bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA methylation as a pharmacodynamic marker of glucocorticoid response and glioma survival
Authors: Wiencke J. K. , Molinaro Annette M. , Warrier Gayathri , Rice Terri , Clarke Jennifer , Taylor Jennie W. , Wrensch Margaret , Hansen Helen , McCoy Lucie , Tang Emily , Tamaki Stan J. , Tamaki Courtney M. , Nissen Emily , Bracci Paige , Salas Lucas A. , Koestler Devin C. , Christensen Brock C. , Zhang Ze , Kelsey Karl T. 
Published: September 2022

AbstractAssessing individual responses to glucocorticoid drug therapies that compromise immune status and affect survival outcomes in neuro-oncology is a great challenge. Here we introduce a blood-based neutrophil dexamethasone methylation index (NDMI) that provides a measure of the epigenetic response of subjects to dexamethasone. This marker outperforms conventional approaches based on leukocyte composition as a marker of glucocorticoid response. The NDMI is associated with low CD4 T cells and the accumulation of monocytic myeloid-derived suppressor cells and also serves as prognostic factor in glioma survival. In a non-glioma population, the NDMI increases with a history of prednisone use. Therefore, it may also be informative in other conditions where glucocorticoids are employed. We conclude that DNA methylation remodeling within the peripheral immune compartment is a rich source of clinically relevant markers of glucocorticoid response.
Negative electrostatic potentials in a Hofmann-type metal-organic framework for efficient acetylene separation
Authors: Liu Yuan , Liu Junhui , Xiong Hanting , Chen Jingwen , Chen Shixia , Zeng Zheling , Deng Shuguang , Wang Jun 
Published: September 2022

AbstractEfficient adsorptive separation of acetylene (C2H2) from carbon dioxide (CO2) or ethylene (C2H4) is industrially important but challenging due to the identical dynamic diameter or the trace amount. Here we show an electrostatic potential compatible strategy in a nitroprusside-based Hofmann-type metal-organic framework, Cu(bpy)NP (NP = nitroprusside, bpy = 4,4’-bipyridine), for efficient C2H2separation. The intruding cyanide and nitrosyl groups in undulating one-dimensional channels induce negative electrostatic potentials for preferential C2H2recognition instead of open metal sites in traditional Hofmann-type MOFs. As a result, Cu(bpy)NP exhibits a 50/50 C2H2/CO2selectivity of 47.2, outperforming most rigid MOFs. The dynamic breakthrough experiment demonstrates a 99.9% purity C2H4productivity of 20.57 mmol g−1from C2H2/C2H4(1/99,v/v) gas-mixture. Meanwhile, C2H2can also be captured and recognized from ternary C2H2/CO2/C2H4(25/25/50,v/v/v) gas-mixture. Furthermore, computational studies and in-situ infrared spectroscopy reveal that the selective C2H2binding arises from the compatible pore electro-environment generated by the electron-rich N and O atoms from nitroprusside anions.
Structural materials with afterglow room temperature phosphorescence activated by lignin oxidation
Authors: Wan Keliang , Tian Bing , Zhai Yingxiang , Liu Yuxuan , Wang He , Liu Shouxin , Li Shujun , Ye Wenpeng , An Zhongfu , Li Changzhi , Li Jian , James Tony D. , Chen Zhijun 
Published: September 2022

AbstractSustainable afterglow room temperature phosphorescence (RTP) materials, especially afterglow RTP structural materials, are crucial but remain difficult to achieve. Here, an oxidation strategy is developed to convert lignin to afterglow materials with a lifetime of ~ 408 ms. Specifically, lignin is oxidized to give aromatic chromophores and fatty acids using H2O2. The aromatic chromophores are locked by a fatty acid-based matrix by hydrogen bonds, triggering enhanced spin orbit coupling and long afterglow emission. More interestingly, motivated by this discovery, an auto fabrication line is built to convert wood (natural structural materials) to wood with afterglow RTP emission (RTP wood) via in situ oxidation of naturally-occurring lignin located in the wood cell walls to oxidized lignin (OL). The as-prepared RTP wood exhibits great potential for the construction of sustainable afterglow furniture. With this research we provide a new strategy to promote the sustainability of afterglow RTP materials and structural materials.
Cognitive load, fatigue and aversive simulator symptoms but not manipulated zeitgebers affect duration perception in virtual reality
Authors: Sabat Magdalena , Haładus Bartosz , Klincewicz Michał , Nalepa Grzegorz J. 
Published: September 2022

AbstractThe perceived duration of an interval depends on numerous aspects of the passed event both endogenous, including physiological arousal, level of wakefulness, attention, and surprise, as well as exogenous such as valence, salience, or context in the environment. There is some evidence that "time-giving" cues from the environment (zeitgebers) are coupled with time perception. The movement of the sun on the horizon was demonstrated to affect interval perception in a study conducted by Schatzschneider et al. (2016) claiming that the sun’s motion is a zeitgeber that influences time perception. In the present study, we undertake the first to our knowledge replication of this effect, extending the analysis to confounding aspects of the used paradigm. We aimed to test the effect of immersion, cognitive load, and changes in the speed of the sun on the horizon of the virtual environment on the perceived interval duration. We did not replicate the original effect, as reported by Schatzschneider et al., however, we did find that the perceived duration of an interval was affected by cognitive load, fatigue, and unpleasant symptoms caused by VR. In our analysis, we used Bayesian statistics to support our conclusion and offer its results as having some important consequences for the field.
Comparison of lamina cribrosa depth shallowing after trabeculectomy between primary open-angle glaucoma and exfoliation glaucoma
Authors: Park Do Young , Son Sunggeun , Cha Soon Cheol 
Published: September 2022

AbstractThe lamina cribrosa (LC) becomes shallower as intraocular pressure (IOP) decreases after trabeculectomy. The LC in eyes with exfoliation syndrome has distinctive properties in the connective tissue and extracellular matrix, but how these affect the changes in LC depth in response to IOP reduction after trabeculectomy is unknown. We analyzed pre- and postoperative spectral-domain optical coherence tomography of exfoliation glaucoma (XFG) and primary open-angle glaucoma (POAG) patients who underwent trabeculectomy and investigated whether LC depth differed between XFG and POAG eyes after trabeculectomy. In total, 30 XFG eyes and 30 visual field mean deviation-matched POAG eyes were included. LC depth was determined at an average of 3.9 months after trabeculectomy. Postoperatively, the LC depth became shallower and the BMO-MRW became thicker in both XFG and POAG eyes. XFG eyes showed lesser amount of LC depth shallowing than POAG eyes. Greater preoperative LC depth, lower postoperative IOP, and absence of XFG were all associated with a greater degree of postoperative LC depth shallowing. These findings suggest that the LC of XFG eyes may inherently possess the distinctive properties of the connective tissue and extracellular matrix contained within it, which could affect the LC response to the reduction in IOP after trabeculectomy.
Extracellular vesicles derived from microgreens of Raphanus sativus L. var. caudatus Alef contain bioactive macromolecules and inhibit HCT116 cells proliferation
Authors: Kaimuangpak Karnchanok , Tamprasit Kawintra , Thumanu Kanjana , Weerapreeyakul Natthida 
Published: September 2022

AbstractExtracellular vesicles (EVs) are phospholipid bilayer vesicles released from cells, containing natural cargos. Microgreens of Raphanus sativus L. var. caudatus Alef were used in this study as the source of EVs. EVs were isolated by differential centrifugation. The physical properties were determined by dynamic light scattering (DLS) and electron microscopy. The biological and chemical composition were studied by Fourier-transform infrared (FTIR) microspectroscopy and high-performance liquid chromatography analysis, respectively. EVs had a median size of 227.17 and 234.90 ± 23.30 nm determined by electron microscopy and DLS, respectively with a polydispersity index of 0.293 ± 0.019. Electron microscopy indicated the intact morphology and confirmed the size. The FTIR spectra revealed that EVs are composed of proteins as the most abundant macromolecules. Using a curve-fitting analysis, β-pleated sheets were the predominant secondary structure. Notably, the micromolecular biomarkers were not detected. EVs exerted anti-cancer activity on HCT116 colon cancer over Vero normal cells with an IC50 of 448.98 µg/ml and a selectivity index of > 2.23. To conclude, EVs could be successfully prepared with a simple and effective isolation method to contain nano-sized macromolecules possessing anti-cancer activity.
Mutation analysis for newly suggested 30 Y-STR loci with high mutation rates in Chinese father-son pairs
Authors: Wang Fei , Song Feng , Wang Xindi , Song Mengyuan , Zhou Yuxiang , Liu Jing , Wang Zheng , Hou Yiping 
Published: September 2022

AbstractRapidly mutating Y-STRs (RM Y-STRs) harbor great potential to distinguish male relatives and achieve male identification. However, forensic applications were greatly limited by the small number of the initially identified 14 RM Y-STRs. Recently, with the emergence of 12 novel RM Y-STRs, an integrated panel named RMplex was introduced, which contains all 26 RM Y-STRs and four fast mutating Y-STRs (FM Y-STRs). To obtain the first data on the mutation rates and father-son differentiation rates of the 30 newly proposed Y-STRs in Chinese populations, we performed an empirical mutation study on 307 DNA-confirmed Chinese paternal pairs. Previously reported mutation rates for 14 RM Y-STRs in Chinese and European populations were pooled and merged with our data. The highest meiosis number for the two groups reached 4771 and 2687, respectively. Five loci showed significant differences between the populations (DYS570, DYS399S1, DYS547, DYS612, and DYF403S1b). For the new panel covering 30 Y-STR loci, our results show extensive differences in the mutation rates between the two populations, as well. 10 RM Y-STR loci showed relatively low mutation rates (10–3–10–2 per meiosis) and 2 FM Y-STR loci had rapid mutation rates (> 10–2 per meiosis) in the Chinese population. Several-fold differences in mutation rates were found in nine Y-STR loci between the Chinese and reference populations, with two loci having significantly higher mutation rates and one locus with a significantly lower mutation rate in the Chinese population (P < 0.05). Eighteen RM Y-STRs (> 10–2 per meiosis), 8 FM Y-STR loci (5×10–3-10–2 per meiosis), 3 moderately mutating Y-STRs (MM Y-STRs, 10–3-5×10–3 per meiosis), and one locus with no observed mutation events were identified in the Chinese population. 40.06% of the Chinese paternity pairs were discriminated with RMplex while only 20.84% with the initial 14 RM Y-STRs, indicating that RMplex is beneficial for distinguishing paternally related males. Future studies on populations of different genetic backgrounds are necessary to obtain comprehensive estimates of mutation rates at these new loci.
Valproic acid restricts mast cell activation by Listeria monocytogenes
Authors: Soria-Castro Rodolfo , Meneses-Preza Yatsiri G. , Rodríguez-López Gloria M. , Ibarra-Sánchez Alfredo , González-Espinosa Claudia , Pérez-Tapia Sonia M. , Flores-Borja Fabián , Estrada-Parra Sergio , Chávez-Blanco Alma D. , Chacón-Salinas Rommel 
Published: September 2022

AbstractMast cells (MC) play a central role in the early containment of bacterial infections, such as that caused by Listeria monocytogenes (L.m). The mechanisms of MC activation induced by L.m infection are well known, so it is possible to evaluate whether they are susceptible to targeting and modulation by different drugs. Recent evidence indicates that valproic acid (VPA) inhibits the immune response which favors L.m pathogenesis in vivo. Herein, we examined the immunomodulatory effect of VPA on L.m-mediated MC activation. To this end, bone marrow-derived mast cells (BMMC) were pre-incubated with VPA and then stimulated with L.m. We found that VPA reduced MC degranulation and cytokine release induced by L.m. MC activation during L.m infection relies on Toll-Like Receptor 2 (TLR2) engagement, however VPA treatment did not affect MC TLR2 cell surface expression. Moreover, VPA was able to decrease MC activation by the classic TLR2 ligands, peptidoglycan and lipopeptide Pam3CSK4. VPA also reduced cytokine production in response to Listeriolysin O (LLO), which activates MC by a TLR2-independent mechanism. In addition, VPA decreased the activation of critical events on MC signaling cascades, such as the increase on intracellular Ca2+ and phosphorylation of p38, ERK1/2 and -p65 subunit of NF-κB. Altogether, our data demonstrate that VPA affects key cell signaling events that regulate MC activation following L.m infection. These results indicate that VPA can modulate the functional activity of different immune cells that participate in the control of L.m infection.
Schrödinger–Poisson systems under gradient fields
Authors: Ourabah Kamel 
Published: September 2022

AbstractA singularity-free generalisation of Newtonian gravity can be constructed (Lazar in Phys Rev D 102:096002, 2020) within the framework of gradient field theory. This procedure offers a straightforward regularisation of Newtonian gravity and remains equally well applicable to other fields, such as electromagnetic fields. Here, with the aim of finding potentially measurable effects of gradient fields on the dispersion properties of various media, we present a quantum kinetic treatment of matter under gradient fields. The method is based on the application of the Wigner–Moyal procedure to the modified Schrödinger–Poisson equation emerging in the framework of gradient field theory. This allows us to treat, on equal footing, three different scenarios, namely self-gravitating systems, plasmas, and cold atoms in magneto-optical traps. We address the signature of gradient fields in the elementary excitations of these media. In particular, we estimate this effect to be accessible in state-of-the-art plasma-based experiments. We discuss in detail the classical kinetic and hydrodynamic limits of our approach and obtain a class of generalised Lane–Emden equations, in the context of gradient field theory, which remain valid in the three scenarios discussed here.
Identification and development of a subtype-selective allosteric AKT inhibitor suitable for clinical development
Authors: Page Natalie , Wappett Mark , O’Dowd Colin R. , O’Rourke Martin , Gavory Gerald , Zhang Lixin , Rountree J. S. Shane , Jordan Linda , Barker Oliver , Gibson Hayley , Boyd Caroline , Feutren-Burton Stephanie , McLean Estelle , Trevitt Graham , Harrison Timothy 
Published: September 2022

AbstractThe serine/threonine protein kinase AKT plays a pivotal role within the PI3K pathway in regulating cellular proliferation and apoptotic cellular functions, and AKT hyper-activation via gene amplification and/or mutation has been implicated in multiple human malignancies. There are 3 AKT isoenzymes (AKT1-3) which mediate critical, non-redundant functions. We present the discovery and development of ALM301, a novel, allosteric, sub-type selective inhibitor of AKT1/2. ALM301 binds in an allosteric pocket created by the combined movement of the PH domain and the catalytic domain, resulting in a DFG out conformation. ALM301 was shown to be highly selective against a panel of over 450 kinases and potently inhibited cellular proliferation. These effects were particularly pronounced in MCF-7 cells containing a PI3KCA mutation. Subsequent cellular downstream pathway analysis in this sensitive cell line revealed potent inhibition of pAKT signalling up to 48 h post dosing. ALM301 treatment was well tolerated in an MCF-7 xenograft model and led to a dose-dependent reduction in tumour growth. Enhanced efficacy was observed in combination with tamoxifen. In summary, ALM301 is a highly specific AKT 1/2 inhibitor with an excellent pharmacological profile suitable for further clinical development.
Integrated multimodal artificial intelligence framework for healthcare applications
Authors: Soenksen Luis R. , Ma Yu , Zeng Cynthia , Boussioux Leonard , Villalobos Carballo Kimberly , Na Liangyuan , Wiberg Holly M. , Li Michael L. , Fuentes Ignacio , Bertsimas Dimitris 
Published: September 2022

AbstractArtificial intelligence (AI) systems hold great promise to improve healthcare over the next decades. Specifically, AI systems leveraging multiple data sources and input modalities are poised to become a viable method to deliver more accurate results and deployable pipelines across a wide range of applications. In this work, we propose and evaluate a unified Holistic AI in Medicine (HAIM) framework to facilitate the generation and testing of AI systems that leverage multimodal inputs. Our approach uses generalizable data pre-processing and machine learning modeling stages that can be readily adapted for research and deployment in healthcare environments. We evaluate our HAIM framework by training and characterizing 14,324 independent models based on HAIM-MIMIC-MM, a multimodal clinical database (N = 34,537 samples) containing 7279 unique hospitalizations and 6485 patients, spanning all possible input combinations of 4 data modalities (i.e., tabular, time-series, text, and images), 11 unique data sources and 12 predictive tasks. We show that this framework can consistently and robustly produce models that outperform similar single-source approaches across various healthcare demonstrations (by 6–33%), including 10 distinct chest pathology diagnoses, along with length-of-stay and 48 h mortality predictions. We also quantify the contribution of each modality and data source using Shapley values, which demonstrates the heterogeneity in data modality importance and the necessity of multimodal inputs across different healthcare-relevant tasks. The generalizable properties and flexibility of our Holistic AI in Medicine (HAIM) framework could offer a promising pathway for future multimodal predictive systems in clinical and operational healthcare settings.
Soft skin-interfaced mechano-acoustic sensors for real-time monitoring and patient feedback on respiratory and swallowing biomechanics
Authors: Kang Youn J. , Arafa Hany M. , Yoo Jae-Young , Kantarcigil Cagla , Kim Jin-Tae , Jeong Hyoyoung , Yoo Seonggwang , Oh Seyong , Kim Joohee , Wu Changsheng , Tzavelis Andreas , Wu Yunyun , Kwon Kyeongha , Winograd Joshua , Xu Shuai , Martin-Harris Bonnie , Rogers John A. 
Published: September 2022

AbstractSwallowing is a complex neuromuscular activity regulated by the autonomic nervous system. Millions of adults suffer from dysphagia (impaired or difficulty swallowing), including patients with neurological disorders, head and neck cancer, gastrointestinal diseases, and respiratory disorders. Therapeutic treatments for dysphagia include interventions by speech-language pathologists designed to improve the physiology of the swallowing mechanism by training patients to initiate swallows with sufficient frequency and during the expiratory phase of the breathing cycle. These therapeutic treatments require bulky, expensive equipment to synchronously record swallows and respirations, confined to use in clinical settings. This paper introduces a wireless, wearable technology that enables continuous, mechanoacoustic tracking of respiratory activities and swallows through movements and vibratory processes monitored at the skin surface. Validation studies in healthy adults (n = 67) and patients with dysphagia (n = 4) establish measurement equivalency to existing clinical standard equipment. Additional studies using a differential mode of operation reveal similar performance even during routine daily activities and vigorous exercise. A graphical user interface with real-time data analytics and a separate, optional wireless module support both visual and haptic forms of feedback to facilitate the treatment of patients with dysphagia.
Reference source‐aided coordinate registration method for over‐the‐horizon radar using ensemble learning
Authors: Lei Zhenshuo , Chen Jianwen , Chen Hui , Zhang Zhaojian , Dou Gaoqi , Wang Yongliang 
Published: September 2022

AbstractSince solving the path of radio wave propagation by an analytic method in the process of coordinate registration (CR) for skywave over‐the‐horizon radar (OTHR) is difficult, a reference source‐aided CR method that uses ensemble learning is proposed. First, the OTHR wave propagation principle is briefly described, and the ionospheric channel characteristics implied by reference sources and target information are explained, which provides a theoretical basis for modelling. Then, multiple machine learning models, such as random forest, support vector machine and elastic network, are used to build a mapping network between known information and the actual ground distance of the targets. Moreover, the prediction ability and correlation of each machine learning model are evaluated. Finally, with stacking ensemble learning, machine learning models with better performance to solve CR problems are effectively combined as base learners. The models develop the advantages of each base learner to achieve a perception of the ionospheric environment and accurate OTHR CR. The simulation results show that the proposed method can mine the ionospheric channel propagation characteristics and effectively reduce the CR error of the targets of interest. When the information provided by 4 reference sources 200 km away from the target is used, the average error of target positioning is 13 km.