bluuebunny/crossref_metadata_2025 huggingface dataset:
Normative Considerations Reintroduced
Authors: Shields Christopher
Published: May 2024

Until this point, all of Aristotle’s arguments have been axiological, which is to say that they have dealt with the metaphysics of goodness. Now he shifts, arguing that even if Plato’s axiology were correct, even if there were a Form of the Good, it would be otiose. No one would, or could, appeal to the Form of the Good in the conduct of life. So, talking about it is, in the end, a waste of time—wholly irrelevant to ethical theory, which deals precisely with the question of how we ought to conduct our lives.
Good, Bad, Better, Worse
Authors: Shields Christopher
Published: May 2024

A sober assessment of Aristotle’s anti-Platonic arguments shows them to be formidable, if not yet fully decisive. Still, plainly Aristotle thinks they succeed; this is why he advances them. Suppose he is right about that. In that case, he owes an alternative. To offer one, though, he must navigate a tension in his own axiology. He seems to embrace an inconsistent triad: (i) good things are commensurable as good things only if goodness is univocal; (ii) (many) good things are commensurable as good things; and (iii) goodness is non-univocal. Now, it would be wrong to allege on this basis that Aristotle has contradicted himself. It is fair, however, to ask him to address this tension.
Goodness qua Goodness: a Concluding Scientific Postscript?
Authors: Shields Christopher
Published: May 2024

Aristotle argues that since neither being nor goodness is univocal, there cannot be a science of either. Every science requires a unified domain, and a domain is unified only if it admits of univocal essence for all its members. Yet Aristotle eventually offers, if not a science of being, a science of being qua being. The suggestion lies near, then, that he may equally make room for a science of goodness qua goodness. He shows no signs of offering any such science. Could there be such a science, parallel to the science of being qua being?
A prospective cohort study of persistent endocrine-disrupting chemicals and perceived stress
Authors: Schildroth Samantha , Wesselink Amelia K , Bethea Traci N , Claus Henn Birgit , Friedman Alexa , Fruh Victoria , Coleman Chad M , Lovett Sharonda M , Vines Anissa I , Sjodin Andreas , Botelho Julianne Cook , Calafat Antonia M , Wegienka Ganesa , Weuve Jennifer , Baird Donna D , Wise Lauren A
Published: May 2024

Persistent endocrine-disrupting chemicals (EDCs) can dysregulate the stress response. We evaluated associations between persistent EDCs and perceived stress among participants in the Study of Environment, Lifestyle, and Fibroids (n = 1394), a prospective cohort study of Black women. Participants completed the Perceived Stress Scale 4 (PSS-4) at baseline and every 20 months through 60 months (score range: 0-16); higher scores indicate higher stress. Endocrine-disrupting chemicals, including per- and polyfluoroalkyl substances, polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides, were quantified in plasma samples at baseline. We fit bayesian kernel machine regression and linear mixed-effects models to estimate associations of EDCs (as a mixture and individually) with PSS-4 scores at baseline and at each follow-up visit, respectively. Increasing percentiles of the mixture were not strongly associated with PSS-4 scores at baseline, and no interactions were observed among EDCs. Several individual EDCs (eg, perfluorodecanoic acid, PCB 118, PBDE 99) were associated with higher PSS-4 scores at baseline or follow-up, and other EDCs (eg PCB 138/158) were associated with lower PSS-4 scores at baseline or follow-up. The directionality of associations for individual EDCs was inconsistent across follow-up visits. In conclusion, specific EDCs may be associated with perceived stress in Black women.

This article is part of a Special Collection on Environmental Epidemiology.
Counterfactuals and indeterminate possibility
Authors: Werner Jonas
Published: May 2024

This paper discusses a puzzle raised by Sharon Berry, published in Analysis. The question in the background of this puzzle is how we should deal with seemingly plausible possibility judgements that commit us to counterfactual truths that find no basis in reality. Three answers to this question and their corresponding solutions to the puzzle will be discussed. The last answer provides a way to make sense of the claim that it is in some cases indeterminate whether a proposition is possible and offers an account of indeterminate modal status.
Assessing the validity of driver gene identification tools for targeted genome sequencing data
Authors: Rojas-Rodriguez Felipe , Schmidt Marjanka K , Canisius Sander
Published: May 2024

Motivation

Most cancer driver gene identification tools have been developed for whole-exome sequencing data. Targeted sequencing is a popular alternative to whole-exome sequencing for large cancer studies due to its greater depth at a lower cost per tumor. Unlike whole-exome sequencing, targeted sequencing only enables mutation calling for a selected subset of genes. Whether existing driver gene identification tools remain valid in that context has not previously been studied.

Results

We evaluated the validity of seven popular driver gene identification tools when applied to targeted sequencing data. Based on whole-exome data of 14 different cancer types from TCGA, we constructed matching targeted datasets by keeping only the mutations overlapping with the pan-cancer MSK-IMPACT panel and, in the case of breast cancer, also the breast-cancer-specific B-CAST panel. We then compared the driver gene predictions obtained on whole-exome and targeted mutation data for each of the seven tools. Differences in how the tools model background mutation rates were the most important determinant of their validity on targeted sequencing data. Based on our results, we recommend OncodriveFML, OncodriveCLUSTL, 20/20+, dNdSCv, and ActiveDriver for driver gene identification in targeted sequencing data, whereas MutSigCV and DriverML are best avoided in that context.

Availability and implementation

Code for the analyses is available at https://github.com/SchmidtGroupNKI/TGSdrivergene_validity.
Biological Variation Data in Triathletes for Metabolism and Growth-Related Biomarkers Included in the Athlete Biological Passport
Authors: Moreno-Parro Isabel , Diaz-Garzon Jorge , Aarsand Aasne K , Sandberg Sverre , Aikin Reid , Equey Tristan , Ríos-Blanco Juan José , Buño Soto Antonio , Fernandez-Calle Pilar
Published: May 2024

Background

When using biological variation (BV) data, BV estimates need to be robust and representative. High-endurance athletes represent a population under special physiological conditions, which could influence BV estimates. Our study aimed to estimate BV in athletes for metabolism and growth-related biomarkers involved in the Athlete Biological Passport (ABP), by 2 different statistical models.

Methods

Thirty triathletes were sampled monthly for 11 months. The samples were analyzed for human growth hormone (hGH), insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), insulin, and N-terminal propeptide of type III procollagen (P-III-NP) by immunoassay. Bayesian and ANOVA methods were applied to estimate within-subject (CVI) and between-subject BV.

Results

CVI estimates ranged from 7.8% for IGFBP-3 to 27.0% for insulin, when derived by the Bayesian method. The 2 models gave similar results, except for P-III-NP. Data were heterogeneously distributed for P-III-NP for the overall population and in females for IGF-1 and IGFBP-3. BV components were not estimated for hGH due to lack of steady state. The index of individuality was below 0.6 for all measurands, except for insulin.

Conclusions

In an athlete population, to apply a common CVI for insulin would be appropriate, but for IGF-1 and IGFBP-3 gender-specific estimates should be applied. P-III-NP data were heterogeneously distributed and using a mean CVI may not be representative for the population. The high degree of individuality for IGF-1, IGFBP-3, and P-III-NP makes them good candidates to be interpreted through reference change values and the ABP.
A geometric morphometric analysis of wing variations in shape and size of the blue bottle fly, Calliphora vicina (Diptera: Calliphoridae)
Authors: Gemmellaro M Denise , Forzisi Elena G , Anderson Gail S , Hamilton George C , Weidner Lauren M
Published: May 2024

A geometric morphometric analysis was performed on the right wing of adult Calliphora vicina (Robineau-Desvoidy) collected across 4 altitudinal levels in Sicily. The objective of this study was to assess differences in shape and centroid size (CS) between females and males and across elevations. The wings analyzed in this study were removed from adults of C. vicina collected with baited traps at 20, 700, 1,153, and 1,552; for this study, 19 landmarks were identified in each wing. The coordinates of the landmarks were aligned and superimposed to prevent variations due to position, orientation, and scale; they were then scaled to the same CS and recentered. CS and Procrustes differences were, respectively, used to assess variations in size and shape. Significant differences were observed in wing shape between males and females but not between all altitudinal levels. Female wings were found to be significantly larger than males (P < 0.01). Wings of flies collected at the highest altitudinal level resulted in significantly larger wings than those collected at lower altitudes (P < 0.001), with CS values ranging from 12.1 to 14.1. Variation in wing shape can impact thermal regulation, and therefore, oxygen content, temperature, atmospheric pressure, and solar radiation can have an effect on an insect’s body and activity levels. At high elevations and lower temperatures, larger wings could mean less energy expenditure when flying to increase body temperature.
Stratifying cities: the effect of outdoor recreation areas on children’s well-being
Authors: Rubio-Cabañez Maria
Published: May 2024

This study examines how the presence of outdoor recreation areas such as parks and playgrounds affects children’s well-being and how this effect is moderated by families’ socioeconomic status. Specifically, I aim to answer two research questions. First, does the presence of outdoor recreation areas in children’s neighbourhoods affect their cognitive well-being? Second, is there a differential effect depending on children’s socioeconomic status? The main part of the study uses data from the International Survey of Children’s Well-Being. The results suggest that the presence of outdoor recreation areas in children’s neighbourhoods has a positive effect on their well-being. In addition, the estimated effect of outdoor recreation areas is larger for children from families with low socioeconomic status. Finally, findings from the Growing Up in Ireland data set suggest that children’s reduced mental problems are a plausible mechanism through which outdoor recreation areas affect children’s well-being. These findings have meaningful policy implications. Providing better access to appropriate outdoor recreation areas appears to benefit disadvantaged children more and thus reduce inequality in children’s well-being.
Neighborhood Walkability Is Associated With Global Positioning System-Derived Community Mobility of Older Adults
Authors: Moored Kyle D , Crane Breanna M , Carlson Michelle C , Dunlap Pamela M , Brach Jennifer S , Rosso Andrea L
Published: May 2024

Background

Neighborhood walkability may encourage greater out-of-home travel (ie, community mobility) to support independent functioning in later life. We examined associations between a novel walkability audit index and Global Positioning System (GPS)-derived community mobility in community-dwelling older adults. We compared associations with the validated Environmental Protection Agency (EPA) National Walkability Index and further examined moderation by clinical walking speed.

Methods

Participants were 146 older adults (Mean = 77.0 ± 6.5 years, 68% women) at baseline of a randomized trial to improve walking speed. A walkability index (range: 0–5; eg, land-use mix, crosswalks, and so on) was created using Google Street View audits within 1/8-mile of the home. Participants carried a GPS device for 5–7 days to derive objective measures of community mobility (eg, time spent out of home, accumulated distance from home).

Results

Each 1 SD (~1.3-point) greater walkability audit score was associated with a median 2.16% more time spent out of home (95% confidence interval [95% CI]: 0.30–4.03, p = .023), adjusting for individual demographics/health and neighborhood socioeconomic status. For slower walkers (4-m walking speed <1 m/s), each 1 SD greater audit score was also associated with a median 4.54 km greater accumulated distance from home (95% CI: 0.01–9.07, p (interaction) = .034). No significant associations were found for the EPA walkability index.

Conclusions

Walkability immediately outside the home was related to greater community mobility, especially for older adults with slower walking speeds. Results emphasize the need to consider the joint influence of local environment and individual functioning when addressing community mobility in older populations.
A concept for the global assessment of tomographic resolution and uncertainty
Authors: Freissler Roman , Schuberth Bernhard S A , Zaroli Christophe
Published: May 2024

A major challenge in seismic tomography consists in quantifying and representing model resolution and uncertainty, particularly at global scales. This information is crucial for interpretations of tomographic images and their technical application in geodynamics. However, due to large computational costs, there have been only few attempts so far to coherently analyse the spatially varying resolving power for a complete set of model parameters. Here, we present a concept for an effective evaluation and global representation of the 3-D resolution information contained in a full set of averaging kernels. In our case, these kernels are constructed using the ‘Subtractive Optimally Localized Averages’ (SOLA) method, a variant of classic Backus-Gilbert inversion suitable for global tomography. Our assessment strategy incorporates the following steps: (1) a 3-D Gaussian function is fitted to each averaging kernel to measure resolution lengths in different directions and (2) we define a classification scheme for the quality of the averaging kernels based on their focus with respect to the estimated 3-D Gaussian, allowing us to reliably identify whether the inferred resolution lengths are robust. This strategy is not restricted to SOLA inversions, but can, for example, be applied in all cases where point-spread functions are computed in other tomographic frameworks. Together with model uncertainty estimates that are derived from error propagation in the SOLA method, our concept reveals at which locations, resolution lengths and interpretations of model values are actually meaningful. We finally illustrate how the complete information from our analysis can be used to calibrate the SOLA inversion parameters—locally tunable target resolution kernels and trade-off parameters—without the need for visual inspection of the individual resulting averaging kernels. Instead, our global representations provide a tool for designing tomographic models with specific resolution-uncertainty properties that are useful in geodynamic applications, especially for linking seismic inversions to models of mantle flow.
A UK Mw catalogue derived from coda envelopes
Authors: Peach Charlie , Nippress Stuart E J , Green David N , Mayeda Kevin , Wookey James M , Werner Maximilian J
Published: May 2024

The United Kingdom (UK) experiences low-to-moderate levels of seismicity; only 12 onshore earthquakes with local magnitude (ML) ≥ 4.0 have been recorded in the past 20 yr. It is therefore difficult to estimate moment magnitude (Mw) using conventional moment tensor inversion for the majority of UK seismicity, resulting in limited reliable estimates of Mw. To address this, we calibrated coda envelopes at 16 broad-band seismic stations distributed across the UK to produce an Mw catalogue for 100 events with Mw ≥ 2.13 that occurred since 2006. This was achieved using the open-source Coda Calibration Tool, which requires independent source parameter estimates for calibration. For 13 UK events between 2006 and 2022, we used spectral modelling to estimate apparent stress (0.32–1.74 MPa) and moment tensor inversion to estimate Mw (3.35–4.52). These independent source parameters formed a subset of the inputs into the final calibration, which used seismic data from 33 events with coda-derived values of 2.57$\le $ Mw$\le $4.49. The resultant coda calibration parameters were applied to 67 further events (Mw ≥ 2.13). The coda envelopes exhibit slow seismic coda decay across the UK, with significant energy up to 20 Hz, consistent with other regions of low tectonic activity. This Mw catalogue, and the application of the calibration to future UK seismic events, will be useful for both assessing seismic hazard and event characterization.
Tools for editing the mammalian mitochondrial genome
Authors: Moraes Carlos T
Published: May 2024

The manipulation of animal mitochondrial genomes has long been a challenge due to the lack of an effective transformation method. With the discovery of specific gene editing enzymes, designed to target pathogenic mitochondrial DNA mutations (often heteroplasmic), the selective removal or modification of mutant variants has become a reality. Because mitochondria cannot efficiently import RNAs, CRISPR has not been the first choice for editing mitochondrial genes. However, the last few years witnessed an explosion in novel and optimized non-CRISPR approaches to promote double-strand breaks or base-edit of mtDNA in vivo. Engineered forms of specific nucleases and cytidine/adenine deaminases form the basis for these techniques. I will review the newest developments that constitute the current toolbox for animal mtDNA gene editing in vivo, bringing these approaches not only to the exploration of mitochondrial function, but also closer to clinical use.
Challenges in IBD Research 2024: Novel Technologies
Authors: Prasad Shalini , Cross Raymond K , Monroe Mary Beth , Dolinger Michael T , Motte Rachel , Hong Sungmo , Stidham Ryan W , Kumar Narendra , Levine Deborah , Larijani Anthony , Simone Ashley , Chachu Karen A , Wyborski Russell , Heller Caren A , Moss Alan C , Schwerbrock Nicole M J , Selaru Florin M
Published: May 2024

Novel technology is one of the five focus areas of the Challenges in Inflammatory Bowel Disease (IBD) Research 2024 document. Building off the Challenges in IBD Research 2019 document, the Foundation aims to provide a comprehensive overview of current gaps in IBD research and deliver actionable approaches to address them with a focus on how these gaps can lead to advancements in interception, remission, and restoration for these diseases. The document is the result of a multidisciplinary collaboration from scientists, clinicians, patients, and funders and represents a valuable resource for patient-centric research prioritization.

Specifically, the Novel Technologies section focuses on addressing key research gaps to enable interception and improve remission rates in IBD. This includes testing predictions of disease onset and progression, developing novel technologies tailored to specific phenotypes, and facilitating collaborative translation of science into diagnostics, devices, and therapeutics.

Proposed priority actions outlined in the document include real-time measurement of biological changes preceding disease onset, more effective quantification of fibrosis, exploration of technologies for local treatment of fistulas, and the development of drug delivery platforms for precise, location-restricted therapies. Additionally, there is a strong emphasis on fostering collaboration between various stakeholders to accelerate progress in IBD research and treatment.

Addressing these research gaps necessitates the exploration and implementation of bio-engineered novel technologies spanning a spectrum from materials to systems. By harnessing innovative ideas and technologies, there’s a collective effort to enhance patient care and outcomes for individuals affected by IBD.
Challenges in IBD Research 2024: Precision Medicine
Authors: Syed Sana , Boland Brigid S , Bourke Lauren T , Chen Lea Ann , Churchill Laurie , Dobes Angela , Greene Adam , Heller Caren , Jayson Christina , Kostiuk Benjamin , Moss Alan , Najdawi Fedaa , Plung Lori , Rioux John D , Rosen Michael J , Torres Joana , Zulqarnain Fatima , Satsangi Jack
Published: May 2024

Precision medicine is part of 5 focus areas of the Challenges in IBD Research 2024 research document, which also includes preclinical human IBD mechanisms, environmental triggers, novel technologies, and pragmatic clinical research. Building on Challenges in IBD Research 2019, the current Challenges aims to provide a comprehensive overview of current gaps in inflammatory bowel diseases (IBDs) research and deliver actionable approaches to address them with a focus on how these gaps can lead to advancements in interception, remission, and restoration for these diseases. The document is the result of multidisciplinary input from scientists, clinicians, patients, and funders, and represents a valuable resource for patient-centric research prioritization. In particular, the precision medicine section is focused on the main research gaps in elucidating how to bring the best care to the individual patient in IBD. Research gaps were identified in biomarker discovery and validation for predicting disease progression and choosing the most appropriate treatment for each patient. Other gaps were identified in making the best use of existing patient biosamples and clinical data, developing new technologies to analyze large datasets, and overcoming regulatory and payer hurdles to enable clinical use of biomarkers. To address these gaps, the Workgroup suggests focusing on thoroughly validating existing candidate biomarkers, using best-in-class data generation and analysis tools, and establishing cross-disciplinary teams to tackle regulatory hurdles as early as possible. Altogether, the precision medicine group recognizes the importance of bringing basic scientific biomarker discovery and translating it into the clinic to help improve the lives of IBD patients.
A payroll efficiency analysis of Europe’s top football leagues
Authors: Villa G , Lozano S
Published: May 2024

Accepted by: Ali Emrouznejad

Top European football teams have large budgets mainly due to the high wage bills they pay to the players. Therefore, it would be interesting to determine if these football teams are paying inflated salaries considering the sports results that they obtain each season in both national and international competitions. This study focuses on the top five European football leagues (Italian, Spanish, English, French and German). We propose a novel non-convex, non-parametric metafrontier analysis approach to determine whether the football clubs are overpaying their players considering their sporting performance. Goals against in both national and international competitions are modelled as undesirable outputs. Each football team is benchmarked first within its own league and then against all five leagues. From this, apart from estimating the payroll efficiency of each team, the average efficiency of each of these five leagues can also be computed. An exhaustive analysis and discussion of the results is presented using data from three seasons (2020–2023). Some ‘important’ football clubs pay salaries that are not justified by their performance when compared with other, more modest, clubs that pay salaries more in line with the sports results obtained. Ligue 1 is the league that, on average, makes the most efficient use of their payroll, followed by the Bundesliga and, somewhat behind, La Liga and Serie A. The Premier League occupies the last position in terms of average payroll efficiency.
Hepatitis B Virus DNA and RNA Persist in Liver After Serologic Recovery in Persons With Hepatitis C Virus
Authors: Grudda Tanner , Thomas David L , Kirk Gregory D , Mehta Shruti H , Astemborski Jacquie , Lauer Georg M , Balagopal Ashwin , Thio Chloe L
Published: May 2024

After recovery from a hepatitis B virus (HBV) infection, reactivation can occur with immunosuppression; thus, it is assumed that replication competent HBV persists in the liver. We sought to detect persistent HBV from 13 people with spontaneous recovery. We quantified HBV DNA and RNA in core liver biopsy specimens (median, 1.72 × 106 cells) from persons who inject drugs. Of 13 biopsy specimens, 8 (61%) had evidence of HBV DNA or RNA and 5 (38%) had both HBV DNA and RNA. Messenger RNAs were derived from covalently closed circular DNA and integrated HBV DNA. Here, we show prevalent HBV DNA and RNA despite clinical recovery in persons who inject drugs.
CoRTEx: contrastive learning for representing terms via explanations with applications on constructing biomedical knowledge graphs
Authors: Ying Huaiyuan , Zhao Zhengyun , Zhao Yang , Zeng Sihang , Yu Sheng
Published: May 2024

Objectives

Biomedical Knowledge Graphs play a pivotal role in various biomedical research domains. Concurrently, term clustering emerges as a crucial step in constructing these knowledge graphs, aiming to identify synonymous terms. Due to a lack of knowledge, previous contrastive learning models trained with Unified Medical Language System (UMLS) synonyms struggle at clustering difficult terms and do not generalize well beyond UMLS terms. In this work, we leverage the world knowledge from large language models (LLMs) and propose Contrastive Learning for Representing Terms via Explanations (CoRTEx) to enhance term representation and significantly improves term clustering.

Materials and Methods

The model training involves generating explanations for a cleaned subset of UMLS terms using ChatGPT. We employ contrastive learning, considering term and explanation embeddings simultaneously, and progressively introduce hard negative samples. Additionally, a ChatGPT-assisted BIRCH algorithm is designed for efficient clustering of a new ontology.

Results

We established a clustering test set and a hard negative test set, where our model consistently achieves the highest F1 score. With CoRTEx embeddings and the modified BIRCH algorithm, we grouped 35 580 932 terms from the Biomedical Informatics Ontology System (BIOS) into 22 104 559 clusters with O(N) queries to ChatGPT. Case studies highlight the model’s efficacy in handling challenging samples, aided by information from explanations.

Conclusion

By aligning terms to their explanations, CoRTEx demonstrates superior accuracy over benchmark models and robustness beyond its training set, and it is suitable for clustering terms for large-scale biomedical ontologies.
Impact of high-quality, mixed-domain data on the performance of medical language models
Authors: Griot Maxime , Hemptinne Coralie , Vanderdonckt Jean , Yuksel Demet
Published: May 2024

Objective

To optimize the training strategy of large language models for medical applications, focusing on creating clinically relevant systems that efficiently integrate into healthcare settings, while ensuring high standards of accuracy and reliability.

Materials and Methods

We curated a comprehensive collection of high-quality, domain-specific data and used it to train several models, each with different subsets of this data. These models were rigorously evaluated against standard medical benchmarks, such as the USMLE, to measure their performance. Furthermore, for a thorough effectiveness assessment, they were compared with other state-of-the-art medical models of comparable size.

Results

The models trained with a mix of high-quality, domain-specific, and general data showed superior performance over those trained on larger, less clinically relevant datasets (P < .001). Our 7-billion-parameter model Med5 scores 60.5% on MedQA, outperforming the previous best of 49.3% from comparable models, and becomes the first of its size to achieve a passing score on the USMLE. Additionally, this model retained its proficiency in general domain tasks, comparable to state-of-the-art general domain models of similar size.

Discussion

Our findings underscore the importance of integrating high-quality, domain-specific data in training large language models for medical purposes. The balanced approach between specialized and general data significantly enhances the model’s clinical relevance and performance.

Conclusion

This study sets a new standard in medical language models, proving that a strategically trained, smaller model can outperform larger ones in clinical relevance and general proficiency, highlighting the importance of data quality and expert curation in generative artificial intelligence for healthcare applications.
Effectiveness of Postburn Pruritus Treatment and Improvement of Insomnia—A Randomized Trial
Authors: Arko-Boham Elliott , Paintsil Albert Bedford , Arko-Boham Benjamin , Adjei George Obeng
Published: May 2024

Postburn pruritus is difficult to assess and treat. Antihistamines used in its treatment provide little relief. Identification of the itch neuronal pathway has inspired new alternatives, including gabapentin, for its management. The study compared the effectiveness of cetirizine, gabapentin, and a combination of gabapentin and cetirizine in treating postburn pruritus. Burn patients were randomly assigned to treatment with Cetirizine (n = 23), Gabapentin (n = 23), or Cetirizine plus Gabapentin (n = 23). A baseline assessment of the intensity or the severity of pruritus was evaluated, after which treatment commenced with standard doses of the 3 study regimens. Quality of sleep was assessed at baseline (day 0) and repeated on day 3, day 7, and day 14. Approximately 97% of participants presented with moderate or severe itch; 69% with acute itch; and the majority (94.2%) experienced pruritus between the first and fourth weeks. Gabapentin reduced itch by 92.9% in 14 days compared to cetirizine’s 61.8%. The combined effect of cetirizine and gabapentin was comparable using gabapentin alone. When the itch became protracted over 6 weeks, the effectiveness of cetirizine in controlling itch worsened. It reduced itch intensity by only 37.7%, whilst gabapentin did so at 89.4%. Itch intensity correlated positively with insomnia, and controlling itch intensity improved sleep. Gabapentin was more effective for the treatment of postburn pruritus than cetirizine. Controlling itch intensity improved sleep. In acute and moderate itch, low-dose gabapentin could be added if cetirizine is the drug intended for its treatment.
Elevated Cardiac Troponin I Level Associated to Cardiac Dysfunction in Burned Patients
Authors: Segura Carolina , Golovko George , Obias Isabel , Shah Suhaib , El Ayadi Amina , Wolf Steven , Song Juquan
Published: May 2024

Severely burned patients often develop cardiac dysfunction and heart failure. The purpose of this retrospective study is to evaluate the role of cardiac troponin I (cTI) and its association to patients with burns. Patients deidentified data were collected from a national database in May 2023. Adult patients with burns who had cTnI lab counted were enrolled in this study. Patients were grouped by the cTnI mean level within 72 h including patients with elevated cTnI levels at >0.3 ng/mL (n = 2188 patients) and patients with nonelevated cTnI level (<0.04 ng/mL) (n = 3200). The cohorts were further stratified by less than 20% TBSA mild burn population and >20% TBSA severe burn population to replicate the severity of burns. The 30-day incidences of acute myocardial infarction (MI), sepsis, and mortality were investigated after the cohorts were propensity-matching balanced. The odds ratios (ORs) with 95% CI for MI were (9.829/7.081-13.645), sepsis (1.527/1.269-1.959), and mortality (2.586/2.110-3.170), respectively (P < .05). The groups that were further stratified into mild burn and severe burn had the following results: The mild burn ORs and 95% CI for MI was (6.237/3.986-9.785), sepsis (1.603/1.132-2.270), and mortality was (2.298/1.629-3.242). The severe burn cohort had ORs and 95% CI for MI (3.145/1.469-6.732), sepsis (0.993/0.555-1.777), and mortality (2.934/1.924-4.475). In conclusion, the patients with earlier elevated cTnI levels had worse outcomes of MI and mortality in both severe and mild burns.
Irisin prevents trabecular bone damage and tumor invasion in a mouse model of multiple myeloma
Authors: Zerlotin Roberta , Oranger Angela , Pignataro Patrizia , Dicarlo Manuela , Sanesi Lorenzo , Suriano Clelia , Storlino Giuseppina , Rizzi Rita , Mestice Anna , Di Gioia Sante , Mori Giorgio , Grano Maria , Colaianni Graziana , Colucci Silvia
Published: May 2024

Bone disease associated with multiple myeloma (MM) is characterized by osteolytic lesions and pathological fractures, which remain a therapeutic priority despite new drugs improving MM patient survival. Antiresorptive molecules represent the main option for the treatment of MM-associated bone disease (MMBD), whereas osteoanabolic molecules are under investigation. Among these latter, we here focused on the myokine irisin, which is able to enhance bone mass in healthy mice, prevent bone loss in osteoporotic mouse models, and accelerate fracture healing in mice. Therefore, we investigated irisin effect on MMBD in a mouse model of MM induced by intratibial injection of myeloma cells followed by weekly administration of 100 μg/kg of recombinant irisin for 5 wk. By micro-Ct analysis, we demonstrated that irisin improves MM-induced trabecular bone damage by partially preventing the reduction of femur Trabecular Bone Volume/Total Volume (P = .0028), Trabecular Number (P = .0076), Trabecular Fractal Dimension (P = .0044), and increasing Trabecular Separation (P = .0003) in MM mice. In cortical bone, irisin downregulates the expression of Sclerostin, a bone formation inhibitor, and RankL, a pro-osteoclastogenic molecule, while in BM it upregulates Opg, an anti-osteoclastogenic cytokine. We found that in the BM tibia of irisin-treated MM mice, the percentage of MM cells displays a reduction trend, while in the femur it decreases significantly. This is in line with the in vitro reduction of myeloma cell viability after 48 h of irisin stimulation at both 200 and 500 ng/mL and, after 72 h already at 100 ng/mL rec-irisin. These results could be due to irisin ability to downregulate the expression of Notch 3, which is important for cell-to-cell communication in the tumor niche, and Cyclin D1, supporting an inhibitory effect of irisin on MM cell proliferation. Overall, our findings suggest that irisin could be a new promising strategy to counteract MMBD and tumor burden in one shot.
Hover fly (Diptera: Syrphidae) diversity and seasonality in North Georgia apple and peach orchards
Authors: McCravy Kenneth W , Clem C Scott , Bailey Jordan B , Elgar Sabrina A , Blaauw Brett R
Published: May 2024

Crop pollination and natural biological control provided by beneficial insects have an economic worth of hundreds of billions of dollars annually. Apple and peach production in North Georgia are economically important industries that benefit from these ecological services. Hover flies are dual ecosystem service providers that have been relatively understudied in orchard ecosystems. We investigated the diversity and seasonal activity of hover flies in apple and peach orchards at 2 sites in North Georgia from March to October 2020 and 2021. Bowl traps were used to sample hover flies in orchard edge and interior habitats. The aphidophagous species Toxomerus geminatus (Say) (Diptera: Syrphidae) and Toxomerus marginatus (Say) (Diptera: Syrphidae) comprised 86.6% of the total hover flies collected. Apple orchards yielded the greatest hover fly presence, species richness, and Toxomerus spp. abundance. Hover fly richness and diversity were greatest during postbloom, but Toxomerus spp. abundance was greatest during the bloom period. No differences in presence, richness, diversity, or Toxomerus spp. abundance were found between edge and interior habitats. Toxomerus geminatus and T. marginatus were dominant from March through August, with T. geminatus being more abundant than T. marginatus in March, early April, and August. October sampling produced the greatest hover fly richness. Our results suggest that hover flies are abundant in North Georgia orchards and exhibit substantial spatial and temporal variation in richness and diversity. Expanded studies incorporating additional sampling efforts and methods are needed to further characterize the hover fly fauna and their impact on North Georgia apple and peach orchards.
Photoperiod and temperature synergistically regulate heading date and regional adaptation in rice
Authors: Zong Wubei , Guo Xiaotong , Zhang Kai , Chen Letian , Liu Yao-Guang , Guo Jingxin
Published: May 2024

Plants must accurately integrate external environmental signals with their own development to initiate flowering at the appropriate time for reproductive success. Photoperiod and temperature are key external signals that determine flowering time; both are cyclical and periodic, and they are closely related. In this review, we describe photoperiod-sensitive genes that simultaneously respond to temperature signals in rice (Oryza sativa). We introduce the mechanisms by which photoperiod and temperature synergistically regulate heading date and regional adaptation in rice. We also discuss the prospects for designing different combinations of heading date genes and other cold tolerance or thermo-tolerance genes to help rice better adapt to changes in light and temperature via molecular breeding to enhance yield in the future.
Biolistics-mediated transformation of hornworts and its application to study pyrenoid protein localization
Authors: Lafferty Declan J , Robison Tanner A , Gunadi Andika , Schafran Peter W , Gunn Laura H , Van Eck Joyce , Li Fay-Wei
Published: May 2024

Hornworts are a deeply diverged lineage of bryophytes and a sister lineage to mosses and liverworts. Hornworts have an array of unique features that can be leveraged to illuminate not only the early evolution of land plants, but also alternative paths for nitrogen and carbon assimilation via cyanobacterial symbiosis and a pyrenoid-based CO2-concentrating mechanism (CCM), respectively. Despite this, hornworts are one of the few plant lineages with limited available genetic tools. Here we report an efficient biolistics method for generating transient expression and stable transgenic lines in the model hornwort, Anthoceros agrestis. An average of 569 (±268) cells showed transient expression per bombardment, with green fluorescent protein expression observed within 48–72 h. A total of 81 stably transformed lines were recovered across three separate experiments, averaging six lines per bombardment. We followed the same method to transiently transform nine additional hornwort species, and obtained stable transformants from one. This method was further used to verify the localization of Rubisco and Rubisco activase in pyrenoids, which are central proteins for CCM function. Together, our biolistics approach offers key advantages over existing methods as it enables rapid transient expression and can be applied to widely diverse hornwort species.
Diagnostic value of serum STIP1 in HCC and AFP-negative HCC
Authors: Sun Haiqing , Liu Ning , Lou Jinli
Published: May 2024

Objective

This study aimed to investigate the diagnostic value of stress-induced phosphoprotein 1 (STIP1) in serum for hepatocellular carcinoma (HCC) and alpha-fetoprotein (AFP)–negative HCC (ANHC).

Methods

In this study, serum samples were collected from 158 HCC patients and 63 non-HCC patients. Logistic regression analysis was performed to identify independent risk factors associated with HCC and ANHC. The diagnostic values of each index for HCC and ANHC were analyzed using receiver operating characteristic (ROC) curve analysis.

Results

The STIP1, des-γ-carboxy prothrombin (DCP), and AFP levels were higher in the HCC groups than in the non-HCC groups (P < .05). Age, DCP, STIP1, and hepatitis B virus infection were independent predictors of HCC (P < .05). The diagnostic value of STIP1 for HCC was higher than that of DCP. Additionally, age, STIP1, and hepatitis B virus infection were independent predictors for ANHC patients. The ROC curve exhibited an area under the curve value of 0.919 for STIP1, with a diagnostic cutoff value of 68.5 U/mL. Moreover, 36 ANHC patients and 19 AFP-negative non-HCC patients were included to validate the diagnostic model. A total of 20 patients had STIP1 levels greater than 68.5 U/mL, resulting in diagnostic accuracy of 67.3%, sensitivity of 55.6%, and specificity of 89.5%.

Conclusion

STIP1 demonstrates excellent diagnostic value for HCC and ANHC.
Transient perivascular inflammation of the carotid artery syndrome – A rare differential for anterior neck pain: Series of three cases and review of literature
Authors: Kamath Navaneeth , Kharkhele Reena , Waghela Rajendra , Aggrawal Anup , Mathew John , Padiyar Shivraj
Published: May 2024

We report a series of three cases of transient perivascular inflammation of the carotid artery (TIPIC) syndrome in an otherwise healthy individual. We would also like to review this rare entity and compare it with other similar cases reported in the literature. Our first case was a young male with right-sided neck pain of 1-week duration with magnetic resonance imaging (MRI) showing right carotid perivascular inflammation which completely resolved after 2 weeks with anti-inflammatory drugs. In the second case, a young male presented with left-sided neck pain and odynophagia of 5 days duration with an MRI showing left carotid perivascular inflammation which completely resolved after 2 weeks with anti-inflammatory drugs. In the third case, a young male presented with right-sided neck pain of 1-day duration with an MRI showing right common carotid perivascular inflammation near the bifurcation with complete resolution in pain but with residual wall thickening. We want to highlight the existence of this new entity by reporting these three case series with a brief review of the literature. The cause and pathogenesis of this rare entity remain unknown. It has been hypothesised to be autoimmune or viral-mediated inflammation which requires further understanding.
#1458 Adverse muscle composition predicts all-cause mortality in CKD
Authors: Indurain Ainhoa , Karlsson Markus , Uhlin Fredrik , Fernström Anders , Segelmark Mårten , Leinhard Olof Dahlqvist
Published: May 2024

Background and Aims

Sarcopenia is common in CKD and associates with morbidity and mortality. A rapid and standardized MRI (Magnetic Resonance Imaging) scan protocol allows an accurate muscle composition analysis by quantification of skeletal muscle volume and muscle fat infiltration (MFI). The combined observation of low muscle volume and high muscle fat infiltration, i.e. adverse muscle composition (AMC), is a prevalent muscle composition phenotype within CKD and associates to poor function, high prevalence of comorbidity, and an increased risk for coronary heart disease (CHD). It has also been shown that AMC is an independent predictor of all-cause mortality in patients with non-alcoholic fatty liver disease and in general population.

In this study we aimed to investigate muscle composition as predictor of all-cause mortality within participants with CKD in the UK Biobank imaging study (UKB).

Method

This is a prospective study including UKB participants with CKD defined as having an eGFR cystatin C < 60 ml/min/1, 73 m2. A control group was created by matching each participant with CKD for sex, age, and BMI to four participants with normal eGFR. Cystatin C was analyzed based on blood samples at time of study enrolment 7-9 years prior to the MRI. Fat-tissue free thigh muscle volume and MFI were quantified using a rapid neck-to-knee water and fat separated MRI protocol and automated image analysis (AMRA® Researcher). For each participant, a personalized muscle volume z-score (sex- and body size-specific) was calculated and combined with MFI to divide the participants into four muscle composition phenotype groups; 1) normal muscle composition, 2) only low muscle volume, 3) only high MFI and 4) AMC, using previously published thresholds based on the whole UKB cohort. The thresholds were the 25th percentile (< -0.68 SD) for muscle volume z-score and the 75th percentile (men >7.69%; women >8.82%) for MFI. The mortality data were obtained through the UKB´s linkage to national death registries.

All-cause mortality was investigated using Kaplan-Meier curves and Cox regression. Models within participants with CKD were crude and subsequently adjusted for sex, age, BMI, low hand grip strength (<16/27 kg for females/males), physical activity, smoking, alcohol, and previous diagnosis of cancer, prevalent CHD and type 2 diabetes, all assessed at the time of imaging.

Results

Conclusion

AMC, determined by standardized MRI, was a strong predictor of all-cause mortality in CKD. The study results indicate that CKD patients with poor muscle health, identified as having both low muscle volume z-score and high MFI, have a significantly higher mortality risk. This vulnerable group would potentially benefit from targeted interventions and is also of specific interest when evaluating new treatments for CKD.
#58 SGLT2 inhibitor kidney outcome trials: under-representation of the majority of people with chronic kidney disease in real-world clinical practice
Authors: Forbes Anna , Hinton William , Feher Michael , Ordonez-Mena Jose , Joy Mark , Banerjee Debasish , Cole Nicholas , Munro Neil , Whyte Martin , Suckling Rebecca , Swift Pauline , de Lusignan Simon
Published: May 2024

Background and Aims

Observational studies suggest that sodium-glucose co-transporter-2 (SGLT2) inhibitor kidney outcome trials are not representative of people with chronic kidney disease (CKD). However, there are limited data on the generalisability to those without co-existing type 2 diabetes (T2D) and representativeness of the EMPA-KIDNEY trial.

Method

A cross-sectional analysis of adults with CKD in English primary care was conducted using the Oxford-Royal College of General Practitioners Clinical Information Digital Hub database. The proportions of people with CKD that met the eligibility criteria of SGLT2 inhibitor kidney outcome trials were determined, and their characteristics described. Logistic regression analyses were performed to identify factors associated with trial eligibility.

Results

Of 6 670 829 adults, 516 491 (7.7%) with CKD were identified, including 32.8% (n  =  169 443) with co-existing T2D. In the total CKD cohort, 0.9%, 2.2%, and 8.0% met the CREDENCE, DAPA-CKD, and EMPA-KIDNEY eligibility criteria, respectively. All trials were more representative of people with co-existing T2D than those without T2D. Trial participants were 9-14 years younger than the trial eligible populations, and had more advanced CKD, including higher levels of albuminuria. A higher proportion of the CREDENCE (100%), DAPA-CKD (67.6%) and EMPA-KIDNEY (44.5%) trial participants had T2D compared to the total CKD population (32.8%). Renin-angiotensin-aldosterone system inhibitors were prescribed in almost all trial participants compared to less than half of the total CKD population. Females were underrepresented and less likely to be eligible for the trials.

Conclusion

SGLT2 inhibitor kidney outcome trials are not representative of most people with CKD in English Primary Care. These findings highlight the importance of complementing trials with real-world studies, exploring the effectiveness of SGLT2 inhibitors in the broader population of people with CKD treated in routine clinical practice.