bluuebunny/crossref_metadata_2025_split huggingface dataset:
The GABAA receptor modulator zolpidem augments hippocampal-prefrontal coupling during non-REM sleep
Authors: Kersanté Flavie , Purple Ross J. , Jones Matthew W. 
Published: June 2022

AbstractBenzodiazepines and ‘Z-drugs’ (including zolpidem and zopiclone) are GABAA receptor (GABAAR) positive modulators commonly prescribed as hypnotics to treat insomnia and/or anxiety. However, alongside sedation, augmenting GABAAR function may also alter coordinated neuronal activity during sleep, thereby influencing sleep-dependent processes including memory consolidation. We used simultaneous recordings of neural population activity from the medial prelimbic cortex (PrL) and CA1 of the dorsal hippocampus (dCA1) of naturally sleeping rats to detail the effects of zolpidem on network activity during the cardinal oscillations of non-REM sleep. For comparison, we also characterized the effects of diazepam and 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol (THIP/gaboxadol), which acts predominantly at extra-synaptic GABAARs. Zolpidem and THIP significantly increased the amplitudes of slow-waves, which were attenuated by diazepam. Zolpidem increased hippocampal ripple density whereas diazepam decreased both ripple density and intrinsic frequency. While none of the drugs affected thalamocortical spindles in isolation, zolpidem augmented the temporal coordination between slow-waves and spindles. At the cellular level, analyses of spiking activity from 523 PrL and 579 dCA1 neurons revealed that zolpidem significantly enhanced synchronized pauses in cortical firing during slow-wave down states, while increasing correlated activity within and between dCA1 and PrL populations. Of the drugs compared here, zolpidem was unique in augmenting coordinated activity within and between hippocampus and neocortex during non-REM sleep. Zolpidem’s enhancement of hippocampal-prefrontal coupling may reflect the cellular basis of its potential to modulate offline memory processing.
The adrenal steroid profile in adolescent depression: a valuable bio-readout?
Authors: Hirtz Raphael , Libuda Lars , Hinney Anke , Föcker Manuel , Bühlmeier Judith , Holterhus Paul-Martin , Kulle Alexandra , Kiewert Cordula , Hauffa Berthold P. , Hebebrand Johannes , Grasemann Corinna 
Published: June 2022

AbstractThere is preliminary evidence that adrenal steroids other than cortisol may be valuable biomarkers for major depressive disorder (MDD). So far, studies have been conducted in adults only, and conclusions are limited, mainly due to small sample sizes. Therefore, the present study assessed whether adrenal steroids serve as biomarkers for adolescent MDD. In 261 depressed adolescents (170 females) treated at a single psychiatric hospital, serum adrenal steroids (progesterone, 17-hydroxyprogesterone, 21-deoxycortisol, 11-deoxycortisol, cortisol, cortisone, deoxycorticosterone, corticosterone) were determined by liquid chromatography-tandem mass spectrometry. Findings were compared to that of an age- and sex-matched reference cohort (N = 255) by nonparametric analysis of variance. Nonparametric receiver operating characteristics (ROC) analyses were conducted to evaluate the diagnostic performance of single steroids and steroid ratios to classify depression status. Sensitivity analyses considered important confounders of adrenal functioning, and ROC results were verified by cross-validation. Compared to the reference cohort, levels of deoxycorticosterone and 21-deoxycortisol were decreased (P < 0.001). All other glucocorticoid- and mineralocorticoid-related steroids were increased (P < 0.001). The corticosterone to deoxycorticosterone ratio evidenced excellent classification characteristics, especially in females (AUC: 0.957; sensitivity: 0.902; specificity: 0.891). The adrenal steroid metabolome qualifies as a bio-readout reflecting adolescent MDD by a distinct steroid pattern that indicates dysfunction of the hypothalamus–pituitary–adrenal axis. Moreover, the corticosterone to deoxycorticosterone ratio may prospectively qualify to contribute to precision medicine in psychiatry by identifying those patients who might benefit from antiglucocorticoid treatment or those at risk for recurrence when adrenal dysfunction has not resolved.
An mTOR and DNA-PK dual inhibitor CC-115 hinders non-small cell lung cancer cell growth
Authors: Chen Fagui , Zhao Huasi , Li Chenhui , Li Ping , Zhang Qichuan 
Published: June 2022

AbstractMolecularly-targeted agents are still urgently needed for better non-small cell lung cancer (NSCLC) therapy. CC-115 is a potent DNA-dependent protein kinase (DNA-PK) and mammalian target of rapamycin (mTOR) dual blocker. We evaluated its activity in different human NSCLC cells. In various primary human NSCLC cells and A549 cells, CC-115 potently inhibited viability, cell proliferation, cell cycle progression, and hindered cell migration/invasion. Apoptosis was provoked in CC-115-stimulated NSCLC cells. The dual inhibitor, however, was unable to induce significant cytotoxic and pro-apoptotic activity in the lung epithelial cells. In primary NSCLC cells, CC-115 blocked activation of mTORC1/2 and DNA-PK. Yet, CC-115-induced primary NSCLC cell death was more potent than combined inhibition of DNA-PK plus mTOR. Further studies found that CC-115 provoked robust oxidative injury in primary NSCLC cells, which appeared independent of mTOR-DNA-PK dual blockage. In vivo studies showed that CC-115 oral administration in nude mice remarkably suppressed primary NSCLC cell xenograft growth. In CC-115-treated NSCLC xenograft tissues, mTOR-DNA-PK dual inhibition and oxidative injury were detected. Together, CC-115 potently inhibits NSCLC cell growth.
Chromosome-level and haplotype-resolved genome provides insight into the tetraploid hybrid origin of patchouli
Authors: Shen Yanting , Li Wanying , Zeng Ying , Li Zhipeng , Chen Yiqiong , Zhang Jixiang , Zhao Hong , Feng Lingfang , Ma Dongming , Mo Xiaolu , Ouyang Puyue , Huang Lili , Wang Zheng , Jiao Yuannian , Wang Hong-bin 
Published: June 2022

AbstractPatchouli (Pogostemon cablin (Blanco) Benth.), a member of the Lamiaceae family, is an important aromatic plant that has been widely used in medicine and perfumery. Here, we report a 1.94 Gb chromosome-scale assembly of the patchouli genome (contig N50 = 7.97 Mb). The gene annotation reveals that tandem duplication of sesquiterpene biosynthetic genes may be a major contributor to the biosynthesis of patchouli bioactivity components. We further phase the genome into two distinct subgenomes (A and B), and identify a chromosome substitution event that have occurred between them. Further investigations show that a burst of universal LTR-RTs in the A subgenome lead to the divergence between two subgenomes. However, no significant subgenome dominance is detected. Finally, we track the evolutionary scenario of patchouli including whole genome tetraploidization, subgenome divergency, hybridization, and chromosome substitution, which are the key forces to determine the complexity of patchouli genome. Our work sheds light on the evolutionary history of patchouli and offers unprecedented genomic resources for fundamental patchouli research and elite germplasm development.
Marine siliceous ecosystem decline led to sustained anomalous Early Triassic warmth
Authors: Isson Terry T. , Zhang Shuang , Lau Kimberly V. , Rauzi Sofia , Tosca Nicholas J. , Penman Donald E. , Planavsky Noah J. 
Published: June 2022

AbstractIn the wake of rapid CO2release tied to the emplacement of the Siberian Traps, elevated temperatures were maintained for over five million years during the end-Permian biotic crisis. This protracted recovery defies our current understanding of climate regulation via the silicate weathering feedback, and hints at a fundamentally altered carbon and silica cycle. Here, we propose that the development of widespread marine anoxia and Si-rich conditions, linked to the collapse of the biological silica factory, warming, and increased weathering, was capable of trapping Earth’s system within a hyperthermal by enhancing ocean-atmosphere CO2recycling via authigenic clay formation. While solid-Earth degassing may have acted as a trigger, subsequent biotic feedbacks likely exacerbated and prolonged the environmental crisis. This refined view of the carbon-silica cycle highlights that the ecological success of siliceous organisms exerts a potentially significant influence on Earth’s climate regime.
A randomized placebo-controlled clinical trial for pharmacological activation of BCAA catabolism in patients with type 2 diabetes
Authors: Vanweert Froukje , Neinast Michael , Tapia Edmundo Erazo , van de Weijer Tineke , Hoeks Joris , Schrauwen-Hinderling Vera B. , Blair Megan C. , Bornstein Marc R. , Hesselink Matthijs K. C. , Schrauwen Patrick , Arany Zoltan , Phielix Esther 
Published: June 2022

AbstractElevations in plasma branched-chain amino acid (BCAA) levels associate with insulin resistance and type 2 diabetes (T2D). Pre-clinical models suggest that lowering BCAA levels improve glucose tolerance, but data in humans are lacking. Here, we used sodium phenylbutyrate (NaPB), an accelerator of BCAA catabolism, as tool to lower plasma BCAA levels in patients with T2D, and evaluate its effect on metabolic health. This trial (NetherlandsTrialRegister: NTR7426) had a randomized, placebo-controlled, double-blind cross-over design and was performed in the Maastricht University Medical Center (MUMC+), the Netherlands, between February 2019 and February 2020. Patients were eligible for the trial if they were 40–75years, BMI of 25–38 kg/m², relatively well-controlled T2D (HbA1C < 8.5%) and treated with oral glucose-lowering medication. Eighteen participants were randomly assigned to receive either NaPB 4.8 g/m²/day and placebo for 2 weeks via controlled randomization and sixteen participants completed the study. The primary outcome was peripheral insulin sensitivity. Secondary outcomes were ex vivo muscle mitochondrial oxidative capacity, substrate oxidation and ectopic fat accumulation. Fasting blood samples were collected to determine levels of BCAA, their catabolic intermediates, insulin, triglycerides, free fatty acids (FFA) and glucose. NaPB led to a robust 27% improvement in peripheral insulin sensitivity compared to placebo (ΔRd:13.2 ± 1.8 vs. 9.6 ± 1.8 µmol/kg/min, p = 0.02). This was paralleled by an improvement in pyruvate-driven muscle mitochondrial oxidative capacity and whole-body insulin-stimulated carbohydrate oxidation, and a reduction in plasma BCAA and glucose levels. No effects were observed on levels of insulin, triglycerides and FFA, neither did fat accumulation in muscle and liver change. No adverse events were reported. These data establish the proof-of-concept in humans that modulating the BCAA oxidative pathway may represent a potential treatment strategy for patients with T2D.
Complex regulation of Gephyrin splicing is a determinant of inhibitory postsynaptic diversity
Authors: Dos Reis Raphaël , Kornobis Etienne , Pereira Alyssa , Tores Frederic , Carrasco Judit , Gautier Candice , Jahannault-Talignani Céline , Nitschké Patrick , Muchardt Christian , Schlosser Andreas , Maric Hans Michael , Ango Fabrice , Allemand Eric 
Published: June 2022

AbstractGephyrin (GPHN) regulates the clustering of postsynaptic components at inhibitory synapses and is involved in pathophysiology of neuropsychiatric disorders. Here, we uncover an extensive diversity of GPHN transcripts that are tightly controlled by splicing during mouse and human brain development. Proteomic analysis reveals at least a hundred isoforms of GPHN incorporated at inhibitory Glycine and gamma-aminobutyric acid A receptors containing synapses. They exhibit different localization and postsynaptic clustering properties, and altering the expression level of one isoform is sufficient to affect the number, size, and density of inhibitory synapses in cerebellar Purkinje cells. Furthermore, we discovered that splicing defects reported in neuropsychiatric disorders are carried by multiple alternative GPHN transcripts, demonstrating the need for a thorough analysis of the GPHN transcriptome in patients. Overall, we show that alternative splicing of GPHN is an important genetic variation to consider in neurological diseases and a determinant of the diversity of postsynaptic inhibitory synapses.
Peptide fusion improves prime editing efficiency
Authors: Velimirovic Minja , Zanetti Larissa C. , Shen Max W. , Fife James D. , Lin Lin , Cha Minsun , Akinci Ersin , Barnum Danielle , Yu Tian , Sherwood Richard I. 
Published: June 2022

AbstractPrime editing enables search-and-replace genome editing but is limited by low editing efficiency. We present a high-throughput approach, the Peptide Self-Editing sequencing assay (PepSEq), to measure how fusion of 12,000 85-amino acid peptides influences prime editing efficiency. We show that peptide fusion can enhance prime editing, prime-enhancing peptides combine productively, and a top dual peptide-prime editor increases prime editing significantly in multiple cell lines across dozens of target sites. Top prime-enhancing peptides function by increasing translation efficiency and serve as broadly useful tools to improve prime editing efficiency.
A spin-crossover framework endowed with pore-adjustable behavior by slow structural dynamics
Authors: Xue Jin-Peng , Hu Yang , Zhao Bo , Liu Zhi-Kun , Xie Jing , Yao Zi-Shuo , Tao Jun 
Published: June 2022

AbstractHost-guest interactions play critical roles in achieving switchable structures and functionalities in porous materials, but design and control remain challenging. Here, we report a two-dimensional porous magnetic compound, [FeII(prentrz)2PdII(CN)4] (prentrz = (1E,2E)−3-phenyl-N-(4H-1,2,4-triazol-4-yl)prop-2-en-1-imine), which exhibits an atypical pore transformation that directly entangles with a spin state transition in response to water adsorption. In this material, the adsorption-induced, non-uniform pedal motion of the axial prentrz ligands and the crumpling/unfolding of the layer structure actuate a reversible narrow quasi-discrete pore (nqp) to large channel-type pore (lcp) change that leads to a pore rearrangement associated with simultaneous pore opening and closing. The unusual pore transformation results in programmable adsorption in which the lcp structure type must be achieved first by the long-time exposure of the nqp structure type in a steam-saturated atmosphere to accomplish the gate-opening adsorption. The structural transformation is accompanied by a variation in the spin-crossover (SCO) property of FeII, i.e., two-step SCO with a large plateau for the lcp phase and two-step SCO with no plateau for the nqp phase. The unusual adsorption-induced pore rearrangement and the related SCO property offer a way to design and control the pore structure and physical properties of dynamic frameworks.
X-ray computed microtomography datasets for osteogenic nanofibrous coated titanium implants
Authors: Das Siddhartha , Dholam Kanchan , Gurav Sandeep , Bendale Kiran , Ingle Arvind , Mohanty Bhabani , Chaudhari Pradip , Bellare Jayesh R. 
Published: June 2022

AbstractSurface modifications of titanium implant influences the quality of osseointegration and are associated with favourable treatment prognosis in orthopaedic and cranio-maxillofacial cases. Hence, unlike previous works, the peri-implant region details of our novel osteogenic nanofibrous coated implants placed in rabbits (n = 6 + 1) were recorded over a 12-week period using a micro-CT imaging system. In this unique contribution, we have created a computed tomography (CT) library of rabbit’s tibiae anatomy with osteogenic nanofibrous coated/uncoated implants and are introductory useful assets for investigating the correlation between osteogenic nanofibers coated implants and its effect on improved osseointegration. Apart from using this CT dataset to conduct serial 2D image studies, three-dimensional (3D) reconstructions, assessing segmentation algorithms and developing adequate image quantitation tools, there may be positive applications of these in comparative investigations of similar or related preclinical as well as future clinical studies, further design planning, development etc. required for evolution of implants beyond the present state of art.
REFLACX, a dataset of reports and eye-tracking data for localization of abnormalities in chest x-rays
Authors: Bigolin Lanfredi Ricardo , Zhang Mingyuan , Auffermann William F. , Chan Jessica , Duong Phuong-Anh T. , Srikumar Vivek , Drew Trafton , Schroeder Joyce D. , Tasdizen Tolga 
Published: June 2022

AbstractDeep learning has shown recent success in classifying anomalies in chest x-rays, but datasets are still small compared to natural image datasets. Supervision of abnormality localization has been shown to improve trained models, partially compensating for dataset sizes. However, explicitly labeling these anomalies requires an expert and is very time-consuming. We propose a potentially scalable method for collecting implicit localization data using an eye tracker to capture gaze locations and a microphone to capture a dictation of a report, imitating the setup of a reading room. The resulting REFLACX (Reports and Eye-Tracking Data for Localization of Abnormalities in Chest X-rays) dataset was labeled across five radiologists and contains 3,032 synchronized sets of eye-tracking data and timestamped report transcriptions for 2,616 chest x-rays from the MIMIC-CXR dataset. We also provide auxiliary annotations, including bounding boxes around lungs and heart and validation labels consisting of ellipses localizing abnormalities and image-level labels. Furthermore, a small subset of the data contains readings from all radiologists, allowing for the calculation of inter-rater scores.
Gridded maps of wetlands dynamics over mid-low latitudes for 1980–2020 based on TOPMODEL
Authors: Xi Yi , Peng Shushi , Ducharne Agnès , Ciais Philippe , Gumbricht Thomas , Jimenez Carlos , Poulter Benjamin , Prigent Catherine , Qiu Chunjing , Saunois Marielle , Zhang Zhen 
Published: June 2022

AbstractDynamics of global wetlands are closely linked to biodiversity conservation, hydrology, and greenhouse gas emissions. However, long-term time series of global wetland products are still lacking. Using a diagnostic model based on the TOPography-based hydrological MODEL (TOPMODEL), this study produced an ensemble of 28 gridded maps of monthly global/regional wetland extents (with more reliable estimates at mid-low latitudes) for 1980–2020 at 0.25° × 0.25° spatial resolution, calibrated with a combination of four observation-based wetland data and seven gridded soil moisture reanalysis datasets. The gridded dynamic maps of wetlands capture the spatial distributions, seasonal cycles, and interannual variabilities of observed wetland extent well, and also show a good agreement with independent satellite-based terrestrial water storage estimates over wetland areas. The long temporal coverage extending beyond the era of satellite datasets, the global coverage, and the opportunity to provide real-time updates from ongoing soil moisture data make these products helpful for various applications such as analyzing the wetland-related methane emission.
Investigating the turbulent dynamics of small-scale surface fires
Authors: Desai Ajinkya , Goodrick Scott , Banerjee Tirtha 
Published: June 2022

AbstractHigh frequency (30 Hz) two-dimensional particle image velocimetry data recorded during a field experiment exploring fire spread from point ignition in hand-spread pine needles under calm ambient wind conditions are analysed in this study. In the initial stages, as the flame spreads approximately radially away from the ignition point in the absence of a preferred wind-forcing direction, it entrains cooler ambient air into the warmer fire core, thereby experiencing a dynamic pressure resistance. The fire-front, comprising a flame that is tilted inward, is surrounded by a region of downdraft. Coherent structures describe the initial shape of the fire-front and its response to local wind shifts while also revealing possible fire-spread mechanisms. Vortex tubes originating outside the fire spiral inward and get stretched thinner at the fire-front leading to higher vorticity there. These tubes comprise circulation structures that induce a radially outward velocity close to the fuel bed, which pushes hot gases outward, thereby causing the fire to spread. Moreover, these circulation structures confirm the presence of counter-rotating vortex pairs that are known to be a key mechanism for fire spread. The axis of the vortex tubes changes its orientation alternately towards and away from the surface of the fuel bed, causing the vortex tubes to be kinked. The strong updraft observed at the location of the fire-front could potentially advect and tilt the kinked vortex tube vertically upward leading to fire-whirl formation. As the fire evolves, its perimeter disintegrates in response to flow instabilities to form smaller fire “pockets”. These pockets are confined to certain points in the flow field that remain relatively fixed for a while and resemble the behavior of a chaotic system in the vicinity of an attractor. Increased magnitudes of the turbulent fluxes of horizontal momentum, computed at certain such fixed points along the fire-front, are symptomatic of irregular fire bursts and help contextualize the fire spread. Most importantly, the time-varying transport terms of the turbulent kinetic energy budget equation computed at adjacent fixed points indicate that local fires along the fire-front primarily interact via the horizontal turbulent transport term.
Optimizing plant density and balancing NPK inputs in combination with innovative fertilizer product for sustainable maize production in North China Plain
Authors: Feyissa Tesema , Zhao Shuaixiang , Ma Hailong , Duan Zhiping , Zhang Weifeng 
Published: June 2022

AbstractExcessive NPK inputs but low grain yield and high environmental impact are common issues in maize production in North China Plain (NCP). The objective of our study was to test whether a combined strategy of optimizing plant density, balancing NPK input, and innovating one-time fertilizer products could achieve a more sustainable maize production in NCP. Thus, a field experiment was conducted at Luanna County NCP with the treatments of unfertilized control (CK), farmer practice (FP, conventional plant density and NPK input), conventional one-time urea-based coated fertilizer (CF, optimized plant density and NPK input), and five newly designed innovative one-time NPK fertilizers of ammonium sulphate and urea synergy (IF, optimized plant density and NPK input), innovative fertilizer with various additives of urea inhibitors (IF + UI), double inhibitors (IF + DI), micro-organisms (IF + MI), and trace elements (IF + TE). The grain yield, N sustainability indicators (N use efficiency NUE, partial factor productivity of N PFPN, and N surplus), and cost-benefits analysis were examined over the maize growing season of 2020. Results had shown that on average the five innovative fertilizers (IF, IF + UI, IF + DI, IF + MI, and IF + TE) and CF that had optimized plant density and NPK input achieved 13.5%, 98.6%, 105.9%, 37.4% higher yield, PFPN, NUE, net-benefits as well as 207.1% lower N surplus compared with FP respectively. Notably, the innovative fertilizer with various effective additives (IF + UI, IF + DI, IF + MI, and IF + TE) which can be commonly found in the fertilizer market hadn’t resulted in a significant improvement in yield and NUE rather a greater cost and lower net benefits in comparison to IF. In summary, our study highlighted the effectiveness of the combined strategy of optimized plant density, balancing NPK input, and innovative NPK fertiliser on sustainable maize production in NCP, however, the innovative fertilisers with effective additives should be properly selected for better economic benefits.