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Etherification and amination of aryl halide scaffolds are commonly used reactions in parallel medicinal chemistry to rapidly scan structure–activity relationships with abundant building blocks. Electrochemical methods for aryl etherification and amination demonstrate broad functional group tolerance and extended nucleophile scope compared to traditional methods. Nevertheless, there is a need for robust and scale‐transferable workflows for electrochemical compound library synthesis. Herein we describe a platform for automated electrochemical synthesis of C−X arylation (X=NH, OH) in flow to access compound libraries. A comprehensive Design of Experiment (DoE) study identifies an optimal protocol which generates high yields across>30 aryl halide scaffolds, diverse amines (including electron‐deficient sulfonamides, sulfoximines, amides, and anilines) and alcohols (including serine residues within peptides). Reaction sequences are automated on commercially available equipment to generate libraries of anilines and aryl ethers. The unprecedented application of potentiostatic alternating polarity in flow is essential to avoid accumulating electrode passivation. Moreover, it enables reactions to be performed in air, without supporting electrolyte and with high reproducibility over consecutive runs. Our method represents a powerful means to rapidly generate nucleophile independent C−X arylation compound libraries using flow electrochemistry. [ABSTRACT FROM AUTHOR]

Periodic duodenoscope cultures are essential to timely detect contamination, but their sensitivity remains unknown. This study aims to determine the sensitivity of duodenoscope cultures and to estimate the prevalence of contaminated duodenoscope use. We combined duodenoscope microbiologic surveillance data from March 2015 to June 2022 with usage data to evaluate patient exposure to duodenoscopes contaminated with microorganisms of gut or oral origin (MGO). We identified duodenoscopes with repeated species-level contamination within a year and used molecular typing to confirm genetic relatedness. Genetically related microorganisms over multiple duodenoscope cultures of a single duodenoscope indicated a period of sustained contamination, and a cluster was defined as overlapping periods of sustained contamination between different duodenoscopes. If microorganisms were not available for molecular analysis, we marked the period as unconfirmed. A sample was defined as false negative if it did not show the target microorganism(s) in a period of sustained contamination. We used 3 scenarios to hypothesize about contaminated use and culture sensitivity. We included 556 duodenoscope cultures with 185 (33.3%) contaminated with MGO. The total usage of duodenoscopes was 5226. We identified 1 period of sustained contamination, 6 unconfirmed periods, and 2 clusters. Depending on our scenario assumptions, the percentage of contaminated use varied from 12.3% to 23.7% and culture sensitivity ranged from 82.2% to 98.9%. Limited sensitivity of duodenoscope cultures leads to improper clearance of duodenoscopes for clinical use, increasing risks of outbreaks. The applicability of a single culture to end a duodenoscope's quarantine should be re-evaluated. [ABSTRACT FROM AUTHOR]

• What is the primary question addressed by this study? This study investigated if tau accumulation is higher in late life depression (LLD) than in a healthy comparison group and in patients with mild cognitive impairment due to Alzheimer's (MCI). • What is the main finding of this study? LLD patients exhibited lower gray matter volume than the comparison group in temporal regions but similar tau accumulation, in contrast to mild cognitive impairment due to Alzheimer's (MCI) patients who showed significantly higher tau burden. • What is the meaning of the finding? Alzheimer associated tau pathology is unlikely to contribute to lower gray matter volume in major depressive disorder in older adults. To investigate whether tau accumulation is higher in late life depression (LLD) compared to non-depressed cognitively unimpaired (CU) older adults. To situate these findings in the neurodegeneration model of LLD by assessing group differences in tau and grey matter volume (GMV) between LLD, non-depressed CU and mild cognitive impairment due to Alzheimer's Disease (MCI). Monocentric, cross-sectional study. University Psychiatric hospital, memory clinic and outpatient neurology practice. A total of 102 adults over age 60, of whom 19 currently depressed participants with LLD, 19 with MCI and 36 non-depressed CU participants completed neuropsychological testing and tau PET-MR imaging. PET-MRI: 18F-MK-6240 tracer SUVR for tau assessment; 3D T1-weighted structural MRI derived GMV in seven brain regions (temporal, cingulate, prefrontal and parietal regions); amyloid PET to assess amyloid positivity; Neuropsychological test scores: MMSE, RAVLT, GDS, MADRS. ANCOVA and Spearman's rank correlations to investigate group differences in tau and GMV, and correlations with neuropsychological test scores respectively. Compared to non-depressed CU participants, LLD patients showed lower GMV in temporal and anterior cingulate regions but similar tau accumulation and amyloid positivity rate. In contrast, MCI patients had significantly higher tau accumulation in all regions. Tau did not correlate with any neuropsychological test scores in LLD. Our findings suggest AD-type tau is not higher in LLD compared to non-depressed, cognitively unimpaired older adults and appears unlikely to contribute to lower gray matter volume in LLD, further underscoring the need to distinguish major depressive disorder from depressive symptoms occurring in early AD. [ABSTRACT FROM AUTHOR]

The article "Debate: A relational agenda for changing public administration research and practice" discusses the importance of relational theory and practice in public administration. It highlights the need for a clear agenda that enables conceptual integration and concerted action to organize governance systems on a relational basis. The authors emphasize the significance of adopting a relational mindset to accelerate transformative change and promote socially just processes of interactive meaning-making. They outline five leverage points for relational change, including starting with relationships, letting processes and outcomes emerge, building space for mutual change, adopting a relational leadership approach, and creating systemic conditions for collaboration. The article calls upon readers to center their research and praxis around relational assumptions, practices, and values to leverage transformative change towards relational ecosystems. [Extracted from the article]

Objective: Patients with therapy-refractory chronic spinal pain after spinal surgery experience increased disability, resulting in substantial loss of employment and consequently lower quality of life. Despite findings that rehabilitation improves socio-economic outcomes in other chronic pain conditions, evidence for patients with chronic spinal pain after spinal surgery is limited. A systematic review was conducted to provide an overview of rehabilitation interventions and their effectiveness to improve work participation for patients with chronic spinal pain after spinal surgery. Methods: MEDLINE (via PubMed), Scopus, Embase, and Web of Science, were systematically searched. Risk of bias was assessed using the modified Downs and Black checklist and GRADE was used to assess certainty of evidence. The review protocol was prospectively registered on PROSPERO (CRD42022346091). Results: The search yielded 1,289 publications. Full-text screening of 48 articles resulted in the inclusion of 6 publications. The included interventions comprised multiple treatment components, consisting of back school, self-care, functional restoration, multidisciplinary rehabilitation, physiotherapy, and digital care programmes to improve work participation. Conclusion: Rehabilitation to improve return to work for patients with chronic spinal pain after spinal surgery was supported only by low-certainty evidence. Rehabilitation therapies that are personalized and that integrate the patient’s work seem most suitable.

BACKGROUND: In the era of first-generation drug-eluting stents and angiography-guided percutaneous coronary intervention (PCI), the presence of a bifurcation lesion was associated with adverse outcomes after PCI. In contrast, the presence of a bifurcation lesion had no impact on outcomes following coronary artery bypass grafting (CABG). Therefore, the presence of a coronary bifurcation lesion requires special attention when choosing between CABG and PCI. The aim of this study is to assess whether the presence of a bifurcation lesion still influences clinical outcomes after contemporary PCI using second-generation drug-eluting stent and fractional flow reserve (FFR) guidance versus CABG. METHODS: The randomized FAME 3 trial (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) compared FFR-guided PCI using current drug-eluting stents with CABG in patients with 3-vessel coronary artery disease. The prespecified key end point at 3-year follow-up was the composite of death, myocardial infarction, or stroke. In this substudy, the impact of bifurcation lesions on outcomes after FFR-guided PCI and CABG was investigated. RESULTS: The FAME 3 trial enrolled 1500 patients and 653 (45.2%) patients had at least 1 true bifurcation lesion. There was no difference in the composite of death, myocardial infarction, or stroke at the 3-year follow-up between patients with or without at least 1 true bifurcation lesion (11.6% versus 10.0%; hazard ratio, 1.17 [95% CI, 0.86–1.61]; P =0.32), regardless of revascularization strategy. The composite end point was not statistically different between FFR-guided PCI and CABG in patients with at least 1 true bifurcation lesion (hazard ratio, 1.27 [95% CI, 0.80–2.00]) or without a true bifurcation lesion (hazard ratio, 1.36 [95% CI, 0.87–2.12]), with no significant interaction (P interaction=0.81). CONCLUSIONS: In patients with 3-vessel coronary artery disease, the presence of a true bifurcation lesion was not associated with a different treatment effect after FFR-guided PCI with contemporary drug-eluting stent versus CABG. [ABSTRACT FROM AUTHOR]

Studies on digital issues in rural development usually build on concepts that stem from literature on urban contexts. This urban dependence in rural research bears the risk of conceptual blind spots, and missing factors that might be relevant for the rural. In this paper, we present a narrative review on the development of 'digital rural studies'. We start from two earlier review papers that often serve as a departure point for rural scholars who work on digital issues. Different to urban-based studies on digitalisation that use a more generic social inequalities framework, rural studies acknowledge the existence of both urban-rural and intra-rural divides, as well as material and social divides. By combining the latest state of the art studies and our own experiences from digitalisation projects, we construct an updated narrative that helps to shape a more rural-just framework, and shows how the 'rural' and the 'digital' mutually shape each other. By applying the concept of remapping to rural digitalisation, we show that digitalisation is formed in, from and by place, and future studies need to acknowledge this. • A narrative review on digitalisation in rural areas is presented. • The concepts of 'remapping' and 'mutual shaping' are used. • Digitalisation is remapped in, by, and from places. • Community leaders, local entrepreneurs, and policies shape digital-rural interplay. • Good practices and successes are formed in, by, and from rural places. [ABSTRACT FROM AUTHOR]