bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of early detection and steroid treatment on fetal ventricular heart rate and pacemaker implantation in anti‐Ro/SSA positive congenital heart block
Authors: Sonesson Sven‐Erik , Ambrosi Aurelie , Nordenstam Felicia , Eliasson Håkan , Wahren‐Herlenius Marie 
Published: October 2024

AbstractIntroductionWe investigated the effects of timing of detection and transplacental fluorinated steroid treatment on ventricular heart rate (HR) and age at pacemaker implantation in fetal third‐degree atrioventricular block (AVB).Material and MethodsTwenty‐five of 31 fetuses diagnosed with Ro/SSA autoantibody‐positive AVB II‐III at our tertiary fetal cardiology center (2000–2020) and AVB III as final feto‐neonatal outcome were reviewed.ResultsAVB was detected approximately 5 weeks earlier in pregnancy if followed in a surveillance program compared to cases referred from primary care for bradycardia (20.6 [2.3] [mean (SD)] vs. 25.4 [3.2] weeks, p = 0.001). AVB detected before 24 weeks had higher HR than those detected later in gestation (63.3 [6.9] vs. 57.2 [6.9] bpm, p = 0.042), with a larger proportion having HR >60 bpm (80% vs. 33%, p = 0.041). The 17/25 cases that received treatment with fluorinated steroid were diagnosed earlier in gestation, with higher HR at diagnosis (61.7 [7.1] vs. 54.7 [6.3] bpm, p = 0.026), 1–2 weeks after diagnosis/treatment start, and before birth (65.4 [12.4] vs. 54.9 [5.7] bpm, p = 0.030) than untreated cases. Overall, 11 cases were commenced on betamimetics: three at diagnosis and eight at or after the examination made 1–2 weeks after diagnosis/treatment start, without any HR improvement. Two of 24 surviving babies were born preterm, and 4/24 received a neonatal pacemaker. Age at pacemaker implantation correlated significantly with HR before birth (Spearman R 0.57, p = 0.004), and fetuses with HR >60 bpm had a higher rate of pacemaker‐free survival at three (90% vs. 40%, p = 0.018) and 12 months of age (80% vs. 13%, p = 0.002). The same trend was observed in pacemaker‐free survival at 3 months of age in fluorinated steroid‐treated compared to untreated cases (71% vs. 38%, ns).ConclusionsOur data confirm that AVB III detected earlier in gestation have a higher HR, and suggest that this higher HR can be successfully maintained to the end of gestation in cases treated with fluorinated steroids. Fetuses with HR >60 bpm before birth had a lower rate of pacemaker implantation at 3 and 12 months of age.
Hyperreflective ganglion cell layer band in a large cohort of non‐syndromic retinitis pigmentosa: Frequency and clinical correlations
Authors: Dias Margarida Q. , Gouveia Nuno , Franca Maria , Murta Joaquim , Silva Rufino , Marques João Pedro 
Published: October 2024

AbstractPurposeRecently, an ‘hyperreflective ganglion cell layer band’ (HGB) has been described on spectral‐domain optical coherence tomography (SD‐OCT) in a subset of patients with retinitis pigmentosa (RP). This study aims to validate and describe the frequency of HGB in a large cohort of Portuguese patients with RP.MethodsThis single‐centre, cross‐sectional cohort study included consecutive patients with a genetic diagnosis of RP. SD‐OCT images were reviewed to identify the presence of the HGB and other retinal comorbidities. The HGB was defined as a continuous hyperreflective band within the thickness of the ganglion cell layer (GCL). We built mixed‐effects regression models, accounting for inter‐eye correlations, to investigate features predictive of visual acuity. Subsequently, a reduced model was fitted.ResultsA total of 398 eyes from 201 patients were included. HGB was identified in 69 (17.3%) eyes from 39 (19.4%) patients. Patients presenting with the HGB were significantly younger at diagnosis and at symptom onset. Median BCVA [ETDRS (IQR)] was 65 (29) letters in eyes with the HGB and 70 (21) letters in eyes without HGB (p < 0.001). In both the full and reduced mixed‐effects models, the presence of HGB and macular hole (MH) was significantly associated with worse BCVA.ConclusionsThis study validates the recent description of HGB within the GCL in a subset of patients with RP. Eyes with HGB demonstrated significantly worse BCVA compared to those without HGB, suggesting that the presence of HGB may serve as an SD‐OCT biomarker of worse visual prognosis in these patients.
Letter: Zinc and Selenium—Potential Biomarkers for Chronic Liver Disease? Authors' Reply
Authors: Dominik Nina , Balcar Lorenz , Semmler Georg , Simbrunner Benedikt , Schwarz Michael , Hofer Benedikt S. , Hartl Lukas , Jachs Mathias , Scheiner Bernhard , Pinter Matthias , Trauner Michael , Mandorfer Mattias , Pilger Alexander , Reiberger Thomas 
Published: October 2024

LINKED CONTENTThis article is linked to Dominik et al papers. To view these articles, visit https://doi.org/10.1111/apt.18179 and https://doi.org/10.1111/apt.18293.
Coping strategies employed by transgender youth with higher and lower quality of life
Authors: Chinazzo Ítala Raymundo , Vaitses Fontanari Anna Martha , Riva Annelise , de Brito Silva Bruno , Rodrigues Lucca P. , Trajano Ana Carolina , Feijó Marina , Brandelli Costa Angelo , Lobato Maria Inês Rodrigues 
Published: October 2024

AbstractUnderstanding transgender youth coping mechanisms may help create strategies that reduce the influence of stress on quality of life. Our study aims to measure the quality of life of Brazilian transgender youth and analyse the association with their coping strategies used for dealing with general and gender‐related stress. The sample consisted of 185 participants (μ = 18.49 years; SD 2.42); of which 95 (46.34%) transgender boys, 45 (21.95%) transgender girls, 65 (31.71%) non‐binary. Better quality of life was related to social support, whereas lower quality of life was related to the use of avoidance coping style in the context of general stress. The study found no association between coping strategies for gender‐related stress and quality of life. Thus, the increase in quality of life in the context of gender distress among transgender youth should involve other mechanisms than promoting coping skills.
Combined MEK1/2 and ATR inhibition promotes myeloma cell death through a STAT3‐dependent mechanism in vitro and in vivo
Authors: Li Lin , Hu Xiaoyan , Nkwocha Jewel , Kmieciak Maciej , Meads Mark B. , Shain Kenneth H. , Alugubelli Raghunandan R. , Silva Ariosto S. , Mann Hashim , Sudalagunta Praneeth R. , Canevarolo Rafael R. , Zhou Liang , Grant Steven 
Published: October 2024

SummaryMechanisms underlying potentiation of the anti‐myeloma (MM) activity of ataxia telangiectasia Rad3 (ATR) antagonists by MAPK (Mitogen‐activated protein kinases)‐related extracellular kinase 1/2 (MEK1/2) inhibitors were investigated. Co‐administration of the ATR inhibitor (ATRi) BAY1895344 (BAY) and MEK1/2 inhibitors, for example, cobimetinib, synergistically increased cell death in diverse MM cell lines. Mechanistically, BAY and cobimetinib blocked STAT3 Tyr705 and Ser727 phosphorylation, respectively, and dual dephosphorylation triggered marked STAT3 inactivation and downregulation of STAT3 (Signal transducer and activator of transcription 3) downstream targets (c‐Myc and BCL‐XL). Similar events occurred in highly bortezomib‐resistant (PS‐R) cells, in the presence of patient‐derived conditioned medium, and with alternative ATR (e.g. M1774) and MEK1/2 (trametinib) inhibitors. Notably, constitutively active STAT3 c‐MYC or BCL‐XL ectopic expression significantly protected cells from BAY/cobimetinib. In contrast, transfection of cells with a dominant‐negative form of STAT3 (Y705F) sensitized cells to cobimetinib, as did ATR shRNA knockdown. Conversely, MEK1/2 knockdown markedly increased ATRi sensitivity. The BAY/cobimetinib regimen was also active against primary CD138+ MM cells, but not normal CD34+ cells. Finally, the ATR inhibitor/cobimetinib regimen significantly improved survival in MM xenografts, including bortezomib‐resistant models, with minimal toxicity. Collectively, these findings suggest that combined ATR/MEK1/2 inhibition triggers dual STAT3 Tyr705 and Ser727 dephosphorylation, pronounced downregulation of cytoprotective targets and MM cell death, warranting attention as a novel therapeutic strategy in MM.
The Diversity of Voices in Universities: A Critical Reflection on Representation Based on Two University Projects in Iceland and Germany
Authors: Leonhardt Nico , Björnsdóttir Kristín , Goldbach Anne , Smára Ragnar , Martick Steffen , Schlothauer Beate 
Published: October 2024

ABSTRACTBackgroundUniversities are deeply rooted in a tradition of exclusivity. However, for the past several years, they have been called upon to develop in an inclusive and socially responsible manner that does justice to the plurality of society. This has led to the emergence of diverse practices and projects around the world that are intended to open up universities to previously excluded and marginalised groups of people. At the same time, findings from postcolonial studies, such as Spivak's discussions on the topic of representation, show that such processes of change must always be accompanied by critical reflection. This article offers a reflexive analysis of two university projects—one in Iceland and one in Germany—where people with learning difficulties are employed as academic staff, engaged in both teaching and research.MethodsThis article is a result of a collaboration between three nondisabled lecturers and three lecturers with learning disabilities, co‐written across three languages—German, Icelandic and English. The authors worked together to explore theories of representation, ensuring that their discussions and writing were accessible to all members, regardless of language or disability. The article discusses two projects from Iceland and Germany.FindingsThe article shows that inclusive higher education developments are necessary. The projects presented in the article have created work opportunities for people with learning disabilities in the previously exclusive setting of the university. The article provides descriptions of the exemplary life paths of the three lecturers with learning disabilities who co‐authored this article. They have had to navigate the precarious balance between being reduced to mere representatives of their disability and contributing valuable academic knowledge. The findings suggest that an inclusive university can foster equitable academic environments, contributing to the transformation of higher education by reflecting diverse viewpoints and experiences.ConclusionsInitiatives in Iceland and Germany highlight significant progress towards more inclusive universities by integrating individuals with learning disabilities into academic roles, challenging traditional power dynamics. Spivak's (2008) concept of representation emphasises the need to include marginalised voices in academic discourse, ensuring they are genuinely reflected. While these efforts are crucial, continuous critical reflection is necessary to avoid reinforcing inequalities. Moving forward, universities must embed inclusion into all aspects of their structures, creating meaningful opportunities for marginalised groups to influence decision‐making. This approach will ensure that representation is transformative and drives genuine social change.
Beneficial effects of CHF6467, a modified human nerve growth factor, in experimental neonatal hypoxic–ischaemic encephalopathy
Authors: Landucci Elisa , Mango Dalila , Carloni Silvia , Mazzantini Costanza , Pellegrini‐Giampietro Domenico E. , Saidi Amira , Balduini Walter , Schiavi Elisa , Tigli Laura , Pioselli Barbara , Imbimbo Bruno P. , Facchinetti Fabrizio 
Published: October 2024

AbstractBackground and PurposeTherapeutic hypothermia (TH) has become the standard care to reduce morbidity and mortality in neonates affected by moderate‐to‐severe hypoxic–ischaemic encephalopathy (HIE). Despite the use of TH for HIE, the incidence of mortality and disabilities remains high.Experimental ApproachNerve growth factor (NGF) is a potent neurotrophin, but clinical use is limited by its pain eliciting effects. CHF6467 is a recombinant modified form of human NGF devoid of algogenic activity (painless NGF).Key ResultsIn rodent hippocampal slices exposed to oxygen and glucose deprivation, CHF6467 protected neurons from death and reverted neurotransmission impairment when combined with hypothermia. In a model of rat neonatal HIE, intranasal CHF6467 (20 μg kg−1) significantly reduced brain infarct volume versus vehicle when delivered 10 min or 3 h after the insult. CHF6467 (20 and 40 μg kg−1, i.n.), significantly decreased brain infarct volume to a similar extent to TH and when combined, showed a synergistic neuroprotective effect. CHF6467 (20 μg kg−1, i.n.) per se and in combination with hypothermia reversed locomotor coordination impairment (Rotarod test) and memory deficits (Y‐maze and novel object recognition test) in the neonatal HIE rat model. Intranasal administration of CHF6467 resulted in meaningful concentrations in the brain, blunted HIE‐induced mRNA elevation of brain neuroinflammatory markers and, when combined to TH, significantly counteracted the increase in plasma levels of neurofilament light chain, a peripheral marker of neuroaxonal damage.Conclusion and ImplicationsCHF6467 administered intranasally is a promising therapy, in combination with TH, for the treatment of HIE.
Computational Insights Into the Mechanism of EGCG's Binding and Inhibition of the TDP‐43 Aggregation
Authors: Meshram Vini D. , Balaji Ramkumar , Saravanan Preethi , Subbamanda Yashashwini , Deeksha Waghela , Bajpai Akarsh , Joshi Himanshu , Bhargava Anamika , Patel Basant K. 
Published: October 2024

ABSTRACTMisfolding and aggregation of TAR DNA‐binding protein, TDP‐43, is linked to devastating proteinopathies such as ALS. Therefore, targeting TDP‐43's aggregation is significant for therapeutics. Recently, green tea polyphenol, EGCG, was observed to promote non‐toxic TDP‐43 oligomer formation disallowing TDP‐43 aggregation. Here, we investigated if the anti‐aggregation effect of EGCG is mediated via EGCG's binding to TDP‐43. In silico molecular docking and molecular dynamics (MD) simulation suggest a strong binding of EGCG with TDP‐43's aggregation‐prone C‐terminal domain (CTD). Three replicas, each having 800 ns MD simulation of the EGCG‐TDP‐43‐CTD complex, yielded a high negative binding free energy (ΔG) inferring a stable complex formation. Simulation snapshots show that EGCG forms close and long‐lasting contacts with TDP‐43's Phe‐313 and Ala‐341 residues, which were previously identified for monomer recruitment in CTD's aggregation. Notably, stable physical interactions between TDP‐43 and EGCG were also detected in vitro using TTC staining and isothermal titration calorimetry which revealed a high‐affinity binding site of EGCG on TDP‐43 (Kd, 7.8 μM; ΔG, −6.9 kcal/mol). Additionally, TDP‐43 co‐incubated with EGCG was non‐cytotoxic when added to HEK293 cells. In summary, EGCG's binding to TDP‐43 and blocking of residues important for aggregation can be a possible mechanism of its anti‐aggregation effects on TDP‐43.
Reactive Gaze during Locomotion in Natural Environments
Authors: Melgare J. K. , Rohmer D. , Musse S. R. , Cani M‐P. 
Published: October 2024

AbstractAnimating gaze behavior is crucial for creating believable virtual characters, providing insights into their perception and interaction with the environment. In this paper, we present an efficient yet natural‐looking gaze animation model applicable to real‐time walking characters exploring natural environments. We address the challenge of dynamic gaze adaptation by combining findings from neuroscience with a data‐driven saliency model. Specifically, our model determines gaze focus by considering the character's locomotion, environment stimuli, and terrain conditions. Our model is compatible with both automatic navigation through pre‐defined character trajectories and user‐guided interactive locomotion, and can be configured according to the desired degree of visual exploration of the environment. Our perceptual evaluation shows that our solution significantly improves the state‐of‐the‐art saliency‐based gaze animation with respect to the character's apparent awareness of the environment, the naturalness of the motion, and the elements to which it pays attention.
Pose‐to‐Motion: Cross‐Domain Motion Retargeting with Pose Prior
Authors: Zhao Qingqing , Li Peizhuo , Yifan Wang , Olga Sorkine‐Hornung , Wetzstein Gordon 
Published: October 2024

AbstractCreating plausible motions for a diverse range of characters is a long‐standing goal in computer graphics. Current learning‐based motion synthesis methods rely on large‐scale motion datasets, which are often difficult if not impossible to acquire. On the other hand, pose data is more accessible, since static posed characters are easier to create and can even be extracted from images using recent advancements in computer vision. In this paper, we tap into this alternative data source and introduce a neural motion synthesis approach through retargeting, which generates plausible motion of various characters that only have pose data by transferring motion from one single existing motion capture dataset of another drastically different characters. Our experiments show that our method effectively combines the motion features of the source character with the pose features of the target character, and performs robustly with small or noisy pose data sets, ranging from a few artist‐created poses to noisy poses estimated directly from images. Additionally, a conducted user study indicated that a majority of participants found our retargeted motion to be more enjoyable to watch, more lifelike in appearance, and exhibiting fewer artifacts. Our code and dataset can be accessed here.
Learning to Move Like Professional Counter‐Strike Players
Authors: Durst D. , Xie F. , Sarukkai V. , Shacklett B. , Frosio I. , Tessler C. , Kim J. , Taylor C. , Bernstein G. , Choudhury S. , Hanrahan P. , Fatahalian K. 
Published: October 2024

AbstractIn multiplayer, first‐person shooter games like Counter‐Strike: Global Offensive (CS:GO), coordinated movement is a critical component of high‐level strategic play. However, the complexity of team coordination and the variety of conditions present in popular game maps make it impractical to author hand‐crafted movement policies for every scenario. We show that it is possible to take a data‐driven approach to creating human‐like movement controllers for CS:GO. We curate a team movement dataset comprising 123 hours of professional game play traces, and use this dataset to train a transformer‐based movement model that generates human‐like team movement for all players in a “Retakes” round of the game. Importantly, the movement prediction model is efficient. Performing inference for all players takes less than 0.5 ms per game step (amortized cost) on a single CPU core, making it plausible for use in commercial games today. Human evaluators assess that our model behaves more like humans than both commercially‐available bots and procedural movement controllers scripted by experts (16% to 59% higher by TrueSkill rating of “human‐like”). Using experiments involving in‐game bot vs. bot self‐play, we demonstrate that our model performs simple forms of teamwork, makes fewer common movement mistakes, and yields movement distributions, player lifetimes, and kill locations similar to those observed in professional CS:GO match play.
SketchAnim: Real‐time sketch animation transfer from videos
Authors: Rai Gaurav , Gupta Shreyas , Sharma Ojaswa 
Published: October 2024

AbstractAnimation of hand‐drawn sketches is an adorable art. It allows the animator to generate animations with expressive freedom and requires significant expertise. In this work, we introduce a novel sketch animation framework designed to address inherent challenges, such as motion extraction, motion transfer, and occlusion. The framework takes an exemplar video input featuring a moving object and utilizes a robust motion transfer technique to animate the input sketch. We show comparative evaluations that demonstrate the superior performance of our method over existing sketch animation techniques. Notably, our approach exhibits a higher level of user accessibility in contrast to conventional sketch‐based animation systems, positioning it as a promising contributor to the field of sketch animation. https://graphics-research-group.github.io/SketchAnim/
Creating a 3D Mesh in A‐pose from a Single Image for Character Rigging
Authors: Lee Seunghwan , Liu C. Karen 
Published: October 2024

AbstractLearning‐based methods for 3D content generation have shown great potential to create 3D characters from text prompts, videos, and images. However, current methods primarily focus on generating static 3D meshes, overlooking the crucial aspect of creating an animatable 3D meshes. Directly using 3D meshes generated by existing methods to create underlying skeletons for animation presents many challenges because the generated mesh might exhibit geometry artifacts or assume arbitrary poses that complicate the subsequent rigging process. This work proposes a new framework for generating a 3D animatable mesh from a single 2D image depicting the character. We do so by enforcing the generated 3D mesh to assume an A‐pose, which can mitigate the geometry artifacts and facilitate the use of existing automatic rigging methods. Our approach aims to leverage the generative power of existing models across modalities without the need for new data or large‐scale training. We evaluate the effectiveness of our framework with qualitative results, as well as ablation studies and quantitative comparisons with existing 3D mesh generation models.
Increased coproporphyrin serum levels in healthy volunteers treated with the cholesterol uptake inhibitor ezetimibe
Authors: Kinzi Jonny , Grube Markus , Seibert Isabell , Siegmund Werner , Meyer zu Schwabedissen Henriette E. 
Published: October 2024

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