bluuebunny/crossref_metadata_2025 huggingface dataset:
GNSS Differential Code Bias Determination Using Rao‐Blackwellized Particle Filtering
Authors: Reid Ben , Themens David R. , McCaffrey Anthony , Jayachandran P. T. , Hoque Mainul , Mazzella Andrew J.
Published: April 2024

The Assimilative Canadian High Arctic Ionospheric Model (A‐CHAIM) is a near‐real‐time data assimilation model of the high latitude ionosphere, incorporating measurements from many instruments, including slant Total Electron Content measurements from ground‐based Global Navigation Satellite System (GNSS) receivers. These measurements have receiver‐specific Differential Code Biases (DCB) which must be resolved to produce an absolute measurement, which are resolved simultaneously with the ionospheric state using Rao‐Blackwellized particle filtering. These DCBs are compared to published values and to DCBs determined using eight different Global Ionospheric Maps (GIM), which show small but consistent systematic differences. The potential cause of these systematic biases is investigated using multiple experimental A‐CHAIM test runs, including the effect of plasmaspheric electron content. By running tests using the GIM‐derived DCBs, it is shown that using A‐CHAIM DCBs produces the lowest overall error, and that using GIM DCBs causes an overestimation of the topside electron density which can exceed 100% when compared to in situ measurements from DMSP.
Fault Networks in Triaxial Tectonic Settings: Analog Modeling of Distributed Continental Extension With Lateral Shortening
Authors: Liu Jun , Rosenau Matthias , Brune Sascha , Kosari Ehsan , Rudolf Michael , Oncken Onno
Published: April 2024

Triaxial deformation is a general feature of continental tectonics, but its controls and the systematics of associated fault networks remain poorly understood. We present triaxial analog experiments mimicking crustal thinning resulting from distributed longitudinal extension and lateral shortening. Contemporary longitudinal extension and lateral shortening are related by the principal horizontal strain ratio (PHSR). We investigate the effect of crustal geometry, rheology and strain rate on deformation localization, faulting regime and pattern, and PHSR in brittle and brittle‐viscous crustal‐scale models. We find that in brittle models the fault networks reflect the basal boundary condition and fault‐density scales inversely with brittle layer thickness. In brittle‐viscous models, as strain rate (ė) decreases, (a) Three fault patterns emerge: conjugate sets of strike‐slip faults (ė > 3 × 10−4 s−1, PHSR > 0.31), sets of parallel oblique normal faults (ė = 0.3–3 × 10−4 s−1, PHSR = 0.15–0.25), horst‐and‐graben system (ė < 0.3 × 10−4 s−1, PHSR < 0.1). (b) The strain localization increases systematically and gradually. We interpret the strain rate dependent of faulting regimes to be controlled by vertical coupling between the model upper mantle and model upper crust resulting in spontaneous permutation of principal stress axes. Rate‐dependency of strain localization can be related to mechanical coupling between the upper and lower crust. We identify the following parameters controlling triaxial tectonic deformation: upper crustal thickness and friction coefficient, lower crustal thickness and viscosity, as well as strain rate. We test our models and predictions against natural prototypes (Tibet, Anatolia, Apennines, and Basin and Range Province) thus providing new perspectives on triaxial deformation.
Introducing the Rising Stars of GeoHealth
Authors: Nguyen Thanh H.
Published: April 2024

Early career researchers often asked me: how I became the editor‐in‐chief, what editors, associate editors, and editors do, why I wanted to become an editor, how much time an editor committed, would I rather spend more time on my research and publish another paper or my personal life? All of these questions make sense. When I started as an assistant professor nearly 20 years ago, I did not plan to become an editor; I wanted to do my research and teach to achieve tenure. Sound familiar? Fortunately, I was gradually pulled into the publishing process not as an author but as a reviewer, associate editor, and eventually editor‐in‐chief by several senior colleagues, for whom I am forever grateful. Now, it is my turn to prepare the next generation of editors, the backbone of science.
A Case Study of Ionospheric Storm‐Time Altitudinal Differences at Low Latitudes During the May 2021 Geomagnetic Storm
Authors: Kuai Jiawei , Sun Hao , Liu Libo , Zhong Jiahao , Yue Xinan , Wang Kang , Zhang Ruilong , Li Qiaoling , Yang Yuyan , Jin Yihong , Dong Yi , Wan Xin , Chen Jiawen
Published: April 2024

Previous studies paid little attention to the ionospheric storm‐time altitudinal differences due to insufficiency of ionospheric measurements. In this work, multiple instrumental observations were used to investigate the ionospheric storm‐time response at low latitudes in the American and Asian‐Australian sectors during the May 2021 geomagnetic storm. The ground‐based Global Navigation Satellite Systems (GNSS) total electron content (TEC) and Low Earth Orbit (LEO) satellite topside TEC presented opposite (positive/negative) variations in the low‐latitude and equatorial region of both sectors during this storm. The electron density profiles from the Constellation Observing System for Meteorology, Ionosphere, and Climate‐2 (COSMIC‐2) and the Sanya Incoherent Scatter Radar showed a good agreement and well explained the opposite variations between GNSS TEC and LEO satellite topside TEC. The F2‐layer peak height (hmF2) and peak density (NmF2) displayed inverse variations, and the feature was present mostly in the regions between equatorial ionization anomaly crests. The combined modulation effects of the storm‐time zonal electric fields and the field‐aligned transports possibly resulted in the contrary variations of hmF2 and NmF2 in the low‐latitude and equatorial region, leading to the storm‐time altitudinal differences during this storm. Relatively, the storm‐time thermospheric composition disturbances might be a minor factor responsible for these differences.
Recognizing and Appreciating the 2023 JGR: Biogeosciences Reviewers
Authors: Bond‐Lamberty Ben , Feng Xiaojuan , Huntzinger Deborah , Xenopoulos Marguerite A.
Published: April 2024

Peer review is a crucial but time‐consuming and sometimes frustrating part of science. The Editors of JGR: Biogeosciences are deeply appreciative of, and sincerely thank, the many 2023 reviewers who donated their time and expertise in support of the journal.
Reconfigurable memlogic long wave infrared sensing with superconductors
Authors: Chen Bingxin , Xue Huanyi , Pan Hong , Zhu Liping , Yan Xiaomi , Wang Jingzhe , Song Yanru , An Zhenghua
Published: April 2024

Optical sensors with in-cell logic and memory capabilities offer new horizons in realizing machine vision beyond von Neumann architectures and have been attempted with two-dimensional materials, memristive oxides, phase-changing materials etc. Noting the unparalleled performance of superconductors with both quantum-limited optical sensitivities and ultra-wide spectrum coverage, here we report a superconducting memlogic long-wave infrared sensor based on the bistability in hysteretic superconductor-normal phase transition. Driven cooperatively by electrical and optical pulses, the device offers deterministic in-sensor switching between resistive and superconducting (hence dissipationless) states with persistence > 105 s. This results in a resilient reconfigurable memlogic system applicable for, e.g., encrypted communications. Besides, a high infrared sensitivity at 12.2 μm is achieved through its in-situ metamaterial perfect absorber design. Our work opens the avenue to realize all-in-one superconducting memlogic sensors, surpassing biological retina capabilities in both sensitivity and wavelength, and presents a groundbreaking opportunity to integrate visional perception capabilities into superconductor-based intelligent quantum machines.
Differences in the neural correlates of schizophrenia with positive and negative formal thought disorder in patients with schizophrenia in the ENIGMA dataset
Authors: Sharkey Rachel J. , Bacon Chelsea , Peterson Zeru , Rootes-Murdy Kelly , Salvador Raymond , Pomarol-Clotet Edith , Karuk Andriana , Homan Philipp , Ji Ellen , Omlor Wolfgang , Homan Stephanie , Georgiadis Foivos , Kaiser Stefan , Kirschner Matthias , Ehrlich Stefan , Dannlowski Udo , Grotegerd Dominik , Goltermann Janik , Meinert Susanne , Kircher Tilo , Stein Frederike , Brosch Katharina , Krug Axel , Nenadic Igor , Sim Kang , Spalletta Gianfranco , Banaj Nerisa , Sponheim Scott R. , Demro Caroline , Ramsay Ian S. , King Margaret , Quidé Yann , Green Melissa Jane , Nguyen Dana , Preda Adrian , Calhoun Vince , Turner Jessica , van Erp Theo , Nickl-Jockschat Thomas
Published: April 2024

Formal thought disorder (FTD) is a clinical key factor in schizophrenia, but the neurobiological underpinnings remain unclear. In particular, the relationship between FTD symptom dimensions and patterns of regional brain volume loss in schizophrenia remains to be established in large cohorts. Even less is known about the cellular basis of FTD. Our study addresses these major obstacles by enrolling a large multi-site cohort acquired by the ENIGMA Schizophrenia Working Group (752 schizophrenia patients and 1256 controls), to unravel the neuroanatomy of FTD in schizophrenia and using virtual histology tools on implicated brain regions to investigate the cellular basis. Based on the findings of previous clinical and neuroimaging studies, we decided to separately explore positive, negative and total formal thought disorder. We used virtual histology tools to relate brain structural changes associated with FTD to cellular distributions in cortical regions. We identified distinct neural networks positive and negative FTD. Both networks encompassed fronto-occipito-amygdalar brain regions, but positive and negative FTD demonstrated a dissociation: negative FTD showed a relative sparing of orbitofrontal cortical thickness, while positive FTD also affected lateral temporal cortices. Virtual histology identified distinct transcriptomic fingerprints associated for both symptom dimensions. Negative FTD was linked to neuronal and astrocyte fingerprints, while positive FTD also showed associations with microglial cell types. These results provide an important step towards linking FTD to brain structural changes and their cellular underpinnings, providing an avenue for a better mechanistic understanding of this syndrome.
The DNA damage-independent ATM signalling maintains CBP/DOT1L axis in MLL rearranged acute myeloid leukaemia
Authors: Wang Guangming , Zhang Wenjun , Ren Jie , Zeng Yu , Dang Xiuyong , Tian Xiaoxue , Yu Wenlei , Li Zheng , Ma Yuting , Yang Pingping , Lu Jinyuan , Zheng Junke , Lu Bing , Xu Jun , Liang Aibin
Published: April 2024

The long-term maintenance of leukaemia stem cells (LSCs) is responsible for the high degree of malignancy in MLL (mixed-lineage leukaemia) rearranged acute myeloid leukaemia (AML). The DNA damage response (DDR) and DOT1L/H3K79me pathways are required to maintain LSCs in MLLr-AML, but little is known about their interplay. This study revealed that the DDR enzyme ATM regulates the maintenance of LSCs in MLLr-AML with a sequential protein-posttranslational-modification manner via CBP-DOT1L. We identified the phosphorylation of CBP by ATM, which confers the stability of CBP by preventing its proteasomal degradation, and characterised the acetylation of DOT1L by CBP, which mediates the high level of H3K79me2 for the expression of leukaemia genes in MLLr-AML. In addition, we revealed that the regulation of CBP-DOT1L axis in MLLr-AML by ATM was independent of DNA damage activation. Our findings provide insight into the signalling pathways involoved in MLLr-AML and broaden the understanding of the role of DDR enzymes beyond processing DNA damage, as well as identigying them as potent cancer targets.
Phenotyping of cancer-associated somatic mutations in the BCL2 transmembrane domain
Authors: Leiva Diego , Lucendo Estefanía , García-Jareño Alicia Belén , Sancho Mónica , Orzáez Mar
Published: April 2024

The BCL2 family of proteins controls cell death by modulating the permeabilization of the mitochondrial outer membrane through a fine-tuned equilibrium of interactions among anti- and pro-apoptotic members. The upregulation of anti-apoptotic BCL2 proteins represents an unfavorable prognostic factor in many tumor types due to their ability to shift the equilibrium toward cancer cell survival. Furthermore, cancer-associated somatic mutations in BCL2 genes interfere with the protein interaction network, thereby promoting cell survival. A range of studies have documented how these mutations affect the interactions between the cytosolic domains of BCL2 and evaluate the impact on cell death; however, as the BCL2 transmembrane interaction network remains poorly understood, somatic mutations affecting transmembrane regions have been classified as pathogenic-based solely on prediction algorithms. We comprehensively investigated cancer-associated somatic mutations affecting the transmembrane domain of BCL2 proteins and elucidated their effect on membrane insertion, hetero-interactions with the pro-apoptotic protein BAX, and modulation of cell death in cancer cells. Our findings reveal how specific mutations disrupt switchable interactions, alter the modulation of apoptosis, and contribute to cancer cell survival. These results provide experimental evidence to distinguish BCL2 transmembrane driver mutations from passenger mutations and provide new insight regarding selecting precision anti-tumor treatments.
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

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

E6AP 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

Diphthamide 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

X-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

Electron-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

Traveling 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

A 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

Bioprinting 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

Electrode 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

The 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

Optical 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

It 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

Lysophosphoglycerides (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

For 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.
Lineage tracing reveals a novel PDGFRβ+ satellite cell subset that contributes to myo-regeneration of chronically injured rotator cuff muscle
Authors: Dar Ayelet , Li Angela , Petrigliano Frank A.
Published: April 2024

Massive rotator cuff (RC) tendon tears are associated with progressive fibro-adipogenesis and muscle atrophy that altogether cause shoulder muscle wasting. Platelet derived growth factor β (PDGFRβ) lineage cells, that co-express PDGFRα have previously been shown to directly contribute to scar formation and fat accumulation in a mouse model of irreversible tendon and nerve transection (TTDN). Conversely, PDGFRβ+ lineage cells have also been  shown to be myogenic in cultures and in other models of skeletal muscle injury. We therefore hypothesized that PDGFRβ demarcates two distinct RC residing subpopulations, fibro-adipogenic and myogenic, and aimed to elucidate the identity of the PDGFRβ myogenic precursors and evaluate their contribution, if any, to RC myo-regeneration. Lineage tracing revealed increasing contribution of PDGFRβ+ myo-progenitors to the formation of GFP+ myofibers, which were the most abundant myofiber type in regenerated muscle at 2 weeks post-TTDN. Muscle regeneration preceded muscle atrophy and both advanced from the lateral site of tendon transection to the farthest medial region. GFP+/PDGFRβ+Sca-1−lin−CXCR4+Integrin-β1+ marked a novel subset of satellite cells with confirmed myogenic properties. Further studies are warranted to identify the existence of PDGFRβ+ satellite cells in human and other mouse muscles and to define their myo-regenerative potential following acute and chronic muscle injury.
Numerical and experimental investigation of heat transfer enhancement in double tube heat exchanger using nail rod inserts
Authors: Marzouk S. A. , Almehmadi Fahad Awjah , Aljabr Ahmad , Sharaf Maisa A.
Published: April 2024

The Double-tube heat exchanger (DTHX) is widely favored across various industries due to its compact size, low maintenance requirements, and ability to operate effectively in high-pressure applications. This study explores methods to enhance heat transfer within a DTHX using both experimental and numerical approaches, specifically by integrating a nail rod insert (NRI). A steel nails rod insert, 1000 mm in length, is introduced into the DTHX, which is subjected to turbulent flows characterized by Reynolds numbers ranging from 3200 to 5700. Three different pitches of NRI (100 mm, 50 mm, and 25 mm) are investigated. The results indicate a significant increase in the Nusselt (Nu) number upon the insertion of nail rods, with further improvements achievable by reducing the pitch length. Particularly noteworthy is the Nu number enhancement ratio for the 25 mm pitch NRI, which is 1.81–1.9 times higher than that for the plain tube. However, it is observed that pressure drop increases in all configurations with NRI due to heightened turbulence and obstruction by the NRI. Among the various pitch lengths, the 25 mm pitch exhibits the highest pressure drop values. Moreover, exergy efficiency is found to improve across all cases with NRI, corresponding to increased heat transfer, with the 25 mm pitch length showing a remarkable 128% improvement. Numerical analysis reveals that the novel insert enhances flow turbulence through the generation of secondary flows, thereby enhancing heat transfer within the DTHX. This study provides a comprehensive analysis, including temperature, velocity, and pressure drop distributions derived from numerical simulations.
Mandibular and dental measurements for sex determination using machine learning
Authors: Küchler Erika Calvano , Kirschneck Christian , Marañón-Vásquez Guido Artemio , Schroder Ângela Graciela Deliga , Baratto-Filho Flares , Romano Fábio Lourenço , Stuani Maria Bernadete Sasso , Matsumoto Mírian Aiko Nakane , de Araujo Cristiano Miranda
Published: April 2024

The present study tested the combination of mandibular and dental dimensions for sex determination using machine learning. Lateral cephalograms and dental casts were used to obtain mandibular and mesio-distal permanent teeth dimensions, respectively. Univariate statistics was used for variables selection for the supervised machine learning model (alpha = 0.05). The following algorithms were trained: logistic regression, gradient boosting classifier, k-nearest neighbors, support vector machine, multilayer perceptron classifier, decision tree, and random forest classifier. A threefold cross-validation approach was adopted to validate each model. The areas under the curve (AUC) were computed, and ROC curves were constructed. Three mandibular-related measurements and eight dental size-related dimensions were used to train the machine learning models using data from 108 individuals. The mandibular ramus height and the lower first molar mesio-distal size exhibited the greatest predictive capability in most of the evaluated models. The accuracy of the models varied from 0.64 to 0.74 in the cross-validation stage, and from 0.58 to 0.79 when testing the data. The logistic regression model exhibited the highest performance (AUC = 0.84). Despite the limitations of this study, the results seem to show that the integration of mandibular and dental dimensions for sex prediction would be a promising approach, emphasizing the potential of machine learning techniques as valuable tools for this purpose.
Synthesis, bioactivity assessment, molecular docking and ADMET studies of new chromone congeners exhibiting potent anticancer activity
Authors: Abo-Salem Heba M. , El Souda Sahar S. M. , Shafey Heba I. , Zoheir Khairy M. A. , Ahmed Khadiga M. , Mahmoud Kh. , Mahrous Karima F. , Fawzy Nagwa M.
Published: April 2024

In consideration of the chromones' therapeutic potential and anticancer activity, a new series of chromanone derivatives have been synthesized through a straightforward reaction between 6-formyl-7-hydroxy-5-methoxy-2-methylchromone (2) and various organic active compounds. The cytotoxic activity of the newly synthesized congeners was investigated against MCF-7 (human breast cancer), HCT-116 (colon cancer), HepG2 (liver cancer), and normal skin fibroblast cells (BJ1). The obtained data indicated that compounds 14b, 17, and 19 induce cytotoxic activity in the breast MCF7, while compounds 6a, 6b, 11 and 14c showed highly potent activity in the colon cancer cell lines. Overall, the results demonstrate that the potential cytotoxic effects of the studied compounds may be based on their ability to induce DNA fragmentation in cancer cell lines, down-regulate the expression level of CDK4 as well as the anti-apoptotic gene Bcl-2 and up-regulate the expression of the pro-apoptotic genes P53 and Bax. Furthermore, compounds 14b and 14c showed a dual mechanism of action by inducing apoptosis and cell cycle arrest. The docking studies showed that the binding affinity of the most active cytotoxic compounds within the active pocket of the CDK4 enzyme is stronger due to hydrophobic and H-bonding interactions. These results were found to be consistent with the experimental results.
P2X7 receptor knockout does not alter renal function or prevent angiotensin II-induced kidney injury in F344 rats
Authors: Nespoux Josselin , Monaghan Marie-Louise T. , Jones Natalie K. , Stewart Kevin , Denby Laura , Czopek Alicja , Mullins John J. , Menzies Robert I. , Baker Andrew H. , Bailey Matthew A.
Published: April 2024

P2X7 receptors mediate immune and endothelial cell responses to extracellular ATP. Acute pharmacological blockade increases renal blood flow and filtration rate, suggesting that receptor activation promotes tonic vasoconstriction. P2X7 expression is increased in kidney disease and blockade/knockout is renoprotective. We generated a P2X7 knockout rat on F344 background, hypothesising enhanced renal blood flow and protection from angiotensin-II-induced renal injury. CRISPR/Cas9 introduced an early stop codon into exon 2 of P2rx7, abolishing P2X7 protein in kidney and reducing P2rx7 mRNA abundance by ~ 60% in bone-marrow derived macrophages. The M1 polarisation response to lipopolysaccharide was unaffected but P2X7 receptor knockout suppressed ATP-induced IL-1β release. In male knockout rats, acetylcholine-induced dilation of the renal artery ex vivo was diminished but not the response to nitroprusside. Renal function in male and female knockout rats was not different from wild-type. Finally, in male rats infused with angiotensin-II for 6 weeks, P2X7 knockout did not reduce albuminuria, tubular injury, renal macrophage accrual, and renal perivascular fibrosis. Contrary to our hypothesis, global P2X7 knockout had no impact on in vivo renal hemodynamics. Our study does not indicate a major role for P2X7 receptor activation in renal vascular injury.
A clustering approach to improve our understanding of the genetic and phenotypic complexity of chronic kidney disease
Authors: Eoli A. , Ibing S. , Schurmann C. , Nadkarni G. N. , Heyne H. O. , Böttinger E.
Published: April 2024

Chronic kidney disease (CKD) is a complex disorder that causes a gradual loss of kidney function, affecting approximately 9.1% of the world's population. Here, we use a soft-clustering algorithm to deconstruct its genetic heterogeneity. First, we selected 322 CKD-associated independent genetic variants from published genome-wide association studies (GWAS) and added association results for 229 traits from the GWAS catalog. We then applied nonnegative matrix factorization (NMF) to discover overlapping clusters of related traits and variants. We computed cluster-specific polygenic scores and validated each cluster with a phenome-wide association study (PheWAS) on the BioMe biobank (n = 31,701). NMF identified nine clusters that reflect different aspects of CKD, with the top-weighted traits signifying areas such as kidney function, type 2 diabetes (T2D), and body weight. For most clusters, the top-weighted traits were confirmed in the PheWAS analysis. Results were found to be more significant in the cross-ancestry analysis, although significant ancestry-specific associations were also identified. While all alleles were associated with a decreased kidney function, associations with CKD-related diseases (e.g., T2D) were found only for a smaller subset of variants and differed across genetic ancestry groups. Our findings leverage genetics to gain insights into the underlying biology of CKD and investigate population-specific associations.