bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipidomic Analysis of Microfat and Nanofat Reveals Different Lipid Mediator Compositions
Authors: Grünherz Lisanne , Kollarik Sedef , Sanchez-Macedo Nadia , McLuckie Michelle , Lindenblatt Nicole 
Published: February 2024

Background:
Microfat and nanofat are commonly used in various surgical procedures, from skin rejuvenation to scar correction, to contribute to tissue regeneration. Microfat contains mainly adipocytes and is well suited for tissue augmentation, and nanofat is rich in lipids, adipose-derived stem cells, microvascular fragments, and growth factors, making it attractive for aesthetic use. The authors have previously demonstrated that the mechanical processing of microfat into nanofat significantly changes its proteomic profile. Considering that mechanical fractionation leads to adipocyte disruption and lipid release, they aimed to analyze their lipidomic profiles for their regenerative properties.

Methods:
Microfat and nanofat samples were isolated from 14 healthy patients. Lipidomic profiling was performed by liquid chromatography tandem mass spectrometry. The resulting data were compared against the Human Metabolome and LIPID MAPS Structure Database. MetaboAnalyst was used to analyze metabolic pathways and lipids of interest.

Results:
From 2388 mass-to-charge ratio features, metabolic pathway enrichment analysis of microfat and nanofat samples revealed 109 pathways that were significantly enriched. Microfat samples revealed higher-intensity levels of sphingosines, different eicosanoids, and fat-soluble vitamins. Increased levels of coumaric acids and prostacyclin were found in nanofat.

Conclusions:
This is the first study to analyze the lipidomic profiles of microfat and nanofat, providing evidence that mechanical emulsification of microfat into nanofat leads to changes in their lipid profiles. From 109 biological pathways, antiinflammatory, antifibrotic, and antimelanogenic lipid mediators were particularly enriched in nanofat samples when compared with microfat. Although further studies are necessary for a deeper understanding of the composition of these specific lipid mediators in nanofat samples, the authors propose that they might contribute to its regenerative effects on tissue.

Clinical Relevance Statement:
Profiling the unique lipid mediators in nanofat and microfat enhances our understanding of their different therapeutic effects and allows us to link these specific mediators to antiinflammatory, pro-regenerative, or healing properties. Ultimately, this insight can advance personalized therapeutic strategies, where a specific type of fat is selected based on its optimal therapeutic effect.
Causality Assessment Between Idiopathic Inflammatory Myopathies and Lung Cancer
Authors: Li Hui , Xu Yingying , Guo Qin , Zhang Tiantian , Zhou Shufen , Wang Qianqian , Tian Ye , Cheng Yuanxiong , Guo Chengshan 
Published: February 2024

Background
Although observational studies have revealed associations between idiopathic inflammatory myopathies (IIMs) and lung cancer (LC), they have not established a causal relationship between these 2 conditions.

Methods
We used a 2-sample Mendelian randomization approach to examine the bidirectional causal associations between IIMs and LC, using single-nucleotide polymorphisms selected from high-quality genome-wide association studies in the FinnGen database. Sensitivity analyses were conducted to assess potential heterogeneity and pleiotropy impacts on the Mendelian randomization results.

Results
Our analysis demonstrated a positive causal effect of genetically increased IIM risk on LC (odds ratio, 1.114; 95% confidence interval, 1.057–1.173; p = 5.63 × 10−5), particularly on the lung squamous cell carcinoma subtype (odds ratio, 1.168, 95% confidence interval, 1.049–1.300, p = 0.00451), but not on lung adenocarcinoma or small cell lung cancer. No causal effect of LC on IIMs was identified. Sensitivity analyses indicated that horizontal pleiotropy was unlikely to influence causality, and leave-one-out analysis confirmed that the observed associations were not driven by a single-nucleotide polymorphism.

Conclusion
Our findings offer compelling evidence of a positive causal relationship between IIMs and LC, particularly with regard to lung squamous cell carcinoma, in the European population. Conversely, there is no evidence of LC causing IIMs. We recommend that LC diagnosis consider the specific characteristics of IIMs.
Growth and morphogenesis of an everted tubular biological tissue
Authors: Liu Congshan , Du Yangkun , Li Kecheng , Han Zilong , Lü Chaofeng 
Published: February 2024

Eversion, a ubiquitous phenomenon in living organisms, significantly contributes to the growth and morphogenesis of soft biological tissues and organs. In this study, we examine the role of elasticity and geometry in the morphogenesis of everted tubular biological tissues, both theoretically and experimentally. Our findings demonstrate that the morphogenesis of an everted tubular tissue is primarily influenced by its elasticity and geometry. Through linear stability analysis, we show that an everted bilayer tubular tissue, with isotropic differential growth, can generate a circumferential or two-dimensional pattern, but fails to produce an axial pattern, which distinguishes it from a bilayer tubular tissue without eversion. Furthermore, as the modulus ratio and layer thicknesses increase, the surface instability pattern transitions from a two-dimensional pattern to a circumferential pattern. Notably, when the modulus ratio or layer thickness reaches sufficiently high values, spontaneous instabilities emerge on the inner surface of the everted bilayer tubular tissues pre-growth. To investigate the morphological instability of everted bilayer tubes, we perform a series of quantificational finite-element simulations and swelling experiments. The results of both numerical simulations and experimental observations align well with our theoretical analysis. This study not only enhances our comprehension of everted tubular tissue morphogenesis but also offers valuable insights for biomedical engineering and growth self-assembly applications.
Microenvironment Shapes Small Cell Lung Cancer Neuroendocrine States and Presents Therapeutic Opportunities
Authors: Desai Parth , Takahashi Nobuyuki , Kumar Rajesh , Nichols Samantha , Malin Justin , Hunt Allison , Schultz Christopher , Cao Yingying , Tillo Desiree , Nousome Darryl , Chauhan Lakshya , Sciuto Linda , Jordan Kimberly , Rajapakse Vinodh , Tandon Mayank , Lissa Delphine , Zhang Yang , Kumar Suresh , Pongor Lorinc , Singh Abhay , Schroder Brett , Sharma Ajit Kumar , Chang Tiangen , Vilimas Rasa , Pinkiert Danielle , Graham Chante , Butcher Donna , Warner Andrew , Sebastian Robin , Mahon Mimi , Baker Karen , Cheng Jennifer , Berger Ann , Lake Ross , Abel Melissa , Krishnamurthy Manan , Chrisafis George , Fitzgerald Peter , Nirula Micheal , Goyal Shubhank , Atkinson Devon , Bateman Nicholas W. , Abulez Tamara , Nair Govind , Apolo Andrea , Guha Udayan , Karim Baktiar , Meskini Rajaa El , Ohler Zoe Weaver , Jolly Mohit Kumar , Schaffer Alejandro , Ruppin Eytan , Kleiner David , Miettinen Markku , Brown G Tom , Hewitt Stephen , Conrads Thomas , Thomas Anish 
Published: February 2024

SummarySmall-cell lung cancer (SCLC) is the most fatal form of lung cancer. Intra-tumoral heterogeneity, marked by neuroendocrine (NE) and non-neuroendocrine (non-NE) cell states, defines SCLC, but the drivers of SCLC plasticity are poorly understood. To map the landscape of SCLC tumor microenvironment (TME), we apply spatially resolved transcriptomics and quantitative mass spectrometry-based proteomics to metastatic SCLC tumors obtained via rapid autopsy. The phenotype and overall composition of non-malignant cells in the tumor microenvironment (TME) exhibits substantial variability, closely mirroring the tumor phenotype, suggesting TME-driven reprogramming of NE cell states. We identify cancer-associated fibroblasts (CAF) as a crucial element of SCLC TME heterogeneity, contributing to immune exclusion, and predicting exceptionally poor prognosis. Together, our work provides a comprehensive map of SCLC tumor and TME ecosystems, emphasizing their pivotal role in SCLCs adaptable nature, opening possibilities for re-programming the intercellular communications that shape SCLC tumor states.
The effect of constitutive root isoprene emission on root phenotype and physiology under control and salt stress conditions
Authors: Bellucci Manuel , Mostofa Mohammad Golam , Weraduwage Sarathi M. , Xu Yuan , Abdelrahman Mostafa , De Gara Laura , Loreto Francesco , Sharkey Thomas D. 
Published: February 2024

ABSTRACTIsoprene, a volatile hydrocarbon, is typically emitted from the leaves and other aboveground plant organs; isoprene emission from roots is not well studied. Given its well-known function in plant growth and defense aboveground, isoprene may also be involved in shaping root physiology to resist belowground stress. We used isoprene-emitting transgenic lines (IE) and a non-emitting empty vector and/or wild type lines (NE) ofArabidopsisto elucidate the roles of isoprene in root physiology and salt stress resistance. We assessed root phenotype and metabolic changes, hormone biosynthesis and signaling, and stress-responses under normal and saline conditions of IE and NE lines. We also analyzed the root transcriptome in the presence or absence of salt stress. IE lines emitted isoprene from roots, which was associated with higher primary root growth, root biomass, and root/shoot biomass ratio under both control and salt stress conditions. Transcriptome data indicated that isoprene altered the expression of key genes involved in hormone metabolism and plant responses to stress factors. Our findings reveal that root constitutive isoprene emission sustains root growth also under salinity by regulating and/or priming hormone biosynthesis and signaling mechanisms, amino acids biosynthesis, and expression of key genes relevant to salt stress defense.
A Tale of Two Chains: Geometries of a Chain Model and Protein Native State Structures
Authors: Škrbić Tatjana , Giacometti Achille , Hoang Trinh X. , Maritan Amos , Banavar Jayanth R. 
Published: February 2024

AbstractLinear chain molecules play a central role in polymer physics with innumerable industrial applications. They are also ubiquitous constituents of living cells. Here we highlight the similarities and differences between two distinct ways of viewing a linear chain. We do this, on the one hand, through the lens of simulations for a standard polymer chain of tethered spheres at low and high temperatures and, on the other hand, through published experimental data on an important class of biopolymers, proteins. We present detailed analyses of their local and non-local structures as well as the maps of their closest contacts. We seek to reconcile the startlingly different behaviors of the two types of chains based on symmetry considerations.
GX-I7(rhIL-7-hyFc, efineptakin alfa), a long-acting IL-7, safely and effectively increased peripheral CD8+and CD4+T cells and TILs in patients with solid tumors
Authors: Kim Gun Min , Kim Sojeong , Lee Myung Ah , Byun Mi-Sun , Choi Donghoon , Yang Se Hwan , Woo Jung Won , Sung Young Chul , Shin Eui-Cheol , Park Su-Hyung , Kim Tae Won , Sohn Joohyuk 
Published: February 2024

ABSTRACTPurposeGX-I7 (rhIL-7-hyFc, efineptakin alfa) is a hybrid Fc-fused long-acting recombinant human interleukin-7 (IL-7) developed by Genexine, Inc. with the aim of correcting T-cell deficiency, thereby strengthening the immune response to fight against cancer. This Phase 1b trial (NCT03478995) was designed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of GX-I7 in patients with locally advanced or metastatic solid tumors.MethodsThis study consisted of two phases: dose-escalation and expansion. Eight dose groups were administered GX-I7 intramuscularly at doses ranging from 60 to 1700 μg/kg every three or six weeks.ResultsAll regimens were safe and well tolerated, with the most frequently reported adverse drug reactions being injection site reactions, which were manageable with or without pharmacological intervention. GX-I7 demonstrated dose-dependent increases in the maximum serum concentration (Cmax) and area under the curve up to the last measurable concentration (AUClast). In addition, a dose-dependent increase in circulating CD8+/CD4+T cells was observed. In five patients who consented for biopsy, a statistically significant increase in tumor-infiltrating CD8+/CD4+T cell lymphocytes after GX-I7 treatment was observed.ConclusionThese findings support the use of GX-I7 as a safe and effective T cell-amplifying agent capable of correcting T cell deficiencies. GX-I7 is expected to result in better clinical outcomes when used in combination with other anti-cancer agents by creating a better environment for immune checkpoint inhibitors and anti-cancer treatments to fight cancer.
The lateral habenula is required for maternal behavior in the mouse dam
Authors: Benedict Jessie , Cudmore Robert H. , Oden Diarra , Spruell Aleah , Linden David J. 
Published: February 2024

AbstractMammalian parenting is an unusually demanding commitment. How did evolution co-opt the reward system to ensure parental care? Previous work has implicated the lateral habenula (LHb), an epithalamic nucleus, as a potential intersection of parenting behavior and reward. Here, we examine the role of the LHb in the maternal behavior of naturally parturient mouse dams. We show that kainic acid lesions of the LHb induced a severe maternal neglect phenotype in dams towards their biological pups. Next, we demonstrate that through chronic chemogenetic inactivation of the LHb using DREADDs impaired acquisition and performance of various maternal behaviors, such as pup retrieval and nesting. We present a random intercepts model suggesting LHb-inactivation prevents the acquisition of the novel pup retrieval maternal behavior and decreases nest building performance, an already-established behavior, in primiparous mouse dams. Lastly, we examine the spatial histology of kainic-acid treated dams with a random intercepts model, which suggests that the role of LHb in maternal behavior may be preferentially localized at the posterior aspect of this structure. Together, these findings serve to establish the LHb as required for maternal behavior in the mouse dam, thereby complementing previous findings implicating the LHb in parental behavior using pup-sensitized virgin female mice.Significance StatementWork conducted using rats in the 1990s suggested an important role for the LHb in maternal behavior, but this area of research has since lain dormant. In the interim, the LHb has been garnering attention as a hub for punishment signaling. Recently, interest in the LHb’s role in maternal behavior was renewed, with an important paper examining LHb function during pup-directed behaviors in pup-sensitized virgin female mice. But it is unknown how closely pup-directed behaviors in sensitized virgin females may mimic maternal behavior in natural mouse mothers. This work demonstrates the importance of the LHb in the regulation of natural maternal behavior in the mouse.
Biological management, rather than chemical management, promotes the interaction between plants and their microbiome
Authors: Zhao Tianci , Jia Xiu , Liu Xipeng , Nepal Jyotsna , Attard Eléonore , Guyoneaud Rémy , Treder Krzysztof , Pawłowska Anna , Michałowska Dorota , Berg Gabriele , Stocker Franz , Cernava Tomislav , Elzenga J. Theo M. , Salles Joana Falcão 
Published: February 2024

AbstractIn the face of climate change, developing sustainable agricultural practices to reduce the use of synthetic herbicides and pesticides is crucial. However, breeding for higher yields can lead to the decoupling of plant roots and beneficial rhizosphere microbes. In this study, we aim to identify potato cultivars with functional traits facilitating efficient interactions with the rhizosphere microbiome under various agricultural treatments in the field. With the results of profiling microbial communities with amplicon sequencing data of bacteria (16S rRNA gene fragments) and fungi (ITS2 region), a piecewise structural equation model was developed. This model explains the trade-off effects of agricultural management and potato cultivars on plant growth by affecting the rhizosphere microbiome. Furthermore, we highlight that plant cultivar and the rhizosphere microbiome together determine plant below-ground growth under biological management. In contrast, both components are found to be uncoupled under chemical and control management. Our study reveals the importance of considering microbiomes in the breeding process to achieve the goals of sustainable agriculture.
Infer metabolic velocities from moment differences of molecular weight distributions
Authors: Tuobang Li 
Published: February 2024

ABSTRACTMetabolic pathways are fundamental maps in biochemistry that detail how molecules are transformed through various reactions. The complexity of metabolic network, where a single compound can play a part in multiple pathways, poses a challenge in inferring metabolic balance changes over time or after different treatments. Isotopic labeling experiment is the standard method to infer metabolic flux, which is currently defined as the flow of a single metabolite through a given pathway over time. However, there is still no way to accurately infer the metabolic balance changes after different treatments in an experiment. This study introduces a different concept: molecular weight distribution, which is the empirical distribution of the molecular weights of all metabolites of interest. By estimating the differences of the location and scale estimates of these distributions, it becomes possible to quantitatively infer the metabolic balance changes even without requiring knowledge of the exact chemical structures of these compounds and their related pathways. This research article provides a mathematical framing for a classic biological concept.
Intrinsic diving reflex induces potent antioxidative response by activation of NRF2 signaling
Authors: Powell Keren , Wadolowski Steven , Tambo Willians , Strohl Joshua J. , Kim Daniel , Turpin Justin , Al-Abed Yousef , Brines Michael , Huerta Patricio T. , Li Chunyan 
Published: February 2024

AbstractAimsThis study aims to elucidate the underlying mechanisms of diving reflex, a powerful endogenous mechanism supporting underwater mammalian survival. Antioxidative responses, observed in marine mammals, may be contributing factors. Using a multi-organ approach, this study assesses whether acute and chronic diving reflex activate nuclear factor-erythroid-2-related factor 2 (NRF2) signaling pathways, which regulate cellular antioxidant responses.MethodsMale Sprague-Dawley rats (n=38) underwent either a single diving session to elicit acute diving reflex, or daily diving sessions for 4-weeks to produce chronic diving reflex. NRF2 (total, nuclear, phosphorylated), NRF2-downstream genes, and malondialdehyde were assessed via Western blot, immunofluorescence, RT-PCR, and ELISA in brain, lung, kidney, and serum.ResultsDiving reflex increased nuclear NRF2, phosphorylated NRF2, and antioxidative gene expression, in an organ-specific and exposure time-specific manner. Comparing organs, the brain had the highest increase of phosphorylated NRF2 expression, while kidney had the highest degree of nuclear NRF2 expression. Comparing acute and chronic sessions, phosphorylated NRF2 increased the most with chronic diving reflex, but acute diving reflex had the highest antioxidative gene expression. Notably, calcitonin gene-related peptide appears to mediate diving reflex’ effects on NRF2 activation.ConclusionsAcute and chronic diving reflex activate potent NRF2 signaling in the brain and peripheral organs. Interestingly, acute diving reflex induces higher expression of downstream antioxidative genes compared to chronic diving reflex. This result contradicts previous assumptions requiring chronic exposure to diving for induction of antioxidative effects and implies that the diving reflex has a strong translational potential during preconditioning and postconditioning therapies.Key PointsDiving reflex activates potent NRF2 signaling via multiple mechanisms, including phosphorylation, nuclear translocation, and KEAP1 downregulation with both acute and chronic exposure.Diving reflex activates NRF2 via differential pathways in the brain and other organs; phosphorylated NRF2 increases more in the brain, while nuclear NRF2 increases more in the peripheral organs.Acute diving reflex exposure induces a more pronounced antioxidative effect than chronic diving reflex exposure, indicating that the antioxidative response activated by diving reflex is not dependent upon chronic adaptive responses and supports diving reflex as both a preconditioning and postconditioning treatment.
iSCORE-PD: an isogenic stem cell collection to research Parkinson’s Disease
Authors: Busquets Oriol , Li Hanqin , Syed Khaja Mohieddin , Jerez Pilar Alvarez , Dunnack Jesse , Bu Riana Lo , Verma Yogendra , Pangilinan Gabriella R. , Martin Annika , Straub Jannes , Du YuXin , Simon Vivien M. , Poser Steven , Bush Zipporiah , Diaz Jessica , Sahagun Atehsa , Gao Jianpu , Hernandez Dena G. , Levine Kristin S. , Booth Ezgi O. , Bateup Helen S. , Rio Donald C. , Hockemeyer Dirk , Blauwendraat Cornelis , Soldner Frank 
Published: February 2024

AbstractParkinson’s disease (PD) is a neurodegenerative disorder caused by complex genetic and environmental factors. Genome-edited human pluripotent stem cells (hPSCs) offer the uniique potential to advance our understanding of PD etiology by providing disease-relevant cell-types carrying patient mutations along with isogenic control cells. To facilitate this experimental approach, we generated a collection of 55 cell lines genetically engineered to harbor mutations in genes associated with monogenic PD (SNCAA53T,SNCAA30P,PRKNEx3del,PINK1Q129X,DJ1/PARK7Ex1-5del,LRRK2G2019S,ATP13A2FS,FBXO7R498X/FS,DNAJC6c.801 A>G+FS,SYNJ1R258Q/FS,VPS13CA444P,VPS13CW395C,GBA1IVS2+1). All mutations were generated in a fully characterized and sequenced female human embryonic stem cell (hESC) line (WIBR3; NIH approval number NIHhESC-10-0079) using CRISPR/Cas9 or prime editing-based approaches. We implemented rigorous quality controls, including high density genotyping to detect structural variants and confirm the genomic integrity of each cell line. This systematic approach ensures the high quality of our stem cell collection, highlights differences between conventional CRISPR/Cas9 and prime editing and provides a roadmap for how to generate gene-edited hPSCs collections at scale in an academic setting. We expect that our isogenic stem cell collection will become an accessible platform for the study of PD, which can be used by investigators to understand the molecular pathophysiology of PD in a human cellular setting.
Urinary Metabolomic Profile is Minimally Impacted by Common Storage Conditions and Additives
Authors: Weldon Kelly C. , Panitchpakdi Morgan , Caraballo-Rodríguez Andrés Mauricio , Wolfe Alan J. , Dorrestein Pieter C. , Brubaker Linda , Burnett Lindsey A. 
Published: February 2024

AbstractMetabolomics reflects the molecular communications within a biological system. Urine can be obtained non-invasively and is rich in metabolites that are potential biomarkers for human health and disease. The optimal urine storage conditions for metabolomic analysis are unknown. We measured the impact of common storage conditions and the presence of a DNA-stabilizer, AssayAssure® (Thermo Scientific), on metabolite content of voided human urine. Urinary metabolite composition was not altered across storage conditions. Although addition of AssayAssure® significantly alters metabolic profile by adduct addition, this does not preclude the identification of parent metabolites or overshadow biological differences. These data suggest biobanked urine stored in any of the tested conditions for metabolomic studies may be considered for metabolomic analysis.