophysiological processes, being often suggested as a form of non-pharmacological treatment in different health conditions. Aim: To evaluate the effect of physical exercise on markers of oxidative stress and the purinergic system in young adults. Method: Sixteen women students, aged between 20 and 40 years, were submitted to the physical exercise protocol, both aerobic and resistance (concurrent training) during the period of eight weeks, making a total of 20 h of training. Results: Our findings showed that physical exercise was responsible for increasing the hydrolysis of adenosine diphosphate (ADP) (p = 0.001) and adenosine deaminase (ADA) (p = 0.041) in platelets, indicating an increase in ecto-nucleoside triphosphate diphosphohydrolase (ecto-NTPDase) after eight weeks of physical exercise. Furthermore, there was an increase in the concentration of thiobarbituric acid reactive substances (TBARS) (p = 0.012) and protein thiols (PSH) (p = 0.004) after one week of exercise. Furthermore, it can be considered that resistance exercise can stimulate the antioxidant defense mechanisms as well as promote an anti-inflammatory and anti-platelet aggregation state. Conclusion: In conclusion, physical exercise alters both the mechanisms of oxidative stress and the purinergic system, to have the potential to attenuate inflammatory mechanisms. [ABSTRACT FROM AUTHOR]

In Indonesia, the profession of counselling has a long history. Traditionally, counselling has been practiced within schools, although counsellors are beginning to practice in other contexts. However, regardless of setting, the profession has not yet established a clear and recognizable national professional identity that articulates the role of the counsellor and clearly differentiates counselling from other professions. To help create a shared national identity, the Indonesian counselling profession can implement strategies in three overarching domains: intrapersonal, intraprofessional, and interprofessional identity. Taken together, these strategies can help inform a national agenda for moving forward to create a profession that meets the needs of the Indonesian population and leads to a strong and unified national professional counsellor identity. [ABSTRACT FROM AUTHOR]

With the overnight growth in Working from Home (WFH) owing to the pandemic, organisations and their employees have had to adapt work-related processes and practices quickly with a huge reliance upon technology. Everyday activities such as social interactions with colleagues must therefore be reconsidered. Existing literature emphasises that social interactions, typically conducted in the traditional workplace, are a fundamental feature of social life and shape employees' experience of work. This experience is completely removed for many employees due to the pandemic and, presently, there is a lack of knowledge on how individuals maintain social interactions with colleagues via technology when working from home. Given that a lack of social interaction can lead to social isolation and other negative repercussions, this study aims to contribute to the existing body of literature on remote working by highlighting employees' experiences and practices around social interaction with colleagues. This study takes an interpretivist and qualitative approach utilising the diary-keeping technique to collect data from twenty-nine individuals who had started to work from home on a full-time basis as a result of the pandemic. The study explores how participants conduct social interactions using different technology platforms and how such interactions are embedded in their working lives. The findings highlight the difficulty in maintaining social interactions via technology such as the absence of cues and emotional intelligence, as well as highlighting numerous other factors such as job uncertainty, increased workloads and heavy usage of technology that affect their work lives. The study also highlights that despite the negative experiences relating to working from home, some participants are apprehensive about returning to work in the traditional office place where social interactions may actually be perceived as a distraction. The main contribution of our study is to highlight that a variety of perceptions and feelings of how work has changed via an increased use of digital media while working from home exists and that organisations need to be aware of these differences so that they can be managed in a contextualised manner, thus increasing both the efficiency and effectiveness of working from home. [ABSTRACT FROM AUTHOR]

Incorporation of melanoma prevention behaviors into daily lifestyles is difficult. Data suggest that high school educational programs on skin cancer prevention can be successful and should incorporate evidence-based teaching and learning strategies to achieve greatest impact. The goal of this systematic review is to describe evidence-based educational practices for a high-school melanoma curriculum through a comprehensive review of the literature. Ovid MEDLINE, Embase, CINAHL, and PyscINFO were searched in June 2020 for all original articles published between June 18, 1946 and June 17, 2020. All studies that used an educational curriculum to promote sun safety, skin exams, and early detection to high school students were included. A total of 25 studies with 22,683 adolescent participants were analyzed. Sixteen studies showed a significant increase in knowledge, twenty-one studies showed changes in behavior, and fifteen studies showed significant changes in attitudes. Limitations of this review include the heterogeneity of implementation and outcome reporting of educational curricula. These findings support incorporating active learning strategies as key aspects of creating an effective curriculum aimed at the prevention and early detection of melanoma. [ABSTRACT FROM AUTHOR]

Proper brain development is based on the orchestration of key neurodevelopmental processes (KNDP), including the formation and function of neural networks. If at least one KNDP is affected by a chemical, an adverse outcome is expected. To enable a higher testing throughput than the guideline animal experiments, a developmental neurotoxicity (DNT) in vitro testing battery (DNT IVB) comprising a variety of assays that model several KNDPs was set up. Gap analysis revealed the need for a human-based assay to assess neural network formation and function (NNF). Therefore, we established the human NNF (hNNF) assay. A co-culture comprised of human induced pluripotent stem cell (hiPSC)-derived excitatory and inhibitory neurons as well as primary human astroglia was differentiated for 35 days on microelectrode arrays (MEA), and spontaneous electrical activity, together with cytotoxicity, was assessed on a weekly basis after washout of the compounds 24 h prior to measurements. In addition to the characterization of the test system, the assay was challenged with 28 compounds, mainly pesticides, identifying their DNT potential by evaluation of specific spike-, burst-, and network parameters. This approach confirmed the suitability of the assay for screening environmental chemicals. Comparison of benchmark concentrations (BMC) with an NNF in vitro assay (rNNF) based on primary rat cortical cells revealed differences in sensitivity. Together with the successful implementation of hNNF data into a postulated stressor-specific adverse outcome pathway (AOP) network associated with a plausible molecular initiating event for deltamethrin, this study suggests the hNNF assay as a useful complement to the DNT IVB. [ABSTRACT FROM AUTHOR]

This work investigated the biodegradation and thermal degradation, of PLA oligomers with specific molecular weights, i.e., 800, 4000, and 10000 g/mol, coded as PLA800, PLA4000 and PLA10000, synthesized through ring-opening polymerization of lactide using defined amounts of 1,2-propanediol. From the biodegradation in soil, lower molecular weight oligomers degraded faster. The chemical changes followed through FTIR evidenced increase in OH bands, a shoulder around 1635 cm-1 due to amides bonds (N-H bending) which may be sign of enzymes and biofilm attached on the specimen surface, signs of ester bonds cleavage were also verified. Thermal degradations were investigated under nitrogen, synthetic air, and oxygen atmospheres. In general, higher heating rates provided higher thermal stability and higher degradation rates, with lower molecular weight PLA degrading faster. Distinct trends were verified under oxygen atmosphere due to complex reactions during thermal-oxidative degradation that headed to different molecular weight dependence and activation energy, which was computed using Friedman and Flynn-Ozawa-Wall (OFW) models. Friedman based activation energy is higher as it employs instantaneous rate values, and it is assumed as more realistic model, once activation energy based on OFW is derived assuming constant character along with the whole degradation and thus providing lower accuracy. [ABSTRACT FROM AUTHOR]

Compared to honeybees and bumblebees, the effect of diet on the gut microbiome of Neotropical corbiculate bees such as Melipona spp. is largely unknown. These bees have been managed for centuries, but recently an annual disease is affecting M. quadrifasciata, an endangered species kept exclusively by management in Southern Brazil. Here we report the results of a longitudinal metabarcoding study involving the period of M. quadrifasciata colony weakness, designed to monitor the gut microbiota and diet changes preceding an outbreak. We found increasing amounts of bacteria associated to the gut of forager bees 2 months before the first symptoms have been recorded. Simultaneously, forager bees showed decreasing body weight. The accelerated growth of gut-associated bacteria was uneven among taxa, with Bifidobacteriaceae dominating, and Lactobacillaceae decreasing in relative abundance within the bacterial community. Dominant fungi such as Candida and Starmerella also decreased in numbers, and the stingless bee obligate symbiont Zygosaccharomyces showed the lowest relative abundance during the outbreak period. Such changes were associated with pronounced diet shifts, i.e., the rise of Eucalyptus spp. pollen amount in forager bees' guts. Furthermore, there was a negative correlation between the amount of Eucalyptus pollen in diets and the abundance of some bacterial taxa in the gut-associated microbiota. We conclude that diet and subsequent interactions with the gut microbiome are key environmental components of the annual disease and propose the use of diet supplementation as means to sustain the activity of stingless bee keeping as well as native bee pollination services. [ABSTRACT FROM AUTHOR]

With more than 20 Food and Drug Administration (FDA)-approved poly (ethylene glycol) (PEG) modified drugs on the market, PEG is the gold standard polymer in bioconjugation. The coupling improves stability, efficiency and can prolong blood circulation time of therapeutic proteins. Even though PEGylation is described as non-toxic and non-immunogenic, reports accumulate with data showing allergic reactions to PEG. Since PEG is not only applied in therapeutics, but can also be found in foods and cosmetics, anti-PEG-antibodies can occur even without a medical treatment. Hypersensitivity to PEG thereby can lead to a reduced drug efficiency, fast blood clearance and in rare cases anaphylactic reactions. Therefore, finding alternatives for PEG is crucial. In this study, we present linear polyglycerol (LPG) for bioconjugation as an alternative polymer to PEG. We report the conjugation of LPG and PEG by click-chemistry to the glycoprotein erythropoietin (EPO), synthesized in a eukaryotic cell-free protein synthesis system. Furthermore, the influence of the polymers on EPOs stability and activity on a growth hormone dependent cell-line was evaluated. The similar characteristics of both bioconjugates show that LPGylation can be a promising alternative to PEGylation. [ABSTRACT FROM AUTHOR]

Purpose: Perioperative systemic treatment has significantly improved the outcome in locally advanced esophagogastric cancer. However, still the majority of patients relapse and die. Data on the optimal treatment after relapse are limited, and clinical and biological prognostic factors are lacking. Methods: Patients with a relapse after neoadjuvant/perioperative treatment and surgery for esophagogastric cancer were analyzed using a prospective database. Applied treatment regimens, clinical prognostic factors and biomarkers were analyzed. Results: Of 246 patients 119 relapsed. Among patients with a relapse event, those with an early relapse (< 6 months) had an inferior overall survival (OS 6.3 vs. 13.8 months, p < 0.001) after relapse than those with a late relapse (> 6 months). OS after relapse was longer in patients with a microsatellite-unstable (MSI) tumor. Systemic treatment was initiated in 87 patients (73% of relapsed pat.); among those OS from the start of first-line treatment was inferior in patients with an early relapse with 6.9 vs. 10.0 months (p = 0.037). In 27 patients (23% of relapsed pat.), local therapy (irradiation or surgical intervention) was performed due to oligometastatic relapse, resulting in a prolonged OS in comparison to patients without local therapy (median OS 35.2 months vs. 7.8 months, p < 0.0001). Multivariate analysis confirmed the prognostic benefit of the MSI status and a local intervention. Conclusion: Patients relapsing after multimodal treatment have a heterogeneous prognosis depending on the relapse-free interval (if systemic treatment applied), extent of metastatic disease as well as MSI status. The benefit of additional local intervention after relapse should be addressed in a randomized trial. [ABSTRACT FROM AUTHOR]

Term and especially preterm neonates are much more susceptible to serious bacterial infections than adults. But not only the susceptibility to infection is increased in neonates, but also their risk for developing post-inflammatory diseases such as bronchopulmonary dysplasia (BPD) and periventricular leukomalacia (PVL). This may be due to an impaired ability to terminate inflammation. In the study presented here, we aimed to investigate the proliferative response and the expression of immune-checkpoint molecules (ICM) and activation markers on neonatal T-cells in comparison to adult T-cells with the hypothesis that an increased activation of neonatal T-cells may contribute to the failure of inflammation resolution observed in neonates. We show that neonatal CD4+ and CD8+ T-cells show an increased proliferative capacity and an increased expression of activation markers compared to adult T-cells upon stimulation with OKT3 as well as a decreased expression of ICM, especially PD-L1 on their surface. This decreased expression of PD-L1 by neonatal T-cells was also observed after stimulation with GBS, but not after stimulation with E. coli, the two most important pathogens in neonatal sepsis. Expression of the T-cell receptor CD3 and the co-stimulatory molecule CD28 did not differ between adult and neonatal T-cells upon bacterial stimulation. Decreased expression of ICM upon T-cell activation may be a reason for the increased risk of neonates to develop post-inflammatory diseases. [ABSTRACT FROM AUTHOR]

In this paper, we revisit a frequently employed simplification within the WACC approach that company cost of capital k V is supposed to be invariant to the debt ratio and therefore equal to the unlevered cost k U . Even though we know from Miles and Ezzell (1980) that k V formally differs from k U , treating both costs as equal strongly facilitates the practical firm valuation e.g. when companies strategically change their target debt ratios to a significantly different magnitude after a transaction. We provide both a theoretical model and an empirical analysis using 29 firms of the German stock market to quantify the economic significance between the company cost of a levered and an otherwise identical but unlevered firm. In particular, we can numerically support the usual simplification in the absence of default risk. In case that firms are default-risky, however, empirical findings indicate a clear difference between these costs equal to 1.88 percentage points on average even for moderate assumed bankruptcy costs which translates to a company mispricing of nearly 100%. As a result, the company cost of capital does practically not depend on the debt ratio if the firm is not subject to default risk or if bankruptcy costs are negligible. Otherwise, it does and a negligence of this relationship can cause significant mispricings. [ABSTRACT FROM AUTHOR]

Drug-induced pancreatic injury (DIPI) is an issue seen in drug development both in nonclinical and clinical contexts. DIPI is typically monitored by measurement of lipase and/or amylase, however, both enzymes lack sensitivity and specificity. Although candidate protein biomarkers specific to pancreas exist, antibody-based assay development is difficult due to their small size or the rapid cleavage by proteolytic enzymes released during pancreatic injury. Here we report the development of a novel multiplexed immunoaffinity-based liquid chromatography mass spectrometric assay (IA-LC-MS/MS) for trypsinogen activation peptide (TAP) and carboxypeptidases A1 and A2 (CPA1, CPA2). This method is based on the enzymatic digestion of the target proteins, immunoprecipitation of the peptides with specific antibodies and LC-MS/MS analysis. This assay was used to detect TAP, CPA1, and CPA2 in 470 plasma samples collected from 9 in-vivo rat studies with pancreatic injury and 8 specificity studies with injury in other organs to assess their performance in monitoring exocrine pancreas injury. The TAP, CPA1, and CPA2 response was compared to histopathology, lipase, amylase and microRNA217. In summary, TAP, CPA1, and CPA2 proteins measured in rat plasma were sensitive and specific biomarkers for monitoring drug-induced pancreatic injury; outperforming lipase and amylase both by higher sensitivity of detection and by sustained increases in plasma observed over a longer time period. These protein-based assays and potentially others under development, are valuable tools for use in nonclinical drug development and as future translatable biomarkers for assessment in clinical settings to further improve patient safety. [ABSTRACT FROM AUTHOR]

Cancers have high morbidity and mortality rates worldwide. Current anticancer therapies have demonstrated specific signaling pathways as a target in the involvement of carcinogenesis. Autophagy is a quality control system for proteins and plays a fundamental role in cancer carcinogenesis, exerting an anticarcinogenic role in normal cells and can inhibit the transformation of malignant cells. Therefore, drugs aimed at autophagy can function as antitumor agents. Flavonoids are a class of polyphenolic secondary metabolites commonly found in plants and, consequently, consumed in diets. In this review, the systematic search strategy was used, which included the search for descriptors "flavonoids" AND "mTOR pathway" AND "cancer" AND "autophagy", in the electronic databases of PubMed, Cochrane Library, Web of Science and Scopus, from January 2011 to January 2021. The current literature demonstrates that flavonoids have anticarcinogenic properties, including inhibition of cell proliferation, induction of apoptosis, autophagy, necrosis, cell cycle arrest, senescence, impaired cell migration, invasion, tumor angiogenesis and reduced resistance to multiple drugs in tumor cells. We demonstrate the available evidence on the roles of flavonoids and autophagy in cancer progression and inhibition. (Registration No. CRD42021243071 at PROSPERO) [ABSTRACT FROM AUTHOR]

Managers' interest in the concept of emotional intelligence (EI) has grown steadily due to an accumulation of published articles and books touting EI's benefits. For over thirty years, many researchers have used or designed tools for measuring EI, most of which raise important psychometric, cultural and contextual issues. The aim of this article is to address some of the main limitations observed in previous studies of EI. By developing and validating QEPro we propose a new performance-based measure of EI based on a modified version of Mayer and Salovey's (1997) four-branch model. QEPro is an ability EI measure specifically dedicated to managers and business executives in a French cultural environment (N = 1035 managers and executives). In order to increase both the ecological and the face validity of the test for the target population we used the Situational Judgment Tests framework and a theory-based item development and scoring approach. For all items, correct and incorrect response options were developed using established theories from the emotion and management fields. Our study showed that QEPro has good psychometric qualities such as high measurement precision and internal consistency, an appropriate level of difficulty and a clear factorial structure. The tool also correlates in meaningful and theoretically congruent ways with general intelligence, Trait EI measures, the Big Five factors of personality, and the Affect measures used in this study. For all these reasons, QEPro is a promising tool for studying the role of EI competencies in managerial outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Oncologists are at an increased risk of developing burnout, leading to negative consequences in patient care and in professional satisfaction and quality of life. This study was designed to investigate exhaustion and disengagement among German oncologists and assess the prevalence of burnout among oncologists within different professional settings. Furthermore, we wanted to examine possible relations between sociodemographic factors, the oncological setting, professional experience and different aspects of burnout. Methods: In a cross-sectional study design, an Internet-based survey was conducted with 121 oncologists between April and July 2020 using the Oldenburg Burnout Inventory, which contains items on exhaustion, disengagement, and burnout. Furthermore, sociodemographic data of the participants were assessed. The participants were members of the Working Group Medical Oncology (Arbeitsgemeinschaft Internistische Onkologie) within the German Cancer Society. Results: The survey showed a burnout prevalence of 43.8%, which correlated with age and professional experience; that is, the prevalence is particularly high among younger oncologists. Exhaustion is closely related to employment status; that is, it was significantly higher among employed oncologists. There were remarkably low levels of disengagement among oncologists, highlighting the own demand to fulfil job requirements despite imminent or actual overburdening in daily work. Conclusion: More support is necessary to mitigate the professional stressors in the healthcare system. To ensure quality medical care, employees should be offered preventive mental health services early in their careers. [ABSTRACT FROM AUTHOR]

Purpose: According to the results of FLOT4 trial, perioperative FLOT chemotherapy improved overall survival (OS) in locally advanced, resectable esophagogastric adenocarcinoma (EGA) compared to perioperative ECF/ECX. We report real-life data 10 years after introduction of perioperative FLOT at our institution. Methods: Survival of 356 consecutive EGA patients (cT3/4 and/or cN + and/or cM1) who underwent curative surgical resection was retrospectively analysed from a prospective database. A total of 263 patients received preoperative chemotherapy according to FLOT protocol and 93 patients received an epirubicin/platinum/5FU-based regimen (EPF). Propensity score matching (PSM) according to pretretment characteristics was performed to compensate for heterogeneity between groups. Results: Median OS did not differ between groups (FLOT/EPF 52.1/46.4 months, p = 0.577). After PSM, survival was non-significantly improved after FLOT compared to EPF (median OS not reached/46.4 months, p = 0.156). Perioperative morbidity and mortality did not differ between groups. Histopathologic response rate was 35% after FLOT and 26% after EPF (p = 0.169). R0 resection could be achieved more frequently after FLOT than after EPF (93%/79%, p = 0.023). Conclusion: Overall survival after perioperative FLOT followed by surgery is comparable to clinical trials. However, collective real-life application of FLOT failed to provide a significant survival benefit compared to EPF. In clinical reality, patient selection is triggered by age, comorbidity, tumor localization, and clinical tumor stage. Yet matched analyses support FLOT4 trial findings. [ABSTRACT FROM AUTHOR]

Purpose: Sotrovimab (VIR-7831), a human IgG1κ monoclonal antibody (mAb), binds to a conserved epitope on the SARS-CoV-2 spike protein receptor binding domain (RBD). The Fc region of VIR-7831 contains an LS modification to promote neonatal Fc receptor (FcRn)–mediated recycling and extend its serum half-life. Here, we aimed to evaluate the impact of the LS modification on tissue biodistribution, by comparing VIR-7831 to its non-LS-modified equivalent, VIR-7831-WT, in cynomolgus monkeys. Methods: 89Zr-based PET/CT imaging of VIR-7831 and VIR-7831-WT was performed up to 14 days post injection. All major organs were analyzed for absolute concentration as well as tissue:blood ratios, with the focus on the respiratory tract, and a physiologically based pharmacokinetics (PBPK) model was used to evaluate the tissue biodistribution kinetics. Radiomics features were also extracted from the PET images and SUV values. Results: SUVmean uptake in the pulmonary bronchi for 89Zr-VIR-7831 was statistically higher than for 89Zr-VIR-7831-WT at days 6 (3.43 ± 0.55 and 2.59 ± 0.38, respectively) and 10 (2.66 ± 0.32 and 2.15 ± 0.18, respectively), while the reverse was observed in the liver at days 6 (5.14 ± 0.80 and 8.63 ± 0.89, respectively), 10 (4.52 ± 0.59 and 7.73 ± 0.66, respectively), and 14 (4.95 ± 0.65 and 7.94 ± 0.54, respectively). Though the calculated terminal half-life was 21.3 ± 3.0 days for VIR-7831 and 16.5 ± 1.1 days for VIR-7831-WT, no consistent differences were observed in the tissue:blood ratios between the antibodies except in the liver. While the lung:blood SUVmean uptake ratio for both mAbs was 0.25 on day 3, the PBPK model predicted the total lung tissue and the interstitial space to serum ratio to be 0.31 and 0.55, respectively. Radiomics analysis showed VIR-7831 had mean-centralized PET SUV distribution in the lung and liver, indicating more uniform uptake than VIR-7831-WT. Conclusion: The half-life extended VIR-7831 remained in circulation longer than VIR-7831-WT, consistent with enhanced FcRn binding, while the tissue:blood concentration ratios in most tissues for both drugs remained statistically indistinguishable throughout the course of the experiment. In the bronchiolar region, a higher concentration of 89Zr-VIR-7831 was detected. The data also allow unparalleled insight into tissue distribution and elimination kinetics of mAbs that can guide future biologic drug discovery efforts, while the residualizing nature of the 89Zr label sheds light on the sites of antibody catabolism. [ABSTRACT FROM AUTHOR]