bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crustal Architecture and Magmatism of the Campos Rifted Margin: Along‐Strike Variability and Segmentation
Authors: Alvarez P. , Stanton N. , Péron‐Pinvidic G. , Magnavita L. , Borghi L. 
Published: December 2024

AbstractWe investigate the crustal architecture and structural domains of the Campos rifted margin in southeastern Brazil, focusing on rifting evolution and segmentation. Based on 2‐D and 3‐D seismic reflection interpretation and potential field modeling, our results reveal an along‐strike variability, in terms of margin architecture and magmatism, that segments the basin into three main sectors from south to north. Through the analysis of seismic reflection profiles, we interpret this lateral variability as a product of lower‐ to upper‐plate alternations and different magmatic inputs. We propose the Southern Campos margin to represent a lower‐plate tectonic setting, where the distal domain is characterized by the formation of the here named Gávea Supradetachment Basin associated with the development of a metamorphic core‐complex. The Central Campos margin is characterized by a massive residual block, representing an upper‐plate setting, with exhumation of different crustal levels in the distal domain. Our analysis suggests that the Central Campos sustained a high magmatic input throughout the rift evolution, supporting the interpretation of Seaward Dipping Reflectors and a magmatic crust in a transitional domain. The Northern Campos margin also represents an upper‐plate setting, but characterized by a progressively delaminated crust. Finally, we compare the Brazilian margin architecture with the conjugate Angola margin, discuss the role of transfer zones in the segmentation and propose along‐strike variations in the volume of magmatism.
Correlation of Crustal Kinematic Characteristics and the Uplift of the Southeastern Tibetan Plateau During the Paleogene
Authors: Tong Yabo , Pei Junling , Yang Zhenyu , Li Jianfeng , Hou Lifu , Sun Xinxin , Zhang Zijian 
Published: December 2024

AbstractThe mechanism of the uplift of the southeastern Tibetan Plateau during the Cenozoic is much debated. To address this problem, we conducted a paleomagnetic study of the Eocene sedimentary strata in the Relu Basin, in the southeastern Tibetan Plateau. Two primary magnetic components of Ds = 24.0°, Is = 26.8°, k = 156.8, α95 = 3.5° acquired during ∼48.0–43.0 Ma and Ds = 172.2°, Is = −38.0°, k = 38.6, α95 = 9.8° during ∼43.0–35.0 Ma were isolated. The results combined with previous Paleocene and Eocene paleomagnetic and paleo‐altimetry data sets from the southeastern Tibetan Plateau, revealed a spatio‐temporal correlation between crustal movement and the uplift process of the southeastern Tibetan Plateau. The results showed that the final collision between India and Asia at ∼53.0–47.0 Ma immediately triggered the latitudinal crustal convergence and rotational deformation within the southeastern Tibetan Plateau. Since ∼47.0 Ma the southeastern Tibetan Plateau underwent a coherent crustal rotational pattern, and by at least ∼43.0 Ma, it finished the substantial latitudinal crustal convergence. The crustal movement transformations coincided with the major uplift of the southeastern Tibetan Plateau during ∼47.0–35.0 Ma and the eruption of extensive mafic magmatic rocks across the southeastern Tibetan Plateau and its margin during ∼43.0–33.0 Ma. These spatio‐temporal relationships suggest that the integral uplift of the southeastern Tibetan Plateau was mainly associated with the asthenospheric mantle upwelling and convection resulting from the tearing of the mantle lithosphere of the India Plate beneath the southeastern Tibetan Plateau.
Widespread Increasing Control of Water Supply on Evapotranspiration
Authors: Zhang Yu , Liu Xiaomang , Wang Kaiwen , Zhang Dan , Liu Weihang 
Published: December 2024

AbstractEvapotranspiration (ET), a crucial component of water consumption in the hydrological process, is directly controlled by soil moisture (SM) and vapor pressure deficit (VPD) from the perspectives of water supply and demand. However, SM and VPD are strongly coupled through multiple physical processes, confounding their effects on ET. Here, we decouple the interaction between SM and VPD and then analyze the spatiotemporal pattern of their individual effects on ET based on multiple observation‐based data sets. The results show that ET is limited by SM rather than VPD in approximately 63% of global land areas (60°S–60°N), defined as water supply‐limited regions. From 1982 to 2014, the effect of SM on ET enhances significantly in 43% of the water supply‐limited regions. The trends can be attributed to changes in SM and VPD themselves as well as to changes in vegetation conditions. Using the findings from the observation‐based data sets as the benchmark, we show that Earth System Models (ESMs) can overall reproduce the spatial pattern of SM and VPD effects on ET but fail to capture their temporal trends. Our results highlight that the water supply and demand control on ET varies with changing environments, which should be explicitly considered when analyzing the terrestrial water cycle and land‐atmosphere interaction.
Supra- and sub-threshold intracellular-like recording of 2D and 3D neuronal networks using nanopillar electrode arrays
Authors: Shukla Shivani , Schwartz Joshua L. , Walsh Callum , Wong Wen Mai , Patel Vrund , Hsieh Yu-Peng , Onwuasoanya Chichi , Chen Shaoming , Offenhäusser Andreas , Cauwenberghs Gert , Santoro Francesca , Muotri Alysson R. , Yeo Gene W. , Chalasani Sreekanth H. , Jahed Zeinab 
Published: December 2024

AbstractThe brain integrates activity across networks of interconnected neurons to generate behavioral outputs. Several physiological and imaging-based approaches have been previously used to monitor responses of individual neurons. While these techniques can identify cellular responses greater than the neuron’s action potential threshold, less is known about the events that are smaller than this threshold or are localized to subcellular compartments. Here we use NEAs to obtain temporary intracellular access to neurons allowing us to record information-rich data that indicates action potentials, and sub-threshold electrical activity. We demonstrate these recordings from primary hippocampal neurons, induced pluripotent stem cell-derived (iPSC) neurons, and iPSC-derived brain organoids. Moreover, our results show that our arrays can record activity from subcellular compartments of the neuron. We suggest that these data might enable us to correlate activity changes in individual neurons with network behavior, a key goal of systems neuroscience.
CXCR1+ neutrophil infiltration orchestrates response to third-generation EGFR-TKI in EGFR mutant non-small-cell lung cancer
Authors: Wang Haowei , Xiong Anwen , Chen Xiaoxia , Guo Junhong , Tang Zhuoran , Wu Chunyan , Ren Shengxiang , Zhou Caicun , Chen Jian , Hou Likun , Jiang Tao 
Published: December 2024

AbstractAlthough third-generation Epidermal growth factor receptor—tyrosine kinase inhibitors (EGFR-TKI) is standard of care for patients with EGFR-mutant Non-small cell lung cancer (NSCLC), little is known about the predictors of response or resistance. Here, we integrated single-cell RNA (scRNA) sequencing, bulk RNA sequencing, multiplexed immunofluorescence and flow cytometry data from pretreatment and post-resistant tumor samples of EGFR-mutant NSCLC patients received third-generation EGFR-TKIs. We show that resistant samples had a markedly enriched CXCR1+ neutrophils infiltration (P < 0.01) than pretreatment samples, which were distinguished from other subtypes of neutrophils and displayed immunosupressive characteristics. Spatial analysis showed that increased CXCR1+ neutrophils predominantly infiltrated into the tumor core in resistant samples and the average distance of neutrophils to tumor cells markedly reduced from 33 to 19 μm. Deep analysis of scRNA and bulk RNA sequencing data revealed the increased interactions between CXCR1+ neutrophils and tumor cells and activated TNF-α/NF-κB signaling pathway in tumor cells of resistant samples. In vitro and in vivo experiments validated that CXCR1+ neutrophils resulted in resistance to third-generation EGFR-TKI via activating TNF-α/NF-κB signaling pathway in tumor cells. Importantly, patients with low pretreatment CXCR1+ neutrophil infiltration abundance had a dramatically longer progression-free survival (11.8 vs. 7.5 months; P = 0.019) and overall survival (33.0 vs. 23.5 months; P = 0.029) than those with high infiltration abundance. Collectively, these findings suggest that CXCR1+ neutrophils infiltration was associated with the efficacy of third-generation EGFR-TKI in patients with EGFR-mutant NSCLC.
Neutrophil diversity and function in health and disease
Authors: Zhang Fengyuan , Xia Yidan , Su Jiayang , Quan Fushi , Zhou Hengzong , Li Qirong , Feng Qiang , Lin Chao , Wang Dongxu , Jiang Ziping 
Published: December 2024

AbstractNeutrophils, the most abundant type of granulocyte, are widely recognized as one of the pivotal contributors to the acute inflammatory response. Initially, neutrophils were considered the mobile infantry of the innate immune system, tasked with the immediate response to invading pathogens. However, recent studies have demonstrated that neutrophils are versatile cells, capable of regulating various biological processes and impacting both human health and disease. Cytokines and other active mediators regulate the functional activity of neutrophils by activating multiple receptors on these cells, thereby initiating downstream signal transduction pathways. Dysfunctions in neutrophils and disruptions in neutrophil homeostasis have been implicated in the pathogenesis of numerous diseases, including cancer and inflammatory disorders, often due to aberrant intracellular signaling. This review provides a comprehensive synthesis of neutrophil biological functions, integrating recent advancements in this field. Moreover, it examines the biological roles of receptors on neutrophils and downstream signaling pathways involved in the regulation of neutrophil activity. The pathophysiology of neutrophils in numerous human diseases and emerging therapeutic approaches targeting them are also elaborated. This review also addresses the current limitations within the field of neutrophil research, highlighting critical gaps in knowledge that warrant further investigation. In summary, this review seeks to establish a comprehensive and multidimensional model of neutrophil regulation, providing new perspectives for potential clinical applications and further research.
Prefrontal electrophysiological biomarkers and mechanism-based drug effects in a rat model of alcohol addiction
Authors: Habelt Bettina , Afanasenkau Dzmitry , Schwarz Cindy , Domanegg Kevin , Kuchar Martin , Werner Carsten , Minev Ivan R. , Spanagel Rainer , Meinhardt Marcus W. , Bernhardt Nadine 
Published: December 2024

AbstractPatients with alcohol use disorder (AUD) who seek treatment show highly variable outcomes. A precision medicine approach with biomarkers responsive to new treatments is warranted to overcome this limitation. Promising biomarkers relate to prefrontal control mechanisms that are severely disturbed in AUD. This results in reduced inhibitory control of compulsive behavior and, eventually, relapse. We reasoned here that prefrontal dysfunction, which underlies vulnerability to relapse, is evidenced by altered neuroelectric signatures and should be restored by pharmacological interventions that specifically target prefrontal dysfunction. To test this, we applied our recently developed biocompatible neuroprosthesis to measure prefrontal neural function in a well-established rat model of alcohol addiction and relapse. We monitored neural oscillations and event-related potentials in awake alcohol-dependent rats during abstinence and following treatment with psilocybin or LY379268, agonists of the serotonin 2A receptor (5-HT2AR), and the metabotropic glutamate receptor 2 (mGluR2), that are known to reduce prefrontal dysfunction and relapse. Electrophysiological impairments in alcohol-dependent rats are reduced amplitudes of P1N1 and N1P2 components and attenuated event-related oscillatory activity. Psilocybin and LY379268 were able to restore these impairments. Furthermore, alcohol-dependent animals displayed a dominance in higher beta frequencies indicative of a state of hyperarousal that is prone to relapse, which particularly psilocybin was able to counteract. In summary, we provide prefrontal markers indicative of relapse and treatment response, especially for psychedelic drugs.
Student confidence in clinical competence during dental education
Authors: Brundin Malin , Sjöström Mats 
Published: December 2024

Abstract
Introduction
Dental education blends theoretical and practical training to prepare students for independent patient care. This study examines the confidence levels of dental students at Umeå University, Sweden regarding independent performance of general dentistry tasks, and whether this confidence changes after clinical training.

Material and methods
Surveys were conducted before and after a summer clinical internship, with students rating their comfort levels on a scale from 0 to 10 for various procedures.

Results
Results from 64 initial surveys and 54 follow-up surveys showed no significant difference in confidence before and after the internship except for performing a tooth extraction (p = 0.010). However, confidence levels varied based on whether students had practiced specific tasks during the internship.

Discussion
Students felt least confident in managing acute dental trauma (mean 6.1–6.2) and treating cavities in young children (mean 6.2–6.7), while they were most confident in tasks like obtaining radiographic surveys (mean 8.5–8.6) and debriding periodontally compromised dentition (mean 8.2–8.3). Tooth extraction and dental fillings were the most practiced procedures during the internship.

Conclusions
The study concludes that the internship between the ninth and tenth semesters does not notably boost students’ confidence in specific dental procedures except for dental extractions. This result can possibly be explained due to the short duration of the training. Further exploration, including input from clinical supervisors, is suggested to optimise clinical training in dental education.
Real-world characteristics and outcomes of patients with high-risk and non-high-risk smoldering multiple myeloma using the Flatiron Health database
Authors: Rajkumar S. Vincent , Mateos María-Victoria , Schaeffer Marcy , Lin Xiwu , Bathija Sacheeta , Gupta-Werner Niodita , Lam Annette , Carson Robin , Dennis Robyn , Kaila Shuchita , Matt Kathryn , Duran Joana , Lonial Sagar 
Published: December 2024

AbstractThis study aimed to provide real-world evidence on progression risk in patients with high-risk smoldering multiple myeloma (SMM). This retrospective, observational study leveraged data from the Flatiron Health database. Eligible patients had SMM and relevant measures to apply Mayo 2018, International Myeloma Working Group (IMWG) 2020, and AQUILA trial risk criteria. Time to progression to active MM (TTP), progression or death (PFS), and death or progression on first-line MM therapy (PFS2) were evaluated using Kaplan–Meier methods and multivariate Cox regression models adjusted for age, Charlson Comorbidity Index, and time from SMM diagnosis to risk classification date. Across the three risk models (Mayo 2018, IMWG 2020, and AQUILA trial), high-risk patients with SMM had 3.0–4.0 times the risk of TTP, 2.1–3.5 times the risk of PFS, and 1.7–3.2 times the risk of PFS2 versus non-high-risk patients (p < 0.001 for all comparisons). Similar results were observed when patients with early treatment, early progression, and/or bone disease were excluded. This study demonstrates that high-risk patients with SMM have worse prognoses than non-high-risk patients, regardless of the criteria used, and highlights a need for early intervention testing.
Bispecific antibodies targeting BCMA or GPRC5D are highly effective in relapsed myeloma after CAR T-cell therapy
Authors: Merz Maximilian , Dima Danai , Hashmi Hamza , Ahmed Nausheen , Stölzel Friedrich , Holderried Tobias A. W. , Fenk Roland , Müller Fabian , Tovar Natalia , Oliver-Cáldes Aina , Rathje Kristin , Davis James A. , Fandrei David , Vucinic Vladan , Kharboutli Soraya , Baermann Ben-Niklas , Ayuk Francis , Platzbecker Uwe , Albici Anca-Maria , Schub Nathalie , Schmitz Friederike , Shune Leyla , Khouri Jack , Anwer Faiz , Raza Shahzad , McGuirk Joseph , Mahmoudjafari Zahra , Green Kimberly , Khandanpour Cyrus , Teichert Marcel , Jeker Barbara , Hoffmann Michele , Kröger Nicolaus , von Tresckow Bastian , de Larrea Carlos Fernández , Pabst Thomas , Abdallah Al-Ola , Gagelmann Nico 
Published: December 2024

AbstractDespite the astonishing outcomes after chimeric antigen receptor (CAR) T-cell therapy for relapsed refractory multiple myeloma (RRMM), most patients eventually relapse. There are only limited data available on salvage therapies following relapse after BCMA-directed CAR T-cell therapy. Here, we analyzed outcomes of post-CAR T-cell therapy relapse and impact of different salvage strategies in an international cohort of 139 patients (n = 130 ide-cel, n = 9 cilta-cel), receiving talquetamab (n = 28), teclistamab (n = 37), combinations of immunomodulating drugs (IMiDs), proteasome inhibitors (PIs) or CD38 monoclonal antibodies (n = 43), and others (n = 31). The median time to relapse after CAR T-cell therapy was 5 months, 53% had the extramedullary disease (EMD) at relapse, associated with dismal post-relapse outcome (P = 0.005). Overall response and complete response upon salvage therapies were 79% and 39% for talquetamab, 64% and 32% for teclistamab, 30% and 0% for IMiDs/PIs/CD38, and 26% and 3% for others (P < 0.001). Duration of response, as well as median survival, was significantly improved with bispecific antibodies (P < 0.001, respectively). Bispecific antibodies seemed to overcome the poor prognosis associated with early relapse and EMD, and were independent predictors for improved survival in multivariable analysis. In summary, these results suggest bispecific antibodies as the standard of care for relapse after CAR T-cell therapy for RRMM.
Mitophagy in gynecological malignancies: roles, advances, and therapeutic potential
Authors: Wang Jiao , Wang Dandan 
Published: December 2024

AbstractMitophagy is a process in which impaired or dysfunctional mitochondria are selectively eliminated through the autophagy mechanism to maintain mitochondrial quality control and cellular homeostasis. Based on specific target signals, several mitophagy processes have been identified. Defects in mitophagy are associated with various pathological conditions, including neurodegenerative disorders, cardiovascular diseases, metabolic diseases, and cancer. Mitophagy has been shown to play a critical role in the pathogenesis of gynecological malignancies and the development of drug resistance. In this review, we have summarized and discussed the role and recent advances in understanding the therapeutic potential of mitophagy in the development of gynecological malignancies. Therefore, the valuable insights provided in this review may serve as a basis for further studies that contribute to the development of novel treatment strategies and improved patient outcomes.
Eccentricity pacing and rapid termination of the early Antarctic ice ages
Authors: van Peer Tim E. , Liebrand Diederik , Taylor Victoria E. , Brzelinski Swaantje , Wolf Iris , Bornemann André , Friedrich Oliver , Bohaty Steven M. , Xuan Chuang , Lippert Peter C. , Wilson Paul A. 
Published: December 2024

AbstractEarth’s obliquity and eccentricity cycles are strongly imprinted on Earth’s climate and widely used to measure geological time. However, the record of these imprints on the oxygen isotope record in deep-sea benthic foraminifera (δ18Ob) shows contradictory signals that violate isotopic principles and cause controversy over climate-ice sheet interactions. Here, we present a δ18Ob record of high fidelity from International Ocean Drilling Program (IODP) Site U1406 in the northwest Atlantic Ocean. We compare our record to other records for the time interval between 28 and 20 million years ago, when Earth was warmer than today, and only Antarctic ice sheets existed. The imprint of eccentricity on δ18Ob is remarkably consistent globally whereas the obliquity signal is inconsistent between sites, indicating that eccentricity was the primary pacemaker of land ice volume. The larger eccentricity-paced early Antarctic ice ages were vulnerable to rapid termination. These findings imply that the self-stabilizing hysteresis effects of large land-based early Antarctic ice sheets were strong enough to maintain ice growth despite consecutive insolation-induced polar warming episodes. However, rapid ice age terminations indicate that resistance to melting was weaker than simulated by numerical models and regularly overpowered, sometimes abruptly.
Homeostatic microglia initially seed and activated microglia later reshape amyloid plaques in Alzheimer’s Disease
Authors: Baligács Nóra , Albertini Giulia , Borrie Sarah C. , Serneels Lutgarde , Pridans Clare , Balusu Sriram , De Strooper Bart 
Published: December 2024

AbstractThe role of microglia in the amyloid cascade of Alzheimer’s disease (AD) is debated due to conflicting findings. Using a genetic and a pharmacological approach we demonstrate that depletion of microglia before amyloid-β (Aβ) plaque deposition, leads to a reduction in plaque numbers and neuritic dystrophy, confirming their role in plaque initiation. Transplanting human microglia restores Aβ plaque formation. While microglia depletion reduces insoluble Aβ levels, soluble Aβ concentrations stay consistent, challenging the view that microglia clear Aβ. In later stages, microglial depletion decreases plaque compaction and increases neuritic dystrophy, suggesting a protective role. Human microglia with the TREM2R47H/R47H mutation exacerbate plaque pathology, emphasizing the importance of non-reactive microglia in the initiation of the amyloid cascade. Adaptive immune depletion (Rag2-/-) does not affect microglia’s impact on plaque formation. These findings clarify conflicting reports, identifying microglia as key drivers of amyloid pathology, and raise questions about optimal therapeutic strategies for AD.
Tbx1 haploinsufficiency leads to local skull deformity, paraflocculus and flocculus dysplasia, and motor-learning deficit in 22q11.2 deletion syndrome
Authors: Eom Tae-Yeon , Schmitt J. Eric , Li Yiran , Davenport Christopher M. , Steinberg Jeffrey , Bonnan Audrey , Alam Shahinur , Ryu Young Sang , Paul Leena , Hansen Baranda S. , Khairy Khaled , Pelletier Stephane , Pruett-Miller Shondra M. , Roalf David R. , Gur Raquel E. , Emanuel Beverly S. , McDonald-McGinn Donna M. , Smith Jesse N. , Li Cai , Christie Jason M. , Northcott Paul A. , Zakharenko Stanislav S. 
Published: December 2024

AbstractNeurodevelopmental disorders are thought to arise from intrinsic brain abnormalities. Alternatively, they may arise from disrupted crosstalk among tissues. Here we show the local reduction of two vestibulo-cerebellar lobules, the paraflocculus and flocculus, in mouse models and humans with 22q11.2 deletion syndrome (22q11DS). In mice, this paraflocculus/flocculus dysplasia is associated with haploinsufficiency of the Tbx1 gene. Tbx1 haploinsufficiency also leads to impaired cerebellar synaptic plasticity and motor learning. However, neural cell compositions and neurogenesis are not altered in the dysplastic paraflocculus/flocculus. Interestingly, 22q11DS and Tbx1+/– mice have malformations of the subarcuate fossa, a part of the petrous temporal bone, which encapsulates the paraflocculus/flocculus. Single-nuclei RNA sequencing reveals that Tbx1 haploinsufficiency leads to precocious differentiation of chondrocytes to osteoblasts in the petrous temporal bone autonomous to paraflocculus/flocculus cell populations. These findings suggest a previously unrecognized pathogenic structure/function relation in 22q11DS in which local skeletal deformity and cerebellar dysplasia result in behavioral deficiencies.