bluuebunny/crossref_metadata_2025_split huggingface dataset:
What can hospital emergency admissions prior to cancer diagnosis tell us about socio-economic inequalities in cancer diagnosis? Evidence from population-based data in England
Authors: Exarchakou Aimilia , Rachet Bernard , Lyratzopoulos Georgios , Maringe Camille , Rubio Francisco Javier 
Published: April 2024

Abstract
Background
More deprived cancer patients are at higher risk of Emergency Presentation (EP) with most studies pointing to lower symptom awareness and increased comorbidities to explain those patterns. With the example of colon cancer, we examine patterns of hospital emergency admissions (HEAs) history in the most and least deprived patients as a potential precursor of EP.

Methods
We analysed the rates of hospital admissions and their admission codes (retrieved from Hospital Episode Statistics) in the two years preceding cancer diagnosis by sex, deprivation and route to diagnosis (EP, non-EP). To select the conditions (grouped admission codes) that best predict emergency admission, we adapted the purposeful variable selection to mixed-effects logistic regression.

Results
Colon cancer patients diagnosed through EP had the highest number of HEAs than all the other routes to diagnosis, especially in the last 7 months before diagnosis. Most deprived patients had an overall higher rate and higher probability of HEA but fewer conditions associated with it.

Conclusions
Our findings point to higher use of emergency services for non-specific symptoms and conditions in the most deprived patients, preceding colon cancer diagnosis. Health system barriers may be a shared factor of socio-economic inequalities in EP and HEAs.
Structural insights into the functional mechanism of the ubiquitin ligase E6AP
Authors: Wang Zhen , Fan Fengying , Li Zhihai , Ye Fei , Wang Qingxia , Gao Rongchao , Qiu Jiaxuan , Lv Yixin , Lin Min , Xu Wenwen , Luo Cheng , Yu Xuekui 
Published: April 2024

AbstractE6AP dysfunction is associated with Angelman syndrome and Autism spectrum disorder. Additionally, the host E6AP is hijacked by the high-risk HPV E6 to aberrantly ubiquitinate the tumor suppressor p53, which is linked with development of multiple types of cancer, including most cervical cancers. Here we show that E6AP and the E6AP/E6 complex exist, respectively, as a monomer and a dimer of the E6AP/E6 protomer. The short α1-helix of E6AP transforms into a longer helical structure when in complex with E6. The extended α1-helices of the dimer intersect symmetrically and contribute to the dimerization. The two protomers sway around the crossed region of the two α1-helices to promote the attachment and detachment of substrates to the catalytic C-lobe of E6AP, thus facilitating ubiquitin transfer. These findings, complemented by mutagenesis analysis, suggest that the α1-helix, through conformational transformations, controls the transition between the inactive monomer and the active dimer of E6AP.
Diphthamide deficiency promotes association of eEF2 with p53 to induce p21 expression and neural crest defects
Authors: Shi Yu , Huang Daochao , Song Cui , Cao Ruixue , Wang Zhao , Wang Dan , Zhao Li , Xu Xiaolu , Lu Congyu , Xiong Feng , Zhao Haowen , Li Shuxiang , Zhou Quansheng , Luo Shuyue , Hu Dongjie , Zhang Yun , Wang Cui , Shen Yiping , Su Weiting , Wu Yili , Schmitz Karl , Wei Shuo , Song Weihong 
Published: April 2024

AbstractDiphthamide is a modified histidine residue unique for eukaryotic translation elongation factor 2 (eEF2), a key ribosomal protein. Loss of this evolutionarily conserved modification causes developmental defects through unknown mechanisms. In a patient with compound heterozygous mutations in Diphthamide Biosynthesis 1 (DPH1) and impaired eEF2 diphthamide modification, we observe multiple defects in neural crest (NC)-derived tissues. Knockin mice harboring the patient’s mutations and Xenopus embryos with Dph1 depleted also display NC defects, which can be attributed to reduced proliferation in the neuroepithelium. DPH1 depletion facilitates dissociation of eEF2 from ribosomes and association with p53 to promote transcription of the cell cycle inhibitor p21, resulting in inhibited proliferation. Knockout of one p21 allele rescues the NC phenotypes in the knockin mice carrying the patient’s mutations. These findings uncover an unexpected role for eEF2 as a transcriptional coactivator for p53 to induce p21 expression and NC defects, which is regulated by diphthamide modification.
Understanding X-ray absorption in liquid water using triple excitations in multilevel coupled cluster theory
Authors: Folkestad Sarai Dery , Paul Alexander C. , Paul Regina , Coriani Sonia , Odelius Michael , Iannuzzi Marcella , Koch Henrik 
Published: April 2024

AbstractX-ray absorption (XA) spectroscopy is an essential experimental tool to investigate the local structure of liquid water. Interpretation of the experiment poses a significant challenge and requires a quantitative theoretical description. High-quality theoretical XA spectra require reliable molecular dynamics simulations and accurate electronic structure calculations. Here, we present the first successful application of coupled cluster theory to model the XA spectrum of liquid water. We overcome the computational limitations on system size by employing a multilevel coupled cluster framework for large molecular systems. Excellent agreement with the experimental spectrum is achieved by including triple excitations in the wave function and using molecular structures from state-of-the-art path-integral molecular dynamics. We demonstrate that an accurate description of the electronic structure within the first solvation shell is sufficient to successfully model the XA spectrum of liquid water within the multilevel framework. Furthermore, we present a rigorous charge transfer analysis of the XA spectrum, which is reliable due to the accuracy and robustness of the electronic structure methodology. This analysis aligns with previous studies regarding the character of the prominent features of the XA spectrum of liquid water.
Local gate control of Mott metal-insulator transition in a 2D metal-organic framework
Authors: Lowe Benjamin , Field Bernard , Hellerstedt Jack , Ceddia Julian , Nourse Henry L. , Powell Ben J. , Medhekar Nikhil V. , Schiffrin Agustin 
Published: April 2024

AbstractElectron-electron interactions in materials lead to exotic many-body quantum phenomena, including Mott metal-insulator transitions (MITs), magnetism, quantum spin liquids, and superconductivity. These phases depend on electronic band occupation and can be controlled via the chemical potential. Flat bands in two-dimensional (2D) and layered materials with a kagome lattice enhance electronic correlations. Although theoretically predicted, correlated-electron Mott insulating phases in monolayer 2D metal-organic frameworks (MOFs) with a kagome structure have not yet been realised experimentally. Here, we synthesise a 2D kagome MOF on a 2D insulator. Scanning tunnelling microscopy (STM) and spectroscopy reveal a MOF electronic energy gap of ∼200 meV, consistent with dynamical mean-field theory predictions of a Mott insulator. Combining template-induced (via work function variations of the substrate) and STM probe-induced gating, we locally tune the electron population of the MOF kagome bands and induce Mott MITs. These findings enable technologies based on electrostatic control of many-body quantum phases in 2D MOFs.
Human connectome topology directs cortical traveling waves and shapes frequency gradients
Authors: Koller Dominik P. , Schirner Michael , Ritter Petra 
Published: April 2024

AbstractTraveling waves and neural oscillation frequency gradients are pervasive in the human cortex. While the direction of traveling waves has been linked to brain function and dysfunction, the factors that determine this direction remain elusive. We hypothesized that structural connectivity instrength gradients — defined as the gradually varying sum of incoming connection strengths across the cortex — could shape both traveling wave direction and frequency gradients. We confirm the presence of instrength gradients in the human connectome across diverse cohorts and parcellations. Using a cortical network model, we demonstrate how these instrength gradients direct traveling waves and shape frequency gradients. Our model fits resting-state MEG functional connectivity best in a regime where instrength-directed traveling waves and frequency gradients emerge. We further show how structural subnetworks of the human connectome generate opposing wave directions and frequency gradients observed in the alpha and beta bands. Our findings suggest that structural connectivity instrength gradients affect both traveling wave direction and frequency gradients.
A cluster-randomized trial of water, sanitation, handwashing and nutritional interventions on stress and epigenetic programming
Authors: Lin Audrie , Mertens Andrew N. , Rahman Md. Ziaur , Tan Sophia T. , Il’yasova Dora , Spasojevic Ivan , Ali Shahjahan , Stewart Christine P. , Fernald Lia C. H. , Kim Lisa , Yan Liying , Meyer Ann , Karim Md. Rabiul , Shahriar Sunny , Shuman Gabrielle , Arnold Benjamin F. , Hubbard Alan E. , Famida Syeda L. , Akther Salma , Hossen Md. Saheen , Mutsuddi Palash , Shoab Abul K. , Shalev Idan , Rahman Mahbubur , Unicomb Leanne , Heaney Christopher D. , Kariger Patricia , Colford John M. , Luby Stephen P. , Granger Douglas A. 
Published: April 2024

AbstractA regulated stress response is essential for healthy child growth and development trajectories. We conducted a cluster-randomized trial in rural Bangladesh (funded by the Bill & Melinda Gates Foundation, ClinicalTrials.gov NCT01590095) to assess the effects of an integrated nutritional, water, sanitation, and handwashing intervention on child health. We previously reported on the primary outcomes of the trial, linear growth and caregiver-reported diarrhea. Here, we assessed additional prespecified outcomes: physiological stress response, oxidative stress, and DNA methylation (N = 759, ages 1–2 years). Eight neighboring pregnant women were grouped into a study cluster. Eight geographically adjacent clusters were block-randomized into the control or the combined nutrition, water, sanitation, and handwashing (N + WSH) intervention group (receiving nutritional counseling and lipid-based nutrient supplements, chlorinated drinking water, upgraded sanitation, and handwashing with soap). Participants and data collectors were not masked, but analyses were masked. There were 358 children (68 clusters) in the control group and 401 children (63 clusters) in the intervention group. We measured four F2-isoprostanes isomers (iPF(2α)-III; 2,3-dinor-iPF(2α)-III; iPF(2α)-VI; 8,12-iso-iPF(2α)-VI), salivary alpha-amylase and cortisol, and methylation of the glucocorticoid receptor (NR3C1) exon 1F promoter including the NGFI-A binding site. Compared with control, the N + WSH group had lower concentrations of F2-isoprostanes isomers (differences ranging from −0.16 to −0.19 log ng/mg of creatinine,P < 0.01), elevated post-stressor cortisol (0.24 log µg/dl;P < 0.01), higher cortisol residualized gain scores (0.06 µg/dl;P = 0.023), and decreased methylation of the NGFI-A binding site (−0.04;P = 0.037). The N + WSH intervention enhanced adaptive responses of the physiological stress system in early childhood.
A mechanical-assisted post-bioprinting strategy for challenging bone defects repair
Authors: Yang Jirong , Chen Zhigang , Gao Chongjian , Liu Juan , Liu Kaizheng , Wang Xiao , Pan Xiaoling , Wang Guocheng , Sang Hongxun , Pan Haobo , Liu Wenguang , Ruan Changshun 
Published: April 2024

AbstractBioprinting that can synchronously deposit cells and biomaterials has lent fresh impetus to the field of tissue regeneration. However, the unavoidable occurrence of cell damage during fabrication process and intrinsically poor mechanical stability of bioprinted cell-laden scaffolds severely restrict their utilization. As such, on basis of heart-inspired hollow hydrogel-based scaffolds (HHSs), a mechanical-assisted post-bioprinting strategy is proposed to load cells into HHSs in a rapid, uniform, precise and friendly manner. HHSs show mechanical responsiveness to load cells within 4 s, a 13-fold increase in cell number, and partitioned loading of two types of cells compared with those under static conditions. As a proof of concept, HHSs with the loading cells show an enhanced regenerative capability in repair of the critical-sized segmental and osteoporotic bone defects in vivo. We expect that this post-bioprinting strategy can provide a universal, efficient, and promising way to promote cell-based regenerative therapy.
Electrochemically actuated microelectrodes for minimally invasive peripheral nerve interfaces
Authors: Dong Chaoqun , Carnicer-Lombarte Alejandro , Bonafè Filippo , Huang Botian , Middya Sagnik , Jin Amy , Tao Xudong , Han Sanggil , Bance Manohar , Barone Damiano G. , Fraboni Beatrice , Malliaras George G. 
Published: April 2024

AbstractElectrode arrays that interface with peripheral nerves are used in the diagnosis and treatment of neurological disorders; however, they require complex placement surgeries that carry a high risk of nerve injury. Here we leverage recent advances in soft robotic actuators and flexible electronics to develop highly conformable nerve cuffs that combine electrochemically driven conducting-polymer-based soft actuators with low-impedance microelectrodes. Driven with applied voltages as small as a few hundreds of millivolts, these cuffs allow active grasping or wrapping around delicate nerves. We validate this technology using in vivo rat models, showing that the cuffs form and maintain a self-closing and reliable bioelectronic interface with the sciatic nerve of rats without the use of surgical sutures or glues. This seamless integration of soft electrochemical actuators with neurotechnology offers a path towards minimally invasive intraoperative monitoring of nerve activity and high-quality bioelectronic interfaces.
Apolipoprotein E controls Dectin-1-dependent development of monocyte-derived alveolar macrophages upon pulmonary β-glucan-induced inflammatory adaptation
Authors: Theobald H. , Bejarano D. A. , Katzmarski N. , Haub J. , Schulte-Schrepping J. , Yu J. , Bassler K. , Ament A. L. , Osei-Sarpong C. , Piattini F. , Vornholz L. , T’Jonck W. , Györfi A. H. , Hayer H. , Yu X. , Sheoran S. , Al Jawazneh A. , Chakarov S. , Haendler K. , Brown G. D. , Williams D. L. , Bosurgi L. , Distler J. H. W. , Ginhoux F. , Ruland J. , Beyer M. D. , Greter M. , Bain C. C. , Vazquez-Armendariz A. I. , Kopf M. , Schultze J. L. , Schlitzer A. 
Published: April 2024

AbstractThe lung is constantly exposed to the outside world and optimal adaptation of immune responses is crucial for efficient pathogen clearance. However, mechanisms that lead to lung-associated macrophages’ functional and developmental adaptation remain elusive. To reveal such mechanisms, we developed a reductionist model of environmental intranasal β-glucan exposure, allowing for the detailed interrogation of molecular mechanisms of pulmonary macrophage adaptation. Employing single-cell transcriptomics, high-dimensional imaging and flow cytometric characterization paired with in vivo and ex vivo challenge models, we reveal that pulmonary low-grade inflammation results in the development of apolipoprotein E (ApoE)-dependent monocyte-derived alveolar macrophages (ApoE+CD11b+ AMs). ApoE+CD11b+ AMs expressed high levels of CD11b, ApoE, Gpnmb and Ccl6, were glycolytic, highly phagocytic and produced large amounts of interleukin-6 upon restimulation. Functional differences were cell intrinsic, and myeloid cell-specific ApoE ablation inhibited Ly6c+ monocyte to ApoE+CD11b+ AM differentiation dependent on macrophage colony-stimulating factor secretion, promoting ApoE+CD11b+ AM cell death and thus impeding ApoE+CD11b+ AM maintenance. In vivo, β-glucan-elicited ApoE+CD11b+ AMs limited the bacterial burden of Legionella pneumophilia after infection and improved the disease outcome in vivo and ex vivo in a murine lung fibrosis model. Collectively these data identify ApoE+CD11b+ AMs generated upon environmental cues, under the control of ApoE signaling, as an essential determinant for lung adaptation enhancing tissue resilience.
Optical coherence tomography angiography analysis methods: a systematic review and meta-analysis
Authors: Courtie Ella , Kirkpatrick James Robert Moore , Taylor Matthew , Faes Livia , Liu Xiaoxuan , Logan Ann , Veenith Tonny , Denniston Alastair K. , Blanch Richard J. 
Published: April 2024

AbstractOptical coherence tomography angiography (OCTA) is widely used for non-invasive retinal vascular imaging, but the OCTA methods used to assess retinal perfusion vary. We evaluated the different methods used to assess retinal perfusion between OCTA studies. MEDLINE and Embase were searched from 2014 to August 2021. We included prospective studies including ≥ 50 participants using OCTA to assess retinal perfusion in either global retinal or systemic disorders. Risk of bias was assessed using the National Institute of Health quality assessment tool for observational cohort and cross-sectional studies. Heterogeneity of data was assessed by Q statistics, Chi-square test, and I2 index. Of the 5974 studies identified, 191 studies were included in this evaluation. The selected studies employed seven OCTA devices, six macula volume dimensions, four macula subregions, nine perfusion analyses, and five vessel layer definitions, totalling 197 distinct methods of assessing macula perfusion and over 7000 possible combinations. Meta-analysis was performed on 88 studies reporting vessel density and foveal avascular zone area, showing lower retinal perfusion in patients with diabetes mellitus than in healthy controls, but with high heterogeneity. Heterogeneity was lowest and reported vascular effects strongest in superficial capillary plexus assessments. Systematic review of OCTA studies revealed massive heterogeneity in the methods employed to assess retinal perfusion, supporting calls for standardisation of methodology.
The fractional analysis of thermo-elasticity coupled systems with non-linear and singular nature
Authors: Rab Abdur , Khan Shahbaz , Khan Hassan , Tchier Fairouz , Jebran Samaruddin , Tawfiq Ferdous , Nadeem Muhammad 
Published: April 2024

AbstractIt is mentioned that understanding linear and non-linear thermo-elasticity systems is important for understanding temperature, elasticity, stresses, and thermal conductivity. One of the most crucial aspects of the current research is the solution to these systems. The fractional form of several thermo-elastic systems is explored, and elegant solutions are provided. The solutions of fractional and integer thermo-elastic systems are further discussed using tables and diagrams. The closed contact between the LRPSM and exact solutions is displayed in the graphs. Plotting fractional problem solutions demonstrates their convergence towards integer-order problem solutions for suitable modeling. The tables confirm that greater precision is rapidly attained as the terms of the derived series solution increase. The faster convergence and stability of the suggested method support its modification for other fractional non-linear complex systems in nature.
Arrhythmia onsets triggered by acute myocardial ischemia are not mediated by lysophosphoglycerides accumulation in ventricular myocardium
Authors: Liu Jiawei , Mai Tingting , Ren Han , Chang Yafei , Li Chao , Lv Guoli , Zheng Da , Liao Xinbiao , Yu Yangeng , Zhang Fu , Zhao Shuquan , Liu Xiaoshan , Liu Shuiping , Zhao Hu , Luo Bin , Liu Chao , Huang Erwen 
Published: April 2024

AbstractLysophosphoglycerides (LPLs) have been reported to accumulate in myocardium and serve as a cause of arrhythmias in acute myocardial ischemia. However, in this study we found that LPLs level in the ventricular myocardium was decreased by the onset of acute myocardial ischemia in vivo in rats. Decreasing of LPLs level in left ventricular myocardium, but not right, was observed within 26 min of left myocardial ischemia, regardless of whether arrhythmias were triggered. Lower LPLs level in the ventricular myocardium was also observed in aconitine-simulated ventricular fibrillation (P < 0.0001) and ouabain-simulated III° atrioventricular block (P < 0.0001). Shot-lasting electric shock, e.g., ≤ 40 s, decreased LPLs level, while long-lasting, e.g., 5 min, increased it (fold change = 2.27, P = 0.0008). LPLs accumulation was observed in long-lasting myocardial ischemia, e.g., 4 h (fold change = 1.20, P = 0.0012), when caspase3 activity was elevated (P = 0.0012), indicating increased cell death, but not coincided with higher frequent arrhythmias. In postmortem human ventricular myocardium, differences of LPLs level in left ventricular myocardium was not observed among coronary artery disease- and other heart diseases-caused sudden death and non-heart disease caused death. LPLs level manifested a remarkable increasing from postmortem 12 h on in rats, thus abolishing the potential for serving as biomarkers of sudden cardiac death. Token together, in this study we found that LPLs in ventricular myocardium were initially decreased by the onset of ischemia, LPLs accumulation do not confer arrhythmogenesis during acute myocardial ischemia. It is necessary to reassess the roles of LPLs in myocardial infarction.
Establishment and validation of a nomogram model for predicting the specific mortality risk of melanoma in upper limbs based on the SEER database
Authors: Gao Mingju , Wu Bingwei , Bai Xinping 
Published: April 2024

AbstractFor patients with upper limb melanoma, the significance of specific death is more important than that of all-cause death, and traditional survival analysis may overestimate the mortality rate of patients. Therefore, the nomogram model for predicting the specific mortality risk of melanoma in the upper limbs was developed. A population with melanoma in the upper limbs, diagnosed from 2010 to 2015, were selected from the National Cancer Institute database of Surveillance, Epidemiology, and End Results (SEER). The independent predictive factors of specific death were confirmed by the competing risk model of one-factor analysis and multi-factor analysis, and the nomogram was constructed according to the independent predictive factors. 17,200 patients with upper limb melanoma were enrolled in the study (training cohort: n = 12,040; validation cohort: n = 5160). Multi-factor analysis of the competing risk model showed that age, marital status, gender, tumor stage, T stage, M stage, regional lymph node surgery information, radiotherapy, chemotherapy, mitotic cell count, ulcer and whether there were multiple primary cancers, were independent factors affecting the specific death of upper limb melanoma patients (P < 0.05). The nomogram has good predictive ability regarding the specific mortality risk of melanoma in the upper limbs, and could be of great help to formulate prognostic treatment strategies and follow-up strategies that are conducive to survival.