bluuebunny/crossref_metadata_2025_split huggingface dataset:
Large-scale brain connectivity changes following the administration of lysergic acid diethylamide, d-amphetamine, and 3,4-methylenedioxyamphetamine
Authors: Avram Mihai , Fortea Lydia , Wollner Lea , Coenen Ricarda , Korda Alexandra , Rogg Helena , Holze Friederike , Vizeli Patrick , Ley Laura , Radua Joaquim , Müller Felix , Liechti Matthias E. , Borgwardt Stefan 
Published: September 2024

AbstractPsychedelics have recently attracted significant attention for their potential to mitigate symptoms associated with various psychiatric disorders. However, the precise neurobiological mechanisms responsible for these effects remain incompletely understood. A valuable approach to gaining insights into the specific mechanisms of action involves comparing psychedelics with substances that have partially overlapping neurophysiological effects, i.e., modulating the same neurotransmitter systems. Imaging data were obtained from the clinical trial NCT03019822, which explored the acute effects of lysergic acid diethylamide (LSD), d-amphetamine, and 3,4-methylenedioxymethamphetamine (MDMA) in 28 healthy volunteers. The clinical trial employed a double-blind, placebo-controlled, crossover design. Herein, various resting-state connectivity measures were examined, including within-network connectivity (integrity), between-network connectivity (segregation), seed-based connectivity of resting-state networks, and global connectivity. Differences between placebo and the active conditions were assessed using repeated-measures ANOVA, followed by post-hoc pairwise t-tests. Changes in voxel-wise seed-based connectivity were correlated with serotonin 2 A receptor density maps. Compared to placebo, all substances reduced integrity in several networks, indicating both common and unique effects. While LSD uniquely reduced integrity in the default-mode network (DMN), the amphetamines, in contrast to our expectations, reduced integrity in more networks than LSD. However, LSD exhibited more pronounced segregation effects, characterized solely by decreases, in contrast to the amphetamines, which also induced increases. Across all substances, seed-based connectivity mostly increased between networks, with LSD demonstrating more pronounced effects than both amphetamines. Finally, while all substances decreased global connectivity in visual areas, compared to placebo, LSD specifically increased global connectivity in the basal ganglia and thalamus. These findings advance our understanding of the distinctive neurobiological effects of psychedelics, prompting further exploration of their therapeutic potential.
Impact of blood glucose on cognitive function in insulin resistance: novel insights from ambulatory assessment
Authors: Gruber Judith R. , Ruf Alea , Süß Elena D. , Tariverdian Sewin , Ahrens Kira F. , Schiweck Carmen , Ebner-Priemer Ulrich , Edwin Thanarajah Sharmili , Reif Andreas , Matura Silke 
Published: September 2024

Abstract
Background/objectives
Insulin resistance (IR)-related disorders and cognitive impairment lead to reduced quality of life and cause a significant strain on individuals and the public health system. Thus, we investigated the effects of insulin resistance (IR), and blood glucose fluctuations on cognitive function under laboratory and free-living conditions, using ecological momentary assessment (EMA).

Subjects/methods
Baseline assessments included neuropsychological tests and blood analysis. Individuals were classified as either insulin-sensitive (<2) or insulin-resistant (≥2), based on their Homeostatic Model Assessment (HOMA-IR) values. Continuous glucose monitoring (CGM) using a percutaneous sensor was performed for 1 week. Using multiple linear regression, we examined the effects of HOMA-IR and CGM metrics on cognitive domains. Working memory (WM) performance, which was assessed using EMA, 4 times a day for 3 consecutive days, was matched to short-term pre-task CGM metrics. Multilevel analysis was used to map the within-day associations of HOMA-IR, short-term CGM metrics, and WM.

Results
Analyses included 110 individuals (mean age 48.7 ± 14.3 years, 59% female, n = 53 insulin-resistant). IR was associated with lower global cognitive function (b = −0.267, P = 0.027), and WM (b = −0.316; P = 0.029), but not with executive function (b = −0.216; P = 0.154) during baseline. EMA showed that higher HOMA-IR was associated with lower within-day WM performance (β = −0.20, 95% CI −0.40 to −0.00). CGM metrics were not associated with cognitive performance.

Conclusions
The results confirm the association between IR and decrements in global cognitive functioning and WM, while no effects of CGM metrics were observed, making IR a crucial time point for intervention. Targeting underlying mechanisms (e.g., inflammation) in addition to glycemia could be promising to minimize adverse cognitive effects. Registered under https://drks.de/register/de identifier no. DRKS00022774.
Traumatic spinal cord injury and its correlation to risk of autoimmune/-inflammatory disease
Authors: Nielsen Tim Damgaard , Laursen Thomas Munk , Bech Bodil Hammer , Rasmussen Mikkel Mylius 
Published: September 2024

Abstract
Study design
Nationwide epidemiological open cohort study.

Objectives
To evaluate whether individuals with traumatic spinal cord injury (TSCI) are more prone to develop autoimmune diseases compared to a general non-TSCI population.

Setting
Danish public national registries.

Methods
An open nationwide cohort, including individuals born in Denmark from or alive during 1945-2018 was collected and the study period was 1980-2018. Poissons Log-linear regression estimated the incidence rate ratio (IRR) for developing eight groups of autoimmune diseases. A dose-response relationship based on the cervical/thoracic level of injury was assessed by stratification.

Results
The cohort included 3,272 individuals with TSCI and 4.8 million background individuals, accounting for 50,865 and 140 million person-years respectively. The TSCI population had an overall IRR of 1.81 (95% CI, 1.59 to 2.05) of getting any autoimmune disease. Subgroup analysis found positive associations for; a) Other neurologic IRR 5.19 (95% CI, 2.79 to 9.65), b) multiple sclerosis IRR 3.70 (95% CI, 2.54 to 5.40), c) Dermatologic IRR 2.57 (95% CI, 1.86 to 3.55), d) Type 1 diabetes mellitus IRR 2.01 (95% CI, 1.54 to 2.61), e) Systemic 1.92 (95% CI, 1.44 to 2.55), and f) Gastroenterologic IRR 1.42 (95% CI, 1.05 to 1.92). Cervical levels of TSCI showed an IRR of 1.70 (95% CI, 1.43 to 2.02), while thoracic levels had an IRR 1.98 (95% CI, 1.63 to 2.39).

Conclusions
TSCI may be an individual risk factor of developing an autoimmune disease. There does not appear to exist a dose-response relationship from the level of injury.

Sponsorship
None.
Association of ADAM family members with proliferation signaling and disease progression in multiple myeloma
Authors: Evers Marietheres , Stühmer Thorsten , Schreder Martin , Steinbrunn Torsten , Rudelius Martina , Jundt Franziska , Ebert Regina , Hartmann Tanja Nicole , Bargou Ralf Christian , Rosenwald Andreas , Leich Ellen 
Published: September 2024

AbstractMultiple myeloma (MM) is a hematological malignancy whose curability is greatly challenged by recurrent patient relapses and therapy resistance. We have previously proposed the high expression of ADAM8, ADAM9 and ADAM15 (A Disintegrin And Metalloproteinase 8/9/15) as adverse prognostic markers in MM. This study focused on the so far scarcely researched role of ADAM8/9/15 in MM using two patient cohorts and seven human MM cell lines (HMCL). High ADAM8/9/15 expression was associated with high-risk cytogenetic abnormalities and extramedullary disease. Furthermore, ADAM8/15 expression increased with MM progression and in relapsed/refractory MM compared to untreated patient samples. RNA sequencing and gene set enrichment analysis comparing ADAM8/9/15high/low patient samples revealed an upregulation of proliferation markers and proliferation-associated gene sets in ADAM8/9/15high patient samples. High ADAM8/9/15 expression correlated with high Ki67 and high ADAM8/15 expression with high MYC protein expression in immunohistochemical stainings of patient tissue. Conversely, siRNA-mediated knockdown of ADAM8/9/15 in HMCL downregulated proliferation-related gene sets. Western blotting revealed that ADAM8 knockdown regulated IGF1R/AKT signaling and ADAM9 knockdown decreased mTOR activation. Lastly, high ADAM8/9/15 expression levels were verified as prognostic markers independent of Ki67/MYC expression and/or high-risk abnormalities. Overall, these findings suggest that ADAM8/9/15 play a role in MM progression and proliferation signaling.
A bird’s eye view of mitochondrial unfolded protein response in cancer: mechanisms, progression and further applications
Authors: Zhang Xinyu , Fan Yumei , Tan Ke 
Published: September 2024

AbstractMitochondria are essential organelles that play critical roles in energy metabolism, apoptosis and various cellular processes. Accumulating evidence suggests that mitochondria are also involved in cancer development and progression. The mitochondrial unfolded protein response (UPRmt) is a complex cellular process that is activated when the protein-folding capacity of the mitochondria is overwhelmed. The core machinery of UPRmt includes upstream regulatory factors, mitochondrial chaperones and proteases. These components work together to eliminate misfolded proteins, increase protein-folding capacity, and restore mitochondrial function. Recent studies have shown that UPRmt is dysregulated in various cancers and contributes to tumor initiation, growth, metastasis, and therapeutic resistance. Considering the pivotal role of the UPRmt in oncogenesis, numerous compounds and synthetic drugs targeting UPRmt-related components induce cancer cell death and suppress tumor growth. In this review, we comprehensively summarize recent studies on the molecular mechanisms of UPRmt activation in C. elegans and mammals and elucidate the conceptual framework, functional aspects, and implications of the UPRmt for cancer therapy. In summary, we paint a developmental landscape of the UPRmt in different types of cancer and offer valuable insights for the development of novel cancer treatment strategies by targeting the UPRmt.
RNA-mediated double-strand break repair by end-joining mechanisms
Authors: Jeon Youngkyu , Lu Yilin , Ferrari Margherita Maria , Channagiri Tejasvi , Xu Penghao , Meers Chance , Zhang Yiqi , Balachander Sathya , Park Vivian S. , Marsili Stefania , Pursell Zachary F. , Jonoska Nataša , Storici Francesca 
Published: September 2024

AbstractDouble-strand breaks (DSBs) in DNA are challenging to repair. Cells employ at least three DSB-repair mechanisms, with a preference for non-homologous end joining (NHEJ) over homologous recombination (HR) and microhomology-mediated end joining (MMEJ). While most eukaryotic DNA is transcribed into RNA, providing complementary genetic information, much remains unknown about the direct impact of RNA on DSB-repair outcomes and its role in DSB-repair via end joining. Here, we show that both sense and antisense-transcript RNAs impact DSB repair in a sequence-specific manner in wild-type human and yeast cells. Depending on its sequence complementarity with the broken DNA ends, a transcript RNA can promote repair of a DSB or a double-strand gap in its DNA gene via NHEJ or MMEJ, independently from DNA synthesis. The results demonstrate a role of transcript RNA in directing the way DSBs are repaired in DNA, suggesting that RNA may directly modulate genome stability and evolution.
IL-1β promotes adipogenesis by directly targeting adipocyte precursors
Authors: Hofwimmer Kaisa , de Paula Souza Joyce , Subramanian Narmadha , Vujičić Milica , Rachid Leila , Méreau Hélène , Zhao Cheng , Dror Erez , Barreby Emelie , Björkström Niklas K. , Wernstedt Asterholm Ingrid , Böni-Schnetzler Marianne , Meier Daniel T. , Donath Marc Y. , Laurencikiene Jurga 
Published: September 2024

AbstractPostprandial IL-1β surges are predominant in the white adipose tissue (WAT), but its consequences are unknown. Here, we investigate the role of IL-1β in WAT energy storage and show that adipocyte-specific deletion of IL-1 receptor 1 (IL1R1) has no metabolic consequences, whereas ubiquitous lack of IL1R1 reduces body weight, WAT mass, and adipocyte formation in mice. Among all major WAT-resident cell types, progenitors express the highest IL1R1 levels. In vitro, IL-1β potently promotes adipogenesis in murine and human adipose-derived stem cells. This effect is exclusive to early-differentiation-stage cells, in which the adipogenic transcription factors C/EBPδ and C/EBPβ are rapidly upregulated by IL-1β and enriched near important adipogenic genes. The pro-adipogenic, but not pro-inflammatory effect of IL-1β is potentiated by acute treatment and blocked by chronic exposure. Thus, we propose that transient postprandial IL-1β surges regulate WAT remodeling by promoting adipogenesis, whereas chronically elevated IL-1β levels in obesity blunts this physiological function.
Omicron COVID-19 immune correlates analysis of a third dose of mRNA-1273 in the COVE trial
Authors: Zhang Bo , Fong Youyi , Fintzi Jonathan , Chu Eric , Janes Holly E. , Kenny Avi , Carone Marco , Benkeser David , van der Laan Lars W. P. , Deng Weiping , Zhou Honghong , Wang Xiaowei , Lu Yiwen , Yu Chenchen , Borate Bhavesh , Chen Haiyan , Reeder Isabel , Carpp Lindsay N. , Houchens Christopher R. , Martins Karen , Jayashankar Lakshmi , Huynh Chuong , Fichtenbaum Carl J. , Kalams Spyros , Gay Cynthia L. , Andrasik Michele P. , Kublin James G. , Corey Lawrence , Neuzil Kathleen M. , Priddy Frances , Das Rituparna , Girard Bethany , El Sahly Hana M. , Baden Lindsey R. , Jones Thomas , Donis Ruben O. , Koup Richard A. , Gilbert Peter B. , Follmann Dean ,   On behalf of the United States Government (USG) COVID-19 Immune Assays Team,   Moderna, Inc. Team,   Coronavirus Vaccine Prevention Network (CoVPN)/Coronavirus Efficacy (COVE) Team,   USG/CoVPN Biostatistics Team, van der Laan Lars W. P. 
Published: September 2024

AbstractIn the phase 3 Coronavirus Efficacy (COVE) trial (NCT04470427), post-dose two Ancestral Spike-specific binding (bAb) and neutralizing (nAb) antibodies were shown to be correlates of risk (CoR) and of protection against Ancestral-lineage COVID-19 in SARS-CoV-2 naive participants. In the SARS-CoV-2 Omicron era, Omicron subvariants with varying degrees of immune escape now dominate, seropositivity rates are high, and booster doses are administered, raising questions on whether and how these developments affect the bAb and nAb correlates. To address these questions, we assess post-boost BA.1 Spike-specific bAbs and nAbs as CoRs and as correlates of booster efficacy in COVE. For naive individuals, bAbs and nAbs inversely correlate with Omicron COVID-19: hazard ratios (HR) per 10-fold marker increase (95% confidence interval) are 0.16 (0.03, 0.79) and 0.31 (0.10, 0.96), respectively. In non-naive individuals the analogous results are similar: 0.15 (0.04, 0.63) and 0.28 (0.07, 1.08). For naive individuals, three vs two-dose booster efficacy correlates with predicted nAb titer at exposure, with estimates -8% (-126%, 48%), 50% (25%, 67%), and 74% (49%, 87%), at 56, 251, and 891 Arbitrary Units/ml. These results support the continued use of antibody as a surrogate endpoint.
The Polycomb system sustains promoters in a deep OFF state by limiting pre-initiation complex formation to counteract transcription
Authors: Szczurek Aleksander T. , Dimitrova Emilia , Kelley Jessica R. , Blackledge Neil P. , Klose Robert J. 
Published: September 2024

AbstractThe Polycomb system has fundamental roles in regulating gene expression during mammalian development. However, how it controls transcription to enable gene repression has remained enigmatic. Here, using rapid degron-based depletion coupled with live-cell transcription imaging and single-particle tracking, we show how the Polycomb system controls transcription in single cells. We discover that the Polycomb system is not a constitutive block to transcription but instead sustains a long-lived deep promoter OFF state, which limits the frequency with which the promoter can enter into a transcribing state. We demonstrate that Polycomb sustains this deep promoter OFF state by counteracting the binding of factors that enable early transcription pre-initiation complex formation and show that this is necessary for gene repression. Together, these important discoveries provide a rationale for how the Polycomb system controls transcription and suggests a universal mechanism that could enable the Polycomb system to constrain transcription across diverse cellular contexts.
One month convection timescale on the surface of a giant evolved star
Authors: Vlemmings Wouter , Khouri Theo , Bojnordi Arbab Behzad , De Beck Elvire , Maercker Matthias 
Published: September 2024

AbstractThe transport of energy through convection is important during many stages of stellar evolution1,2, and is best studied in our Sun3 or giant evolved stars4. Features that are attributed to convection are found on the surface of massive red supergiant stars5–8. Also for lower-mass evolved stars, indications of convection are found9–13, but convective timescales and sizes remain poorly constrained. Models indicate that convective motions are crucial to produce strong winds that return the products of stellar nucleosynthesis into the interstellar medium14. Here we report a series of reconstructed interferometric images of the surface of the evolved giant star R Doradus. The images reveal a stellar disk with prominent small-scale features that provide the structure and motions of convection on the stellar surface. We find that the dominant structure size of the features on the stellar disk is 0.72 ± 0.05 astronomical units. We measure the velocity of the surface motions to vary between −18 and +20 km s−1, which means that the convective timescale is approximately one month. This indicates a possible difference between the convection properties of low-mass and high-mass evolved stars.
Brain-wide dynamics linking sensation to action during decision-making
Authors: Khilkevich Andrei , Lohse Michael , Low Ryan , Orsolic Ivana , Bozic Tadej , Windmill Paige , Mrsic-Flogel Thomas D. 
Published: September 2024

AbstractPerceptual decisions rely on learned associations between sensory evidence and appropriate actions, involving the filtering and integration of relevant inputs to prepare and execute timely responses1,2. Despite the distributed nature of task-relevant representations3–10, it remains unclear how transformations between sensory input, evidence integration, motor planning and execution are orchestrated across brain areas and dimensions of neural activity. Here we addressed this question by recording brain-wide neural activity in mice learning to report changes in ambiguous visual input. After learning, evidence integration emerged across most brain areas in sparse neural populations that drive movement-preparatory activity. Visual responses evolved from transient activations in sensory areas to sustained representations in frontal-motor cortex, thalamus, basal ganglia, midbrain and cerebellum, enabling parallel evidence accumulation. In areas that accumulate evidence, shared population activity patterns encode visual evidence and movement preparation, distinct from movement-execution dynamics. Activity in movement-preparatory subspace is driven by neurons integrating evidence, which collapses at movement onset, allowing the integration process to reset. Across premotor regions, evidence-integration timescales were independent of intrinsic regional dynamics, and thus depended on task experience. In summary, learning aligns evidence accumulation to action preparation in activity dynamics across dozens of brain regions. This leads to highly distributed and parallelized sensorimotor transformations during decision-making. Our work unifies concepts from decision-making and motor control fields into a brain-wide framework for understanding how sensory evidence controls actions.
Ultrahigh electromechanical response from competing ferroic orders
Authors: Lin Baichen , Ong Khuong Phuong , Yang Tiannan , Zeng Qibin , Hui Hui Kim , Ye Zhen , Sim Celine , Yen Zhihao , Yang Ping , Dou Yanxin , Li Xiaolong , Gao Xingyu , Tan Chee Kiang Ivan , Lim Zhi Shiuh , Zeng Shengwei , Luo Tiancheng , Xu Jinlong , Tong Xin , Li Patrick Wen Feng , Ren Minqin , Zeng Kaiyang , Sun Chengliang , Ramakrishna Seeram , Breese Mark B. H. , Boothroyd Chris , Lee Chengkuo , Singh David J. , Lam Yeng Ming , Liu Huajun 
Published: September 2024

AbstractMaterials with electromechanical coupling are essential for transducers and acoustic devices as reversible converters between mechanical and electrical energy1–6. High electromechanical responses are typically found in materials with strong structural instabilities, conventionally achieved by two strategies—morphotropic phase boundaries7 and nanoscale structural heterogeneity8. Here we demonstrate a different strategy to accomplish ultrahigh electromechanical response by inducing extreme structural instability from competing antiferroelectric and ferroelectric orders. Guided by the phase diagram and theoretical calculations, we designed the coexistence of antiferroelectric orthorhombic and ferroelectric rhombohedral phases in sodium niobate thin films. These films show effective piezoelectric coefficients above 5,000 pm V−1 because of electric-field-induced antiferroelectric–ferroelectric phase transitions. Our results provide a general approach to design and exploit antiferroelectric materials for electromechanical devices.
Connectome-constrained networks predict neural activity across the fly visual system
Authors: Lappalainen Janne K. , Tschopp Fabian D. , Prakhya Sridhama , McGill Mason , Nern Aljoscha , Shinomiya Kazunori , Takemura Shin-ya , Gruntman Eyal , Macke Jakob H. , Turaga Srinivas C. 
Published: September 2024

AbstractWe can now measure the connectivity of every neuron in a neural circuit1–9, but we cannot measure other biological details, including the dynamical characteristics of each neuron. The degree to which measurements of connectivity alone can inform the understanding of neural computation is an open question10. Here we show that with experimental measurements of only the connectivity of a biological neural network, we can predict the neural activity underlying a specified neural computation. We constructed a model neural network with the experimentally determined connectivity for 64 cell types in the motion pathways of the fruit fly optic lobe1–5 but with unknown parameters for the single-neuron and single-synapse properties. We then optimized the values of these unknown parameters using techniques from deep learning11, to allow the model network to detect visual motion12. Our mechanistic model makes detailed, experimentally testable predictions for each neuron in the connectome. We found that model predictions agreed with experimental measurements of neural activity across 26 studies. Our work demonstrates a strategy for generating detailed hypotheses about the mechanisms of neural circuit function from connectivity measurements. We show that this strategy is more likely to be successful when neurons are sparsely connected—a universally observed feature of biological neural networks across species and brain regions.