bluuebunny/crossref_metadata_2025_split huggingface dataset:
Late Cretaceous‐Early Paleogene Extensional Ancestry of the Harcuvar and Buckskin‐Rawhide Metamorphic Core Complexes, Western Arizona
Authors: Wong Martin S. , Singleton John S. , Seymour Nikki M. , Gans Phillip B. , Wrobel Alexander J. 
Published: February 2023

AbstractMetamorphic core complexes in the western North American Cordillera are commonly interpreted as the result of a single phase of large‐magnitude extension during the middle to late Cenozoic. We present evidence that mylonitic shear zones in the Harcuvar and Buckskin‐Rawhide core complexes in west‐central Arizona also accommodated an earlier phase of extension during the Late Cretaceous to early Paleocene. Microstructural data indicate substantial top‐NE mylonitization occurred at amphibolite‐facies, and40Ar/39Ar thermochronology documents post‐tectonic footwall cooling to <500°C by the Paleocene to mid‐Eocene. Amphibolite‐facies mylonites are spatially associated with voluminous and variably deformed footwall leucogranites that were emplaced from ca. 74–64 Ma, and a late kinematic ca. 63 Ma dike indicates this phase of mylonitization had waned by the early Paleocene. Reconstruction of the footwall architecture indicates that this latest Cretaceous—early Paleocene deformation occurred within a NE‐dipping extensional shear zone. The leucogranites were likely the result of crustal melting due to orogenic thickening, consistent with a model whereby crustal heating triggered gravitational collapse of overthickened crust. Other tectonic processes, such as the Laramide underplating of Orocopia Schist or mantle delamination, may have also contributed to this episode of orogenic extension. Miocene large‐magnitude extension was superimposed on this older shear zone and had similar kinematics, suggesting that the location and geometry of Miocene extension was strongly influenced by tectonic inheritance. We speculate that other Cordilleran core complexes also experienced a more complex and polyphase extensional history than previously recognized, but in many cases the evidence may be obscured by later Miocene overprinting.
Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma (CHANCE001)
Authors: Zhu Hai-Dong , Li Hai-Liang , Huang Ming-Sheng , Yang Wei-Zhu , Yin Guo-Wen , Zhong Bin-Yan , Sun Jun-Hui , Jin Zhi-Cheng , Chen Jian-Jian , Ge Nai-Jian , Ding Wen-Bin , Li Wen-Hui , Huang Jin-Hua , Mu Wei , Gu Shan-Zhi , Li Jia-Ping , Zhao Hui , Wen Shu-Wei , Lei Yan-Ming , Song Yu-Sheng , Yuan Chun-Wang , Wang Wei-Dong , Huang Ming , Zhao Wei , Wu Jian-Bing , Wang Song , Zhu Xu , Han Jian-Jun , Ren Wei-Xin , Lu Zai-Ming , Xing Wen-Ge , Fan Yong , Lin Hai-Lan , Zhang Zi-Shu , Xu Guo-Hui , Hu Wen-Hao , Tu Qiang , Su Hong-Ying , Zheng Chuan-Sheng , Chen Yong , Zhao Xu-Ya , Fang Zhu-Ting , Wang Qi , Zhao Jin-Wei , Xu Ai-Bing , Xu Jian , Wu Qing-Hua , Niu Huan-Zhang , Wang Jian , Dai Feng , Feng Dui-Ping , Li Qing-Dong , Shi Rong-Shu , Li Jia-Rui , Yang Guang , Shi Hai-Bin , Ji Jian-Song , Liu Yu-E , Cai Zheng , Yang Po , Zhao Yang , Zhu Xiao-Li , Lu Li-Gong , Teng Gao-Jun ,   for the CHANCE001 Investigators
Published: February 2023

AbstractThere is considerable potential for integrating transarterial chemoembolization (TACE), programmed death-(ligand)1 (PD-[L]1) inhibitors, and molecular targeted treatments (MTT) in hepatocellular carcinoma (HCC). It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations. In this nationwide, retrospective, cohort study, 826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT (combination group, n = 376) or TACE monotherapy (monotherapy group, n = 450) were included from January 2018 to May 2021. The primary endpoint was progression-free survival (PFS) according to modified RECIST. The secondary outcomes included overall survival (OS), objective response rate (ORR), and safety. We performed propensity score matching approaches to reduce bias between two groups. After matching, 228 pairs were included with a predominantly advanced disease population. Median PFS in combination group was 9.5 months (95% confidence interval [CI], 8.4–11.0) versus 8.0 months (95% CI, 6.6–9.5) (adjusted hazard ratio [HR], 0.70, P = 0.002). OS and ORR were also significantly higher in combination group (median OS, 19.2 [16.1–27.3] vs. 15.7 months [13.0–20.2]; adjusted HR, 0.63, P = 0.001; ORR, 60.1% vs. 32.0%; P < 0.001). Grade 3/4 adverse events were observed at a rate of 15.8% and 7.5% in combination and monotherapy groups, respectively. Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS, OS, and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice, with an acceptable safety profile.
Aryl hydrocarbon receptor dependent anti-inflammation and neuroprotective effects of tryptophan metabolites on retinal ischemia/reperfusion injury
Authors: Yang Yijie , Wang Ning , Xu Li , Liu Yixin , Huang Lulu , Gu Mengyang , Wu Yue , Guo Wenyi , Sun Hao 
Published: February 2023

AbstractGlaucoma is the major cause of irreversible blindness in the world characterized by progressive retinal neurodegeneration, in which local inflammation in retina is involved in persistent loss of retinal ganglion cells (RGCs). In order to explore whether aryl hydrocarbon receptor (AhR) and its agonists tryptophan metabolites are involved in the development of glaucoma, we collected serum and retinas from non-glaucoma controls and patients with glaucoma. Results showed altered serum tryptophan metabolism and reduced retinal AhR expression in glaucoma patients. We also showed intraperitoneally injection of tryptophan metabolite 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) down-regulated retinal local inflammation and protected RGC apoptosis from retinal ischemia/reperfusion (IR) injury via AhR activation. We further revealed that ITE could inhibit inflammation in BV2 microglia and alleviate the neurotoxicity of microglial conditioned medium to RGCs under IR. Finally, we illustrated the possible mechanism that ITE limited ERK and NFκB dependent microglial inflammation. In summary, these findings suggest the critical role of tryptophan metabolism and retinal AhR signaling in modulating local inflammation mediated by microglia in glaucoma, and provide a novel avenue to targeting the intrinsically altered AhR signaling resulted from disturbed tryptophan metabolism for glaucoma treatment.
Gasdermin D inhibition ameliorates neutrophil mediated brain damage in acute ischemic stroke
Authors: Hu Ruiyao , Liang Jing , Ding Lan , Zhang Wan , Wang Yuying , Zhang Yige , Zhang Ding , Pei Lulu , Liu Xinjing , Xia Zongping , Xu Yuming , Song Bo 
Published: February 2023

AbstractAcute ischemic stroke (AIS) induces high level of neutrophils, which correlates inversely with patient survival. Pyroptosis induced by gasdermin D (GSDMD) has been shown to have an important role in the pathophysiology of several inflammatory disorders. The role of GSDMD in the high level of neutrophils after AIS is unknown. Using a middle cerebral artery occlusion (MCAO) mouse model, we identified activation of pyroptosis signal, including expression of caspase-1/11, GSDMD, and interleukin-1β/18 (IL-1β/18), in the brain and spleen at early ischemic injury. Knockout of GSDMD in mice reduced infarct size, improved neurological function, and increased survival after MCAO. GSDMD deficiency decreased the overall degree of inflammation and the proportion of neutrophils in the brain after MCAO. Quantitative studies of neutrophils at several time intervals and organs demonstrated that early inflammatory leucocyte production and supplement (1 day after MCAO) was GSDMD-dependent. A series of bone marrow transplantation experiments, neutrophil depletion experiments, and RNA sequencing results demonstrated that neutrophil specific GSDMD is essential for the production and supply of neutrophil in bone marrow to blood. Moreover, pharmacological suppression of GSDMD decreased pathological abnormalities, infarct volume, and ameliorated neurological function. These results provided a new viewpoint on the immunological modulation of neutrophils after MCAO and suggest that suppression of GSDMD may relieve the neuroinflammatory load, thereby providing a potential treatment strategy for stroke.
Higher consumption of ultra-processed foods and increased likelihood of central nervous system demyelination in a case-control study of Australian adults
Authors: Mannino Adriana , Daly Alison , Dunlop Eleanor , Probst Yasmine , Ponsonby Anne-Louise , van der Mei Ingrid A. F. ,   the Ausimmune Investigator Group, Chapman Caron , Coulthard Alan , Dear Keith , Dwyer Terry , Kilpatrick Trevor , Lucas Robyn , McMichael Tony , Ponsonby Anne-Louise , Taylor Bruce , Valery Patricia , van der Mei Ingrid A. F. , Williams David , Black Lucinda J. 
Published: February 2023

Abstract
Background
Consumption of ultra-processed foods (UPFs) has been linked to risk of chronic diseases, with scant evidence in relation to multiple sclerosis (MS).

Methods
We tested associations between UPF consumption and likelihood of a first clinical diagnosis of central nervous system demyelination (FCD) (267 cases, 508 controls), a common precursor to MS. We used data from the 2003–2006 Ausimmune Study and logistic regression with full propensity score matching for age, sex, region of residence, education, smoking history, body mass index, physical activity, history of infectious mononucleosis, dietary misreporting, and total energy intake.

Results
Higher UPF consumption was statistically significantly associated with an increased likelihood of FCD (adjusted odds ratio = 1.08; 95% confidence interval = 1.0,1.15; p = 0.039), representing an 8% increase in likelihood of FCD per one energy-adjusted serving/day of UPFs.

Conclusion
Higher intakes of UPF were associated with increased likelihood of FCD in this Australian cohort. Nutrition education and awareness of healthy eating patterns may benefit those at high risk of FCD.
Design and implementation of a hybrid cloud system for large-scale human genomic research
Authors: Nagasaki Masao , Sekiya Yayoi , Asakura Akihiro , Teraoka Ryo , Otokozawa Ryoko , Hashimoto Hiroki , Kawaguchi Takahisa , Fukazawa Keiichiro , Inadomi Yuichi , Murata Ken T. , Ohkawa Yasuyuki , Yamaguchi Izumi , Mizuhara Takamichi , Tokunaga Katsushi , Sekiya Yuji , Hanawa Toshihiro , Yamada Ryo , Matsuda Fumihiko 
Published: February 2023

AbstractIn the field of genomic medical research, the amount of large-scale information continues to increase due to advances in measurement technologies, such as high-performance sequencing and spatial omics, as well as the progress made in genomic cohort studies involving more than one million individuals. Therefore, researchers require more computational resources to analyze this information. Here, we introduce a hybrid cloud system consisting of an on-premise supercomputer, science cloud, and public cloud at the Kyoto University Center for Genomic Medicine in Japan as a solution. This system can flexibly handle various heterogeneous computational resource-demanding bioinformatics tools while scaling the computational capacity. In the hybrid cloud system, we demonstrate the way to properly perform joint genotyping of whole-genome sequencing data for a large population of 11,238, which can be a bottleneck in sequencing data analysis. This system can be one of the reference implementations when dealing with large amounts of genomic medical data in research centers and organizations.
CryoET reveals organelle phenotypes in huntington disease patient iPSC-derived and mouse primary neurons
Authors: Wu Gong-Her , Smith-Geater Charlene , Galaz-Montoya Jesús G. , Gu Yingli , Gupte Sanket R. , Aviner Ranen , Mitchell Patrick G. , Hsu Joy , Miramontes Ricardo , Wang Keona Q. , Geller Nicolette R. , Hou Cathy , Danita Cristina , Joubert Lydia-Marie , Schmid Michael F. , Yeung Serena , Frydman Judith , Mobley William , Wu Chengbiao , Thompson Leslie M. , Chiu Wah 
Published: February 2023

AbstractHuntington’s disease (HD) is caused by an expanded CAG repeat in the huntingtin gene, yielding a Huntingtin protein with an expanded polyglutamine tract. While experiments with patient-derived induced pluripotent stem cells (iPSCs) can help understand disease, defining pathological biomarkers remains challenging. Here, we used cryogenic electron tomography to visualize neurites in HD patient iPSC-derived neurons with varying CAG repeats, and primary cortical neurons from BACHD, deltaN17-BACHD, and wild-type mice. In HD models, we discovered sheet aggregates in double membrane-bound organelles, and mitochondria with distorted cristae and enlarged granules, likely mitochondrial RNA granules. We used artificial intelligence to quantify mitochondrial granules, and proteomics experiments reveal differential protein content in isolated HD mitochondria. Knockdown of Protein Inhibitor of Activated STAT1 ameliorated aberrant phenotypes in iPSC- and BACHD neurons. We show that integrated ultrastructural and proteomic approaches may uncover early HD phenotypes to accelerate diagnostics and the development of targeted therapeutics for HD.
Engineering the lymph node environment promotes antigen-specific efficacy in type 1 diabetes and islet transplantation
Authors: Gammon Joshua M. , Carey Sean T. , Saxena Vikas , Eppler Haleigh B. , Tsai Shannon J. , Paluskievicz Christina , Xiong Yanbao , Li Lushen , Ackun-Farmmer Marian , Tostanoski Lisa H. , Gosselin Emily A. , Yanes Alexis A. , Zeng Xiangbin , Oakes Robert S. , Bromberg Jonathan S. , Jewell Christopher M. 
Published: February 2023

AbstractAntigen-specific tolerance is a key goal of experimental immunotherapies for autoimmune disease and allograft rejection. This outcome could selectively inhibit detrimental inflammatory immune responses without compromising functional protective immunity. A major challenge facing antigen-specific immunotherapies is ineffective control over immune signal targeting and integration, limiting efficacy and causing systemic non-specific suppression. Here we use intra-lymph node injection of diffusion-limited degradable microparticles that encapsulate self-antigens with the immunomodulatory small molecule, rapamycin. We show this strategy potently inhibits disease during pre-clinical type 1 diabetes and allogenic islet transplantation. Antigen and rapamycin are required for maximal efficacy, and tolerance is accompanied by expansion of antigen-specific regulatory T cells in treated and untreated lymph nodes. The antigen-specific tolerance in type 1 diabetes is systemic but avoids non-specific immune suppression. Further, microparticle treatment results in the development of tolerogenic structural microdomains in lymph nodes. Finally, these local structural and functional changes in lymph nodes promote memory markers among antigen-specific regulatory T cells, and tolerance that is durable. This work supports intra-lymph node injection of tolerogenic microparticles as a powerful platform to promote antigen-dependent efficacy in type 1 diabetes and allogenic islet transplantation.
MORF and MOZ acetyltransferases target unmethylated CpG islands through the winged helix domain
Authors: Becht Dustin C. , Klein Brianna J. , Kanai Akinori , Jang Suk Min , Cox Khan L. , Zhou Bing-Rui , Phanor Sabrina K. , Zhang Yi , Chen Ruo-Wen , Ebmeier Christopher C. , Lachance Catherine , Galloy Maxime , Fradet-Turcotte Amelie , Bulyk Martha L. , Bai Yawen , Poirier Michael G. , Côté Jacques , Yokoyama Akihiko , Kutateladze Tatiana G. 
Published: February 2023

AbstractHuman acetyltransferases MOZ and MORF are implicated in chromosomal translocations associated with aggressive leukemias. Oncogenic translocations involve the far amino terminus of MOZ/MORF, the function of which remains unclear. Here, we identified and characterized two structured winged helix (WH) domains, WH1 and WH2, in MORF and MOZ. WHs bind DNA in a cooperative manner, with WH1 specifically recognizing unmethylated CpG sequences. Structural and genomic analyses show that the DNA binding function of WHs targets MORF/MOZ to gene promoters, stimulating transcription and H3K23 acetylation, and WH1 recruits oncogenic fusions to HOXA genes that trigger leukemogenesis. Cryo-EM, NMR, mass spectrometry and mutagenesis studies provide mechanistic insight into the DNA-binding mechanism, which includes the association of WH1 with the CpG-containing linker DNA and binding of WH2 to the dyad of the nucleosome. The discovery of WHs in MORF and MOZ and their DNA binding functions could open an avenue in developing therapeutics to treat diseases associated with aberrant MOZ/MORF acetyltransferase activities.
Weak CO binding sites induced by Cu–Ag interfaces promote CO electroreduction to multi-carbon liquid products
Authors: Li Jing , Xiong Haocheng , Liu Xiaozhi , Wu Donghuan , Su Dong , Xu Bingjun , Lu Qi 
Published: February 2023

AbstractElectrochemical reduction of carbon monoxide to high-value multi-carbon (C2+) products offers an appealing route to store sustainable energy and make use of the chief greenhouse gas leading to climate change, i.e., CO2. Among potential products, C2+liquid products such as ethanol are of particular interest owing to their high energy density and industrial relevance. In this work, we demonstrate that Ag-modified oxide-derive Cu catalysts prepared via high-energy ball milling exhibit near 80% Faradaic efficiencies for C2+liquid products at commercially relevant current densities (>100 mA cm−2) in the CO electroreduction in a microfluidic flow cell. Such performance is retained in an over 100-hour electrolysis in a 100 cm2membrane electrode assembly (MEA) electrolyzer. A method based on surface-enhanced infrared absorption spectroscopy is developed to characterize the CO binding strength on the catalyst surface. The lower C and O affinities of the Cu–Ag interfacial sites in the prepared catalysts are proposed to be responsible for the enhanced selectivity for C2+oxygenates, which is the experimental verification of recent computational predictions.
Finding stable multi-component materials by combining cluster expansion and crystal structure predictions
Authors: Carlsson Adam , Rosen Johanna , Dahlqvist Martin 
Published: February 2023

AbstractA desired prerequisite when performing a quantum mechanical calculation is to have an initial idea of the atomic positions within an approximate crystal structure. The atomic positions combined should result in a system located in, or close to, an energy minimum. However, designing low-energy structures may be a challenging task when prior knowledge is scarce, specifically for large multi-component systems where the degrees of freedom are close to infinite. In this paper, we propose a method for identification of low-energy crystal structures within multi-component systems by combining cluster expansion and crystal structure predictions with density-functional theory calculations. Crystal structure prediction searches are applied to the Mo2AlB2 and Sc2AlB2 ternary systems to identify candidate structures, which are subsequently used to explore the quaternary (pseudo-binary) (MoxSc1–x)2AlB2 system through the cluster expansion formalism utilizing the ground-state search approach. Furthermore, we show that utilizing low-energy structures found within the cluster expansion ground-state search as seed structures within crystal structure predictions of (MoxSc1–x)2AlB2 can significantly reduce the computational demands. With this combined approach, we not only correctly identified the recently discovered Mo4/3Sc2/3AlB2i-MAB phase, comprised of in-plane chemical ordering of Mo and Sc and with Al in a Kagomé lattice, but also predict additional low-energy structures at various concentrations. This result demonstrates that combining crystal structure prediction with cluster expansion provides a path for identifying low-energy crystal structures in multi-component systems by employing the strengths from both frameworks.
Key recommendations for primary care from the 2022 Global Initiative for Asthma (GINA) update
Authors: Levy Mark L. , Bacharier Leonard B. , Bateman Eric , Boulet Louis-Philippe , Brightling Chris , Buhl Roland , Brusselle Guy , Cruz Alvaro A. , Drazen Jeffrey M. , Duijts Liesbeth , Fleming Louise , Inoue Hiromasa , Ko Fanny W. S. , Krishnan Jerry A. , Mortimer Kevin , Pitrez Paulo M. , Sheikh Aziz , Yorgancıoğlu Arzu , Reddel Helen K. 
Published: February 2023

AbstractThe Global Initiative for Asthma (GINA) was established in 1993 by the World Health Organization and the US National Heart Lung and Blood Institute to improve asthma awareness, prevention and management worldwide. GINA develops and publishes evidence-based, annually updated resources for clinicians. GINA guidance is adopted by national asthma guidelines in many countries, adapted to fit local healthcare systems, practices, and resource availability. GINA is independent of industry, funded by the sale and licensing of its materials. This review summarizes key practical guidance for primary care from the 2022 GINA strategy report. It provides guidance on confirming the diagnosis of asthma using spirometry or peak expiratory flow. GINA recommends that all adults, adolescents and most children with asthma should receive inhaled corticosteroid (ICS)-containing therapy to reduce the risk of severe exacerbations, either taken regularly, or (for adults and adolescents with “mild” asthma) as combination ICS–formoterol taken as needed for symptom relief. For patients with moderate–severe asthma, the preferred regimen is maintenance-and-reliever therapy (MART) with ICS–formoterol. Asthma treatment is not “one size fits all”; GINA recommends individualized assessment, adjustment, and review of treatment. As many patients with difficult-to-treat or severe asthma are not referred early for specialist review, we provide updated guidance for primary care on diagnosis, further investigation, optimization and treatment of severe asthma across secondary and tertiary care. While the GINA strategy has global relevance, we recognize that there are special considerations for its adoption in low- and middle-income countries, particularly the current poor access to inhaled medications.
Effects of adjuvants in a rabies-vectored Ebola virus vaccine on protection from surrogate challenge
Authors: Yankowski Catherine , Kurup Drishya , Wirblich Christoph , Schnell Matthias J. 
Published: February 2023

AbstractEbola virus is the primary contributor to the global threat of filovirus severe hemorrhagic fever, and Ebola virus disease has a case fatality rate of 50–90%. An inactivated, bivalent filovirus/rabies virus vaccine, FILORAB1, consists of recombinant rabies virus virions expressing the Ebola virus glycoprotein. FILORAB1 is immunogenic and protective from Ebola virus challenge in mice and non-human primates, and protection is enhanced when formulated with toll-like receptor 4 agonist Glucopyranosyl lipid adjuvant (GLA) in a squalene oil-in-water emulsion (SE). Through an adjuvant comparison in mice, we demonstrate that GLA-SE improves FILORAB1 efficacy by activating the innate immune system and shaping a Th1-biased adaptive immune response. GLA-SE adjuvanted mice and those adjuvanted with the SE component are better protected from surrogate challenge, while Th2 alum adjuvanted mice are not. Additionally, the immune response to FILORAB1 is long-lasting, as exhibited by highly-maintained serum antibody titers and long-lived cells in the spleen and bone marrow.