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Abstract Thin film interference is integral to modern photonics, e.g., allowing for precise design of high performance optical filters, photovoltaics and light-emitting devices. However, interference inevitably leads to a generally undesired change of spectral characteristics with angle. Here, we introduce a strategy to overcome this fundamental limit in optics by utilizing and tuning the exciton-polariton modes arising in ultra-strongly coupled microcavities. We demonstrate optical filters with narrow pass bands that shift by less than their half width (

Increased hazards threatening the United Nations Educational, Scientific and Cultural Organization (UNESCO)-designated sites and endangering cultural heritage and community well-being require attention and action. Considering the pivotal role of UNESCO sites in conservation and development, this study assessed their levels of disaster preparedness. The absence of studies assessing disaster awareness, risk perception, and preparedness among UNESCO site actors, as well as the pivotal place of preparedness within the Disaster Risk Management (DRM) cycle justifies this research. Applying the tenets of the Person-Relative-to-Event framework, we hypothesized that a strong positive correlation exists between perceived risks, resources, and disaster preparedness. To collect pertinent data, we employed an embedded mixed-method design and conducted an online questionnaire survey yielding 141 responses from 59 countries. From the results of relevant analyses, wildfires, floods, and droughts are top hazards occurring frequently in UNESCO sites, with significant concerns about pollution and habitat loss during future events. Smartphones emerged as the most available crucial DRM resource, with higher availability of DRM resources correlating positively and significantly with sites’ preparedness. Our findings contribute valuable insights to address missing links for disaster-ready and resilient UNESCO sites, promoting their preservation for future generations.

Abstract Background Rollover crashes continue to be a substantial public health issue in North America. Previous research has shown that the cervical spine is the most injured spine segment in rollovers, but much of the past research has focused on risk factors rather than the actual cervical spine injuries. We sought to examine how different types of cervical spine injuries (vertebral and/or cord injury) vary with different occupant-related factors in rollovers and to compare these with non-rollovers. Methods We obtained crash and injury information from the National Automotive Sampling System–Crashworthiness Data System (NASS-CDS) for 2005–2015 and Crash Investigation Sampling System (CISS) for 2017–2022. Based on weighted data, we calculated relative risks to assess how occupant sex, seat belt use, ejection status, and fatal outcome relate to the rate of different cervical spine injuries in rollovers and non-rollovers. Results In NASS-CDS occupants with cervical spine injuries (N = 111,040 weighted cases), about 91.5% experienced at least one vertebral injury whereas only 11.3% experienced a spinal cord injury (most of which had a concomitant vertebral fracture). All types of cervical spine injuries we examined were 3.4–5.2 times more likely to occur in rollovers compared to non-rollovers. These relative risks were similar for both sexes, belted and unbelted, non-ejected, and non-fatal occupants. The number of weighted CISS occupants with cervical spine injuries (N = 42,003) was smaller than in the NASS analysis, but cervical spine injuries remained 6.25 to 6.36 times more likely in rollovers compared to non-rollovers despite a more modern vehicle fleet. Conclusions These findings underscore the continued need for rollover-specific safety countermeasures, especially those focused on cervical spine injury prevention, and elucidate the frequency, severity and other characteristics of the specific vertebral and spinal cord injuries being sustained in rollovers. Our findings suggest that countermeasures focused on preventing cervical vertebral fractures will also effectively prevent most cervical spinal cord injuries.

Gut microbiota-derived metabolites play a pivotal role in the maintenance of intestinal immune homeostasis. Here, we demonstrate that the human commensal Clostridium sporogenes possesses a specific metabolic fingerprint, consisting predominantly of the tryptophan catabolite indole-3-propionic acid (IPA), the branched-chain acids (BCFAs) isobutyrate and isovalerate and the short-chain fatty acids (SCFAs) acetate and propionate. Mono-colonization of germ-free mice with C. sporogenes (CS mice) affected colonic mucosal immune cell phenotypes, including up-regulation of Il22 gene expression, and increased abundance of transcriptionally active colonic tuft cells and Foxp3+ regulatory T cells (Tregs). In DSS-induced colitis, conventional mice suffered severe inflammation accompanied by loss of colonic crypts. These symptoms were absent in CS mice. In conventional, but not CS mice, bulk RNAseq analysis of the colon revealed an increase in inflammatory and Th17-related gene signatures. C. sporogenes-derived IPA reduced IL-17A protein expression by suppressing mTOR activity and by altering ribosome-related pathways in Th17 cells. Additionally, BCFAs and SCFAs generated by C. sporogenes enhanced the activity of Tregs and increased the production of IL-22, which led to protection from colitis. Collectively, we identified C. sporogenes as a therapeutically relevant probiotic bacterium that might be employed in patients with inflammatory bowel disease (IBD).

Accurately identifying life-threatening prostate cancer (PCa) at time of diagnosis remains an unsolved problem. We evaluated whether DNA methylation status of selected candidate genes can predict the risk of metastasis beyond clinical risk factors in men with untreated PCa. A nested case-control study was conducted among men diagnosed with localized PCa at Kaiser Permanente California between 01/01/1997–12/31/2006 who did not receive curative treatments. Cases were those who developed metastasis within 10 years from diagnosis. Controls were selected using density sampling. Ninety-eight candidate genes were selected from functional categories of cell cycle control, metastasis/tumour suppressors, cell signalling, cell adhesion/motility/invasion, angiogenesis, and immune function, and 41 from pluripotency genes. Cancer DNA from diagnostic biopsy blocks were extracted and analysed. Associations of methylation status were assessed using CpG site level and principal components-based analysis in conditional logistic regressions. In 215 cases and 404 controls, 27 candidate genes were found to be statistically significant in at least one of the two analytical approaches. The agreement between the methods was 25.9% (7 candidate genes, including 2 pluripotency markers). The DNA methylation status of several candidate genes was significantly associated with risk of metastasis in untreated localized PCa patients. These findings may inform future risk prediction models for PCa metastasis beyond clinical characteristics.

Abstract Ezetimibe undergoes glucuronidation that results in the active metabolite ezetimibe phenoxy‐glucuronide (ezetimibe‐glucuronide). This phase‐II metabolite was shown to interact with the clinically relevant hepatic transporter organic anion transporting polypeptide (OATP) 1B1. In recent years, coproporphyrin I (CPI) was established as a Tier 1 biomarker for OATP1B‐mediated interactions among other endogenous substrates like CPIII. To evaluate whether levels of the biomarker are affected by ezetimibe treatment, we assessed the impact of ezetimibe and ezetimibe‐glucuronide on OATP1B1‐mediated transport of CPs in vitro. Then, we quantified CP levels in serum samples of healthy volunteers treated with a single oral dose of ezetimibe (20 mg) alone or in combination with rifampin (600 mg). Results from our in vitro experiments showed a significant reduction in cellular CPI accumulation in the presence of ezetimibe‐glucuronide with an IC50 of 1.97 μM [95% CI: 1.04 to 3.96], while CPIII accumulation was impacted by 10 μM and above. In the in vivo study, we observed peak CP concentrations 1.33 h after dosing, which is closest to the tmax of the ezetimibe metabolite. Co‐administration of ezetimibe with rifampin resulted in even higher serum CP levels. The AUC0–24h of CPI and CPIII increased two‐ and threefold, respectively, after concomitant dosing compared to ezetimibe alone. Moreover, we quantified CP levels in cumulative urine from both study phases where the renally excreted amount (Ae) of CPI and CPIII increased after ezetimibe and rifampin co‐administration compared to ezetimibe alone. In conclusion, our findings indicate that rifampin co‐administration results in additional inhibition of OATP1B1 in vivo.

Objective In the digital age, patients turn to online sources for lumbar spine fusion information, necessitating a careful study of large language models (LLMs) like chat generative pre-trained transformer (ChatGPT) for patient education. Methods Our study aims to assess the response quality of Open AI (artificial intelligence)’s ChatGPT 3.5 and Google’s Bard to patient questions on lumbar spine fusion surgery. We identified 10 critical questions from 158 frequently asked ones via Google search, which were then presented to both chatbots. Five blinded spine surgeons rated the responses on a 4-point scale from ‘unsatisfactory’ to ‘excellent.’ The clarity and professionalism of the answers were also evaluated using a 5-point Likert scale. Results In our evaluation of 10 questions across ChatGPT 3.5 and Bard, 97% of responses were rated as excellent or satisfactory. Specifically, ChatGPT had 62% excellent and 32% minimally clarifying responses, with only 6% needing moderate or substantial clarification. Bard’s responses were 66% excellent and 24% minimally clarifying, with 10% requiring more clarification. No significant difference was found in the overall rating distribution between the 2 models. Both struggled with 3 specific questions regarding surgical risks, success rates, and selection of surgical approaches (Q3, Q4, and Q5). Interrater reliability was low for both models (ChatGPT: k = 0.041, p = 0.622; Bard: k = -0.040, p = 0.601). While both scored well on understanding and empathy, Bard received marginally lower ratings in empathy and professionalism. Conclusion ChatGPT3.5 and Bard effectively answered lumbar spine fusion FAQs, but further training and research are needed to solidify LLMs’ role in medical education and healthcare communication.

The development of a knowledge-based decision support system for the evaluation and planning of location and urban development concepts was implemented. In order to achieve this goal, cross-domain ontologies were developed for interdisciplinary databases, which are then mapped in semantic networks. The exponential growth in computing power in the hardware sector alone can no longer solve this problem, but at the same time enables the application of new methods for storing and evaluating data. Essentially, it is no longer just about the digital recording of object properties in conventional databases, but also about the digital representation of their significance for specific questions and the linking of meanings across the boundaries of specialist domains. This information is stored in a multimedia knowledge base, together with the methods and rules for its use and the evaluations and decisions based on it. The motivation for this project is the rapidly growing amount of data, which extends across ever new specialist domains and can no longer be sufficiently integrated into the decision-making of experts using conventional methods of knowledge acquisition. After determining this data, it was linked to a georeferencing. Within the framework of the project, documents were analyzed with the help of AI and examined for semantic text corpora. This data was georeferenced. Various algorithms were used to accomplish this task, including TF-IDF, TextRank and Word2Vec.

Remote video imagery using shoreline edge detection is widely used in coastal monitoring in order to acquire measurements of nearshore and swash features. Some of these systems are constrained by their long setup time, positioning requirements and considerable hardware costs. As such, there is a need for an autonomous low-cost system (~EUR 500), such as Timex cameras, that can be rapidly deployed in the field, while still producing the outcomes required for coastal monitoring. This research presents an assessment of the effect of the sampling strategy (time-lapse intervals) on the precision of shoreline detection for two low-cost cameras located in a remote coastal area in western Ireland, overlooking a dissipative beach–dune system. The analysis shows that RMSD in the detected shoreline is similar to other studies for sampling intervals ranging between 1 s and 30 s (i.e., RMSDmean for Camera 1 = 1.4 m and Camera 2 = 0.9 m), and an increase in the sampling interval from 1 s to 30 s had no significant adverse effect on the precision of shoreline detection. The research shows that depending on the intended use of the detected shorelines, the current standard of 1 s image sampling interval when using Timex cameras can be increased up to 30 s without any significant loss of accuracy. This positively impacts battery life and memory storage, making the systems more autonomous; for example, the battery life increased from ~10 days to ~100 days when the sampling interval was increased from 1 to 5 s.

Abstract The COVID-19 pandemic has posed a major challenge to healthcare systems globally. Millions of people have been infected, and millions of deaths have been reported worldwide. Glucocorticoids have attracted worldwide attention for their potential efficacy in the treatment of COVID-19. Various glucocorticoids with different dosages and treatment durations have been studied in patients with different severities, with a suitable dosage and treatment duration not yet defined. This study aimed to investigate whether in-hospital survival differs between critically ill patients treated with low-dose glucocorticoids, high-dose glucocorticoids or no glucocorticoids. All critically ill patients admitted to the intensive care unit of the Charité Hospital—Universitätsmedizin Berlin between February 2020 and December 2021 with COVID-19 pneumonia receiving supplemental oxygen were eligible to participate in this multicenter real-world data study. Patients were retrospectively assigned to one of three groups: the high corticosteroid dose (HighC) group (receiving 6 mg parenteral dexamethasone or an equivalent corticosteroid dosage for ten days), the low corticosteroid dose (LowC) group (receiving less than 6 mg parenteral dexamethasone or an equivalent corticosteroid dosage for ten days), or the no corticosteroid (NoC) group. Overall survival and risk effects were compared among groups within the total observation period, as well as at 35 days after the onset of COVID-19 symptoms. Adjusted multivariable Cox proportional hazard regression analysis was performed to compare the risk of death between the treatment groups. Out of 1561 critically ill COVID-19 patients, 1014 were included in the baseline analysis. In the survival study, 1009 patients were assigned to the NoC (n = 346), HighC (n = 552), or LowC group (n = 111). The baseline characteristics were balanced between groups, except for age, BMI, APACHE II score, SOFA and SAPS II. While the 35-day survival did not show any differences, a landmark analysis of the patients surviving beyond 35 days revealed differences between groups. The restricted mean survival time was 112 days in the LowC group [95% CI: 97 – 128], 133 days in the HighC group [95% CI: 124 – 141] and 144 days in the NoC group [95% CI: 121 – 167]. The multivariable-adjusted Cox proportional hazard analysis indicated that, regardless of age, sex, health status or invasive oxygenation, a low-dose treatment increased the hazard of death of critically ill COVID-19 patients by a factor of 2.09 ([95% CI: 0.99, 4.4], p = 0.05) and a high-dose corticosteroid treatment increased the risk by a factor of 1.07 ([95% CI: 0.53, 2.15], p = 0.85) compared to no treatment with glucocorticoids. The analysis reveals that corticosteroid treatment does not influence the survival of critically ill COVID-19 patients in the intensive care unit within 35 days. Our evaluations further suggest that regardless of ventilation status, the decision-making process for administering corticosteroid therapy should account for the individual severity of the illness.

Abstract Drowsiness while driving negatively impacts road safety, especially in truck drivers. The present study investigated the feasibility and alerting effects of a daylight-supplementing in-truck lighting system (DS) providing short-wavelength enriched light before, during, and after driving. In a within-participants design, eight truck drivers drove a fully-loaded truck under wintry Scandinavian conditions (low daylight levels) with a DS or placebo system for five days. Subjective and objective measures of alertness were recorded several times daily, and evening melatonin levels were recorded three times per study condition. DS significantly increased daytime light exposure without causing negative side effects while driving. In addition, no negative carry-over effects were observed on evening melatonin and sleepiness levels or on nighttime sleep quality. Moreover, objective alertness (i.e., psychomotor vigilance) before and after driving was significantly improved by bright light exposure. This effect was accompanied by improved subjective alertness in the morning. This field study demonstrated that DS was able to increase daytime light exposure in low-daylight conditions and to improve alertness in truck drivers before and after driving (e.g., during driving rest periods). Further studies are warranted to investigate the effects of daylight-supplementing in-cabin lighting on driving performance and road safety measures.

Aims: Periprosthetic joint infection (PJI) demonstrates the most feared complication after total joint replacement (TJR). The current work analyzes the demographic, comorbidity, and complication profiles of all patients who had in-hospital treatment due to PJI. Furthermore, it aims to evaluate the in-hospital mortality of patients with PJI and analyze possible risk factors in terms of secondary diagnosis, diagnostic procedures, and complications. Methods: In a retrospective, cross-sectional study design, we gathered all patients with PJI (International Classification of Diseases (ICD)-10 code: T84.5) and resulting in-hospital treatment in Germany between 1 January 2019 and 31 December 2022. Data were provided by the Institute for the Hospital Remuneration System in Germany. Demographic data, in-hospital deaths, need for intensive care therapy, secondary diagnosis, complications, and use of diagnostic instruments were assessed. Odds ratios (ORs) with 95% confidence intervals (CIs) for in-hospital mortality were calculated. Results: A total of 52,286 patients were included, of whom 1,804 (3.5%) died. Hypertension, diabetes mellitus, and obesity, the most frequent comorbidities, were not associated with higher in-hospital mortality. Cardiac diseases as atrial fibrillation, cardiac pacemaker, or three-vessel coronary heart disease showed the highest risk for in-hospital mortality. Postoperative anaemia occurred in two-thirds of patients and showed an increased in-hospital mortality (OR 1.72; p < 0.001). Severe complications, such as organ failure, systemic inflammatory response syndrome (SIRS), or septic shock syndrome showed by far the highest association with in-hospital mortality (OR 39.20; 95% CI 33.07 to 46.46; p < 0.001). Conclusion: These findings highlight the menace coming from PJI. It can culminate in multi-organ failure, SIRS, or septic shock syndrome, along with very high rates of in-hospital mortality, thereby highlighting the vulnerability of these patients. Particular attention should be paid to patients with cardiac comorbidities such as atrial fibrillation or three-vessel coronary heart disease. Risk factors should be optimized preoperatively, anticoagulant therapy stopped and restarted on time, and sufficient patient blood management should be emphasized. Cite this article: Bone Jt Open 2024;5(4):367–373.

Lipids play a major role in inflammatory diseases by altering inflammatory cell functions, either through their function as energy substrates or as lipid mediators such as oxylipins. Autophagy, a lysosomal degradation pathway that limits inflammation, is known to impact on lipid availability, however, whether this controls inflammation remains unexplored. We found that upon intestinal inflammation visceral adipocytes upregulate autophagy and that adipocyte-specific loss of the autophagy gene Atg7 exacerbates inflammation. While autophagy decreased lipolytic release of free fatty acids, loss of the major lipolytic enzyme Pnpla2/Atgl in adipocytes did not alter intestinal inflammation, ruling out free fatty acids as anti-inflammatory energy substrates. Instead, Atg7-deficient adipose tissues exhibited an oxylipin imbalance, driven through an NRF2-mediated upregulation of Ephx1. This shift reduced secretion of IL-10 from adipose tissues, which was dependent on the cytochrome P450-EPHX pathway, and lowered circulating levels of IL-10 to exacerbate intestinal inflammation. These results suggest an underappreciated fat-gut crosstalk through an autophagy-dependent regulation of anti-inflammatory oxylipins via the cytochrome P450-EPHX pathway, indicating a protective effect of adipose tissues for distant inflammation.

Among the various molecular CO2 reduction catalysts, the [Ni(cyclam)]2+ (Ni-{N4}) complex with its earth-abundant metal center and macrocyclic ligand proved to be efficient for the selective electrochemical conversion of CO2 to CO. In the present study we now connected the two Ni-cyclam units by using para- and meta-xylene as organic linkers attached to the amines of the macrocycle to form the p-{Ni2} and m-{Ni2} complexes, respectively, and test them as catalysts for the electrochemical CO2 reduction reactions. Notably, the p-{Ni2} complex demonstrates a higher faraday efficiency in the electrochemical reduction of CO2 to CO compared to the m-{Ni2} complex. This finding highlights the significant role played by the M-M distance in influencing this catalytic process.