bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk of Staphylococcus aureus Bacteremia Before and After Solid Organ Transplantation
Authors: Inagaki Kengo , Weinberg Jason B. , Kaul Daniel R. 
Published: March 2023

Background.Solid organ transplant recipients are at high risk forStaphylococcus aureusbacteremia, but the risks before and after transplantation require further research.Methods.We performed a population-based retrospective self-controlled study using the State Inpatient Database from 10 states in the United States. Adult and pediatric patients who had solid organ transplantation from 2004 to 2018 were tracked longitudinally for 1 y before and after transplantation outside of the immediate peritransplant periods. The exposure of interest was solid organ transplantation, and the outcome of interest was hospitalization withS. aureusbacteremia.Results.Of 75 549 patients, 581 (0.77%) and 239 (0.32%) were hospitalized withS. aureusbacteremia in the pretransplant and posttransplant periods, respectively (P< 0.001). Overall, the odds of hospitalization withS. aureusbacteremia increased from 7 to 12 mo to 1 to 6 mo before transplantation (odds ratio, 1.24; 95% confidence interval, 1.05-1.46) and then decreased following transplantation (odds ratio, 0.35; 95% confidence interval, 0.28-0.45; 7–12 mo after transplantation). The decreased rate after transplantation was driven by the cases associated with central line-associated bloodstream infections and endocarditis among kidney and heart transplant recipients. Odds of hospitalization withS. aureusbacteremia did not change after liver transplantation, whereas they increased after lung transplantation.Conclusions.In addition to immunosuppression, the reversal of organ failure and associated requirements for organ support following transplantation may play an important role in the risk ofS. aureusbacteremia in solid organ transplant recipients. These results can guide infection prevention approaches and future research onS. aureusinfections in transplant patients.
Differences in Implicit Attitudes in West and East Germans as Measured by the Go/NoGo Association Task and Event-related EEG Potentials
Authors: Wagner-Altendorf Tobias A. , van der Lugt Arie H. , Kroeber Anna , Cirkel Anna , Heldmann Marcus , Münte Thomas F. 
Published: March 2023

Background and Objective:

Implicit social cognition refers to attitudes and stereotypes that may reside outside conscious awareness and control but that still affect human behavior. In particular, the implicit favoritism of an ingroup, to which an individual belongs, as opposed to an outgroup, to which the individual does not belong, characterized as ingroup bias, is of interest and is investigated here.

Method:
We used a Go/NoGo association task (GNAT) and behavioral and electroencephalographic (event-related EEG potential [ERP] analysis) measures to investigate the implicit bias toward cities in East Germany, West Germany, and Europe, in 16 individuals each from West and East Germany (mixed gender, Mage = 24). The GNAT assesses an individual’s Go and NoGo responses for a given association between a target category and either pole (positive or negative) of an evaluative dimension.

Results:
Behavioral measures revealed slightly faster reaction times to the combination of European city names and negative, as compared with positive, evaluative words in both groups. ERP analysis showed an increased negativity at 400–800 ms poststimulus in the incongruent conditions of East German city/positive word pairings (in West Germans) and West German city/positive word pairings (in East Germans).

Conclusion:
An implicitly moderately negative evaluation of Europe by both groups was exhibited based on the behavioral data, and an increased level of conflict arising from the “incongruent” pairings (ie, as manifestation of an implicitly negative attitude toward East Germany in West Germans, and toward West Germany in East Germans) was exhibited based on the electrophysiological data.
Hypoxia-induced activation of NDR2 underlies brain metastases from Non-Small Cell Lung Cancer
Authors: Levallet Jérôme , Biojout Tiphaine , Bazille Céline , Douyère Manon , Dubois Fatéméh , Leite Ferreira Dimitri , Taylor Jasmine , Teulier Sylvain , Toutain Jérôme , Bernaudin Myriam , Valable Samuel , Bergot Emmanuel , Levallet Guénaëlle 
Published: March 2023

AbstractThe molecular mechanisms induced by hypoxia are misunderstood in non-small cell lung cancer (NSCLC), and above all the hypoxia and RASSF1A/Hippo signaling relationship.We confirmed that human NSCLC (n=45) as their brain metastases (BM) counterpart are hypoxic since positive with CAIX-antibody (target gene of Hypoxia-inducible factor (HIF)). A severe and prolonged hypoxia (0.2% O2, 48h) activated YAP (but not TAZ) in Human Bronchial Epithelial Cells (HBEC) lines by downregulating RASSF1A/kinases Hippo (except for NDR2) regardless their promoter methylation status. Subsequently, the NDR2-overactived HBEC cells exacerbated a HIF-1A, YAP and C-Jun-dependent-amoeboid migration, and mainly, support BM formation. Indeed, NDR2 is more expressed in human tumour of metastatic NSCLC than in human localized NSCLC while NDR2 silencing in HBEC lines (by shRNA) prevented the xenograft formation and growth in a lung cancer-derived BM model in mice.Collectively, our results indicated that NDR2 kinase is over-active in NSCLC by hypoxia and supports BM formation. NDR2 expression is thus a useful biomarker to predict the metastases risk in patients with NSCLC, easily measurable routinely by immunohistochemistry on tumour specimens.
Tumour mitochondrial DNA mutations drive aerobic glycolysis to enhance checkpoint blockade
Authors: Mahmood Mahnoor , Liu Eric Minwei , Shergold Amy L. , Tolla Elisabetta , Tait-Mulder Jacqueline , Uribe Alejandro Huerta , Shokry Engy , Young Alex L. , Lilla Sergio , Kim Minsoo , Park Tricia , Manchon J.L. , Rodríguez-Antona Crístina , Walters Rowan C. , Springett Roger J. , Blaza James N. , Zanivan Sara , Sumpton David , Roberts Edward W. , Reznik Ed , Gammage Payam A. 
Published: March 2023

SummaryThe mitochondrial genome encodes essential machinery for respiration and metabolic homeostasis but is paradoxically among the most common targets of somatic mutation in the cancer genome, with truncating mutations in respiratory complex I genes being most over-represented1. While mitochondrial DNA (mtDNA) mutations have been associated with both improved and worsened prognoses in several tumour lineages1–,3, whether these mutations are drivers or exert any functional effect on tumour biology remains controversial. Here we discovered that complex I-encoding mtDNA mutations are sufficient to remodel the tumour immune landscape and therapeutic resistance to immune checkpoint blockade. Using mtDNA base editing technology4we engineered recurrent truncating mutations in the mtDNA-encoded complex I gene,Mt-Nd5, into murine models of melanoma. Mechanistically, these mutations promoted utilisation of pyruvate as a terminal electron acceptor and increased glycolytic flux without major effects on oxygen consumption, driven by an over-reduced NAD pool and NADH shuttling between GAPDH and MDH1, mediating a Warburg-like metabolic shift. In turn, without modifying tumour growth, this altered cancer cell-intrinsic metabolism reshaped the tumour microenvironment in both mice and humans, promoting an anti- tumour immune response characterised by loss of resident neutrophils. This subsequently sensitised tumours bearing high mtDNA mutant heteroplasmy to immune checkpoint blockade, with phenocopy of key metabolic changes being sufficient to mediate this effect. Strikingly, patient lesions bearing >50% mtDNA mutation heteroplasmy also demonstrated a >2.5-fold improved response rate to checkpoint inhibitor blockade. Taken together these data nominate mtDNA mutations as functional regulators of cancer metabolism and tumour biology, with potential for therapeutic exploitation and treatment stratification.
Artificial contractile actomyosin gels recreate the curved and wrinkling shapes of cells and tissues
Authors: Livne Gefen , Gat Shachar , Armon Shahaf , Bernheim-Groswasser Anne 
Published: March 2023

AbstractLiving systems adopt a diversity of curved and highly dynamic shapes. These diverse morphologies appear on many length-scales, from cells to tissues and organismal scales. The common driving force for these dynamic shape changes are contractile stresses generated by myosin motors in the cell cytoskeleton, an intrinsically active filamentous material, while converting chemical energy into mechanical work. A good understanding of how contractile stresses in the cytoskeleton arise into different 3D shapes and what are the selection rules that determine their final configurations still lacks. Aiming to identify the selection rules governing the shapes formed by contractile forces in living systems, we recreate the actomyosin cytoskeleton in-vitro, with precisely controlled composition and initial geometry. A set of actomyosin gel discs, intrinsically identical but of variable initial geometry, spontaneously self-organize into a family of 3D shapes. This process occurs through robust distinct dynamical pathways, without specific pre-programming and additional regulation. Shape selection is encoded in the initial disc radius to thickness aspect ratio, and thus scale-free. This may indicate a universal process of shape selection, that works across scales, from cells to tissues and organelles. Finally, our results suggest that, while the dynamical pathways may depend on the detailed interactions of the different microscopic components within the gel, the final selected shapes obey the general theory of elastic deformations of thin sheets. Altogether, these results provide novel insights on the mechanically induced spontaneous shape transitions in active contractile matter and uncover new mechanisms that drive shape selections in living systems across scales.Significance statementLiving systems adopt a diversity of curved and highly dynamic shapes. These diverse morphologies appear on many length-scales, from cells to organismal scales, and are commonly driven by contractile stresses generated by myosin motors in the cell cytoskeleton. By recreating the actomyosin cytoskeleton in-vitro, with precisely controlled composition and initial geometry, we identify the shape selection rules that determine the final adopted configuration. Specifically, we find that shape selection is scale-free, which may indicate a universal process of shape selection, that works across scales, from cells to tissues and organelles. Altogether, our results provide novel insights on the mechanically induced spontaneous shape transitions in contractile active matter and uncover new mechanisms that drive shape selections in living systems.
A glutamatergic DRN-VTA pathway for neuropathic pain and comorbid depression-like behavior modulation
Authors: Wang Xin-Yue , Jia Wen-Bin , Xu Xiang , Chen Rui , Wang Liang-Biao , Su Xiao-Jing , Xu Peng-Fei , Liu Xiao-Qing , Wen Jie , Liu Yuan-Yuan , Zhang Zhi , Liu Xin-Feng , Zhang Yan 
Published: March 2023

AbstractChronic pain causes both physical suffering and comorbid mental disorders such as depression. However, the neural circuits and molecular mechanisms underlying these maladaptive behaviors remain elusive. Here, we report a pathway from vesicular glutamate transporter3 neurons in the dorsal raphe nucleus to dopamine neurons in the ventral tegmental area (VGluT3DRN→DAVTA), of which population activity in response to innocuous mechanical stimuli and sucrose consumption, is respectively inhibited and attenuated by chronic neuropathic pain. Mechanistically, neuropathic pain dampens VGluT3DRN→DAVTAglutamatergic transmission and DAVTAneural excitability. VGluT3DRN→DAVTAactivation alleviates neuropathic pain and comorbid depression-like behavior (CDB) by releasing glutamate, which subsequently promotes DA release in the nucleus accumbens medial shell (NAcMed) and produces analgesia and antidepressant effects via D2 and D1 receptors, respectively. In addition, VGluT3DRN→DAVTAinhibition produces pain-like hypersensitivity and depression-like behavior in healthy mice. These findings reveal a novel VGluT3DRN→DAVTA→D2/D1NAcMedpathway in establishing and modulating chronic pain and comorbid depressive-like behavior.
Hepatobiliary manganese homeostasis is dynamic in the setting of illness in mice
Authors: Sunuwar Laxmi , Tomar Vartika , Wildeman Asia , Culotta Valeria , Melia Joanna 
Published: March 2023

AbstractManganese is a diet−derived micronutrient that is essential for critical cellular processes like redox homeostasis, protein glycosylation, and lipid and carbohydrate metabolism. Control of Mn availability, especially at the local site of infection, is a key component of the innate immune response. Less has been elucidated about Mn homeostasis at the systemic level. In this work, we demonstrate that systemic Mn homeostasis is dynamic in response to illness in mice. This phenomenon is evidenced in male and female mice, mice of two genetic backgrounds (C57/BL6 and BALB/c), in multiple models of acute (dextran−sodium sulfate−induced) and chronic (enterotoxigenic Bacteriodes fragilis) colitis, and systemic infection withCandida albicans. When mice were fed a standard corn−based chow with excess Mn (100 ppm), liver Mn decreased and biliary Mn increased 3−fold in response to infection or colitis. Liver iron, copper, and zinc were unchanged. When dietary Mn was restricted to minimally adequate amounts (10ppm), baseline hepatic Mn levels decreased by approximately 60% in the liver, and upon induction of colitis, liver Mn did not decrease further, however biliary Mn still increased 20−fold. In response to acute colitis, hepaticSlc39a8mRNA (gene encoding the Mn importer, Zip8) andSlc30a10mRNA (gene encoding the Mn exporter, Znt10) are decreased. Zip8 protein is decreased. Illness− associated dynamic Mn homeostasis may represent a novel host immune/inflammatory response that reorganizes systemic Mn availability through differential expression of key Mn transporters with down−regulation of Zip8.Graphical AbstractCreated withBioRender.com
MAP kinase ERK5 modulates cancer cell sensitivity to extrinsic apoptosis induced by death-receptor agonists and Natural Killer cells
Authors: Espinosa-Gil Sergio , Ivanova Saska , Alari-Pahissa Elisenda , Denizli Melek , Villafranca-Magdalena Beatriz , Viñas-Casas Maria , Bolinaga-Ayala Idoia , Gámez-García Andrés , Colas Eva , Lopez-Botet Miguel , Zorzano Antonio , Lizcano José Miguel 
Published: March 2023

AbstractDeath receptor ligand TRAIL is a promising cancer therapy due to its ability to selectively trigger extrinsic apoptosis in cancer cells. However, TRAIL–based therapies in humans have shown limitations, mainly due inherent or acquired resistance of tumor cells. To address this issue, current efforts are focussed on dissecting the intracellular signaling pathways involved in resistance to TRAIL, to identify strategies that sensitize cancer cells to TRAIL-induced cytotoxicity. In this work, we describe the oncogenic MEK5-ERK5 pathway as a critical regulator of cancer cell resistance to the apoptosis induced by death receptor ligands. Using 2D and 3D cell cultures and transcriptomic analyses, we show that ERK5 controls the proteostasis of TP53INP2, a protein necessary for full activation of caspase-8 activation in response to TNFα, FasL or TRAIL. Mechanistically, ERK5 phosphorylates and induces ubiquitylation and proteasomal degradation of TP53INP2, resulting in cancer cell resistance to TRAIL. Concordantly, ERK5 inhibition or genetic deletion, by stabilizing TP53INP2, sensitizes cancer cells to the apoptosis induced by recombinant TRAIL and TRAIL/FasL expressed by Natural Killer cells. The MEK5-ERK5 pathway regulates cancer cell proliferation and survival, and ERK5 inhibitors have shown anticancer activity in preclinical models of solid tumors. Using endometrial cancer patient-derived xenograft organoids, we propose ERK5 inhibition as an effective strategy to sensitize cancer cells to TRAIL-based therapies and Natural Killer cells.
Metabolic perturbations to anE. coli-based cell-free system reveal a trade-off between transcription and translation
Authors: Kapasiawala Manisha , Murray Richard M. 
Published: March 2023

AbstractCell-free transcription-translation (TX-TL) systems have been used for diverse applications, but their performance and scope are limited by variability and poor predictability. To understand the drivers of this variability, we explored the effects of metabolic perturbations to anE. coliRosetta2 TX-TL system. We targeted three classes of molecules: energy molecules, in the form of nucleotide triphosphates (NTPs); central carbon “fuel” molecules, which regenerate NTPs; and magnesium ions (Mg2+). Using malachite green mRNA aptamer (MG aptamer) and destabilized enhanced Green Fluorescent Protein (deGFP) as transcriptional and translational readouts, respectively, we report the presence of a trade-off between optimizing total protein yield and optimizing total mRNA yield, as measured by integrating the area under the curve for mRNA time-course dynamics. We found that a system’s position along the trade-off curve is strongly determined by Mg2+concentration, fuel type and concentration, and cell lysate batch, and that variability can be reduced by modulating these components. Our results further suggest the trade-off arises from limitations in translation regulation and inefficient energy regeneration. This work advances our understanding of the effects of fuel and energy metabolism on TX-TL in cell-free systems and lays a foundation for improving TX-TL performance, lifetime, standardization, and prediction.For Table of Contents Use Only
User testing to inform modification of the MyHealthyGut digital health application in inflammatory bowel disease
Authors: Erlich Madeline , Lindblad Sarah , Haskey Natasha , Clarkin Darlene Higbee , Dong Taojie , Harvie Ruth , Lunken Genelle , Pirnack Jess , Jacobson Kevan 
Published: March 2023

AbstractIntroductionInflammatory bowel disease (IBD), characterized by chronic intestinal inflammation, can be subcategorized into Crohn’s disease and ulcerative colitis. The treatment for these conditions is unique to each patient, and may include lifestyle changes, pharmaceutical intervention, and surgery. Lifestyle changes, such as dietary intervention, are a cornerstone of IBD symptom management. Given the daily burden of this disease, self-management is paramount in coping with and/or minimizing symptoms. The MyHealthyGut application (app), successfully proven to be a self-management tool for celiac disease, shows promise for use in an IBD patient population.ObjectiveTo undertake user testing to inform the development of an IBD-focused version of the current MyHealthyGut app.MethodsThis study was undertaken between October 2021 and April 2022. Participants included IBD patients and healthcare practitioners (HCPs) (physicians, registered dietitians [RD], and registered nurses [RN]), using social media postings and convenience sampling. Two RDs demonstrated how to use the current functions and features of the app with each participant. Participants used the app for a 2-week period which was followed by participation in a focus group or individual interview to provide feedback on the app. Qualitative questionnaires, tailored to each patient category, were administered verbally and feedback was recorded. Thematic analysis techniques were used for data quantification and analysis.Results15 participants were recruited and enrolled. Of these, 14 participants took part in the focus group and/or individual interviews. The feedback suggested changes related to clinical uses (e.g. incorporating information collected by the app into electronic medical record systems), food and symptom tracking (e.g. the option to track water intake), ease of use (e.g. the option to autofill food tracker with frequently consumed meals), and app content (e.g. information about IBD treatments). All (100%) of participants reported that they would either use the app themselves or recommend the app to patients, once their suggestions were implemented.ConclusionThrough user testing and feedback collection, priorities for app modification were identified. Areas of modification in the app functions and features, ease of use, and content were identified. Once updated to meet the needs of IBD patients, the MyHealthyGut app may be a useful tool for IBD self-management.Funding SourceCanadian Foundation of Dietetic Research
Amino acid auxotrophies in human gut bacteria are linked to higher microbiome diversity and long-term stability
Authors: Starke Svenja , Harris Danielle MM , Zimmermann Johannes , Schuchardt Sven , Oumari Mhmd , Frank Derk , Bang Corinna , Rosenstiel Philip , Schreiber Stefan , Frey Norbert , Franke Andre , Aden Konrad , Waschina Silvio 
Published: March 2023

AbstractAmino acid auxotrophies are prevalent among bacteria. They can govern ecological dynamics in microbial communities and indicate metabolic cross-feeding interactions among coexisting genotypes. Despite the ecological importance of auxotrophies, their distribution and impact on the diversity and function of the human gut microbiome remain poorly understood. This study performed the first systematic analysis of the distribution of amino acid auxotrophies in the human gut microbiome using a combined metabolomic, metagenomic, and metabolic modeling approach. Results showed that amino acid auxotrophies are ubiquitous in the colon microbiome, with tryptophan auxotrophy being the most common. Auxotrophy frequencies were higher for those amino acids that are also essential to the human host. Moreover, a higher overall abundance of auxotrophies was associated with greater microbiome diversity and stability, and the distribution of auxotrophs was found to be related to the human host’s metabolome, including trimethylamine oxide, small aromatic acids, and secondary bile acids. Thus, our results suggest that amino acid auxotrophies are important factors contributing to microbiome ecology and host-microbiome metabolic interactions.
Killing the enemy or making it your ally? The effects of thiostrepton on tumor associated macrophages
Authors: Pereira-Martins Diego A. , Hilberink Jacobien R. , Weinhäuser Isabel , Rego Eduardo M. , Huls Gerwin , Schuringa Jan Jacob 
Published: March 2023

AbstractAttempts to convert a tumor supportive M2-polarized macrophage microenvironment into a tumor suppressive M1-polarized one have recently received considerable attention. However, the specificity of novel compounds, their mode-of-action, and efficacy on presumed target cellsin vivoneeds to be interpreted with caution.
An extended Painlevé integrable Kadomtsev--Petviashvili equation with lumps and multiple soliton solutions
Authors: Wazwaz Abdul-Majid , Alyousef Haifa A. , El-Tantawy Samir 
Published: March 2023

Purpose
This study aims to propose an extended (3 + 1)-dimensional integrable Kadomtsev–Petviashvili equation characterized by adding three new linear terms.

Design/methodology/approach
This study formally uses Painlevé test to confirm the integrability of the new system.

Findings
The Painlevé analysis shows that the compatibility condition for integrability does not die away by adding three new linear terms with distinct coefficients.

Research limitations/implications
This study uses the Hirota's bilinear method to explore multiple soliton solutions where phase shifts and phase variable are explored.

Practical implications
This study also furnishes a class of lump solutions (LSs), which are rationally localized in all directions in space, using distinct values of the parameters via using the positive quadratic function method.

Social implications
This study also shows the power of the simplified Hirota’s method in handling integrable equations.

Originality/value
This paper introduces an original work with newly developed Painlevé integrable model and shows new useful findings.