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Background: Intraoperative molecular imaging (IMI) uses a cancer-targeted fluorescent agent injected into patients to localize tumor nodules. Pafolacianine is a folate receptor (FR)–targeted near-infrared fluorescent probe. Almost 10% of patients have false negative fluorescence findings intraoperatively. We hypothesized that tumor histology explains why lung cancer may not fluoresce. Methods: Adenocarcinoma (AC) (A549, LKR) and squamous cell carcinoma (SCC) (H127, H1264) cell lines were stained with pafolacianine. Near-infrared fluorescent microscopy was used to quantify mean fluorescence intensity. Tissue microarray slides of patients with AC and SCC were evaluated by immunohistochemistry for FR alpha (FRα) and beta (FRβ) expression. Finally, we retrospectively analyzed IMI data from clinical trials of patients with AC and SCC receiving pafolacianine. Results: AC (intensity 30.31) cell lines have a higher fluorescence intensity than SCC cell lines (intensity 5.4) (P < .001). On slide analysis, 93.8% of ACs expressed FRα compared with 44.4% of SCCs (P = .002). Finally, there were 326 patients enrolled in clinical trials: 211 had lesions localized in vivo, and 134 of these patients had pure AC or SCC. All 9 patients with SCC have a positive smoking history and a mean pack-year of 60.2 (SD 3,6), whereas 76% of patients with AC have a history of smoking and a mean pack-year of 29.3 (P = .02). The odds ratio for fluorescence of (AC/SCC) was 2.05 (P = .004) and 2.01 (P = .02) on univariate and multivariate logistic regression, respectively. Conclusions: During IMI with pafolacianine, a nonfluorescent nodule is more likely to be SCC than AC. AC has a high probability of fluorescing because of higher expression of FRα or FRβ, or both.

Abstract Deployment of ultracold atom interferometers (AI) into space will capitalize on quantum advantages and the extended freefall of persistent microgravity to provide high-precision measurement capabilities for gravitational, Earth, and planetary sciences, and to enable searches for subtle forces signifying physics beyond General Relativity and the Standard Model. NASA’s Cold Atom Lab (CAL) operates onboard the International Space Station as a multi-user facility for fundamental studies of ultracold atoms and to mature space-based quantum technologies. We report on pathfinding experiments utilizing ultracold 87Rb atoms in the CAL AI. A three-pulse Mach–Zehnder interferometer was studied to understand the influence of ISS vibrations. Additionally, Ramsey shear-wave interferometry was used to manifest interference patterns in a single run that were observable for over 150 ms free-expansion time. Finally, the CAL AI was used to remotely measure the Bragg laser photon recoil as a demonstration of the first quantum sensor using matter-wave interferometry in space.

Abstract Malawi experienced its deadliest Vibrio cholerae (Vc) outbreak following devastating cyclones, with >58,000 cases and >1700 deaths reported between March 2022 and May 2023. Here, we use population genomics to investigate the attributes and origin of the Malawi 2022–2023 Vc outbreak isolates. Our results demonstrate the predominance of ST69 clone, also known as the seventh cholera pandemic El Tor (7PET) lineage, expressing O1 Ogawa (~ 80%) serotype followed by Inaba (~ 16%) and sporadic non-O1/non-7PET serogroups (~ 4%). Phylogenetic reconstruction revealed that the Malawi outbreak strains correspond to a recent importation from Asia into Africa (sublineage AFR15). These isolates harboured known antimicrobial resistance and virulence elements, notably the ICEGEN/ICEVchHai1/ICEVchind5 SXT/R391-like integrative conjugative elements and a CTXφ prophage with the ctxB7 genotype compared to historical Malawian Vc isolates. These data suggest that the devastating cyclones coupled with the recent importation of 7PET serogroup O1 strains, may explain the magnitude of the 2022–2023 cholera outbreak in Malawi.

Abstract Intrinsic and extrinsic factors, including lifestyle and sun exposure, can contribute to cell senescence, which impairs skin homeostasis, that may in turn lead to skin aging. Senescent cells have a specific secretome, called the senescence-associated secretory phenotype (SASP) that includes MMPs, CXCLs and S100A8/9. Reducing the SASP with senotherapeutics is a promising strategy to reduce skin aging. Here we evaluated the effect of a formula containing niacinamide and hyaluronic acid, which are known to limit senescence and skin aging. We conducted three different studies. (1) Ex vivo explants treated with the formula had more collagen and glycosaminoglycan. (2) In a clinical trial with forty-four women, two months of treatment improved fine lines, wrinkles, luminosity, smoothness, homogeneity, and plumpness. (3) In a third study on thirty women, we treated one arm for two months and took skin biopsies to study gene expression. 101 mRNAs and 13 miRNAs were differentially expressed. We observed a likely senomorphic effect, as there was a decrease in many SASP genes including MMP12 and CXCL9 and a significant downregulation of autocrine signaling genes: S100A8 and S100A9. These pharmaco-clinical results are the first to demonstrate the senomorphic properties of an effective anti-aging formula in skin.

Objective Hypermobile Ehlers‐Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD) are characterized by joint hypermobility, joint subluxations and dislocations, hyperextensible skin, and chronic and progressive multiorgan comorbidities. Diagnosing hEDS and HSD is difficult because of variable phenotypes and unknown genetic etiology. In our clinic, we observed many patients with hEDS and HSD with a high serum level of unmetabolized folate, which suggests that hypermobility may be linked to methylenetetrahydrofolate reductase (MTHFR)–mediated folate metabolism. The present study aims to examine the prevalence of MTHFR polymorphisms, C677T and A1298C, among patients with hEDS and HSD. Methods Clinical and demographic information of patients visiting our hypermobility clinic from January 2023 to July 2023 were retrospectively reviewed. Continuous variables were reported as mean ± SD and range, whereas categorical variables were reported as total count and percentage. Results Among 157 patients, 93% of patients were female patients, 52.2% were diagnosed with hEDS, and 47.8% were diagnosed with HSD. Interestingly, 85% of the patients had MTHFR C677T and/or A1298C polymorphisms in heterozygous or homozygous state. MTHFR 677CT/TT genotype was present in 52.9% of cases, and 49.7% of patients had 1298AC/CC genotype. In addition,14% of patients with hypermobility exhibited MTHFR 677TT genotype, 10.2% showed 1298CC genotype, and 17.2% displayed combined heterozygosity, collectively representing 41.4% hypermobile patients with two copies of MTHFR variant alleles. Conclusion There is a high prevalence of MTHFR polymorphisms among patients with hypermobility, which supports the hypothesis that hypermobility may be dependent on folate status.

Abstract 137Cs is a long-lived man-made radionuclide introduced in the environment worldwide at the early beginning of the nuclear Era during atmospheric nuclear testing’s followed by the civil use of nuclear energy. Atmospheric fallout deposition of this major artificial radionuclide was reconstructed at the scale of French large river basins since 1945, and trajectories in French nuclearized rivers were established using sediment coring. Our results show that 137Cs contents in sediments of the studied rivers display a large spatial and temporal variability in response to the various anthropogenic pressures exerted on their catchment. The Loire, Rhone, and Rhine rivers were the most affected by atmospheric fallout from the global deposition from nuclear tests. Rhine and Rhone also received significant fallout from the Chernobyl accident in 1986 and recorded significant 137Cs concentrations in their sediments over the 1970–1985 period due to the regulatory releases from the nuclear industries. The Meuse River was notably impacted in the early 1970s by industrial releases. In contrast, the Seine River display the lowest 137Cs concentrations regardless of the period. All the rivers responded similarly over time to atmospheric fallout on their catchment, underlying a rather homogeneous resilience capacity of these river systems to this source of contamination.

Evaluating and selecting players to suit football clubs and decision-makers (coaches, managers, technical, and medical staff) is a difficult process from a managerial-financial and sporting perspective. Football is a highly competitive sport where sponsors and fans are attracted by success. The most successful players, based on their characteristics (criteria and sub-criteria), can influence the outcome of a football game at any given time. Consequently, the D-day of selection should employ a more appropriate approach to human resource management. To effectively address this issue, a detailed study and analysis of the available literature are needed to assist practitioners and professionals in making decisions about football player selection and hiring. Peer-reviewed journals were selected for collecting published papers between 2018 and 2023. A total of 66 relevant articles (journal articles, conference articles, book sections, and review articles) were selected for evaluation and analysis. The purpose of the study is to present a systematic literature review (SLR) on how to solve this problem and organize the published research papers that answer our four research questions.

Abstract Background Direct RNA sequencing (dRNA-seq) on the Oxford Nanopore Technologies (ONT) platforms can produce reads covering up to full-length gene transcripts, while containing decipherable information about RNA base modifications and poly-A tail lengths. Although many published studies have been expanding the potential of dRNA-seq, its sequencing accuracy and error patterns remain understudied. Results We present the first comprehensive evaluation of sequencing accuracy and characterisation of systematic errors in dRNA-seq data from diverse organisms and synthetic in vitro transcribed RNAs. We found that for sequencing kits SQK-RNA001 and SQK-RNA002, the median read accuracy ranged from 87% to 92% across species, and deletions significantly outnumbered mismatches and insertions. Due to their high abundance in the transcriptome, heteropolymers and short homopolymers were the major contributors to the overall sequencing errors. We also observed systematic biases across all species at the levels of single nucleotides and motifs. In general, cytosine/uracil-rich regions were more likely to be erroneous than guanines and adenines. By examining raw signal data, we identified the underlying signal-level features potentially associated with the error patterns and their dependency on sequence contexts. While read quality scores can be used to approximate error rates at base and read levels, failure to detect DNA adapters may be a source of errors and data loss. By comparing distinct basecallers, we reason that some sequencing errors are attributable to signal insufficiency rather than algorithmic (basecalling) artefacts. Lastly, we generated dRNA-seq data using the latest SQK-RNA004 sequencing kit released at the end of 2023 and found that although the overall read accuracy increased, the systematic errors remain largely identical compared to the previous kits. Conclusions As the first systematic investigation of dRNA-seq errors, this study offers a comprehensive overview of reproducible error patterns across diverse datasets, identifies potential signal-level insufficiency, and lays the foundation for error correction methods.

Abstract Background Increasing rates of maternal mortality and morbidity, coupled with ever-widening racial health disparities in maternal health outcomes, indicate that radical improvements need to be made in the delivery of maternity care. This study explored the provision of patient-centered maternity care from the perspective of pregnant and postpartum people; experiences of respect and autonomy were examined through the multi-dimensional contexts of identity, relational trust, and protection of informed choices. Methods We conducted primary data collection among individuals who experienced a pregnancy in the five years preceding the survey (N = 484) using the validated Mothers on Respect Index (MORi) and Mothers Autonomy in Decision Making (MADM) scale. We conducted an exploratory factor analysis (EFA) which produced three factor variables: trust, informed choice, and identity. Using these factor variables as dependent variables, we conducted bivariate and multivariate analysis to examine the relationship between these factor variables and social marginalization, as measured by race, disability, justice-involvement, and other social risk factors, such as food and housing insecurity. Results Results of our bivariate and multivariate models generally confirmed our hypothesis that increased social marginalization would be associated with decreased experiences of maternity care that was perceived as respectful and protective of individual autonomy. Most notably, AI/AN individuals, individuals who are disabled, and individuals who had at least one social risk factor were more likely to report experiencing identity-related disrespect and violations of their autonomy. Conclusions In light of the findings that emphasize the importance of patient identity in their experience in the healthcare system, patient-centered and respectful maternity care must be provided within a broader social context that recognizes unequal power dynamics between patient and provider, historical trauma, and marginalization. Provider- and facility-level interventions that improve patient experiences and health outcomes will be more effective if they are contextualized and informed by an understanding of how patients’ identities and traumas shape their healthcare experience, health-seeking behaviors, and potential to benefit from clinical interventions and therapies.

BackgroundQuality assessment of diagnostic accuracy studies (QUADAS), and more recently QUADAS-2, were developed to aid the evaluation of methodological quality within primary diagnostic accuracy studies. However, its current form, QUADAS-2 does not address the unique considerations raised by artificial intelligence (AI)–centered diagnostic systems. The rapid progression of the AI diagnostics field mandates suitable quality assessment tools to determine the risk of bias and applicability, and subsequently evaluate translational potential for clinical practice. ObjectiveWe aim to develop an AI-specific QUADAS (QUADAS-AI) tool that addresses the specific challenges associated with the appraisal of AI diagnostic accuracy studies. This paper describes the processes and methods that will be used to develop QUADAS-AI. MethodsThe development of QUADAS-AI can be distilled into 3 broad stages. Stage 1—a project organization phase had been undertaken, during which a project team and a steering committee were established. The steering committee consists of a panel of international experts representing diverse stakeholder groups. Following this, the scope of the project was finalized. Stage 2—an item generation process will be completed following (1) a mapping review, (2) a meta-research study, (3) a scoping survey of international experts, and (4) a patient and public involvement and engagement exercise. Candidate items will then be put forward to the international Delphi panel to achieve consensus for inclusion in the revised tool. A modified Delphi consensus methodology involving multiple online rounds and a final consensus meeting will be carried out to refine the tool, following which the initial QUADAS-AI tool will be drafted. A piloting phase will be carried out to identify components that are considered to be either ambiguous or missing. Stage 3—once the steering committee has finalized the QUADAS-AI tool, specific dissemination strategies will be aimed toward academic, policy, regulatory, industry, and public stakeholders, respectively. ResultsAs of July 2024, the project organization phase, as well as the mapping review and meta-research study, have been completed. We aim to complete the item generation, including the Delphi consensus, and finalize the tool by the end of 2024. Therefore, QUADAS-AI will be able to provide a consensus-derived platform upon which stakeholders may systematically appraise the methodological quality associated with AI diagnostic accuracy studies by the beginning of 2025. ConclusionsAI-driven systems comprise an increasingly significant proportion of research in clinical diagnostics. Through this process, QUADAS-AI will aid the evaluation of studies in this domain in order to identify bias and applicability concerns. As such, QUADAS-AI may form a key part of clinical, governmental, and regulatory evaluation frameworks for AI diagnostic systems globally. International Registered Report Identifier (IRRID)DERR1-10.2196/58202

Abstract Explosive volcanic eruptions represent a serious threat to agriculture in many countries. Ashfall can cause substantial damage to crops, jeopardizing farmers' livelihoods and potentially endangering food security. Previous field‐based studies have associated ash impact on crops with the deposit thickness, or, correspondingly, with the mass load. However, non‐volcanic factors, including plant traits and growth stage, also influence the vulnerability of crops to ashfall. To accurately estimate the risk of crop production loss in ash‐prone areas, it is essential to evaluate how these factors govern the impact of ash on crops. We grew leafy (lettuce, Lactuca sativa; hative d'Heverlée, and cabbage, Brassica oleracea; cabus de Chateaurenard) and bulb and root (onion, Allium cepa; blanc premier, and carrot, Daucus carota; hative d‘Oxhella) vegetables in a greenhouse and exposed them at two growth stages to simulated ash deposits ranging from 5 to 40 kg m−2. Our results confirm that crop production loss increases with higher ash mass load, reaching 27%–69% for deposits of 20–40 kg m−2. Additionally, they indicate a higher vulnerability of carrot and onion plants than previously reported. Lettuce and cabbage plants were more severely impacted by ash compared to onion and carrot plants, illustrating the role of plant traits in controlling ash interception and retention on foliage. Furthermore, the plant growth stage emerged as another vulnerability factor. Using the new impact data, we calculated a theoretical production loss in a cultivated area potentially affected by ashfall. This revealed that a significant portion of the crop production loss can be associated with low ash mass loads (5 kg m−2), emphasizing the importance of including distal regions in the impact assessment of ashfall on crops.

In Michigan, police crash reports are the primary source of data on traffic crashes. Though many aspects are very reliable, some details are difficult to observe or require subjective judgement. Injury severity, which is central to the road safety issue, unfortunately falls into the second category. The KABCO injury scale used by law enforcement classifies injuries as “possible,” “suspected minor,” and “suspected serious” which may not correspond to determinations made by medical professionals. EMS records can provide a means to improve crash injury data using medical evaluations, but these records are not linked to the police reports. This project explores the linkage of police crash reports and EMS records using both Michigan data sources from 2018 to 2021. Given the association between severity of injuries and person type, three crash subsets with high injury risk were the focus: pedestrians, bicyclists, and motorcyclists. Collectively, these person types represent 25.1% of the police reported fatalities and suspected serious injuries in Michigan in 2022 despite being only 1.2% of the crashing population. Person-level records for pedestrians, bicyclists, and motorcyclists were identified and divided into three separate datasets for each data source. EMS data events were restricted cases believed to be associated with traffic crashes using ICD-10 injury codes. Personal identifiers were not provided, so probabilistic linkage was used to link person crash records to EMS records. Event date, location, ambulance ID, and person demographic variables were utilized. Linkage rates and injury severity agreement was computed to assess differences between the two datasets.

Background Regular screening reduces mortality from colorectal cancer (CRC). The Canton of Vaud, Switzerland, has a regional screening programme offering faecal immunochemical tests (FITs) or colonoscopy. Participation in the screening programme has been low, particularly among complex patients. Patient navigation has strong evidence for increasing the CRC screening rate.Design and objective This feasibility study tested patient navigation performed by medical assistants for complex patients at an academic primary care practice.Baseline measurements A review of 328 patients’ medical charts revealed that 51% were up-to-date with screening (16% within the programme), 24% were ineligible, 5% had a documented refusal and 20% were not up-to-date, of whom 58 (18%) were complex patients.Intervention (February 2023 to May 2023) We tried to help complex patients participate in the screening programme using either in-person or telephone patient navigation. Each intervention was piloted by a physician-researcher and then performed by a medical assistant. Based on the reach, effectiveness, adoption, implementation, maintenance framework, we collected: Intervention participation and refusal, screening acceptance and completion and both patients and medical assistant acceptability (ie, qualitative interviews).Results Only 4/58 (7%) patients participated in the in-person patient navigation test phase due to scheduling problems. All four patients accepted a prescription and 2/4 (50%) completed their test. We piloted a telephone intervention to bypass scheduling issues but all patients refused a telephone discussion with the medical assistant. At two months after the last intervention, the proportion of patients up-to-date increased from 51% to 56%.Conclusion Our overall approach was resource-intensive and had little impact on the overall participation rate. It was likely not sustainable. New approaches and reimbursement for a specific patient navigator role are needed to increase CRC screening of complex patients.

La Cellule de Veille Hydrologique (CVH) de La Réunion assure la surveillance de 17 cours d’eau sur ce territoire montagneux sous climat tropical. Du fait des spécificités hydrométéorologiques de l’île et de la jeunesse de la CVH, la cellule n’affiche pas encore pour le grand public une vigilance crues à 24 h mais émet, depuis 2015 via le site www.vigicruesreunion.re, des vigilances “à réaction ou avec une faible anticipation”, qui s’apparentent à de la surveillance. Une stratégie de passage à la prévision a été mise en place depuis 2020 avec des résultats opérationnels déjà présents. Cette stratégie repose sur le croisement des résultats issus d’abaques et de deux modèles hydrologiques développés par INRAE (GRP et SMASH) alimentés par les lames d’eau observées (ANTILOPE) et prévues (AROMEOI). Les scores de performance des outils de prévision hydrologique sont jugés satisfaisants avec des perspectives qui laissent espérer le passage à une vigilance à 24 h à moyen terme.

Abstract Background Healthcare workers (HCWs) are commonly not prepared to properly communicate with D/deaf and hard of hearing (HoH) patients. The resulting communication challenges reinforce the existing barriers to accessing and benefiting from quality of care in these populations. In response, this study aimed to develop and evaluate a capacity-building intervention for HCWs to raise their awareness of D/deaf and HoH individuals’ experiences in healthcare and improve their capacity to communicate with these populations. Methods This study featured a participatory action research design using qualitative and quantitative methods. The intervention was developed and tested through 4 iterative phases. Reactions (i.e., satisfaction and perception of the intervention content, quality, appropriateness and usefulness) were assessed quantitatively and qualitatively after the intervention, whereas perceived knowledge and self-efficacy in communicating with D/deaf and HoH patients and organizational payoffs (use frequency of basic rules and tools improving communication) were quantitatively assessed before, after and 6-month post-intervention. Results Main qualitative and quantitative findings showed that the final version of the intervention reached high levels of satisfaction among participants. Next, perceived knowledge and self-efficacy scores obtained after receiving the intervention and 6 months later were significantly higher than those yielded in the initial assessment, although both scores significantly decreased at 6 months (compared to the scores obtained just after the intervention). Finally, findings showed no significant changes in organizational payoffs after receiving the intervention. Echoing these results, main qualitative findings documented that after receiving the intervention, participants felt more confident yet not more equipped to communicate with D/deaf and HoH patients. Conclusions Findings suggest that the capacity-building intervention is a promising means to sustainably increase HCWs’ perceived knowledge and self-efficacy on how communicating with D/deaf and HoH patients, although complementary approaches and follow-up intervention reminders may be necessary to enable practice changes in the working environment.

Abstract Foam formation is a massive challenge in submerged aerated bioprocesses, e.g., in beer fermentation. While the use of antifoam may easily overcome foaming at laboratory scale, it is often an unattractive solution since the challenge remains in future upscaling, as reduced mass transfer and extra steps in product purification and analytics result in increased costs. Interestingly, the number of studies tackling this challenge is relatively low, although literature suggests a range of alternatives, from avoiding foaming to means of controlling or even using foaming as an in situ product removal. Here we give an overview of the topic in five subsections. (1) We argue that a sound understanding of the molecular origin of foaming can facilitate solutions for overcoming the challenge while introducing some long-known challenges (i.e., in beer fermentation). We then review in (2) the apparent avoidance of foam formation before we in (3) summarize possibilities to reduce and control foam after its formation. Subsequently, in (4), we discuss possible solutions that take advantage of foam formation, for example, via foam fractionation for in situ product removal. Finally, in (5), we provide an overview of microbial strain engineering approaches to cope with some aspects of foaming in fermentations. With this review, we would like to sensitize and inform the interested reader while offering an overview of the current literature for the expert, particularly with regard to the foam special issue in Discover Chemical Engineering.

IntroductionFuture urban stormwater flood risk is determined by the confluence of both climate-driven changes in precipitation patterns and the effectiveness of flood mitigation systems, such as urban drainage and pump systems. This is especially true in coastal cities protected by levee systems like New Orleans, where even present-day rainfall would be enough to cause serious flooding in the absence of extensive stormwater drainage and pumping. However, while the uncertainties associated with climate change have been well studied, uncertainties in infrastructure performance and operation have received less attention.MethodsWe investigated how these interrelated sets of uncertainties drive flood risk in New Orleans using a Robust Decision Making (RDM) approach. RDM is a framework for Decision Making Under Deep Uncertainty (DMDU) that leverages simulation models to facilitate exploration across many possible futures and the identification of decision-relevant scenarios. For our work, we leveraged a detailed Storm Water Management Model (SWMM) representation of the New Orleans urban stormwater management system to examine flood depths across the city when faced with different levels of future precipitation, sea-level rise, drainage pipe obstruction, and pumping system failure. We also estimated direct flood damage for each neighborhood in the city for this scenario ensemble. These damage estimates were then subjected to vulnerability analysis using scenario discovery—a technique designed to determine which combinations of uncertainties are most stressful to the system in terms of an outcome of interest (excess flood damage).ResultsOur results suggest that key drivers of vulnerability depend on geographic scale. Specifically, we find that possible climate-driven precipitation increases are the most important determinant of vulnerability at the citywide level. However, for some individual neighborhoods, infrastructure operation challenges under present day conditions are a more significant driver of vulnerability than possible climate-driven precipitation increases.

Background: While abnormalities of liver function and imaging are common in patients with end-stage heart failure, advanced fibrosis is uncommon. Liver biopsy (LB) is used to identify advanced fibrosis in heart transplant (HT) candidates but can delay or limit access to definitive therapies and cause complications. We sought to develop and determine the utility of a clinical risk score for advanced fibrosis in HT candidates. Methods: We conducted a retrospective, single-center review of patients evaluated for HT between 2012 and 2019 (n = 1,651) and identified those who underwent LB (n = 137) as well as a matched control cohort (n = 160). Patients with congenital heart disease were excluded. All biopsies were reviewed by a liver pathologist. Univariate logistic modeling was used to identify factors predictive of advanced liver fibrosis. Simulation using synthetic data bootstraps was performed to determine the utility of using a score-based approach to trigger LB. Kaplan-Meier curves were used to assess survival. Results: We identified 32 (23%) patients with stage 0, 79 (58%) with stage 1 to 2, and 26 (19%) with stage 3 to 4/advanced fibrosis. The factor most associated with pursuit of LB was abnormal liver parenchyma on ultrasound. We found that a score combining severe tricuspid regurgitation, alcohol use, and low-density lipoprotein improved specificity and reduced the number of LBs required. We found no difference in survival at 3 years post-HT based on pre-HT fibrosis stage. Conclusions: A score composed of noninvasive factors may help reduce the number of patients who require LB for diagnosis of advanced fibrosis. Additional multicenter studies are needed to validate this score.

Summary: Background: Extended-spectrum cephalosporins (ESCs) are third and fourth generation cephalosporin antimicrobials used in humans and animals to treat infections due to multidrug-resistant (MDR) bacteria. Resistance to ESCs (ESC-R) in Enterobacterales is predominantly due to the production of extended-spectrum β-lactamases (ESBLs) and plasmid-mediated AmpC β-lactamases (AmpCs). The dynamics of ESBLs and AmpCs are changing across countries and host species, the result of global transmission of ESC-R genes. Plasmids are known to play a key role in this dissemination, but the relative importance of different types of plasmids is not fully understood. Methods: In this study, Escherichia coli with the major ESC-R genes blaCTX-M-1, blaCTX-M-15, blaCTX-M-14 (ESBLs) and blaCMY-2 (AmpC), were selected from diverse host species and other sources across Canada, France and Germany, collected between 2003 and 2017. To examine in detail the vehicles of transmission of the ESC-R genes, long- and short-read sequences were generated to obtain complete contiguous chromosome and plasmid sequences (n = 192 ESC-R E. coli). The types, gene composition and genetic relatedness of these plasmids were investigated, along with association with isolate year, source and geographical origin, and put in context with publicly available plasmid sequences. Findings: We identified five epidemic resistance plasmid subtypes with distinct genetic properties that are associated with the global dissemination of ESC-R genes across multiple E. coli lineages and host species. The IncI1 pST3 blaCTX-M-1 plasmid subtype was found in more diverse sources than the other main plasmid subtypes, whereas IncI1 pST12 blaCMY-2 was more frequent in Canadian and German human and chicken isolates. Clonal expansion also contributed to the dissemination of the IncI1 pST12 blaCMY-2 plasmid in ST131 and ST117 E. coli harbouring this plasmid. The IncI1 pST2 blaCMY-2 subtype was predominant in isolates from humans in France, while the IncF F31:A4:B1 blaCTX-M-15 and F2:A-:B- blaCTX-M-14 plasmid subtypes were frequent in human and cattle isolates across multiple countries. Beyond their epidemic nature with respect to ESC-R genes, in our collection almost all IncI1 pST3 blaCTX-M-1 and IncF F31:A4:B1 blaCTX-M-15 epidemic plasmids also carried multiple antimicrobial resistance (AMR) genes conferring resistance to other antimicrobial classes. Finally, we found genetic signatures in the regions surrounding specific ESC-R genes, identifying the predominant mechanisms of ESC-R gene movement, and using publicly available databases, we identified these epidemic plasmids from widespread bacterial species, host species, countries and continents. Interpretation: We provide evidence that epidemic resistance plasmid subtypes contribute to the global dissemination of ESC-R genes, and in addition, some of these epidemic plasmids confer resistance to multiple other antimicrobial classes. The success of these plasmids suggests that they may have a fitness advantage over other plasmid types and subtypes. Identification and understanding of the vehicles of AMR transmission are crucial to develop and target strategies and interventions to reduce the spread of AMR. Funding: This project was supported by the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR), through the Medical Research Council (MRC, MR/R000948/1), the Canadian Institutes of Health Research (CFC-150770), and the Genomics Research and Development Initiative (Government of Canada), the German Federal Ministry of Education and Research (BMBF) grant no. 01KI1709, the French Agency for food environmental and occupational health & safety (Anses), and the French National Reference Center (CNR) for antimicrobial resistance. Support was also provided by the Biotechnology and Biological Sciences Research Council (BBSRC) through the BBSRC Institute Strategic Programme Microbes in the Food Chain BB/R012504/1 and its constituent project BBS/E/F/000PR10348 (Theme 1, Epidemiology and Evolution of Pathogens in the Food Chain).

Abstract Following acute retinal damage, zebrafish possess the ability to regenerate all neuronal subtypes through Müller glia (MG) reprogramming and asymmetric cell division that produces a multipotent Müller glia-derived neuronal progenitor cell (MGPC). This raises three key questions. First, do MG reprogram to a developmental retinal progenitor cell (RPC) state? Second, to what extent does regeneration recapitulate retinal development? And finally, does loss of different retinal cell subtypes induce unique MG regeneration responses? We examined these questions by performing single-nuclear and single-cell RNA-Seq and ATAC-Seq in both developing and regenerating retinas. Here we show that injury induces MG to reprogram to a state similar to late-stage RPCs. However, there are major transcriptional differences between MGPCs and RPCs, as well as major transcriptional differences between activated MG and MGPCs when different retinal cell subtypes are damaged. Validation of candidate genes confirmed that loss of different subtypes induces differences in transcription factor gene expression and regeneration outcomes.

Abstract Background A psychometrically robust patient-reported outcome measure (PROM) to assess digital health literacy for chronic patients is needed in the context of digital health. We defined measurement constructs for a new PROM in previous studies using a systematic review, a qualitative description of constructs from patients, health professionals and an item pool identification process. This study aimed to evaluate the content validity of a digital health literacy PROM for chronic patients using an e-Delphi technique. Methods An international three-round online Delphi (e-Delphi) study was conducted among a francophone expert panel gathering academics, clinicians and patient partners. These experts rated the relevance, improvability, and self-ratability of each construct (n = 5) and items (n = 14) of the preliminary version of the PROM on a 5-point Likert scale. Consensus attainment was defined as strong if ≥ 70% panelists agree or strongly agree. A qualitative analysis of comments was carried out to describe personal coping strategies in healthcare expressed by the panel. Qualitative results were presented using a conceptually clustered matrix. Results Thirty-four experts completed the study (with 10% attrition at the second round and 5% at the third round). The panel included mostly nurses working in clinical practice and academics from nursing science, medicine, public health background and patient partners. Five items were excluded, and one question was added during the consensus attainment process. Qualitative comments describing the panel view of coping strategies in healthcare were analysed. Results showed two important themes that underpin most of personal coping strategies related to using information and communications technologies: 1) questionable patient capacity to assess digital health literacy, 2) digital devices as a factor influencing patient and care. Conclusion Consensus was reached on the relevance, improvability, and self-ratability of 5 constructs and 11 items for a digital health literacy PROM. Evaluation of e-health programs requires validated measurement of digital health literacy including the empowerment construct. This new PROM appears as a relevant tool, but requires further validation.

In humans, α-tocopherol (α-TOC) is mainly stored in adipose tissue, where it participates in preventing damages induced by inflammation and reactive oxygen species. Factors, including genetic ones, that explain adipose tissue α-TOC concentration remain poorly understood. This study, therefore, aimed to characterize the interindividual variability of adipose tissue α-TOC concentration in healthy individuals and to identify single nucleotide polymorphisms (SNPs) associated with it. The study used a randomized cross-over design with 42 healthy adult males. α-TOC concentration was measured in fasting plasma and periumbilical adipose tissue samples, both at fast and 8 h after consumption of three standard meals. Partial least squares (PLS) regression was performed to identify SNPs associated with the interindividual variability of adipose tissue α-TOC concentration. Adipose tissue α-TOC concentration was not associated with fasting plasma concentration (Pearson’s r = 0.24, 95% CI: [−0.08, 0.51]). There was a high interindividual variability of adipose tissue α-TOC concentration (CV = 61%). A PLS regression model comprising 10 SNPs in five genes (PPARG, ABCA1, BUD13, CD36, and MGLL) explained 60% (adjusted R2) of the variability of this concentration. The interindividual variability of adipose tissue α-TOC concentration in humans is due, at least partly, to SNPs in genes involved in α-TOC and triglyceride metabolism.

In September 2021 at a United Nations climate summit in New York, Xi Jinping announced that there would be no further Chinese coal-fired power plants along the Belt and Road Initiative, which stretches as far as South Africa. Instead, the Chinese operator of South Africa’s single largest Special Economic Zone proposal – in rural Makhado – and his local allies suggested that solar power could supply energy for the $10 billion project, including high-emissions industrial projects. This raised the question of whether firms engaged in mining, smelting, processing and other carbon-intensive activities would pick ‘low-hanging fruits’ within the renewable energy sector (instead of that power going into the grid for broader consumption). Their incentive is to do so, in order to safeguard the so-called Minerals-Energy Complex from Western climate sanctions – threatened, on grounds of high CO2-inputs to export products including steel, aluminium and petrochemicals. In spite of a 2022 United Nations Development Programme endorsement of the project, social and environmental resistance has intensified, but the introduction of solar power for high-emissions metal manufacturing presents a special challenge. Two techniques associated with ecological modernisation – natural capital accounting and the Social Cost of Carbon – may prove relevant to civil society critics of ‘extractivism’, in shifting the narrative further across space, time and scale.

To understand how patients perceive their experiences leading up to, during, and after a clinical trial, and the relationship these experiences had with future willingness to participate, we conducted 3 focus groups with patients who had prior clinical trial involvement (n = 25). Discussion topics included clinical trial discovery, enrollment, communication, trust, patient-centricity, and future enrollment. Patient focus groups revealed a variety of motivations for enrolling in clinical trials (eg, altruism, efficacious treatment, curiosity, desperation, etc.). Patients learned about clinical trials through trusted sources (eg, primary care physicians, patient advocacy groups) and social media. Access and uncertainty about clinical trials were barriers to enrollment. Patient-centric communication and attention given to disease states and symptom severity were valued and made patients feel genuinely cared about. Post-trial follow up and being informed of trial results were inconsistently reported by patients. Critically, patients described frustration with an overall lack of patient experience measurement. Patients identified a need to measure experiences before, during, and after clinical trials and emphasized that doing so would facilitate patient trust and overall experience.

L’article offre une série de questionnements autour des visages que peuvent prendre les communautés urbaines en s’appuyant sur une approche pluridisciplinaire. Ces différentes communautés sont ensuite analysées à partir d’un cas particulier, celui du double aménagement de la place des Terreaux à Lyon opéré en 1994 et en 2019. Le texte revient sur la notion de communautés et de communautés urbaines, décrit un contexte – celui de la place de Terreaux – avant d’analyser différentes formes de groupes urbains et leurs fondements.

Study region: Ghana, West Africa. Study focus: NASA's Prediction of Worldwide Energy Resource (NASA POWER) satellite-based reanalysis products are used for estimating the aridity index (AI) in Ghana, West Africa. The NASA estimates are compared and bias-corrected with temperature-based potential evapotranspiration estimates and rainfall data from 22 synoptic climate stations. The cumulative distribution function (CDF) matching technique was used for bias correction New Hydrological Insights for the region: The results indicated a previous 36% over-estimation of arid conditions in dryland climates and an under-estimation of wetland climate regions by the NASA POWER data compared with the station-based estimation. Post bias-correction, the satellite-based estimates showed substantial improvements, as evidenced by a correlation coefficient of R2 = 0.87. The rectified data suggests that with accurate interpretations and calibrations, satellite-based metrics can play a pivotal role in advancing hydrological studies and water resource management in West Africa Sub-region. This insight underscores the potential of satellite data in augmenting regional hydrological research, establishing a foundation for similar studies in analogous global environments.

Drought is a persistent challenge for horticulture, affecting various aspects of fruit development and ultimately fruit quality, but the effect on nutritional value has been under-investigated. Here, fruit quality was studied on six tomato genotypes and one goji cultivar under deficit irrigation (DI), from fruit composition to in vitro bioaccessibility of carotenoids. For both species, DI concentrated most health-related metabolites in fresh fruit. On a dry mass basis, DI increased total phenolic and sugar concentration, but had a negative or insignificant impact on fruit ascorbic acid, organic acid, and alcohol-insoluble matter contents. DI also reduced total carotenoids content in tomato (−18.7% on average), especially β-carotene (−32%), but not in goji berry DW (+15.5% and +19.6%, respectively). DI reduced the overall in vitro bioaccessibility of carotenoids to varying degrees depending on the compound and plant species. Consequently, mixed micelles produced by digestion of fruits subjected to DI contained either the same or lesser quantities of carotenoids, even though fresh fruits could contain similar or higher quantities. Thus, DI effects on fruit composition were species and genotype dependent, but an increase in the metabolite concentration did not necessarily translate into greater bioaccessibility potentially due to interactions with the fruit matrix

Abstract Background NPM1 is a phosphoprotein highly abundant in the nucleolus. However, additional nuclear functions have been attributed to NPM1, probably through interaction with other nuclear factors. DOT1L is one interaction partner of NPM1 that catalyzes methylation of histone H3 at lysine 79 (H3K79). DOT1L, playing functional roles in several biological processes, is known for its capability to organize and regulate chromatin. For example, DOT1L modulates DNA repeats expression within peri-nucleolar heterochromatin. NPM1 also affects peri-nucleolar heterochromatin spatial organization. However, it is unclear as of yet whether NPM1 and DOT1L functionally synergize to preserve nucleoli organization and genome stability, and generally, which molecular mechanisms would be involved. Results We characterized the nuclear function of NPM1 on peri-nucleolar heterochromatin organization. We show that (i) monomeric NPM1 interacts preferentially with DOT1L in the nucleus; (ii) NPM1 acts in concert with DOT1L to maintain each other’s protein homeostasis; (iii) NPM1 depletion results in H3K79me2 upregulation and differential enrichment at chromatin binding genes including Ezh2; (iv) NPM1 and DOT1L modulate DNA repeats expression and peri-nucleolar heterochromatin organization via epigenetic mechanisms dependent on H3K27me3. Conclusions Our findings give insights into molecular mechanisms employed by NPM1 and DOT1L to regulate heterochromatin activity and structural organization around the nucleoli and shed light on one aspect of the complex role of both proteins in chromatin dynamics.

Abstract Background Pleurectomy and decortication (PD) in malignant pleural mesothelioma has a high morbidity mostly associated with aspiration pneumonia (PNA), deep vein thrombosis (DVT), and foreign catheter sepsis. We instituted four strategies to reduce these complications and report our experience. Methods This was a retrospective review of patients who underwent PD at the University of Pennsylvania between 2015 and 2022. Our patients underwent standard of care PD in addition to tracheostomy and gastrostomy/jejunostomy tube with therapeutic anticoagulation (AC) leading up to surgery. Measured outcomes were postoperative PNA, DVT, and sepsis. The predicted risk of those same outcomes had patients not undergone the interventions was calculated based on the American College of Surgeons (ACS) surgical risk calculator (SRC). A McNemar's test was used to determine whether the risk of having PNA, DVT and sepsis differed between the two subgroups. Results Fifty‐five patients were included in the study. The mean age was 70 years (SD 6.2) with a mean of 21 (SD 19) pack‐years of smoking. PNA, DVT, and catheter‐related sepsis occurred in 12, four, and seven patients, respectively. Upon using the ACS SRC prediction model of the nonintervention group, PNA, DVT and catheter related sepsis was predicted to occur in 24 (paired data OR 5, 95% CI: 1.4–17.2; McNemar's test p = 0.008), 14 (paired data OR 3.5, 95% CI: 1.15–10.6; McNemar's test p = 0.03), and 17 (paired OR 3, 95% CI: 1.09–8.3; McNemar's test p = 0.04) patients, respectively. Discussion Patients undergoing tracheostomy creation, therapeutic AC at the time of diagnosis, and gastrostomy tube placement had a reduced risk of aspiration PNA, DVT, and catheter sepsis.

Abstract Detection of molecules is a key issue for many applications. Surface enhanced infrared absorption (SEIRA) uses arrays of resonant nanoantennas with good quality factors which can be used to locally enhance the illumination of molecules. The technique has proved to be an effective tool to detect small amount of material. However, nanoresonators can detect molecules on a narrow bandwidth so that a set of resonators is necessary to identify a molecule fingerprint. Here, we introduce an alternative paradigm and use low quality factor resonators with large radiative losses (over-coupled resonators). The bandwidth enables to detect all absorption lines between 5 and 10 μm, reproducing the molecular absorption spectrum. Counterintuitively, despite a lower quality factor, the system sensitivity is improved and we report a reflectivity variation as large as one percent per nanometer of molecular layer of PMMA. This paves the way to specific identification of molecules. We illustrate the potential of the technique with the detection of the explosive precursor 2,4-dinitrotoluene (DNT). There is a fair agreement with electromagnetic simulations and we also introduce an analytic model of the SEIRA signal obtained in the over-coupling regime.

Abstract Fluoride is recognized as a vital ion for human and animal growth because of the critical role it plays in preventing skeletal and dental problems. However, when it is ingested at a higher concentration it can cause demineralization of teeth and bones resulting in fluorosis, therefore, the production of high-adsorptive capacity material which is also cost-effective is necessary for the treatment of fluorides. In this study, aluminium foil is valorised into alumina nanoparticles. The as-prepared alumina was modified with alum in two different ratios of 1:0.5 and 1:1 (alumina to alum w/w%) and later used as adsorbents for the removal of fluoride from groundwater. The adsorbents were characterized by Fourier transform infrared spectroscopy, point of zero charge and X-ray diffraction. Different factors that influence the removal efficiency of fluorides such as pH, initial concentrations, contact time and adsorbent dosage were studied and optimized using a simulated fluoride solution. The optimum conditions obtained were used to test real groundwater. The static experiment conditions were used to calibrate a PHREEQC geochemical model which was later used to simulate the fluoride sorption onto the modified alumina at different conditions. PHREEQC was also coupled with parameter estimation software to determine equilibrium constants for the surface reactions between the fluoride species and the adsorbent in a way that the simulations accurately reflect the outcomes of laboratory experiments. Isotherm studies were carried out on the adsorbents. Both Langmuir and Freundlich's non-linear models fitted well for the equilibrium data. However, with a higher coefficient of regression and low chi-square test values, the adsorption process was more of chemisorption on a monolayer surface. Kinetic studies were also carried out by using the non-linear equations from the pseudo-first-order and pseudo-second-order models. The pseudo-second-order model fitted well for the equilibrium data. The mechanism for the fluoride ion adsorption was also studied by the intraparticle (IP) diffusion model and was found that IP was not the rate-determining factor, and therefore the most plausible mechanism for the sorption process was ion exchange or attraction of fluoride ions to the sorbent surface. The findings obtained from this research show that readily available aluminium waste could be valorised into a useful product that could be employed in the removal of fluoride from water samples, including groundwater, that may contain too much fluoride and pose a risk to the general public's health.

Abstract Rejection remains the main cause of premature graft loss after kidney transplantation, despite the use of potent immunosuppression. This highlights the need to better understand the composition and the cell-to-cell interactions of the alloreactive inflammatory infiltrate. Here, we performed droplet-based single-cell RNA sequencing of 35,152 transcriptomes from 16 kidney transplant biopsies with varying phenotypes and severities of rejection and without rejection, and identified cell-type specific gene expression signatures for deconvolution of bulk tissue. A specific association was identified between recipient-derived FCGR3A+ monocytes, FCGR3A + NK cells and the severity of intragraft inflammation. Activated FCGR3A+ monocytes overexpressed CD47 and LILR genes and increased paracrine signaling pathways promoting T cell infiltration. FCGR3A + NK cells overexpressed FCRL3, suggesting that antibody-dependent cytotoxicity is a central mechanism of NK-cell mediated graft injury. Multiplexed immunofluorescence using 38 markers on 18 independent biopsy slides confirmed this role of FcγRIII+ NK and FcγRIII+ nonclassical monocytes in antibody-mediated rejection, with specificity to the glomerular area. These results highlight the central involvement of innate immune cells in the pathogenesis of allograft rejection and identify several potential therapeutic targets that might improve allograft longevity.

V̇O2max is recognized as a key measure in exercise physiology and sports medicine. However, only 20–50% of maximal incremental exercise tests (IET) result in a plateau of V̇O2 (V̇O2pl). To our knowledge, no study has yet examined the possible difference in brain activity during an IET, in V̇O2pl and non-plateau athletes with the same V̇O2max and age. This study aimed to shed light on the central governor hypothesis, namely that the inability to reach a V̇O2pl may be dictated by the brain rather than by a peripheral physical limit. This hypothesis can now be explored using electroencephalography (EEG) during IET, measuring concomitant power in specific frequency bands. Forty-two athletes were divided into two groups: those who practiced endurance sports and those who did not, and were asked to perform an IET. EEG signals and gas exchange were recorded. A V̇O2pl was observed in twenty-two subjects (52%). EEG power increased in all subjects during IET, except in the alpha band, which showed variability, but not significantly (64% increase, 34% decrease, p = 0.07). No differences were found between endurance athletes and non-endurance athletes, except for V̇O2max (60.10 ± 6.16 vs. 51.77 ± 6.41, p < 0.001). However, the baseline-corrected ratio of EEG power to V̇O2 was found to decrease in all subjects during IET, in the alpha, beta and theta bands. In conclusion, the presence or absence of a V̇O2pl is not related to the type of EEG response during an IET. Nevertheless, the decline in brain and V̇O2 powers/ratios in all frequency bands suggests that aerobic power may be constrained by brain mobilization.

Abstract Background Salmonella enterica serovar Typhi (Salmonella Typhi) is the cause of typhoid fever. Salmonella Typhi may be transmitted through shedding in the stool, which can continue after recovery from acute illness. Shedding is detected by culturing stool, which is challenging to co-ordinate at scale. We hypothesised that sero-surveillance would direct us to those shedding Salmonella Typhi in stool following a typhoid outbreak. Methods In 2016 a typhoid outbreak affected one in four residents of a Nursing School in Malosa, Malawi. The Department of Health asked for assistance to identify nursing students that might spread the outbreak to other health facilities. We measured IgG antibody titres against Vi capsular polysaccharide (anti-Vi IgG) and IgM / IgG antibodies against H:d flagellin (anti-H:d) three and six months after the outbreak. We selected participants in the highest and lowest deciles for anti-Vi IgG titre (measured at visit one) and obtained stool for Salmonella culture and PCR. All participants reported whether they had experienced fever persisting for three days or more during the outbreak (in keeping with the WHO definitions of ‘suspected typhoid’). We tested for salmonellae in the Nursing School environment. Results We obtained 320 paired serum samples from 407 residents. We cultured stool from 25 residents with high anti-Vi IgG titres and 24 residents with low titres. We did not recover Salmonella Typhi from stool; four stool samples yielded non-typhoidal salmonellae; one sample produced a positive PCR amplification for a Salmonella Typhi target. Median anti-Vi and anti-H:d IgG titres fell among participants who reported persistent fever. There was a smaller fall in anti-H:d IgG titres among participants who did not report persistent fever. Non-typhoidal salmonellae were identified in water sampled at source and from a kitchen tap. Conclusion High titres of anti-Vi IgG did not identify culture-confirmed shedding of Salmonella Typhi. There was a clear serologic signal of recent typhoid exposure in the cohort, represented by waning IgG antibody titres over time. The presence of non-typhoidal salmonellae in drinking water indicates sub-optimal sanitation. Developing methods to detect and treat shedding remains an important priority to complement typhoid conjugate vaccination in efforts to achieve typhoid elimination.

Abstract Background Cognitive and implicit biases negatively impact clinicians’ decision-making capacity and can have devastating consequences for safe, effective, and equitable healthcare provision. Internationally, health care clinicians play a critical role in identifying and overcoming these biases. To be workforce ready, it is important that educators proactively prepare all pre-registration healthcare students for real world practice. However, it is unknown how and to what extent health professional educators incorporate bias training into curricula. To address this gap, this scoping review aims to explore what approaches to teaching cognitive and implicit bias, for entry to practice students, have been studied, and what are the evidence gaps that remain. Methods This scoping review was guided by the Joanna Briggs Institute (JBI) methodology. Databases were searched in May 2022 and included CINAHL, Cochrane, JBI, Medline, ERIC, Embase, and PsycINFO. The Population, Concept and Context framework was used to guide keyword and index terms used for search criteria and data extraction by two independent reviewers. Quantitative and qualitative studies published in English exploring pedagogical approaches and/or educational techniques, strategies, teaching tools to reduce the influence of bias in health clinicians' decision making were sought to be included in this review. Results are presented numerically and thematically in a table accompanied by a narrative summary. Results Of the 732 articles identified, 13 met the aim of this study. Most publications originated from the United States (n=9). Educational practice in medicine accounted for most studies (n=8), followed by nursing and midwifery (n=2). A guiding philosophy or conceptual framework for content development was not indicated in most papers. Educational content was mainly provided via face-to-face (lecture/tutorial) delivery (n=10). Reflection was the most common strategy used for assessment of learning (n=6). Cognitive biases were mainly taught in a single session (n=5); implicit biases were taught via a mix of single (n=4) and multiple sessions (n=4). Conclusions A range of pedagogical strategies were employed; most commonly, these were face-to-face, class-based activities such as lectures and tutorials. Assessments of student learning were primarily based on tests and personal reflection. There was limited use of real-world settings to educate students about or build skills in biases and their mitigation. There may be a valuable opportunity in exploring approaches to building these skills in the real-world settings that will be the workplaces of our future healthcare workers.

Abstract Background Malignant pleural mesothelioma (MPM) is an aggressive cancer of the cells lining the pleural cavity with a low overall incidence. The National Cancer Database (NCDB) released in August 2022 updated data that reflect the newest trends in MPM. Methods The NCDB was queried for patients diagnosed with MPM between 2004 and 2020. Variables collected included demographics, tumor characteristics, and treatment. Student's t‐test and independent‐samples proportions test were used for means analysis. Survival was assessed by the Kaplan–Meier method using SPSS version 28. Results A total of 41,074 patients were diagnosed with mesothelioma, with a steady incidence (0.25%) between 2004 and 2017. The mean age of diagnosis was 70 (SD 13). 73.2% of the patients were males, 69% had no comorbidities, and 93.3% were white. More patients were diagnosed at Stage 1 after 2008 (p

Abstract Social media has created new opportunities to map cultural ecosystem services (CES) related to biodiversity at large scales. However, using these novel data to understand people's preferences in relation to these CES remains a challenge. To address this, we trained a deep learning model to capture people's interactions with selected flora and fauna on Flickr as a cultural service related to biodiversity and compared this with citizen science data on iNaturalist, with photos of individual species considered as human–species interactions. After mapping the distribution of people's interactions in Great Britain on Flickr and iNaturalist, we find significant spatial differences in people's preferences on the two platforms. Using a second, pretrained deep learning model, we were also able to identify different preferences for species groups such as birds on social media versus citizen science. To better understand people's preferences, we also compared people's interactions with species richness and abundance for a group of 36 bird species, sometimes finding large differences between people's interactions and these ecological measures. Our findings demonstrate that social media can be used to include a wider range of preferences in CES assessments along‐side citizen science data. However, these preferences reflect only a limited first‐hand experience of biodiversity. Read the free Plain Language Summary for this article on the Journal blog.

Introduction : Ces dernières années, le développement de biomatériaux à faible impact environnemental a attiré un intérêt croissant. Dans ce contexte, les nanoparticules lipidiques ont émergé comme une solution privilégiée dans la recherche et l'industrie. L'objectif de cette étude était de mettre au point des émulsions Pickering O/W stabilisées exclusivement par des nanoparticules lipidiques solides (SLNs). Ces émulsions de Pickering sont une nouvelle génération de transporteurs lipidiques, à la fois sûrs, non toxiques, biocompatibles et sensibles à la température. Matériel et Méthodes : La première partie de l'étude se concentre sur la compréhension du comportement interfacial des SLNs et les mécanismes de stabilisation associés aux nanoémulsions formulées par ultrasons. Les recherches ont exploré la couverture de surface en fonction des fractions volumiques des phases dispersées et de la taille des SLNs. La deuxième partie de l'étude aborde l'adsorption des SLNs à une interface modèle entre l'huile et l'eau, en évaluant la tension superficielle et la rhéologie. Cela a été réalisé au moyen d'une analyse de la forme d'une goutte axi-symétrique (à l'aide d'un tensiomètre de goutte), en suivant l'évolution de la tension interfaciale et du comportement rhéologique. Résultats : Ces expériences ont démontré de manière concluante que la stabilisation des nanogouttelettes est effectivement assurée par les nanoparticules, tout en mettant en lumière les limites de cette formulation. La caractérisation des dimensions et de la morphologie des émulsions a permis de confirmer nos hypothèses. Par ailleurs, nous avons procédé à la caractérisation du phénomène régissant les interactions entre les nanogouttelettes et l'interface, tout en décrivant le comportement rhéologique de la monocouche de SLNs à l'interface. Conclusion : En conclusion, les émulsions de Pickering stabilisées par les SLNs se révèlent être des nano-transporteurs de médicaments innovants et très efficaces. Elles ouvrent ainsi de nouvelles perspectives en tant que système de délivrance de médicaments sensible à la température.

ABSTRACT Many strains have been used and selected by the food industry for their capacities to ferment, produce flavors, or produce heterologous molecules. Very little is known about the diversity of foodborne yeasts and their potential effect on gut microbiota and gut health. We initiated a complete characterization of five strains belonging to five species with a long history of safe use in food: Cyberlindnera jadinii, Debaryomyces hansenii, Kazachstania unispora, Kluyveromyces lactis, and Pichia membranifaciens, with a focus on their capacity to protect against gut inflammation using an in vivo dextran sodium sulfate-induced colitis model in mice. C. jadinii and K. lactis living cells showed a clear reduction in mouse sensitivity to colitis in vivo. Interestingly, we observed that C. jadinii had the capacity to survive transit in the gut, while K. lactis did not. We demonstrated that C. jadinii was unable to efficiently adhere to epithelial cells and did not survive more than 24 to 48 h in the gut. Transcriptomic analysis using NanoString technology suggested a potential role of IL-8 through Mif and Fkbp5 in the effect of C. jadinii on the immune system. Bacterial and fungal microbiota characterization showed a modification of both microbiota after C. jadinii treatment, with a significant increase in positive microorganisms and a decrease in pathobionts. Altogether, these data suggest that both C. jadinii and K. lactis strains have potential as probiotic yeast strains to fight against inflammation in the gut, but further studies are needed to understand the mechanisms by which these strains act on gut health.IMPORTANCEThe food industry has always used many strains of microorganisms including fungi in their production processes. These strains have been widely characterized for their biotechnological value, but we still know very little about their interaction capacities with the host at a time when the intestinal microbiota is at the center of many pathologies. In this study, we characterized five yeast strains from food production which allowed us to identify two new strains with high probiotic potential and beneficial effects in a model of intestinal inflammation.

ABSTRACTFood waste can be converted to a useful product such as biochar as a way of recycling waste to retain nutrients in the soil, which in turn contributes to carbon sequestration and offset some greenhouse gas emissions in the struggle to achieve carbon neutrality. Mixed food waste-derived biochars (FWB1–300°C, FWB2–450°C and FWB3–600°C) were pyrolysed at 300°C, 450°C and 600°C, respectively, using an electric kiln. Tests for physiochemical parameters and germination tests were performed. It was realized that at 300°C biochars produced had high nitrogen, organic matter, bulk density, biochar yield, and longer root lengths. The results indicate that municipal food waste biochars produced at three temperatures were suitable for use as fertilizer. However, biochar produced at a moderately lower temperature is favourable for agriculture purposes, FWB1–300°C and FWB2–450°C obtained moderate pH and ash levels and so are less toxic to the growth of plants.

Damage to light-sensing photoreceptors (PRs) occurs in highly prevalent retinal diseases. As humans cannot regenerate new PRs, these diseases often lead to irreversible blindness. Intriguingly, animals, such as the zebrafish, can regenerate PRs efficiently and restore functional vision. Upon injury, mature Müller glia (MG) undergo reprogramming to adopt a stem cell-like state. This process is similar to cellular dedifferentiation, and results in the generation of progenitor cells, which, in turn, proliferate and differentiate to replace lost retinal neurons. In this study, we tested whether factors involved in dedifferentiation of Drosophila CNS are implicated in the regenerative response in the zebrafish retina. We found that hairy-related 6 (her6) negatively regulates of PR production by regulating the rate of cell divisions in the MG-derived progenitors. prospero homeobox 1a (prox1a) is expressed in differentiated PRs and may promote PR differentiation through phase separation. Interestingly, upon Her6 downregulation, Prox1a is precociously upregulated in the PRs, to promote PR differentiation; conversely, loss of Prox1a also induces a downregulation of Her6. Together, we identified two novel candidates of PR regeneration that cross regulate each other; these may be exploited to promote human retinal regeneration and vision recovery.

BackgroundNon-alcoholic steatohepatitis (NASH) has become a major public health issue as one of the leading causes of liver disease and transplantation worldwide. The instrumental role of the gut microbiota is emerging but still under investigation. Endogenous ethanol (EtOH) production by gut bacteria and yeasts is an emerging putative mechanism. Microbial metagenomics and culture studies targeting enterobacteria or yeasts have been reported, but no culturomics studies have been conducted so far.AimTo assess fecal EtOH and other biochemical parameters, characterize NASH-associated dysbiosis and identify EtOH-producing gut microbes associated with the disease, fecal samples from 41 NASH patients and 24 controls were analyzed. High-performance liquid chromatography (HPLC) was used for EtOH, glucose, total proteins, triglyceride and total cholesterol. Viable bacteria were assessed with microbial culturomics. Microbial genetic material was assessed using 16S metagenomics targeting the hypervariable V3V4 region.ResultsFecal EtOH and glucose was elevated in the stools of NASH patients (p < 0.05) but not triglyceride, total cholesterol or proteins. In culturomics, EtOH-producing Enterocloster bolteae and Limosilactobacillus fermentum were enriched in NASH. V3V4 16S rRNA amplicon sequencing confirmed the enrichment in EtOH-producing bacteria including L. fermentum, Mediterraneibacter gnavus and Streptococcus mutans, species previously associated with NASH and other dysbiosis-associated diseases. Strikingly, E. bolteae was identified only by culturomics. The well-known Lacticaseibacillus casei was identified in controls but never isolated in patients with NASH (p < 0.05).ConclusionElevated fecal EtOH and glucose is a feature of NASH. Several different EtOH-producing gut bacteria may play an instrumental role in the disease. Culturomics and metagenomics, two complementary methods, will be critical to identify EtOH-producing bacteria for future diagnostic markers and therapeutic targets for NASH. Suppression of EtOH-producing gut microbes and L. casei administration are options to be tested in NASH treatment.

BackgroundDigital health literacy is considered a health determinant that can influence improved health and well-being, health equity, and the reduction of social health inequalities. Therefore, it serves as an asset for individuals to promote their health. However, low digital health literacy is a major problem among forced migrant populations. They do not always have the capacity and skills to access digital health resources and use them appropriately. To our knowledge, no studies are currently available to examine effective interventions for improving digital health literacy among forced migrant populations. ObjectiveThis paper presents the protocol for a systematic review that aims to assess the effectiveness of digital health literacy interventions among forced migrant populations. With this review, our objectives are as follows: (1) identify interventions designed to improve digital health literacy among forced migrant populations, including interventions aimed at creating enabling conditions or environments that cater to the needs and expectations of forced migrants limited by low levels of digital health literacy, with the goal of facilitating their access to and use of eHealth resources; (2) define the categories and describe the characteristics of these interventions, which are designed to enhance the abilities of forced migrants or adapt digital health services to meet the needs and expectations of forced migrant populations. MethodsA mixed methods systematic review will be conducted according to the PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) checklist. The research will be conducted in an iterative process among the different authors. With the help of a medical information specialist, a specific search strategy will be formulated for the 6 most relevant databases (ie, MEDLINE, Embase, CINAHL, Web of Science, Academic Search Premier, PsycINFO, and the Google Scholar search engine). A literature search covering studies published between 2000 and 2022 has already been conducted. Two reviewers then proceeded, individually and independently, to conduct a double selection of titles, abstracts, and then full texts. Data extraction will be conducted by a reviewer and validated by a senior researcher. We will use the narrative synthesis method (ie, structured narrative summaries of key themes) to present a comprehensive picture of effective digital health literacy interventions among forced migrant populations and the success factors of these interventions. ResultsThe search strategy and literature search were completed in December 2022. A total of 1232 articles were identified. The first selection was completed in July 2023. The second selection is still in progress. The publication of the systematic review is scheduled for December 2023. ConclusionsThis mixed methods systematic review will provide comprehensive knowledge on effective interventions for digital literacy among forced migrant populations. The evidence generated will further inform stakeholders and aid decision makers in promoting equitable access to and use of digital health resources for forced migrant populations and the general population in host countries. International Registered Report Identifier (IRRID)DERR1-10.2196/50798

Flow, a state of mind that occurs when persons are deeply immersed in an activity, plays an important role in enhancing the tourist experience through a variety of activities. Historically, flow is explored from the perspective of how tourists' experience the state, while little attention has been given to how tourism businesses can facilitate flow states to improve their product offerings. This prelminary study explores a tourism business in Tasmania, Australia, whose ethos is centred around a desire to facilitate a flow state for their guests, including the design of infrastructure, guide training and the design of itineraries. The impact of these mechanisms upon guests' experiences is assessed to understand whether and how these design elements influence the attainment of flow.

Abstract Since the 2008 publication of the reports of the Commission on Social Determinants of Health and its nine knowledge networks, substantial research has been undertaken to document and describe health inequities. The COVID-19 pandemic has underscored the need for a deeper understanding of, and broader action on, the social determinants of health. Building on this unique and critical opportunity, the World Health Organization is steering a multi-country Initiative to reduce health inequities through an action-learning process in ‘Pathfinder’ countries. The Initiative aims to develop replicable and reliable models and practices that can be adopted by WHO offices and UN staff to address the social determinants of health to advance health equity. This paper provides an overview of the Initiative by describing its broad theory of change and work undertaken in three regions and six Pathfinder countries in its first year-and-a-half. Participants engaged in the Initiative describe results of early country dialogues and promising entry points for implementation that involve model, network and capacity building. The insights communicated through this note from the field will be of interest for others aiming to advance health equity through taking action on the social determinants of health, in particular as regards structural determinants.

In this paper, the design and realization of quasi-elliptical waveguide filters with reduced manufacturing complexity are discussed. The filters are based on TE mode cavities, which are loaded with TM mode stubs. It is shown that dual-, triple- and quadruple-resonance segments are obtained by using up to three stubs loaded on the broad side of a TE mode cavity. The structures obtained can either be used as a stand-alone filter or even as a building block suitable for the realization of higher order filters. The multi-resonance blocks reveal several advantages in the mm-wave area: The manufacturing complexity is easy to handle and comparable to simple all-pole filters, which is especially important at high frequencies. Therefore, three prototypes are manufactured as proof of concept in the D-band (110 GHz–170 GHz). Moreover, the building blocks are able to produce $n-1$ transmission zeros (TZs) with $n$ being the number of resonances. Therefore, the blocks generate between one (dual-resonance) and up to three (quadruple-resonance) TZs. Advantageously, the filters can be cut in the E-plane in order to reduce the insertion loss and hence consist of only two components. Three examples are manufactured by high precision CNC milling and reveal good agreement to the simulation by obtaining unloaded Q-factors of up to 1000.

This paper discusses dielectric TM-mode filters based on high permittivity Y-shaped ceramics. It is shown that this type of ceramic operates as a dual-mode resonator and therefore contributes two reflection zeros as well as one transmission zero (TZ) to the filter response. Hence, it can be interpreted as a doublet structure and used for the realization of quasi-elliptical filter responses of different order. The dual-mode resonator can be used in multiple different filter set-ups: On the one hand, a combination with classical TM$_{010}$-mode resonators is possible to allow the realization of TZs in an in-line filter configuration without using cross-coupling apertures. Therefore, negative or diagonal cross-couplings, which are often difficult to realize and handle, can be avoided. On the other hand, several Y-shaped ceramics can be coupled directly with each other to increase the number of TZs to $n_{fz}=n/2$, where $n$ is the order of the filter. Finally, it is shown that even a combination with extracted pole elements is realizable. Prototypes based on modular segments are manufactured as proof of concept.

Background: A mid-fidelity simulation mannequin, equipped with an instrumented cervical and lumbar spine, was developed to investigate best practices and train healthcare professionals in applying spinal motion restrictions (SMRs) during the early mobilization and transfer of accident victims with suspected spine injury. The study objectives are to (1) examine accuracy of the cervical and lumbar motions measured with the mannequin; and (2) confirm that the speed of motion has no bearing on this accuracy. Methods: Accuracy was evaluated by concurrently comparing the orientation data obtained with the mannequin with that from an optoelectronic system. The mannequin’s head and pelvis were moved in all anatomical planes of motion at different speeds. Results: Accuracy, assessed by root-mean-square error, varied between 0.7° and 1.5° in all anatomical planes of motion. Bland–Altman analysis revealed a bias ranging from −0.7° to 0.6°, with the absolute limit of agreement remaining below 3.5°. The minimal detectable change varied between 1.3° and 2.6°. Motion speed demonstrated no impact on accuracy. Conclusions: The results of this validation study confirm the mannequin’s potential to provide accurate measurements of cervical and lumbar motion during simulation scenarios for training and research on the application of SMR.