bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Multistage Mixed Methods Methodology to Develop a Toolkit to Reduce Infections Following Durable LVAD Implantation
Authors: Chandanabhumma P. Paul , Swaminathan Sriram , Cabrera Lourdes , Zhou Shiwei , Chenoweth Carol E. , Hou Hechuan , Comstock Sarah , Malani Preeti N. , Aaronson Keith D. , Pagani Francis D. , Likosky Donald S. 
Published: February 2025

ABSTRACTBackgroundInfections following durable left ventricular assist device (dLVAD) implantation are common and associated with increased morbidity and mortality. Despite documented interhospital variability, few studies have identified strategies to mitigate their occurrence. This national study uses a multistage mixed methods design to develop a customizable and deployable toolkit of expert-guided recommendations to reduce infections post-dLVAD.MethodsRepresentatives from low, medium, and high-performance hospitals across the U.S. were interviewed to assess factors contributing to post-dLVAD infections. Draft toolkit recommendations were iteratively developed after integrating thematically analyzed qualitative and quantitative data. A national advisory team of ventricular assist device (VAD) subject matter experts provided mixed methods input to refine the toolkit’s content and structure.ResultsSeventy-three clinical and operational VAD team members were interviewed, and 14 subject matter experts provided stakeholder feedback to refine the toolkit. The resulting toolkit contains 39 infection prevention recommendations that address VAD program care processes (e.g., real-time provider communication), clinicians (e.g., multidisciplinary protocol development), patients & caregivers (e.g., engaging patient advisors in patient education), and VAD leadership (e.g., unit and service level data reporting). Accompanying resources (e.g., team-based exercises, data collection worksheets) support implementing and evaluating site-specific strategies. Input from clinical and research experts provided preliminary evidence of the toolkit’s acceptability and considerations for enhancing the toolkit’s adoption and implementation.ConclusionsUsing mixed methods approaches, an infection prevention toolkit was developed to enhance care coordination among VAD team members and mitigate post-dLVAD infections. Future work should evaluate the effectiveness of implementing this infection prevention toolkit within the dLVAD setting.What is KnownSix out of every 10 patients develop an infection within 2 years of durable left ventricular assist device (dLVAD) implantation.Infections contribute to an increased risk of major morbidity and mortality.Post-dLVAD infection rates vary across hospitals, even after risk adjustment.What the Study AddsA customizable toolkit of infection prevention recommendations was developed and pilot tested using mixed methods approaches.Recommendations focus on modifiable aspects of organizational structure, patient care, patient education, quality reporting.
Squash flowers as microhabitats: the effects of floral temperature and humidity on pollen viability and visitor behavior
Authors: Dahake Ajinkya , Coates Charlotte , Obregon Diana , Chai Jonathan , Nunes-Silva Patricia , Kevan Peter , Raguso Robert A. 
Published: February 2025

SummaryFlowers represent intricate microcosms shaped by their chemical and micrometeorological properties. Notable examples include thermogenic flowers that create a warm microclimate for visitors and residents. We document a distinct microclimate within the large flowers of both wild and domesticated squashes (Cucurbita spp.). Unlike thermogenic flowers, squash flower temperatures remain near ambient, but their humidity consistently exceeds ambient levels from bud to senescence, resulting from stomatal and petal transpiration rather than nectar evaporation. Experimentally reducing humidity in greenhouse-grown male squash flowers results in significant pollen tube rupture, directly impacting plant fitness. To explore the role of floral humidity within a broader ecological context, we performed similar humidity manipulations on squash farms to assess impacts on the behavior of their specialist squash bee pollinator (Xenoglossa pruinosa), generalist pollinators (bumblebees, honeybees), and specialist herbivores (cucurbit beetles). Experimentally reduced floral humidity lower visitation frequency by squash bees but have no effect on generalist pollinators. Manipulation of floral humidity did not influence the foraging duration of any pollinators but impacted the residence of male squash bees in wilted flowers compared with unmanipulated flowers. Finally, there was a positive correlation between the dryness of the ambient air and the abundance of squash bees and cucurbit beetles residing in the humid wilted floral chambers. In conclusion, our findings showcase squash flowers as a humid microhabitat that influences reproductive success directly by affecting pollen viability and indirectly by altering interactions with squash bees, their specialist pollinators.
Divergent granulopoiesis at extramedullary sites safeguards host defense
Authors: Silvestre-Roig Carlos , Chevre Raphael , Bender Alexander , Vöcking Lina M. , Hageb Ali , Richter Mathis , Farjia Merieme , Braster Quinte , Guzman Mauricio , Sintes Jordi , Sharma Samriti , Lemnitzer Patricia , Ahern David , Osei-Sarpong Collins , Engel Daniel R. , Monaco Claudia , Dersch Petra , Kibler Artur , Cerutti Andrea , Chavakis Triantafyllos , Jablonska Jadwiga , Soehnlein Oliver 
Published: February 2025

AbstractExtramedullary organs such as the spleen can assume granulopoiesis as a supportive mechanism to cope with the demands during persistent inflammation. However, the quantitative output of extramedullary granulopoiesis is limited, thus raising the question if the spleen in fact provides neutrophils of a qualitative difference rather than merely contributing to neutrophil numbers. Here we report splenic stress granulopoiesis with distinct production and differentiation trajectories. Myeloid progenitors in the spleen engage in accelerated production of neutrophils with an immature phenotype. Yet, neutrophils generated during persistent stress granulopoiesis are fully competent to exert antimicrobial functions and are necessary to contain bacterial invasion. Activation of type I interferon signaling in the spleen is required for splenic neutrophil production and its loss impairs host defense. Thus, the spleen provides an immunological environment for stress-induced rapid production and priming of highly active neutrophils to meet the demands during infection.
Apoptotic caspases silence spontaneous innate immune signals by specifically cleaving activated mitochondrial antiviral signalling protein (MAVS)
Authors: Gradzka-Boberda Sylwia , Parui Ishita , Chakraborty Pallab , Anthony Danielle Paige , Puthussery Bhagya K. , Weber Arnim , Brokatzky Dominik , Giansanti Piero , Mergner Julia , Öllinger Rupert , Rad Roland , Kirschnek Susanne , Gentle Ian E. , Häcker Georg 
Published: February 2025

SummaryCaspases-9, -3 and -7 are activated in the mitochondrial apoptosis pathway and lead to the apoptotic phenotype. Caspases also function to limit inflammation upon apoptotic mitochondrial permeabilization through degradation of the signalling proteins cGAS, MAVS and IRF3. Cells and mice lacking caspases have higher interferon levels and are resistant to viral infection. We report that in unstimulated, non-apoptotic cells caspase-3 functions to cleave specifically activated MAVS and very likely cGAS. In unstimulated HeLa cells, constitutive caspase-9- and -3-but not 7-dependent proteolytic events were observed. Inhibition of the mitochondrial apoptosis pathway in various healthy cells induced type I interferon (IFN I) through increased cGAS activity in the absence of changes to cGAS levels. We observed enhanced MAVS-dependent signals upon RIG-I-like helicase stimulation in the absence of BAX, caspase-9 or caspase-3 or upon caspase-inhibition. During activation, MAVS forms complexes, and blockade of mitochondrial apoptosis signalling increased complex abundance in unstimulated and stimulated cells. MAVS complexes were more sensitive to caspase-degradation than the monomer, and mutation of caspase-3-cleavage sites in MAVS spontaneously increased complex formation. Inhibition of voltage-dependent anion channel 1 (VDAC1) oligomerization blocked BAX/BAK- and caspase-regulated IFN induction, suggesting a stimulating role of leakage of mitochondrial DNA. We propose that low level, spontaneous activity of the mitochondrial apoptosis pathway, through specific caspase-3-mediated cleavage of only active signaling proteins, counteracts mitochondrial release of nucleic acids to reduce inflammation in the absence of infection. Caspase-3 therefore has a novel function in conformation- and activation-specific cleavage of substrates.
In vivo anti-FAP CAR T therapy reduces fibrosis and restores liver homeostasis in metabolic dysfunction-associated steatohepatitis
Authors: Yashaswini Chittampalli N. , Cogliati Bruno , Qin Tianyue , To Tran , Williamson Thomas , Papp Tyler E. , Li Kenneth , Rasul Raisa , Chen Li , Lightstone Adi , Aghajanian Haig , Parhiz Hamideh , Wang Shuang , Rurik Joel G. , Epstein Jonathan A. , Friedman Scott L. 
Published: February 2025

AbstractIn this study, we aimed to determine the efficacy of in vivo chimeric antigen receptor (CAR) T cell therapy, generated by targeted lipid nanoparticles (t-LNPs), as an anti-fibrotic in metabolic dysfunction-associated steatotic liver disease. Hepatic fibrosis is a key predictor of mortality in liver disease, driven by fibrogenic hepatic stellate cells (HSCs). In heart, chimeric antigen receptor (CAR) T cells targeting fibroblast activation protein alpha (FAP) reduce murine cardiac fibrosis. However, the value of this approach in liver is unknown. We explored the anti-fibrotic potential of in vivo-generated anti-FAP CAR T cells in metabolic dysfunction-associated steatohepatitis (MASH), a highly prevalent disease with no approved anti-fibrotic therapies. We first established that FAP expression in both human and murine MASH is specific to HSCs. We then used flow cytometry, Sirius Red morphometry, digital pathology analysis, and single nuclear RNA-sequencing to assess the impact of anti-FAP CAR T cell therapy on murine MASH. Anti-CD5 targeted-LNPs carrying anti-FAPCAR mRNA generate activated, transient anti-FAP CAR T cells, which significantly reduced fibrosis by depleting pro-fibrogenic HSCs, and by modulating immune cells, endothelial cells and hepatocytes in a non-cell autonomous manner to mitigate inflammation and restore hepatic homeostasis. These findings reinforce the potential of in vivo CAR T therapy to attenuate a highly morbid and pervasive liver disease through integrated, multicellular salutary effects.One Sentence SummaryRNA-based treatment transiently reprograms immune cells to target scar-forming cells in fatty liver disease, thus improving liver health overall.
Metagenomics reveals potential interactions between CPR bacteria and their phages in groundwater ecosystems
Authors: Hu Bingxin , An Liyun , Wu Mengdi , Xu Jinbo , Nie Yong , Wu Xiao-Lei 
Published: February 2025

AbstractCandidate phyla radiation (CPR) is a vast lineage composed of bacteria with ultra-small size, streamlined genomes, notable defects in core metabolic potential and symbiotic lifestyle, which are widely detected in groundwater ecosystems. Increasing attention has focused on the physiological and ecological significance of CPR bacteria, while the potential interactions between CPR bacteria and their phages still need more exploration. Here, we collected 82 groundwater metagenomic datasets and further derived 1,162 phages with the potential to infect 2,439 groundwater CPR metagenome-assembled genomes (MAGs). Notably, the groundwater CPR MAGs were predominantly infected by temperate phages, and the abundance profiles of phage-CPR interactions in groundwater ecosystems supported the ‘Piggybacking the Winner’ (PtW) hypothesis, suggesting that lysogenic infection was a strategy co-evolved by CPR bacteria and their phages in groundwater ecosystems. Intriguingly, the groundwater CPR phages encoded various auxiliary metabolic genes (AMGs) that might promote symbiotic lifestyle and metabolic potential of host CPR MAGs. These included AMGs associated with concanavalin A-like lectin/glucanases superfamily and O-Antigen nucleotide sugar biosynthesis, which could enhance surface adhesion of host CPR MAGs. Moreover, AMGs related to ABC transport system and P-type transporter could strengthen metabolic exchange and uptake of essential nutrients from surroundings. Additionally, AMGs involved in various metabolic pathways might alleviate metabolic deficiencies in host CPR MAGs. This study elucidated the mechanisms of phage-CPR interactions and the potential roles of phages in modulating the physiology and ecology of CPR bacteria within groundwater ecosystems.
A monophyletic origin of domesticated barley
Authors: Tan Cong , Ye Lingzhen , Chen Jing , Zhang Chenyang , Zhou Ping , Tong Cen , Chen Zhonghua , Waugh Robbie , Li Chengdao , He Tianhua 
Published: February 2025

AbstractThe origin of domesticated barley has been debated extensively over the past century. Early botanical and comparative morphological research and recent genetic research supported a polyphyletic origin. A monophyletic origin was proposed after the discovery that a single genetic locus controls the presence of hull-less grains in all domesticated barley. Interpreting the origin of domesticated barley is further complicated by the archaeological record showing that the first domesticates had two rows of grain on the inflorescence, as does its wild progenitor. However, these two-rowed types effectively disappeared from the record for thousands of years, and they were replaced by derived six-rowed types that dominated barley’s cultivation history and only reappeared in the record around one thousand years ago. Here, we used two independent datasets with large sample sizes and genome-wide genetic markers to re-evaluate barley cultivation history. We unequivocally demonstrate that modern domesticated barley has a monophyletic origin. Phylogenetic reconstruction and examination of current archaeological records suggests that the west Fertile Crescent was most likely where barley was first domesticated. Modern two-rowed types were likely derived from six-rowed domesticated types not earlier than 3,500 years ago in modern Türkiye and Iran. We conclude that the two distinct non-brittle rachis haplotypes, coinciding with distinct row types in cultivated barley, are likely the results of two chronological events along the same evolutionary line. Our results provide a reconcilable framework for explaining genetic and phytogeographic patterns and pave the way for a consensus on the origin of barley domestication.
Diffeomorphic Independent Contrasts for Ancestral Reconstruction of Shapes
Authors: Severinsen Michael Lind , Akhøj Morten , Nielsen Rasmus , Sommer Stefan , Hipsley Christy Anna 
Published: February 2025

AbstractAncestral reconstruction is a fundamental challenge in evolutionary biology, requiring methods that can capture complex morphological changes while accounting for phylogenetic relationships. Current approaches are based on linear assumptions that often oversimplify the spatial relationships between anatomical features and fail to account for landmark correlations within shapes. Here, we introduce a novel method that combines the ability of Large Deformation Diffeomorphic Metric Mapping (LDDMM) to model smooth, invertible transformations between shapes while preserving the relationships between landmarks with Felsenstein’s Independent Contrasts (IC) to iteratively reconstruct ancestral shapes along the branches of a phylogenetic tree. We call this method Diffeomorphic Independent Contrasts for Ancestral Reconstruction of Shapes (DICAROS). We validate DICAROS against two existing methods: (1) Linear predictors using Ordinary Least Squares and (2) Ancestral character estimation using maximum likelihood under Brownian Motion and apply DICAROS to a dataset of swallowtail butterfly species (Family Papilonidae, Order Lepiodetra) to reconstruct the ancestral shape and visualize evolutionary trajectories in a phylomorphospace from the contrasts. We conclude that DICAROS outperforms the existing methods in terms of accuracy and provides a more accurate reconstruction of the ancestral shape for non-symmetric phylogenetic trees. With DICAROS we show a transition between un-tailed and tailed papilinodae species while also illustrating how images of modern species would look under the DICAROS ancestral reconstruction
Identification of 4-Amino-2-Nitrophenol as a novel inducer of phenotypic antibiotic resistance inEscherichia coli: roles of Lon protease and its substrate MarA
Authors: Nandini Santhi Sanil , Jagdish Sirisha , Rana Subinoy , Nandi Dipankar 
Published: February 2025

AbstractIn prokaryotes, the energy-dependent protein degradation is controlled primarily by two ATP-dependent proteases, Lon and Clp. This study investigates the roles of the Lon protease in the metabolism of 2,4-dinitrophenol (2,4-DNP), a toxic industrial compound, inEscherichia coli(E. coli). During the study, an observation was made that the absence of Lon protease resulted in an enhanced conversion of yellow coloured 2,4-DNP to a reddish-brown product. This study aims to characterise the compound observed in the media with wild type (WT) and Δlonstrains, understand the mechanisms of 2,4-DNP conversion and decipher the roles of Lon protease in the conversion of 2,4-DNP. UV-visible and LC-MS analyses revealed differences in the conversion products between the WT and Δlonstrains. One of the substrates of Lon protease is MarA, a transcription factor. Growth studies with different mutants and trans-complemented strains demonstrated MarA-dependent conversion. The bathochromic shift of spectral peaks suggested a reduction process and possible involvement of nitroreductase enzymes. Indeed, the expression of two nitroreductases,nfsAandnfsB, increased with 2,4-DNP and was dependent on MarA. Importantly, the production of the reddish-brown product was lower in strains lackingnfsAornfsB. Finally, LC-MS analysis identified one of the conversion products of 2,4-DNP to be 4-Amino-2-nitrophenol (4,2-ANP). Dose studies with purified 4,2-ANP demonstrated that it did not lower the growth ofE. coli(unlike 2,4-DNP) but induced phenotypic antibiotic resistance (like 2,4-DNP). This study contributes to our understanding of biological treatment of nitroaromatics and may offer insights into environmental pollution mitigation strategies.ImportanceThis study identifies the roles of Lon protease and its substrate MarA in inducing nitroreductases, NfsA and NfsB, in reducing toxic 2,4-DNP to less toxic 4,2-ANP, a novel inducer of phenotypic antibiotic resistance. This study contributes to understanding the biological treatment of nitroaromatics, offering insights into environmental pollution mitigation strategies and the development of efficient bioremediation techniques.
Activity of human-specific Interlaminar Astrocytes in a Chimeric Mouse Model of Fragile X Syndrome
Authors: Anding Alexandria , Ren Baiyan , Padmashri Ragunathan , Burkovetskaya Maria , Dunaevsky Anna 
Published: February 2025

AbstractAstrocytes, a type of glial cells, have multiple roles in regulating neuronal development and homeostasis. In addition to the typical mammalian astrocytes, in the primate cortex interlaminar astrocytes are located in the superficial layer and project long processes traversing multiple layers of the cerebral cortex. Previously, we described a human stem cell based chimeric mouse model where interlaminar astrocytes develop. Here, we utilized this model to study the calcium signaling properties of interlaminar astrocytes. To determine how interlaminar astrocytes could contribute to neurodevelopmental disorders, we generated a chimeric mouse model for Fragile X syndrome. We report that FXS interlaminar astrocytes exhibit hyperexcitable calcium signaling and cause an increase in dendritic spine dynamics.
Eukaryotes’ closest relatives are internally simple syntrophic archaea
Authors: Imachi Hiroyuki , Nobu Masaru K. , Ishii Shun’ichi , Hirakata Yuga , Ikuta Tetsuro , Isaji Yuta , Miyata Makoto , Miyazaki Masayuki , Morono Yuki , Murata Kazuyoshi , Nakagawa Satoshi , Ogawara Miyuki , Okada Satoshi , Saito Yumi , Sakai Sanae , Shimamura Shigeru , Tahara Yuhei O. , Takaki Yoshihiro , Takano Yoshinori , Tasumi Eiji , Uematsu Katsuyuki , Yoshimura Toshihiro , Takai Ken 
Published: February 2025

AbstractEukaryotes are theorized to have originated from an archaeal phylumPromethearchaeota(formerly ‘Asgard’ archaea)1,2. The first cultured representatives revealed valuable insight3,4but are distantly related to the first eukaryotic common ancestor (FECA), leaving many unknowns regarding this archaeon’s biology. Here, we report isolation of two strains belonging to the order proposed as FECA’s closest relative, ‘Hodarchaeales’,5as members of a pure co- and tri-culture with methanogenic partners. Both are obligately anaerobic, syntrophic, peptide-degrading, and mesophilic archaea that have simple internal cell structure and produce protrusions and vesicles, likePromethearchaeales3,4. All strains demonstrate behavior focused on cell construction rather than division, unlike typical prokaryotes6. Strain HC1 possesses genes associated with aerobic lifestyles but lacks complete pathways for aerobic respiration and co-cultures cannot grow under (micro)aerobic conditions, suggesting the genes support oxygen detoxification rather than respiration. Reflecting this, HC1 can survive and grow under microaerobic conditions only when aerobic organisms are present. Phylogenetic analyses indicate FECA may have possessed these genes and thus some aerotolerance. Physiological, genomic, and phylogenetic observations indicate FECA was a simple-celled anaerobic syntrophic peptide-degrading archaeon with a non-growth-centric lifestyle and potential adaptations towards an oxygenated planet—the archaea-eukaryote transition was steep in both cell structure and aerobiosis.
Electrodynamics of vortices in quasi-two-dimensional scalar Bose-Einstein condensates
Authors: Shinn Seong-Ho , del Campo Adolfo 
Published: February 2025

In two spatial dimensions, vortex-vortex interactions approximately vary with the logarithm of the inter-vortex distance, making it possible to describe an ensemble of vortices as a Coulomb gas. We introduce a duality between vortices in a quasi-two-dimensional (quasi-2D) scalar Bose-Einstein condensates (BEC) and effective Maxwell's electrodynamics. Specifically, we address the general scenario of inhomogeneous, time-dependent BEC number density with dissipation or rotation. Starting from the Gross-Pitaevskii equation (GPE), which describes the mean-field dynamics of a quasi-2D scalar BEC without dissipation, we show how to map vortices in a quasi-2D scalar BEC to 2D electrodynamics beyond the point-vortex approximation, even when dissipation is present or in a rotating system. The physical meaning of this duality is discussed.

Published by the American Physical Society
2025