bluuebunny/crossref_metadata_2025 huggingface dataset:
Blood-based cardiometabolic phenotypes in atrial fibrillation and their associated risk: EAST-AFNET 4 biomolecule study
Authors: Fabritz Larissa , Chua Winnie , Cardoso Victor R , Al-Taie Christoph , Borof Katrin , Suling Anna , Krause Linda , Kany Shinwan , Magnussen Christina , Wegscheider Karl , Breithardt Guenter , Crijns Harry J G M , Camm A John , Gkoutos George , Ellinor Patrick T , Goette Andreas , Schotten Ulrich , Wienhues-Thelen Ursula-Henrike , Zeller Tanja , Schnabel Renate B , Zapf Antonia , Kirchhof Paulus
Published: April 2024

Aims

Atrial fibrillation (AF) and concomitant cardiometabolic disease processes interact and combine to lead to adverse events, such as stroke, heart failure, myocardial infarction, and cardiovascular death. Circulating biomolecules provide quantifiable proxies for cardiometabolic disease processes. The aim of this study was to test whether biomolecule combinations can define phenotypes in patients with AF.

Methods and results

This pre-specified analysis of the EAST-AFNET 4 biomolecule study assigned patients to clusters using polytomous variable latent-class analysis based on baseline concentrations of 13 precisely quantified biomolecules potentially reflecting ageing, cardiac fibrosis, metabolic dysfunction, oxidative stress, cardiac load, endothelial dysfunction, and inflammation. In each cluster, rates of cardiovascular death, stroke, or hospitalization for heart failure or acute coronary syndrome, the primary outcome of EAST-AFNET 4, were calculated and compared between clusters over median 5.1 years follow-up. Findings were independently validated in a prospective cohort of 748 patients with AF (BBC-AF; median follow-up 2.9 years).

Unsupervised biomolecule analysis assigned 1586 patients (71 years old, 46% women) into four clusters. The highest risk cluster was dominated by elevated bone morphogenetic protein 10, insulin-like growth factor–binding protein 7, N-terminal pro-B-type natriuretic peptide, angiopoietin 2, and growth differentiation factor 15. Patients in the lowest risk cluster showed low concentrations of these biomolecules. Two intermediate-risk clusters differed by high or low concentrations of C-reactive protein, interleukin-6, and D-dimer. Patients in the highest risk cluster had a five-fold higher cardiovascular event rate than patients in the low-risk cluster. Early rhythm control was effective across clusters (Pinteraction = 0.63). Sensitivity analyses and external validation in BBC-AF replicated clusters and risk gradients.

Conclusion

Biomolecule concentrations identify cardiometabolic subphenotypes in patients with AF at high and low cardiovascular risk.
Hypertrophic cardiomyopathy detection with artificial intelligence electrocardiography in international cohorts: an external validation study
Authors: Siontis Konstantinos C , Wieczorek Mikolaj A , Maanja Maren , Hodge David O , Kim Hyung-Kwan , Lee Hyun-Jung , Lee Heesun , Lim Jaehyun , Park Chan Soon , Ariga Rina , Raman Betty , Mahmod Masliza , Watkins Hugh , Neubauer Stefan , Windecker Stephan , Siontis George C M , Gersh Bernard J , Ackerman Michael J , Attia Zachi I , Friedman Paul A , Noseworthy Peter A
Published: April 2024

Aims

Recently, deep learning artificial intelligence (AI) models have been trained to detect cardiovascular conditions, including hypertrophic cardiomyopathy (HCM), from the 12-lead electrocardiogram (ECG). In this external validation study, we sought to assess the performance of an AI-ECG algorithm for detecting HCM in diverse international cohorts.

Methods and results

A convolutional neural network-based AI-ECG algorithm was developed previously in a single-centre North American HCM cohort (Mayo Clinic). This algorithm was applied to the raw 12-lead ECG data of patients with HCM and non-HCM controls from three external cohorts (Bern, Switzerland; Oxford, UK; and Seoul, South Korea). The algorithm’s ability to distinguish HCM vs. non-HCM status from the ECG alone was examined. A total of 773 patients with HCM and 3867 non-HCM controls were included across three sites in the merged external validation cohort. The HCM study sample comprised 54.6% East Asian, 43.2% White, and 2.2% Black patients. Median AI-ECG probabilities of HCM were 85% for patients with HCM and 0.3% for controls (P < 0.001). Overall, the AI-ECG algorithm had an area under the receiver operating characteristic curve (AUC) of 0.922 [95% confidence interval (CI) 0.910–0.934], with diagnostic accuracy 86.9%, sensitivity 82.8%, and specificity 87.7% for HCM detection. In age- and sex-matched analysis (case–control ratio 1:2), the AUC was 0.921 (95% CI 0.909–0.934) with accuracy 88.5%, sensitivity 82.8%, and specificity 90.4%.

Conclusion

The AI-ECG algorithm determined HCM status from the 12-lead ECG with high accuracy in diverse international cohorts, providing evidence for external validity. The value of this algorithm in improving HCM detection in clinical practice and screening settings requires prospective evaluation.
Durable left ventricular assist device explantation following recovery in paediatric patients: Determinants and outcome after explantation
Authors: Rohde Sofie , Miera Oliver , Sliwka Joanna , Sandica Eugen , Amodeo Antonio , Veen Kevin , de By Theo M M H , Bogers Ad J J C , Schweiger Martin
Published: April 2024

OBJECTIVES

Myocardial recovery in children supported by a durable left ventricular assist device is a rare, but highly desirable outcome because it could potentially eliminate the need for a cardiac transplant and the lifelong need for immunosuppressant therapy and the risk of complications. However, experience with this specific outcome is extremely limited.

METHODS

All patients < 19 years old supported by a durable left ventricular assist device from the European Registry for Patients with Mechanical Circulatory Support database were included. Participating centres were approached for additional follow-up data after explantation. Associated factors for explantation due to myocardial recovery were explored using Cox proportional hazard models.

RESULTS

The incidence of recovery in children supported by a durable left ventricular assist device was 11.7% (52/445; median duration of support, 122.0 days). Multivariable analyses showed body surface area (hazard ratio 0.229; confidence interval 0.093–0.565; P = 0.001) and a primary diagnosis of myocarditis (hazard ratio 4.597; confidence interval 2.545–8.303; P < 0.001) to be associated with recovery. Left ventricular end-diastolic diameter in children with myocarditis was not associated with recovery. Follow-up after recovery was obtained for 46 patients (88.5%). Sustained myocardial recovery was reported in 33/46 (71.7%) at the end of the follow-up period (28/33; >2 year). Transplants were performed in 6/46 (11.4%) (in 5 after a ventricular assist device was reimplanted). Death occurred in 7/46 (15.2%).

CONCLUSIONS

Myocardial recovery occurs in a substantial portion of paediatric patients supported with durable left ventricular assist devices, and sustainable recovery is seen in around three-quarters of them. Even children with severely dilated ventricles due to myocarditis can show recovery. Clinicians should be attentive to (developing) myocardial recovery. These results can be used to develop internationally approved paediatric weaning guidelines.
Evidence-based potential of generative artificial intelligence large language models in orthodontics: a comparative study of ChatGPT, Google Bard, and Microsoft Bing
Authors: Makrygiannakis Miltiadis A , Giannakopoulos Kostis , Kaklamanos Eleftherios G
Published: April 2024

Background

The increasing utilization of large language models (LLMs) in Generative Artificial Intelligence across various medical and dental fields, and specifically orthodontics, raises questions about their accuracy.

Objective

This study aimed to assess and compare the answers offered by four LLMs: Google’s Bard, OpenAI’s ChatGPT-3.5, and ChatGPT-4, and Microsoft’s Bing, in response to clinically relevant questions within the field of orthodontics.

Materials and methods

Ten open-type clinical orthodontics-related questions were posed to the LLMs. The responses provided by the LLMs were assessed on a scale ranging from 0 (minimum) to 10 (maximum) points, benchmarked against robust scientific evidence, including consensus statements and systematic reviews, using a predefined rubric. After a 4-week interval from the initial evaluation, the answers were reevaluated to gauge intra-evaluator reliability. Statistical comparisons were conducted on the scores using Friedman’s and Wilcoxon’s tests to identify the model providing the answers with the most comprehensiveness, scientific accuracy, clarity, and relevance.

Results

Overall, no statistically significant differences between the scores given by the two evaluators, on both scoring occasions, were detected, so an average score for every LLM was computed. The LLM answers scoring the highest, were those of Microsoft Bing Chat (average score = 7.1), followed by ChatGPT 4 (average score = 4.7), Google Bard (average score = 4.6), and finally ChatGPT 3.5 (average score 3.8). While Microsoft Bing Chat statistically outperformed ChatGPT-3.5 (P-value = 0.017) and Google Bard (P-value = 0.029), as well, and Chat GPT-4 outperformed Chat GPT-3.5 (P-value = 0.011), all models occasionally produced answers with a lack of comprehensiveness, scientific accuracy, clarity, and relevance.

Limitations

The questions asked were indicative and did not cover the entire field of orthodontics.

Conclusions

Language models (LLMs) show great potential in supporting evidence-based orthodontics. However, their current limitations pose a potential risk of making incorrect healthcare decisions if utilized without careful consideration. Consequently, these tools cannot serve as a substitute for the orthodontist’s essential critical thinking and comprehensive subject knowledge. For effective integration into practice, further research, clinical validation, and enhancements to the models are essential. Clinicians must be mindful of the limitations of LLMs, as their imprudent utilization could have adverse effects on patient care.
A long and winding road: culture change on data sharing in exposomics
Authors: Wright Robert O , Makris Konstantinos C , Natsiavas Pantelis , Fennell Timothy , Rushing Blake R , Wilson Ander ,   Members of the Exposomics Consortium, Adamu Yau , Adar Sara D , Adebamowo Clement , Akhtari Farida , Akhtari Farida , Argos Maria , Arunachalam Saravanan , Baumert Brittney , Beglarian Emily , Berger Kimberly , Bhutani Jessie , Cai Lu , Calafat Antonia , Chao Mu-Rong , Chatziioannou Anastasia Chrysovalantou , Cheng Qiwen , Chung Ming Kei , Chung Ming Kei , Chung Ming Kei , Clark Robert , Hubal Elaine Cohen , Cooke Marcus , Costello Elizabeth , Cui Yuxia , Dierickx Erin , Dolinoy Dana , Du Xiuxia , Folle Aline Duarte , Gao Peng , Gaulke Christopher , Giebelhaus Ryland T , Goodrich Jesse , Grafanaki Katerina , Gullapalli Rama , Habre Rima , Hanson Heidi , Harari Homero , Hart Jaime , He Jingxuan , Holmes Philip , Hood Darryl B , House John , Hu Hui , Hu Chiung-Wen , James Peter , Jankowska Marta , Ji Hong , Kannan Srimathik , Konstantinou Corina , Lai Yunjia , Langston Mike , Lasalle Janine , Liang Donghai , Liao Jiawen , Luo Jiajun , Makris Konstantinos C , Manz Katherine , Miller Gary , Motsinger-Reif Alison , Ouidir Marion , Page Grier , Pan Shudi , Parker Graham , Paul Kimberly , Peluso Alina , Penning Trevor , Pierce Brandon , Prajapati Nirmala , Quintana Penelope J E , Rajasekar Arcot (Raja) , Ramesh Aramandla , Ruden Douglas , Rushing Blake , Schmitt Charles , Schüssler-Fiorenza Rose Sophia Miryam , Shah Ruchir , Shahriar Mohammad , Soares Lissa , Soliman Ghada , Stanek Lindsay , States J Christopher , Stingone Jeanette , Irizarry Savannah Sturla , Sun Yangbo , Teitelbaum Susan , Tong Ai Phuong , Vijayakumar Nisha , Walker Ryan , Wang Yi , Whyte Kathryn , Wu Lang , Wu K Lily , Yuan Xin/Jean , Zhang Qiong , Zhang Xinyue , Zhang Kai , Zhao Neil
Published: April 2024

Data sharing requires cooperation from data generators (eg, epidemiologists, lab investigators) and data users (eg, epidemiologists, biostatisticians, computer scientists). Data generation and data use in human exposome studies require significant but different skill sets and are separated temporally in many cases. Sharing will require maintaining a history of data generation and a system to address the concerns of data generators around credit for conducting rigorous work (eg, authorship). Sharing also requires addressing the needs of data users to facilitate harmonization, searchability and QA/QC of data. We present these issues from the perspectives of data generators and data users and include the special case of real-world data (eg, electronic health records). We conclude with recommendations to address how to better promote data sharing in exposomics through authorship, cost recovery and addressing ethical issues.
Volatiles profiles and factors affecting absorption of key odorants in Osmanthus black tea
Authors: Dai Binwei , Chen Weixuan , Huang Weihong , Liu Junsheng , Li Bo , He Puming , Grierson Donald , Tu Youying , Wu Yuanyuan
Published: April 2024

Objectives

Osmanthus black tea (OBT) is produced by reprocessing black tea while it absorbs the fragrance of Osmanthus fragrans and this scenting process is crucial for forming the unique aroma of OBT. This work intended to reveal the effects of scenting parameters, the types of base tea, and scenting technologies on the aroma quality of OBT.

Materials and Methods

In this study, volatile compounds of OBTs with different scenting parameters, types of base tea, and scenting technologies were analyzed by solid-phase microextraction and gas chromatography–mass spectrometry. Weighted gene co-expression network analysis and orthogonal partial least squares discriminant analysis were used to identify the key volatile compounds of OBT.

Results

More than 80 volatile compounds of OBT were found, and six compounds, α-ionone, β-ionone, γ-decalactone, dihydro-β-ionone, dihydro-β-ionol, and 6-pentyl-2-pyrone, were identified as the key volatiles of OBT. As scenting time (ST) increased, the key volatile compounds in OBT showed an upward trend or increased initially and then decreased. Meanwhile, the contents of key volatile compounds increased as the ratio of flowers to tea (RFT) increased. In addition, base teas with a high proportion of pekoes produced higher-quality OBT by absorbing more key volatile compounds from O. fragrans. Comparing OBTs made from the fast-scenting process and the traditional scenting process (TS), showed that higher aroma quality was obtained through repeated scenting rounds of TS.

Conclusions

Appropriate long ST and high RFT, as well as base tea with a high proportion of pekoes and TS with repeated scenting rounds are beneficial for the accumulation of odorants and the improvement of aroma quality in OBT.
Current advances and future directions in combined hepatocellular and cholangiocarcinoma
Authors: Zhang Yu-Zhu , Liu Yu-Chen , Su Tong , Shi Jiang-Nan , Huang Yi , Liang Bo
Published: April 2024

The low incidence of combined hepatocellular cholangiocarcinoma (cHCC-CCA) is an important factor limiting research progression. Our study extensively included nearly three decades of relevant literature and assembled the most comprehensive database comprising 5,742 patients with cHCC-CCA. We summarized the characteristics, tumor markers, and clinical features of these patients. Additionally, we present the evolution of cHCC-CCA classification and explain the underlying rationale for these classification standards. We reviewed cHCC-CCA diagnostic advances using imaging features, tumor markers, and postoperative pathology, as well as treatment options such as surgical, adjuvant, and immune-targeted therapies. In addition, recent advances in more effective chemotherapeutic regimens and immune-targeted therapies were explored. Furthermore, we described the molecular mutation features and potential specific markers of cHCC-CCA. The prognostic value of Nestin has been proven, and we speculate that Nestin will also play a role in classification and diagnosis. However, further research is needed. Moreover, we believe that the possibility of using machine learning liquid biopsy for preoperative diagnosis and establishing a scoring system are directions for future research.
Enhancing tomato fruit antioxidant potential through hydrogen nanobubble irrigation
Authors: He Jing , Zhou Yunpeng , Geilfus Christoph-Martin , Cao Jiankang , Fu Daqi , Baram Shahar , Liu Yanzheng , Li Yunkai
Published: April 2024

Eating fruits and vegetables loaded with natural antioxidants can boost human health considerably and help fight off diseases linked to oxidative stress. Hydrogen has unique antioxidant effects. However, its low-solubility and fast-diffusion has limited its applications in agriculture. Integration of hydrogen with nanobubble technology could address such problems. However, the physiological adaptation and response mechanism of crops to hydrogen nanobubbles is still poorly understood. Antioxidant concentrations of lycopene, ascorbic acid, flavonoids, and resveratrol in hydrogen nanobubble water drip-irrigated tomato fruits increased by 16.3–264.8% and 2.2–19.8%, respectively, compared to underground water and oxygen nanobubble water. Transcriptomic and metabolomic analyses were combined to investigate the regulatory mechanisms that differed from the controls. Comprehensive multi-omics analysis revealed differences in the abundances of genes responsible for hormonal control, hydrogenase genes, and necessary synthetic metabolites of antioxidants, which helped to clarify the observed improvements in antioxidants. This is the first case of hydrogen nanobubble water irrigation increasing numerous natural antioxidant parts in fruits. Considering the characteristics of hydrogen and the application of the nanobubble technology in agriculture, the findings of the present study could facilitate the understanding of the potential effects of hydrogen on biological processes and the mechanisms of action on plant growth and development.
Response to Food Restriction, but Not Social Information Use, Varies Seasonally in Captive Cardueline Finches
Authors: Cornelius J M , Vernasco B J , Mori N , Watts H E
Published: April 2024

Synopsis

Temperate winters can impose severe conditions on songbirds that threaten survival, including shorter days and often lower temperatures and food availability. One well-studied mechanism by which songbirds cope with such conditions is seasonal acclimatization of thermal metabolic traits, with strong evidence for both preparative and responsive changes in thermogenic capacity (i.e., the ability to generate heat) to low winter temperatures. However, a bird’s ability to cope with seasonal extremes or unpredictable events is likely dependent on a combination of behavioral and physiological traits that function to maintain allostatic balance. The ability to cope with reduced food availability may be an important component of organismal response to temperate winters in songbirds. Here, we compare responses to experimentally reduced food availability at different times of year in captive red crossbills (Loxia curvirostra) and pine siskins (Spinus pinus)—two species that cope with variable food resources and live in cold places—to investigate seasonal changes in the organismal response to food availability. Further, red crossbills are known to use social information to improve responses to reduced food availability, so we also examine whether the use of social information in this context varies seasonally in this species. We find that pine siskins and red crossbills lose less body mass during time-restricted feedings in late winter compared to summer, and that red crossbills further benefit from social information gathered from observing other food-restricted red crossbills in both seasons. Observed changes in body mass were only partially explained by seasonal differences in food intake. Our results demonstrate seasonal acclimation to food stress and social information use across seasons in a controlled captive environment and highlight the importance of considering diverse physiological systems (e.g., thermogenic, metabolic, digestive, etc.) to understand organismal responses to environmental challenges.
Epidemiology, aetiology and diagnosis of congenital hearing loss via hearing screening of 153 913 newborns
Authors: Yoshimura Hidekane , Okubo Takuya , Shinagawa Jun , Nishio Shin-Ya , Takumi Yutaka , Usami Shin-Ichi
Published: April 2024

Background

Congenital hearing loss (HL), one of the most common paediatric chronic conditions, significantly affects speech and language development. Its early diagnosis and medical intervention can be achieved via newborn hearing screening. However, data on the prevalence and aetiology of congenital HL in infants who fail newborn hearing screening are limited.

Methods

The sample population included 153 913 infants who underwent newborn hearing screening, and the prevalence of congenital HL, defined as moderate to profound bilateral HL (BHL) or unilateral HL (UHL) (≥40 dB HL), in one prefecture of Japan was measured to minimize the loss-to-follow-up rate, a common factor affecting the screening procedure. Comprehensive aetiological investigation, including physiology, imaging, genetic tests, and congenital cytomegalovirus screening, was performed on children diagnosed with congenital HL.

Results

The calculated prevalence of congenital HL was 1.62 per 1000 newborns (bilateral, 0.84; unilateral, 0.77). More than half of the cases with congenital bilateral or severe to profound UHL showed genetic aetiology or cochlear nerve deficiency (CND), respectively. Approximately 4% and 6% of the cases of congenital BHL and UHL were associated with congenital cytomegalovirus infection and auditory neuropathy spectrum disorder, respectively.

Conclusions

This is an epidemiological and comprehensive aetiological study of congenital HL, as determined via newborn hearing screening according to its severity and laterality, in a large-scale general population of a developed country. Our findings can serve as a reference for optimizing care and intervention options for children with HL and their families.
Carbon emission measurement of the envelope of a university teaching building in Hefei City
Authors: Gan Shenqi , Feng Jiawang , Fang Bigen , Chen Wenxiang
Published: April 2024

In response to the challenges posed by global warming, China has formulated dual carbon goals. In this context, the construction industry, a key carbon emitter, is vital for implementing energy-saving and emission-reducing strategies. This study zeroes in on the pivotal role of building envelope structures in carbon emissions, with a focus on a university building in Hefei. Commencing with onsite measurements to gather initial data, the study leverages simulation software to conduct an in-depth analysis. Employing orthogonal experimental design and variance analysis, it meticulously assesses the carbon emissions associated with different materials used in exterior walls, roofs and windows, considering both the material production and building operation phases. The research scrutinizes the impact of these materials on carbon emissions, with a special focus on the performance of seven distinct building retrofit schemes. Key findings of the study underscore that the type and thickness of exterior wall materials substantially influence carbon emissions during the production phase. Conversely, the choice of window materials emerges as more critical in reducing emissions during the building operation phase. The implementation of the various retrofit schemes demonstrates a tangible reduction in overall building carbon emissions. Specifically, these schemes yield a yearly reduction in carbon emissions of 2.96–3.62 tons during operation and a substantial decrease of 30.36–165.97 tons in the production phase, compared to the original structure of the case study building. These insights not only offer practical and viable strategies for the construction industry’s low-carbon development but also provide theoretical underpinnings and references for future building designs and retrofits.
National Pride, Economic Evaluation, and Public Support for Economic Sanctions: The Case of Japan’s Economic Sanctions Against South Korea
Authors: Kim Seongjo , Kim Hanna
Published: April 2024

This study addresses a research gap by exploring the impact of emotional factors, specifically national pride, on public support for economic sanctions, which has received relatively limited attention compared to the strategic aspects of sanctions. Our proposal posits that citizens’ national pride, acting as a symbolic motivation, particularly in the context of hostile national competition, can result in increased support for economic sanctions. Furthermore, we suggest that among individuals with strong national pride, the likelihood of supporting economic sanctions tends to rise as their economic perceptions improve. To investigate this relationship, we analyzed data from Japan Electoral Study VI, conducted during Japan’s economic sanctions against South Korea in 2019. These findings reveal that national pride significantly shapes public opinion on economic sanctions and that among individuals with strong national pride, positive perceptions of economic conditions act as a catalyst, strengthening their support for economic sanctions.
Reckoning with Colonial Legacies of Harm: Victoria’s Yoorrook Justice Commission
Authors: Bracka Jeremie M
Published: April 2024

Australia’s colonial era is formally over. Yet the legacies of structural inequality, dispossession, exploitation and racism against Indigenous Australia remain alive and well. In 2021, Victoria established the Yoorrook Justice Commission, culminating in a formal truth-telling and treaty process. Seeking to address harm since colonization, the state process is unprecedented both nationally and abroad. This article considers the relevance of the commission to truth recovery, accountability and structural reform in Australia. To date, national efforts to deal with the colonial past have been piecemeal and relatively ineffective. The Yoorrook Justice Commission departs from previous single-issue inquiries as well as from reconciliation policies driven by white-Australian federal institutions. While the Commission is not a panacea for resolving colonial injustice, it provides an important means of relational and structural truth-telling towards more just relations and righting racial wrongs. Ultimately, the Yoorrook Justice Commission sets a valuable precedent for Australia and other postcolonial nations. Its level of Indigenous ownership, its authority as a Royal Commission and the breadth of its inquiry make it a significant transitional justice project.
The Costs of Caring: Quantifying Compassion Fatigue and Compassion Satisfaction in Burn Therapists
Authors: Yelvington Miranda L , Corson Tyler , Hu Jiale , Wood Rachel E , Reynolds Stacey
Published: April 2024

Recovery from a severe burn injury requires early and aggressive therapy, which is often painful and distressing to the patient. Burn therapists who guide these interventions may be prone to experiencing secondary trauma and compassion fatigue through repeated exposure to difficult situations. At the same time, therapists may gain a sense of purpose and altruism from their work, fostering compassion satisfaction. Despite being well documented in other health professions, compassion fatigue and compassion satisfaction have not been sufficiently explored among burn therapists. This study aimed to quantify and characterize burn therapists’ compassion fatigue and satisfaction using the Professional Quality of Life scale and to answer the question of what job-related factors may impact these outcomes. A total of 143 burn therapists participated in this study. Results revealed compassion fatigue subsale scores of burnout and secondary traumatic stress in the low or moderate range and compassion satisfaction scores in the moderate or high ranges for all participants. This study presents new knowledge for the field of burn care in its quantification of professional quality of life in burn therapists. While burn therapists experienced moderate-to-high levels of compassion satisfaction in their work, burnout and stress also approached moderate levels. Years of practice was a significant predictor of compassion. Although the reasons for this are not clear, it may be related to increased competence or confidence in practice and may suggest a need for different support strategies for practitioners at each stage of their burn therapy career.
Submarine cable detection using an end-to-end neural network-based magnetic data inversion
Authors: Liu Yutao , Wu Yuquan , Li Gang , Abbas Aqeel , Shi Taikun
Published: April 2024

To process magnetic anomaly data, appropriate parameters for field separation, denoising, and Euler deconvolution must be manually selected. The traditional workflow is inefficient and cannot fulfill the rapid detection of submarine cables due to complex processing and manual parameter tuning. This study presents an end-to-end deep learning approach for the identification and positioning of submarine cables based on magnetic anomalies. The proposed approach effectively establishes a direct mapping correlation between the magnetic field data and the position of the submarine cable. Synthetic tests suggest that our method performs better in terms of positioning accuracy than the conventional Euler method. Our results for the field data are comparable to those obtained using conventional techniques. Furthermore, the proposed method achieves an optimal solution by employing a clustering technique and selecting the solution with the maximum confidence, which avoids spurious solutions associated with traditional methods. The proposed method can directly determine the position of the submarine cables using the raw magnetic field data. Contrary to the traditional processing workflow, field separation and denoising are not necessary in this novel approach, resulting in higher processing efficiency and a simpler processing process.
Gian Giacomo Poldi Pezzoli and Florence
Authors: Giacomelli Luca
Published: April 2024

Gian Giacomo Poldi Pezzoli visited Florence repeatedly throughout his life, starting in childhood, when he accompanied his mother, Rosina Trivulzio (1800–1859). Drawing on a number of documented visits, such as one that took in the Italian National Exhibition of 1861 and another to the Dante celebrations of 1865, the aim of this essay is to examine Poldi Pezzoli’s relationship with the artistic environment, the collections and the important art market of Florence.
Multi-modular metabolic engineering and efflux engineering for enhanced lycopene production in recombinant Saccharomyces cerevisiae
Authors: Huang Guangxi , Li Jiarong , Lin Jingyuan , Duan Changqing , Yan Guoliang
Published: April 2024

Lycopene has been widely used in the food industry and medical field due to its antioxidant, anti-cancer, and anti-inflammatory properties. However, achieving efficient manufacture of lycopene using chassis cells on an industrial scale remains a major challenge. Herein, we attempted to integrate multiple metabolic engineering strategies to establish an efficient and balanced lycopene biosynthetic system in Saccharomyces cerevisiae. First, the lycopene synthesis pathway was modularized to sequentially enhance the metabolic flux of the mevalonate pathway, the acetyl-CoA supply module, and lycopene exogenous enzymatic module. The modular operation enabled the efficient conversion of acetyl-CoA to downstream pathway of lycopene synthesis, resulting in a 3.1-fold increase of lycopene yield. Second, we introduced acetate as an exogenous carbon source and utilized an acetate-repressible promoter to replace the natural ERG9 promoter. This approach not only enhanced the supply of acetyl-CoA but also concurrently diminished the flux toward the competitive ergosterol pathway. As a result, a further 42.3% increase in lycopene production was observed. Third, we optimized NADPH supply and mitigated cytotoxicity by overexpressing ABC transporters to promote lycopene efflux. The obtained strain YLY-PDR11 showed a 12.7-fold increase in extracellular lycopene level compared to the control strain. Finally, the total lycopene yield reached 343.7 mg/L, which was 4.3 times higher than that of the initial strain YLY-04. Our results demonstrate that combining multi-modular metabolic engineering with efflux engineering is an effective approach to improve the production of lycopene. This strategy can also be applied to the overproduction of other desirable isoprenoid compounds with similar synthesis and storage patterns in S. cerevisiae.

One-Sentence Summary

In this research, lycopene production in yeast was markedly enhanced by integrating a multi-modular approach, acetate signaling-based down-regulation of competitive pathways, and an efflux optimization strategy.
Limbic-predominant age-related TDP-43 encephalopathy (LATE-NC): Co-pathologies and genetic risk factors provide clues about pathogenesis
Authors: Nelson Peter T , Fardo David W , Wu Xian , Aung Khine Zin , Cykowski Matthew D , Katsumata Yuriko
Published: April 2024

Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is detectable at autopsy in more than one-third of people beyond age 85 years and is robustly associated with dementia independent of other pathologies. Although LATE-NC has a large impact on public health, there remain uncertainties about the underlying biologic mechanisms. Here, we review the literature from human studies that may shed light on pathogenetic mechanisms. It is increasingly clear that certain combinations of pathologic changes tend to coexist in aging brains. Although “pure” LATE-NC is not rare, LATE-NC often coexists in the same brains with Alzheimer disease neuropathologic change, brain arteriolosclerosis, hippocampal sclerosis of aging, and/or age-related tau astrogliopathy (ARTAG). The patterns of pathologic comorbidities provide circumstantial evidence of mechanistic interactions (“synergies”) between the pathologies, and also suggest common upstream influences. As to primary mediators of vulnerability to neuropathologic changes, genetics may play key roles. Genes associated with LATE-NC include TMEM106B, GRN, APOE, SORL1, ABCC9, and others. Although the anatomic distribution of TDP-43 pathology defines the condition, important cofactors for LATE-NC may include Tau pathology, endolysosomal pathways, and blood-brain barrier dysfunction. A review of the human phenomenology offers insights into disease-driving mechanisms, and may provide clues for diagnostic and therapeutic targets.
Are prophylactic antibiotics required for combined intracavitary and interstitial brachytherapy of gynecologic cancers?
Authors: Kumazawa Takuya , Ohkubo Yu , Mochida Keishiro , Kondo Saori , Oguchi Osamu , Yoshida Daisaku
Published: April 2024

The purpose of this study is to evaluate the need for prophylactic antibiotic treatment prior to combined intracavitary and interstitial (hybrid) brachytherapy for gynecologic cancer. A total of 105 gynecologic cancer patients received 405 brachytherapy sessions, including 302 sessions of intracavitary brachytherapy and 103 sessions of hybrid brachytherapy. Prophylactic antibiotics were administered before 35% of the hybrid brachytherapy sessions. The incidence of postbrachytherapy fever and the frequency of subsequent antibiotic use for infection were compared between treatment groups. Among patients treated with hybrid brachytherapy, fever ≥37.5°C occurred in 16.4% of those not receiving prophylactic antibiotics and 16.7% of those receiving prophylactic antibiotics (P > 0.05). Similarly, fever ≥38.0°C occurred in 4.9% of patients not receiving prophylactic antibiotics and 2.4% of those receiving prophylactic antibiotics (P > 0.05). Additional antibiotics were used to treat postbrachytherapy infections in 4.8% of the group receiving prophylactic antibiotics and 0% of those not receiving prophylactic antibiotics, again without statistically significant difference. There were also no significant differences in posttreatment fever incidence and antibiotics use for infection between intracavitary brachytherapy and hybrid brachytherapy sessions. In conclusion, the incidences of infection and fever are low following hybrid brachytherapy, so prophylactic antibiotics are generally unnecessary.
The Individuated, Messianic Servant of OG Isaiah 41–45
Authors: Martin Michael Wade
Published: April 2024

The study examines the servant oracles of Isaiah 41–45, which in the MT present a collectivist, national understanding of the figure, but in the OG are rendered so that the servant is individuated, both in the sense that he is granted clearly the quality of individuality, and in the sense that he is distinguished clearly from the collective nation he serves. The servant is also thereby rendered messianic, as Israel’s eschatological rule is transferred to this individual, along with God’s epithet, ‘your king’, and as intertextual references identify this figure as one and the same with the Davidic king of Isaiah 9 and 11. Thus OG Isaiah 41–45 attests the emergence of individualist interpretation of the servant well before the common era. These chapters also show the place of messianism in the Septuagint and in second century Alexandria.
Probing and imaging phospholipid dynamics in live cells
Authors: Wu Zhongsheng , Du Yongtao , Kirchhausen Tom , He Kangmin
Published: April 2024

Distinct phospholipid species display specific distribution patterns across cellular membranes, which are important for their structural and signaling roles and for preserving the integrity and functionality of the plasma membrane and organelles. Recent advancements in lipid biosensor technology and imaging modalities now allow for direct observation of phospholipid distribution, trafficking, and dynamics in living cells. These innovations have markedly advanced our understanding of phospholipid function and regulation at both cellular and subcellular levels. Herein, we summarize the latest developments in phospholipid biosensor design and application, emphasizing the contribution of cutting-edge imaging techniques to elucidating phospholipid dynamics and distribution with unparalleled spatiotemporal precision.
The EBLM project – XIII. The absolute dynamical masses of the circumbinary planet host TOI-1338/BEBOP-1, and applications to the study of exoplanet atmospheres
Authors: Sebastian D , Triaud A H M J , Brogi M , Baycroft Thomas A , Standing Matthew R , Maxted Pierre F L , Martin David V , Sairam Lalitha , Nielsen Martin B
Published: April 2024

High-contrast eclipsing binaries with low mass M-dwarf secondaries are precise benchmark stars to build empirical mass–radius relationships for fully convective low-mass ($\rm M_{\star } \lt 0.35\, M_{\odot }$) dwarf stars. The contributed light of the M-dwarf in such binaries is usually much less than one per cent at optical wavelengths. This enables the detection of circumbinary planets from precise radial velocity measurements. High-resolution cross-correlation techniques are typically used to detect exoplanet atmospheres. One key aspect of these techniques is the post-processing, which includes the removal of telluric and spectral lines of the host star. We introduce the application of such techniques to optical high-resolution spectra of the circumbinary planet-host TOI-1338/BEBOP-1, turning it effectively into a double-lined eclipsing binary. By using simulations, we further explore the impact of post-processing techniques for high-contrast systems. We detect the M-dwarf secondary with a significance of 11σ and measure absolute dynamical masses for both components. Compared to previous model-dependent mass measurements, we obtain a four times better precision. We further find that the post-processing results in negligible systematic impact on the radial velocity precision for TOI-1338/BEBOP-1 with more than $96.6\,$ per cent (1σ) of the M-dwarf’s signal being conserved. We show that these methods can be used to robustly measure dynamical masses of high-contrast single-lined binaries providing important benchmark stars for stellar evolution particularly near the bottom of the main sequence. We also demonstrate how to retrieve the phase curve of an exoplanet with high-resolution spectroscopy using our data.
The EBLM Project XII. An eccentric, long-period eclipsing binary with a companion near the hydrogen-burning limit
Authors: Davis Yasmin T , Triaud Amaury H M J , Freckelton Alix V , Mortier Annelies , Sebastian Daniel , Brahm Rafael , Baycroft Thomas , Dransfield Georgina , Duck Alison , Henning Thomas , Hobson Melissa J , Jordán Andrés , Kunovac Vedad , Martin David V , Maxted Pierre F L , Sairam Lalitha , Standing Matthew R , Swayne Matthew I , Trifonov Trifon , Udry Stéphane
Published: April 2024

In the hunt for Earth-like exoplanets, it is crucial to have reliable host star parameters, as they have a direct impact on the accuracy and precision of the inferred parameters for any discovered exoplanet. For stars with masses between 0.35 and 0.5 M⊙, an unexplained radius inflation is observed relative to typical stellar models. However, for fully convective objects with a mass below 0.35 M⊙, it is not known whether this radius inflation is present, as there are fewer objects with accurate measurements in this regime. Low-mass eclipsing binaries present a unique opportunity to determine empirical masses and radii for these low-mass stars. Here, we report on such a star, EBLM J2114−39 B. We have used HARPS and FEROS radial velocities and TESS photometry to perform a joint fit of the data and produce one of the most precise estimates of a very low mass star’s parameters. Using a precise and accurate radius for the primary star using Gaia DR3 data, we determine J2114−39 to be a M1 = 0.998 ± 0.052 M⊙ primary star hosting a fully convective secondary with mass $M_2~=~0.0993~\pm 0.0033~\, \mathrm{M_{\odot }}$, which lies in a poorly populated region of parameter space. With a radius $R_2 =~0.1250~\pm 0.0016~\, \mathrm{R_{\odot }}$, similar to TRAPPIST-1, we see no significant evidence of radius inflation in this system when compared to stellar evolution models. We speculate that stellar models in the regime where radius inflation is observed might be affected by how convective overshooting is treated.
Impact of astrophysical effects on the dark matter mass constraint with 21 cm intensity mapping
Authors: Murakami Koya , Nishizawa Atsushi J , Nagamine Kentaro , Shimizu Ikko
Published: April 2024

We present an innovative approach to constraining the non-cold dark matter model using a convolutional neural network (CNN). We perform a suite of hydrodynamic simulations with varying dark matter particle masses and generate mock 21 cm radio intensity maps to trace the dark matter distribution at z = 3 in the postreionization epoch. Our proposed method complements the traditional power-spectrum analysis. We compare the results of the CNN classification between the mock maps with different dark matter masses with those from the two-dimensional power spectrum of the differential brightness temperature map of 21 cm radiation. We find that the CNN outperforms the power spectrum. Moreover, we investigate the impact of baryonic physics on the dark matter model constraint, including star formation, self-shielding of H i gas, and ultraviolet background model. We find that these effects may introduce some contamination in the dark matter constraint, but they are insignificant compared to the system noise of the SKA instruments.
The long non-coding RNA Meg3 mediates imprinted gene expression during stem cell differentiation
Authors: Farhadova Sabina , Ghousein Amani , Charon François , Surcis Caroline , Gomez-Velazques Melisa , Roidor Clara , Di Michele Flavio , Borensztein Maud , De Sario Albertina , Esnault Cyril , Noordermeer Daan , Moindrot Benoit , Feil Robert
Published: April 2024

The imprinted Dlk1-Dio3 domain comprises the developmental genes Dlk1 and Rtl1, which are silenced on the maternal chromosome in different cell types. On this parental chromosome, the domain's imprinting control region activates a polycistron that produces the lncRNA Meg3 and many miRNAs (Mirg) and C/D-box snoRNAs (Rian). Although Meg3 lncRNA is nuclear and associates with the maternal chromosome, it is unknown whether it controls gene repression in cis. We created mouse embryonic stem cells (mESCs) that carry an ectopic poly(A) signal, reducing RNA levels along the polycistron, and generated Rian−/− mESCs as well. Upon ESC differentiation, we found that Meg3 lncRNA (but not Rian) is required for Dlk1 repression on the maternal chromosome. Biallelic Meg3 expression acquired through CRISPR-mediated demethylation of the paternal Meg3 promoter led to biallelic Dlk1 repression, and to loss of Rtl1 expression. lncRNA expression also correlated with DNA hypomethylation and CTCF binding at the 5′-side of Meg3. Using Capture Hi-C, we found that this creates a Topologically Associating Domain (TAD) organization that brings Meg3 close to Dlk1 on the maternal chromosome. The requirement of Meg3 for gene repression and TAD structure may explain how aberrant MEG3 expression at the human DLK1-DIO3 locus associates with imprinting disorders.
Quantifying the activity profile of ASO and siRNA conjugates in glioblastoma xenograft tumors in vivo
Authors: Sarli Samantha L , Fakih Hassan H , Kelly Karen , Devi Gitali , Rembetsy-Brown Julia M , McEachern Holly R , Ferguson Chantal M , Echeverria Dimas , Lee Jonathan , Sousa Jacquelyn , Sleiman Hanadi F , Khvorova Anastasia , Watts Jonathan K
Published: April 2024

Glioblastoma multiforme is a universally lethal brain tumor that largely resists current surgical and drug interventions. Despite important advancements in understanding GBM biology, the invasiveness and heterogeneity of these tumors has made it challenging to develop effective therapies. Therapeutic oligonucleotides—antisense oligonucleotides and small-interfering RNAs—are chemically modified nucleic acids that can silence gene expression in the brain. However, activity of these oligonucleotides in brain tumors remains inadequately characterized. In this study, we developed a quantitative method to differentiate oligonucleotide-induced gene silencing in orthotopic GBM xenografts from gene silencing in normal brain tissue, and used this method to test the differential silencing activity of a chemically diverse panel of oligonucleotides. We show that oligonucleotides chemically optimized for pharmacological activity in normal brain tissue do not show consistent activity in GBM xenografts. We then survey multiple advanced oligonucleotide chemistries for their activity in GBM xenografts. Attaching lipid conjugates to oligonucleotides improves silencing in GBM cells across several different lipid classes. Highly hydrophobic lipid conjugates cholesterol and docosanoic acid enhance silencing but at the cost of higher neurotoxicity. Moderately hydrophobic, unsaturated fatty acid and amphiphilic lipid conjugates still improve activity without compromising safety. These oligonucleotide conjugates show promise for treating glioblastoma.