bluuebunny/crossref_metadata_2025_split huggingface dataset:
Colossal barocaloric effect achieved by exploiting the amorphous high entropy of solidified polyethylene glycol
Authors: Yu Zibing , Zhou Houbo , Hu Fengxia , Liu Chang , Yuan Shuaikang , Wang Donghui , Hao Jiazheng , Gao Yihong , Wang Yangxin , Wang Bingjie , Tian Zhengying , Lin Yuan , Zhang Cheng , Yin Zhuo , Wang Jing , Chen Yunzhong , Li Yunliang , Sun Jirong , Zhao Tongyun , Shen Baogen 
Published: December 2022

AbstractThe barocaloric effect (BCE) has emerged as an intense research topic in regard to efficient and clean solid-state refrigeration. Materials with solid-liquid phase transitions (SL-PTs) usually show huge melting entropies but cannot work in full solid-state refrigeration. Here, we report a colossal barocaloric effect realized by exploiting high entropy inherited from huge disorder of liquid phase in amorphous polyethylene glycol (PEG), which is solidified by introducing 5 wt.% polyethylene terephthalate (PET). Transmission electron microscopy (TEM) combined with X-ray diffraction (XRD) demonstrates the amorphous nature of the high-temperature phase after fixation by PET. Although PEG loses its –OH end mobility in amorphous solid, high entropy still retains owing to the retained high degrees of freedom of its molecular chains. The remaining entropy of amorphous PEG is up to 83% of that of liquid PEG in PEG10000/PET15000, and the barocaloric entropy change reaches ΔSp ∼ 416 J·kg−1·K−1 under a low pressure of 0.1 GPa, which exceeds the performance of most other BCE materials. Infrared spectra combined with density function theory (DFT) calculations disclose conformational change from the liquid to amorphous state, which explains the origin of the large entropy retained and hence the colossal BCE of the solidified PEG. This research opens a new avenue for exploring full solid-state barocaloric materials by utilizing genetic high entropy from huge disordering of liquid phases in various materials with SL-PTs.
Allosteric rescue of catalytically impaired ATP phosphoribosyltransferase variants links protein dynamics to active-site electrostatic preorganisation
Authors: Fisher Gemma , Corbella Marina , Alphey Magnus S. , Nicholson John , Read Benjamin J. , Kamerlin Shina C. L. , da Silva Rafael G. 
Published: December 2022

AbstractATP phosphoribosyltransferase catalyses the first step of histidine biosynthesis and is controlled via a complex allosteric mechanism where the regulatory protein HisZ enhances catalysis by the catalytic protein HisGS while mediating allosteric inhibition by histidine. Activation by HisZ was proposed to position HisGS Arg56 to stabilise departure of the pyrophosphate leaving group. Here we report active-site mutants of HisGS with impaired reaction chemistry which can be allosterically restored by HisZ despite the HisZ:HisGS interface lying ~20 Å away from the active site. MD simulations indicate HisZ binding constrains the dynamics of HisGS to favour a preorganised active site where both Arg56 and Arg32 are poised to stabilise leaving-group departure in WT-HisGS. In the Arg56Ala-HisGS mutant, HisZ modulates Arg32 dynamics so that it can partially compensate for the absence of Arg56. These results illustrate how remote protein-protein interactions translate into catalytic resilience by restoring damaged electrostatic preorganisation at the active site.
Uncomputably complex renormalisation group flows
Authors: Watson James D. , Onorati Emilio , Cubitt Toby S. 
Published: December 2022

AbstractRenormalisation group methods are among the most important techniques for analysing the physics of many-body systems: by iterating a renormalisation group map, which coarse-grains the description of a system and generates a flow in the parameter space, physical properties of interest can be extracted. However, recent work has shown that important physical features, such as the spectral gap and phase diagram, may be impossible to determine, even in principle. Following these insights, we construct a rigorous renormalisation group map for the original undecidable many-body system that appeared in the literature, which reveals a renormalisation group flow so complex that it cannot be predicted. We prove that each step of this map is computable, and that it converges to the correct fixed points, yet the resulting flow is uncomputable. This extreme form of unpredictability for renormalisation group flows had not been shown before and goes beyond the chaotic behaviour seen previously.
A Multifaceted benchmarking of synthetic electronic health record generation models
Authors: Yan Chao , Yan Yao , Wan Zhiyu , Zhang Ziqi , Omberg Larsson , Guinney Justin , Mooney Sean D. , Malin Bradley A. 
Published: December 2022

AbstractSynthetic health data have the potential to mitigate privacy concerns in supporting biomedical research and healthcare applications. Modern approaches for data generation continue to evolve and demonstrate remarkable potential. Yet there is a lack of a systematic assessment framework to benchmark methods as they emerge and determine which methods are most appropriate for which use cases. In this work, we introduce a systematic benchmarking framework to appraise key characteristics with respect to utility and privacy metrics. We apply the framework to evaluate synthetic data generation methods for electronic health records data from two large academic medical centers with respect to several use cases. The results illustrate that there is a utility-privacy tradeoff for sharing synthetic health data and further indicate that no method is unequivocally the best on all criteria in each use case, which makes it evident why synthetic data generation methods need to be assessed in context.
An umbrella review of the evidence linking oral health and systemic noncommunicable diseases
Authors: Botelho João , Mascarenhas Paulo , Viana João , Proença Luís , Orlandi Marco , Leira Yago , Chambrone Leandro , Mendes José João , Machado Vanessa 
Published: December 2022

AbstractOral diseases are highly prevalent worldwide. Recent studies have been supporting a potential bidirectional association of oral diseases with systemic noncommunicable diseases (NCDs). Available evidence supports that people with NCDs have a greater prevalence of oral diseases particularly those with limited ability of oral self-care. Regarding the reverse relationship, the lines of evidence pointing out NCDs as putative risk factors for oral diseases have increased significantly but not with a consistent agreement. This umbrella review of meta-analyses appraises the strength and validity of the evidence for the association between oral health and systemic health (registered at PROSPERO, ID: CRD42022300740). An extensive search included systematic reviews that have provided meta-analytic estimates on the association of oral diseases with NCDs. The overall strength of evidence was found to be unfavorable and with methodological inconsistencies. Twenty-eight NCDs were strongly associated with oral diseases. Among those NCDs are five types of cancer, diabetes mellitus, cardiovascular diseases, depression, neurodegenerative conditions, rheumatic diseases, inflammatory bowel disease, gastric helicobacter pylori, obesity, and asthma. According to fail-safe number statistics, the evidence levels are unlikely to change in the future, indicating a fairly robust consistency.
Immunogenetic losses co-occurred with seahorse male pregnancy and mutation in tlx1 accompanied functional asplenia
Authors: Liu Yali , Qu Meng , Jiang Han , Schneider Ralf , Qin Geng , Luo Wei , Yu Haiyan , Zhang Bo , Wang Xin , Zhang Yanhong , Zhang Huixian , Zhang Zhixin , Wu Yongli , Zhang Yingyi , Yin Jianping , Zhang Si , Venkatesh Byrappa , Roth Olivia , Meyer Axel , Lin Qiang 
Published: December 2022

AbstractIn the highly derived syngnathid fishes (pipefishes, seadragons & seahorses), the evolution of sex-role reversed brooding behavior culminated in the seahorse lineage’s male pregnancy, whose males feature a specialized brood pouch into which females deposit eggs during mating. Then, eggs are intimately engulfed by a placenta-like tissue that facilitates gas and nutrient exchange. As fathers immunologically tolerate allogenic embryos, it was suggested that male pregnancy co-evolved with specific immunological adaptations. Indeed, here we show that a specific amino-acid replacement in the tlx1 transcription factor is associated with seahorses’ asplenia (loss of spleen, an organ central in the immune system), as confirmed by a CRISPR-Cas9 experiment using zebrafish. Comparative genomics across the syngnathid phylogeny revealed that the complexity of the immune system gene repertoire decreases as parental care intensity increases. The synchronous evolution of immunogenetic alterations and male pregnancy supports the notion that male pregnancy co-evolved with the immunological tolerance of the embryo.
High-throughput robust single-cell DNA methylation profiling with sciMETv2
Authors: Nichols Ruth V. , O’Connell Brendan L. , Mulqueen Ryan M. , Thomas Jerushah , Woodfin Ashley R. , Acharya Sonia , Mandel Gail , Pokholok Dmitry , Steemers Frank J. , Adey Andrew C. 
Published: December 2022

AbstractDNA methylation is a key epigenetic property that drives gene regulatory programs in development and disease. Current single-cell methods that produce high quality methylomes are expensive and low throughput without the aid of extensive automation. We previously described a proof-of-principle technique that enabled high cell throughput; however, it produced only low-coverage profiles and was a difficult protocol that required custom sequencing primers and recipes and frequently produced libraries with excessive adapter contamination. Here, we describe a greatly improved version that generates high-coverage profiles (~15-fold increase) using a robust protocol that does not require custom sequencing capabilities, includes multiple stopping points, and exhibits minimal adapter contamination. We demonstrate two versions of sciMETv2 on primary human cortex, a high coverage and rapid version, identifying distinct cell types using CH methylation patterns. These datasets are able to be directly integrated with one another as well as with existing snmC-seq2 datasets with little discernible bias. Finally, we demonstrate the ability to determine cell types using CG methylation alone, which is the dominant context for DNA methylation in most cell types other than neurons and the most applicable analysis outside of brain tissue.
CO2 electroreduction to multicarbon products in strongly acidic electrolyte via synergistically modulating the local microenvironment
Authors: Ma Zesong , Yang Zhilong , Lai Wenchuan , Wang Qiyou , Qiao Yan , Tao Haolan , Lian Cheng , Liu Min , Ma Chao , Pan Anlian , Huang Hongwen 
Published: December 2022

AbstractElectrochemical CO2reduction to multicarbon products faces challenges of unsatisfactory selectivity, productivity, and long-term stability. Herein, we demonstrate CO2electroreduction in strongly acidic electrolyte (pH ≤ 1) on electrochemically reduced porous Cu nanosheets by combining the confinement effect and cation effect to synergistically modulate the local microenvironment. A Faradaic efficiency of 83.7 ± 1.4% and partial current density of 0.56 ± 0.02 A cm−2, single-pass carbon efficiency of 54.4%, and stable electrolysis of 30 h in a flow cell are demonstrated for multicarbon products in a strongly acidic aqueous electrolyte consisting of sulfuric acid and KCl with pH ≤ 1. Mechanistically, the accumulated species (e.g., K+and OH−) on the Helmholtz plane account for the selectivity and activity toward multicarbon products by kinetically reducing the proton coverage and thermodynamically favoring the CO2conversion. We find that the K+cations facilitate C-C coupling through local interaction between K+and the key intermediate *OCCO.
Gradient area-selective deposition for seamless gap-filling in 3D nanostructures through surface chemical reactivity control
Authors: Nguyen Chi Thang , Cho Eun-Hyoung , Gu Bonwook , Lee Sunghee , Kim Hae-Sung , Park Jeongwoo , Yu Neung-Kyung , Shin Sangwoo , Shong Bonggeun , Lee Jeong Yub , Lee Han-Bo-Ram 
Published: December 2022

AbstractThe integration of bottom-up fabrication techniques and top-down methods can overcome current limits in nanofabrication. For such integration, we propose a gradient area-selective deposition using atomic layer deposition to overcome the inherent limitation of 3D nanofabrication and demonstrate the applicability of the proposed method toward large-scale production of materials. Cp(CH3)5Ti(OMe)3 is used as a molecular surface inhibitor to prevent the growth of TiO2 film in the next atomic layer deposition process. Cp(CH3)5Ti(OMe)3 adsorption was controlled gradually in a 3D nanoscale hole to achieve gradient TiO2 growth. This resulted in the formation of perfectly seamless TiO2 films with a high-aspect-ratio hole structure. The experimental results were consistent with theoretical calculations based on density functional theory, Monte Carlo simulation, and the Johnson-Mehl-Avrami-Kolmogorov model. Since the gradient area-selective deposition TiO2 film formation is based on the fundamentals of molecular chemical and physical behaviours, this approach can be applied to other material systems in atomic layer deposition.
Strategies to capitalize on cell spheroid therapeutic potential for tissue repair and disease modeling
Authors: Griffin Katherine H. , Fok Shierly W. , Kent Leach J. 
Published: December 2022

AbstractCell therapies offer a tailorable, personalized treatment for use in tissue engineering to address defects arising from trauma, inefficient wound repair, or congenital malformation. However, most cell therapies have achieved limited success to date. Typically injected in solution as monodispersed cells, transplanted cells exhibit rapid cell death or insufficient retention at the site, thereby limiting their intended effects to only a few days. Spheroids, which are dense, three-dimensional (3D) aggregates of cells, enhance the beneficial effects of cell therapies by increasing and prolonging cell–cell and cell–matrix signaling. The use of spheroids is currently under investigation for many cell types. Among cells under evaluation, spheroids formed of mesenchymal stromal cells (MSCs) are particularly promising. MSC spheroids not only exhibit increased cell survival and retained differentiation, but they also secrete a potent secretome that promotes angiogenesis, reduces inflammation, and attracts endogenous host cells to promote tissue regeneration and repair. However, the clinical translation of spheroids has lagged behind promising preclinical outcomes due to hurdles in their formation, instruction, and use that have yet to be overcome. This review will describe the current state of preclinical spheroid research and highlight two key examples of spheroid use in clinically relevant disease modeling. It will highlight techniques used to instruct the phenotype and function of spheroids, describe current limitations to their use, and offer suggestions for the effective translation of cell spheroids for therapeutic treatments.
Effects of small molecule-induced dimerization on the programmed death ligand 1 protein life cycle
Authors: Chai Ilean , Kornyeyev Dmytro , Hsieh Edward , Magombedze Gesham , Stapleton Lance , Hung Magdeleine , Kwon Hyock Joo , Stefanutti Erin , Belzile JeanPhilippe , Czerwieniec Gregg , Wang Adele Y. , Morar Mariya , Lad Latesh 
Published: December 2022

AbstractThe programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) checkpoint blockade is central to Immuno-Oncology based therapies, and alternatives to antibody blockers of this interaction are an active area of research due to antibody related toxicities. Recently, small molecule compounds that induce PD-L1 dimerization and occlusion of PD-1 binding site have been identified and developed for clinical trials. This mechanism invokes an oligomeric state of PD-L1 not observed in cells previously, as PD-L1 is generally believed to function as a monomer. Therefore, understanding the cellular lifecycle of the induced PD-L1 dimer is of keen interest. Our report describes a moderate but consistent increase in the PD-L1 rate of degradation observed upon protein dimerization as compared to the monomer counterpart. This subtle change, while not resolved by measuring total PD-L1 cellular levels by western blotting, triggered investigations of the overall protein distribution across various cellular compartments. We show that PD-L1 dimerization does not lead to rapid internalization of neither transfected nor endogenously expressed protein forms. Instead, evidence is presented that dimerization results in retention of PD-L1 intracellularly, which concomitantly correlates with its reduction on the cell surface. Therefore, the obtained data for the first time points to the ability of small molecules to induce dimerization of the newly synthesized PD-L1 in addition to the protein already present on the plasma membrane. Overall, this work serves to improve our understanding of this important target on a molecular level in order to guide advances in drug development.
Evaluation of drug prescribing patterns and therapeutic drug monitoring practice using electronic medical records
Authors: Lee Sangmi , Yoon Seonghae , Jang In-Jin 
Published: December 2022

AbstractTherapeutic drug monitoring (TDM) is performed for drugs with narrow therapeutic indices. At Seoul National University Hospital (SNUH) and Seoul National University Bundang Hospital (SNUBH), TDM services are provided for various drugs such as antibiotics and antiepileptics. This study aimed to identify prescription patterns over time using electronic medical records and analyze their relationship with TDM practice. Data were collected from a clinical data warehouse from 2007 to 2020, and the number of patients, total number of drug administration days, serum level tests, and TDM were calculated. The ratio was calculated as the number of serum level tests or TDM to the total number of drug administration days. The study included 136,427 and 162,927 patients from SNUH and SNUBH who were prescribed 11 specified drugs. Each drug showed different prescription patterns over time, and the serum level test and TDM also changed with prescription pattern changes. Serum level test or TDM of antibiotics was frequently used compared to antiepileptics. As some drugs’ usage and test for drugs have decreased newly developed drugs are replacing old drugs. It is recommended that TDM services include these new drugs as well for an effective and safe therapy.
Canonical NF-κB signaling pathway and GRO-α/CXCR2 axis are activated in unruptured intracranial aneurysm patients
Authors: Kamińska Joanna , Tylicka Marzena , Dymicka-Piekarska Violetta , Mariak Zenon , Matowicka-Karna Joanna , Koper-Lenkiewicz Olga Martyna 
Published: December 2022

AbstractActivation of the nuclear factor kappa-B (NF-κB) stimulates the production of pro-inflammatory molecules involved in the formation of intracranial aneurysms (IA). The study aimed to assess the NF-κB p65 subunit and the GRO-α chemokine and its receptor CXCR2 concentrations in unruptured intracranial aneurysm patients (UIA, n = 25) compared to individuals without vascular changes in the brain (n = 10). It was also analyzed whether tested proteins are related to the size and number of aneurysms. Cerebrospinal fluid (CSF) and serum protein levels were measured using the ELISA method. Median CSF and serum NF-κB p65 concentrations were significantly lower, while median CSF GRO-α and CXCR2 concentrations were significantly higher in UIA patients compared to the control group. CSF and serum NF-κB p65 concentrations negatively correlated with the number of aneurysms. In UIA patients the median GRO-α concentration was two-fold and CXCR2 almost four-fold higher in CSF compared to the serum value. CSF GRO-α concentration positively correlated with the size of aneurysms.Significantly decreased CSF NF-κB p65 and significantly increased CSF GRO-α and its CXCR2 receptor concentrations in UIA patients compared to the control group may altogether suggest that the canonical NF-κB signaling pathway is activated and its target pro-inflammatory genes are highly expressed in UIA patients. However, to unequivocally assess the involvement of the classical NF-κB pathway with the participation of the NF-κB p65 subunit and the GRO-α/CXCR2 axis in the formation of IA, further in vivo model studies are needed.
Differentially expressed long noncoding RNAs in RAW264.7 macrophages during Brucella infection and functional analysis on the bacterial intracellular replication
Authors: Guan Xiang , Hu Hai , Tian Minxing , Zhuang Hongxu , Ding Chan , Yu Shengqing 
Published: December 2022

AbstractLong noncoding RNAs (lncRNAs) are a group of functional RNA molecules without protein-coding potential and play vital roles in majority of biological processes. To date, the expression profiles of lncRNAs and their influence on Brucella replication in RAW264.7 cells are poorly understood. In this study, we performed high-throughput transcriptome analysis to investigate the differentially expressed lncRNAs associated with Brucella abortus S2308 infection. Of these, 8, 6, 130 and 94 cellular lncRNAs were differentially expressed at 4, 8, 24 and 48 h post-infection, respectively. Moreover, 1918 protein-coding genes are predicted as potential cis target genes of differentially expressed lncRNAs by searching protein-coding genes located at upstream and downstream of lncRNA loci on the chromosome DNA of Mus musculus. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that majority of lncRNA target genes were associated with B. abortus infection. Fourteen lncRNAs from transcriptome data were selected for qRT-PCR verification, confirming 13 were differentially expressed. Animal experiments revealed three were differentially expressed in vivo by qRT-PCR analysis. Furthermore, knockdown of LNC_000428 by CRISPR/dCas9 inhibition or Locked Nucleic Acids transfection downregulated Tnfrsf8 expression at mRNA level and increased Brucella intracellular replication. Thus, we provide a novel evidence that lncRNAs induced by Brucella-infection function on Brucella intracellular replication.