bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oligodendrocyte‐derived exosomes‐containing SIRT2 ameliorates depressive‐like behaviors and restores hippocampal neurogenesis and synaptic plasticity via the AKT/GSK‐3β pathway in depressed mice
Authors: Zhang Honghan , Xie Xin‐hui , Xu Shu‐xian , Wang Chao , Sun Siqi , Song Xinhua , Li Ruiling , Li Ningyuan , Feng Yuqi , Duan Hao , Li Di , Liu Zhongchun 
Published: March 2024

AbstractAimsTo investigate the antidepressant role of oligodendrocyte‐derived exosomes (ODEXs)‐containing sirtuin 2 (SIRT2) and the underlying mechanism both in vivo and in vitro.MethodsOligodendrocyte‐derived exosomes isolated from mouse serum were administered to mice with chronic unpredictable mild stress (CUMS)‐induced depression via the tail vein. The antidepressant effects of ODEXs were assessed through behavioral tests and quantification of alterations in hippocampal neuroplasticity. The role of SIRT2 was confirmed using the selective inhibitor AK‐7. Neural stem/progenitor cells (NSPCs) were used to further validate the impact of overexpressed SIRT2 and ODEXs on neurogenesis and synapse formation in vitro.ResultsOligodendrocyte‐derived exosome treatment alleviated depressive‐like behaviors and restored neurogenesis and synaptic plasticity in CUMS mice. SIRT2 was enriched in ODEXs, and blocking SIRT2 with AK‐7 reversed the antidepressant effects of ODEXs. SIRT2 overexpression was sufficient to enhance neurogenesis and synaptic protein expression. Mechanistically, ODEXs mediated transcellular delivery of SIRT2, targeting AKT deacetylation and AKT/GSK‐3β signaling to regulate neuroplasticity.ConclusionThis study establishes how ODEXs improve depressive‐like behaviors and hippocampal neuroplasticity and might provide a promising therapeutic approach for depression.
Liraglutide 3.0 mg in the treatment of adults with obesity and prediabetes using real‐world UK data: A clinical evaluation of a multi‐ethnic population
Authors: Dobbie Laurence J. , Coelho Claudia , Mgaieth Farah , Chauhan Keisha , Campbell Scott , Shuriye Sumaya , Hollington Joanna , Appleton Sarah , Sen Gupta Piya , Duncan Alastair , McGowan Barbara 
Published: March 2024

SummaryUK guidelines recommend liraglutide 3.0 mg in adults treated within specialist weight management services with BMI ≥35 kg/m2, prediabetes and high cardiovascular disease risk. We aimed to clinically evaluate liraglutide 3.0 mg in specialist weight management services. We evaluated liraglutide 3.0 mg in weight management services at Guys and St Thomas' NHS Foundation Trust. Objective body weight (BW) was measured at baseline and 4 months, allowing classification as ‘responders’ (≥5% BW reduction) and ‘non‐responders’ (<5% BW reduction). One hundred and twenty‐one patients were evaluated. At 4 months, 76.0% attended follow‐up (82.6% responders, 17.4% non‐responders); BW (−8.6 kg, 95%CI:‐9.8, −7.4 kg), BMI (−3.2 kg/m2, 95%CI: −3.6, −2.8) and %‐BW (−6.6%, IQR: −8.8%, −5.2%) significantly reduced. In responders, HbA1c reduced by −5.0 mmol/mol (IQR: −7.0. −4.0 mmol/mol). In responders BW continued to reduce up to 12 months (4 m: −10.2 kg, p < .0001; 6 m: −15.6 kg, p < .0001; 9 m: −16.5 kg, p < .0001; 12 m: −16.7 kg, p < .01). Those of Black African and Caribbean ethnicity experienced less BW loss than those of white ethnicity (4.12 kg, p = .017) and had a greater attrition rate. In adults with obesity and prediabetes who are treated within specialist weight management services, liraglutide 3.0 mg reduces BW and HbA1c. Those of Black African and Caribbean ethnicity experienced less BW reduction and greater attrition at 4 months. Further evaluation of the ethnic differences in response to obesity pharmacotherapy is required.
Aberrant thalamocortical connectivity and shifts between the resting state and task state in patients with schizophrenia
Authors: Takai Yoshifumi , Tamura Shunsuke , Hoaki Nobuhiko , Kitajima Kazutoshi , Nakamura Itta , Hirano Shogo , Ueno Takefumi , Nakao Tomohiro , Onitsuka Toshiaki , Hirano Yoji 
Published: March 2024

AbstractProminent pathological hypotheses for schizophrenia include auditory processing deficits and dysconnectivity within cerebral networks. However, most neuroimaging studies have focused on impairments in either resting‐state or task‐related functional connectivity in patients with schizophrenia. The aims of our study were to examine (1) blood oxygen level‐dependent (BOLD) signals during auditory steady‐state response (ASSR) tasks, (2) functional connectivity during the resting‐state and ASSR tasks and (3) state shifts between the resting‐state and ASSR tasks in patients with schizophrenia. To reduce the functional consequences of scanner noise, we employed resting‐state and sparse sampling auditory fMRI paradigms in 25 schizophrenia patients and 25 healthy controls. Auditory stimuli were binaural click trains at frequencies of 20, 30, 40 and 80 Hz. Based on the detected ASSR‐evoked BOLD signals, we examined the functional connectivity between the thalamus and bilateral auditory cortex during both the resting state and ASSR task state, as well as their alterations. The schizophrenia group exhibited significantly diminished BOLD signals in the bilateral auditory cortex and thalamus during the 80 Hz ASSR task (corrected p < 0.05). We observed a significant inverse relationship between the resting state and ASSR task state in altered functional connectivity within the thalamo‐auditory network in schizophrenia patients. Specifically, our findings demonstrated stronger functional connectivity in the resting state (p < 0.004) and reduced functional connectivity during the ASSR task (p = 0.048), which was mediated by abnormal state shifts, within the schizophrenia group. These results highlight the presence of abnormal thalamocortical connectivity associated with deficits in the shift between resting and task states in patients with schizophrenia.
Conflicts and opportunities for commercial tree plantation expansion and biodiversity restoration across Brazil
Authors: Cerullo Gianluca , Worthington Thomas , Brancalion Pedro , Brandão Joyce , d'Albertas Francisco , Eyres Alison , Swinfield Thomas , Edwards David , Balmford Andrew 
Published: March 2024

AbstractSubstantial global restoration commitments are occurring alongside a rapid expansion in land‐hungry tropical commodities, including to supply increasing demand for wood products. Future commercial tree plantations may deliver high timber yields, shrinking the footprint of production forestry, but there is an as‐yet unquantified risk that plantations may expand into priority restoration areas, with marked environmental costs. Focusing on Brazil—a country of exceptional restoration importance and one of the largest tropical timber producers—we use random forest models and information on the economic, social, and spatial drivers of historic commercial tree plantation expansion to estimate and map the probability of future monoculture tree plantation expansion between 2020 and 2030. We then evaluate potential plantation‐restoration conflicts and opportunities at national and biome‐scales and under different future production and restoration pathways. Our simulations show that of 2.8 Mha of future plantation expansion (equivalent to plantation expansion 2010–2020), ~78,000 ha (3%) is forecast to occur in the top 1% of restoration priority areas for terrestrial vertebrates, with ~547,500 ha (20%) and ~1,300,000 ha (46%) in the top 10% and 30% of priority areas, respectively. Just ~459,000 ha (16%) of expansion is forecast within low‐restoration areas (bottom 30% restoration priorities), and the first 1 Mha of plantation expansion is likely to have disproportionate impacts, with potential restoration‐plantation overlap starkest in the Atlantic Forest but prominent in the Pampas and Cerrado as well. Our findings suggest that robust, coherent land‐use policies must be deployed to ensure that significant trade‐offs between restoration and production objectives are navigated, and that commodity expansion does not undermine the most tractable conservation gains under emerging global restoration agendas. They also highlight the potentially significant role an engaged forestry sector could play in improving biodiversity outcomes in restoration projects in Brazil, and presumably elsewhere.
Conservation planning for retention, not just protection
Authors: Negret Pablo Jose , Venegas Ruben , Sonter Laura J. , Possingham Hugh P. , Maron Martine 
Published: March 2024

AbstractMost protected area (PA) planning aims to improve biota representation within the PA system, but this does not necessarily achieve the best outcomes for biota retention across regions when we also consider habitat loss in areas outside the PA system. Here, we assess the implications that different PA expansion strategies can have on the retention of species habitat across an entire region. Using retention of forest habitat for Colombia's 550 forest‐dependent bird species as our outcome variable, we found that when a minimum of 30% of each species' habitat was included in the PA system, a pattern of PA expansion targeting areas at highest deforestation risk (risk‐prevention) led to the retention, on average, of 7.2% more forest habitat per species by 2050 than did a pattern that targeted areas at lowest risk (risk‐avoidance). The risk‐prevention approach cost more per km2 of land conserved, but it was more cost‐effective in retaining habitat in the landscape (50%–69% lower cost per km2 of avoided deforestation). To have the same effectiveness preventing habitat loss in Colombia, the risk‐avoidance approach would require more than twice as much protected area, costing three times more in the process. Protected area expansion should focus on the contributions of PAs to outcomes not only within PA systems themselves, but across entire regions.
Impact of artificial intelligence arrhythmia mapping on time to first ablation, procedure duration, and fluoroscopy use
Authors: Fox Sutton R. , Toomu Avinash , Gu Kelly , Kang Jessica , Sung Kevin , Han Frederick T. , Hoffmayer Kurt S. , Hsu Jonathan C. , Raissi Farshad , Feld Gregory K. , McCulloch Andrew D. , Ho Gordon , Krummen David E. 
Published: March 2024

AbstractIntroductionArtificial intelligence (AI) ECG arrhythmia mapping provides arrhythmia source localization using 12‐lead ECG data; whether this information impacts procedural efficiency is unknown. We performed a retrospective, case‐control study to evaluate the hypothesis that AI ECG mapping may reduce time to ablation, procedural duration, and fluoroscopy.Materials and MethodsCases in which system output was used were retrospectively enrolled according to IRB‐approved protocols at each site. Matched control cases were enrolled in reverse chronological order beginning on the last day for which the technology was unavailable. Controls were matched based upon physician, institution, arrhythmia, and a predetermined complexity rating. Procedural metrics, fluoroscopy data, and clinical outcomes were assessed from time‐stamped medical records.ResultsThe study group consisted of 28 patients (age 65 ± 11 years, 46% female, left atrial dimension 4.1 ± 0.9 cm, LVEF 50 ± 18%) and was similar to 28 controls. The most common arrhythmia types were atrial fibrillation (n = 10), premature ventricular complexes (n = 8), and ventricular tachycardia (n = 6). Use of the system was associated with a 19.0% reduction in time to ablation (133 ± 48 vs. 165 ± 49 min, p = 0.02), a 22.6% reduction in procedure duration (233 ± 51 vs. 301 ± 83 min, p < 0.001), and a 43.7% reduction in fluoroscopy (18.7 ± 13.3 vs. 33.2 ± 18.0 min, p < 0.001) versus controls. At 6 months follow‐up, arrhythmia‐free survival was 73.5% in the study group and 63.3% in the control group (p = 0.56).ConclusionUse of forward‐solution AI ECG mapping is associated with reductions in time to first ablation, procedure duration, and fluoroscopy without an adverse impact on procedure outcomes or complications.
Molecular regulation of the key specialized metabolism pathways in medicinal plants
Authors: Shi Min , Zhang Siwei , Zheng Zizhen , Maoz Itay , Zhang Lei , Kai Guoyin 
Published: March 2024

ABSTRACTThe basis of modern pharmacology is the human ability to exploit the production of specialized metabolites from medical plants, for example, terpenoids, alkaloids, and phenolic acids. However, in most cases, the availability of these valuable compounds is limited by cellular or organelle barriers or spatio‐temporal accumulation patterns within different plant tissues. Transcription factors (TFs) regulate biosynthesis of these specialized metabolites by tightly controlling the expression of biosynthetic genes. Cutting‐edge technologies and/or combining multiple strategies and approaches have been applied to elucidate the role of TFs. In this review, we focus on recent progress in the transcription regulation mechanism of representative high‐value products and describe the transcriptional regulatory network, and future perspectives are discussed, which will help develop high‐yield plant resources.
Quantifying isotope parameters associated with carbonyl‐water oxygen exchange during sucrose translocation in tree phloem
Authors: Pan Yonghui , Li Fang , Lin Wen , Zhou Youping , Song Xin 
Published: March 2024

Summary

Stable oxygen isotope ratio of tree‐ring α‐cellulose (δ18Ocel) yields valuable information on many aspects of tree–climate interactions. However, our current understanding of the mechanistic controls on δ18Ocel is incomplete, with a knowledge gap existent regarding the fractionation effect characterizing carbonyl‐water oxygen exchange during sucrose translocation from leaf to phloem.

To address this insufficiency, we set up an experimental system integrating a vapor 18O‐labeling feature to manipulate leaf‐level isotopic signatures in tree saplings enclosed within whole‐canopy gas‐exchange cuvettes. We applied this experimental system to three different tree species to determine their respective relationships between 18O enrichment of sucrose in leaf lamina (Δ18Ol_suc) and petiole phloem (Δ18Ophl_suc) under environmentally/physiologically stable conditions.

Based on the determined Δ18Ophl_suc‐Δ18Ol_suc relationships, we estimated that on average, at least 25% of the oxygen atoms in sucrose undergo isotopic exchange with water along the leaf‐to‐phloem translocation path and that the biochemical fractionation factor accounting for such exchange is c. 34‰, markedly higher than the conventionally assumed value of 27‰.

Our study represents a significant step toward quantitative elucidation of the oxygen isotope dynamics during sucrose translocation in trees. This has important implications with respect to improving the δ18Ocel model and its related applications in paleoclimatic and ecophysiological contexts.
Nuclear imaging to visualize periodontal inflammation: Findings of a randomized controlled trial
Authors: Arefnia Behrouz , Horina Anja , Nazerani‐Zemann Tina , Seinost Gerald , Rieder Marcus , Wimmer Gernot 
Published: March 2024

AbstractObjectiveTo investigate non‐surgical periodontal therapy by 18F‐fluorodeoxyglucose (2‐[18F]FDG) uptake using positron emission tomography (PET) integrated with computed tomography (CT).SubjectsEighty‐five patients with peripheral artery disease and severe periodontitis—randomized into three groups receiving therapy with (PT1; n = 29) or without (PT2; n = 28) systemic antibiotics or no treatment (controls: n = 28)—underwent nuclear imaging at baseline and at 3 months.ResultsClinical inflammation (periodontal inflamed surface area; PISA) did not significantly differ across the groups at baseline (p = 0.395) but was significantly reduced at 3 months (p < 0.001), and significantly more so in the PT1/PT2 groups than in the control group (p < 0.001/=0.025) and in the PT1 than in the P2 group (p = 0.001). Radiotracer uptake was measured in both jaws using maximum and mean ‘standardized uptake values’ (SUVmax, SUVmean) and ‘target‐to‐background ratios’ (TBRmax, TBRmean). At 3 months, reductions were relatively small in absolute numbers and fell short of revealing correlations with PISA or significant differences across the groups. Still, they were very consistent in both treatment groups, whereas reductions were not consistently seen in the control group.Conclusions2‐[18F]FDG PET/CT scans did reflect the clinical effects of periodontal treatment very consistently but, for reasons yet to be clarified, less closely than expected.
Efficacy and safety of donepezil in patients with dementia with Lewy bodies: results from a 12‐week multicentre, randomised, double‐blind, and placebo‐controlled phase IV study
Authors: Mori Etsuro , Ikeda Manabu , Iseki Eizo , Katayama Sadao , Nagahama Yasuhiro , Ohdake Megumi , Takase Takao 
Published: March 2024

AbstractBackgroundDonepezil has been approved in Japan for the treatment of dementia with Lewy bodies (DLB) based on clinical trials showing its beneficial effects on cognitive impairment. This phase IV study evaluated the efficacy of donepezil by focusing on global clinical status during a 12‐week double‐blind phase.MethodsPatients with probable DLB were randomly assigned to the placebo (n = 79) or 10 mg donepezil (n = 81) groups. The primary endpoint was changes in global clinical status, assessed using the Clinician's Interview‐Based Impression of Change plus Caregiver Input (CIBIC‐plus). We also assessed four CIBIC‐plus domains (general condition, cognitive function, behaviour, and activities of daily living) and changes in cognitive impairment and behavioural and neuropsychiatric symptoms measured using the Mini‐Mental State Examination (MMSE) and the Neuropsychiatric Inventory (NPI), respectively.ResultsAlthough donepezil's superiority was not shown in the global clinical status, a significant favourable effect was detected in the cognitive domain (P = 0.006). MMSE scores improved in the donepezil group after adjustments in post hoc analysis (MMSE mean difference, 1.4 (95% confidence interval (CI), 0.42–2.30), P = 0.004). Improvements in NPIs were similar between the groups (NPI‐2: −0.2 (95% CI, −1.48 to 1.01), P = 0.710; NPI‐10: 0.1 (95% CI, −3.28 to 3.55), P = 0.937).ConclusionThe results support the observation that the efficacy of 10 mg donepezil in improving cognitive function is clinically meaningful in DLB patients. The evaluation of global clinical status might be affected by mild to moderate DLB patients enrolled in this study. No new safety concerns were detected.
‘A Voice Amidst Mine Ears’: Silent Angels on the Early Modern Stage
Authors: Rankin‐McCabe Caitlín 
Published: March 2024

AbstractUnlike the carts that crawled with angels in the medieval pageant plays, angels of the early modern stage were a rare breed. Eventually they disappeared from the stage altogether; they did not, however, disappear all at once in a puff of celestial smoke. This article reveals a pattern of suppression in the representation of angels on the English stage, ranging from Christopher Marlowe's Doctor Faustus in 1592 until 1645, three years after the closure of the theatres in England. This study examines plays that present angels as characters who contribute to the play's action and denouement; however, by noting plays that include allegorical and decorative angels too, it comprises the most comprehensive survey of angels within plays from the period to date. Angels do not appear in many plays performed at the commercial playhouses of Elizabethan and Jacobean England; but when they do, it becomes clear that early modern playwrights gradually developed more calculated ways of staging these controversial creatures. As stage angels assume more silent roles, but before angels leave the stage entirely, human characters begin to communicate with these celestial figures differently and encounters with angels become a far more intimate experience.
Safe Reinforcement Learning-Based Balance Control for Multi-Cylinder Hydraulic Press
Authors: Jia Chao , Song Zijian , Du Lifeng , Wang Hongkun 
Published: March 2024

Abstract
Considering the load uncertainty and unmodeled dynamics in multicylinder hydraulic systems, this paper proposes a balance control algorithm based on safe reinforcement learning to release the restrictions of classical model-based control methods that depend on fixed gain. In this paper, the hydraulic press is controlled by a trained agent that directly maps the system states to control commands in an end-to-end manner. By introducing an action modifier into the algorithm, the system states are kept within security constraints from the beginning of training, making safe exploration possible. Furthermore, a normalized exponential reward function has been proposed. Compared with a quadratic reward function, the precision is greatly improved under the same training steps. The experiment shows that our algorithm can achieve high precision and fast balance for multicylinder hydraulic presses while being highly robust. To the best of our knowledge, this research is the first to attempt the application of a reinforcement learning algorithm to multi-execution units of hydraulic systems.
Numerical Characterization of Prestall Disturbances in a Compressor Stage
Authors: de Almeida Victor Bicalho Civinelli , Tüzüner Ergin , Eck Mario , Peitsch Dieter 
Published: March 2024

Abstract
Compared to the subject of rotating stall, less attention has been given to prestall flow disturbances in turbomachinery. This is mostly due to the fact that these phenomena, often referred to as Rotating Instabilities, do not necessarily or distinctly occur in every compressor and usually last for a long period without posing serious threats to stable operation. The present study aims at numerically characterizing prestall disturbances in detail in a compressor stage in which they have been experimentally observed. Full-annulus computational fluid dynamics (CFD) computations employing a hybrid scale-resolving turbulence model are performed and compared against unsteady experimental data. Assessment of specific prestall disturbance metrics, including power spectral density, coherence, and circumferential mode distribution at the rotor clearance, shows that the numerical model is successful in reproducing the unsteady phenomena close to stall inception. Moreover, dynamic mode decomposition is employed to directly link each peak of the unique prestall disturbance spectral signature to spatial structures with a different circumferential order. This procedure is done for both 1D circumferential modes, based on flush-mounted pressure probes, and for 2D surfaces exposing the tip clearance dynamics. The high-resolution numerical model, supplemented with vortex identification criteria and data-driven decompositions, enhances the understanding of prestall disturbances and their associated coherent flow structures.