bluuebunny/crossref_metadata_2025_split huggingface dataset:
Actinium chelation and crystallization in a macromolecular scaffold
Authors: Wacker Jennifer N. , Woods Joshua J. , Rupert Peter B. , Peterson Appie , Allaire Marc , Lukens Wayne W. , Gaiser Alyssa N. , Minasian Stefan G. , Strong Roland K. , Abergel Rebecca J. 
Published: July 2024

AbstractTargeted alpha therapy (TAT) pairs the specificity of antigen targeting with the lethality of alpha particles to eradicate cancerous cells. Actinium-225 [225Ac; t1/2 = 9.920(3) days] is an alpha-emitting radioisotope driving the next generation of TAT radiopharmaceuticals. Despite promising clinical results, a fundamental understanding of Ac coordination chemistry lags behind the rest of the Periodic Table due to its limited availability, lack of stable isotopes, and inadequate systems poised to probe the chemical behavior of this radionuclide. In this work, we demonstrate a platform that combines an 8-coordinate synthetic ligand and a mammalian protein to characterize the solution and solid-state behavior of the longest-lived Ac isotope, 227Ac [t1/2 = 21.772(3) years]. We expect these results to direct renewed efforts for 225Ac-TAT development, aid in understanding Ac coordination behavior relative to other +3 lanthanides and actinides, and more broadly inform this element’s position on the Periodic Table.
Large-scale 2D heterostructures from hydrogen-bonded organic frameworks and graphene with distinct Dirac and flat bands
Authors: Zhang Xin , Li Xiaoyin , Cheng Zhengwang , Chen Aixi , Wang Pengdong , Wang Xingyue , Lei Xiaoxu , Bian Qi , Li Shaojian , Yuan Bingkai , Gao Jianzhi , Li Fang-Sen , Pan Minghu , Liu Feng 
Published: July 2024

AbstractThe current strategies for building 2D organic-inorganic heterojunctions involve mostly wet-chemistry processes or exfoliation and transfer, leading to interface contaminations, poor crystallizing, or limited size. Here we show a bottom-up procedure to fabricate 2D large-scale heterostructure with clean interface and highly-crystalline sheets. As a prototypical example, a well-ordered hydrogen-bonded organic framework is self-assembled on the highly-oriented-pyrolytic-graphite substrate. The organic framework adopts a honeycomb lattice with faulted/unfaulted halves in a unit cell, resemble to molecular “graphene”. Interestingly, the topmost layer of substrate is self-lifted by organic framework via strong interlayer coupling, to form effectively a floating organic framework/graphene heterostructure. The individual layer of heterostructure inherits its intrinsic property, exhibiting distinct Dirac bands of graphene and narrow bands of organic framework. Our results demonstrate a promising approach to fabricate 2D organic-inorganic heterostructure with large-scale uniformity and highly-crystalline via the self-lifting effect, which is generally applicable to most of van der Waals materials.
Efficient and reproducible generation of human iPSC-derived cardiomyocytes and cardiac organoids in stirred suspension systems
Authors: Prondzynski Maksymilian , Berkson Paul , Trembley Michael A. , Tharani Yashasvi , Shani Kevin , Bortolin Raul H. , Sweat Mason E. , Mayourian Joshua , Yucel Dogacan , Cordoves Albert M. , Gabbin Beatrice , Hou Cuilan , Anyanwu Nnaemeka J. , Nawar Farina , Cotton Justin , Milosh Joseph , Walker David , Zhang Yan , Lu Fujian , Liu Xujie , Parker Kevin Kit , Bezzerides Vassilios J. , Pu William T. 
Published: July 2024

AbstractHuman iPSC-derived cardiomyocytes (hiPSC-CMs) have proven invaluable for cardiac disease modeling and regeneration. Challenges with quality, inter-batch consistency, cryopreservation and scale remain, reducing experimental reproducibility and clinical translation. Here, we report a robust stirred suspension cardiac differentiation protocol, and we perform extensive morphological and functional characterization of the resulting bioreactor-differentiated iPSC-CMs (bCMs). Across multiple different iPSC lines, the protocol produces 1.2E6/mL bCMs with ~94% purity. bCMs have high viability after cryo-recovery (>90%) and predominantly ventricular identity. Compared to standard monolayer-differentiated CMs, bCMs are more reproducible across batches and have more mature functional properties. The protocol also works with magnetically stirred spinner flasks, which are more economical and scalable than bioreactors. Minor protocol modifications generate cardiac organoids fully in suspension culture. These reproducible, scalable, and resource-efficient approaches to generate iPSC-CMs and organoids will expand their applications, and our benchmark data will enable comparison to cells produced by other cardiac differentiation protocols.
Investigating grey matter volumetric trajectories through the lifespan at the individual level
Authors: Shi Runye , Xiang Shitong , Jia Tianye , Robbins Trevor W. , Kang Jujiao , Banaschewski Tobias , Barker Gareth J. , Bokde Arun L. W. , Desrivières Sylvane , Flor Herta , Grigis Antoine , Garavan Hugh , Gowland Penny , Heinz Andreas , Brühl Rüdiger , Martinot Jean-Luc , Martinot Marie-Laure Paillère , Artiges Eric , Nees Frauke , Orfanos Dimitri Papadopoulos , Paus Tomáš , Poustka Luise , Hohmann Sarah , Millenet Sabina , Fröhner Juliane H. , Smolka Michael N. , Vaidya Nilakshi , Walter Henrik , Whelan Robert , Schumann Gunter , Lin Xiaolei , Sahakian Barbara J. , Feng Jianfeng ,   IMAGEN Consortium, Jia Tianye , Banaschewski Tobias , Barker Gareth J. , Bokde Arun L. W. , Desrivières Sylvane , Flor Herta , Grigis Antoine , Garavan Hugh , Gowland Penny , Heinz Andreas , Brühl Rüdiger , Martinot Jean-Luc , Martinot Marie-Laure Paillère , Artiges Eric , Nees Frauke , Orfanos Dimitri Papadopoulos , Paus Tomáš , Poustka Luise , Hohmann Sarah , Millenet Sabina , Fröhner Juliane H. , Smolka Michael N. , Vaidya Nilakshi , Walter Henrik , Whelan Robert , Schumann Gunter 
Published: July 2024

AbstractAdolescents exhibit remarkable heterogeneity in the structural architecture of brain development. However, due to limited large-scale longitudinal neuroimaging studies, existing research has largely focused on population averages, and the neurobiological basis underlying individual heterogeneity remains poorly understood. Here we identify, using the IMAGEN adolescent cohort followed up over 9 years (14–23 y), three groups of adolescents characterized by distinct developmental patterns of whole-brain gray matter volume (GMV). Group 1 show continuously decreasing GMV associated with higher neurocognitive performances than the other two groups during adolescence. Group 2 exhibit a slower rate of GMV decrease and lower neurocognitive performances compared with Group 1, which was associated with epigenetic differences and greater environmental burden. Group 3 show increasing GMV and lower baseline neurocognitive performances due to a genetic variation. Using the UK Biobank, we show these differences may be attenuated in mid-to-late adulthood. Our study reveals clusters of adolescent neurodevelopment based on GMV and the potential long-term impact.
LARP3, LARP7, and MePCE are involved in the early stage of human telomerase RNA biogenesis
Authors: Kao Tsai-Ling , Huang Yu-Cheng , Chen Yi-Hsuan , Baumann Peter , Tseng Chi-Kang 
Published: July 2024

AbstractHuman telomerase assembly is a highly dynamic process. Using biochemical approaches, we find that LARP3 and LARP7/MePCE are involved in the early stage of human telomerase RNA (hTR) and that their binding to RNA is destabilized when the mature form is produced. LARP3 plays a negative role in preventing the processing of the 3′-extended long (exL) form and the binding of LARP7 and MePCE. Interestingly, the tertiary structure of the exL form prevents LARP3 binding and facilitates hTR biogenesis. Furthermore, low levels of LARP3 promote hTR maturation, increase telomerase activity, and elongate telomeres. LARP7 and MePCE depletion inhibits the conversion of the 3′-extended short (exS) form into mature hTR and the cytoplasmic accumulation of hTR, resulting in telomere shortening. Taken together our data suggest that LARP3 and LARP7/MePCE mediate the processing of hTR precursors and regulate the production of functional telomerase.
Charge-parity switching effects and optimisation of transmon-qubit design parameters
Authors: Papič Miha , Tuorila Jani , Auer Adrian , de Vega Inés , Hosseinkhani Amin 
Published: July 2024

AbstractEnhancing the performance of noisy quantum processors requires improving our understanding of error mechanisms and the ways to overcome them. A judicious selection of qubit design parameters plays a pivotal role in improving the performance of quantum processors. In this study, we identify optimal ranges for qubit design parameters, grounded in comprehensive noise modeling. To this end, we also analyze the effect of a charge-parity switch caused by quasiparticles on a two-qubit gate. Due to the utilization of the second excited state of a transmon, where the charge dispersion is significantly larger, a charge-parity switch will affect the conditional phase of the two-qubit gate. We derive an analytical expression for the infidelity of a diabatic controlled-Z gate and see effects of similar magnitude in adiabatic controlled-phase gates in the tunable coupler architecture. Moreover, we show that the effect of a charge-parity switch can be the dominant quasiparticle-related error source of a two-qubit gate. We also demonstrate that charge-parity switches induce a residual longitudinal interaction between qubits in a tunable-coupler circuit. Furthermore, we introduce a performance metric for quantum circuit execution, encompassing the fidelity and number of single- and two-qubit gates in an algorithm, as well as the state preparation fidelity. This comprehensive metric, coupled with a detailed noise model, enables us to determine an optimal range for the qubit design parameters, as confirmed by numerical simulation. Our systematic analysis offers insights and serves as a guiding framework for the development of the next generation of transmon-based quantum processors.
Zeb1 mediates EMT/plasticity-associated ferroptosis sensitivity in cancer cells by regulating lipogenic enzyme expression and phospholipid composition
Authors: Schwab Annemarie , Rao Zhigang , Zhang Jie , Gollowitzer André , Siebenkäs Katharina , Bindel Nino , D’Avanzo Elisabetta , van Roey Ruthger , Hajjaj Yussuf , Özel Ece , Armstark Isabell , Bereuter Leonhard , Su Fengting , Grander Julia , Bonyadi Rad Ehsan , Groenewoud Arwin , Engel Felix B. , Bell George W. , Henry Whitney S. , Angeli José Pedro Friedmann , Stemmler Marc P. , Brabletz Simone , Koeberle Andreas , Brabletz Thomas 
Published: July 2024

AbstractTherapy resistance and metastasis, the most fatal steps in cancer, are often triggered by a (partial) activation of the epithelial–mesenchymal transition (EMT) programme. A mesenchymal phenotype predisposes to ferroptosis, a cell death pathway exerted by an iron and oxygen-radical-mediated peroxidation of phospholipids containing polyunsaturated fatty acids. We here show that various forms of EMT activation, including TGFβ stimulation and acquired therapy resistance, increase ferroptosis susceptibility in cancer cells, which depends on the EMT transcription factor Zeb1. We demonstrate that Zeb1 increases the ratio of phospholipids containing pro-ferroptotic polyunsaturated fatty acids over cyto-protective monounsaturated fatty acids by modulating the differential expression of the underlying crucial enzymes stearoyl-Co-A desaturase 1 (SCD), fatty acid synthase (FASN), fatty acid desaturase 2 (FADS2), elongation of very long-chain fatty acid 5 (ELOVL5) and long-chain acyl-CoA synthetase 4 (ACSL4). Pharmacological inhibition of selected lipogenic enzymes (SCD and FADS2) allows the manipulation of ferroptosis sensitivity preferentially in high-Zeb1-expressing cancer cells. Our data are of potential translational relevance and suggest a combination of ferroptosis activators and SCD inhibitors for the treatment of aggressive cancers expressing high Zeb1.
Consumer wearable devices for evaluation of heart rate control using digoxin versus beta-blockers: the RATE-AF randomized trial
Authors: Gill Simrat K. , Barsky Andrey , Guan Xin , Bunting Karina V. , Karwath Andreas , Tica Otilia , Stanbury Mary , Haynes Sandra , Folarin Amos , Dobson Richard , Kurps Julia , Asselbergs Folkert W. , Grobbee Diederick E. , Camm A. John , Eijkemans Marinus J. C. , Gkoutos Georgios V. , Kotecha Dipak ,   BigData@Heart Consortium,   the cardAIc group,   the RATE-AF trial team
Published: July 2024

AbstractConsumer-grade wearable technology has the potential to support clinical research and patient management. Here, we report results from the RATE-AF trial wearables study, which was designed to compare heart rate in older, multimorbid patients with permanent atrial fibrillation and heart failure who were randomized to treatment with either digoxin or beta-blockers. Heart rate (n = 143,379,796) and physical activity (n = 23,704,307) intervals were obtained from 53 participants (mean age 75.6 years (s.d. 8.4), 40% women) using a wrist-worn wearable linked to a smartphone for 20 weeks. Heart rates in participants treated with digoxin versus beta-blockers were not significantly different (regression coefficient 1.22 (95% confidence interval (CI) −2.82 to 5.27; P = 0.55); adjusted 0.66 (95% CI −3.45 to 4.77; P = 0.75)). No difference in heart rate was observed between the two groups of patients after accounting for physical activity (P = 0.74) or patients with high activity levels (≥30,000 steps per week; P = 0.97). Using a convolutional neural network designed to account for missing data, we found that wearable device data could predict New York Heart Association functional class 5 months after baseline assessment similarly to standard clinical measures of electrocardiographic heart rate and 6-minute walk test (F1 score 0.56 (95% CI 0.41 to 0.70) versus 0.55 (95% CI 0.41 to 0.68); P = 0.88 for comparison). The results of this study indicate that digoxin and beta-blockers have equivalent effects on heart rate in atrial fibrillation at rest and on exertion, and suggest that dynamic monitoring of individuals with arrhythmia using wearable technology could be an alternative to in-person assessment. ClinicalTrials.gov identifier: NCT02391337.
Unlocking opioid neuropeptide dynamics with genetically encoded biosensors
Authors: Dong Chunyang , Gowrishankar Raajaram , Jin Yihan , He Xinyi Jenny , Gupta Achla , Wang Huikun , Sayar-Atasoy Nilüfer , Flores Rodolfo J. , Mahe Karan , Tjahjono Nikki , Liang Ruqiang , Marley Aaron , Or Mizuno Grace , Lo Darren K. , Sun Qingtao , Whistler Jennifer L. , Li Bo , Gomes Ivone , Von Zastrow Mark , Tejeda Hugo A. , Atasoy Deniz , Devi Lakshmi A. , Bruchas Michael R. , Banghart Matthew R. , Tian Lin 
Published: July 2024

AbstractNeuropeptides are ubiquitous in the nervous system. Research into neuropeptides has been limited by a lack of experimental tools that allow for the precise dissection of their complex and diverse dynamics in a circuit-specific manner. Opioid peptides modulate pain, reward and aversion and as such have high clinical relevance. To illuminate the spatiotemporal dynamics of endogenous opioid signaling in the brain, we developed a class of genetically encoded fluorescence sensors based on kappa, delta and mu opioid receptors: κLight, δLight and µLight, respectively. We characterized the pharmacological profiles of these sensors in mammalian cells and in dissociated neurons. We used κLight to identify electrical stimulation parameters that trigger endogenous opioid release and the spatiotemporal scale of dynorphin volume transmission in brain slices. Using in vivo fiber photometry in mice, we demonstrated the utility of these sensors in detecting optogenetically driven opioid release and observed differential opioid release dynamics in response to fearful and rewarding conditions.
An efficient learning based approach for automatic record deduplication with benchmark datasets
Authors: Ravikanth M , Korra Sampath , Mamidisetti Gowtham , Goutham Maganti , Bhaskar T. 
Published: July 2024

AbstractWith technological innovations, enterprises in the real world are managing every iota of data as it can be mined to derive business intelligence (BI). However, when data comes from multiple sources, it may result in duplicate records. As data is given paramount importance, it is also significant to eliminate duplicate entities towards data integration, performance and resource optimization. To realize reliable systems for record deduplication, late, deep learning could offer exciting provisions with a learning-based approach. Deep ER is one of the deep learning-based methods used recently for dealing with the elimination of duplicates in structured data. Using it as a reference model, in this paper, we propose a framework known as Enhanced Deep Learning-based Record Deduplication (EDL-RD) for improving performance further. Towards this end, we exploited a variant of Long Short Term Memory (LSTM) along with various attribute compositions, similarity metrics, and numerical and null value resolution. We proposed an algorithm known as Efficient Learning based Record Deduplication (ELbRD). The algorithm extends the reference model with the aforementioned enhancements. An empirical study has revealed that the proposed framework with extensions outperforms existing methods.
LINE1-mediated epigenetic repression of androgen receptor transcription causes androgen insensitivity syndrome
Authors: Pozojevic Jelena , Sivaprasad Radhika , Laß Joshua , Haarich Franziska , Trinh Joanne , Kakar Naseebullah , Schulz Kristin , Händler Kristian , Verrijn Stuart Annemarie A. , Giltay Jacques C. , van Gassen Koen L. , Caliebe Almuth , Holterhus Paul-Martin , Spielmann Malte , Hornig Nadine C. 
Published: July 2024

AbstractAndrogen insensitivity syndrome (AIS) is a difference of sex development (DSD) characterized by different degrees of undervirilization in individuals with a 46,XY karyotype despite normal to high gonadal testosterone production. Classically, AIS is explained by hemizygous mutations in the X-chromosomal androgen receptor (AR) gene. Nevertheless, the majority of individuals with clinically diagnosed AIS do not carry an AR gene mutation. Here, we present a patient with a 46,XY karyotype, born with undervirilized genitalia, age-appropriate testosterone levels and no uterus, characteristic for AIS. Diagnostic whole exome sequencing (WES) showed a maternally inherited LINE1 (L1) retrotransposon insertion in the 5′ untranslated region (5′UTR) of the AR gene. Long-read nanopore sequencing confirmed this as an insertion of a truncated L1 element of ≈ 2.7 kb and showed an increased DNA methylation at the L1 insertion site in patient-derived genital skin fibroblasts (GSFs) compared to healthy controls. The insertion coincided with reduced AR transcript and protein levels in patient-derived GSFs confirming the clinical diagnosis AIS. Our results underline the relevance of retrotransposons in human disease, and expand the growing list of human diseases associated with them.
Intratumoral microbiome of adenoid cystic carcinomas and comparison with other head and neck cancers
Authors: Karpinets Tatiana V. , Mitani Yoshitsugu , Chang Chia-Chi , Wu Xiaogang , Song Xingzhi , Flores Ivonne I. , McDaniel Lauren K. , Hoballah Yasmine M. , Veguilla Fabiana J. , Ferrarotto Renata , Colbert Lauren E. , Ajami Nadim J. , Jenq Robert R. , Zhang Jianhua , Futreal Andrew P. , El-Naggar Adel K. 
Published: July 2024

AbstractAdenoid cystic carcinoma (ACC) is a rare, usually slow-growing yet aggressive head and neck malignancy. Despite its clinical significance, our understanding of the cellular evolution and microenvironment in ACC remains limited. We investigated the intratumoral microbiomes of 50 ACC tumor tissues and 33 adjacent normal tissues using 16S rRNA gene sequencing. This allowed us to characterize the bacterial communities within the ACC and explore potential associations between the bacterial community structure, patient clinical characteristics, and tumor molecular features obtained through RNA sequencing. The bacterial composition in the ACC was significantly different from that in adjacent normal salivary tissue, and the ACC exhibited diverse levels of species richness. We identified two main microbial subtypes within the ACC: oral-like and gut-like. Oral-like microbiomes, characterized by increased diversity and abundance of Neisseria, Leptotrichia, Actinomyces, Streptococcus, Rothia, and Veillonella (commonly found in healthy oral cavities), were associated with a less aggressive ACC-II molecular subtype and improved patient outcomes. Notably, we identified the same oral genera in oral cancer and head and neck squamous cell carcinomas. In both cancers, they were part of shared oral communities associated with a more diverse microbiome, less aggressive tumor phenotype, and better survival that reveal the genera as potential pancancer biomarkers for favorable microbiomes in ACC and other head and neck cancers. Conversely, gut-like intratumoral microbiomes, which feature low diversity and colonization by gut mucus layer-degrading species, such as Bacteroides, Akkermansia, Blautia, Bifidobacterium, and Enterococcus, were associated with poorer outcomes. Elevated levels of Bacteroides thetaiotaomicron were independently associated with significantly worse survival and positively correlated with tumor cell biosynthesis of glycan-based cell membrane components.
Putting ICAP to the test: how technology-enhanced learning activities are related to cognitive and affective-motivational learning outcomes in higher education
Authors: Wekerle Christina , Daumiller Martin , Janke Stefan , Dickhäuser Oliver , Dresel Markus , Kollar Ingo 
Published: July 2024

AbstractDigital technology is considered to have great potential to promote learning in higher education. In line with the Interactive, Constructive, Active, Passive (ICAP) framework, this seems to be particularly true when instructors stimulate high-quality learning activities such as constructive and interactive learning activities instead of active and passive learning activities. Against the background of a lack of empirical studies in authentic, technology-enhanced instructional settings, we investigated the cognitive and affective-motivational effects of these learning activity modes in technology-enhanced higher education courses. To this end, we used 3.820 student assessments regarding 170 course sessions for which the teachers stated the learning activities students were engaged in. Results of multilevel structural equation modelling highlight the importance of technology-enhanced interactive learning activities for students’ perception of learning and the potential negative consequences of passive learning activities for affective-motivational outcomes. However, the superiority of constructive and interactive learning activities compared to passive and active learning activities for cognitive and affective-motivational outcomes was not supported by the findings. Instead, the findings point to potential differential effects of the individual learning activities within one activity mode. Future research should follow up on these effects to gain a more fine-grained understanding of how technology-enhanced learning activities can be optimized to enhance students’ learning outcomes.