bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decoding the dual recognition mechanism of the glucocorticoid receptor for DNA and RNA: sequence versus shape
Authors: Hörberg Johanna , Reymer Anna 
Published: September 2023

AbstractTranscription factors (TFs) regulate eukaryotic transcription through selective DNA-binding, can also specifically interact with RNA, which may present another layer of transcriptional control. The mechanisms of the TFs-DNA recognition are often well-characterised, while the details of TFs-RNA complexation are less understood. Here we investigate the dual recognition mechanism of the glucocorticoid receptor (GR), which interacts with similar affinities with consensus DNA and diverse RNA hairpin motifs but discriminates against uniform dsRNA. Using atomic molecular dynamics simulations, we demonstrate that the GR binding to nucleic acids requires a wide and shallow groove pocket. The protein effectively moulds its binding site within DNA major groove, which enables base-specific interactions. Contrary, the GR binding has little effect on the grooves geometry of RNA systems, most notably in uniform dsRNA. Instead, a hairpin motif in RNA yields a wide and shallow major groove pocket, allowing the protein to anchor itself through nonspecific electrostatic contacts with RNA backbone. Addition of a bulge increases RNA hairpin flexibility, which leads to a greater number of GR-RNA contacts and, thus, higher affinity. Thus, the combination of structural motifs defines the GR-RNA selective binding: a recognition mechanism, which may be shared by other zinc finger TFs.
PET imaging of microglia using PBR28suv determines therapeutic efficacy of autologous bone marrow mononuclear cells therapy in traumatic brain injury
Authors: Bedi Supinder S. , Scott Michael C. , Skibber Max A. , Kumar Akshita , Caplan Henry W. , Xue Hasen , Sequeira David , Speer Alison L. , Cardenas Fanni , Gudenkauf Franciska , Uray Karen , Srivastava Amit K. , Prossin Alan R. , Cox Charles S. 
Published: September 2023

AbstractTraumatic brain injury (TBI) results in activated microglia. Activated microglia can be measured in vivo by using positron emission topography (PET) ligand peripheral benzodiazepine receptor standardized uptake values (PBR28suv). Cell based therapies have utilized autologous bone marrow mononuclear cells (BMMNCs) to attenuate activated microglia after TBI. This study aims to utilize in vivo PBR28suv to assess the efficacy of BMMNCs therapy after TBI. Seventy-two hours after CCI injury, BMMNCs were harvested from the tibia and injected via tail-vein at 74 h after injury at a concentration of 2 million cells per kilogram of body weight. There were three groups of rats: Sham, CCI-alone and CCI-BMMNCs (AUTO). One hundred twenty days after injury, rodents were imaged with PBR28 and their cognitive behavior assessed utilizing the Morris Water Maze. Subsequent ex vivo analysis included brain volume and immunohistochemistry. BMMNCs therapy attenuated PBR28suv in comparison to CCI alone and it improved spatial learning as measured by the Morris Water Maze. Ex vivo analysis demonstrated preservation of brain volume, a decrease in amoeboid-shaped microglia in the dentate gyrus and an increase in the ratio of ramified to amoeboid microglia in the thalamus. PBR28suv is a viable option to measure efficacy of BMMNCs therapy after TBI.
Conservative versus operative treatment of FFP II fractures in a geriatric cohort: a prospective randomized pilot trial
Authors: Thiesen Darius M. , Althoff Gerrit , Strahl André , Rolvien Tim , Frosch Karl-Heinz , Koepke Leon-Gordian , Arras Christian , Ballhause Tobias M. , Dalos Dimitris , Hartel Maximilian J. 
Published: September 2023

AbstractA clear recommendation regarding treatment strategy of fragility fractures of the pelvic ring is missing. The most typical fracture pattern is a lateral compression type injury with non-displaced fractures of the anterior pubic rami and a unilateral os sacrum fracture (FFP II). We hypothesized that operative treatment would be superior to conservative treatment. From October 2017 to April 2020, a randomized prospective non-blinded trial with n = 39 patients was carried out. Two arms with 17 operative versus 22 conservative cases were created. Inclusion criteria were a posterior pelvic ring fracture FFP type II, age over 60 years and acute fracture (< 3 weeks). Barthel index, pain level (VAS), quality of life (EQ-5D-3L), and Tinetti–Gait Test were determined on admission, at discharge, and after 3, 6, 12 and 24 months. Median follow-up was 12.9 months. The Barthel index (= 0.325), VAS (p = 0.711), quality of life (p = 0.824), and Tinetti–Gait Test (p = 0.913) showed no significant differences between the two groups after 12 months. Two patients switched from the conservative to the operative arm due to persistent immobilization and pain. The one-year mortality rate showed no significant difference (p = 0.175). Our hypothesis that surgical treatment is superior was refuted. No significant benefit was shown in terms of quality of life, mortality and pain levels. The results suggest a more differentiated treatment approach in the future, with initial conservative treatment preferred. A larger multi-center trial is required to confirm these findings.Trial registration: The study was retrospectively registered with the German Clinical Trials Registry (DRKS00013703) on 10/12/2018.
Effect of copper oxide (CuO) and vanadium oxide (V2O5) addition on the structural, optical and electrical properties of corundum (α-Al2O3)
Authors: Al-Mushaki Mohammed Abdullah Ali , Al-Ariki Sami Amin , Alnehia Adnan 
Published: September 2023

AbstractIn this work, we prepared a pure α-Al2O3, α-Al2O3/CuO (AC) and α-Al2O3/V2O5 (AV) nanocomposite. The sol–gel method was used to prepare pure α-Al2O3, (AC) and (AV) samples at 1200 °C. Structural, electrical, and optical properties of the prepared samples were investigated using the X-ray diffraction (XRD), UV–Visible spectrophotometer, and conductivity meter, respectively. The XRD results confirmed the crystalline nature and the presence of the hexagonal structure of α-Al2O3, the rhombohedra structure of CuAlO2 and the tetragonal structure of V2O5. Moreover, the crystallite size of pure α-Al2O3 was 43.1 nm, while the crystallite size of α-Al2O3 in samples AC and AV nanocompsite was 24.05 nm and 34.84 nm respectively. The optical measurements showed that the band gap α-Al2O3 decreased significantly from 5.28 eV for pure to 3.7 and 3.4 eV to AC and AV respectively. The DC electrical conductivity (σd.c) values were measured for all prepared samples at room temperature. The electrical conductivity was 2.4 × 10–7 and 1.8 × 10–7 (Ω cm)−1 in AC and AV nanocompsite respectively, while ionic conductivity (σion) decreased from 3 × 10–10 in pure α-Al2O3 to 7 × 10–5 and 1 × 10–5 in AC and AV nanocompsite, respectively. The results showed an improvement in the structural, optical, and electrical properties, which may make these materials a candidate for use in many applications, such as photocatalytic, gas sensors, optoelectronics, microelectronics, semiconductor devices, ……etc.
Effects of extracorporeal circulation with different time on platelet count after cardiac surgery: a retrospective study based on medical records
Authors: Wang Na , Zhao Ting , Li Jiabei , Zeng Sisi , Wan Jixiang , Li Xuechao , Wang Fangjun 
Published: September 2023

AbstractOur objective was to observe the effects of extracorporeal circulation (ECC) with different time on platelet count in patients undergoing cardiac surgery. A total of 427 patients who underwent elective cardiac surgery under ECC in affiliated hospital of north Sichuan medical college from January 1, 2018 to July 31, 2021 were divided into three groups according to ECC time. We concluded that thrombocytopenia was common after ECC, maximum drop of the platelet counts after ECC was usually seen on the second day after ECC, and platelet counts started to recover on the fifth day after ECC. With the extension of ECC time, the drop in platelet counts is more pronounced, the volume of perioperative blood loss and blood products transfusion are more, and the recovery level and speed of platelet counts is lower.
Effect of delayed hospitalization on patients with non-ST-segment elevation myocardial infarction and complex lesions undergoing successful new-generation drug-eluting stents implantation
Authors: Kim Yong Hoon , Her Ae-Young , Rha Seung-Woon , Choi Cheol Ung , Choi Byoung Geol , Kim Ji Bak , Park Soohyung , Kang Dong Oh , Park Ji Young , Choi Woong Gil , Park Sang-Ho , Jeong Myung Ho 
Published: September 2023

AbstractIn the absence of available data, we evaluated the effects of delayed hospitalization (symptom-to-door time [SDT] ≥ 24 h) on major clinical outcomes after new-generation drug-eluting stent implantation in patients with non-ST-segment elevation myocardial infarction (NSTEMI) and complex lesions. In total, 4373 patients with NSTEMI were divided into complex (n = 2106) and non-complex (n = 2267) groups. The primary outcome was the 3-year rate of major adverse cardiac events (MACE), defined as all-cause death, recurrent MI, and any repeat revascularization. Secondary outcomes included the individual MACE components. In the complex group, all-cause death (adjusted hazard ratio [aHR], 1.752; p = 0.004) and cardiac death (aHR, 1.966; p = 0.010) rates were significantly higher for patients with SDT ≥ 24 h than for those with SDT < 24 h. In the non-complex group, all patients showed similar clinical outcomes. Patients with SDT < 24 h (aHR, 1.323; p = 0.031) and those with SDT ≥ 24 h (aHR, 1.606; p = 0.027) showed significantly higher rates of any repeat revascularization and all-cause death, respectively, in the complex group than in the non-complex group. Thus, in the complex group, delayed hospitalization was associated with higher 3-year mortalities.
Recovery of the histamine H3 receptor activity lost in yeast cells through error-prone PCR and in vivo selection
Authors: Watanabe Ayami , Nakajima Ami , Shiroishi Mitsunori 
Published: September 2023

AbstractG protein-coupled receptors (GPCRs) are the largest protein family in humans and are important drug targets. Yeast, especially Saccharomyces cerevisiae, is a useful host for modifying the function and stability of GPCRs through protein engineering, which is advantageous for mammalian cells. When GPCRs are expressed in yeast, their function is often impaired. In this study, we performed random mutagenesis using error-prone PCR and then an in vivo screening to obtain mutants that recovered the activity of the human histamine H3 receptor (H3R), which loses its signaling function when expressed in yeast. Four mutations with recovered activity were identified after screening. Three of the mutations were identified near the DRY and NPxxY motifs of H3R, which are important for activation and are commonly found in class A GPCRs. The mutants responded exclusively to the yeast YB1 strain harboring Gi-chimera proteins, showing retention of G protein specificity. Analysis of one of the mutants with recovered activity, C415R, revealed that it maintained its ligand-binding characteristics. The strategy used in this study may enable the recovery of the activity of other GPCRs that do not function in S. cerevisiae and may be useful in creating GPCRs mutants stabilized in their active conformations.
Facilitation of imitative movement in patients with chronic hemiplegia triggered by illusory ownership
Authors: Aizu Naoki , Sudo Tamami , Oouchida Yutaka , Izumi Shin-Ichi 
Published: September 2023

AbstractThe sense of body ownership, the feeling that one’s body belongs to oneself, is a crucial subjective conscious experience of one’s body. Recent methodological advances regarding crossmodal illusions have provided novel insights into how multisensory interactions shape human perception and cognition, underpinning conscious experience, particularly alteration of body ownership. Moreover, in post-stroke rehabilitation, encouraging the use of the paretic limb in daily life is considered vital, as a settled sense of ownership and attentional engagement toward the paralyzed body part may promote increased frequency of its use and prevent learned nonuse. Therefore, in addition to traditional methods, novel interventions using neurorehabilitation techniques that induce self-body recognition are needed. This study investigated whether the illusory experience of a patient’s ownership alterations of their paretic hand facilitates the enhancement in the range of motion of succeeding imitation movements. An experiment combining a modified version of the rubber hand illusion with imitation training was conducted with chronic hemiplegia. A larger imitation movement of the paretic hand was observed in the illusion-induced condition, indicating that the feeling of ownership toward the observed limb promotes the induction of intrinsic potential for motor performance. This training, using subjective experience, may help develop new post-stroke rehabilitation interventions.
Formulation development, in vivo bioequivalence and pediatric PBPK modeling studies of taste-masked ciprofloxacin chewable tablets
Authors: Usmani Muhammad Talha , Shoaib Muhammad Harris , Siddiqui Fahad , Ahmed Farrukh Rafiq , Yousuf Rabia Ismail , Saleem Muhammad Talha 
Published: September 2023

AbstractA taste-masked chewable tablet of ciprofloxacin using ion exchange resin Kyron T-134 for enhancing compliance for the paediatric population was developed. The drug-to-resin ratio was optimized for maximum taste masking by studying the effects of soaking time (X1) and mixing time (X2) on complexation (%) using Central Composite Rotatable Design (CCRD). The resin complexes were characterized by bitterness score, DSC, FTIR, and PXRD. The complex was further formulated and optimized into chewable tablets through full factorial design, The optimized formulation was subjected to a bioequivalence study, and a virtual approach of PBPK modelling was adapted to predict the pharmacokinetics of the drug in the paediatric group. The drug resin ratio of 1:1.5 yielded an optimum drug loading of 99.05%. The optimized formulation shows minimum disintegration time with more than 99% drug release within 30 min. The formulation F-9 was found to be bioequivalent with a geometric mean ratio of Cmax, Tmax, AUC0–t, and AUC0–∞ within 90% CI. It was concluded that quality by design approach can successfully be applied to optimize the drug resin ratio and PBPK modeling is a successful predictive tool for estimating the pharmacokinetics of ciprofloxacin HCl in the paediatric population.
Principal component analysis–artificial neural network-based model for predicting the static strength of seasonally frozen soils
Authors: Sun Yiqiang , Zhou Shijie , Meng Shangjiu , Wang Miao , Mu Hailong 
Published: September 2023

AbstractSeasonally frozen soils are exposed to freeze‒thaw cycles every year, leading to mechanical property deterioration. To reasonably describe the deterioration of soil under different conditions, machine learning (ML) technology is used to establish a prediction model for soil static strength. Six key influencing factors (moisture content, compaction degree, confining pressure, freezing temperature, number of freeze‒thaw cycles and thawing duration) are included in the modelling database. The accuracy of three typical ML algorithms (support vector machine (SVM), random forest (RF) and artificial neural network (ANN)) is compared. The results show that the ANN outperforms the SVM and RF. Principal component analysis (PCA) is combined with the ANN, and the PCA–ANN algorithm is proposed, which further improves the prediction accuracy. The deterioration of soil static strength is systematically researched using the PCA–ANN algorithm. The results show that the soil static strength decreased considerably after the first several freeze‒thaw cycles before the strength plateau occurred, and the strength reduction increased significantly with increasing moisture content and compaction degree. The PCA–ANN model can generate a reasonable prediction for the static strength or other soil properties of seasonally frozen soil, which will provide a scientific reference for practical engineering.
The Iterative Mindset Method: a neuroscientific theoretical approach for sustainable behavior change and weight-loss in digital medicine
Authors: Bobinet Kyra , Greer Stephanie M. 
Published: September 2023

AbstractWith the growing prevalence of chronic conditions driving 85% of all healthcare costs, digital health offers a promising opportunity to reverse disease and improve health at-scale. The healthcare industry’s predominant approach to behavior change is performance-based with a focus on goals and tracking. This has not reversed the epidemic of chronic diseases and also can harm chronically ill and vulnerable patients via perceived failure-induced loss of motivation. Still nascent, the digital health industry is uniquely positioned to adopt and scale new and better behavior change approaches. In this paper, we present the theoretical foundation and initial findings of a neuroscience-based behavior change approach—what we call the Iterative Mindset MethodTM. We discuss its promise, as a potentially more effective, neuroscience-based approach to changing health behaviors long-term, particularly in vulnerable populations. We conclude with avenues for future research.
Digital Fellowships: Inspiring use of contemporary technologies in applied healthcare
Authors: Salisbury Thomas , Deng Alexander T. , Burch Emily , Godfrey Alan 
Published: September 2023

AbstractThe adoption of digital technologies in healthcare, accelerated by the COVID-19 pandemic, requires a well-prepared workforce capable of implementing those technologies. Here, we examine the role and impact of digital fellowships in facilitating digital transformation in healthcare systems. Digital fellowships are structured educational programmes designed to equip healthcare professionals with advanced digital skills. Focusing on UK-based initiatives like the Topol Digital Fellowship and the Fellowship in Clinical AI, we explore their efforts to prepare healthcare leaders for digital and AI adoption. Each fellowship programme provides participants with hands-on experience in digital healthcare projects and fosters interdisciplinary collaboration and post-fellowship support. We discuss how these fellowships contribute to staff retention by diversifying professional experiences and opportunities. We call for increased collaborations between universities, industry, and professional bodies to integrate lessons from digital fellowships into relevant curricula, acknowledging that digital fellowships are just one piece of the puzzle in bridging the digital skills gap in the healthcare workforce.
Cortical temporal integration can account for limits of temporal perception: investigations in the binaural system
Authors: Singh Ravinderjit , Bharadwaj Hari M. 
Published: September 2023

AbstractThe auditory system has exquisite temporal coding in the periphery which is transformed into a rate-based code in central auditory structures, like auditory cortex. However, the cortex is still able to synchronize, albeit at lower modulation rates, to acoustic fluctuations. The perceptual significance of this cortical synchronization is unknown. We estimated physiological synchronization limits of cortex (in humans with electroencephalography) and brainstem neurons (in chinchillas) to dynamic binaural cues using a novel system-identification technique, along with parallel perceptual measurements. We find that cortex can synchronize to dynamic binaural cues up to approximately 10 Hz, which aligns well with our measured limits of perceiving dynamic spatial information and utilizing dynamic binaural cues for spatial unmasking, i.e. measures of binaural sluggishness. We also find that the tracking limit for frequency modulation (FM) is similar to the limit for spatial tracking, demonstrating that this sluggish tracking is a more general perceptual limit that can be accounted for by cortical temporal integration limits.
Long-term trends in carbon and color signal uneven browning and terrestrialization of northern lakes
Authors: Rodríguez-Cardona Bianca M. , Houle Daniel , Couture Suzanne , Lapierre Jean-François , del Giorgio Paul A. 
Published: September 2023

AbstractThe widespread browning of northern lakes has been associated with long-term increases in dissolved organic carbon and color and should be linked to changes in surface water carbon dioxide, yet the long-term covariation in these three key carbon components of lake functioning remains to be assessed. We present long-term trends in dissolved organic carbon, color, and carbon dioxide from lakes, with generally positive but highly variable trends in organic carbon and a large degree of uncoupling with color and carbon dioxide. The highest rates of change in color and carbon dioxide were in lakes with greatest increasing dissolved organic carbon trends. Lakes with the lowest water retention times had greater increases and stronger coupling between all three parameters, coinciding with dominance of terrestrially derived carbon. These results suggest an uneven terrestrialization of northern lakes, where the increases and coupling in the three carbon components depends on hydrology and watershed connectivity.
The Marine Spatial Planning Index: a tool to guide and assess marine spatial planning
Authors: Reimer Julie M. , Devillers Rodolphe , Zuercher Rachel , Groulx Pascale , Ban Natalie C. , Claudet Joachim 
Published: September 2023

AbstractMarine spatial planning (MSP) has the potential to balance demands for ocean space with environmental protection and is increasingly considered crucial for achieving global ocean goals. In theory, MSP should adhere to six principles, being: (1) ecosystem-based, (2) integrated, (3) place-based, (4) adaptive, (5) strategic, and (6) participatory. Despite nearly two decades of practice, MSP continues to face critical challenges to fully realize these principles, hindering its ability to deliver positive outcomes for people and nature. Here, we present the MSP Index, a tool for assessing progress in MSP processes based on MSP principles that can guide practitioners in operationalizing these principles. Using qualitative analysis of fundamental MSP guides, complemented with a literature review, we identified key features of MSP principles and developed these features into a scoring guide that assesses progress relative to each principle. We trialed and validated the MSP Index on six case studies from distinct regions. We found that the MSP Index allows for high-level comparison across diverse marine spatial plans, highlighting the extent to which MSP principles have permeated practice. Our results reveal successes, especially for the place-based principle, and failures to fully adhere to the adaptive and participatory principles of MSP. The Index serves as a guidance tool that would be best employed by practitioners and can inform science on the evolution of MSP. It is a user-friendly tool that translates MSP principles into practice, allowing for assessment of individual initiatives and comparison of diverse initiatives across ocean regions and nations.
Hypoglycemic effect of Lactobacillus plantarum-fermented mulberry pomace extract in vitro and in Caenorhabditis elegans
Authors: Tang Shuxin , Cheng Yuxin , Xu Tingting , Wu Ting , Pan Siyi , Xu Xiaoyun 
Published: September 2023

It has been found that FMPE showed hypoglycemic effects in vitro and in C. elegans. In addition, 2,4,6-trihydroxybenzaldehyde, cyanidin, and taxifolin were the important polyphenols to improve the hypoglycemic effects after fermentation.