bluuebunny/crossref_metadata_2025_split huggingface dataset:
Edoxaban use in the context of dental procedures: analysis from the EMIT-AF/VTE database
Authors: Chen Cathy , Saxena Manish , von Heymann Christian , Vanassche Thomas , Jin James , Lersch Robert , Köhler Sabine , Santamaria Amparo , Unverdorben Martin , Colonna Paolo 
Published: August 2023

Abstract
Introduction
Literature reviews support continuing anticoagulation during dental procedures. However, studies often present grouped anticoagulation data, and information on individual anticoagulant management would be helpful to dentists. The Edoxaban Management in Diagnostic and Therapeutic Procedures (EMIT-AF/VTE) programme (NCT02950168; NCT02951039) demonstrated low periprocedural bleeding and thrombotic event rates in patients with atrial fibrillation receiving edoxaban.

Aims
To report periprocedural edoxaban interruption and clinical events in patients from EMIT-AF/VTE who underwent dental procedures.

Methods
Dental procedures were categorised by type (cleaning/noncleaning). Edoxaban interruption, bleeding events, and thrombotic events were observed 5 days preprocedure through 29 days postprocedure.

Results
Overall, 196 patients underwent 350 cleaning and/or noncleaning procedures; most patients (171/196 [87.2%]) underwent noncleaning procedures (282/350 [80.6%]), whereas 48/196 (24.5%) underwent 68/350 (19.4%) cleaning procedures. Edoxaban was uninterrupted for most cleanings (53/68 [77.9%]). Preprocedural interruption was common for single and multiple tooth extractions (single, 67/100 [67.0%]; multiple, 16/30 [53.3%]). The only major bleeding occurred after an unrelated cleaning. Minor bleeding occurred in 1/68 (1.5%) cleaning and 4/282 (1.4%) noncleaning procedures. There were no thrombotic events.

Conclusions
For most cleanings, edoxaban was not interrupted, whereas preprocedural interruption was more common for tooth extractions. Overall, bleeding rates were low, and no thrombotic events occurred.
Direct or indirect composite for restoring permanent first molars affected by Molar Incisor Hypomineralisation (MIH): a randomized clinical controlled trial
Authors: Hakmi Abdulrhman , Dashash Mayssoon 
Published: August 2023

Abstract
Aim
This study was undertaken to compare direct composite resin restorations (DCRR) and indirect composite resin restorations (ICRR) for treating permanent first molars affected by MIH in terms of clinical performance.

Materials and methods
This was a controlled, randomized, clinical split-mouth study. The studied sample consisted of 40 asymptomatic first permanent hypomineralised mandibular molars in 20 children aged between 7–11 years, these cases were divided randomly into two groups: Group 1 (experimental): 20 first permanent mandibular molars were restored with ICRR, and Group 2 (control): 20 first permanent mandibular molars that were restored with DCRR. The cavity was prepared using a diamond bur on a high-speed handpiece, and the prepared cavity was wiped with cotton moistened with sodium hypochlorite. The composite was applied directly with a total-etch bonding system. In the ICRR group, an impression for the prepared cavity was taken using a silicon-based material, and the restoration was adhesive with self-adhesive resin cement. The child’s satisfaction with each of the two application techniques was assessed through the scale FACES. Restorations were evaluated during follow-up periods (3, 6, and 12 months) according to Modified USHPH criteria.

Results
The clinical success rate was 90% in the ICRR group versus 85% in the DCRR group after 12 months of follow-up without statistically significant differences (P = 0.218). Children were significantly more satisfied (P = 0.0351) with ICRR than DCRR.

Conclusions
Both DCRR and ICRR can be considered effective restorations with acceptable clinical performance in the restoration of hypomineralised first permanent molars with an advantage of ICRR in terms of child acceptance of the restoration application technique.
The APC/C E3 ligase subunit ANAPC11 mediates FOXO3 protein degradation to promote cell proliferation and lymph node metastasis in urothelial bladder cancer
Authors: Yan Dong , He Qingqing , Pei Lu , Yang Meihua , Huang Lifang , Kong Jianqiu , He Wang , Liu Hao , Xu Shizhong , Qin Haide , Lin Tianxin , Huang Jian 
Published: August 2023

AbstractUrothelial bladder cancer (UBC) is one of the most prevalent malignancies worldwide, with striking tumor heterogeneity. Elucidating the molecular mechanisms that can be exploited for the treatment of aggressive UBC is a particularly relevant goal. Protein ubiquitination is a critical post-translational modification (PTM) that mediates the degradation of target protein via the proteasome. However, the roles of aberrant protein ubiquitination in UBC development and the underlying mechanisms by which it drives tumor progression remain unclear. In this study, taking advantage of clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein (Cas) 9 technology, we identified the ubiquitin E3 ligase ANAPC11, a critical subunit of the anaphase-promoting complex/cyclosome (APC/C), as a potential oncogenic molecule in UBC cells. Our clinical analysis showed that elevated expression of ANAPC11 was significantly correlated with high T stage, positive lymph node (LN) metastasis, and poor outcomes in UBC patients. By employing a series of in vitro experiments, we demonstrated that ANAPC11 enhanced the proliferation and invasiveness of UBC cells, while knockout of ANAPC11 inhibited the growth and LN metastasis of UBC cells in vivo. By conducting immunoprecipitation coupled with mass spectrometry, we confirmed that ANAPC11 increased the ubiquitination level of the Forkhead transcription factor FOXO3. The resulting decrease in FOXO3 protein stability led to the downregulation of the cell cycle regulator p21 and decreased expression of GULP1, a downstream effector of androgen receptor signaling. Taken together, these findings indicated that ANAPC11 plays an oncogenic role in UBC by modulating FOXO3 protein degradation. The ANAPC11–FOXO3 regulatory axis might serve as a novel therapeutic target for UBC.
Deubiquitinase YOD1 suppresses tumor progression by stabilizing E3 ligase TRIM33 in head and neck squamous cell carcinoma
Authors: Wu Yue , Duan Yuansheng , Han Wei , Cao Jiayan , Ye Beibei , Chen Peng , Li Hong , Wang Yuxuan , Liu Jin , Fang Yan , Yue Kai , Wu Yansheng , Wang Xudong , Jing Chao 
Published: August 2023

AbstractUbiquitination is a reversible process that not only controls protein synthesis and degradation, but also is essential for protein transport, localization and biological activity. Deubiquitinating enzyme (DUB) dysfunction leads to various diseases, including cancer. In this study, we aimed to explore the functions and mechanisms of crucial DUBs in head and neck squamous cell carcinoma (HNSCC). Based on bioinformatic analysis and immunohistochemistry detection, YOD1 was identified to be significantly downregulated in HNSCC specimens compared with adjacent normal tissues. Further analysis revealed that reduced YOD1 expression was associated with the malignant progression of HNSCC and indicated poor prognosis. The results of the in vitro and in vivo experiments verified that YOD1 depletion significantly promoted growth, invasion, and epithelial-mesenchymal transition in HNSCC. Mechanistically, YOD1 inhibited the activation of the ERK/β-catenin pathway by suppressing the ubiquitination and degradation of TRIM33, leading to the constriction of HNSCC progression. Overall, our findings reveal the molecular mechanism underlying the role of YOD1 in tumor progression and provide a novel potential therapeutic target for HNSCC treatment.
Co-inhibition of glutaminolysis and one-carbon metabolism promotes ROS accumulation leading to enhancement of chemotherapeutic efficacy in anaplastic thyroid cancer
Authors: Hwang Yeseong , Yun Hyeok Jun , Jeong Jae Woong , Kim Minki , Joo Seyeon , Lee Hae-Kyung , Chang Hang-Seok , Kim Seok-Mo , Fang Sungsoon 
Published: August 2023

AbstractAnaplastic thyroid cancer (ATC) is one of the most aggressive tumors with an extremely poor prognosis. Based on the several biological features related to glutamine metabolism in ATC, we hypothesized glutaminolysis inhibition induces cell death in ATC cells. However, glutamine metabolism inhibition triggered cell growth arrest independent of cell death in ATC, suggesting that other signaling pathways avoid glutamine metabolism inhibition-induced stress exist. To investigate the functional mechanism against glutamine metabolism inhibition, we conducted mRNA and ATAC-Sequencing data analysis and found that glutamine deprivation increased ATF4-mediated one-carbon metabolism. When we inhibited PHGDH, the first rate-limiting enzyme for one-carbon metabolism, cell growth arrest was promoted upon glutamine metabolism inhibition by accumulating intracellular ROS. We next observed that the co-inhibition of glutamine and one-carbon metabolism could augment the anticancer effects of drugs used in patients with ATC. Finally, single-cell RNA sequencing analysis revealed that one-carbon metabolism was strengthened through the evolutionary process from PTC to ATC. Collectively, our data demonstrate that one-carbon metabolism has a potential role of modulation of cell fate in metabolic stress and can be a therapeutic target for enhancing antitumor effects in ATC.
Hypertonic saline induces inflammation in human macrophages through the NLRP1 inflammasome
Authors: Sposito Francesca , Northey Sarah , Charras Amandine , McNamara Paul S. , Hedrich Christian M. 
Published: August 2023

AbstractNebulized hypertonic saline (3–7%) is commonly used to increase mucociliary clearance in patients with chronic airway disease and/or virus infections. However, altered salt concentrations may contribute to inflammatory responses. The aim of this study was to investigate whether 500 mM NaCl (3%) triggers inflammation in human macrophages and identify the molecular mechanisms involved. NaCl-induced pyroptosis, IL-1β, IL-18 and ASC speck release were measured in primary human monocyte-derived macrophages. Treatment with the recombinant IL-1 receptor antagonist anakinra or the NLRP3 inhibitor MCC950 did not affect NaCl-mediated inflammasome assembly. Knock-down of NLRP1 expression, but not of NLRP3 and NLRC4, reduced NaCl-induced pyroptosis, pro-inflammatory cytokine and ASC speck release from human THP-1-derived macrophages. Data from this study suggest that 3% NaCl-induced inflammatory responses in human macrophages depend on NLRP1 and inflammasome assembly. Targeting inflammation in addition to inhalation with hypertonic saline may benefit patients with inflammatory airway disease.
Non-interferometric stand-alone single-shot holographic camera using reciprocal diffractive imaging
Authors: Oh Jeonghun , Hugonnet Herve , Park YongKeun 
Published: August 2023

AbstractAn ideal holographic camera measures the amplitude and phase of the light field so that the focus can be numerically adjusted after the acquisition, and depth information about an imaged object can be deduced. The performance of holographic cameras based on reference-assisted holography is significantly limited owing to their vulnerability to vibration and complex optical configurations. Non-interferometric holographic cameras can resolve these issues. However, existing methods require constraints on an object or measurement of multiple-intensity images. In this paper, we present a holographic image sensor that reconstructs the complex amplitude of scattered light from a single-intensity image using reciprocal diffractive imaging. We experimentally demonstrate holographic imaging of three-dimensional diffusive objects and suggest its potential applications by imaging a variety of samples under both static and dynamic conditions.
Identification of a drug binding pocket in TMEM16F calcium-activated ion channel and lipid scramblase
Authors: Feng Shengjie , Puchades Cristina , Ko Juyeon , Wu Hao , Chen Yifei , Figueroa Eric E. , Gu Shuo , Han Tina W. , Ho Brandon , Cheng Tong , Li Junrui , Shoichet Brian , Jan Yuh Nung , Cheng Yifan , Jan Lily Yeh 
Published: August 2023

AbstractThe dual functions of TMEM16F as Ca2+-activated ion channel and lipid scramblase raise intriguing questions regarding their molecular basis. Intrigued by the ability of the FDA-approved drug niclosamide to inhibit TMEM16F-dependent syncytia formation induced by SARS-CoV-2, we examined cryo-EM structures of TMEM16F with or without bound niclosamide or 1PBC, a known blocker of TMEM16A Ca2+-activated Cl- channel. Here, we report evidence for a lipid scrambling pathway along a groove harboring a lipid trail outside the ion permeation pore. This groove contains the binding pocket for niclosamide and 1PBC. Mutations of two residues in this groove specifically affect lipid scrambling. Whereas mutations of some residues in the binding pocket of niclosamide and 1PBC reduce their inhibition of TMEM16F-mediated Ca2+ influx and PS exposure, other mutations preferentially affect the ability of niclosamide and/or 1PBC to inhibit TMEM16F-mediated PS exposure, providing further support for separate pathways for ion permeation and lipid scrambling.
Characterizing cancer metabolism from bulk and single-cell RNA-seq data using METAFlux
Authors: Huang Yuefan , Mohanty Vakul , Dede Merve , Tsai Kyle , Daher May , Li Li , Rezvani Katayoun , Chen Ken 
Published: August 2023

AbstractCells often alter metabolic strategies under nutrient-deprived conditions to support their survival and growth. Characterizing metabolic reprogramming in the tumor microenvironment (TME) is of emerging importance in cancer research and patient care. However, recent technologies only measure a subset of metabolites and cannot provide in situ measurements. Computational methods such as flux balance analysis (FBA) have been developed to estimate metabolic flux from bulk RNA-seq data and can potentially be extended to single-cell RNA-seq (scRNA-seq) data. However, it is unclear how reliable current methods are, particularly in TME characterization. Here, we present a computational framework METAFlux (METAbolic Flux balance analysis) to infer metabolic fluxes from bulk or single-cell transcriptomic data. Large-scale experiments using cell-lines, the cancer genome atlas (TCGA), and scRNA-seq data obtained from diverse cancer and immunotherapeutic contexts, including CAR-NK cell therapy, have validated METAFlux’s capability to characterize metabolic heterogeneity and metabolic interaction amongst cell types.
Biosensor Guided Polyketide Synthases Engineering for Optimization of Domain Exchange Boundaries
Authors: Englund Elias , Schmidt Matthias , Nava Alberto A. , Klass Sarah , Keiser Leah , Dan Qingyun , Katz Leonard , Yuzawa Satoshi , Keasling Jay D. 
Published: August 2023

AbstractType I modular polyketide synthases (PKSs) are multi-domain enzymes functioning like assembly lines. Many engineering attempts have been made for the last three decades to replace, delete and insert new functional domains into PKSs to produce novel molecules. However, inserting heterologous domains often destabilize PKSs, causing loss of activity and protein misfolding. To address this challenge, here we develop a fluorescence-based solubility biosensor that can quickly identify engineered PKSs variants with minimal structural disruptions. Using this biosensor, we screen a library of acyltransferase (AT)-exchanged PKS hybrids with randomly assigned domain boundaries, and we identify variants that maintain wild type production levels. We then probe each position in the AT linker region to determine how domain boundaries influence structural integrity and identify a set of optimized domain boundaries. Overall, we have successfully developed an experimentally validated, high-throughput method for making hybrid PKSs that produce novel molecules.
Triplet correlations in Cooper pair splitters realized in a two-dimensional electron gas
Authors: Wang Qingzhen , ten Haaf Sebastiaan L. D. , Kulesh Ivan , Xiao Di , Thomas Candice , Manfra Michael J. , Goswami Srijit 
Published: August 2023

AbstractCooper pairs occupy the ground state of superconductors and are typically composed of maximally entangled electrons with opposite spin. In order to study the spin and entanglement properties of these electrons, one must separate them spatially via a process known as Cooper pair splitting (CPS). Here we provide the first demonstration of CPS in a semiconductor two-dimensional electron gas (2DEG). By coupling two quantum dots to a superconductor-semiconductor hybrid region we achieve efficient Cooper pair splitting, and clearly distinguish it from other local and non-local processes. When the spin degeneracy of the dots is lifted, they can be operated as spin-filters to obtain information about the spin of the electrons forming the Cooper pair. Not only do we observe a near perfect splitting of Cooper pairs into opposite-spin electrons (i.e. conventional singlet pairing), but also into equal-spin electrons, thus achieving triplet correlations between the quantum dots. Importantly, the exceptionally large spin-orbit interaction in our 2DEGs results in a strong triplet component, comparable in amplitude to the singlet pairing. The demonstration of CPS in a scalable and flexible platform provides a credible route to study on-chip entanglement and topological superconductivity in the form of artificial Kitaev chains.
Stability follows efficiency based on the analysis of a large perovskite solar cells ageing dataset
Authors: Hartono Noor Titan Putri , Köbler Hans , Graniero Paolo , Khenkin Mark , Schlatmann Rutger , Ulbrich Carolin , Abate Antonio 
Published: August 2023

AbstractWhile perovskite solar cells have reached competitive efficiency values during the last decade, stability issues remain a critical challenge to be addressed for pushing this technology towards commercialisation. In this study, we analyse a large homogeneous dataset of Maximum Power Point Tracking (MPPT) operational ageing data that we collected with a custom-built High-throughput Ageing System in the past 3 years. In total, 2,245 MPPT ageing curves are analysed which were obtained under controlled conditions (continuous illumination, controlled temperature and atmosphere) from devices comprising various lead-halide perovskite absorbers, charge selective layers, contact layers, and architectures. In a high-level statistical analysis, we find a correlation between the maximum reached power conversion efficiency (PCE) and the relative PCE loss observed after 150-hours of ageing, with more efficient cells statistically also showing higher stability. Additionally, using the unsupervised machine learning method self-organising map, we cluster this dataset based on the degradation curve shapes. We find a correlation between the frequency of particular shapes of degradation curves and the maximum reached PCE.
Deep learning for obstructive sleep apnea diagnosis based on single channel oximetry
Authors: Levy Jeremy , Álvarez Daniel , Del Campo Félix , Behar Joachim A. 
Published: August 2023

AbstractObstructive sleep apnea (OSA) is a serious medical condition with a high prevalence, although diagnosis remains a challenge. Existing home sleep tests may provide acceptable diagnosis performance but have shown several limitations. In this retrospective study, we used 12,923 polysomnography recordings from six independent databases to develop and evaluate a deep learning model, called OxiNet, for the estimation of the apnea-hypopnea index from the oximetry signal. We evaluated OxiNet performance across ethnicity, age, sex, and comorbidity. OxiNet missed 0.2% of all test set moderate-to-severe OSA patients against 21% for the best benchmark.
Molecular mechanism underlying regulation of Arabidopsis CLCa transporter by nucleotides and phospholipids
Authors: Yang Zhao , Zhang Xue , Ye Shiwei , Zheng Jingtao , Huang Xiaowei , Yu Fang , Chen Zhenguo , Cai Shiqing , Zhang Peng 
Published: August 2023

AbstractChloride channels (CLCs) transport anion across membrane to regulate ion homeostasis and acidification of intracellular organelles, and are divided into anion channels and anion/proton antiporters. Arabidopsis thaliana CLCa (AtCLCa) transporter localizes to the tonoplast which imports NO3− and to a less extent Cl− from cytoplasm. The activity of AtCLCa and many other CLCs is regulated by nucleotides and phospholipids, however, the molecular mechanism remains unclear. Here we determine the cryo-EM structures of AtCLCa bound with NO3− and Cl−, respectively. Both structures are captured in ATP and PI(4,5)P2 bound conformation. Structural and electrophysiological analyses reveal a previously unidentified N-terminal β-hairpin that is stabilized by ATP binding to block the anion transport pathway, thereby inhibiting the AtCLCa activity. While AMP loses the inhibition capacity due to lack of the β/γ- phosphates required for β-hairpin stabilization. This well explains how AtCLCa senses the ATP/AMP status to regulate the physiological nitrogen-carbon balance. Our data further show that PI(4,5)P2 or PI(3,5)P2 binds to the AtCLCa dimer interface and occupies the proton-exit pathway, which may help to understand the inhibition of AtCLCa by phospholipids to facilitate guard cell vacuole acidification and stomatal closure. In a word, our work suggests the regulatory mechanism of AtCLCa by nucleotides and phospholipids under certain physiological scenarios and provides new insights for future study of CLCs.
A lab-based test of the gravitational redshift with a miniature clock network
Authors: Zheng Xin , Dolde Jonathan , Cambria Matthew C. , Lim Hong Ming , Kolkowitz Shimon 
Published: August 2023

AbstractEinstein’s theory of general relativity predicts that a clock at a higher gravitational potential will tick faster than an otherwise identical clock at a lower potential, an effect known as the gravitational redshift. Here we perform a laboratory-based, blinded test of the gravitational redshift using differential clock comparisons within an evenly spaced array of 5 atomic ensembles spanning a height difference of 1 cm. We measure a fractional frequency gradient of [ − 12.4 ± 0. 7(stat) ± 2. 5(sys)] × 10−19/cm, consistent with the expected redshift gradient of − 10.9 × 10−19/cm. Our results can also be viewed as relativistic gravitational potential difference measurements with sensitivity to mm scale changes in height on the surface of the Earth. These results highlight the potential of local-oscillator-independent differential clock comparisons for emerging applications of optical atomic clocks including geodesy, searches for new physics, gravitational wave detection, and explorations of the interplay between quantum mechanics and gravity.
Self-anticoagulant sponge for whole blood auto-transfusion and its mechanism of coagulation factor inactivation
Authors: Xu Tao , Ji Haifeng , Xu Lin , Cheng Shengjun , Liu Xianda , Li Yupei , Zhong Rui , Zhao Weifeng , Kizhakkedathu Jayachandran N. , Zhao Changsheng 
Published: August 2023

AbstractClinical use of intraoperative auto-transfusion requires the removal of platelets and plasma proteins due to pump-based suction and water-soluble anticoagulant administration, which causes dilutional coagulopathy. Herein, we develop a carboxylated and sulfonated heparin-mimetic polymer-modified sponge with spontaneous blood adsorption and instantaneous anticoagulation. We find that intrinsic coagulation factors, especially XI, are inactivated by adsorption to the sponge surface, while inactivation of thrombin in the sponge-treated plasma effectively inhibits the common coagulation pathway. We show whole blood auto-transfusion in trauma-induced hemorrhage, benefiting from the multiple inhibitory effects of the sponge on coagulation enzymes and calcium depletion. We demonstrate that the transfusion of collected blood favors faster recovery of hemostasis compared to traditional heparinized blood in a rabbit model. Our work not only develops a safe and convenient approach for whole blood auto-transfusion, but also provides the mechanism of action of self-anticoagulant heparin-mimetic polymer-modified surfaces.