bluuebunny/crossref_metadata_2025_split huggingface dataset:
Melt-Rock Reaction in the Lower Oceanic Crust and the Influence on the Evolution of Mid-Ocean Ridge Basalts at the Central Indian Ridge (7°50′–8°30′S)
Authors: Choi Sarang , Park Jung-Woo , Kim Jonguk , Oh Jihye , Park Changkun , Han Seunghee 
Published: June 2024

Abstract
Various crustal processes shape both the lower oceanic crust and mid-ocean ridge basalts (MORBs). To better understand how these crustal processes influence MORB compositions, we conducted comprehensive petrographic and geochemical investigations on gabbroic rocks and erupted lavas dredged from a segment of the Central Indian Ridge (CIR) spanning from 7°50′S to 8°30′S. The petrographic and geochemical analyses of the gabbroic rocks revealed evidence of melt-rock reaction through reactive porous flow in olivine gabbro and gabbro. This process resulted in distinctive features in clinopyroxene, including disequilibrium textures with a troctolite/anorthosite matrix, complex variations in Mg#-Cr-Ti [Mg# = molar Mg/(Mg + Fe2+)] relationships, and considerable enrichment and fractionation of incompatible trace elements. A significant finding of our study is the close resemblance of trace element ratios in MORB and olivine-hosted melt inclusions to those of melts in equilibrium with clinopyroxene from olivine gabbro and gabbro with Sr anomaly (Sr/Sr* = SrN/sqrt[PrN*NdN]; N refers to chondrite-normalized values) greater than ~0.7. This observation strongly indicates that the composition of MORB is influenced by the melt-rock reaction taking place in the lower oceanic crust. Furthermore, our findings suggest that evolved melts in equilibrium with clinopyroxene having Sr/Sr* values lower than ~0.7 are less likely to erupt onto the seafloor and are instead trapped within the lower oceanic crust. Oxide gabbronorite is characterized by coarse-granular, pegmatitic textures and exhibits mineralogically and chemically more evolved characteristics compared to olivine gabbro and gabbro. It is inferred that the oxide gabbronorite formed through the in situ freezing of highly evolved melts within a melt-rich layer. Finally, we present a comprehensive model for melt evolution in the lower oceanic crust at the 7°50′S–8°30′S CIR by integrating all petrological and geochemical data obtained from gabbroic rocks, MORB, and olivine-hosted melt inclusions. This holistic model contributes to a better understanding of the intricate processes governing MORB composition in the context of the lower oceanic crust dynamics at slow-spreading ridges.
Which advanced treatment should be used following the failure of a first-line anti-TNF in patients with rheumatoid arthritis? 15 years of evidence from the Quebec registry RHUMADATA
Authors: Choquette Denis , Haraoui Boulos , Movahedi Mohammad , Bessette Louis , Sauvageau Loïc Choquette , Ferdinand Isabelle , Joly-Chevrier Maxine , Masetto Ariel , Massicotte Frédéric , Nadon Valérie , Pelletier Jean-Pierre , Raynauld Jean-Pierre , Sauvageau Diane , Villeneuve Édith , Coupal Louis 
Published: June 2024

Abstract

Background
Since 2000, advanced therapies (AT) have revolutionized the treatment of moderate to severe RA. Randomized control trials as well as observational studies together with medication availability often determine second-line choices after the failure of first TNF inhibitors (TNFi). This led to the observation that specific sequences provide better long-term effectiveness. We investigated which alternative medication offers the best long-term sustainability following the first TNFi failure in RA.

Methods
Data were extracted from RHUMADATA from January2007. Patients were followed until treatment discontinuation, loss to follow-up or 25 November 2022. Kaplan–Meier and Cox regression models were used to compare discontinuation between groups. Missing data were imputed, and propensity scores were computed to reduce potential attribution bias. Complete, unadjusted and propensity score-adjusted imputed data analyses were produced.

Results
Six hundred eleven patients [320 treated with a TNFi and 291 treated with molecules having another mechanism of action (OMA)] were included. The mean age at diagnosis was 44.5 and 43.9 years, respectively. The median retention was 2.84 and 4.48 years for TNFi and OMAs groups. Using multivariable analysis, the discontinuation rate of the OMA group was significantly lower than TNFi (adjHR: 0.65; 95% CI: 0.44–0.94). This remained true for the PS-adjusted MI Cox models. In a stratified analysis, rituximab (adjHR: 0.39; 95% CI: 0.18–0.84) had better retention than TNFi after adjusting for patient characteristics.

Conclusion
Switching to an OMA, especially rituximab, in patients with failure to a first TNFi appears to be the best strategy as a second line of therapy.
Vascular endothelial growth factor secretion and immunosuppression are distinct potency mechanisms of human bone marrow mesenchymal stromal cells
Authors: Faircloth Tyler U , Temple Sara , Parr Rhett N , Tucker Anna B , Rajan Devi , Hematti Peiman , Kugathasan Subra , Chinnadurai Raghavan 
Published: June 2024

Abstract
Mesenchymal stromal cells (MSCs) are investigated as cellular therapeutics for inflammatory bowel diseases and associated perianal fistula, although consistent efficacy remains a concern. Determining host factors that modulate MSCs’ potency including their secretion of angiogenic and wound-healing factors, immunosuppression, and anti-inflammatory properties are important determinants of their functionality. We investigated the mechanisms that regulate the secretion of angiogenic and wound-healing factors and immune suppression of human bone marrow MSCs. Secretory analysis of MSCs focusing on 18 angiogenic and wound-healing secretory molecules identified the most abundancy of vascular endothelial growth factor A (VEGF-A). MSC viability and secretion of other angiogenic factors are not dependent on VEGF-A secretion which exclude the autocrine role of VEGF-A on MSC’s fitness. However, the combination of inflammatory cytokines IFNγ and TNFα reduces MSC’s VEGF-A secretion. To identify the effect of intestinal microvasculature on MSCs’ potency, coculture analysis was performed between human large intestine microvascular endothelial cells (HLMVECs) and human bone marrow-derived MSCs. HLMVECs do not attenuate MSCs’ viability despite blocking their VEGF-A secretion. In addition, HLMVECs neither attenuate MSC’s IFNγ mediated upregulation of immunosuppressive enzyme indoleamine 2,3-dioxygenase nor abrogate suppression of T-cell proliferation despite the attenuation of VEGF-A secretion. We found that HLMVECs express copious amounts of endothelial nitric oxide synthase and mechanistic analysis showed that pharmacological blocking reverses HLMVEC-mediated attenuation of MSC’s VEGF-A secretion. Together these results suggest that secretion of VEGF-A and immunosuppression are separable functions of MSCs which are regulated by distinct mechanisms in the host.
Analysis of the Genetic Variation and Geographic Distribution Patterns of Xanthomonas citri pv. citri Strains in Citrus Production in Burkina Faso
Authors: Zerbo Kevin Ben Fabrice , Yameogo Florence , Wonni Issa , Somda Irénée 
Published: June 2024

It is essential to have a thorough knowledge of the genetic variation among different strains of Xanthomonas citri pv. citri, which is responsible for causing citrus bacterial canker. This understanding is important for studying disease characteristics, population structure, and evolution and ultimately for developing sustainable methods of control. A total of 48 strains obtained from citrus production areas in Burkina Faso in 2012, 2020, and 2021 were subjected to Polymerase Chain reaction (PCR) tests using specific primers. The aim was to examine the distribution of type 3 effectors and determine the geographical origins of the strains. The examination of the distribution of type 3 non-transcription-activator-like effectors (TALEs) revealed a broader range of strains obtained in 2020 and 2021 than in 2012. However, all the strains possessed a shared set of three genes, specifically, XopE2, XopN, and AvrBs2. Furthermore, all examined effectors were observed in the Bobo-Dioulasso region. Regarding the characterization of TALEs, two profiles containing two to three TALEs were discovered. Profile 1, consisting of two TALEs, was found in 37 X. citri pv. citri strains, whereas Profile 2, comprising three TALEs, was detected in 11 strains. Among the three TALEs (A, B, and C) that were identified, TALEs B and C were present in all the strains. The correlation matrix indicated a positive association between the type 3 effector content of strains and the duration of their isolation. Principal component analysis revealed a limited organization of the strains under investigation. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Increased Gremlin1 Expression in Pancreatic Ductal Adenocarcinoma Promotes a Fibrogenic Stromal Microenvironment
Authors: Tindall Rachel R. , Faraoni Erika Y. , Li Jiajing , Zhang Yinjie , Ting Shun-Ming , Okeugo Beanna , Zhao Xiurong , Liu Yuying , Younes Mamoun , Shen Qiang , Bailey-Lundberg Jennifer M. , Cao Yanna , Ko Tien C. 
Published: June 2024

Objective
Pancreatic ductal adenocarcinoma (PDAC) microenvironment is primarily composed of cancer-associated fibroblasts and immune cells. Gremlin1 (Grem1) is a profibrogenic factor that promotes tumorigenesis in several cancers. However, the role of Grem1 in the PDAC microenvironment is not defined.

Materials and Methods
We correlated Grem1 levels with activated stroma and immune cells in human PDAC using The Cancer Genome Atlas RNA-sequencing data and characterized expression of Grem1 transcripts and isoforms in pancreatic cell lines and PDAC tissues. We assessed the role of Grem1 in the microenvironment by in vitro studies.

Results
Grem1 expression is associated with an activated stroma and increased M1 and M2 macrophages. Only full length Grem1 variant 1 and isoform 1 were detectable in human pancreatic cells, and remarkably high levels of Grem1 were observed in pancreatic fibroblasts. Immunohistochemistry detected Grem1 protein in PDAC tumor and stromal cells, which correlated with infiltrating macrophages in PDAC tumors. Grem1 knockdown in cancer-associated fibroblasts suppressed transforming growth factor β–induced extracellular matrix proteins. Grem1 recombinant protein treatment in vitro increased M1 and M2 macrophages.

Conclusions
Grem1 acts as a profibrogenic factor in the PDAC microenvironment via modulation of fibroblasts and macrophages. Grem1 may have the potential to be developed as a therapeutic target for PDAC.
The Mediating Effect of Coping Style in the Relationship Between Sleep Quality and Perceived Cognitive Impairment Among Breast Cancer Patients
Authors: Chen Fan , Li Changzai , Zhu Jingwen , Zhao Yaning , Zhang Pan , Gao Jianru , Yang Yuqi , Guo Lin 
Published: June 2024

Background
Perceived cognitive impairment is a significant symptom experienced by breast cancer patients and may be affected by sleep quality. Coping styles have potential relevancies with both sleep quality and perceived cognitive impairment. However, the empirical evidence supporting their association among breast cancer patients is limited.

Objective
This study explored the associations between sleep quality, coping styles, and perceived cognitive impairment and tested the mediating role of coping styles in breast cancer patients.

Methods
A total of 294 breast cancer patients were included in this cross-sectional study. Patients were assessed using the Pittsburgh Sleep Index Scale, the Simplified Coping Styles Questionnaire, and the Functional Assessment of Cancer Therapy-Cognitive Functioning (Version 3) Scale. The data were analyzed using SPSS and Process macros.

Results
The direct effect of sleep quality on reported cognitive impairment was significant (β = −0.245, P < .001). Furthermore, sleep quality was found to have a significant indirect effect on perceived cognitive impairment through positive coping style (β = −0.026, P < .05) and negative coping style (β = −0.131, P < .05).

Conclusions
Our research suggests that sleep quality has both a direct effect on perceived cognitive impairment and an indirect effect through positive and negative coping styles in breast cancer patients. Moreover, negative coping style had a more pronounced mediating effect than positive coping style.

Implications for Practice
Clinical medical staff could reduce the perceived cognitive impairment of breast cancer patients by improving their sleep quality and encouraging them to adopt a more positive coping style.
Retracing the horizontal transfer of a novel innate immune factor inDrosophila
Authors: Tarnopol Rebecca L. , Tamsil Josephine , Cinege Gyöngyi , Ha Ji Heon , Verster Kirsten I. , Ábrahám Edit , Magyar Lilla B. , Kim Bernard Y. , Bernstein Susan L. , Lipinszki Zoltán , Andó István , Whiteman Noah K. 
Published: June 2024

SummaryImmune systems are among the most dynamically evolving traits across the tree of life, and long-lived macroparasites play an outsized role in shaping animal immunity. Even without adaptive immunity, insects have evolved potent innate immune strategies to neutralize such enemies, including nematodes and parasitoid wasps. One such strategy relies on endosymbioses between insects and toxin-expressing bacteria. Here, we use genome editing inDrosophila melanogasterto retrace the evolution of two of such toxins —cytolethal distending toxin B(cdtB) andapoptosis inducing protein of 56kDa(aip56) — that were horizontally transferred from bacteriophages to insects. We found that acdtB::aip56fusion gene (fusionB), which is conserved inDrosophila ananassaesubgroup species, dramatically promoted fly survival and suppressed wasp development when expressed inD. melanogasterimmune tissues. FusionB, a functional nuclease, was secreted into the host hemolymph where it targeted the parasitoid embryo’s serosal tissue and is to our knowledge the first humoral anti-parasitoid toxin inDrosophila. When expressed ubiquitously,fusionBslowed development in late stage fly larvae and eventually killed flies, pointing to the salience of regulatory constraint in preventing autoimmunity. Our findings demonstrate how horizontal gene transfer, in the right regulatory context, can instantly provide new and potent innate immune modules in animals.
Reconstructing Langevin systems from high and low-resolution time series using Euler and Hermite reconstructions
Authors: Arani Babak M. S. , Carpenter Stephen R. , van Nes Egbert H. 
Published: June 2024

AbstractThe ecological literature often features phenomenological dynamic models lacking robust validation against observational data. Reverse engineering is an alternative approach, where time series data are utilized to infer or fit a stochastic differential equation. This process, known as system reconstruction, presents significant challenges. This paper addresses the estimation of the (often) non-linear deterministic and stochastic parts of Langevin models, one of the simplest yet commonly used stochastic differential equations. We introduce a Maximum Likelihood Estimation (MLE) inference method, termed Euler reconstruction, tailored for time series data with medium to high resolution. However, the Euler approach is not reliable for low-resolution data. To fill the gap for sparsely sampled data, we present an MLE inference method pioneered by Aït-Sahalia, that we term Hermite reconstruction. We employ a powerful modeling framework utilizing splines to detect inherent nonlinearities in the unknown data-generating system to achieve high accuracy with minimal computational burden. Applying Euler and Hermite reconstructions to a range of simulated, ecological, and climate datasets, we demonstrate their efficacy and versatility. We provide a user-friendly tutorial and a MATLAB package called the ‘MATLAB reconstruction package’.
Direct β1/ β2 AMPK activation reduces liver steatosis but not fibrosis in a mouse model of non-alcoholic steatohepatitis
Authors: Mather Karly M. , Boland Michelle L. , Rivers Emma L. , Srivastava Abhishek , Schimpl Marianne , Hemsley Paul , Robinson James , Wan Paul T. , Hansen Josefine , Read Jon A. , Trevaskis James L. , Smith David M. 
Published: June 2024

Abstract5’AMP-activated protein kinase (AMPK) activators show potential for treating Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) due to their inhibiting effects on fatty acid and cholesterol synthesis. The absence of treatments for NASH, and its propensity for progression to severe disease, lead us to identify and characterize BI9774, a small molecule AMPK activator, which we used to evaluate this potential, including its ability to reduce the NASH specific qualities of fibrosis and inflammation in a preclinical study.MaleLepob/Lepobmice on a control or NASH inducing (AMLN) diet, with liver fibrosis were given BI9774 or vehicle for 6 weeks while metabolic and NASH endpoints were evaluated.BI9774 treatment decreased plasma ALT, terminal liver weight, and liver lipids. RNA expression of collagen-related genes decreased, although collagen protein and inflammation remained unaltered. We also observed increased heart weight and glycogen levels, and increased expression of genes associated with cardiac hypertrophy.AMPK activation improved many metabolic endpoints, but lack of significant improvement in liver fibrosis and negative cardiac effects suggest systemic AMPK activation is not an ideal NASH therapy. Reductions in steatosis and fibrosis-related genes indicate that, with extended treatment, a liver specific AMPK activator has potential to resolve hepatic fibrosis.Summary StatementFatty liver disease affects up to 30 percent of adults worldwide with 30% of patients progressing to more sever liver disease. AMPK activation can help reduce liver fat.
A bioinformatic approach for the prediction and functional classification ofToxoplasma gondiilong non-coding RNAs
Authors: Vanagas Laura , Cristaldi Constanza , Bella Gino La , Ganuza Agustina , Angel Sergio O. , Alonso Andrés M. 
Published: June 2024

ABSTRACTLong non-coding RNAs (lncRNAs) have emerged as significant players in diverse cellular processes, including cell differentiation. Advancements in computational methodologies have facilitated the prediction of lncRNA functions, enabling insights even in non-model organisms like pathogenic parasites, in roles such as parasite development, antigenic variation, and epigenetics. In this work, we focus on the apicomplexanToxoplasma gondiidifferentiation process, where the infective stage, tachyzoite, can develop into the cysted stage, bradyzoite, under stress conditions. Using a publicly available transcriptome dataset, we predicted lncRNA sequences associated with this differentiation process. Notably, a substantial proportion of these predicted lncRNAs exhibited stage-specific expression, particularly at the bradyzoite stage. Furthermore, co-expression patterns between coding transcripts and lncRNAs suggest their involvement in shared processes, such as bradyzoite development. TglncRNA loci analysis revealed their potential influence on the expression of nearby coding genes, including subtelomeric genes unique to theT. gondiigenome. Finally, with a k-mer analysis approach, we identified functional relationships between characterized lncRNAs from model organisms likeHomo sapiensand predictedT. gondiilncRNAs. Our perspective led to the identification of aT. gondiilncRNA potentially mediating DNA damage repair pathways, shedding light on the adaptive mechanisms ofT. gondiiin response to stress conditions.
Genomic introgression between critically endangered and stable species of Darwin’s tree finches on the Galapagos Islands
Authors: Dudaniec Rachael Y. , Yadav Sonu , Catchen Julian , Kleindorfer Sonia 
Published: June 2024

AbstractNatural hybridisation among rare or endangered species and stable congenerics is increasingly topical for the conservation of species-level diversity under anthropogenic impacts. Evidence for beneficial genes being introgressed into or selected for in hybrids raises concurrent questions about its evolutionary significance. In Darwin’s tree finches on the island of Floreana (Galapagos Islands, Ecuador), the Critically Endangered medium tree finch (Camarhynchus pauper) undergoes introgression with the stable small tree finch (Camarhynchus parvulus), and hybrids regularly backcross withC. parvulus.Earlier studies in 2005-2013 documented an increase in the frequency ofCamarhynchushybridisation on Floreana using field-based and microsatellite data. With single nucleotide polymorphism (SNP) data from the same Floreana tree finches sampled in 2005 and 2013 (n = 95), we examine genome-wide divergence across parental and hybrid birds and evidence for selection in hybrids. In assessing previous estimates of introgression we found that just 18% of previously assigned hybrid birds based on microsatellites were assigned to hybrids using SNPs. Over half of the previously assigned hybrids (63%) were reassigned toC. parvulus,though parental species showed concordance with prior assignments. Of 4869 private alleles found in hybrid birds, 348 were at a high frequency (≥0.30) that exceeded their parental species of origin 89-96% of the time. Across the two years, 3436 (70.6%) private alleles underwent a substantial (≥0.30) allele frequency increase or decrease. Of these, 28 private alleles were identified as candidate loci under selection via local PCA genome scans and outlier tests.Alleles were annotated to genes associated with inflammation, immunity, brain function and development. We provide evidence that introgression among a critically endangered and stable species of Darwins’ tree finch is being retained by selection across years and may aid in the retention of genetic diversity in birds threatened with extinction.
Extracellular Respiration is a Latent Energy Metabolism inEscherichia coli
Authors: Kundu Biki Bapi , Krishnan Jayanth , Szubin Richard , Patel Arjun , Palsson Bernhard O. , Zielinski Daniel C. , Ajo-Franklin Caroline M. 
Published: June 2024

ABSTRACTDiverse microbial species utilize redox shuttles to exchange electrons with their environment through mediated extracellular electron transfer (EET). This process maintains redox homeostasis and supports anaerobic survival across diverse microbial communities. Although mediated EET has been extensively leveraged for bioelectrocatalysis and bioelectronics for decades, fundamental questions remain about how these redox shuttles are reduced within cells and their bioenergetic implications. This knowledge gap limits our understanding of the physiological roles of mediated EET in various microbes and hampers the development of efficient microbial electrochemical technologies. To address this, we developed a methodology integrating genome editing, electrochemistry, and systems biology to investigate the mechanism and bioenergetic implications of mediated EET in bacteria. Using this approach, we uncovered a mediated EET mechanism inEscherichia coli. In the absence of alternative electron sinks, the redox cycling of 2-hydroxy-1,4-naphthoquinone (HNQ) via a cytoplasmic nitroreductase enabledE. colito respire and grow on an extracellular electrode. Genome-scale metabolic modeling suggested that HNQ- mediated EET offers a more energetically favorable route for supporting anaerobic growth than canonical fermentation. Transcriptome analysis revealed redox perturbations in response to HNQ and identified rapid metabolic adaptations that support growth. This work demonstrates thatE. colican grow independently of classical electron transport chains and fermentative pathways, unveiling a new type of anaerobic energy metabolism.