bluuebunny/crossref_metadata_2025 huggingface dataset:
Meta-Analysis of Biochar as an Amendment for Arsenic Mitigation in Paddy Soils
Authors: Mandal Jajati , Sharma Pushpa Kumari , Mondal Debapriya , Wood Michael D. , Hutchinson Simon M. , Kirby Jason , Srivastava Prashant
Published: January 2024

Purpose of Review

The purpose of this review is to evaluate the effectiveness of biochar in immobilizing arsenic (As) in contaminated paddy soils and its impact on As availability and bioaccumulation in rice, as well as rice plant biomass.

Recent Findings

Recent studies have focused on managing As contamination in agricultural fields, with a particular focus on South and Southeast Asia, where rice, a primary food source and As accumulator, is of significant concern. Biochar, a product of biomass pyrolysis, has emerged as a viable solution for environmental remediation due to its effectiveness in immobilizing metal(loid)s in water and soil. The successful implementation of biochar as a soil amendment strategy has led to growing interest in its use as an effective means of reducing the bioaccumulation and availability of metal(loid)s, including As.

A meta-analysis of 25 studies revealed that biochar generated from maize and sewage sludge successfully reduced As availability and bioaccumulation in rice grains. In addition, the use of biochar led to higher biomass and yield of rice crops compared to control groups. Modified biochar was more effective in decreasing As availability, likely due to interactions with iron and calcium phases or complexes occurring in or on the biochars. Nevertheless, at elevated biochar dosages, As mobilization was noted in field conditions which warrants further investigation.
An enhanced abnormal information expression spatiotemporal model for anomaly detection in multivariate time-series
Authors: Ge Di , Cheng Yuhang , Cao Shuangshuang , Ma Yanmei , Wu Yanwen
Published: January 2024

The detection of anomalies in high-dimensional time-series has always played a crucial role in the domain of system security. Recently, with rapid advancements in transformer model and graph neural network (GNN) technologies, spatiotemporal modeling approaches for anomaly detection tasks have been greatly improved. However, most methods focus on optimizing upstream time-series prediction tasks by leveraging joint spatiotemporal features. Through experiments, we found that this modeling approach not only risks the loss of some original anomaly information during data preprocessing, but also focuses on optimizing the performance of the upstream prediction task and does not directly enhance the performance of the downstream detection task. We propose a spatiotemporal anomaly detection model that incorporates an improved attention mechanism in the process of temporal modeling. We adopt a heterogeneous graph contrastive learning approach in spatio modeling to compensate for the representation of anomalous behavioral information, thereby guiding the model through thorough training. Through validation on two widely used real-world datasets, we demonstrate that our model outperforms baseline methods. We also explore the impact of multivariate time-series prediction tasks on the detection task, and visualize the reasons behind the benefits gained by our model.
Indefinitely repeated contests with incumbency advantage
Authors: Deck Cary , Dorobiala Zachary , Jindapon Paan
Published: January 2024

We study an indefinitely repeated Tullock contest in which the stage-game winner gains an incumbency advantage in the next stage-game. The incumbent's advantage allows the incumbent to carry over a proportion of their expenditure in the previous contest to the next contest. Theoretically, this advantage is not predicted to have a large impact on total expenditure. However, in a controlled laboratory experiment, we find the incumbency advantage increases total expenditure by a significant amount. Further, we find that carryover has a discouraging effect on challengers while encouraging incumbents react in a retaliatory manner.
Early Maladaptive Schemas and Their Associations with Perceived Parental Bonding among Adolescents Entering Specialized Health Care
Authors: Saarijärvi Pauliina , Salmivalli Christina , Helmi Saija , Karukivi Max
Published: January 2024

Early maladaptive schemas (EMSs) have scarcely been studied in adolescents. The present study investigates EMSs in two clinical samples of 12–22-year-olds recruited from patients entering a specialized adolescent psychiatry clinic [n = 190] or a pediatric clinic [n = 119] in Finland. The endorsement of EMSs was compared between these samples, and the association of EMSs with perceived parental bonding was assessed. EMSs were assessed with the Young Schema Questionnaire-Short Form 2-Extended and particularly affectionless control parenting style with the Parental Bonding Instrument. The main analyses were conducted using general linear modeling. Significant differences existed between the two samples, with most EMSs and EMS domains being stronger in the adolescent psychiatry sample. The Disconnection and Rejection domain was associated with maternal affectionless control in the adolescent psychiatry sample and paternal affectionless control in the pediatric sample. The results provide novel findings of EMSs in adolescents and their links to parenting.
2023—A twofold commemoration: the 100th birthday of Walsh functions and the 50th anniversary of Professor Joseph Leonard Walsh’s death
Authors: Butzer Paul L. , Pichler Franz , Schipp Ferenc , Stanković Radomir S. , Stens Rudolf L.
Published: January 2024

In 2023, it is 100 years after the introduction of Walsh functions and 50 years after the death of their introducer Joseph Leonard Walsh. This paper is an homage to J. L. Walsh and presents some insights into the development of Walsh and dyadic analysis with applications of Walsh functions in both mathematics and various areas of computing and engineering. The presentation is based on reminiscences of the authors acting in these areas.
Machine Learning Interpretability of Outer Radiation Belt Enhancement and Depletion Events
Authors: Ma Donglai , Bortnik Jacob , Ma Qianli , Hua Man , Chu Xiangning
Published: January 2024

We investigate the response of outer radiation belt electron fluxes to different solar wind and geomagnetic indices using an interpretable machine learning method. We reconstruct the electron flux variation during 19 enhancement and 7 depletion events and demonstrate the feature attribution analysis called SHAP (SHapley Additive exPlanations) on the superposed epoch results for the first time. We find that the intensity and duration of the substorm sequence following an initial dropout determine the overall enhancement or depletion of electron fluxes, while the solar wind pressure drives the initial dropout in both types of events. Further statistical results from a data set with 71 events confirm this and show a significant correlation between the resulting flux levels and the average AL index, indicating that the observed “depletion” event can be more accurately described as a “non‐enhancement” event. Our novel SHAP‐Enhanced Superposed Epoch Analysis (SHESEA) method can offer insight in various physical systems.
The Interplay Between Pore‐Scale Heterogeneity, Surface Roughness, and Wettability Controls Trapping in Two‐Phase Fluid Displacement in Porous Media
Authors: Geistlinger Helmut , Golmohammadi Saeed , Zulfiqar Bilal , Schlueter Steffen , Segre Enrico , Holtzman Ran
Published: January 2024

Predicting the compactness of the invasion front and the amount of trapped fluid left behind is of crucial importance to applications ranging from microfluidics and fuel cells to subsurface storage of carbon and hydrogen. We examine the interplay of wettability, macro‐ and pore scale heterogeneity (pore angularity and pore wall roughness), and its influence on flow patterns formation and trapping efficiency in porous media by a combination of 3D micro‐CT imaging with 2D direct visualization of micromodels. We observe various phase transitions between the following capillary flow regimes (phases): (a) compact advance, (b) wetting and drainage Invasion percolation, (c) Ordinary percolation.
Performance of Regional Climate Model Precipitation Simulations Over the Terrain‐Complex Andes‐Amazon Transition Region
Authors: Gutierrez Ricardo A. , Junquas Clémentine , Armijos Elisa , Sörensson Anna A. , Espinoza Jhan‐Carlo
Published: January 2024

Regional climate models (RCMs) are widely used to assess future impacts associated with climate change at regional and local scales. RCMs must represent relevant climate variables in the present‐day climate to be considered fit‐for‐purpose for impact assessment. This condition is particularly difficult to meet over complex regions such as the Andes‐Amazon transition region, where the Andean topography and abundance of tropical rainfall regimes remain a challenge for numerical climate models. In this study, we evaluate the ability of 30 regional climate simulations (6 RCMs driven by 10 global climate models) to reproduce historical (1981–2005) rainfall climatology and temporal variability over the Andes‐Amazon transition region. We assess spatio‐temporal features such as spatial distribution of rainfall, focusing on the orographic effects over the Andes‐Amazon “rainfall hotspots” region, and seasonal and interannual precipitation variability. The Eta RCM exhibits the highest spatial correlation (up to 0.6) and accurately reproduces mean annual precipitation and orographic precipitation patterns across the region, while some other RCMs have good performances at specific locations. Most RCMs simulate a wet bias over the highlands, particularly at the eastern Andean summits, as evidenced by the 100%–2,500% overestimations of precipitation in these regions. Annual cycles are well represented by most RCMs, but peak seasons are exaggerated, especially at equatorial locations. No RCM is particularly skillful in reproducing the interannual variability patterns. Results highlight skills and weaknesses of the different regional climate simulations, and can assist in the selection of regional climate simulations for impact studies in the Andes‐Amazon transition zone.
Mobile Observations of Ozone and Aerosols in Alabama: Southeastern US Summer Pollution and Coastal Variability
Authors: Kuang Shi , Newchurch Michael J. , McKinney Todd , Perlaky Nicolas , Tucker Paula , Stevenson Darby , Alexander Susan , Pour‐Biazar Arastoo , Knupp Kevin , Johnson Matthew S. , Sullivan John T.
Published: January 2024

We present a detailed analysis of measurements of ozone (O3) and aerosols collected using multiple platforms and instruments during a 5‐day mini‐campaign in Alabama, for improving our understanding of the chemistry and air quality in the Southeastern United States. Our study features the first on‐road O3 lidar profiling on highways and the coordinated airborne observations that captured O3 and aerosol structures associated with synoptic weather conditions, stratospheric intrusions, wildfire smoke transport, and enhancements in urban areas. The Doppler wind lidar data suggest that the vertical structures and variability of O3 and aerosols at Dauphin Island, a coastal site in the Gulf of Mexico, were related to both the synoptic flow and local‐scale land‐sea breeze circulation. The onshore gulf breeze, which typically started in the afternoon, helped to quickly dilute air pollutants near the surface, resulting in large gradients toward inland areas. In contrast, gradients were much smaller on days without a gulf breeze. O3 and humidity were highly anti‐correlated in the lower free troposphere, but weakly anti‐correlated in the planetary boundary layer (PBL) suggesting more complicated emissions and sink of O3 in the PBL. Our on‐road and airborne measurement strategies to quantify the vertical and horizontal chemical gradients will be useful for future geostationary satellite validation.
Deciphering Martian Flood Infiltration Processes at Hebrus Valles: Insights From Laboratory Experiments and Remote Sensing Observations
Authors: Costard F. , Rodriguez J. A. P. , Godin E. , Séjourné A. , Kargel J. S.
Published: January 2024

In evaluating the unique geomorphology of Hebrus Valles on Mars, an outflow channel southeast of Utopia Planitia, we investigated the role of fluvial dynamics in forming subsurface conduits. Unlike typical Martian channels that terminate under younger sediment rocks, Hebrus Valles retains its downstream features, thus offering a window into surface and subsurface interactions between liquid water and regolith. Employing physical lab simulations, we utilized buried polygonal tunneling configurations in a sandy matrix to replicate the incision features observed at the channel's terminus. This study provides the first lab‐based evidence demonstrating the role of conduits in conveying large floods in the Hebrus Valles. Our results lend support to the interpretation that Hebrus Valles conveyed high‐volume floods by demonstrating that conduits are necessary to form the features observed on the surface of Hebrus Valles. The experiments also highlight the role of sinkholes as floodwater capture points, which suggests the formation of a regional interconnected network of subsurface channels and caverns. These findings affirm that fluvial dynamics in Hebrus Valles could have expanded subsurface discontinuities into functioning conduit systems, potentially directing floodwaters through an interconnected subterranean network.
DMT1-dependent endosome-mitochondria interactions regulate mitochondrial iron translocation and metastatic outgrowth
Authors: Barra Jonathan , Crosbourne Isaiah , Roberge Cassandra L. , Bossardi-Ramos Ramon , Warren Janine S. A. , Matteson Kailie , Wang Ling , Jourd’heuil Frances , Borisov Sergey M. , Bresnahan Erin , Bravo-Cordero Jose Javier , Dmitriev Ruslan I. , Jourd’heuil David , Adam Alejandro P. , Lamar John M. , Corr David T. , Barroso Margarida M.
Published: January 2024

Transient early endosome (EE)-mitochondria interactions can mediate mitochondrial iron translocation, but the associated mechanisms are still elusive. We showed that Divalent Metal Transporter 1 (DMT1) sustains mitochondrial iron translocation via EE-mitochondria interactions in triple-negative MDA-MB-231, but not in luminal A T47D breast cancer cells. DMT1 silencing increases labile iron pool (LIP) levels and activates PINK1/Parkin-dependent mitophagy in MDA-MB-231 cells. Mitochondrial bioenergetics and the iron-associated protein profile were altered by DMT1 silencing and rescued by DMT1 re-expression. Transcriptomic profiles upon DMT1 silencing are strikingly different between 2D and 3D culture conditions, suggesting that the environment context is crucial for the DMT1 knockout phenotype observed in MDA-MB-231 cells. Lastly, in vivo lung metastasis assay revealed that DMT1 silencing promoted the outgrowth of lung metastatic nodules in both human and murine models of triple-negative breast cancer cells. These findings reveal a DMT1‐dependent pathway connecting EE-mitochondria interactions to mitochondrial iron translocation and metastatic fitness of breast cancer cells.
ECP versus ruxolitinib in steroid-refractory chronic GVHD – a retrospective study by the EBMT transplant complications working party
Authors: Penack Olaf , Peczynski Christophe , Boreland William , Lemaitre Jessica , Reinhardt H. Christian , Afanasyeva Ksenia , Avenoso Daniele , Holderried Tobias A. W. , Kornblit Brian Thomas , Gavriilaki Eleni , Martinez Carmen , Chiusolo Patrizia , Mico Maria Caterina , Daguenet Elisabeth , Wichert Stina , Ozdogu Hakan , Piekarska Agnieszka , Kinsella Francesca , Basak Grzegorz W. , Schoemans Hélène , Koenecke Christian , Moiseev Ivan , Peric Zinaida
Published: January 2024

Ruxolitinib has become the new standard of care for steroid-refractory and steroid-dependent chronic GVHD (SR-cGVHD). Our aim was to collect comparative data between ruxolitinib and extracorporeal photophoresis (ECP). We asked EBMT centers if they were willing to provide detailed information on GVHD grading, -therapy, -dosing, -response and complications for each included patient. 31 centers responded positively and we included all patients between 1/2017-7/2019 treated with ECP or ruxolitinib for moderate or severe SR-cGVHD. We identified 84 and 57 patients with ECP and ruxolitinib, respectively. We performed multivariate analyses adjusted on grading and type of SR-cGVHD (steroid dependent vs. refractory vs. intolerant to steroids). At day+180 after initiation of treatment for SR-cGVHD the odds ratio in the ruxolitinib group to achieve overall response vs. the ECP group was 1.35 (95% CI = [0.64; 2.91], p = 0.43). In line, we detected no statistically significant differences in overall survival, progression-free survival, non-relapse mortality and relapse incidence. The clinical significance is limited by the retrospective study design and the current data can’t replace prospective studies on ECP in SR-cGVHD. However, the present results contribute to the accumulating evidence on ECP as an effective treatment option in SR-cGVHD.
Dendritic cell therapy for neurospoagioma: Immunomodulation mediated by tumor vaccine
Authors: Qian Da , Liu Yuxiang , Zheng Jie , Cai Jinquan
Published: January 2024

Neurospagioma, arising from different glial cells such as astrocytes, oligodendrocytes, and ependymal cells, stands as the prevalent intracranial tumor within the central nervous system. Among its variants, glioblastoma (GBM) represents the most aggressive form, characterized by a notably high occurrence rate and a discouragingly low survival prognosis. The formidable challenge posed by glioblastoma underscores its critical importance as a life-threatening ailment. Currently, clinical approaches often involve surgical excision along with a combination of radiotherapy and chemotherapy. However, these treatments frequently result in a notable recurrence rate, accompanied by substantial adverse effects that significantly compromise the overall prognosis. Hence, there is a crucial need to investigate novel and dependable treatment strategies. Dendritic cells (DCs), being specialized antigen-presenting cells (APCs), hold a significant position in both innate and adaptive immune responses. Presently, DC vaccines have gained widespread application in the treatment of various tumors, including neurospoagioma. In this review, we summarize the immunomodulatory effects and related mechanisms of DC vaccines in neurospoagioma as well as the progress of clinical trials to propose possible challenges of DC vaccines and new development directions.
Fatty acid amide hydrolase drives adult mammary gland development by promoting luminal cell differentiation
Authors: Tundidor Isabel , Seijo-Vila Marta , Blasco-Benito Sandra , Rubert-Hernández María , Moreno-Bueno Gema , Bindila Laura , de la Rosa Rubén Fernández , Guzmán Manuel , Sánchez Cristina , Pérez-Gómez Eduardo
Published: January 2024

Mammary gland development occurs primarily in adulthood, undergoing extensive expansion during puberty followed by cycles of functional specialization and regression with every round of pregnancy/lactation/involution. This process is ultimately driven by the coordinated proliferation and differentiation of mammary epithelial cells. However, the endogenous molecular factors regulating these developmental dynamics are still poorly defined. Endocannabinoid signaling is known to determine cell fate-related events during the development of different organs in the central nervous system and the periphery. Here, we report that the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) plays a pivotal role in adult mammary gland development. Specifically, it is required for luminal lineage specification in the mammary gland, and it promotes hormone-driven secretory differentiation of mammary epithelial cells by controlling the endogenous levels of anandamide and the subsequent activation of cannabinoid CB1 receptors. Together, our findings shed light on the role of the endocannabinoid system in breast development and point to FAAH as a therapeutic target in milk-production deficits.
A role and mechanism for redox sensing by SENP1 in β-cell responses to high fat feeding
Authors: Lin Haopeng , Suzuki Kunimasa , Smith Nancy , Li Xi , Nalbach Lisa , Fuentes Sonia , Spigelman Aliya F. , Dai Xiao-Qing , Bautista Austin , Ferdaoussi Mourad , Aggarwal Saloni , Pepper Andrew R. , Roma Leticia P. , Ampofo Emmanuel , Li Wen-hong , MacDonald Patrick E.
Published: January 2024

Pancreatic β-cells respond to metabolic stress by upregulating insulin secretion, however the underlying mechanisms remain unclear. Here we show, in β-cells from overweight humans without diabetes and mice fed a high-fat diet for 2 days, insulin exocytosis and secretion are enhanced without increased Ca2+ influx. RNA-seq of sorted β-cells suggests altered metabolic pathways early following high fat diet, where we find increased basal oxygen consumption and proton leak, but a more reduced cytosolic redox state. Increased β-cell exocytosis after 2-day high fat diet is dependent on this reduced intracellular redox state and requires the sentrin-specific SUMO-protease-1. Mice with either pancreas- or β-cell-specific deletion of this fail to up-regulate exocytosis and become rapidly glucose intolerant after 2-day high fat diet. Mechanistically, redox-sensing by the SUMO-protease requires a thiol group at C535 which together with Zn+-binding suppresses basal protease activity and unrestrained β-cell exocytosis, and increases enzyme sensitivity to regulation by redox signals.
PIEZO1 loss-of-function compound heterozygous mutations in the rare congenital human disorder Prune Belly Syndrome
Authors: Amado Nathalia G. , Nosyreva Elena D. , Thompson David , Egeland Thomas J. , Ogujiofor Osita W. , Yang Michelle , Fusco Alexandria N. , Passoni Niccolo , Mathews Jeremy , Cantarel Brandi , Baker Linda A. , Syeda Ruhma
Published: January 2024

Prune belly syndrome (PBS), also known as Eagle-Barret syndrome, is a rare, multi-system congenital myopathy primarily affecting males. Phenotypically, PBS cases manifest three cardinal pathological features: urinary tract dilation with poorly contractile smooth muscle, wrinkled flaccid ventral abdominal wall with skeletal muscle deficiency, and intra-abdominal undescended testes. Genetically, PBS is poorly understood. After performing whole exome sequencing in PBS patients, we identify one compound heterozygous variant in the PIEZO1 gene. PIEZO1 is a cation-selective channel activated by various mechanical forces and widely expressed throughout the lower urinary tract. Here we conduct an extensive functional analysis of the PIEZO1 PBS variants that reveal loss-of-function characteristics in the pressure-induced normalized open probability (NPo) of the channel, while no change is observed in single-channel currents. Furthermore, Yoda1, a PIEZO1 activator, can rescue the NPo defect of the PBS mutant channels. Thus, PIEZO1 mutations may be causal for PBS and the in vitro cellular pathophysiological phenotype could be rescued by the small molecule, Yoda1. Activation of PIEZO1 might provide a promising means of treating PBS and other related bladder dysfunctional states.
Functional host-specific adaptation of the intestinal microbiome in hominids
Authors: Rühlemann M. C. , Bang C. , Gogarten J. F. , Hermes B. M. , Groussin M. , Waschina S. , Poyet M. , Ulrich M. , Akoua-Koffi C. , Deschner T. , Muyembe-Tamfum J. J. , Robbins M. M. , Surbeck M. , Wittig R. M. , Zuberbühler K. , Baines J. F. , Leendertz F. H. , Franke A.
Published: January 2024

Fine-scale knowledge of the changes in composition and function of the human gut microbiome compared that of our closest relatives is critical for understanding the evolutionary processes underlying its developmental trajectory. To infer taxonomic and functional changes in the gut microbiome across hominids at different timescales, we perform high-resolution metagenomic-based analyzes of the fecal microbiome from over two hundred samples including diverse human populations, as well as wild-living chimpanzees, bonobos, and gorillas. We find human-associated taxa depleted within non-human apes and patterns of host-specific gut microbiota, suggesting the widespread acquisition of novel microbial clades along the evolutionary divergence of hosts. In contrast, we reveal multiple lines of evidence for a pervasive loss of diversity in human populations in correlation with a high Human Development Index, including evolutionarily conserved clades. Similarly, patterns of co-phylogeny between microbes and hosts are found to be disrupted in humans. Together with identifying individual microbial taxa and functional adaptations that correlate to host phylogeny, these findings offer insights into specific candidates playing a role in the diverging trajectories of the gut microbiome of hominids. We find that repeated horizontal gene transfer and gene loss, as well as the adaptation to transient microaerobic conditions appear to have played a role in the evolution of the human gut microbiome.
A uniform data processing pipeline enables harmonized nanoparticle protein corona analysis across proteomics core facilities
Authors: Gharibi Hassan , Ashkarran Ali Akbar , Jafari Maryam , Voke Elizabeth , Landry Markita P. , Saei Amir Ata , Mahmoudi Morteza
Published: January 2024

Protein corona, a layer of biomolecules primarily comprising proteins, forms dynamically on nanoparticles in biological fluids and is crucial for predicting nanomedicine safety and efficacy. The protein composition of the corona layer is typically analyzed using liquid chromatography-mass spectrometry (LC-MS/MS). Our recent study, involving identical samples analyzed by 17 proteomics facilities, highlighted significant data variability, with only 1.8% of proteins consistently identified across these centers. Here, we implement an aggregated database search unifying parameters such as variable modifications, enzyme specificity, number of allowed missed cleavages and a stringent 1% false discovery rate at the protein and peptide levels. Such uniform search dramatically harmonizes the proteomics data, increasing the reproducibility and the percentage of consistency-identified unique proteins across distinct cores. Specifically, out of the 717 quantified proteins, 253 (35.3%) are shared among the top 5 facilities (and 16.2% among top 11 facilities). Furthermore, we note that reduction and alkylation are important steps in protein corona sample processing and as expected, omitting these steps reduces the number of total quantified peptides by around 20%. These findings underscore the need for standardized procedures in protein corona analysis, which is vital for advancing clinical applications of nanoscale biotechnologies.
Dietary emulsifier consumption accelerates type 1 diabetes development in NOD mice
Authors: Delaroque Clara , Chassaing Benoit
Published: January 2024

The rapidly increasing prevalence of type 1 diabetes (T1D) underscores the role of environmental (i.e. non-genetic) determinants of T1D development. Such factors include industrialized diets as well as the intestinal microbiota with which they interact. One component of industrialized diets that deleteriously impact gut microbiota is dietary emulsifiers, which perturb intestinal microbiota to encroach upon their host promoting chronic low-grade intestinal inflammation and metabolic syndrome. Hence, we investigated whether 2 dietary emulsifiers, carboxymethylcellulose (CMC) and polysorbate-80 (P80), might influence the development of T1D in NOD mice, which spontaneously develop this disorder. We observed that chronic emulsifier exposure accelerated T1D development in NOD mice, which was associated with increased insulin autoantibody levels. Such accelerated T1D development was accompanied by compositional and functional alterations of the intestinal microbiota as well as low-grade intestinal inflammation. Moreover, machine learning found that the severity of emulsifier-induced microbiota disruption had partial power to predict subsequent disease development, suggesting that complex interactions occur between the host, dietary factors, and the intestinal microbiota. Thus, perturbation of host–microbiota homeostasis by dietary emulsifiers may have contributed to the post-mid-20th-century increase in T1D.
Loss of the extracellular matrix glycoprotein EMILIN1 accelerates Δ16HER2-driven breast cancer initiation in mice
Authors: Favero Andrea , Segatto Ilenia , Capuano Alessandra , Mattevi Maria Chiara , Rampioni Vinciguerra Gian Luca , Musco Lorena , D’Andrea Sara , Dall’Acqua Alessandra , Gava Chiara , Perin Tiziana , Massarut Samuele , Marchini Cristina , Baldassarre Gustavo , Spessotto Paola , Belletti Barbara
Published: January 2024

The extracellular matrix (ECM) is an important component of the tumor microenvironment and undergoes extensive remodeling during both initiation and progression of breast cancer (BC). EMILIN1 is an ECM glycoprotein, whose function has been linked to cancer and metastasis. However, EMILIN1 role during mammary gland and BC development has never been investigated. In silico and molecular analyses of human samples from normal mammary gland and BC showed that EMILIN1 expression was lower in tumors than in healthy mammary tissue and it predicted poor prognosis, particularly in HER2-positive BC. HER2+ BC accounts for 15-20% of all invasive BC and is characterized by high aggressiveness and poor prognosis. The Δ16HER2 isoform, a splice variant with very high oncogenic potential, is frequently expressed in HER2+ BC and correlates with metastatic disease. To elucidate the role of EMILIN1 in BC, we analyzed the phenotype of MMTV-Δ16HER2 transgenic mice, developing spontaneous multifocal mammary adenocarcinomas, crossed with EMILIN1 knock-out (KO) animals. We observed that Δ16HER2/EMILIN1 KO female mice exhibited an accelerated normal mammary gland development and a significantly anticipated appearance of palpable tumors (13.32 vs 15.28 weeks). This accelerated tumor initiation was corroborated by an increased number of tumor foci observed in mammary glands from Δ16HER2/EMILIN1 KO mice compared to the wild-type counterpart. Altogether our results underscore the centrality of ECM in the process of BC initiation and point to a role for EMILIN1 during normal mammary gland development and in protecting from HER2-driven breast tumorigenesis.
Influence of Cr(III) on the formation and transformation of corrosion products of steel in marine environments
Authors: Serjaouan M. , Rémazeilles C. , Refait Ph.
Published: January 2024

A fundamental approach is used to better understand the influence of Cr on the resistance of low alloy steel to marine corrosion. It focuses on the formation and transformation of corrosion products of steel in seawater-like electrolytes. Fe(OH)2 precipitates are then prepared by mixing a solution of NaCl, Na2SO4·10H2O, FeCl2·4H2O or FeCl2·4H2O + CrCl3·6H2O (so that Cr = 8% and Fe = 92%), with a solution of NaOH. The initial concentration ratio of reactants, $$Q=\frac{2[{{{\rm{Fe}}}}^{2+}]+3[{{{\rm{Cr}}}}^{3+}]}{[{{{\rm{OH}}}}^{-}]}$$

Q
=

2

[

Fe

2
+

]

+
3

[

Cr

3
+

]

[

OH

−

]

, is set at Q = 0.88, 1, and 1.136. In a first approach, the obtained aqueous suspension is stirred, at a controlled temperature of 25 ± 0.5 °C, to be oxidized by air. The resulting oxidation product is characterized by XRD and Raman spectroscopy. In a second approach, the Fe(OH)2 precipitates are aged one week in suspension in anoxic conditions, filtered, mixed as a wet paste with glycerol and set as a thin compact layer on the sample holder of a X-ray diffraction system. The oxidation process of Fe(OH)2 is then monitored in situ during the acquisition of the X-ray diffractogram. The obtained results demonstrate that Cr(III) hinders the formation of green rust compounds, hence hindering the formation of γ-FeOOH, i.e., the main oxidation product of green rust compounds. The other oxidation pathways of Fe(OH)2, which lead to Fe3O4 or α-FeOOH, are thus favored. Nevertheless, Cr(III) favors mainly the solid state transformation pathway of Fe(OH)2, thus promoting α-FeOOH via the formation of poorly ordered Fe(III) oxyhydroxides, namely feroxyhyte and ferrihydrite.
Unveiling multipole physics and frustration of icosahedral magnetic quasicrystals
Authors: Jeon Junmo , Lee SungBin
Published: January 2024

Multipolar physics and their hidden orders have been widely discussed in the context of heavy fermions and frustrated magnets. However, despite extensive research, there are few examples of purely multipolar systems in the absence of magnetic dipoles. Here, we show the magnetic behavior of an icosahedral quasicrystal is generally described by multipoles, and in a specific case by pure magnetic octupoles, resulting from the interplay of spin-orbit coupling and crystal field splitting. Importantly, we emphasize that non-crystallographic symmetries of quasicrystals result in multipolar degrees of freedom, in contrast to the conventional crystals. We first classify the characteristics of multipoles and derive the effective spin Hamiltonian. We then explore how frustration and quantum fluctuations induce entangled quantum phases. Our study presents the magnetic icosahedral quasicrystal as a platform for investigating the exotic multipolar physics.
PvDBPII elicits multiple antibody-mediated mechanisms that reduce growth in a Plasmodium vivax challenge trial
Authors: Martinez Francisco J. , White Michael , Guillotte-Blisnick Micheline , Huon Christèle , Boucharlat Alix , Agou Fabrice , England Patrick , Popovici Jean , Hou Mimi M. , Silk Sarah E. , Barrett Jordan R. , Nielsen Carolyn M. , Reimer Jenny M. , Mukherjee Paushali , Chauhan Virander S. , Minassian Angela M. , Draper Simon J. , Chitnis Chetan E.
Published: January 2024

The receptor-binding domain, region II, of the Plasmodium vivax Duffy binding protein (PvDBPII) binds the Duffy antigen on the reticulocyte surface to mediate invasion. A heterologous vaccine challenge trial recently showed that a delayed dosing regimen with recombinant PvDBPII SalI variant formulated with adjuvant Matrix-MTM reduced the in vivo parasite multiplication rate (PMR) in immunized volunteers challenged with the Thai P. vivax isolate PvW1. Here, we describe extensive analysis of the polyfunctional antibody responses elicited by PvDBPII immunization and identify immune correlates for PMR reduction. A classification algorithm identified antibody features that significantly contribute to PMR reduction. These included antibody titre, receptor-binding inhibitory titre, dissociation constant of the PvDBPII-antibody interaction, complement C1q and Fc gamma receptor binding and specific IgG subclasses. These data suggest that multiple immune mechanisms elicited by PvDBPII immunization are likely to be associated with protection and the immune correlates identified could guide the development of an effective vaccine for P. vivax malaria. Importantly, all the polyfunctional antibody features that correlated with protection cross-reacted with both PvDBPII SalI and PvW1 variants, suggesting that immunization with PvDBPII should protect against diverse P. vivax isolates.
Gene modelling and annotation for the Hawaiian bobtail squid, Euprymna scolopes
Authors: Rogers Thea F. , Yalçın Gözde , Briseno John , Vijayan Nidhi , Nyholm Spencer V. , Simakov Oleg
Published: January 2024

Coleoid cephalopods possess numerous complex, species-specific morphological and behavioural adaptations, e.g., a uniquely structured nervous system that is the largest among the invertebrates. The Hawaiian bobtail squid (Euprymna scolopes) is one of the most established cephalopod species. With its recent publication of the chromosomal-scale genome assembly and regulatory genomic data, it also emerges as a key model for cephalopod gene regulation and evolution. However, the latest genome assembly has been lacking a native gene model set. Our manuscript describes the generation of new long-read transcriptomic data and, made using this combined with a plethora of publicly available transcriptomic and protein sequence data, a new reference annotation for E. scolopes.
Experimental study on dynamic characteristics of tailings under different consolidation conditions
Authors: Du Changbo , Jiang Xinqi , Wang Laigui , Yi Fu , Niu Ben
Published: January 2024

The dynamic stability of tailing ponds depend largely on the dynamic characteristics of tailings sand. To explore the dynamic characteristics of tailings sand under different consolidation conditions, consolidated undrained triaxial tests under different dry densities, consolidation ratios and containing pressures, the dynamic shear stress, liquefaction stress ratio, dynamic strength index, dynamic pore water pressure, dynamic modulus, and damping ratio of tailings sand under different consolidation conditions were analyzed. The dynamic shear stress linearly changed with the number of failure vibrations. The liquefaction stress ratio increases with an increase in consolidation ratio, conforming to the quadratic polynomial of the origin. With an increase in failure vibration times, the dynamic internal friction angle decreases gradually. Under different failure vibration times, the dynamic internal friction angle increases with an increase in consolidation ratio and dry density. An exponential function model of dynamic pore pressure growth suitable for equal pressure and bias consolidation conditions is proposed, and the fitting effect is favorable. The dynamic shear modulus ratio decreases with an increase in dynamic shear strain; the damping ratio increases with an increase in dynamic shear strain. The research results can provide a theoretical reference for seismic liquefaction of tailings dams in high-intensity seismic areas.
Investigating clot-flow interactions by integrating intravital imaging with in silico modeling for analysis of flow, transport, and hemodynamic forces
Authors: Teeraratkul Chayut , Tomaiuolo Maurizio , Stalker Timothy J. , Mukherjee Debanjan
Published: January 2024

As a blood clot forms, grows, deforms, and embolizes following a vascular injury, local clot-flow interactions lead to a highly dynamic flow environment. The local flow influences transport of biochemical species relevant for clotting, and determines the forces on the clot that in turn lead to clot deformation and embolization. Despite this central role, quantitative characterization of this dynamic clot-flow interaction and flow environment in the clot neighborhood remains a major challenge. Here, we propose an approach that integrates dynamic intravital imaging with computer geometric modeling and computational flow and transport modeling to develop a unifiedin silicoframework to quantify the dynamic clot-flow interactions. We outline the development of the methodology referred to as Intravital Integrated In Silico Modeling or , and then demonstrate the method on a sample set of simulations comprising clot formation following laser injury in two mouse cremaster arteriole injury model data: one wild-type mouse case, and one diYF knockout mouse case. Simulation predictions are verified against experimental observations of transport of caged fluorescent Albumin (cAlb) in both models. Through these simulations, we illustrate how the methodology can provide insights into hemostatic processes, the role of flow and clot-flow interactions, and enable further investigations comparing and contrasting different biological model scenarios and parameter variations.
An innovative staged prosthetic lengthening reconstruction strategy for osteosarcoma-related leg discrepancy
Authors: Xu Hairong , Li Yuan , Yu Feng , Liu Weifeng , Hao Lin , Zhang Qing , Niu Xiaohui
Published: January 2024

Correction of leg length discrepancy (LLD) in skeletally mature patients with osteosarcoma was rarely reported and quite challenging. This study aimed to propose a treatment strategy of staged lengthening and reconstruction with a standard static prosthesis to address LLD and restore limb function. It also evaluated the effectiveness of the strategy in terms of leg lengthening, functional outcomes, and complications. The strategy for lengthening included three stages. In stage 1, the previous prosthesis was removed and an external fixator with a temporary rod-cement spacer was placed. In this stage, the external fixator was used to lengthen the limb to the appropriate length. In stage 2, the external fixator was removed and the old rod-cement spacer was replaced with a new one. In stage 3, the rod-cement spacer was removed and the standard static prosthesis was planted. Nine skeletally mature distal femoral osteosarcoma patients with unacceptable LLD were treated in our institution from 2019 to 2021. We performed a chart review on nine patients for the clinical and radiographic assessment of functional outcomes, LLD, and complications. The mean (range) leg lengthening was 7.3 cm (3.6–15.6). The mean (range) LLD of the lower limbs decreased from 7.6 cm (4.1–14.2) before the lengthening to 0.3 cm (− 0.3 to 2.1) at the final follow-up with statistical significance (P = 0.000). The mean (range) Musculoskeletal Tumor Society score improved from 30.3% (16.7%–53.3%) before the lengthening to 96.3% (86.7%–100%) at the final follow-up with statistical significance (P = 0.000). Three patients (33.3%) had a minor complication; none needed additional surgical intervention. In the short term, the current staged lengthening and reconstruction with standard static prosthesis provided satisfactory functional outcomes and LLD correction with few complications. The long-term effects of this method need further exploration.
Studying SARS-CoV-2 interactions using phage-displayed receptor binding domain as a model protein
Authors: Pérez-Massón Beatriz , Quintana-Pérez Yazmina , Tundidor Yaima , Pérez-Martínez Dayana , Castro-Martínez Camila , Pupo-Meriño Mario , Orosa Ivette , Relova-Hernández Ernesto , Villegas Rosmery , Guirola Osmany , Rojas Gertrudis
Published: January 2024

SARS-CoV-2 receptor binding domain (RBD) mediates viral entry into human cells through its interaction with angiotensin converting enzyme 2 (ACE2). Most neutralizing antibodies elicited by infection or vaccination target this domain. Such a functional relevance, together with large RBD sequence variability arising during viral spreading, point to the need of exploring the complex landscape of interactions between RBD-derived variants, ACE2 and antibodies. The current work was aimed at developing a simple platform to do so. Biologically active and antigenic Wuhan-Hu-1 RBD, as well as mutated RBD variants found in nature, were successfully displayed on filamentous phages. Mutational scanning confirmed the global plasticity of the receptor binding motif within RBD, highlighted residues playing a critical role in receptor binding, and identified mutations strengthening the interaction. The ability of vaccine-induced antibodies to inhibit ACE2 binding of many mutated RBD variants, albeit at different extents, was shown. Amino acid replacements which could compromise such inhibitory potential were underscored. The expansion of our approach could be the starting point for a large-scale phage-based exploration of diversity within RBD of SARS-CoV-2 and related coronaviruses, useful to understand structure–function relationships, to engineer RBD proteins, and to anticipate changes to watch during viral evolution.
The development and internal pilot trial of a digital physical activity and emotional well-being intervention (Kidney BEAM) for people with chronic kidney disease
Authors: Young Hannah M. L. , Castle Ellen M. , Briggs Juliet , Walklin Christy , Billany Roseanne E. , Asgari Elham , Bhandari Sunil , Bishop Nicolette , Bramham Kate , Burton James O. , Campbell Jackie , Chilcot Joseph , Cooper Nicola , Deelchand Vashist , Graham-Brown Matthew P. M. , Haggis Lynda , Hamilton Alexander , Jesky Mark , Kalra Philip A. , Koufaki Pelagia , Macdonald Jamie , McCafferty Kieran , Nixon Andrew C. , Noble Helen , Saynor Zoe L. , Taal Maarten W. , Tollitt James , Wheeler David C. , Wilkinson Thomas J. , Greenwood Sharlene A.
Published: January 2024

This trial assessed the feasibility and acceptability of Kidney BEAM, a physical activity and emotional well-being self-management digital health intervention (DHI) for people with chronic kidney disease (CKD), which offers live and on-demand physical activity sessions, educational blogs and videos, and peer support. In this mixed-methods, multicentre randomised waitlist-controlled internal pilot, adults with established CKD were recruited from five NHS hospitals and randomised 1:1 to Kidney BEAM or waitlist control. Feasibility outcomes were based upon a priori progression criteria. Acceptability was primarily explored via individual semi-structured interviews (n = 15). Of 763 individuals screened, n = 519 (68%, 95% CI 65 to 71%) were eligible. Of those eligible, n = 303 (58%, 95% CI 54–63%) did not respond to an invitation to participate by the end of the pilot period. Of the 216 responders, 50 (23%, 95% CI 18–29%) consented. Of the 42 randomised, n = 22 (10 (45%) male; 49 ± 16 years; 14 (64%) White British) were allocated to Kidney BEAM and n = 20 (12 (55%) male; 56 ± 11 years; 15 (68%) White British) to the waitlist control group. Overall, n = 15 (30%, 95% CI 18–45%) withdrew during the pilot phase. Participants completed a median of 14 (IQR 5–21) sessions. At baseline, 90–100% of outcome data (patient reported outcome measures and a remotely conducted physical function test) were completed and 62–83% completed at 12 weeks follow-up. Interview data revealed that remote trial procedures were acceptable. Participants’ reported that Kidney BEAM increased their opportunity and motivation to be physically active, however, lack of time remained an ongoing barrier to engagement with the DHI. An randomised controlled trial of Kidney BEAM is feasible and acceptable, with adaptations to increase recruitment, retention and engagement.

Trial registration NCT04872933. Date of first registration 05/05/2021.
Plasma-derived exosomal miR-326, a prognostic biomarker and novel candidate for treatment of drug resistant pediatric acute lymphoblastic leukemia
Authors: Saffari Neda , Rahgozar Soheila , Faraji Elaheh , Sahin Fikrettin
Published: January 2024

Acute lymphoblastic leukemia (ALL) is a cancer with high incidence rate in pediatrics and drug resistance is a major clinical concern for ALL treatment. The current study was designed to evaluate the role of exosomal miR-326 in diagnosis and treatment of children with B-ALL. Exosomes were isolated from plasma samples of 30 patients and B-ALL cell lines followed by characterization, using nanoparticle tracking analysis, immunoblotting assay and electron microscopy. qPCR showed significantly increased levels of miR-326 in patients exosomes compared with non-cancer controls (P < 0.05, AUC = 0.7500). Moreover, a comparison between the sensitive and drug resistant patients revealed a prognostic value for the exosomal miR326 (P < 0.05, AUC = 0.7755). Co-culture studies on drug resistant patient primary cells and B-ALL cell lines suggested that exosomes with high miR-326 level act as vehicles for reducing cells viability. B-ALL cell line transfection with naked miR-326 mimic confirmed the results, and fluorescence microscopy validated uptake and internalization of exosomes by target cells. The novel introduced features of the exosomal miR-326 address a non-invasive way of diagnosing primary drug resistance in pediatric ALL and advocates a novel therapeutic strategy for this cancer.