bluuebunny/crossref_metadata_2025 huggingface dataset:
Jellyfish: integrative visualization of spatio-temporal tumor evolution and clonal dynamics
Authors: Lavikka Kari , Maarala Altti Ilari , Oikkonen Jaana , Hautaniemi Sampsa
Published: February 2025

Spatial and temporal intra-tumor heterogeneity drives tumor evolution and therapy resistance. Existing visualization tools often fail to capture both dimensions simultaneously. To address this, we developed Jellyfish, a tool that integrates phylogenetic and sample trees into a single plot, providing a holistic view of tumor evolution and capturing both spatial and temporal evolution. Available as a JavaScript library and R package, Jellyfish generates interactive visualizations from tumor phylogeny and clonal composition data. We demonstrate its ability to visualize complex subclonal dynamics using data from ovarian high-grade serous carcinoma.

Availability and implementation

Jellyfish is freely available with MIT license at https://github.com/HautaniemiLab/jellyfish (JavaScript library) and https://github.com/HautaniemiLab/jellyfisher (R package)
Patient-reported outcomes 3 and 18 months after mastectomy and immediate prepectoral implant-based breast reconstruction in the UK Pre-BRA prospective multicentre cohort study
Authors: Harvey Kate L , Johnson Leigh , Sinai Parisa , Mills Nicola , White Paul , Holcombe Christopher , Potter Shelley ,   The Pre-BRA Feasibility Study Steering Group, Barry Peter , Cawthorn Simon , Gardiner Matthew , Irwin Gareth , Kirwan Cliona , McKenzie Mairead , McKenzie Shireen , O’Connell Rachel , Oni Georgette , Rattay Tim , Roy Pankaj , Skillman Joanna , Soumian Soni , Vidya Raghavan , Whisker Lisa , Williams Samantha
Published: February 2025

Introduction

Prepectoral techniques are becoming standard of care for implant-based breast reconstruction due to reduced impact on chest wall function and improved patient satisfaction. Evidence to support these benefits, however, is lacking. Here, patient-reported outcomes (PROs) of prepectoral breast reconstruction (PPBR) in the Pre-BRA cohort are reported.

Methods

Women undergoing PPBR after mastectomy for breast cancer or risk reduction between July 2019 and December 2020 were recruited. Participants completed the BREAST-Q preoperatively and at 3 and 18 months following surgery together with a single item evaluating overall satisfaction at 18 months. Women completing at least one BREAST-Q scale at any timepoint were eligible for inclusion. Questionnaires were scored according to the developers’ instructions and scores compared over time. Exploratory analysis, adjusting for baseline scores was performed to explore factors impacting PROs.

Results

In total 338 of 343 (98.5%) women undergoing PPBR at 40 UK centres were included in the analysis. Compared with baseline scores, women reported statistically significant and clinically meaningful decreases in both ‘Physical’ and ‘Sexual well-being’ at 3 and 18 months. Adjusting for baseline, at 18 months, those experiencing implant loss or having surgery for malignancy reported lower scores in all BREAST-Q domains. Overall, two-thirds of women (167/251) rated the outcome of their reconstruction as ‘excellent/very good’, but experiencing major complications, implant loss, and being dissatisfied with wrinkling/rippling in the reconstructed breast were associated with reduced satisfaction.

Conclusions

PPBR impacts postoperative physical well-being and PROs are variable. These findings should be discussed with patients to support informed decision-making based on realistic expectations of outcome.

Study registration

ISRCTN11898000.
Anti-seizure medication tapering correlates with daytime delta band power reduction in the cortex
Authors: Besné Guillermo M , Evans Nathan , Panagiotopoulou Mariella , Smith Billy , Chowdhury Fahmida A , Diehl Beate , Duncan John S , McEvoy Andrew W , Miserocchi Anna , de Tisi Jane , Walker Matthew C , Taylor Peter N , Thornton Chris , Wang Yujiang
Published: February 2025

Anti-seizure medications are the primary treatment for epilepsy; yet medication tapering effects have not been investigated in a dose, region and time-dependent manner, despite their potential impact on research and clinical practice. We examined over 3000 h of intracranial EEG recordings in 32 subjects during long-term monitoring, of which 22 underwent concurrent anti-seizure medication tapering. We estimated anti-seizure medication plasma levels based on known pharmaco-kinetics of all the major anti-seizure medication types. We found an overall decrease in the power of delta band (δ) activity around the period of maximum medication withdrawal in most (80%) subjects, independent of their epilepsy type or medication combination. The degree of withdrawal correlated positively with the magnitude of δ power decrease. This dose-dependent effect was evident across all recorded cortical regions during daytime; but not in subcortical regions, or during night time. We found no evidence of a differential effect in seizure onset, spiking, or pathological brain regions. The finding of decreased δ band power during anti-seizure medication tapering agrees with previous literature. Our observed dose-dependent effect indicates that monitoring anti-seizure medication levels in cortical regions may be feasible for applications such as medication reminder systems, or closed-loop anti-seizure medication delivery systems. Anti-seizure medications are also used in other neurological and psychiatric conditions, making our findings relevant to a general neuroscience and neurology audience.
Neural substrates of multidimensional psychological characteristics of remembering episodes with autobiographical significance
Authors: Hashimoto Ryu-ichiro , Aoki Ryuta , Ohta Haruhisa , Itahashi Takashi
Published: February 2025

Autobiographic remembering often involves types of constructive processes for psychological experiences and hypothetical scenarios of past events. Previous psychological research revealed a range of phenomenological and functional characteristics associated with recalls of episodes with high autobiographical significance. However, neural bases of such psychological characteristics and their association with memory construction processes remain unclear. In this functional magnetic resonance imaging study, we collected autobiographical episodes from 28 young adults and their extensive metrics of phenomenological and functional characteristics related to autobiographical significance. We then sought to identify neural correlates of the psychological characteristics by measuring brain activity while participants recalled specified episodes as accurately as possible or in counterfactual simulation. Multiple-regression analysis using latent factors of psychological characteristics revealed that a factor representing autobiographical significance was associated with activation in the posterior medial memory system, including the angular cortex, precuneus, and posterior cingulate cortex, during counterfactual simulation. Furthermore, representation similarity analysis using patterns of factor scores revealed significant clusters in the posterior medial system and parts of cerebellar parcels, mainly during counterfactual simulation. These findings indicate that multidimensional psychological characteristics of episodes with autobiographical significance are associated with hypothetical constructive processes in the cortical posterior medial system and cerebellum.
Test–retest reliability of resting-state EEG intrinsic neural timescales
Authors: Tang Xiaoling , Wang Shan , Xu Xinye , Luo Wenbo , Zhang Mingming
Published: February 2025

Intrinsic neural timescales, which reflect the duration of neural information storage within local brain regions and capacity for information integration, are typically measured using autocorrelation windows (ACWs). Extraction of intrinsic neural timescales from resting-state brain activity has been extensively applied in psychiatric disease research. Given the potential of intrinsic neural timescales as a neural marker for psychiatric disorders, investigating their reliability is crucial. This study, using an open-source database, aimed to evaluate the test–retest reliability of ACW-0 and ACW-50 under both eyes-open and eyes-closed conditions across three sessions. The intraclass correlation coefficients (ICCs) were employed to quantify the reliability of the intrinsic neural timescales. Our results showed that intrinsic neural timescales exhibited good reliability (ICC > 0.6) at the whole-brain level across different index types and eye states. Spatially, except for the right temporal region in the eyes-open condition, all other regions showed moderate-to-high ICCs. Over 60% of the electrodes demonstrated moderate-to-high intrinsic neural timescale ICCs under both eyes-open and eyes-closed conditions, with ACW-0 being more stable than ACW-50. Moreover, in the new dataset, the above results were consistently reproduced. The present study comprehensively assessed the reliability of intrinsic neural timescale under various conditions, providing robust evidence for their stability in neuroscience and psychiatry.
Causal relationships between immune cell phenotypes and primary glomerular diseases: genetic evidence from bidirectional Mendelian randomization study
Authors: Tang Wenhao , Li Qiu , Yang Xueying , Yang Haiping
Published: February 2025

Background

Primary glomerular diseases (PGDs), including nephrotic syndrome (NS), membranous nephropathy (MN), and IgA nephropathy (IgAN), are complex renal conditions influenced by immune system dysregulation. Although associations between immune cell phenotypes and PGDs have been observed, the precise causal relationships have not been fully elucidated.

Methods

Utilizing genetic association data from genome-wide association studies (GWASs), we investigated 731 immunophenotypes in relation to PGDs. A bidirectional two-sample Mendelian Randomization (MR) approach, primarily employing inverse variance weighting (IVW), was conducted to establish causality. MR-Egger, weighted median, simple mode, and weighted mode were used as complementary methods to reinforce the robustness and validity of the results. Sensitivity analyses further validated the sensitivity and stability of our results.

Results

We identified 38 immunophenotypes suggestively related to IgAN, with 20 as risk factors and 18 as protective effects. Six immunophenotypes remained significant after Bonferroni correction: The percentage of CD25hi among T cells; the percentage of CD25hi CD45RA- CD4 not Treg among T cells; the percentage of CD25hi CD45RA- CD4 not Treg within CD4 + T cell population; CX3CR1 expression on monocyte; CD40 expression on monocyte; and CD64 expression on CD14 + CD16- monocyte. In the validation analysis of IgAN, CD3 expression on effector memory CD4 + T cells further confirmed the predisposing risk role of effector memory T cells in the development of IgAN. Additionally, the MR analysis demonstrated suggestive associations between 25 immunophenotypes and MN (8 risk factors and 17 protective factors), as well as between 22 immunophenotypes and NS (10 risk factors and 12 protective factors). Lastly, by intersecting the immunophenotypes showing suggestive associations with PGDs, we identified two common immunophenotypes shared by IgAN and MN, three by IgAN and NS, and one by MN and NS.

Conclusions

This genetic-level investigation uncovers causal associations between immunophenotypes and PGDs, providing valuable insights into the immunological underpinnings of PGDs. Our findings suggest potential targets for treatment strategies, thereby facilitating more personalized and effective therapeutic approaches in PGDs management.
Critical thermal limits of the seasonal migrant, Euxoa auxiliaris (Lepidoptera: Noctuidae)
Authors: Kennedy Taylor E , Sing Sharlene E , Peterson Robert K D
Published: February 2025

The larval stage of the army cutworm, Euxoa auxiliaris (Grote), is an agricultural pest in the Great Plains region of North America. Adult migration to alpine aggregation sites to escape extreme summer temperatures and depleted food resources provides a critical food resource for the grizzly bear, Ursus arctos horribilis (Linnaeus, Carnivora: Ursidae), in the Rocky Mountains. However, little is understood about the ecological consequences of the thermal tolerance of adult E. auxiliaris. Therefore, we investigated thermal tolerance of lab-reared and wild-caught individuals by assessing their critical thermal limits (CTLmax and CTLmin). Using a ramping tolerance assay, we began at 25 °C and adjusted the temperature at a rate of 0.3 °C/min until individuals lost control of their righting response. Adult moths had a CTLmax (lab-reared: 44.13 °C, wild-caught moths: 43.28 °C) typical for a temperate lepidopteran species. However, their CTLmin (lab-reared: −2.24 °C, wild-caught: −1.9 °C) reflects an extraordinary ability to remain active and feed when ambient temperatures are low. These findings provide insights into the thermal ecology of E. auxiliaris which are essential for predicting the range distribution of the species, and, consequently, the continued availability of this key food source for Rocky Mountain grizzly bears. As climate change continues to affect ambient temperatures, these results underscore the importance of studying thermal tolerance to anticipate ecological shifts and ensure the conservation of both E. auxiliaris and the grizzly bears that depend on them.
Eclipsed Mitral Regurgitation and the Role of Multimodality Imaging - A Case Report
Authors: Kounas S , Pilatis N , Solomou E , Koukos M , Aroni M
Published: February 2025

Background

Eclipsed mitral regurgitation (MR) is a rare, reversible condition that leads to transient severe MR and acute heart failure in patients with preserved left ventricular (LV) ejection fraction. Its diagnosis is challenging due to its intermittent presentation, necessitating advanced imaging techniques to reveal the underlying pathology.

Case Summary

We present a case of a 74-year-old female with recurrent severe MR associated with a non-obstructive lesion in the proximal left anterior descending (LAD) artery. Multimodality imaging played a pivotal role in diagnosing this condition, as conventional vasodilator stress tests failed to uncover the ischemic mechanism. Exercise stress echocardiography and myocardial perfusion scintigraphy successfully demonstrated a small ischemic region affecting the mitral valve apparatus, which triggered severe MR during physical exertion. This dynamic ischemia, undetected by routine tests, was essential in diagnosing the pathophysiology behind the patient’s recurrent MR. Following percutaneous coronary intervention (PCI) to the LAD, her symptoms resolved, confirming the ischemic origin of the MR.

Conclusion

This case underscores the critical role of multimodality imaging in revealing the pathophysiology of recurrent MR. Advanced imaging techniques, particularly under physiologic stress, are crucial for diagnosing dynamic ischemia and its impact on valvular function. By identifying the ischemic cause of MR, individualized treatment strategies, such as PCI, can be implemented, avoiding unnecessary valve surgery and improving patient outcomes.
Rapidly Progressive Mitral Valve Disease from Nonbacterial Thrombotic Endocarditis to Mitral Stenosis in Systemic Lupus Erythematosus: A Case Report
Authors: Ichikawa-Ogura Saaya , Mochizuki Yasuhide , Toyosaki Eiji , Fukuoka Hiroto , Shinke Toshiro
Published: February 2025

Background

Libman-Sacks endocarditis (LSE), a nonbacterial thrombotic endocarditis (NBTE) linked to systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS), typically causes valve regurgitation and embolism but can rarely mimic rheumatic mitral stenosis (MS).

Case summary

This case involves a 59-year-old woman with a history of APS and SLE who presented with worsening dyspnoea and congestive heart failure. Initially, severe mitral regurgitation (MR) due to NBTE resolved with vitamin K antagonist therapy, yet she subsequently developed significant MS with commissural fusion, a rheumatic-like feature. Despite stable SLE activity, echocardiography revealed severe MS with high pulmonary pressures, warranting surgical valve replacement. Intraoperative findings confirmed rheumatic-like degeneration, but the patient experienced a fatal cerebral infarction post-surgery, likely due to APS.

Discussion

This case highlights the progression of NBTE-related MR to rheumatic-like MS in an SLE patient with APS, an unusual clinical course. It underscores the importance of echocardiographic monitoring in similar cases, as chronic inflammatory changes in APS might mimic rheumatic pathology, necessitating vigilant management and timely intervention.
A case report of Long COVID and Chronic active myocarditis
Authors: Elia S , De Vecchi S , D’Amario D , Patti G
Published: February 2025

Background

Post-acute sequelae of SARS-CoV-2 infection (PASC), commonly known as “Long COVID”, are progressively emerging in the population. While it was clear from the pandemic outbreak that pre-existing cardiac conditions were exacerbated by the infection even after its resolution, little is known about the rare cases of de novo heart failure onset, whose mechanisms are still not fully understood.

Case Summary

A 74-year-old man was admitted to the emergency department with SARS-Cov-2 bilateral interstitial pneumonia at the CT scan. A few months after he developed acute myocarditis that slowly led to progressive myocardial fibrosis, systolic dysfunction, and a pro-arrhythmic state. Furthermore, these manifestations were associated with growing “mental dullness” and chronic psychophysical asthenia. The patient underwent two CMR over three years witnessing the worsening of cardiac involvement and started full pharmacological therapy for heart failure. We report here the initial presentation, medical care, and clinical course of this patient.

Discussion

In SARS-Cov-2 patients, Long COVID-related myocarditis is one of the more severe complications.

A thorough multimodal evaluation of these patients should be conducted, as presentation symptoms can appear subtle or misleading. Early identification of a chronic process of myocardial damage is crucial to implement early therapeutic strategies and prevent the potential worsening of heart failure.
Trial-level Surrogacy of non-High-Density and Low-Density Lipoprotein Cholesterol Reduction on the Clinical Efficacy of Statins
Authors: Liaigre Léa , Guigui Alicia , Manceau Marc , Cracowski Jean-Luc , Khouri Charles , Roustit Matthieu
Published: February 2025

Aims

Low-density lipoprotein cholesterol (LDL-c) and non-high-density lipoprotein cholesterol (non-HDL-c) are prognostic factors of cardiovascular risk. However, their validity as trial-level surrogates for cardiovascular outcomes is debated. This study aimed to determine whether LDL-c and non-HDL-c are reliable surrogates for cardiovascular events in statin trials, and to explore discrepancies in previous studies.

Methods and results

We conducted an umbrella review of meta-analyses of randomized controlled trials (RCTs) assessing statin efficacy versus placebo or usual care on all-cause mortality and cardiovascular events. We search studies published between 1987 and August 2023 from PubMed, Embase, and the Cochrane Library. Baseline lipid levels, absolute rate differences (ARD), and hazard ratios or risk ratios (RR) for major cardiovascular events and all-cause or cardiovascular mortality were analysed. Weighted linear regressions between log RR or ARD, and absolute difference in non-HDL-c or LDL-c were performed. The coefficients of determination (R2trial) were calculated, with their 95%CI computed through bootstrapping. The surrogate threshold effect (STE) was also estimated. Twenty RCTs and 194,686 participants were included, with a median follow-up of 4.85 years. Statin treatment showed significant efficacy in improving all clinical outcomes. However, the association between treatment effects on LDL-c or non-HDL-c reduction and clinical outcomes was weak. The R²trial were ranging from 0 to 0.1 for LDL-c, and from 0 to 0.04 for non-HDL-c. The STE for MACE was 0.76 (0.36-1.69) mmol/L for LDL-c, and 0.87 (0.49-2.19) mmol/L for non-HDL-c.

Conclusion

Neither LDL-c nor non-HDL-c demonstrated trial-level surrogacy for predicting treatment effects on mortality and cardiovascular events in statin trials. Although they are relevant biomarkers for the follow-up of patients treated with statins, their reduction does not reliably predict a similar reduction in cardiovascular risk. As such, they should not be used as pivotal evidence in drug trials.
A new broom sweeps clean: CLDN16 surpasses the BRAF-V600E mutation as an unrivaled biomarker in papillary thyroid cancer
Authors: Cai Yefeng , Guo Yawen , Ma Wenli , Cheng Pu , Jiang Liehao , Shen Shuyan , Song Fahuan , Zhu Lei , Hu Yiqun , Chen Yao , Duan Yanting , Cai Xiujun , Li Quan , Zheng Guowan , Ge Minghua
Published: February 2025

Objective

This study assessed CLDN16 as a potential replacement or improvement biomarker for papillary thyroid cancer (PTC), addressing the limitations associated with the prevalently used BRAF-V600E mutation.

Design

Database analyses, tissue validation, RNA sequencing, and functional assays were conducted to evaluate CLDN16 as a PTC biomarker and its clinical application.

Methods

CLDN16 expression was examined in PTC and normal thyroid/para-tumor tissues and compared across various cancer types. We evaluated diagnostic accuracy, stability in primary and metastatic sites, and associations with aggressive features. Knockdown experiments were performed to investigate the impact on PTC cell behavior. Additionally, we developed a support vector machine model for diagnosing malignant and high-risk PTCs.

Results

CLDN16 demonstrated high specificity for PTC, with positive detection rates (88.0% in The Cancer Genome Atlas [TCGA] and 88.3% in our center) significantly surpassing BRAF-V600E (47.5% in TCGA and 74.3% in our center). This resulted in superior diagnostic accuracy (ROC-CLDN16 = 0.922 vs ROC-BRAF-V600E = 0.742 in TCGA). CLDN16 exhibited stable expression across primary and metastatic sites and was associated with aggressive features, including extrathyroidal extension and lymph node metastasis. CLDN16 knockdown inhibited migration, invasion, and iodine uptake in PTC cells. Clinically, CLDN16 effectively identified malignancy in BRAF wild patients (94.2%), and combined with BRAF-V600E, achieved 96.9% accuracy. The incorporation of CLDN16 into PTC molecular typing facilitated precise high-risk identification (92.0% accuracy in the training set and 100% in the validation set).

Conclusions

CLDN16 presents a promising biomarker that could surpass BRAF-V600E, offering effective clinical utility and revolutionizing PTC molecular typing for precise high-risk identification.
The Global Scope of Competitive Legalities in the Early 19th-Century South China Sea: The Topaz Incident
Authors: Kroncke Jedidiah J , Li Haimo
Published: February 2025

This article examines the 1807 capture of the American merchant vessel Topaz by the British cutter HMS Diana in waters outside of Macau. By unearthing the full transnational context of this event, the article establishes the under-appreciated global scope of post-colonial American foreign policy as well as the early 19th-century Anglo-American rivalry that culminated in the War of 1812. Moreover, explicating the transnational dynamics of the Topaz incident demonstrates the similarly under-appreciated centrality of the China trade to this growing geopolitical rivalry. This trade was materially critical to the resolution of British ambitions in Europe during the Napoleonic Wars, and such importance drove aggressive British reactions to the rapid success of the USA as a re-exporter of Chinese goods. Similarly, Sino-American trade relations were a symbolically charged arena for American ambitions to establish a distinct post-colonial identity as a true adherent to the law of nations. Herein, recovering the full diplomatic and legal aftermath of the Topaz incident also reveals the importance of prize law as a global forum for this era of Anglo-American rivalry as well as how prize law’s particular form of quasi-privatized legality played into often opportunistic American invocations of ‘commercial empire’. The article’s mapping of the local and transnational reactions to the Topaz incident  also challenges extant scholarship’s focus on Opium War-era treaty negotiations as the primary driver of Qing understandings of Western legalities by highlighting the neglected importance of pre-Opium War legal interactions, especially commercial interactions and conflicts.
How I became the man I had always been: Narrating the self in recent English and German life writing by trans men
Authors: Gratzke Michael
Published: February 2025

The literary corpus of this article consists of twenty-first-century life writing by trans men in the United States, Canada and Germany. The books fall broadly into two categories in line with Ruth Pearce’s distinction between trans-as-condition and trans-as-movement. A series of close readings uses Christa Binswanger and Andrea Zimmermann’s notion of palimpsestic queer subjectivity and Paul B. Preciado’s somatheque (trans body-as-archive) to highlight the commonalities of and differences between these two groups. This article concludes that any interpretation of trans people’s narratives needs to account for the position that the transition narrative is assigned in the text. Some writers go into great detail to create a coherent and comprehensive lifespan account, others focus on key episodes and yet another group, more commonly on the side of trans-as-movement, avoid autobiographical depth in favour of a focus on the near present in its social and political contexts.
Suppression of meiotic crossovers in pericentromeric heterochromatin requires synaptonemal complex and meiotic recombination factors in Drosophila melanogaster
Authors: Pazhayam Nila M , Sagar Sasha , Sekelsky Jeff
Published: February 2025

The centromere effect (CE) is a meiotic phenomenon that ensures meiotic crossover suppression in pericentromeric regions. Despite being a critical safeguard against nondisjunction, the mechanisms behind the CE remain unknown. Previous studies found that different regions of the Drosophila pericentromere, encompassing proximal euchromatin, beta and alpha heterochromatin, undergo varying levels of crossover suppression, raising the question of whether distinct mechanisms establish the CE in different regions. We asked whether different pericentromeric regions respond differently to mutations that impair features that may play a role in the CE. In flies with a mutation that affects the synaptonemal complex (SC), a structure is hypothesized to have roles in recombination and crossover patterning, we observed a redistribution of pericentromeric crossovers from proximal euchromatin towards beta heterochromatin but not alpha heterochromatin, indicating a role for the SC in suppressing crossovers in beta heterochromatin. In flies mutant for mei-218 or rec, which encode components of a critical pro-crossover complex, there was a more extreme redistribution of pericentromeric crossovers towards both beta and alpha heterochromatin, suggesting an important role for these meiotic recombination factors in suppressing heterochromatic crossovers. We mapped crossovers in flies mutant for Su(var)3-9, which encodes histone H3-lysine-9 methyltransferase. Although we expected strong alleviation of crossover suppression in heterochromatin, no changes in pericentromeric crossover distribution were observed in this mutant, indicating that this vital heterochromatin factor is dispensable for preventing crossovers in heterochromatin. Thus, in D. melanogaster the meiotic machinery seems to play a more significant role in suppressing centromere-proximal crossovers than chromatin state.
The Divergence of Mean Phenotypes Under Persistent Gaussian Selection
Authors: Lynch Michael , Menor Scott
Published: February 2025

Although multigenic traits are often assumed to be under some form of stabilizing selection, numerous aspects of the population-genetic environment can cause mean phenotypes to deviate from presumed optima, often in ways that effectively transform the fitness landscape to one of directional selection. Focusing on an asexual population, we consider the ways in which such deviations scale with the relative power of selection and genetic drift, number of linked genomic sites, magnitude of mutation bias, and the location of optima with respect to possible genotypic space. Even in the absence of mutation bias, mutation will influence evolved mean phenotypes unless the optimum happens to coincide exactly with the mean expected under neutrality. In the case of directional mutation bias and large numbers of selected sites, effective population sizes (Ne) can be dramatically reduced by selective-interference effects, leading to further mismatches between phenotypic means and optima. Situations in which the optimum is outside or near the limits of possible genotypic space (e.g., a half-Gaussian fitness function) can lead to particularly pronounced gradients of phenotypic means with respect to Ne, but such gradients can also occur when optima are well within the bounds of attainable phenotypes. These results help clarify the degree to which mean phenotypes can vary among populations experiencing identical mutation and selection pressures but differing in Ne, and yield insight into how the expected scaling relationships depend on the underlying features of the genetic system.
Topography Prediction from Marine Gravity and Satellite Imagery and Ship Soundings
Authors: Xu Huan , Wanga Qiuyu , Yu Jinhai , Anderson Ole Baltazar , Tian Yuwei , Xu Nan
Published: February 2025

Marine observation data are plentiful for constructing seafloor topography, and the integration of multi-sources data to construct a more accurate topography model remains a significant subject that continues to be explored and studied. In this study, we use geoid height (GH), Gravity (VG) and Vertical Gravity Gradient (VGG) derived from a single rectangular prism to establish the foundational observation equations for predicting topography. The effectiveness of the foundational observation equations is verified through study cases without the use of the ship measurement depth data. Additionally, the single- and multi-beam soundings data are employed as control points to integrate into the foundational observation equations for predicting topography. The prediction results demonstrate that the prediction accuracy of combined VG anomalies with ship soundings is better than GH and VGG anomalies, which is primarily because VG anomalies are effective than GH amplify high frequency signals of topography and stronger than VGG anomalies in suppressing high frequency errors. Additionally, considering the limited accuracy of marine gravity in sea region with islands and reefs, this study incorporates satellite imagery data to identify the location and size of the islands. Then, the topography of the islands is introduced and the control equations is established to jointly predict topography. The prediction results reveal the RMS errors between prediction results and single- and multi-beam sounding data are 67.4 m, which is 37.4%, 57.8% and 62.8% higher than that of SRTM 15+, DTU and ETOPO-1 models respectively. Notably, compared with the STRM 15+ model, the algorithm improves the topography accuracy of the sea area near the islands by nearly 60.8%.
In silico analysis of pressure distribution and flow profiles across an experimental left ventricular assist device accessory
Authors: Osypka Anna , Meissner Florian , Ozturk Deniz , Windisch Roxane , Vestner Heiko , Galbas Michelle Costa , Czerny Martin , Bothe Wolfgang
Published: February 2025

OBJECTIVES

Implantation of left ventricular assist devices conventionally requires a sternotomy and cardiopulmonary bypass. An experimental accessory was designed to redirect the device’s outflow graft through the left ventricle into the ascending aorta. This design allows for implantation via left thoracotomy only but resulted in significant pressure loss both in vitro and in vivo. We evaluated the reasons for the pressure loss of the experimental accessory by quantifying pressure distribution and flow profiles using computational fluid dynamics simulation tools.

METHODS

A computational fluid dynamics model based on the accessory’s geometry was used to simulate nominal blood flow through the model. Quantities of interest included pressure and flow velocity. Pressure differences between the pump inlet and outlet were calculated at different rotational speeds (4000, 5200, 6400 rpm) and pump flow rates (1, 5, 8.4 L/min). Results were compared with simulations of a generic left ventricular assist device to determine the accessory's impact.

RESULTS

Natural pump characteristics were observed, as increased rotational speed caused an increase in pressure head with a constant flow rate. For all cases, a greater decrease in pressure head was seen between 5 and 8.4 L/min than between 1 and 5 L/min. Curvature intensity and channel bifurcation in the outflow were the main contributors to downstream pressure loss.

CONCLUSIONS

The next iteration of the LVAD accessory should focus on minimizing curvatures and avoiding bifurcations in the outflow. Further development may allow for less invasive left ventricular assist device implantation with negligible alterations in pump performance.
Microbiota contribute to regulation of the gut-testis axis in seasonal spermatogenesis
Authors: Wu Zifang , Li Long , Chen Shaoxian , Gong Ye , Liu Yuyan , Jin Tianqi , Wang Yang , Tang Jie , Dong Qian , Yang Bangzhu , Yang Fangxia , Dong Wuzi
Published: February 2025

Seasonal breeding is an important adaptive strategy for animals. Recent studies have highlighted the potential role of the gut microbiota in reproductive health. However, the relationship between the gut microbiota and reproduction in seasonal breeders remains unclear. In this study, we selected a unique single food source animal, the flying squirrel (Trogopterus xanthipes), as a model organism for studying seasonal breeding. By integrating transcriptomic, metabolomic, and microbiome data, we comprehensively investigated the regulation of the gut-metabolism-testis axis in seasonal breeding. Here, we demonstrated a significant spermatogenic phenotype and highly active spermatogenic transcriptional characteristics in the testes of flying squirrels during the breeding season, which were associated with increased polyamine metabolism, primarily involving spermine and γ-amino butyric acid. Moreover, an enrichment of Ruminococcus was observed in the large intestine during the BS and may contribute to enhanced methionine biosynthesis in the gut. Similar changes in Ruminococcus abundance were also observed in several other seasonal breeders. These findings innovatively revealed that reshaping the gut microbiota regulates spermatogenesis in seasonal breeders through polyamine metabolism, highlighting the great potential of the gut-testis axis in livestock animal breeding and human health management.
Duration of antibiotic treatment for respiratory tract infections in primary care
Authors: Llor Carl , Hansen Malene Plejdrup , Lykkegaard Jesper , Olsen Jonas , Lindberg Bent Håkan , Rebnord Ingrid Keilegavlen , Touboul Lundgren Pia , Bruno Pascale , Kowalczyk Anna , Lionis Christos , Radzeviciene Ruta , Jaruseviciene Lina , Bjerrum Lars , García-Sangenís Ana ,   HAPPY PATIENT Study Group, Mally Stella , Modena Daniela , Bjerrum Anders , Monfà Ramon , Pedrós Rosa Morros , Moragas Ana , Søndergaard Jens , Munck Anders , Berntsen Susanne Døssing , Nexøe Jørgen , Døssing-Poulsen Nina Camilla , Sebjørnsen Isabel , Lesage Vanessa , Godycki-Cwirko Maciek , Karkana Maria-Nefeli , Anastasaki Marilena , López-Valcárcel Beatriz González , Floriano Fabiana Raynal , Vallejo-Torres Laura , Chalkidou Athina , Jensen Jette Nygaard , Hansen Matilde Bøgelund , Cordoba Gloria , Taxis Katja , Lambert Maarten , Vilanova Pere , Álvarez Laura , Ricart Marta , Briones Sergi , Bandzaite Auste , Trečiokienė Indrė , Marquet Pierre , Benkő Ria , Tattevin Pierre , Cailleaux Marine , Ruppe Georg , Balint Andras
Published: February 2025

Objectives

The primary driver of antimicrobial resistance is excessive antibiotic use, posing a global threat to public health. Reducing individual exposure to antibiotics is a key to addressing the problem. This study aimed to assess the duration of antibiotic courses administered to patients with acute respiratory tract infections (RTIs) in primary care.

Methods

Consecutive patients presenting with RTI symptoms were prospectively included from general practices and out-of-hours services in France, Greece, Lithuania, Poland and Spain for two winter periods (February to April 2022 and 2023). Data were collected using a paper-based Audit Project Odense template, with clinicians recording patient age, gender, RTI diagnosis, type of antibiotic prescribed and treatment duration.

Results

A total of 196 doctors (133 in general practice and 63 in out-of-hours services) registered 11 270 cases, with 34.0% (3835) receiving antibiotics. The mean antibiotic course duration was 7.52 days (SD 2.11), which was significantly longer for pneumonia, COVID-19 infection and pharyngotonsillitis (8.01, 8.00 and 7.74 days, respectively), and lowest for predominantly viral infections, such as the common cold and flu infection, laryngitis and acute bronchitis (6.32, 6.48 and 6.98 days, respectively; P < 0.001). A total of 26.7% of the courses were prescribed for 10 days or longer.

Conclusions

Antibiotic courses for common RTIs are often prolonged, which does not align with current recommendations for course duration. Antibiotics should be avoided in cases of predominantly viral infections and most mixed infections; however, if deemed necessary, the courses should be substantially reduced to minimize unnecessary exposure.
Increased sulfate-reducing bacteria can drive microbial dysbiosis in bleached corals
Authors: Sajid Sumbal , Xiao Baohua , Zhang Guoqiang , Zhang Zongyao , Chen Lianguo , Fang James Kar-Hei , Lu Yishan , Cai Lin
Published: February 2025

Aims

Coral bleaching occurs when coral colonies lose their Symbiodiniaceae partner and turn pale or white. Although this event is generally temperature-induced, there is also the possibility of holobiont microbial infection and dysbiosis. To address this issue, this study was conducted to investigate the diversity and composition of Symbiodiniaceae and bacteria in healthy and bleached colonies of Porites lutea collected from eastern Shenzhen.

Methods and results

Internal transcribed spacer 2 (ITS2) and 16S amplicon sequencing analysis were used to explore the diversity and composition of Symbiodiniaceae and bacteria in healthy and bleached colonies of P. lutea. Bacterial diversity and richness were significantly higher in bleached colonies than in healthy colonies (P < 0.05), whereas the diversity and richness of Symbiodiniaceae showed no significant changes. The bleaching event exerted a more significant impact on Symbiodiniaceae composition, which differed between healthy and bleached colonies (PERMANOVA, F = 8.246, P < 0.05). In terms of composition, Clade C (Cladocopium) was the predominant Symbiodiniaceae, whereas subclade C116 and C2r were significantly less abundant in bleached colonies than in healthy colonies (P < 0.05). The phyla Bacteroidetes, Acidobacteria, and Actinobacteria were significantly more abundant in bleached colonies than in healthy colonies (P < 0.05). The sulfate-reducing bacteria (SRB) Desulfobulbus and Desulfobacter at the genus level and Desulfobacterales and Desulfuromonadales at the order level were significantly more abundant in bleached colonies than in healthy colonies (P < 0.05). The co-occurrence patterns of Symbiodiniaceae and bacteria revealed a negative correlation of Desulfofaba, Desulfovibrio, Desulfarculus, and Desulfobulbus with Endozoicomonas, a very common symbiotic bacterial genus found in corals.

Conclusion

Coral bleaching may be associated with significant shifts in microbial communities, including increased SRB abundance, which may disrupt microbial balance and contribute to bleaching.
Deciphering genomic codes using advanced natural language processing techniques: a scoping review
Authors: Cheng Shuyan , Wei Yishu , Zhou Yiliang , Xu Zihan , Wright Drew N , Liu Jinze , Peng Yifan
Published: February 2025

Objectives

The vast and complex nature of human genomic sequencing data presents challenges for effective analysis. This review aims to investigate the application of natural language processing (NLP) techniques, particularly large language models (LLMs) and transformer architectures, in deciphering genomic codes, focusing on tokenization, transformer models, and regulatory annotation prediction. The goal of this review is to assess data and model accessibility in the most recent literature, gaining a better understanding of the existing capabilities and constraints of these tools in processing genomic sequencing data.

Materials and Methods

Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, our scoping review was conducted across PubMed, Medline, Scopus, Web of Science, Embase, and ACM Digital Library. Studies were included if they focused on NLP methodologies applied to genomic sequencing data analysis, without restrictions on publication date or article type.

Results

A total of 26 studies published between 2021 and April 2024 were selected for review. The review highlights that tokenization and transformer models enhance the processing and understanding of genomic data, with applications in predicting regulatory annotations like transcription-factor binding sites and chromatin accessibility.

Discussion

The application of NLP and LLMs to genomic sequencing data interpretation is a promising field that can help streamline the processing of large-scale genomic data while also providing a better understanding of its complex structures. It has the potential to drive advancements in personalized medicine by offering more efficient and scalable solutions for genomic analysis. Further research is also needed to discuss and overcome current limitations, enhancing model transparency and applicability.

Conclusion

This review highlights the growing role of NLP, particularly LLMs, in genomic sequencing data analysis. While these models improve data processing and regulatory annotation prediction, challenges remain in accessibility and interpretability. Further research is needed to refine their application in genomics.
Predictive ability of a commercial mixed-breed genomic test for feedlot performance and carcass traits of beef × Holstein steers
Authors: Basiel Bailey L , Felix Tara L , Dechow Chad D
Published: February 2025

Genomic tests are marketed as a method to appraise cattle value prior to feedlot entry. We aimed to evaluate the use of a commercial, multi-breed genomic test to predict terminal production characteristics of beef × Holstein steers. Phenotypes of feedlot performance and carcass characteristics were evaluated in beef × Holstein steers (n = 259) sired by 8 beef breeds. Steers were genotyped with Igenity Beef (Neogen Corporation, Lansing, MI), which ranks cattle for individual traits and by selection indexes on a scale of 1 to 10. Trait rankings were converted to molecular breeding values (MBV) derived from genotype. Expected progeny differences (EPD) of each steer’s sire were accessed from their respective breed associations. US Meat Animal Research Center across-breed adjustments for beef cattle were applied to growth and carcass sire EPD for all cattle except the 11 Wagyu-sired steers (n = 248 steers with sire EPD). Breed-adjusted sire EPD and MBV of traits were correlated with associated phenotypes of beef × Holstein steers and phenotypes were regressed on sire EPD and MBV. Sire EPD and MBV of yearling weight (YW) and hot carcass weight (HCW) were positively associated with initial and final feedlot body weight, respectively. The MBV of average daily gain (ADG) was not associated with phenotypic ADG, though greater derived sire EPD of ADG was associated with greater ADG and dry matter intake (DMI). The MBV of residual feed intake (RFI) was associated with DMI (P = 0.02) but not RFI or gain to feed ratio. Each kg of RFI predicted by MBV resulted in 0.31 kg greater ADG (P < 0.01), suggesting that MBV of RFI in beef × Holstein steers are not independent of rate of gain. For each kg of HCW predicted by MBV and sire EPD carcasses were 0.52 and 0.80 kg heavier (P < 0.01). Neither sire EPD nor MBV of ribeye area and backfat thickness were related to the corresponding phenotypes of beef × Holstein carcasses (P > 0.05). Both MBV and sire EPD of marbling score were strong predictors of marbling score and intramuscular fat content (P < 0.05). Tenderness MBV accurately predicted tenderness of the longissimus muscle of beef × Holstein progeny (P < 0.01). Igenity Beef Terminal Index ranking was associated with greater feedlot profitability (P = 0.03), but marbling MBV and sire EPD were more strongly associated with feedlot net profit (P < 0.01). Breed-adjusted sire EPD performed similarly to Igenity Beef MBV in predicting growth performance, carcass characteristics, and net profit of beef × Holstein steers.
Chlorantraniliprole as seed treatments against the black cutworm Agrotis ipsilon (Lepidoptera: Noctuidae) via residues in cotton ecosystem and the exposure risks to honeybees as measured in pollen
Authors: Jiang Jiangong , Li Rongyu , Guo Xinjie , Duan Huixue , Liu Wenzhen , Zhao Shuxin , Zhou Xinyuan , Zhang Zhengqun , Liu Feng , Mu Wei
Published: February 2025

The black cutworm Agrotis ipsilon (Hufnagel) (Lepidoptera: Noctuidae) can damage the cotton seedlings and induce destructive yield loss. Seed coating with systemic insecticides is a cost-effective alternative to control A. ipsilon during the early stage of cotton, but the control efficacy and exposure risk to honeybees remain unclear. This study evaluated the control effects of the anthranilic diamide insecticide chlorantraniliprole on A. ipsilon in cotton crops and the corresponding exposure risks to honeybees. Field studies revealed the control efficacy of chlorantraniliprole at 2 or 4 g/kg seed was greater than 75%, which was comparable to its spray control during the seedling development stage. A residual toxicity trial revealed that chlorantraniliprole treatment had a dose–response control effect on A. ipsilon during the 19 days after sowing. The residue levels of chlorantraniliprole in the stem bases and soil were found consistent with the residual toxicity against A. ipsilon. In the cotton flowering period, the highest detection frequency and residue of chlorantraniliprole were found in pollen from the plots treated with 4 g/kg seed. By using 2 independent risk assessment approaches, the exposure risk of chlorantraniliprole seed treatments were evaluated to be acceptable to honeybees. Overall, chlorantraniliprole coated with 2 g/kg seed was an effective alternative for controlling A. ipsilon at the cotton seedling stages.