bluuebunny/crossref_metadata_2025_split huggingface dataset:
Climate, Variability, and Climate Sensitivity of “Middle Atmosphere” Chemistry Configurations of the Community Earth System Model Version 2, Whole Atmosphere Community Climate Model Version 6 (CESM2(WACCM6))
Authors: Davis N. A. , Visioni D. , Garcia R. R. , Kinnison D. E. , Marsh D. R. , Mills M. , Richter J. H. , Tilmes S. , Bardeen C. G. , Gettelman A. , Glanville A. A. , MacMartin D. G. , Smith A. K. , Vitt F. 
Published: September 2023

AbstractSimulating whole atmosphere dynamics, chemistry, and physics is computationally expensive. It can require high vertical resolution throughout the middle and upper atmosphere, as well as a comprehensive chemistry and aerosol scheme coupled to radiation physics. An unintentional outcome of the development of one of the most sophisticated and hence computationally expensive model configurations is that it often excludes a broad community of users with limited computational resources. Here, we analyze two configurations of the Community Earth System Model Version 2, Whole Atmosphere Community Climate Model Version 6 (CESM2(WACCM6)) with simplified “middle atmosphere” chemistry at nominal 1 and 2° horizontal resolutions. Using observations, a reanalysis, and direct model comparisons, we find that these configurations generally reproduce the climate, variability, and climate sensitivity of the 1° nominal horizontal resolution configuration with comprehensive chemistry. While the background stratospheric aerosol optical depth is elevated in the middle atmosphere configurations as compared to the comprehensive chemistry configuration, it is comparable among all configurations during volcanic eruptions. For any purposes other than those needing an accurate representation of tropospheric organic chemistry and secondary organic aerosols, these simplified chemistry configurations deliver reliable simulations of the whole atmosphere that require 35% and 86% fewer computational resources at nominal 1 and 2° horizontal resolution, respectively.
Propagation Analysis Method Considering Angular Spread for Random Electromagnetic Waves in Magnetized Cold Plasma
Authors: Ota Mamoru , Tanaka Yuji , Kasahara Yoshiya 
Published: September 2023

AbstractRandom waves can be described as the sum of numerous plane waves, and stochastic processes describe their properties. Various methods have been used to widely investigate the propagation characteristics of electromagnetic waves in magnetized cold plasma based on a single‐plane wave approximation. On the other hand, the properties of random waves are difficult to analyze using these methods. Instead, a framework of the wave distribution function (WDF) should be employed. In this study, we provide an explicit expression for an integration kernel in a magnetized cold plasma used for the WDF method. We show that the kernel can be approximated in the case of ultralow frequency/very low frequency (ULF/VLF) parts of whistler‐mode waves with quasi‐parallel propagation. We also propose a method for estimating a WDF representing a directional distribution of the wave energy density based on the principle of maximum entropy using three‐component spectral matrix data of the magnetic field. Based on the insights obtained from the proposed method, we define a quantity called “sharpness,” which provides spreading of wave normal angles. The sharpness is particularly effective in showing the spread of the wave normal angles for random non‐single‐plane waves. Compared with the conventional methods which evaluate the propagation properties (such as planarity), the “sharpness” exhibited a low calculation load and can be implemented easily for onboard processing.
Knockdown of PGC1α suppresses dysplastic oral keratinocytes proliferation through reprogramming energy metabolism
Authors: Liu Yunkun , Huang Nengwen , Qiao Xianghe , Gu Zhiyu , Wu Yongzhi , Li Jinjin , Wu Chengzhou , Li Bo , Li Longjiang 
Published: September 2023

AbstractOral potentially malignant disorders (OPMDs) are precursors of oral squamous cell carcinoma (OSCC). Deregulated cellular energy metabolism is a critical hallmark of cancer cells. Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC1α) plays vital role in mitochondrial energy metabolism. However, the molecular mechanism of PGC1α on OPMDs progression is less unclear. Therefore, we investigated the effects of knockdown PGC1α on human dysplastic oral keratinocytes (DOKs) comprehensively, including cell proliferation, cell cycle, apoptosis, xenograft tumor, mitochondrial DNA (mtDNA), mitochondrial electron transport chain complexes (ETC), reactive oxygen species (ROS), oxygen consumption rate (OCR), extracellular acidification rate (ECAR), and glucose uptake. We found that knockdown PGC1α significantly inhibited the proliferation of DOKs in vitro and tumor growth in vivo, induced S-phase arrest, and suppressed PI3K/Akt signaling pathway without affecting cell apoptosis. Mechanistically, downregulated of PGC1α decreased mtDNA, ETC, and OCR, while enhancing ROS, glucose uptake, ECAR, and glycolysis by regulating lactate dehydrogenase A (LDHA). Moreover, SR18292 (an inhibitor of PGC1α) induced oxidative phosphorylation dysfunction of DOKs and declined DOK xenograft tumor progression. Thus, our work suggests that PGC1α plays a crucial role in cell proliferation by reprograming energy metabolism and interfering with energy metabolism, acting as a potential therapeutic target for OPMDs.
A population-based study of transformed marginal zone lymphoma: identifying outcome-related characteristics
Authors: Bult Johanna A. A. , Huisman Francien , Zhong Yujie , Veltmaat Nick , Kluiver Joost , Tonino Sanne H. , Vermaat Joost S. P. , Chamuleau Martine E. D. , Diepstra Arjan , van den Berg Anke , Plattel Wouter J. , Brink Mirian , Nijland Marcel 
Published: September 2023

AbstractHistological transformation of marginal zone lymphoma (tMZL) into diffuse large B-cell lymphoma is associated with poor outcomes. Clinical characteristics associated with transformation risk and outcome after transformation are largely unknown due to scarcity of data. In this population-based study, competing risk analyses were performed to elucidate clinical characteristics associated with developing transformation among 1793 MZL patients using the Netherlands Cancer Registry. Cox regression analyses were performed to elucidate clinical characteristics associated with risk of relapse and mortality after transformation. Transformation occurred in 75 (4%) out of 1793 MZL patients. Elevated LDH and nodal MZL subtype at MZL diagnosis were associated with an increased risk, and radiotherapy with a reduced risk of developing tMZL. Most tMZL patients received R-(mini)CHOP (n = 53, 71%). Age >60 years and (immuno)chemotherapy before transformation were associated with an increased risk of relapse and mortality after transformation. Two-year progression-free survival (PFS) and overall survival (OS) were 66% (95% CI 52–77%) and 75% (95% CI 62–85%) for R-(mini)CHOP-treated tMZL patients, as compared to a PFS and OS both of 41% (95% CI 19–63%) for patients treated otherwise. Our study offers comprehensive insights into characteristics associated with transformation and survival after transformation, thereby optimizing guidelines and patient counseling.
'You just don't have the time to keep bringing them back, bringing them back': the experience of primary care dental professionals in England when treating young children with carious teeth
Authors: Timms Laura , Rodd Helen , Deery Chris , Brocklehurst Paul , Marshman Zoe 
Published: September 2023

AbstractIntroduction Caries in the primary dentition affects around one-quarter of children in England. There is uncertainty and varying practice regarding the management of these children within NHS primary dental care. Silver diamine fluoride (SDF) is an approach that is not well-adopted nationally. This study aims to explore the factors affecting treatment choices for caries management in young children within primary dental care, including the use of SDF.Methods Semi-structured interviews were carried out via video conferencing with general dental practitioners and therapists working in NHS primary care. The topic guide covered factors which influence the management of caries in primary teeth, with SDF-specific questions. These were transcribed verbatim and analysed using thematic analysis.Results A total of 13 interviews were conducted with dental professionals working across Yorkshire and the East Midlands. Decision-making for caries management was dependent on inter-related factors, which also influenced SDF use. Treatment decisions were taken on a case-by-case basis, but were influenced by the child, their parents, the dental professional and service factors, along with the clinical technique.Conclusion Many individual- and system-level factors influence treatment decisions for early childhood caries. However, issues relating to remuneration and governance appear to be specific barriers to adoption of SDF in primary dental care.
Improving the cytotoxic response of tumor-infiltrating lymphocytes towards advanced stage ovarian cancer with an oncolytic adenovirus expressing a human vIL-2 cytokine
Authors: Quixabeira D. C. A. , Jirovec E. , Pakola S. , Havunen R. , Basnet S. , Santos J. M. , Kudling T. V. , Clubb J. H. A. , Haybout L. , Arias V. , Grönberg-Vähä-Koskela S. , Cervera-Carrascon V. , Pasanen A. , Anttila M. , Tapper J. , Kanerva A. , Hemminki A. 
Published: September 2023

AbstractWhile the presence of tumor-infiltrating lymphocytes (TILs) associates with improved survival prognosis in ovarian cancer (OvCa) patients, TIL therapy benefit is limited. Here, we evaluated an oncolytic adenovirus coding for a human variant IL-2 (vIL-2) cytokine, Ad5/3-E2F-d24-vIL2 (vIL-2 virus), also known as TILT-452, as an immunotherapeutic strategy to enhance TIL responsiveness towards advanced stage OvCa tumors. Fragments of resected human OvCa tumors were processed into single-cell suspensions, and autologous TILs were expanded from said samples. OvCa tumor specimens were co-cultured with TILs plus vIL-2 virus, and cell killing was assessed in real time through cell impedance measurement. Combination therapy was further evaluated in vivo through a patient-derived xenograft (PDX) ovarian cancer murine model. The combination of vIL-2 virus plus TILs had best cancer cell killing ex vivo compared to TILs monotherapy. These results were supported by an in vivo experiment, where the best OvCa tumor control was obtained when vIL-2 virus was added to TIL therapy. Furthermore, the proposed therapy induced a highly cytotoxic phenotype demonstrated by increased granzyme B intensity in NK cells, CD4+ T, and CD8+ T cells in treated tumors. Our results demonstrate that Ad5/3-E2F-d24-vIL2 therapy consistently improved TILs therapy cytotoxicity in treated human OvCa tumors.
TGR5 supresses cGAS/STING pathway by inhibiting GRP75-mediated endoplasmic reticulum-mitochondrial coupling in diabetic retinopathy
Authors: Li Yan , Zhu Lingpeng , Cai Meng-Xia , Wang Zi-Li , Zhuang Miao , Tan Cheng-Ye , Xie Tian-Hua , Yao Yong , Wei Ting-Ting 
Published: September 2023

AbstractDiabetic retinopathy (DR) is a serious and relatively under-recognized complication of diabetes. Müller glial cells extend throughout the retina and play vital roles in maintaining retinal homeostasis. Previous studies have demonstrated that TGR5, a member of the bile acid-activated GPCR family, could ameliorate DR. However, the role of TGR5 in regulating Müller cell function and the underlying mechanism remains to be ascertained. To address this, high glucose (HG)-treated human Müller cells and streptozotocin-treated Sprague-Dawley rats were used in the study. The IP3R1-GRP75-VDAC1 axis and mitochondrial function were assessed after TGR5 ablation or agonism. Cytosolic mitochondrial DNA (mtDNA)-mediated cGAS-STING activation was performed. The key markers of retinal vascular leakage, apoptosis, and inflammation were examined. We found that mitochondrial Ca2+ overload and mitochondrial dysfunction were alleviated by TGR5 agonist. Mechanically, TGR5 blocked the IP3R1-GRP75-VDAC1 axis mediated Ca2+ efflux from the endoplasmic reticulum into mitochondria under diabetic condition. Mitochondrial Ca2+ overload led to the opening of the mitochondrial permeability transition pore and the release of mitochondrial DNA (mtDNA) into the cytosol. Cytoplasmic mtDNA bound to cGAS and upregulated 2’3’ cyclic GMP-AMP. Consequently, STING-mediated inflammatory responses were activated. TGR5 agonist prevented retinal injury, whereas knockdown of TGR5 exacerbated retinal damage in DR rats, which was rescued by the STING inhibitor. Based on the above results, we propose that TGR5 might be a novel therapeutic target for the treatment of DR.
Knockdown of ANXA10 induces ferroptosis by inhibiting autophagy-mediated TFRC degradation in colorectal cancer
Authors: Wang Xinyuan , Zhou Yujie , Ning Lijun , Chen Jinnan , Chen Huimin , Li Xiaobo 
Published: September 2023

AbstractAnnexin A10 (ANXA10) belongs to a family of membrane-bound calcium-dependent phospholipid-binding proteins, but its precise function remains unclear. Further research is required to understand its role in sessile serrated lesions (SSL) and colorectal cancer (CRC). We conducted transcriptome sequencing on pairs of SSL and corresponding normal control (NC) samples. Bioinformatic methods were utilized to assess ANXA10 expression in CRC. We knocked down and overexpressed ANXA10 in CRC cells to examine its effects on cell malignant ability. The effect of ANXA10 on lung metastasis of xenograft tumor cells in nude mice was also assessed. Furthermore, we used quantitative polymerase chain reaction, western blotting, and flow cytometry for reactive oxygen species (ROS), lipid ROS, and intracellular Fe2+ to measure ferroptosis. Immunoblotting and Immunofluorescence staining were used to detect autophagy. We found that ANXA10 was significantly overexpressed in SSL compared to NC. ANXA10 was also highly expressed in BRAF mutant CRCs and was associated with poor prognosis. ANXA10 knockdown reduced the survival, proliferation, and migration ability of CRC cells. Knockdown of ANXA10 inhibited lung metastasis of CRC cells in mice. ANXA10 knockdown increased transferrin receptor (TFRC) protein levels and led to downregulation of GSH/GSSG, increased Fe2+, MDA concentration, and ROS and lipid ROS in cells. Knockdown of ANXA10 inhibited TFRC degradation and was accompanied by an accumulation of autophagic flux and an increase in SQSTM1. Finally, Fer-1 rescued the migration and viability of ANXA10 knockdown cell lines. In brief, the knockdown of ANXA10 induces cellular ferroptosis by inhibiting autophagy-mediated TFRC degradation, thereby inhibiting CRC progression. This study reveals the mechanism of ANXA10 in ferroptosis, suggesting that it may serve as a potential therapeutic target for CRC of the serrated pathway.
Acid-sensing ion channel 1a modulation of apoptosis in acidosis-related diseases: implications for therapeutic intervention
Authors: Zhang Zhenyu , Chen Minnan , Zhan Wenjing , Chen Yuechun , Wang Tongtong , Chen Zhonghua , Fu Yifei , Zhao Gang , Mao Dong , Ruan Jingjing , Yuan Feng-Lai 
Published: September 2023

AbstractAcid-sensing ion channel 1a (ASIC1a), a prominent member of the acid-sensing ion channel (ASIC) superfamily activated by extracellular protons, is ubiquitously expressed throughout the human body, including the nervous system and peripheral tissues. Excessive accumulation of Ca2+ ions via ASIC1a activation may occur in the acidified microenvironment of blood or local tissues. ASIC1a-mediated Ca2+‑induced apoptosis has been implicated in numerous pathologies, including neurological disorders, cancer, and rheumatoid arthritis. This review summarizes the role of ASIC1a in the modulation of apoptosis via various signaling pathways across different disease states to provide insights for future studies on the underlying mechanisms and development of therapeutic strategies.
The role and implication of autophagy in cholangiocarcinoma
Authors: Khizar Hayat , Hu Yufei , Wu Yanhua , Yang Jianfeng 
Published: September 2023

AbstractCholangiocarcinoma (CCA) is a malignant tumor that originates from the biliary epithelial cells. It is characterized by a difficult diagnosis and limited treatment options. Autophagy is a cellular survival mechanism that maintains nutrient and energy homeostasis and eliminates intracellular pathogens. It is involved in various physiological and pathological processes, including the development of cancer. However, the role, mechanism, and potential therapeutic targets of autophagy in CCA have not been thoroughly studied. In this review, we introduce the classification, characteristics, process, and related regulatory genes of autophagy. We summarize the regulation of autophagy on the progression of CCA and collect the latest research progress on some autophagy modulators with clinical potential in CCA. In conclusion, combining autophagy modulators with immunotherapy, chemotherapy, and targeted therapy has great potential in the treatment of CCA. This combination may be a potential therapeutic target for CCA in the future.
Dissociable roles of human frontal eye fields and early visual cortex in presaccadic attention
Authors: Hanning Nina M. , Fernández Antonio , Carrasco Marisa 
Published: September 2023

AbstractShortly before saccadic eye movements, visual sensitivity at the saccade target is enhanced, at the expense of sensitivity elsewhere. Some behavioral and neural correlates of this presaccadic shift of attention resemble those of covert attention, deployed during fixation. Microstimulation in non-human primates has shown that presaccadic attention modulates perception via feedback from oculomotor to visual areas. This mechanism also seems plausible in humans, as both oculomotor and visual areas are active during saccade planning. We investigated this hypothesis by applying TMS to frontal or visual areas during saccade preparation. By simultaneously measuring perceptual performance, we show their causal and differential roles in contralateral presaccadic attention effects: Whereas rFEF+ stimulation enhanced sensitivity opposite the saccade target throughout saccade preparation, V1/V2 stimulation reduced sensitivity at the saccade target only shortly before saccade onset. These findings are consistent with presaccadic attention modulating perception through cortico-cortical feedback and further dissociate presaccadic and covert attention.
Designing nanohesives for rapid, universal, and robust hydrogel adhesion
Authors: Pan Zhao , Fu Qi-Qi , Wang Mo-Han , Gao Huai-Ling , Dong Liang , Zhou Pu , Cheng Dong-Dong , Chen Ying , Zou Duo-Hong , He Jia-Cai , Feng Xue , Yu Shu-Hong 
Published: September 2023

AbstractNanoparticles-based glues have recently been shown with substantial potential for hydrogel adhesion. Nevertheless, the transformative advance in hydrogel-based application places great challenges on the rapidity, robustness, and universality of achieving hydrogel adhesion, which are rarely accommodated by existing nanoparticles-based glues. Herein, we design a type of nanohesives based on the modulation of hydrogel mechanics and the surface chemical activation of nanoparticles. The nanohesives can form robust hydrogel adhesion in seconds, to the surface of arbitrary engineering solids and biological tissues without any surface pre-treatments. A representative application of hydrogel machine demonstrates the tough and compliant adhesion between dynamic tissues and sensors via nanohesives, guaranteeing accurate and stable blood flow monitoring in vivo. Combined with their biocompatibility and inherent antimicrobial properties, the nanohesives provide a promising strategy in the field of hydrogel based engineering.
DNA nanopores as artificial membrane channels for bioprotonics
Authors: Luo Le , Manda Swathi , Park Yunjeong , Demir Busra , Sanchez Jesse , Anantram M. P. , Oren Ersin Emre , Gopinath Ashwin , Rolandi Marco 
Published: September 2023

AbstractBiological membrane channels mediate information exchange between cells and facilitate molecular recognition. While tuning the shape and function of membrane channels for precision molecular sensing via de-novo routes is complex, an even more significant challenge is interfacing membrane channels with electronic devices for signal readout, which results in low efficiency of information transfer - one of the major barriers to the continued development of high-performance bioelectronic devices. To this end, we integrate membrane spanning DNA nanopores with bioprotonic contacts to create programmable, modular, and efficient artificial ion-channel interfaces. Here we show that cholesterol modified DNA nanopores spontaneously and with remarkable affinity span the lipid bilayer formed over the planar bio-protonic electrode surface and mediate proton transport across the bilayer. Using the ability to easily modify DNA nanostructures, we illustrate that this bioprotonic device can be programmed for electronic recognition of biomolecular signals such as presence of Streptavidin and the cardiac biomarker B-type natriuretic peptide, without modifying the biomolecules. We anticipate this robust interface will allow facile electronic measurement and quantification of biomolecules in a multiplexed manner.
Turing structuring with multiple nanotwins to engineer efficient and stable catalysts for hydrogen evolution reaction
Authors: Gu Jialun , Li Lanxi , Xie Youneng , Chen Bo , Tian Fubo , Wang Yanju , Zhong Jing , Shen Junda , Lu Jian 
Published: September 2023

AbstractLow-dimensional nanocrystals with controllable defects or strain modifications are newly emerging active electrocatalysts for hydrogen-energy conversion and utilization; however, a crucial challenge remains in insufficient stability due to spontaneous structural degradation and strain relaxation. Here we report a Turing structuring strategy to activate and stabilize superthin metal nanosheets by incorporating high-density nanotwins. Turing configuration, realized by constrained orientation attachment of nanograins, yields intrinsically stable nanotwin network and straining effects, which synergistically reduce the energy barrier of water dissociation and optimize the hydrogen adsorption free energy for hydrogen evolution reaction. Turing PtNiNb nanocatalyst achieves 23.5 and 3.1 times increase in mass activity and stability index, respectively, compared against commercial 20% Pt/C. The Turing PtNiNb-based anion-exchange-membrane water electrolyser with a low Pt mass loading of 0.05 mg cm−2 demonstrates at least 500 h stability at 1000 mA cm−2, disclosing the stable catalysis. Besides, this new paradigm can be extended to Ir/Pd/Ag-based nanocatalysts, illustrating the universality of Turing-type catalysts.
Addressing mechanism bias in model-based impact forecasts of new tuberculosis vaccines
Authors: Tovar M. , Moreno Y. , Sanz J. 
Published: September 2023

AbstractIn tuberculosis (TB) vaccine development, multiple factors hinder the design and interpretation of the clinical trials used to estimate vaccine efficacy. The complex transmission chain of TB includes multiple routes to disease, making it hard to link the vaccine efficacy observed in a trial to specific protective mechanisms. Here, we present a Bayesian framework to evaluate the compatibility of different vaccine descriptions with clinical trial outcomes, unlocking impact forecasting from vaccines whose specific mechanisms of action are unknown. Applying our method to the analysis of the M72/AS01E vaccine trial -conducted on IGRA+ individuals- as a case study, we found that most plausible models for this vaccine needed to include protection against, at least, two over the three possible routes to active TB classically considered in the literature: namely, primary TB, latent TB reactivation and TB upon re-infection. Gathering new data regarding the impact of TB vaccines in various epidemiological settings would be instrumental to improve our model estimates of the underlying mechanisms.