bluuebunny/crossref_metadata_2025 huggingface dataset:
E
r measurements in JET L-mode plasmas for a wide range of densities—from the low-recycling regime up to the density limit
Authors: Silva C. , Groth M. , Aleiferis S. , Carvalho P. , Gil L. , Giroud C. , Morales R.B. , Nina D. , Solano E.R. , Thomas B. , Vaz M. , Vianello N. ,   JET Contributors
Published: February 2025

This study investigates the dependence of the radial electric field (E
r) on the line-averaged density in JET L-mode plasmas, utilizing Doppler backscattering measurements. Density ramp discharges up to the density limit are analyzed to investigate the physical processes that determine the edge E
r profile. At low densities, the E
r profile at the midplane exhibits a pronounced peak in the near scrape-off layer (SOL) and a shallow well inside the separatrix. As density increases, the SOL E
r peak diminishes quickly and the E
r well deepens until a Greenwald fraction of f
GW ≈ 0.8, followed by a slight reduction near the density limit. Our findings indicate that no collapse of edge flow shear occurs prior to the density limit onset, within a time scale of 10 ms. The E
r at the divertor target does not appear to play a significant role in the density limit as it is only significant in the low recycling regime, not changing appreciably above f
GW ≈ 0.35. A steep edge density gradient persists up to f
GW ≈ 0.95 with the density limit disruption onset coinciding roughly with a reduction in the pedestal top density. The edge E × B shear appears to be sufficient to maintain a steep density gradient region near the density limit. Finally, it is shown that the density limit is not due to a reduction in the shear induced by oscillating flows, as the amplitude of the geodesic acoustic modes vanishes around f
GW ≈ 0.5.
High-performance affinity peptide sensor for prostate specific antigen detection
Authors: Cheng Ao , Guo Shuangjia , Wang Zhehang , Lan Kuibo , Liu Zihao , Wang Yong , Chen Ruibing , Qin Guoxuan
Published: February 2025

Prostate-specific antigen (PSA) is the best serum biomarker for prostate cancer (PCa), and the detection of PSA concentration can be used to assess the risk of malignancy. Given the current lack of effective treatment options for PCa, early detection and intervention are particularly important. To address this, we developed a novel electronic biosensor aimed at highly sensitive detection of PSA. The core materials of this sensor consist of the receptor material, PSA-affinity peptides, and the support material, single-walled carbon nanotubes. These materials are cost-effective, can operate at room temperature, and exhibit good stability, which aids in optimizing the sensor’s performance and stability. We attached the carbon nanotubes to a gold fork electrode and successfully fabricated the device by chemically linking the peptides to the carbon nanotubes. PSA was subsequently detected through the binding of PSA molecules to specific peptide sequences in standard solution. The sensor achieved a detection limit as low as 10−13 μg μL−1, which is lower than that of currently used detection methods, demonstrating exceptional sensitivity. This biosensor offers advantages such as low cost, high efficiency, and strong specificity, indicating its broad application prospects in medical diagnostics, particularly in PCa screening.
Asymptotic behavior of solutions to some classes of multi-order fractional cooperative systems
Authors: Thinh La , Tuan Hoang
Published: February 2025

This paper is devoted to the study of the asymptotic behavior of solutions to multi-order fractional cooperative systems. First, we demonstrate the boundedness of solutions to fractional-order systems under certain conditions imposed on the vector field. We then prove the global attractivity and the convergence rate of solutions to such systems (in the case when the orders of fractional derivatives are equal, the convergence rate of solutions is sharp and optimal). To our knowledge, these kinds of results are new contributions to the qualitative theory of multi-order fractional positive systems and they seem to have been unknown before in the literature. As a consequence of this result, we obtain the convergence of solutions toward a nontrivial equilibrium point in an ecosystem model (a particular class of fractional-order Kolmogorov systems). Finally, some numerical examples are also provided to illustrate the obtained theoretical results.
Witnessing Conflict and Resilience
Authors: Borum Caty , Conrad-Pérez David
Published: February 2025

Chapter 3, “Witnessing Conflict and Resilience,” explores the exponential risk and motivations of documentary filmmakers who endeavor to expose the harsh complexities and realities of war that powerful figures wish to keep silent, provide a cultural memory of atrocities in the context of conflict, and offer a deeply intimate lens into lived experiences. To bring this theme to life and explore challenges, practices, and motivations of documentary filmmakers whose work seeks to ensure present-day awareness and long-term cultural memorializing, alongside testimony about human resilience, the case studies of this chapter include The Cave (Syria), For Sama (Syria), Peace for Nina (Ukraine), and No Simple Way Home (South Sudan).
Upholding Freedom of Expression
Authors: Borum Caty , Conrad-Pérez David
Published: February 2025

Chapter 4: “Upholding Freedom of Expression,” probes films that exemplify freedom of expression, a hallmark of an open, pluralistic society, for centuries threatened by political regulation and suppression as a form of social control. Over the past decade, artistic and media freedoms have declined around the world—in both authoritarian regimes and liberal democracies. In this context, how are independent documentaries telling stories that push hard against censorship and media repression? Chapter 4 explores this topic with profiled films that include A Thousand Cuts (Philippines), Writing with Fire (India), and The First Step (United States).
What states and EU institutions care about
Authors: Steinbach Armin
Published: February 2025

With their attachment to positive law, lawyers rarely ask why EU Member States crafted EU law the way they did or why no agreement on EU law was reached at all. Inquiring into the rationale and motives behind cooperation through EU law elucidates EU members’ willingness to surrender authority to the supranational EU. To that end, this chapter starts from the rational choice premise that states pursue their own interests. This standard assumption is challenged from public choice perspectives questioning the uniform state will and emphasizing the interaction among different actors optimizing a diverse set of preferences. While the initial design of EU Treaties was the outcome of states-only cooperation, the emergence of EU institutions has brought new players with a peculiar set of interests that particularly play out in the enforcement of EU primary law and in the making of EU secondary law. Unlike other international organizations, the EU evolved from a ‘dependent’ variable, in which it was merely the outcome of inter-state deliberate choice, to an ‘independent’ variable by being a state-like actor that exerts autonomous influence on other state actors.
Reducing transaction costs
Authors: Steinbach Armin
Published: February 2025

Saving on transaction costs may serve as a stimulus for cooperation, while the abundance of transaction costs may hamper cooperation. The cost perspective links to the scholarship researching international organizations with respect to why and how they are shaped. Transaction costs occur on every level of EU law-making: treaty negotiations, compromise search in the Council, the loss of national sovereignty, and sluggish implementation of EU secondary law. Context-specific costs must therefore be taken into account to understand whether and how cooperation unfolds.
Supplying public goods and addressing external effects
Authors: Steinbach Armin
Published: February 2025

The ‘Europeanization’ of public goods is a driver of European integration, as trends towards internationalization and globalization have been giving public goods such as peace, security, monetary stability, and climate protection an increasingly pan-European dimension. Public goods analysis and federalism theory offer guidance on when and under what conditions the delivery of public goods in the EU should be provided at the EU level or, conversely, at the level of the Member State. These approaches also offer insight into how the allocation of competencies by the EU Treaties can optimize the effective provision of public goods. Public goods cooperation in the EU varies depending on whether the goods can be characterized as a coordination game, a ‘weakest-link public good’ or a ‘substitute public good’, or whether externalities occur as pecuniary or non-pecuniary, or as network externalities. With the EU comprising cooperation across many policy sectors and goods, where some produce network externalities (trade or financial regulation), while others exhibit weakest-link public goods (eg security, migration), the variable nature of public goods gives rise to a diverse pattern of cooperation and to differentiated integration.
Systematic review: severe endoscopic lesions in inflammatory bowel disease
Authors: Tyrode Gaëlle , Rivière Pauline , Sebastian Shaji , Poullenot Florian , Vuitton Lucine , Laharie David
Published: February 2025

Background

Endoscopy and biopsy are the standard tool for the diagnosis of inflammatory bowel disease (IBD) and the assessment of treatment response. Severe endoscopic lesions (SEL) are commonly observed in IBD, but have been poorly described in the literature. The aim of this review is to provide an overview of the current understanding and gaps in knowledge about these lesions.

Methods

We performed a systematic review of studies of SEL in patients with IBD. A search was performed in MEDLINE, Embase and Cochrane CENTRAL databases in July 2024. Studies were eligible if they investigated SEL, its involvement in the disease, its evolution with treatment and its prognostic implications.

Results

We found 1172 articles in the Pubmed database and 46 were included. Of the various definitions of SEL used in the literature, most of them are based on the most severe endoscopic items from existing endoscopic scores, but none have been validated. Despite the paucity of literature, the prevalence of SEL is estimated to be 33-75% in acute severe ulcerative colitis (ASUC) and 22.5-87% in Crohn’s disease (CD). In terms of prognosis, SEL are associated with steroid refractoriness in ASUC and, do not affect response to infliximab or ciclosporin. In CD, the response to biologics, especially anti-TNF, is not affected by the presence of SEL.

Conclusion

There is currently no validated definition of SEL in IBD. When present, they are associated with steroid failure in the setting of ASUC, but do not affect response to anti-TNF in either CD or ASUC.
Physiological and molecular responses of the chorioallantoic membranes to diluted bitumen exposures in multiple bird species
Authors: Wallace Sarah J , de Solla Shane R , Lavoie Raphaël A , Triffault-Bouchet Gaëlle , King Mason D , Langlois Valérie S
Published: February 2025

Embryotoxicity is a well-known consequence of polycyclic aromatic compound (PAC) exposure, but the molecular mechanisms of action of PAC mixtures, especially for unconventional crude petroleum types such as diluted bitumen (dilbit), remain to be fully elucidated in birds. To explore the mechanism of action of PAC in birds, the egg-injection model was used. Eggs of domestic chicken (Gallus gallus), double-crested cormorant (Nannopterum auritum), and northern gannet (Morus bassanus) were injected with 0.5 μL/g of average species-specific egg weight of 1:10–1:10,000 dilutions of Clearwater or Cold Lake Blend dilbits into the air cell on embryonic Day 0 and were artificially incubated until the liver was formed. The injections of <0.16–335 ng total PAC/g egg were consistent with PAC concentrations measured in wild bird eggs and in embryos exposed to dilbit through eggshell oiling. Mortality and frequency of malformations were low across treatments. The expression of genes involved in xenobiotic detoxification in both liver and chorioallantoic membrane (CAM) differed among species in response to dilbit exposure. Cytochrome P450 1a (cyp1a) in the CAM of dilbit-exposed chickens was induced to a higher fold-change at a lower PAC concentration than the liver, but this pattern was not consistent in wild birds. The expression of additional genes involved in the aryl hydrocarbon receptor activation adverse outcome pathway were variable in the double-crested cormorant and northern gannet CAMs. Our study demonstrates the usefulness of CAM as a target tissue for PAC metabolism in embryotoxicity. Future studies should address the differential CAM physiology across bird species to better understand the variation of species responses to contaminants and consider the use of CAM in addition to liver.
Factors underpinning the performance of implemented artificial intelligence-based patient deterioration prediction systems: reasons for selection and implications for hospitals and researchers
Authors: van der Vegt Anton H , Campbell Victoria , Wang Shuyi , Malycha James , Scott Ian A
Published: February 2025

Objective

The degree to which deployed artificial intelligence-based deterioration prediction algorithms (AI-DPA) differ in their development, the reasons for these differences, and how this may impact their performance remains unclear. Our primary objective was to identify design factors and associated decisions related to the development of AI-DPA and highlight deficits that require further research.

Materials and Methods

Based on a systematic review of 14 deployed AI-DPA and an updated systematic search, we identified studies of 12 eligible AI-DPA from which data were extracted independently by 2 investigators on all design factors, decisions, and justifications pertaining to 6 machine learning development stages: (1) model requirements, (2) data collection, (3) data cleaning, (4) data labeling, (5) feature engineering, and (6) model training.

Results

We found 13 design factors and 315 decision alternatives likely to impact AI-DPA performance, all of which varied, together with their rationales, between all included AI-DPA. Variable selection, data imputation methods, training data exclusions, training sample definitions, length of lookback periods, and definition of outcome labels were key design factors accounting for most variation. In justifying decisions, most studies made no reference to prior research or compared with other state-of-the-art algorithms.

Discussion

Algorithm design decisions regarding factors impacting AI-DPA performance have little supporting evidence, are inconsistent, do not learn from prior work, and lack reference standards.

Conclusion

Several deficits in AI-DPA development that prevent implementers selecting the most accurate algorithm have been identified, and future research needs to address these deficits as a priority.
Development of a prototype genetic evaluation for teat and udder score in American Angus cattle
Authors: McEwin Rudi A , Retallick Kelli J , Miller Stephen P , Garcia Andre
Published: February 2025

Improving traits related to teat size (TS) and udder suspension score (US) can have long term benefits for the health and productivity of beef herds. Well-structured udders and teats contribute to better calf health and growth, through un-inhibited suckling as well as improved cow longevity and milk production. No genetic evaluation is currently available for these traits in American Angus; the aim of the study was to investigate and develop a prototype genetic evaluation for TS and US. Teat and udder suspension score were subjectively assessed on farm following the American Angus Association guidelines. After quality control, the final dataset comprised 41,914 complete scores recorded on 23,886 Angus cows. Scores ranged from 1 to 9 for both teat and udder with similar mean (SD) scores of 7.1 (1.6) respectively. A series of multi-trait, animal models (pedigree size of 154,330 individuals) between TS, US and growth traits were run to estimate trait heritability and genetic correlations. TS and US were found to be moderately heritable (0.31 and 0.34 respectively) and highly repeatable (0.51 and 0.47 respectively). TS and US had a high genetic correlation (0.76) between them and generally low negative genetic correlations with birth weight, weaning weight, yearling gain and yearling height (0 to -0.19). Udder score was moderately genetically correlated to the maternal genetic component of weaning weight (MILK; -0.24). Mimicking a standard American Angus evaluation, model prediction accuracies for TS and US were estimated for BLUP and ssGBLUP scenarios. Accuracies ranged from 0.39-0.61 indicating that the starting set of phenotypes and models is sufficient to produce an accurate national evaluation. ssGWAS found that TS and US are likely polygenic, with no large SNP effects noted. Angus breeders are encouraged to submit annual teat and udder scores on their cows, to continue to improve model accuracy and expedite genetic improvement for these traits.
It is not σ8: constraining the non-linear matter power spectrum with the Dark Energy Survey Year-5 supernova sample
Authors: Shah P , Davis T M , Vincenzi M , Armstrong P , Brout D , Camilleri R , Galbany L , Gill M S S , Huterer D , Jeffrey N , Lahav O , Lee J , Lidman C , Möller A , Sullivan M , Whiteway L , Wiseman P , Allam S , Aguena M , Annis J , Blazek J , Brooks D , Rosell A Carnero , Carretero J , Conselice C , da Costa L N , Pereira M E S , Desai S , Diehl H T , Doel P , Everett S , Ferrero I , Flaugher B , Frieman J , García-Bellido J , Gaztanaga E , Giannini G , Gruen D , Gruendl R A , Gutierrez G , Hinton S R , Hollowood D L , Honscheid K , James D J , Lee S , Marshall J L , Mena-Fernández J , Miquel R , Palmese A , Pieres A , Malagón A A Plazas , Porredon A , Samuroff S , Sanchez E , Sevilla-Noarbe I , Smith M , Suchyta E , Swanson M E C , Tarle G , Tucker D L , Weaverdyck N ,   DES Collaboration, Casas Ricard , Challis Pete , Childress Michael , Covarrubias Ricardo , D'Andrea Chris , Filippenko Alex , Finley David , Fisher John , Förster Francisco , Goldstein Daniel , González-Gaitán Santiago , Gupta Ravi , Hamuy Mario , Kuhlmann Steve , Lasker James , March Marisa , Marriner John , Morganson Eric , Mosher Jennifer , Swann Elizabeth , Thomas Rollin , Wolf Rachel
Published: February 2025

The weak gravitational lensing magnification of Type Ia supernovae (SNe Ia) is sensitive to the matter power spectrum on scales $k\gt 1 h$ Mpc$^{-1}$, making it unwise to interpret SNe Ia lensing in terms of power on linear scales. We compute the probability density function of SNe Ia magnification as a function of standard cosmological parameters, plus an empirical parameter $A_{\rm mod}$ which describes the suppression or enhancement of matter power on non-linear scales compared to a cold dark matter only model. While baryons are expected to enhance power on the scales relevant to SN Ia lensing, other physics such as neutrino masses or non-standard dark matter may suppress power. Using the Dark Energy Survey Year-5 sample, we find $A_{\rm mod} = 0.77^{+0.69}_{-0.40}$ (68 per cent credible interval around the median). Although the median is consistent with unity there are hints of power suppression, with $A_{\rm mod} \lt 1.09$ at 68 per cent credibility.
Global chromatin reorganization and regulation of genes with specific evolutionary ages during differentiation and cancer
Authors: Raynal Flavien , Sengupta Kaustav , Plewczynski Dariusz , Aliaga Benoît , Pancaldi Vera
Published: February 2025

Cancer cells are highly plastic, favoring adaptation to changing conditions. Genes related to basic cellular processes evolved in ancient species, while more specialized genes appeared later with multicellularity (metazoan genes) or even after mammals evolved. Transcriptomic analyses have shown that ancient genes are up-regulated in cancer, while metazoan-origin genes are inactivated. Despite the importance of these observations, the underlying mechanisms remain unexplored. Here, we study local and global epigenomic mechanisms that may regulate genes from specific evolutionary periods. Using evolutionary gene age data, we characterize the epigenomic landscape, gene expression regulation, and chromatin organization in several cell types: human embryonic stem cells, normal primary B-cells, primary chronic lymphocytic leukemia malignant B-cells, and primary colorectal cancer samples. We identify topological changes in chromatin organization during differentiation observing patterns in Polycomb repression and RNA polymerase II pausing, which are reversed during oncogenesis. Beyond the non-random organization of genes and chromatin features in the 3D epigenome, we suggest that these patterns lead to preferential interactions among ancient, intermediate, and recent genes, mediated by RNA polymerase II, Polycomb, and the lamina, respectively. Our findings shed light on gene regulation according to evolutionary age and suggest this organization changes across differentiation and oncogenesis.
Probabilistic and machine-learning methods for predicting local rates of transcription elongation from nascent RNA sequencing data
Authors: Liu Lingjie , Zhao Yixin , Hassett Rebecca , Toneyan Shushan , Koo Peter K , Siepel Adam
Published: February 2025

Rates of transcription elongation vary within and across eukaryotic gene bodies. Here, we introduce new methods for predicting elongation rates from nascent RNA sequencing data. First, we devise a probabilistic model that predicts nucleotide-specific elongation rates as a generalized linear function of nearby genomic and epigenomic features. We validate this model with simulations and apply it to public PRO-seq (Precision Run-On Sequencing) and epigenomic data for four cell types, finding that reductions in local elongation rate are associated with cytosine nucleotides, DNA methylation, splice sites, RNA stem-loops, CTCF (CCCTC-binding factor) binding sites, and several histone marks, including H3K36me3 and H4K20me1. By contrast, increases in local elongation rate are associated with thymines, A+T-rich and low-complexity sequences, and H3K79me2 marks. We then introduce a convolutional neural network that improves our local rate predictions. Our analysis is the first to permit genome-wide predictions of relative nucleotide-specific elongation rates.
Nmnat2 deficiency in the arcuate nucleus or paraventricular nucleus induces Sarm1‐independent neuron loss and liraglutide‐reversible obesity
Authors: Yu Huimin , Feng Ning , Zhong Wuling , Han Yumo , Cheng Yalan , Zhang Zhentong , Wang Yingqi , Gao Peidong , Huang Rui , Zhang Cong , Liu Zongyang , Dong Jieya , He Zhishui , Lai Hejin , Shen Ziru , Zhai Qiwei
Published: February 2025

Nicotinamide mononucleotide adenylyltransferase 2 (Nmnat2) plays an important role in maintaining axon integrity, and the arcuate nucleus (ARC), and paraventricular nucleus (PVN) are crucial nuclei in the control of energy balance. However, the effect of Nmnat2 deficiency in ARC and PVN is still unclear. Nmnat2

loxP/loxP
or Nmnat2

loxP/loxP
, Sarm1

−/−
mice were bilaterally injected with AAV‐CMV‐GFP‐Cre once into the ARC, PVN, or lateral parabrachial nucleus (LPBN) to obtain Nmnat2

ARC−/−
, Nmnat2

PVN−/−
, Nmnat2

LPBN−/−
, Nmnat2

ARC−/−
, SKO, Nmnat2

PVN−/−
, SKO, or Nmnat2

LPBN−/−
, SKO mice. Syn1‐Cre mice were bilaterally injected with AAV‐EF1a‐flex‐taCasp3‐TEVp once into the ARC or PVN to specifically induce neuron loss. Metabolic changes were measured in the mice intraperitoneally injected with or without liraglutide, a glucagon‐like peptide‐1 (GLP‐1) analog. Neuron loss and neuron activation were monitored by immunofluorescence. Deletion of Nmnat2 in ARC or PVN of mice leads to neuron loss, increased food intake, and obesity in a Sarm1‐independent manner. Intraperitoneal injection of liraglutide activates neurons in PVN and LPBN, and attenuates hyperphagia and obesity induced by Nmnat2 deletion or apoptosis of Syn1‐positive neurons in ARC or PVN, but has no significant effect on neuron loss. Nmnat2 deficiency in LPBN leads to death within 2 weeks, which can be markedly rescued by Sarm1 deficiency. These data show that deletion of Nmnat2 in ARC or PVN in adult mice leads to Sarm1‐independent neuron loss, and liraglutide‐reversible hyperphagia and obesity. These findings also elucidate the integrated role of ARC or PVN for downregulating food intake, the requirement of LPBN for survival, and the ARC‐ or PVN‐independent effect of GLP‐1 on food intake.
ASSOCIATION BETWEEN OBESITY AND ALTERATIONS IN PHOTORECEPTOR–RETINAL PIGMENT EPITHELIUM–CHORIOCAPILLARIS COMPLEX IN HEALTHY EYES
Authors: Cheng Hongling , Lin Zhiyang , Lin Kuangching , Chen Hao , Zhang Xi , Shen Meixiao , Xu Suzhong
Published: February 2025

Purpose:

To investigate the effect of obesity on alterations in the photoreceptor–retinal pigment epithelium (RPE)–choriocapillaris complex.

Methods:

Two hundred and twenty participants with varying body mass index were enrolled and categorized into three groups: normal weight, overweight, and obese. Retinal and choroidal images were obtained using swept-source optical coherence tomography. Automatic segmentation was used for image analysis, evaluating retina thickness parameters such as retinal nerve fiber layer, ganglion cell layer and inner plexiform layer, inner nuclear layer, outer plexiform layer, outer nuclear layer, myoid and ellipsoid zone, outer segment of photoreceptors, RPE, and choroidal parameters including choroidal thickness, luminal area, stromal area, total choroidal area, choroidal vascular index, and choriocapillaris flow void percentage. Differences in photoreceptor–RPE–choriocapillaris complex among the groups and their correlation with body mass index were explored.

Results:

Compared with the control subjects, participants with obesity exhibited thinner myoid and ellipsoid zone and outer segment of photoreceptors, increased choriocapillaris flow void percentage, and thicker RPE. Correlation analysis revealed a negative correlation between body mass index and myoid and ellipsoid zone (r = −0.17, P = 0.01) and outer segment of photoreceptors (r = −0.16, P = 0.02), whereas a positive correlation was observed with RPE (r = 0.15, P = 0.00).

Conclusion:

Individuals with obesity may present with a thinner myoid and ellipsoid zone and outer segment of photoreceptors, thicker RPE, and reduced choriocapillaris perfusion, suggesting potential damage to the photoreceptor–RPE–choriocapillaris complex. These alterations in the photoreceptor–RPE–choriocapillaris complex alterations could serve as potential biomarkers for monitoring early pathologic and physiologic changes associated with obesity.
Functional Benefits of Behind-the-Ear Processors Compared With Off-the-Ear Processors in Adult Cochlear Implant Users
Authors: Salvador Craig D. , Sinacori Zachary , Camposeo Elizabeth L. , Meyer Ted A. , McRackan Theodore R.
Published: February 2025

Objective

Cochlear implant (CI) devices are fitted with two external processor styles—a behind-the-ear (BTE) or an off-the-ear (OTE) option. Although previous research has predominantly focused on speech recognition abilities between processor styles, the current study aims to examine the potential real-world functional differences between processor types.

Study Design

Retrospective case-control, matched at a 1:2 ratio.

Setting

Tertiary Otolaryngology Referral Center.

Patients

Patients with bilateral sensorineural hearing loss

Intervention

Cochlear implantation

Main Outcome Measures

Cochlear Implant Quality of Life 35 Profile (CIQOL-35 Profile), and CNC word (CNCw) and AzBio sentence (quiet) recognition.

Results

A total of 36 patients were included (n = 12 OTE and n = 24 BTE users). The overall study population demonstrated improvements in CNCw (d = 1.9 [1.3, 2.4]), AzBio sentences in quiet (d = 2.1 [1.5, 2.6]), and medium-to-large effect sizes for domains of the CIQOL-35 (d range: 0.5–0.9) after cochlear implantation. Between-group analysis demonstrated that BTE users performed better in CNCw (d = 0.4 [−0.3, 1.1]) and AzBio quiet (d = 0.5 [−0.2, 1.2]) than their OTE counterparts. However, there were minimal differences identified between processor types based on CIQOL domain and global scores (d range: 0.04–0.2).

Conclusion

BTE users may have a better speech recognition ability than their OTE counterparts. However, CIQOL domain and global scores are comparable between the two processor types. A prospective, randomized controlled trial will be needed to address the limitations of a retrospective analysis.
Early Extracorporeal Membrane Oxygenation Initiation May Improve Outcomes in Select Patients With Primary Pulmonary Hypertension: An Extracorporeal Life Support Organization Registry Analysis
Authors: Smood Benjamin , Vasquez Charles R. , Olia Salim E. , Han Jason J. , Iyengar Amit , Patrick William L. , Helmers Mark R. , Kelly John J. , Richards Thomas , Usman Asad , Cantu Edward , Takeda Koji , Langer Nathaniel , Cevasco Marisa
Published: February 2025

Extracorporeal membrane oxygenation (ECMO) utilization for primary pulmonary hypertension (PPHTN) remains controversial. This multicenter, retrospective analysis of the Extracorporeal Life Support Organization Registry evaluated 221 PPHTN patients placed on ECMO in 2000–2019. Survival by ECMO indications and cannulation strategies were compared with Kaplan–Meier analyses. ECMO mortality risk factors were analyzed using Cox proportional hazards regressions. The overall rate of survival to ECMO decannulation was 140/221 (63.3%), of which 112/140 (80.0%) survived to hospital discharge. Survival to decannulation increased between 2000–2009 (14/30, 46.7%) and 2010–2019 (126/191, 66.0%, p = 0.041) alongside survival to hospital discharge (9/30, 30.0% vs. 103/191, 53.9%, p = 0.015). Survival to decannulation was similar when patients were supported with either venovenous-ECMO (VV-ECMO; 39/54, 72.2%) or venoarterial-ECMO (VA-ECMO) for respiratory failure (43/71, 60.6%, p = 0.174), although VV-ECMO was associated with fewer complications (25/54, 46% vs. 25/71, 35%, respectively, p = 0.039) and increased survival to hospital discharge (34/54, 63.0% vs. 33/71, 46.5%, p = 0.067). The strongest independent predictor of ECMO morality was isolated vasopressor use before cannulation (hazard ratio [HR]: 3.37 [95% confidence interval {CI95%}: 1.16–9.81], p = 0.026). Extracorporeal membrane oxygenation mortality risk was lower among patients bridged-to-transplantation (HR: 0.37 [CI95%: 0.14–0.97], p = 0.043), and was inversely correlated with pre-ECMO pH (HR: 0.03 [CI95%: 0.00–0.49], p = 0.013). Extracorporeal membrane oxygenation use for PPHTN has grown alongside improved outcomes. Early ECMO initiation may improve outcomes in select individuals with PPHTN.
Developing a Competency Assessment Index System for Hematology Nurses in China
Authors: Xu Baohui , Gu Daoqin , Wu Yun , Tu Meijuan , Sun Li , Li Fengxia , Hu Chengwen
Published: February 2025

Purpose

Patient management, care, and education are influenced by the core competencies of hematology nurses. Nurse specialists enhance patient safety and nursing care quality. However, no study has constructed an index of core competence assessment for hematology nurses.

Design

In this study, a literature review, theoretical analysis, and group discussion were performed to construct the core competency evaluation index system for hematology nurses.

Methods

Twenty-six experts from 7 provinces and cities across China were selected by purposive sampling for 2 rounds of Delphi expert consultation, and the indicators were selected based on the mean importance score >3.5 and coefficient of variation <0.25. A precedence chart determined the indicator weights at all levels.

Results

The evaluation index included 6 primary, 18 secondary, and 70 tertiary indicators. The positive coefficients of the questionnaire on the 2 rounds were 100% and 92.86%. The Kendall’s harmony coefficients for indicators at all levels were 0.176 to 0.461 and 0.197 to 0.220. Experts’ familiarity, judgment, and authority coefficients were 0.892, 0.871, and 0.882, respectively.

Conclusions

The evaluation index system may provide references for the training, curriculum setting, assessment, and qualification certification of hematology nurses.
Geriatric hip fracture with proximal upper extremity fracture increases morbidity and mortality
Authors: Jodoin Zachary , Kotzur Travis , Singh Aaron , Paul Kyle , Martin Case , Karia Ravi , Hand Thomas
Published: February 2025

Objectives:

This study investigates differences in medical, surgical, and hospital-related outcomes within 30 days between patients sustaining a hip fracture with and without concomitant upper extremity fracture. Further subgroup analysis based on fracture location was also completed.

Methods

Design:

Retrospective review.

Setting:

National Readmissions Database.

Patient Selection Criteria:

International Classification of Diseases, 10th Revision codes were used to identify patients with geriatric hip fracture with and without a concomitant upper extremity fracture. Patients were subclassified as having a shoulder girdle, humerus, forearm, or hand fracture.

Outcomes:

Demographics, complications, cost, and in-house mortality were recorded. Validated logistic and linear regression models were used to determine significance and odds ratios.

Results:

367,007 patients sustained a hip fracture, and 19,852 had a concomitant upper extremity fracture. Aggregate data for hip fracture with any upper extremity fracture showed an increased risk of mortality, length of hospital stay, cost, and medical and surgical complications (P < 0.001). There was a 41% increase in mortality across all upper extremity fractures, a 77%–83% increase in in-hospital mortality with a concomitant proximal upper extremity fracture (humerus and shoulder), and no significant change in mortality in the forearm and hand subgroup (P < 0.001). Concomitant shoulder and humerus fractures had an increased risk of all-cause medical and medical complication (P < 0.001).

Conclusions:

This study reported an increased risk of mortality, complications, and cost of geriatric hip fractures with concomitant upper extremity fracture. Subgroup analysis demonstrated that these effects were most pronounced in proximal—versus more distal—upper extremity fractures. Surgeons should be aware of these increased risks for prognostic and patient education purposes and, with future research, may consider alternate interventions, to include surgery on the concomitant proximal upper extremity injury aimed at producing a functional and weight-bearing upper extremity to help optimize postoperative recovery.

Level of Evidence:

Level 3.
Association of Sphincter Pharyngoplasty and Long-term Maxillary Hypoplasia in Patients with Cleft Palate
Authors: Nguyen Nghiem H. , Chin Madeline G. , Huang Kelly X. , Shariati Kaavian , Taylor Jeremiah M. , Panchura Juliana , Gishen Kriya , Lee Justine C. , Wilson Libby F.
Published: February 2025

Background:

The current literature on orthognathic growth outcomes after velopharyngeal insufficiency (VPI) surgery is limited by cohort size or short follow-up duration after surgery. This study evaluates the relationship between sphincter pharyngoplasty and long-term maxillomandibular growth.

Methods:

All patients with cleft lip and palate (CLP) or isolated cleft palate (iCP) ≥15 years of age who underwent sphincter pharyngoplasty from 1992 to 2023 were retrospectively reviewed. An age- and diagnosis-matched control group with CLP/iCP was also identified. Postoperative outcomes include clinical diagnosis of maxillary and mandibular hypoplasia, indication for Lefort surgery, as well as sella-nasion-A point (SNA) and sella-nasion-B point (SNB) angles.

Results:

200 CLP/iCP patients with a mean age of 20.0±3.2 years were included (n=114 with pharyngoplasty, n=86 control). Within the surgery cohort, pharyngoplasty occurred at a mean age of 12.0±4.5 years with a follow-up duration 9.2 (IQR 3.5-12.2) years after surgery. Maxillary hypoplasia was diagnosed twice as frequently in pharyngoplasty patients compared to controls (60.5% vs. 33.7%, p<0.001), corresponding to a higher incidence of Lefort I surgery (45.6% vs. 15.1%, p<0.001) and smaller SNA angles (75.4±4.5° vs. 78.2±5.4°, p=0.03). There were no differences in mandibular hypoplasia or SNB angles. Multivariable analysis indicated that pharyngoplasty was independently associated with a three-fold increase in later diagnosis of maxillary hypoplasia (OR=3.8, 95%CI 1.9-7.5, p<0.001).

Conclusions:

Patients with a history of pharyngoplasty were 3.8 times more likely to be subsequently diagnosed with maxillary hypoplasia, highlighting the need for longitudinal follow-up of patients after VPI surgery as there may be long-term orthognathic consequences.
Neutrophil Reprogramming Underlie Vasculopathy and Lung Disease in Systemic Sclerosis
Authors: Maugeri Norma , Ramirez Giuseppe A. , Capobianco Annalisa , Monno Antonella , Bianchi Marco E. , Rovere-Querini Patrizia , Matucci-Cerinic Marco , Manfredi Angelo A.
Published: February 2025

The role of neutrophils in systemic sclerosis (SSc) remains incompletely understood. To address this, blood samples from 39 SSc patients, 39 healthy controls, and 22 systemic lupus erythematosus (SLE) patients were analyzed. In SSc, neutrophils exhibited substantial activation, evidenced by granule mobilization, elevated plasma levels of Neutrophil Extracellular Trap (NET) byproducts, and upregulated TIE2 expression. In parallel, they underwent metabolic reprogramming, characterized by increased autophagy, likely to support the heightened energy demands of activation. By contrast, neutrophils from SLE patients displayed minimal autophagy, lacked TIE2 expression, and shifted toward low-density granulocytes. Neutrophil reprogramming in SSc correlated with plasma levels of HMGB1+EVs. Mechanistically, EVs purified from the plasma of patients with SSc adhered to neutrophils when injected in immunodeficient NSG mice, inducing autophagy, TIE2 expression, and promoting lung inflammation and fibrosis. These effects were abrogated by HMGB1 inhibitors and required the HMGB1 receptor, RAGE. Recombinant HMGB1 recapitulated EV-induced effects, while neutrophil targeting by liposome-encapsulated clodronate prevented them. In summary, neutrophils in SSc exhibit a dual phenotype of autophagy and activation driven by HMGB1+EVs, representing a pathogenic mechanism and a potential therapeutic target in SSc.

Graphical abstract
Co-translational determination of quaternary structures in chaperone factories
Authors: Philippe Manon , Salloum Soha , Slimani Floric , Chassé Héloïse , Robert Marie-Cécile , Urbach Serge , Imbert Jacques , Séveno Martial , Georges Simon , Boulon Séverine , Verheggen Céline , Bertrand Edouard
Published: February 2025

The HSP90/R2TP quaternary chaperone assembles key cellular machines, including the three nuclear RNA polymerases and many non-coding RNPs. Here, we characterized the RNA associated to R2TP and found that it binds many partners co-translationally. Its co-translational interactome further reveals many novel potential clients and identifies clients bound only co-translationally, only post-translationally, or both. For pairs of subunits assembling together and bound co-translationally by R2TP, only a marginal proportion of their mRNAs is co-localized and co-translated. Instead, the HSP90 and R2TP chaperones induce the formation of condensates accumulating client mRNAs and thus favoring co-translational interactions between chaperones and clients. The R2TP then cycles between co- and post-translational steps and this is regulated by ATP: it binds co-translationally in absence of ATP and becomes released from post-translational assembly intermediates by ATP hydrolysis. Assembly of protein complexes is thus initiated early by chaperones and this mechanism, dubbed co-translational chaperone channeling (cha-cha), substitutes for the rarity of co-localized/co-translated mRNAs.
Engineering affinity-matured variants of an anti-polysialic acid monoclonal antibody with superior cytotoxicity-mediating potency
Authors: Wang Weiyao , Bunyatov Mehman , Lopez-Barbosa Natalia , DeLisa Matthew P.
Published: February 2025

Monoclonal antibodies (mAbs) that specifically recognize cell surface glycans associated with cancer and infectious disease hold tremendous value for both basic research and clinical applications. However, high-quality anti-glycan mAbs, especially those with sufficiently high affinity and specificity, remain scarce, highlighting the need for protein engineering approaches based on rational design or directed evolution that enable optimization of antigen-binding properties. To this end, we sought to enhance the affinity of a polysialic acid (polySia)-specific antibody called mAb735, which was raised by animal immunization and possesses only modest affinity, using a combination of rational design and directed evolution. The application of these approaches led to the discovery of affinity-matured IgG variants with up to ∼7-fold stronger affinity for polySia relative to the parental antibody. The higher affinity IgG variants were observed to opsonize polySia- positive cancer cells more avidly, which in turn resulted in significantly greater cytotoxicity as determined by both antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) assays. Collectively, these results demonstrate the effective application of both rational and random molecular evolution techniques to an important anti-glycan antibody, providing insights into its carbohydrate recognition while at the same time uncovering variants with greater therapeutic promise due to their enhanced affinity and potency.
Improved Graph-Based Antibody-Aware Epitope Prediction with Protein Language Model-Based Embeddings
Authors: Ahmed Mansoor , Ali Sarwan , Jan Avais , Khan Imdad Ullah , Patterson Murray
Published: February 2025

The accurate identification of B-cell epitopes is critical in antibody design, diagnostics, and immunotherapies. Manyin silicoapproaches have recently been proposed to predict epitopes, but these approaches struggle primarily because of the variational and conformational nature of epitopes. However, deep learning-based approaches have recently shown great promise in achieving better performance at the epitope prediction task. In this paper, we employ a graph convolutional network (GCN) coupled with pre-trained protein language model (PLM)-based embeddings for epitope prediction on a benchmark antibody-specific epitope prediction (AsEP) dataset. We explore the use of different PLM-embedding methods on the epitope prediction task and show that the choice of PLM embeddings impacts the performance. Specifically, we find that antibody-specific PLMs such as AntiBERTy and general PLMs such as ProtTrans and ESM-2 for antigens provide improved epitope prediction performance with an AUCROC of 0.65, precision of 0.28, and recall of 0.46. The source code is available at:https://github.com/mansoor181/walle-pp.git.
Single-cell multiome and spatial profiling reveals pancreas cell type-specific gene regulatory programs driving type 1 diabetes progression
Authors: Melton Rebecca , Jimenez Sara , Elison Weston , Tucciarone Luca , Howell Abigail , Wang Gaowei , Berti Denise , Beebe Elisha , Miller Michael , Zeng Chun , McGrail Carolyn , VanderStel Kennedy , Korgaonkar Katha , Elgamal Ruth , Mummey Hannah , Chiou Joshua , Griffin Emily , Kusmartseva Irina , Atkinson Mark , Preissl Sebastian , Theis Fabian J. , Sander Maike , Gaulton Kyle J.
Published: February 2025

Cell type-specific regulatory programs that drive type 1 diabetes (T1D) in the pancreas are poorly understood. Here we performed single nucleus multiomics and spatial transcriptomics in up to 32 non-diabetic (ND), autoantibody-positive (AAB+), and T1D pancreas donors. Genomic profiles from 853,005 cells mapped to 12 pancreatic cell types, including multiple exocrine sub-types. Beta, acinar, and other cell types, and related cellular niches, had altered abundance and gene activity in T1D progression, including distinct pathways altered in AAB+ compared to T1D. We identified epigenomic drivers of gene activity in T1D and AAB+ which, combined with genetic association, revealed causal pathways of T1D risk including antigen presentation in beta cells. Finally, single cell and spatial profiles together revealed widespread changes in cell-cell signaling in T1D including signals affecting beta cell regulation. Overall, these results revealed drivers of T1D progression in the pancreas, which form the basis for therapeutic targets for disease prevention.
Bilateral neuromuscular adaptation to acute unilateral resistance exercise in healthy older adults
Authors: Gamage Nishadi N. , Altheyab Abdulmajeed , Guo Yuxiao , Phillips Bethan E. , Opie George M. , Semmler John G. , Atherton Philip , Piasecki Mathew
Published: February 2025

Introduction

Resistance exercise (RE) enhances functionality in older adults and has proven effective as a means of cross-education in scenarios of unilateral disuse. However, the extent to which older adults demonstrate cross-limb transfer at the motor unit (MU) level following a single bout of unilateral RE is unclear.

Methods

Thirteen healthy older adults (74.9 ± 4.8 years; 5 females) underwent bilateral neuromuscular assessments pre- and post- a single bout of unilateral RE consisting of 3-4 sets of 8-12 repetitions of leg extension of the dominant (exercise) leg, at 75% of 1 repetition maximum, performed to failure. Maximum voluntary contraction (MVC) and force steadiness (FS) were measured. Central and peripheral features of individual MU were recorded using high-density surface electromyography and intramuscular electromyography (HDs/iEMG), during contractions normalised to 25% MVC.

Results

Following unilateral RE, MVC reduced in exercise (-14.8%,p< 0.001) and control (-6.9%,p= 0.003) legs, with reduced FS performance in the exercise leg compared to the control(p= 0.002). MU firing rate increased during contractions normalised to 25% baseline MVC in the exercised leg (p< 0.05), with no adaptation in the control leg (p> 0.05). All iEMG recorded measures of MU potentials remained unchanged in both legs (allp> 0.05).

Conclusion

Acute unilateral RE leads to bilateral MVC reduction in older males and females, demonstrating the cross-limb transfer effect. However, adaptation of MU features was only apparent in the exercised limb, and mechanisms underlying the force decline in the non- exercised limb remain uncertain.
Accuracy and Scalability of Machine Learning Methods for Genotype-Phenotype Association Data
Authors: Collienne Kieran , Zhang Lilin , Gavryushkin Alex
Published: February 2025

Many machine learning methods can be applied to predicting phenotypes from genetic data. Which of these methods work best remains an open question, however. To answer this question, we propose to compare a variety of approaches’ ability to predict a simulated non-linear complex trait. Specifically, we evaluate these methods on their accuracy and scalability with respect to the amount training data available, the noise present in the data, the complexity of the simulated (trait) functions, and their ability to provide insight into the simulated trait. We then compare the best approach to state-of-the-art models in real data, predicting gout in the UK Biobank. We find that transformer encoders outperform all other methods in simulations, and perform comparably to the state-of-the-art with real data, with a promise to scale to significantly larger datasets.