bluuebunny/crossref_metadata_2025_split huggingface dataset:
SARS-CoV-2 N protein recruits G3BP to double membrane vesicles to promote translation of viral mRNAs
Authors: Long Siwen , Guzyk Mykhailo , Perez Vidakovics Laura , Han Xiao , Sun Renhua , Wang Megan , Panas Marc D. , Urgard Egon , Coquet Jonathan M. , Merits Andres , Achour Adnane , McInerney Gerald M. 
Published: December 2024

AbstractRas-GTPase-activating protein SH3-domain-binding proteins (G3BP) are critical for the formation of stress granules (SGs) through their RNA- and ribosome-binding properties. SARS-CoV-2 nucleocapsid (N) protein exhibits strong binding affinity for G3BP and inhibits infection-induced SG formation soon after infection. To study the impact of the G3BP-N interaction on viral replication and pathogenesis in detail, we generated a mutant SARS-CoV-2 (RATA) that specifically lacks the G3BP-binding motif in the N protein. RATA triggers a stronger and more persistent SG response in infected cells, showing reduced replication across various cell lines, and greatly reduced pathogenesis in K18-hACE2 transgenic mice. At early times of infection, G3BP and WT N protein strongly colocalise with dsRNA and with non-structural protein 3 (nsp3), a component of the pore complex in double membrane vesicles (DMVs) from which nascent viral RNA emerges. Furthermore, G3BP-N complexes promote highly localized translation of viral mRNAs in the immediate vicinity of the DMVs and thus contribute to efficient viral gene expression and replication. In contrast, G3BP is absent from the DMVs in cells infected with RATA and translation of viral mRNAs is less efficient. This work provides a fuller understanding of the multifunctional roles of G3BP in SARS-CoV-2 infection.
Simulating microgravity with 60 days of 6 degree head-down tilt bed rest compromises sleep
Authors: Strauch Luise , von der Wiesche Melanie , Noppe Alexandra , Mulder Edwin , Rieger Iris , Aeschbach Daniel , Elmenhorst Eva-Maria 
Published: December 2024

AbstractAstronauts in space often experience sleep loss. In the AGBRESA (Artificial Gravity Bed Rest) study, we examined 24 participants (mean age ± SD, 33 ± 9 years) during two months of 6o head-down tilt (HDT) bed rest, which is a well-established spaceflight analogue. Polysomnography was recorded during baseline (BDC-9), HDT (nights 1, 8, 30 and 58) and recovery (R, nights 1 and 12). Mixed ANOVAs with post-hoc step-down Bonferroni adjustment indicated that compared to BDC-9, arousals were increased, while sleep duration, N3, and sleep efficiency were all decreased during HDT. Significant quadratic associations between sleep duration and quality with time into HDT did not indicate adaptive improvements during the course of HDT. While sleep duration recovered quickly after the end of bed rest, participants still displayed protracted sleep fragmentation. We conclude that physiological changes caused by exposure to microgravity may contribute to persistent sleep deficits experienced during real space missions.
Neutralizing antibodies elicited in macaques recognize V3 residues on altered conformations of HIV-1 Env trimer
Authors: DeLaitsch Andrew T. , Keeffe Jennifer R. , Gristick Harry B. , Lee Juliet A. , Ding Wenge , Liu Weimin , Skelly Ashwin N. , Shaw George M. , Hahn Beatrice H. , Björkman Pamela J. 
Published: December 2024

AbstractEliciting broadly neutralizing antibodies that protect against diverse HIV-1 strains is a primary goal of AIDS vaccine research. We characterized Ab1456 and Ab1271, two heterologously-neutralizing antibodies elicited in non-human primates by priming with an engineered V3-targeting SOSIP Env immunogen and boosting with increasingly native-like SOSIP Envs derived from different strain backgrounds. Structures of Env trimers in complex with these antibodies revealed V3 targeting, but on conformational states of Env distinct from the typical closed, prefusion trimeric SOSIP structure. Env trimers bound by Ab1456 adopted conformations resembling CD4-bound open Env states in the absence of soluble CD4, whereas trimers bound by Ab1271 exhibited a trimer apex-altered conformation to accommodate antibody binding. The finding that elicited antibodies cross-neutralized by targeting altered, non-closed, prefusion Env trimer conformations provides important information about Env dynamics that is relevant for HIV-1 vaccine design aimed at raising antibodies to desired epitopes on closed pre-fusion Env trimers.
Generative models of MRI-derived neuroimaging features and associated dataset of 18,000 samples
Authors: Chintapalli Sai Spandana , Wang Rongguang , Yang Zhijian , Tassopoulou Vasiliki , Yu Fanyang , Bashyam Vishnu , Erus Guray , Chaudhari Pratik , Shou Haochang , Davatzikos Christos 
Published: December 2024

AbstractAvailability of large and diverse medical datasets is often challenged by privacy and data sharing restrictions. Successful application of machine learning techniques for disease diagnosis, prognosis, and precision medicine, requires large amounts of data for model building and optimization. To help overcome such limitations in the context of brain MRI, we present GenMIND: a collection of generative models of normative regional volumetric features derived from structural brain imaging. GenMIND models are trained on real brain imaging regional volumetric measures from the iSTAGING consortium, which encompasses over 40,000 MRI scans across 13 studies, incorporating covariates such as age, sex, and race. Leveraging GenMIND, we produce and offer 18,000 synthetic samples spanning the adult lifespan (ages 22-90 years), alongside the model’s capability to generate unlimited data. Experimental results indicate that samples generated from GenMIND align well with the distributions observed in real data. Most importantly, the generated normative data significantly enhances the accuracy of downstream machine learning models on tasks such as disease classification. Dataset and the generative models are publicly available.
Object-based feedback attention in convolutional neural networks improves tumour detection in digital pathology
Authors: Broad Andrew , Wright Alexander , McGenity Clare , Treanor Darren , de Kamps Marc 
Published: December 2024

AbstractHuman visual attention allows prior knowledge or expectations to influence visual processing, allocating limited computational resources to only that part of the image that are likely to behaviourally important. Here, we present an image recognition system based on biological vision that guides attention to more informative locations within a larger parent image, using a sequence of saccade-like motions. We demonstrate that at the end of the saccade sequence the system has an improved classification ability compared to the convolutional neural network (CNN) that represents the feedforward part of the model. Feedback activations highlight salient image features supporting the explainability of the classification. Our attention model deviates substantially from more common feedforward attention mechanisms, which linearly reweight part of the input. This model uses several passes of feedforward and backward activation, which interact non-linearly. We apply our feedback architecture to histopathology patch images, demonstrating a 3.5% improvement in accuracy (p < 0.001) when retrospectively processing 59,057 9-class patches from 689 colorectal cancer WSIs. In the saccade implementation, overall agreement between expert-labelled patches and model prediction reached 93.23% for tumour tissue, surpassing inter-pathologist agreement. Our method is adaptable to other areas of science which rely on the analysis of extremely large-scale images.
Detection of three-rooted mandibular first molars on panoramic radiographs using deep learning
Authors: Jin Long , Tang Ying , Zhou Wenyuan , Bai Bingbing , Yu Zezheng , Zhang Panpan , Gu Yongchun 
Published: December 2024

AbstractThis study aimed to develop a deep learning system for the detection of three-rooted mandibular first molars (MFMs) on panoramic radiographs and to assess its diagnostic performance. Panoramic radiographs, together with cone beam computed tomographic (CBCT) images of the same subjects, were retrospectively collected from 730 patients, encompassing a total of 1444 MFMs (367 teeth were three-rooted and the remaining 1077 teeth were two-rooted). Five convolutional neural network (CNN) models (ResNet-101 and − 50, DenseNet-201, MobileNet-v3 and Inception-v3) were employed to classify three- and two-rooted MFMs on the panoramic radiographs. The diagnostic performance of each model was evaluated using standard metrics, including accuracy, sensitivity, specificity, precision, negative predictive value, and F1 score. Receiver operating characteristic (ROC) curve analyses were performed, with the CBCT examination taken as the gold standard.Among the five CNN models evaluated, ResNet-101 demonstrated superior diagnostic performance, and the AUC value attained was 0.907, significantly higher than that of all other models (all P < 0.01). The accuracy, sensitivity, and specificity were 87.5%, 83.6%, and 88.9%, respectively. DenseNet-201, however, showed the lowest diagnostic performance among the five models (all P < 0.01), with an AUC value of 0.701 and an accuracy of 73.2%. Overall, the performance of the CNNs diminished when using image patches containing only the distal half of MFMs, with AUC values ranging between 0.680 and 0.800. In contrast, the diagnostic performance of the two clinicians was poorer, with AUC values of only 0.680 and 0.632, respectively. In conclusion, the CNN-based deep learning system exhibited a high level of accuracy in the detection of three-rooted MFMs on panoramic radiographs.
Respiratory syncytial virus glycoprotein G impedes CX3CR1-activation by CX3CL1 and monocyte function
Authors: Meineke Robert , Agac Ayse , Knittler Marie-Christin , Ludlow Martin , Osterhaus Albert D. M. E. , Rimmelzwaan Guus F. 
Published: December 2024

AbstractThe soluble form of the Respiratory Syncytial Virus (RSV) G protein (sG) bears resemblance to the chemokine fractalkine (CX₃CL1). Both RSV sG and CX3CL1 possess a mucin-like domain and a CX3C motif, exist in membrane-associated and soluble forms, and bind to the CX₃CR1 receptor expressed on immune and epithelial cells. To explore the biological significance of RSV sG and CX₃CR1 interaction, we produced wild type (WT) and CX₃C motif-deficient (CX3CMut) RSV sG proteins and determined their effects on CX₃CR1 signaling in monocytic cells. Both CX3CMut- and WT RSV sG failed to activate CX₃CR1 signaling directly. However, WT sG competed with CX₃CL1 for CX₃CR1 binding and reduced CX3CL1-induced CX₃CR1-activation, monocyte migration, and adhesion. The CX₃C motif of sG was crucial for competitive blocking of CX3CL1-mediated activation, as CX₃CMut sG did not affect these CX₃CR1 functions significantly. Thus, blockade of CX₃CR1 signaling by sG may allow RSV to dampen host immune responses.
Unveiling the ice and gas nature of active centaur (2060) Chiron using the James Webb Space Telescope
Authors: Pinilla-Alonso N. , Licandro J. , Brunetto R. , Henault E. , Schambeau C. , Guilbert-Lepoutre A. , Stansberry J. , Wong I. , Lunine J. I. , Holler B. J. , Emery J. , Protopapa S. , Cook J. , Hammel H. B. , Villanueva G. L. , Milam S. N. , Cruikshank D. , de Souza-Feliciano A. C. 
Published: December 2024

Context. (2060) Chiron is a large centaur that has been reported active on multiple occasions at relatively large heliocentric distances, including during aphelion passage. Studies of Chiron’s coma during active periods have resulted in the detection of C≡N and CO outgassing. Additionally, Chiron is surrounded by a disk of debris that varies with time. Significant work remains to be undertaken to comprehend the activation mechanisms on Chiron and the parent molecules of the gas phases detected.
Aims. This work reports the study of the ices on Chiron’s surface and coma and seeks spectral indicators of volatiles associated with the activity. Additionally, we discuss how these detections could be related to the activation mechanism for Chiron and, potentially, other centaurs.
Methods. In July 2023, the James Webb Space Telescope (JWST) observed Chiron when it was active near its aphelion. We present JWST/NIRSpec spectra from 0.97 to 5.27 μm with a resolving power of ∼1000, and compare them with laboratory data for identification of the spectral bands.
Results We report the first detections on Chiron of absorption bands of several volatile ices, including CO2, CO, C2H6, C3H8, and C2H2. We also confirm the presence of water ice in its amorphous state. A key discovery arising from these data is the detection of fluorescence emissions of CH4, revealing the presence of a gas coma rich in this hyper-volatile molecule, which we also identify to be in non-local thermal equilibrium (non-LTE). CO2 gas emission is also detected in the fundamental stretching band at 4.27 μm. We argue that the presence of CH4 emission is the first proof of the desorption of CH4 due to a density phase transition of amorphous water ice at low temperature in agreement with the estimated temperature of Chiron during the JWST observations (61 K). Detection of photolytic and proton irradiation products of CH4 and CO2 on the surface, in the coma ice grains, or in the ring material is also detected via a forest of absorption features from 3.5 to 5.3 μm.
The physical and chemical structure of Sagittarius B2
Authors: Möller T. , Schilke P. , Sánchez-Monge Á. , Schmiedeke A. 
Published: December 2024

Context. The giant molecular cloud complex Sagittarius B2 (Sgr B2) in the central molecular zone of our Galaxy hosts several high-mass star formation sites, with Sgr B2(M) and Sgr B2(N) being the main centers of activity. This analysis aims to comprehensively model each core spectrum, considering molecular lines, dust attenuation, and free-free emission interactions. We describe the molecular content analysis of each hot core and identify the chemical composition of detected sources.
Aims. Using ALMA’s high sensitivity, we aim to characterize the hot core population in Sgr B2(M) and N, gaining a better understanding of the different evolutionary phases of star formation processes in this complex.
Methods. We conducted an unbiased ALMA spectral line survey of 47 sources in band 6 (211-275 GHz). Chemical composition and column densities were derived using XCLASS, assuming local thermodynamic equilibrium. Quantitative descriptions for each molecule were determined, considering all emission and absorption features across the spectral range. Temperature and velocity distributions were analyzed, and derived abundances were compared with other spectral line surveys.
Results. We identified 65 isotopologs from 41 different molecules, ranging from light molecules to complex organic compounds, originating from various environments. Most sources in the Sgr B2 complex were assigned different evolutionary phases of high-mass star formation.
Conclusions. Sgr B2(N) hot cores show more complex molecules such as CH3OH, CH3OCHO, and CH3OCH3, while M cores contain lighter molecules such as SO2, SO, and NO. Some sulfur-bearing molecules are more abundant in N than in M. The derived molecular abundances can be used for comparison and to constrain astrochemical models. Inner sources in both regions were generally more developed than outer sources, with some exceptions.
Observations of umbral flashes in the resonant sunspot chromosphere
Authors: Felipe T. , González Manrique S. J. , Martínez-Gómez D. , Gómez-Míguez M. M. , Khomenko E. , Quintero Noda C. , Socas-Navarro H. 
Published: December 2024

Context. In sunspot umbrae, the core of some chromospheric lines exhibits periodic brightness enhancements known as umbral flashes. The consensus is that they are produced by the upward propagation of shock waves. This view has recently been challenged by the detection of downflowing umbral flashes and the confirmation of a resonant cavity above sunspots.
Aims. We aim to determine the propagating or standing nature of the waves in the low umbral chromosphere and confirm or refute the existence of downflowing umbral flashes.
Methods. Spectroscopic temporal series of Ca II 8542 Å, Ca II H, and Hα in a sunspot were acquired with the Swedish Solar Telescope. The Hα velocity was inferred using bisectors. Simultaneous inversions of the Ca II 8542 Å line and the Ca II H core were performed using the code NICOLE. The nature of the oscillations were determined and insights into the resonant oscillatory pattern were gained by analyzing the phase shift between the velocity signals and examining the temporal evolution.
Results. Propagating waves in the low chromosphere are more common in regions with frequent umbral flashes, where the transition region is shifted upward, making resonant cavity signatures less noticeable. In contrast, areas with fewer umbral flashes show velocity fluctuations that align with standing oscillations. Evidence suggests dynamic changes in the location of velocity-resonant nodes due to variations in the transition region height. Downflowing profiles appear at the onset of some umbral flashes, but upflowing motion dominates during most of the flash. These downflowing flashes are more common in standing umbral flashes.
Conclusions. We confirm the existence of a chromospheric resonant cavity above sunspot umbrae. It is produced by wave reflections at the transition region. The oscillatory pattern depends on the transition region height, which exhibits spatial and temporal variations due to the impact of the waves.
[18F]FDG PET/CT Imaging and Hematological Parameters Can Help Predict HPV Status in Head and Neck Cancer
Authors: Cegla Paulina , Currie Geoffrey , Wroblewska Joanna P , Kazmierska Joanna , Cholewinski Witold , Jagiello Inga , Matuszewski Krzysztof , Marszalek Andrzej , Kubiak Anna , Golusinski Pawel , Golusinski Wojciech , Majchrzak Ewa 
Published: December 2024

Abstract
Objective To determine whether [18F]FDG PET/CT and hematological parameters provide supportive data to determine HPV status in HNSCC patients.
Methods Retrospective analysis of clinical and diagnostic data from 106 patients with HNSCC: 26.4% HPV-positive and 73.6% HPV-negative was performed. The following semiquantitative PET/CT parameters for the primary tumor and hottest lymph node and liver were evaluated: SUVmax, SUVmean, TotalSUV, MTV, TLG, maximum, mean and TLG tumor-to-liver ratio (TLRmax, TLRmean,TLRTLG) and heterogeneity index (HI). Following hematological variables were assessed: white blood cell (WBC); lymphocyte (LYMPH); neutrophil (NEU),monocyte (MON); platelet (PLT); neutrophil-to-lymphocyte ratio (NRL); lymphocyte-to-monocyte ratio (LMR); platelet-to lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR). Conventional statistical analyses were performed in parallel with an artificial neural network analysis (Neural Analyzer, v. 2.9.5).
Results Significant between-group differences were observed for two of the semiquantitative PET/CT parameters, with higher values in the HPV-negative group: primary tumor MTV (22.2 vs 9.65; p=0.023), and TLRmax (3.50 vs 2.46; p=0.05). The HPV-negative group also had a significantly higher NEU count (4.84 vs. 6.04; p=0.04), NEU% (58.2 vs. 66.2; p=0.007), and NRL% (2.69 vs. 3.94; p=0.038). Based on ROC analysis (sensitivity 50%, specificity 80%, AUC 0.5), the following variables were independent predictors of HPV-negativity: primary tumor with SUVmax >10; TotalSUV >2800; MTV >23.5; TLG >180; TLRmax >3.7; TLRTLG >5.7; and oropharyngeal localization.
Conclusion Several semiquantitative parameters derived from [18F]FDG PET/CT imaging of the primary tumor (SUVmax, TotalSUV, MTV, TLG, TLRmax and TLRTLG) were independent predictors of HPV-negativity.
Challenging Situations in the Treatment of Cancer-Associated Thrombosis
Authors: Balaian Ekaterina , Marten Sandra , Beyer-Westendorf Jan , Trautmann-Grill Karolin 
Published: December 2024

AbstractCancer-associated thrombosis (CAT) is a common clinical problem in the treatment of cancer patients posing some unique challenges. These include the need to balance between the risk of recurrent thromboembolic events and bleeding complications in the individual cancer patient. A frequently encountered dilemma is the need for long-term anticoagulation in the setting of active malignancy. Until now, optimal duration, intensity, and type of anticoagulation in cancer patients remain an area of ongoing debate. In this case-based review, we present several challenging clinical scenarios and provide guidance on management. For optimal treatment results, CAT generally requires a multidisciplinary approach including specialists for thrombosis and hemostasis as well as hematology and oncology. Individual patient preferences should always be taken into account, especially in clinical situations with weak treatment evidence.
Interaktiv und intersektional: Sexualbildung für Jugendliche mit
dem Digitalspiel „Sibel’s Journey“
Authors: Goetzke Louka Maju , İnal Öykü 
Published: December 2024

ZusammenfassungFür die Sexuelle und geschlechtliche Bildung von Jugendlichen bieten sogenannte Serious Games ein großes und bisher weitgehend ungenutztes Potential. Das interaktive, realitätsnahe Format verspricht einen nachhaltigen Lernerfolg, mit dem kritisches Denken gefördert sowie Veränderungen bei Einstellungen und Verhaltensweisen bewirkt werden können. Das 90-minütige Digitalspiel „Sibel’s Journey“ (https://sibelsjourney.com/) vom Typ narratives Adventure Game macht sich dieses Potential zunutze, um als Bildungsangebot im Sinne einer ganzheitlichen Sexuellen und geschlechtlichen Bildung Jugendliche bei der eigenständigen Auseinandersetzung mit diesen Themen zu unterstützen. Nach einer Einordnung von Serious Games als digitale Tools in der Sexuellen und geschlechtlichen Bildung stellt der vorliegende Praxisbeitrag die Funktionsweise und Inhalte von „Sibel’s Journey“ vor. Er informiert über die Spielentwicklung sowie die dahinterstehende sexualpädagogische Haltung und den Fokus auf Vielfalt und die Intersektionalität verschiedener Diskriminierungen.
Welche Phytotherapeutika werden in medizinischen Leitlinien zur
Behandlung gastroenterologischer Erkrankungen berücksichtigt?*
Authors: Utz Sandra , Langhorst Jost 
Published: December 2024

ZusammenfassungDie zunehmende Beliebtheit und wachsende Wirksamkeitsevidenz führen dazu, dass
Phytotherapeutika vermehrt in medizinische Leitlinien integriert werden.
Entsprechend der aktuellen wissenschaftlichen Datenlage werden gerade bei
gastroenterologischen Erkrankungen einige Empfehlungen für die Anwendung von
Phytotherapeutika ausgesprochen. Phytotherapeutika wie Pfefferminzöl oder
Kümmelölauflagen werden beispielsweise beim Reizdarmsyndrom zur Symptomlinderung
empfohlen. Bei chronischer Obstipation und Colitis ulcerosa werden Ballaststoffe
wie Flohsamen empfohlen. Bei Colitis ulcerosa kann die Kombination von Myrrhe,
Kamillenblütenextrakt und Kaffeekohle komplementär in der remissionserhaltenden
Behandlung eingesetzt werden. Einige Phytotherapeutika (z.B. Wermut
[Artemisia absinthium], Weihrauch [Boswellia serrata]) zeigen
Wirksamkeitshinweise zur Behandlung von Morbus Crohn, jedoch ist die Datenlage
noch nicht ausreichend für Empfehlungen. Einige klare Empfehlungen für den
Einsatz von Phytotherapeutika zur Behandlung gastroenterologischer Erkrankungen
zeigen ihr großes Wirkspektrum. Aufgrund ihrer zusätzlich hohen Verträglichkeit
können sie sehr gut komplementär zu herkömmlichen Medikamenten eingesetzt
werden. Dennoch sind weitere qualitativ hochwertige Wirkungsstudien für weitere
Empfehlungen erforderlich.