bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative modeling of fetal exposure to maternal long-acting injectable versus oral daily antipsychotics
Authors: Bediako-Kakari Philip , Monyo Mariella , Atoyebi Shakir , Olagunju Adeniyi 
Published: October 2024

AbstractThis study employed physiologically based pharmacokinetic (PBPK) modelling to compare the extent of fetal exposure between oral and long-acting injectable (LAI) aripiprazole and olanzapine. Adult and pregnancy PBPK models were developed and validated with relevant clinical data. Relevant indices of fetal exposure during pregnancy were predicted from concentration-time data at steady-state dosing for both oral and LAI formulations. Fetal Cmaxfor aripiprazole was 59-78% higher with LAI than oral, and 68-181% higher with LAI olanzapine than the oral formulation. Predicted C:M ratios (range) was 0.59-0.69 for oral aripiprazole and 0.61-0.66 for LAI aripiprazole, 0.34-0.64 for oral olanzapine and 0.89-0.96 for LAI olanzapine. Also, cumulative fetal exposure over 28 days from oral formulations were generally predicted to be lower compared with their therapeutic-equivalent LAI. Asin uterofetal exposure to maternal drugs does not necessarily translate to risk, these data should be interpreted in a broader context that includes benefit-risk assessments.
Genetically Predicted Blood Metabolites Mediate the Association Between Gut Microbiota and Childhood with obesity: A Mendelian Randomization Study
Authors: Zhang Min , Yan Wenjuan 
Published: October 2024

SummaryBackgroundChildhood with obesity is characterized by metabolic dysregulation and unique gut microbiota profiles. Nevertheless, the comprehensive understanding of gut microbiota and metabolic dysregulation of Childhood with obesity remains unclear.ObjectivesThis study aimed to investigate the causal relationship of gut microbiota and Childhood with obesity and identify the blood metabolites as potential mediators.MethodsThe exposure genome-wide association studies (GWAS) data were sourced from the GWAS Catalog, while the outcome GWAS data were obtained from the Early Growth Genetics (EGG) Consortium. The study used 473 types of gut microbiota, 233 types of blood metabolites, and Childhood with obesity from GWAS. We then performed two-sample Mendelian randomization (TSMR) and bidirectional Mendelian randomization (BDMR) analyses to explore the causal relationships between gut microbiota, blood metabolites, and Childhood with obesity. Additionally, we conducted multivariable Mendelian randomization (MVMR) and two-step Mendelian randomization (2SMR) to identify potential mediating blood metabolites in this process.ResultsMR analysis identified 13 types of gut microbiota and 12 types of blood metabolites that were causally associated with Childhood with obesity. Furthermore, there was no strong evidence that genetically predicted Childhood with obesity had an effect on these gut microbiota and blood metabolites. Further, 2SMR analysis revealed that the association between K10 sp001941205 and Childhood with obesity was mediated by the Total cholesterol to total lipids ratio in medium VLDL, accounting for 2.53% (95%CI; 2.14%-2.92%) of the association. Similarly, the relationship between SM23-33 and Childhood with obesity was mediated by the Ratio of 22:6 docosahexaenoic acid to total fatty acids, which accounted for 4.07% (95%CI; 2.70%-5.44%) of the association.ConclusionsThe present study is the first to investigate the causal relationships among 473 gut microbiota phenotypes, 233 blood metabolites, and Childhood with obesity through Mendelian randomization analysis, identifying 13 gut microbiota types with potential causal links to Childhood with obesity and suggesting that 2 blood metabolites may mediate these associations, thereby providing valuable insights for future intervention strategies aimed at addressing Childhood with obesity.
Emodin-Enhanced hUC-MSC Extracellular Vesicles Alleviate Acute Pancreatitis by Targeting Inflammation and Pyroptosis
Authors: Liu Xiong , Huang Xianwei , Huang Xiaodong , Liu Siyao , Hu Jun , Jiyan Lin 
Published: October 2024

AbstractAcute pancreatitis (AP) is a complex condition requiring immediate treatment. Both extracellular vesicles derived from human umbilical cord mesenchymal stem cells (hUC-MSC-EVs) and emodin, a naturally occurring anthraquinone used in traditional Chinese medicine, have shown therapeutic potential in treating AP. However, the mechanisms by which hUC-MSC-EVs and emodin alleviate AP, and whether they exert a synergistic effect on inflamed pancreatic tissues, remain unclear.In this study, we developed AP cell, organoid, and animal models to compare the effects of emodin, hUC-MSC-EVs, and emodin-loaded hUC-MSC-EVs on cell viability, inflammation, and pyroptosis. Our data revealed that all three treatments improved cell viability, reduced pro-inflammatory cytokine expression, and inhibited pyroptosis in the AP models. Notably, the encapsulation of emodin significantly enhanced the protective effects of hUC-MSC-EVs.These findings suggest that emodin’s protective effects on inflamed pancreatic tissues may be attributed, at least in part, to its anti-inflammatory and anti-pyroptotic properties. Additionally, our study proposes a novel strategy for engineering hUC-MSC-EVs for potential therapeutic applications in AP treatment.
Longitudinal neuromelanin changes in prodromal and early Parkinson’s disease in humans and rat model
Authors: Pérot Jean-Baptiste , Ruze Anthony , Gaurav Rahul , Rebbah Sana , Cadin Capucine , Le Troter Arnaud , Soustelle Lucas , Mouton Laura , Valabrègue Romain , Parent Annabelle , Mangone Graziella , Lejeune François-Xavier , Arnulf Isabelle , Corvol Jean-Christophe , Vidailhet Marie , Santin Mathieu D. , Vila Miquel , Lehéricy Stéphane 
Published: October 2024

AbstractStudies in animal models of Parkinson’s disease (PD) suggested that the accumulation of the neuromelanin (NM), a pigment contained in nigral dopaminergic neurons, could trigger neurodegeneration above a pathogenic threshold. Here we investigated this hypothesis using NM-sensitive MRI in rodents and in patients with isolated rapid eye movement sleep disorders (iRBD) subjects, a prodromal phase of parkinsonism, and early PD. We first combined NM-sensitive MRI and histology to study NM accumulation and neurodegeneration in a humanized rat model of PD. NM-MRI signal changes were biphasic with an initial increase due to the accumulation of NM in dopaminergic neurons, followed signal decrease due to neurodegeneration. In healthy subjects and patients with iRBD, NM-MRI signal increased initially and then decreased similarly as in rodents after reaching a similar maximum signal intensity in both groups. In early PD and converted iRBD patients, NM-MRI signal drop was greater than in healthy individuals. Results in animals and humans show that NM-sensitive MRI is a marker of the intracellular NM accumulation up to a threshold then of neuronal degeneration beyond this threshold and agree with the hypothesis of a pathogenic threshold of NM triggering neurodegeneration.
Fish are poor sentinels for surveillance of riverine AMR
Authors: Tskhay Faina , Köbsch Christoph , Elena Alan X. , Bengtsson-Palme Johan , Berendonk Thomas U. , Klümper Uli 
Published: October 2024

AbstractEffective surveillance of antimicrobial resistance (AMR) in the environment is crucial for assessing the human and animal health risk of AMR pollution. Wastewater treatment plants (WWTPs) are one of the main sources of AMR pollutants discharged into water bodies. One important factor for assessing the risks associated with such pollution is the colonization potential of the resistant bacteria (ARB) and resistance genes (ARGs) from the environment into human or animal microbiomes upon exposure. This study explores whether fish can act as sentinels for surveillance of AMR pollution in general and specifically the human colonization potential of ARB in rivers impacted by WWTP effluents. Two riverine fish species, Brown trout, and European bullhead, were sampled up- and downstream a German WWTP. The two fish species were chosen due to their different lifestyles: Trout are mainly actively swimming in the water phase, while bullheads are sedentary and river sediment-associated. The bacterial microbiomes and resistomes of fish gills, skin, and feces were compared with those of the respective river water and sediment up- and downstream of the WWTP. Microbiomes of both fish mirrored the changes in river water and sediment downstream of the WWTP, with significant shifts in bacterial community composition, particularly an increase in Proteobacteria and Verrucomicrobia. However, increases in ARG abundances observed in water and sediment downstream of the WWTP were not reflected in any of the fish-associated resistomes. This indicates that while the fish microbiome is sensitive to environmental changes, resistomes of poikilothermic animals such as fish are less responsive to colonization by ARB originating from WWTPs and may not serve as effective sentinels for assessing AMR pollution and colonization risks in freshwater environments. This study highlights the complexity of using wildlife as indicators for environmental AMR pollution and suggests that other species are better suited for surveillance efforts.HighlightsWWTP effluent affected downstream river microbiome composition of water and sedimentWWTP effluent significantly increased the level of six tested ARGs downstreamChanges in environmental microbiome composition were mirrored in trout and bullheadNo effect of the WWTP effluent on resistomes and individual ARG abundance in fishes
Parkinsonism disrupts neuronal modulation in the pre-supplementary motor area during movement preparation
Authors: Hendrix Claudia M. , Baker Hannah E. , Yu Ying , Schneck David D. , Wang Jing , Johnson Luke A. , Vitek Jerrold L. 
Published: October 2024

ABSTRACTMultiple studies suggest that Parkinson’s disease (PD) is associated with changes in neuronal activity throughout the basal ganglia-thalamocortical motor circuit. There are limited electrophysiological data, however, describing how parkinsonism impacts neuronal activity in the pre-supplementary motor area (pre-SMA), an area in medial frontal cortex involved in movement planning and motor control. In this study, single unit activity was recorded in the pre-SMA of two non-human primates during a visually cued reaching task in both the naive and parkinsonian state using the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of parkinsonism. In the naive state neuronal discharge rates were dynamically modulated prior to the presentation of the instructional go-cue. In a subset of these modulated cells, the magnitude of modulation correlated linearly with reaction time (RT). In the parkinsonian state, however, modulation of discharge rates in the pre-SMA was disrupted and the predictive encoding of RT was significantly diminished. These findings add to our understanding of the role of pre-SMA in motor behavior and suggest that disrupted encoding in this cortical area contributes to the alteration of early preparatory and pre-movement processes that are present in Parkinson’s disease.SIGNIFICANCE STATEMENTGoal-directed movements, such as reaching for an object, necessitate temporal preparation and organization of information processing within the basal ganglia-thalamocortical motor network. Impaired movement in people with Parkinson’s disease is thought to be the result of pathophysiological activity disrupting information flow within this network. This work provides neurophysiological evidence linking altered motor preplanning processes encoded in pre-supplementary motor area (pre-SMA) neuronal firing to the pathogenesis of motor disturbances in parkinsonism.
MIIST305 mitigates gastrointestinal acute radiation syndrome injury and ameliorates radiation-induced gut microbiome dysbiosis
Authors: Mitra Debmalya , Armijo Gabriel K. , Ober Elizabeth H. , Baker Shenda M. , Turner Helen C. , Broustas Constantinos G. 
Published: October 2024

ABSTRACTHigh-dose radiation exposure results in gastrointestinal (GI) acute radiation syndrome identified by the destruction of mucosal layer, intestinal epithelial barrier dysfunction, and aberrant inflammatory responses. In addition, radiation causes gut microbiome dysbiosis characterized by diminished microbial diversity, reduction in the abundance of beneficial commensal bacteria, and the spread of bacterial pathogens that trigger the recruitment of immune cells and the production of pro-inflammatory factors that lead to further GI tissue damage. Currently, there are no FDA- approved countermeasures that can treat radiation-induced GI injury. To meet this critical need, SynedgenInc., has developed a glycopolymer radiomitigator (MIIST305) that is specifically targeted to the GI tract which acts by intercalating into the mucus layer and the glycocalyx of intestinal epithelial cells that could potentially ameliorate the deleterious effects of radiation. Male C57BL/6J adult mice were exposed to 13 Gy total body X-irradiation with 5% bone marrow shielding and MIIST305 was administered on days 1, 3, and 5 post-irradiation. Approximately 85% of the animals survived the irradiation exposure and were apparently healthy until the end of the 30-day study period. In contrast, no control, vehicle-treated animals survived past day 10 at this radiation dose. We show that MIIST305 improved intestinal epithelial barrier function and suppressed systemic inflammatory response mediated by radiation-induced pro-inflammatory cytokines. Taxonomic profiling and community structure of the fecal and colonic mucosa microbiota demonstrated that MIIST305 treatment increased microbial diversity and restored abundance of beneficial commensal bacteria, includingLactobacillusandBifidobacteriumgenera, while suppressing potentially pathogenic bacteria compared with vehicle-treated animals. In summary, MIIST305 is a novel GI-targeted therapeutic that greatly enhances survival in mice exposed to lethal radiation and protects the GI tract from injury by restoring a balanced gut microbiota and effectively reducing proinflammatory responses. Further development of this drug as an FDA-approved medical countermeasure will be of critical importance in the event of a radiation public health emergency.
Astrocyte TrkB.T1 deficiency disrupts glutamatergic synaptogenesis and astrocyte-synapse interactions
Authors: Pinkston Beatriz T.C. , Browning Jack L. , Olsen Michelle L. 
Published: October 2024

ABSTRACTPerisynaptic astrocyte processes (PAPs) contact pre- and post-synaptic elements to provide structural and functional support to synapses. Accumulating research demonstrates that the cradling of synapses by PAPs is critical for synapse formation, stabilization, and plasticity. The specific signaling pathways that govern these astrocyte-synapse interactions, however, remain to be elucidated. Herein, we demonstrate a role for the astrocyte TrkB.T1 receptor, a truncated isoform of the canonical receptor for brain derived neurotrophic factor (BDNF), in modulating astrocyte-synapse interactions and excitatory synapse development. Neuron-astrocyte co-culture studies revealed that loss of astrocyte TrkB.T1 disrupts the formation of PAPs. To elucidate the role of TrkB.T1 in synapse development, we conditionally deleted TrkB.T1 in astrocytes in mice. Synaptosome preparations were employed to probe for TrkB.T1 localization at the PAP, and confocal three-dimensional microscopy revealed a significant reduction in synapse density and astrocyte-synapse interactions across development in the absence of astrocytic TrkB.T1. These findings suggest that BDNF/TrkB.T1 signaling in astrocytes is critical for normal excitatory synapse formation in the cortex and that astrocyte TrkB.T1 serves a requisite role in astrocyte synapse interactions. Overall, this work provides new insights into the molecular mechanisms of astrocyte-mediated synaptogenesis and may have implications for understanding neurodevelopmental disorders and developing potential therapeutic targets.
Mitochondrial fission controls astrocyte morphogenesis and organization in the cortex
Authors: Salazar Maria Pia Rodriguez , Kolanukuduru Sprihaa , Ramirez Valentina , Lyu Boyu , Sejourne Gabrielle , Sesaki Hiromi , Yu Guoqiang , Eroglu Cagla 
Published: October 2024

ABSTRACTDysfunctional mitochondrial dynamics are a hallmark of devastating neurodevelopmental disorders such as childhood refractory epilepsy. However, the role of glial mitochondria in proper brain development is not well understood. We show that astrocyte mitochondria undergo extensive fission while populating astrocyte distal branches during postnatal cortical development. Loss of mitochondrial fission regulator, Dynamin-related protein 1 (Drp1), decreases mitochondrial localization to distal astrocyte processes, and this mitochondrial mislocalization reduces astrocyte morphological complexity. Functionally, astrocyte-specific conditional deletion of Drp1 induces astrocyte reactivity and disrupts astrocyte organization in the cortex. These morphological and organizational deficits are accompanied by loss of astrocytic gap junction protein Connexin 43. These findings uncover a crucial role for mitochondrial fission in coordinating astrocytic morphogenesis and organization, revealing the regulation of astrocytic mitochondria dynamics as a critical step in neurodevelopment.SummaryDuring cortical astrocyte morphogenesis, mitochondria decrease in size to populate distal astrocyte processes. Drp1-mediated mitochondrial fission is necessary for peripheral astrocyte process formation. Astrocyte-specific Drp1 loss induces astrocyte reactivity, disrupts cortical astrocyte organization, and dysregulates gap-junction protein Connexin 43 abundance.
The NHGRI-EBI GWAS Catalog: standards for reusability, sustainability and diversity
Authors: Cerezo Maria , Sollis Elliot , Ji Yue , Lewis Elizabeth , Abid Ala , Bircan Karatuğ Ozan , Hall Peggy , Hayhurst James , John Sajo , Mosaku Abayomi , Ramachandran Santhi , Foreman Amy , Ibrahim Arwa , McLaughlin James , Pendlington Zoë , Stefancsik Ray , Lambert Samuel A. , McMahon Aoife , Morales Joannella , Keane Thomas , Inouye Michael , Parkinson Helen , Harris Laura W. 
Published: October 2024

AbstractThe NHGRI-EBI GWAS Catalog serves as a vital resource for the genetic research community, providing access to the most comprehensive database of human GWAS results. Currently, it contains close to 7,000 publications for more than 15,000 traits, from which more than 625,000 lead associations have been curated. Additionally, 85,000 full genome-wide summary statistics datasets - containing association data for all variants in the analysis - are available for downstream analyses such as meta-analysis, fine-mapping, Mendelian randomisation or development of polygenic risk scores. As a centralised repository for GWAS results, the GWAS Catalog sets and implements standards for data submission and harmonisation, and encourages the use of consistent descriptors for traits, samples and methodologies. We share processes and vocabulary with the PGS Catalog, improving interoperability for a growing user group. Here, we describe the latest changes in data content, improvements in our user interface, and the implementation of the GWAS-SSF standard format for summary statistics. We address the challenges of handling the rapid increase in large-scale molecular quantitative trait GWAS and the need for sensitivity in the use of population and cohort descriptors while maintaining data interoperability and reusability.
Crystalline electric field excitations and their nonlinear splitting under magnetic fields in YbOCl
Authors: Cai Yanzhen , Ren Wei , Dai Xijing , Kang Jing , Zhuo Weizhen , Xie Mingtai , Zhang Anmin , Ji Jianting , Jin Feng , Zhang Zheng , Zhang Qingming 
Published: October 2024

Recently reported van der Waals layered honeycomb rare-earth chalcohalides REChX (RE = rare earth, Ch = chalcogen, and X = halogen) are considered to be promising Kitaev spin liquid (KSL) candidates. The high-quality single crystals of YbOCl, a representative member of the family with an effective spin of 1/2, are available now. The crystalline electric field (CEF) excitations in a rare-earth spin system are fundamentally important for understanding both finite-temperature and ground-state magnetism but remain unexplored in YbOCl so far. In this paper, we conduct a comprehensive Raman scattering study to unambiguously identify the CEF excitations in YbOCl and determine the CEF parameters and wave functions. Our Raman experiments further reveal the anomalous nonlinear CEF splitting under magnetic fields. We have grown single crystals of YbOCl, the nonmagnetic LuOCl, and the diluted magnetic Lu0.86Yb0.14OCl to make a completely comparative investigation. Polarized Raman spectra on the samples at 1.8 K allow us to clearly assign all the Raman-active phonon modes and explicitly identify the CEF excitations in YbOCl. The CEF excitations are further examined using temperature-dependent Raman measurements and careful symmetry analysis based on Raman tensors related to CEF excitations. By applying the CEF Hamiltonian to the experimentally determined CEF excitations, we extract the CEF parameters and eventually determine the CEF wave functions. The study experimentally pins down the CEF excitations in the Kitaev compound YbOCl and sets a foundation for understanding its finite-temperature magnetism and exploring the possible nontrivial spin ground state.

Published by the American Physical Society
2024
How does blockchain-based food traceability system drive consumers’ repurchase and word-of-mouth intentions toward organic food: a curvilinear role of producer-retailer (in)congruence
Authors: Duong Cong Doanh , Nguyen Thanh Hieu , Ngo Thi Viet Nga , Tran Quang Yen , Nguyen Minh Hoa , Pham Thi Thu Phuong 
Published: October 2024

PurposeThis research applies the stimulus-organism-behavior-consequence framework to explore how blockchain-enabled traceability influences trust in organic food producers and retailers, which impacts consumers’ purchase behaviors and subsequent outcomes.Design/methodology/approachUsing a purposive sample of 5,326 Vietnamese consumers, multiple linear and polynomial regression with response surface analysis were employed to examine the hypotheses.FindingsBlockchain-enabled traceability significantly enhances trust in both producers and retailers, which congruently and incongruently influences organic food purchase behaviors. This behavior also drives consumers’ word-of-mouth and repurchase intentions. Serial mediation analysis confirms blockchain’s impact through trust and purchase behaviors.Research limitations/implicationsStakeholders should adopt blockchain to boost transparency and trust, which increases consumer engagement. Policymakers can support this transition through regulations and incentives to enhance food security and sustainability.Originality/valueThis study expands on blockchain research by applying the stimulus-organism-behavior-consequence framework in the organic food supply chain, showing how blockchain-enhanced trust synergistically affects consumers’ purchase behaviors, word-of-mouth and repurchase intentions.