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Abstract Deep brain stimulation (DBS) with electric field steering may avoid areas responsible for side effects. This prospective randomized cross-over trial compared omnidirectional (OS) and directional (DS) subthalamic DBS in 19 patients. Electromyographically measured rigidity was the primary outcome. Motor and non-motor scores were secondary outcomes. There were no significant differences between OS and DS. In the acute setting, both conditions improved motor scores compared to no stimulation. Motor symptoms improved after 3 weeks of OS relative to acute measurements, whereas they worsened under DS. The more ventral the active contact, and the less the motor improvement sweet spot was stimulated, the greater the benefit of DS over OS for executive function. Accurate OS of the dorsal subthalamic nucleus ensures motor and non-motor improvements. While DS can mitigate executive decline stemming from off-target stimulation, it may lead to worse motor outcomes. Larger, long-term studies are needed to confirm these findings. (Registration: subthalamic steering for therapy optimization in Parkinson’s Disease ClinicalTrials.gov: NCT03548506, 2018-06-06).

Abstract Background Osteoporotic fractures signal severely compromised bone strength and are associated with a greatly increased risk of refracture. Despite the availability of effective and safe medications that reduce fracture risk, 70–80% of patients are inadequately investigated or treated for osteoporosis following an initial fracture, constituting a significant ‘osteoporosis care gap’. Optimal methods of bridging this gap with primary care at the forefront of secondary fracture prevention remain undetermined. This protocol describes a cluster randomised controlled trial to evaluate the effectiveness of a novel integrated model of secondary fracture prevention and management in primary care. Methods The cluster randomised controlled trial involves multiple branches of a community-based radiology provider (CRP), a hospital-based secondary fracture prevention program (SFPP) and numerous primary care practices in metropolitan Sydney that refer to either the CRP or SFPP. Using natural language processing tools, patients diagnosed with a potential osteoporotic fracture will be identified by automatically screening radiology reports generated at the CRP or SFPP. The primary care practices that these patients attend will be randomised (1:1) to either the intervention or usual care. The intervention consists of (i) electronic and fax alerts informing the practice/primary care physician that their patient has been diagnosed with a potential osteoporotic fracture; (ii) provision of osteoporosis management guidelines and (iii) follow-up surveys at 4 weeks and 6 months. Practices in the usual care (control) group will receive no alerts and provide usual care. The primary outcome is the proportion of patients undergoing a bone density scan and/or filling a prescription for osteo-protective pharmacotherapy within 3 months of the initial diagnostic imaging report. Secondary outcomes are the proportion of patients: (i) undergoing an osteoporosis-related blood test within 3 months of the initial diagnostic imaging report; (ii) initiated on a chronic disease management plan within 3 months of the diagnostic report, and (iii) filling a second prescription for osteo-protective pharmacotherapy within 9 months post initial diagnostic imaging report. Outcomes will be obtained through de-identified linked data from Medical Benefits Schedule and Pharmaceutical Benefits Scheme held by the Australian Institute of Health and Welfare. Discussion This is the first randomised trial to integrate case-detection of potential osteoporotic fractures in a hospital and community setting with direct alerts to the patient’s primary care provider. This study will determine whether such an intervention is effective in improving investigation and/or treatment rates of osteoporosis in patients with a potential osteoporotic fracture. Trial registration This study is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12623000658617p.

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.

La succession d’évènements tragiques au cours des XX et XXIe siècles a mis en évidence l’importance de la gestion des risques avec notamment des risques industriels, financiers, sociétaux (les soulèvements), sanitaires (pandémie de covid-19), ou encore les aléas administratifs (fait du prince), etc. à l’occasion de la mise en œuvre des projets d’investissements. Le secteur industriel et minier en particulier a toujours été, depuis la nuit des temps, le secteur à risque. Plusieurs cas d’accidents graves y ont été enregistrés de par le monde. En République Démocratique du Congo, dans le code et règlement minier, les risques majeurs , sont générés par les cas de force majeure qui affectent des projets dans ce secteur. Selon le rapport 2019 du CAMI, au 31 décembre 2019, l’on a noté l’existence de 3 308 sociétés minières créées, pour 306 579 carrés miniers, soit 260 438,86 Km2 de surfaces de la RDC couverte par les mines et les carrières. Environ 76 % (233 150 carrés) sont en Permis de recherches, 19,65 % (60231 titres) de Permis d’Exploitation et 3,48 % (10 672 titres) de Permis d’Exploitation de petites Mines. Environ 20% de carrés miniers (61 279) sont en situation de force majeure. Dans le but de prémunir le titulaire d’un droit minier et de carrières contre les évènements et/ou aléas imprévisibles, insurmontables pouvant subvenir tout au long de ses activités, le législateur congolais a pris le soin d’organiser dans la Loi 007/2002 du 11 juillet 2002 portant Code minier telle que modifiée et complétée par la Loi 18/001 du 9 mars 2018, un régime de force majeure justifiant l’arrêt momentané des activités du titulaire affecté, à tout le moins, la suspension des obligations impactées par le cas de force majeure invoqué, sans préjudice du maintien en validité de ses droits miniers concernés.

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.

AIMS OF THE STUDY: Health equity is a key component of quality of care and an objective for a growing number of quality improvement projects for deontological, ethical, public health and economic reasons. To monitor equity in the delivery of health services in Switzerland, there is a need to implement valid, measurable and actionable equity indicators, along with vulnerability stratifiers such as migrant status, which could lead to differences in quality of care. The aim of this study was to develop a set of healthcare equity indicators and stratifiers targeting inpatient and outpatient populations and to test their feasibility. METHODS: A scoping literature review and inputs from a national interprofessional expert taskforce provided a set of indicators and vulnerability stratifiers. The most valid and measurable indicators and stratifiers were retained using a Delphi process. They were then operationalised, and their implementation tested in three Swiss hospitals from the three language regions. RESULTS: A taskforce of 18 experts, including a patient representative, selected 11 indicators that evaluate structures, processes and outcomes, and five vulnerability stratifiers. Although most indicators and stratifiers could be implemented in all three hospitals, data availability was limited for some variables, including patient satisfaction and access to interpreters for foreign-language patients. CONCLUSIONS: The equity indicators and stratifiers identified by this two-stage process have content validity, wide patient coverage and are focused on inequities in the healthcare system that are actionable through improvement projects. Both the indicators and the project methodology could be replicated in institutions aiming for more equitable care.

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.

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.

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.

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.

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.

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.

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).

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.

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.

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.

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

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.

We present three-dimensional (3D) maps of Jupiter’s atmospheric circulation at cloud-top level from Doppler-imaging data obtained in the visible domain with JIVE, the second node of the JOVIAL network, which is mounted on the Dunn Solar Telescope at Sunspot, New Mexico. We report on 12 nights of observations between 2018 May 4 and May 30, representing a total of about 80 hr. First, the average zonal wind profile derived from our data is compatible with that derived from cloud-tracking measurements performed on Hubble Space Telescope images obtained in 2018 April from the Outer Planet Atmospheres Legacy program. Second, we present the first ever 2D maps of Jupiter’s atmospheric circulation from Doppler measurements. The zonal velocity map highlights well-known atmospheric features, such as the equatorial hot spots and the Great Red Spot (GRS). In addition to zonal winds, we derive meridional and vertical velocity fields from the Doppler data. The motions attributed to vertical flows are mainly located at the boundary between the equatorial belts and tropical zones, which could indicate active motion in theses regions. Qualitatively, these results compare well to recent Juno data that have unveiled the 3D structure of Jupiter’s wind field. To the contrary, the motions attributed to meridional circulation are very different from what is obtained by cloud tracking, except at the GRS. Because of limitations with data resolution and processing techniques, we acknowledge that our measurements of the vertical or meridional flows of Jupiter are still to be confirmed.

Post-synthetic modification of mechanically interlocked molecules (MIMs) is an attractive avenue to add complexity to already intricate systems. This remains an important, challenging topic that is under-developed. In this paper, we report the synthesis and characterization of a [2]rotaxane molecule featuring a ring appended to an emissive cyclometalated Pt II unit. Modulation of the oxidation state at the metal center can transform the interlocked molecule into a new Pt IV [2]rotaxane or a Pt III [3]rotaxane held together by an intermetallic Pt-Pt bond - a first of its kind. These molecules display distinct structural and photophysical properties, as well as shuttling dynamics. This approach for post-synthetic modification could be used to construct more complex MIMs and inorganic supramolecular assemblies with redox properties., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

We report the first bottleable enantiopure P -chiral secondary phosphines from the rhodium-catalyzed asymmetric hydrogenation of phosphaalkenes. Catalytic asymmetric hydrogenation, a reaction of broad academic and industrial importance for C═C, N═C, and O═C bonds, has not previously been reported for the P═C bond. The hydrogenation of ArP═CR 2 (Ar = Mes, m -Xyl and TMOP; R = Ph, 4-C 6 H 4 F) affords four unprecedented P -stereogenic secondary phosphines in 76%-90% isolated yields with 91%-97% enantiomeric excess (ee). These isolable P -chiral secondary phosphines are configurationally stable indefinitely in the solid state and show only modest loss in ee when kept in solution for over a month at room temperature.

A series of new luminescent bimetallic platinum(II) complexes with stimuli-responsive flexible Lewis pair (FlexLP) ligands are described. The FlexLP ligands consist of a dimesitylboron Lewis acid and diphenylphosphine oxide Lewis base which are in equilibrium between the unbound open form and the Lewis adduct, controlled by the hydrogen bond donating strength of the solvent. Spectroscopic techniques and density functional theory (DFT) calculations were used to interpret the photophysics of the platinum(II) complexes. All complexes exhibit tunable absorption in the region of 300-500 nm and green to orange photoluminescence, depending on the ratio of weak (THF) to strong (MeOH) hydrogen bond donating solvent employed. Spectroscopic and computational data shows that phosphine and peripheral acetylide ligands on the platinum(II) centers have limited influence on the emission energy, indicating the emission originates from the FlexLP-dominated fluorescence. Using time-resolved transient absorption spectroscopy it is shown that the complexes undergo intersystem crossing (ISC) to the triplet excited state upon photoexcitation, and the ISC efficiency is affected by the peripheral acetylide ligands. The triplet excited state lifetime can also be manipulated by the state of the FlexLP ligand, with the closed form complexes having longer lifetimes than the open form complexes., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

Cyclometalated platinum complexes play a crucial role in catalysis, bioimaging, and optoelectronics. Phenylpyridines are widespread cyclometalating ligands that generate stable and highly emissive Pt complexes. While it is common practice to modify these ligands to fine-tune their photophysical properties, the incorporation of polycyclic aromatic hydrocarbons into the ligand's structure has been largely overlooked. This report describes the cyclometalation of naphthalenyl- and anthracenylpyridine ligands, which has resulted in ten new luminescent Pt II and Pt IV complexes. These species are enabled by a dual-binding behavior discovered in our polyaromatic-containing ligands. The introduction of naphthalenyl and anthracenyl groups unlocks dual binding modes, with the Pt center bonding to either of two distant carbon atoms within the ligand. These complexes exhibit both symmetric structures with two 5-membered metallacycles and asymmetric structures with 5- and 6-membered metallacycles. This work presents a strategy for the regioselective synthesis of Pt complexes with bespoke structures and photophysical properties. Our findings offer new opportunities in platinum chemistry and beyond, with potential implications for materials and technologies., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

We report a streamlined synthesis of (2 S ,3 R ,4 R )-4,5-dihydroxy isoleucine (DHIle), an amino acid found in α-amanitin, which appears to be critical for toxicity. This synthetic route is transition metal-free and enables the production of significant quantities of DHIle with suitable protection for use in peptide synthesis. Its incorporation into a cytotoxic amatoxin analog is reported.

The Suzuki-Miyaura cross-coupling (SMC) remains one of the most widely used transformations available to chemists. Recently, robust new conditions achieving rapid reactivity under homogeneous aprotic conditions enabled by the use of potassium trimethylsilanolate (TMSOK) as a base were reported. However, the strong inhibitory effect of TMSOK restricts the generality of such conditions. Moreover, the basic nature of TMSOK impedes the use of protic heterocycles as substrates, as these latter anionic species are even more potent catalyst inhibitors. Herein, we report a thorough mechanistic study of these novel SMC conditions. Halide salt additives were found to provide a dramatic rate acceleration and mitigate the inhibitory effect of TMSOK. NMR experiments revealed that this is largely achieved by impacting the unexpected formation of inactive [LnPd(Ar)(μ-OH)] 2 , favoring the formation of active LnPd(Ar)(X) instead. These findings enabled an impressive substrate scope even at low catalyst loadings (0.1 mol %). Finally, halide additives were observed to enable the use of protic heterocyclic substrates, which could otherwise completely inhibit reactivity., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Investigation of extracts from bulbils of Dioscorea bulbifera L. yielded two new norclerodane diterpenoids, diosbulbin N acetate ( 1 ) and epi -diosbulbin B ( 3 ), together with eleven known compounds. Their structures were established based on spectroscopy. The absolute configurations of 1 and diosbulbin B ( 2 ) were determined by X-ray crystallographic analysis using Cu K α radiation. The absolute configuration of 3 was determined by comparison of its ECD spectrum to that of 2 . Isolated phenanthrenes 7 , 9 and 10 exhibited moderate cytotoxicity against the HelaS3 cell line with IC 50 values of 9.03 ± 0.04, 27.13 ± 6.86 and 10.88 ± 2.75 µM, respectively. In addition, 7 - 9 and 11 showed potent inhibition of NO production by LPS-induced RAW 264.7 macrophages.

Phytochemical investigations of the twig and leaf extracts of Uvaria dac Pierre ex Finet & Gagnep. resulted in the isolation and identification of five new highly oxygenated cyclohexenes, uvaridacols M - Q (1-3, 5, and 6), and six known compounds (4 and 7-11). All new structures were elucidated by spectroscopic methods and HRESITOFMS data. The absolute configuration of 1, 5, and 6 was confirmed by single X-ray diffraction analysis with Cu Kα radiation. In contrast, other compounds were established by comparing their specific rotation and ECD spectra with those of known compounds. Some of the isolated compounds with sufficient quantity were evaluated for their α-glucosidase inhibitory activity. Of these, (-)-1,6-desoxypipoxide (10) showed α-glucosidase inhibitory activity with an IC 50 value of 28.6 μM. The in silico molecular docking of active compounds was also studied., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

We describe the synthesis, solid state and electronic structures of a series of tunable five-membered cationic and charge-neutral inorganic heterocycles featuring a P 3 CN core. 1-Aza-2,3,4-triphospholenium cations [(PR) 3 N(H)CR'] + , [1 R ] + (R' = Me, Ph, 4-MeOC 6 H 4 , 4-CF 3 C 6 H 4 ) were formed as triflate salts by the formal [3 + 2]-cyclisation reactions of strained cyclic triphosphanes (PR) 3 (R = t Bu, 2,4,6-Me 3 C 6 H 2 (Mes), 2,6- i Pr 2 C 6 H 3 (Dipp), 2,4,6- i Pr 3 C 6 H 2 (Tipp)) with nitriles R'CN in the presence of triflic acid. The corresponding neutral free bases (PR) 3 NCR' (2 R ) were readily obtained by subsequent deprotonation with NEt 3 . The P 3 CN cores in 2 R show an envelope conformation typical for cyclopentenes and present as yellow to orange compounds in the solid state as well as in solution depending on both substituents R and R' in (PR) 3 NCR'. The P 3 CN cores in [1 R ] + show a significant deviation from planarity with increasing steric bulk of the R groups at phosphorus, which results in a decrease in the HOMO-LUMO gap and distinct low-energy UV-Visible absorption bands. This allows access to colours spanning red, blue, indigo, and magenta. TD-DFT calculations provide valuable insight into this phenomenon and indicate an intramolecular charge-transfer from the HOMO located on the P 3 framework to the N[double bond, length as m-dash]C-R'-based LUMO in the cationic species. The cations [1 R ] + represent rare examples of phosphorus-rich heterocycles with tunable colour, which can be incorporated into polymers by post-polymerization modification to afford coloured polymers, which demonstrate utility as both proton and ammonia sensors., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Sulfilimines, as potential aza-isosteres of sulfoxides, are valued as building blocks, auxiliaries, ligands, bioconjugation handles, and as precursors to versatile S(VI) scaffolds including sulfoximines and sulfondiimines. Here, we report a thioether imination methodology that exploits O-(diphenylphosphinyl)hydroxyl amine (DPPH). Under mild, metal-free, and biomolecule-compatible conditions, DPPH enables late-stage S-imination on peptides, natural products, and a clinically trialled drug, and shows both excellent chemoselectivity and broad functional group tolerance. This methodological report is extended to an efficient and high-yielding one-pot reaction for accessing free-NH sulfoximines with diverse substrates including ones of potential clinical importance. In the presence of a rhodium catalyst, sulfoxides are S-iminated in higher yields to afford free-NH sulfoximines. S-imination was validated on an oxidatively delicate amatoxin to give sulfilimine and sulfoximine congeners. Interestingly, these new sulfilimine and sulfoximine-amatoxins show cytotoxicity. This method is further extended to create sulfilimine and sulfoximine-Fulvestrant and buthionine analogues., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Herein, we report the synthesis of carbene-stabilized 1,3-diaza-2,4-diphosphabutenes CAAC Me PNPNCAAC Me 4 CAAC (CAAC Me = 1-[2,6-bis(isopropyl)phenyl]-3,3,5,5-tetramethyl-2-pyrrolidinylidene) and IPrPNPNIPr 4 NHC (IPr = 1,3-Bis(2,6-diisopropylphenyl)-imidazol-2-ylidene). The bonding in both systems is defined by a delocalized polar covalent π-system, with 4 NHC exhibiting increased conjugation relative to 4 CAAC . The nature of the stabilizing carbene also influences the redox properties of the compound, with 4 CAAC undergoing potassium-mediated reduction to the closed-shell P-P bonded dimer K 2 5 2 , which upon treatment with Kryptofix-2,2,2 converts to the transient radical anion [K crypt ][ 5 ], the formal one-electron reduction product of 4 CAAC . In contrast, 4 NHC undergoes reversible one-electron oxidation to the stable radical cation [ 6 NHC ][SbF 6 ]. Computational and spectroscopic analyses of both radical species are suggestive of unevenly delocalized spin, with the bulk of the spin density residing on phosphorus in both cases.