bluuebunny/crossref_metadata_2025_split huggingface dataset:
GDNF improves the cognitive ability of PD mice by promoting glycosylation and membrane distribution of DAT
Authors: Chengcheng Ma , Panpan An , Yalong Yan , Mingyu Su , Wei Xu , Jing Chen , Chuanxi Tang 
Published: August 2024

AbstractThe core of clinic treatment of Parkinson's disease (PD) is to enhance dopamine (DA) signaling within the brain. The regulation of dopamine transporter (DAT) is integral to this process. This study aims to explore the regulatory mechanism of glial cell line-derived neurotrophic factor (GDNF) on DAT, thereby gaining a profound understanding its potential value in treating PD. In this study, we investigated the effects of GDNF on both cellular and mouse models of PD, including the glycosylation and membrane transport of DAT detected by immunofluorescence and immunoblotting, DA signal measured by neurotransmitter fiber imaging technology, Golgi morphology observed by electron microscopic, as well as cognitive ability assessed by behavior tests. This study revealed that in animal trials, MPTP-induced Parkinson's Disease (PD) mice exhibited a marked decline in cognitive function. Utilizing ELISA and neurotransmitter fiber imaging techniques, we observed a decrease in dopamine levels and a significant reduction in the intensity of dopamine signal release in the Prefrontal Cortex (PFC) of PD mice induced by MPTP. Intriguingly, these alterations were reversed by Glial Cell Line-Derived Neurotrophic Factor (GDNF). In cellular experiments, following MPP + intervention, there was a decrease in Gly-DAT modification in both the cell membrane and cytoplasm, coupled with an increase in Nongly-DAT expression and aggregation of DAT within the cytoplasm. Conversely, GDNF augmented DAT glycosylation and facilitated its membrane transport in damaged dopaminergic neurons, concurrently reversing the effects of GRASP65 depletion and Golgi fragmentation, thereby reducing the accumulation of DAT in the Golgi apparatus. Furthermore, overexpression of GRASP65 enhanced DAT transport in PD cells and mice, while suppression of GRASP65 attenuated the efficacy of GDNF on DAT. Additionally, GDNF potentiated the reutilization of neurotransmitters by the PFC presynaptic membrane, boosting the effective release of dopamine following a single electrical stimulation, ultimately ameliorating the cognitive impairments in PD mice.Therefore, we propose that GDNF enhances the glycosylation and membrane trafficking of DAT by facilitating the re-aggregation of the Golgi apparatus, thereby amplifying the utilization of DA signals. This ultimately leads to the improvement of cognitive abilities in PD mouse models. Our study illuminates, from a novel angle, the beneficial role of GDNF in augmenting DA utilization and cognitive function in PD, providing fresh insights into its therapeutic potential.
Integrated drug resistance and leukemic stemness gene-expression scores predict outcomes in large cohort of over 3500 AML patients from 10 trials
Authors: H. Elsayed Abdelrahman , Cao Xueyuan , Marrero Richard J. , Nguyen Nam H. K. , Wu Huiyun , Ni Yonhui , Ribeiro Raul C. , Tobias Herold , Valk Peter J. , Béliveau François , Richard-Carpentier Guillaume , Hébert Josée , Zwaan C. Michel , Gamis Alan , Kolb Edward Anders , Aplenc Richard , Alonzo Todd A. , Meshinchi Soheil , Rubnitz Jeffrey , Pounds Stanley , Lamba Jatinder K. 
Published: August 2024

AbstractIn this study, we leveraged machine-learning tools by evaluating expression of genes of pharmacological relevance to standard-AML chemotherapy (ara-C/daunorubicin/etoposide) in a discovery-cohort of pediatric AML patients (N = 163; NCT00136084) and defined a 5-gene-drug resistance score (ADE-RS5) that was predictive of outcome (high MRD1 positivity p = 0.013; lower EFS p < 0.0001 and OS p < 0.0001). ADE-RS5 was integrated with a previously defined leukemic-stemness signature (pLSC6) to classify patients into four groups. ADE-RS5, pLSC6 and integrated-score was evaluated for association with outcome in one of the largest assembly of ~3600 AML patients from 10 independent cohorts (1861 pediatric and 1773 adult AML). Patients with high ADE-RS5 had poor outcome in validation cohorts and the previously reported pLSC6 maintained strong significant association in all validation cohorts. For pLSC6/ADE-RS5-integrated-score analysis, using Group-1 (low-scores for ADE-RS5 and pLSC6) as reference, Group-4 (high-scores for ADE-RS5 and pLSC6) showed worst outcome (EFS: p < 0.0001 and OS: p < 0.0001). Groups-2/3 (one high and one low-score) showed intermediate outcome (p < 0.001). Integrated score groups remained an independent predictor of outcome in multivariable-analysis after adjusting for established prognostic factors (EFS: Group 2 vs. 1, HR = 4.68, p < 0.001, Group 3 vs. 1, HR = 3.22, p = 0.01, and Group 4 vs. 1, HR = 7.26, p < 0.001). These results highlight the significant prognostic value of transcriptomics-based scores capturing disease aggressiveness through pLSC6 and drug resistance via ADE-RS5. The pLSC6 stemness score is a significant predictor of outcome and associates with high-risk group features, the ADE-RS5 drug resistance score adds further value, reflecting the clinical utility of simultaneous testing of both for optimizing treatment strategies.
XRCC2 driven homologous recombination subtypes and therapeutic targeting in lung adenocarcinoma metastasis
Authors: Gong Han , Zhang Peihe , Liu Qiang , Tian Yuxuan , Chen Fuxin , Qian Siyi , Tu Chaofeng , Tan Yueqiu , Hu Xingming , Zhang Bin 
Published: August 2024

AbstractLung adenocarcinoma (LUAD) is a leading cause of cancer mortality, with many patients facing poor prognosis, particularly those with metastatic or drug-resistant tumors. Homologous recombination genes (HRGs) are crucial in tumor progression and therapy resistance, but their clinical significance in LUAD is not well understood. In this study, we systematically characterize key HRGs in LUAD patients, identifying two distinct HR subtypes associated with different outcomes and biological functions. We establish a 5-gene scoring system (XRCC2, RAD51, BRCA1, FANCA, and CHEK1) that reliably predicts patient outcomes and immunotherapy responses in LUAD. Bioinformatics analysis and clinical validation highlight XRCC2 as a crucial biomarker in LUAD. Functional investigations through in vivo and in vitro experiments reveal the role of XRCC2 in promoting lung cancer migration and invasion. Mechanistically, XRCC2 stabilizes vimentin (VIM) protein expression through deubiquitylation. We predict c-MYC as a potential regulator of XRCC2 and demonstrate that inhibiting c-MYC with compound 10058-F4 reduces XRCC2 and VIM expression. Preclinical studies show the synergistic inhibition of metastasis in vivo when combining 10058-F4 with doxorubicin (Dox). Our findings present a potential personalized predictive tool for LUAD prognosis, identifying XRCC2 as a critical biomarker. The c-Myc-XRCC2-VIM axis emerges as a promising therapeutic target for overcoming lung metastasis. This study provides valuable insights into LUAD, proposing a prognostic tool for further clinical validation and unveiling a potential therapeutic strategy for combating lung metastasis by targeting c-Myc-XRCC2-VIM.
Designable exciton mixing through layer alignment in WS2-graphene heterostructures
Authors: Kleiner Amir , Hernangómez-Pérez Daniel , Refaely-Abramson Sivan 
Published: August 2024

AbstractOptical properties of heterostructures composed of layered 2D materials, such as transition metal dichalcogenides (TMDs) and graphene, are broadly explored. Of particular interest are light-induced energy transfer mechanisms in these materials and their structural roots. Here, we use state-of-the-art first-principles calculations to study the excitonic composition and the absorption properties of WS2–graphene heterostructures as a function of interlayer alignment and the local strain resulting from it. We find that Brillouin zone mismatch and the associated energy level alignment between the graphene Dirac cone and the TMD bands dictate an interplay between interlayer and intralayer excitons, mixing together in the many-body representation upon the strain-induced symmetry breaking in the interacting layers. Examining the representative cases of the 0° and 30° interlayer twist angles, we find that this exciton mixing strongly varies as a function of the relative alignment. We quantify the effect of these structural modifications on exciton charge separation between the layers and the associated graphene-induced homogeneous broadening of the absorption resonances. Our findings provide guidelines for controllable optical excitations upon interface design and shed light on the importance of many-body effects in the understanding of optical phenomena in complex heterostructures.
An ancient role for CYP73 monooxygenases in phenylpropanoid biosynthesis and embryophyte development
Authors: Knosp Samuel , Kriegshauser Lucie , Tatsumi Kanade , Malherbe Ludivine , Erhardt Mathieu , Wiedemann Gertrud , Bakan Bénédicte , Kohchi Takayuki , Reski Ralf , Renault Hugues 
Published: August 2024

AbstractThe phenylpropanoid pathway is one of the plant metabolic pathways most prominently linked to the transition to terrestrial life, but its evolution and early functions remain elusive. Here, we show that activity of the t-cinnamic acid 4-hydroxylase (C4H), the first plant-specific step in the pathway, emerged concomitantly with the CYP73 gene family in a common ancestor of embryophytes. Through structural studies, we identify conserved CYP73 residues, including a crucial arginine, that have supported C4H activity since the early stages of its evolution. We further demonstrate that impairing C4H function via CYP73 gene inactivation or inhibitor treatment in three bryophyte species—the moss Physcomitrium patens, the liverwort Marchantia polymorpha and the hornwort Anthoceros agrestis—consistently resulted in a shortage of phenylpropanoids and abnormal plant development. The latter could be rescued in the moss by exogenous supply of p-coumaric acid, the product of C4H. Our findings establish the emergence of the CYP73 gene family as a foundational event in the development of the plant phenylpropanoid pathway, and underscore the deep-rooted function of the C4H enzyme in embryophyte biology.
Transition metal-catalyzed C(sp2/sp3)–H α-fluoroalkenylation from gem-(bromo/di)fluoroalkenes to monofluoroalkenes: scope, mechanisms, and synthetic applications
Authors: Eliwa Essam M. , Bedair Ahmed H. , Djukic Jean-Pierre 
Published: August 2024

Synthetically valuable monofluoroalkenes can be obtained via atom- and step-economical transition metal mediated catalysis with high stereoselectivity and functional group tolerance.
Low‐carbon economic schedule of the H2DRI‐EAF steel plant integrated with a power‐to‐hydrogen system driven by blue hydrogen and green hydrogen
Authors: Zou Bokang , Zhang Yuanshi , Chen Qirui , Hu Qinran , Hu Xiaoyan , Shi Jing , Li Zesen , Wang Qi 
Published: August 2024

AbstractHydrogen direct reduction iron coupled with electronic arc furnace (H2DRI‐EAF) technology, as an important technology for decarbonisation in the iron and steel industry, has the advantages of high electrification and low carbon emissions. However, the large demand for hydrogen in this technology relies significantly on the production of electrolytic hydrogen, leading to a substantial increase in power consumption in the steel production process. Moreover, the use of an unclean power source in electrolytic hydrogen production leads to increases in indirect carbon emissions, reducing the low‐carbon attributes of the technology. This study investigates the integrated flexible operation mode of a steel plant. An illustrating method is utilised for modelling the entire steel production process and power to hydrogen (PtH2) process in detail for the H2DRI‐EAF steel plant, which includes natural gas, photovoltaic, wind power self‐provided power plants, and carbon capture and storage (CCS) systems. A mixed integer linear programming (MILP) model is developed for the comprehensive scheduling of the steel mill. The results of the case studies indicate that by reliably integrating the production of renewable energy and natural gas power plants, the PtH2 system can fully consume the renewable energy output while ensuring the smooth progress of steel production and maximising the reduction of carbon emissions from hydrogen production and the total cost of steel production.
Earth-like-planet-hosting systems: Architecture and properties
Authors: Davoult Jeanne , Alibert Yann , Mishra Lokesh 
Published: August 2024

Context. The discovery of Earth-like planets is a major focus of current planetology research and faces a significant technological challenge. Indeed, when it comes to detecting planets as small and cold as the Earth, the cost of observation time is massive. Understanding in what type of systems Earth-like planets (ELPs) form and how to identify them is crucial for preparing future missions such as PLATO, LIFE, or others. Theoretical models suggest that ELPs predominantly form within a certain type of system architecture. Therefore, the presence or absence of ELPs could be inferred from the arrangement of other planets within the same system.
Aims. This study aims to identify the profile of a typical system that harbours an ELP by investigating the architecture of systems and the properties of their innermost detectable planets. Here, we introduce a novel method for determining the architecture of planetary systems and categorising them into four distinct classes. We then conduct a statistical study to identify the most favourable arrangements for the presence of an ELP.
Methods. Using three populations of synthetic planetary systems generated using the Bern model around three different types of stars, we studied the ‘theoretical’ architecture (the architecture of a complete planetary system) and the ‘biased’ architecture (the architecture of a system in which only detectable planets are taken into account after applying an observation bias) of the synthetic systems. To describe a typical system hosting an ELP, we initially examined the distribution of ELPs across different categories of architectures, highlighting the strong link between planetary system architecture and the presence of an ELP. A more detailed analysis was then conducted, linking the biased architecture of a system with the physical properties of its innermost observable planet to establish the most favourable conditions for the presence or absence of an ELP in a system.
Results. First, using synthetic systems, we successfully reproduce the distribution of observed multi-planet systems within the five different architectural classes. This demonstrates the relevance, at the system level, of populations of the synthetic systems derived from the Bern model and the observational bias applied. Secondly, the biased architectures (with observation bias) correspond for the most part to the theoretical architectures (without bias) of the same system. Finally, the biased architecture of a system, studied in conjunction with the mass, radius, and period of the innermost detectable planet, appears to correlate with the presence or absence of an ELP in the same system.
Conclusions. We conclude that the detections of ELPs can be predicted thanks to the already known properties of their systems, and we present a list of the properties of the systems most likely to host such a planet.
Multiplicity of stars with planets in the solar neighbourhood
Authors: González-Payo J. , Caballero J. A. , Gorgas J. , Cortés-Contreras M. , Gálvez-Ortiz M.-C. , Cifuentes C. 
Published: August 2024

Aims. We intended to quantify the impact of stellar multiplicity on the presence and properties of exoplanets.
Methods. We investigated all exoplanet host stars at less than 100 pc using the latest astrometric data from Gaia DR3 and advanced statistical methodologies. We complemented our search for common proper motion and parallax companions with data from the Washington Double Star catalogue and the literature. After excluding a number of systems based on radial velocity data, and membership in clusters and open associations, or with resolved ultracool companions, we kept 215 exoplanet host stars in 212 multiple-star systems.
Results. We found 17 new companions in the systems of 15 known exoplanet host stars, and we measured precise angular and projected physical separations and position angles for 236 pairs of stars, compiled key parameters for 276 planets in multiple systems, and established a comparison sample comprising 687 single stars with exoplanets. With all of this, we statistically analysed a series of hypotheses regarding planets in multiple stellar systems. Although they are only statistically significant at a 2σ level, our analysis pointed to several interesting results on the comparison in the mean number of planets in multiple versus single stellar systems and the tendency of high-mass planets to be located in closer orbits in multiple systems. We confirm that planets in multiple systems tend to have orbits with larger eccentricities than those in single systems. In particular, we found a significant (>4σ) preference for planets to exhibit high orbital eccentricities at small ratios between star-star projected physical separations and star-planet semi-major axes.
Quantitative 2D propagation of smallness and control for 1D heat equations with power growth potentials
Authors: Wang Yunlei 
Published: August 2024

We study the relation between propagation of smallness in the plane and control for heat equations. The former has been proved by Zhu \cite{zhu2023remarks} who showed how the value of solutions in some small set propagates to a larger domain. By reviewing his proof, we establish a quantitative version with the explicit dependence of parameters. Using this explicit version, we establish new exact null-controllability results of 1D heat equations with any nonnegative power growth potentials $V\in L^\infty_{\mathrm{loc}}(\mathbb{R})$. As a key ingredient, new spectral inequalities are established. The control set $\Omega$ that we consider satisfy
\begin{equation*}
\left|\Omega\cap [x-L\langle x\rangle ^{-s},x+L\langle x\rangle ^{-s}]\right|\ge \gamma^{\langle x\rangle^\tau}2L\langle x\rangle^{-s}
\end{equation*}
for some $\gamma\in(0,1)$, $L>0$, $\tau,s\ge 0$, and $\langle x\rangle:=(1+|x|^2)^{1 /2} $. In particular, the null-controllability result for the case of thick sets that allow the decay of the density (\textit{i.e.}, $s=0$ and $\tau\ge 0$) is included. These extend the results in \cite{zhu2023spectral} from $\Omega$ being the union of equidistributive open sets to thick sets in the 1-dimensional case, and in \cite{su2023quantitative} from bounded potentials to certain unbounded ones.
Seminom im klinischen Stadium IIA/B – machen oder nicht machen: welchen Stellenwert hat die retroperitoneale Lymphadenektomie?
Authors: Heidenreich Axel , Seelemeyer Felix , Gößmann Ruben , Heidenreich Julian , Pfister David 
Published: August 2024

ZusammenfassungUngefähr 10% der Patienten mit einem seminomatösen testikulären Keimzelltumor werden im klinischen Stadium (KS) IIA/B diagnostiziert. Die aktuellen Therapieempfehlungen der S3-Leitlinie beinhalten die systemische Chemotherapie mit 3 Zyklen PEB oder die perkutane Radiotherapie mit 30 bzw. 36 Gy. Beide Behandlungsvarianten führen zu einer hohen Kurationsrate von 90–94 bzw. 82–90% in den Stadien IIA bzw. IIB. Jedoch sind beide Optionen nicht nur mit einer signifikant erhöhten langfristigen therapieassoziierten Toxizität bezüglich sekundäre Malignome, kardiovaskulärer und metabolischer Erkrankungen, sondern auch mit einer erhöhten therapiebedingten Sterberate assoziiert. Die primäre retroperitoneale Lymphadenektomie (RLA) hat sich in 5 prospektiven und retrospektiven Studien als eine valide therapeutische Alternative entwickelt. Die Rezidivrate beträgt nach einem medianen Follow-up von 25–33 Monaten 11–30%, sodass 70–90% der Patienten ohne eine begleitende Chemotherapie kuriert werden konnten. Alle Patienten wurden im Rezidiv meist mit einer Salvage-Chemotherapie kuriert. Die Rate an operationsbedingten Komplikationen Clavien-Dindo ≥3a ist gering und beträgt nur 3–13%. Der Erfolg der Operation ist abhängig von der Erfahrung der jeweiligen Operateure und dem gewählten Template, sodass die nsRLA nur an ausgewiesenen Zentren durchgeführt werden sollte. Die präoperative Bestimmung des molekularen Biomarkers miR371 korreliert streng mit dem Vorhandensein lymphonodulärer Mikrometastasen und könnte in das diagnostische Armentarium vor Therapie der Seminome im klinischen Stadium IIA/B integriert werden.
Enhancing Radiological Reporting in Head and Neck Cancer: Converting Free-Text CT Scan Reports to Structured Reports Using Large Language Models
Authors: Gupta Amit , Malhotra Hema , Garg Amit K. , Rangarajan Krithika 
Published: August 2024

Objective The aim of this study was to assess efficacy of large language models (LLMs) for converting free-text computed tomography (CT) scan reports of head and neck cancer (HNCa) patients into a structured format using a predefined template.
Materials and Methods A retrospective study was conducted using 150 CT reports of HNCa patients. A comprehensive structured reporting template for HNCa CT scans was developed, and the Generative Pre-trained Transformer 4 (GPT-4) was initially used to convert 50 CT reports into a structured format using this template. The generated structured reports were then evaluated by a radiologist for instances of missing or misinterpreted information and any erroneous additional details added by GPT-4. Following this assessment, the template was refined for improved accuracy. This revised template was then used for conversion of 100 other HNCa CT reports into structured format using GPT-4. These reports were then reevaluated in the same manner.
Results Initially, GPT-4 successfully converted all 50 free-text reports into structured reports. However, there were 10 places with missing information: tracheostomy tube (n = 3), noninclusion of involvement of sternocleidomastoid muscle (n = 2), extranodal tumor extension (n = 3), and contiguous involvement of the neck structures by nodal mass rather than the primary (n = 2). Few instances of nonsuspicious lung nodules were misinterpreted as metastases (n = 2). GPT-4 did not indicate any erroneous additional findings. Using the revised reporting template, GPT-4 converted all the 100 CT reports into a structured format with no repeated or additional mistakes.
Conclusion LLMs can be used for structuring free-text radiology reports using plain language prompts and a simple yet comprehensive reporting template.
Key Points

Summary Statement
Large language models can successfully and accurately convert conventional radiology reports for oncology scans into a structured format using a comprehensive predefined template and thus can enhance the utility and integration of these reports in routine clinical practice.