bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeted dosing for susceptible heteroresistant subpopulations may improve rational dosage regimen prediction for colistin in broiler chickens
Authors: Mead Andrew , Toutain Pierre-Louis , Richez Pascal , Pelligand Ludovic 
Published: August 2023

AbstractThe dosage of colistin for the treatment of enteric E. coli in animals necessitates considering the heteroresistant (HR) nature of the targeted inoculum, described by the presence of a major susceptible population (S1, representing 99.95% of total population) mixed with an initial minor subpopulation of less susceptible bacteria (S2). Herein, we report the 1-compartment population pharmacokinetics (PK) of colistin in chicken intestine (jejunum and ileum) and combined it with a previously established pharmacodynamic (PD) model of HR in E. coli. We then computed probabilities of target attainment (PTA) with a pharmacodynamic target (AUC24h/MIC) that achieves 50% of the maximal kill of bacterial populations (considering inoculums of pure S1, S2 or HR mixture of S1 + S2). For an MIC of 1 mg/L, PTA > 95% was achieved with the registered dose (75,000 IU/kg BW/day in drinking water) for the HR mixture of S1 + S2 E. coli, whether they harboured mcr or not. For an MIC of 2 mg/L (ECOFF), we predicted PTA > 90% against the dominant susceptible sub-population (S1) with this clinical dose given (i) over 24 h for mcr-negative isolates or (ii) over 6 h for mcr-positive isolates (pulse dosing). Colistin clinical breakpoint S ≤ 2 mg/L (EUCAST rules) should be confirmed clinically.
IL-1β is involved in docetaxel chemoresistance by regulating the formation of polyploid giant cancer cells in non-small cell lung cancer
Authors: Zhao Song , Xing Sining , Wang Lili , Ouyang Mingyue , Liu Shuo , Sun Lingyan , Yu Huiying 
Published: August 2023

AbstractDocetaxel (Doc) is a cornerstone of chemotherapy; however, treatment with Doc often and inevitably leads to drug resistance and the formation of polyploid giant cancer cells (PGCCs). In this study, we investigated the effect of Doc on non-small cell lung cancer to explore the role of PGCCs in drug resistance and the molecular mechanisms that regulate this resistance. We found that Doc induced G2/M cell cycle arrest and cell death in A549 and NCI-H1299 cells. However, many cells remained alive and became PGCCs by decreasing the expression of key regulatory proteins related to the cell cycle and proliferation. Notably, the PGCCs showed typical features of senescence, especially upregulation of p21 and p-histone H2A.X expression. Moreover, the mRNA level of IL-1β in the senescence-associated secretory phenotype was increased significantly with the development of PGCCs. Inhibition of IL-1β reduced the expression of p-histone H2A.X and promoted polyploidy to enhance the proapoptotic effect of Doc. Taken together, our results suggested that IL-1β was involved in the formation of PGCCs and regulated the senescence of PGCCs, which contributed to drug resistance to Doc. Therefore, targeting IL-1β in PGCCs may be a novel approach to overcome drug resistance.
Association between increased anterior cingulate glutamate and psychotic-like experiences, but not autistic traits in healthy volunteers
Authors: Demler Verena F. , Sterner Elisabeth F. , Wilson Martin , Zimmer Claus , Knolle Franziska 
Published: August 2023

AbstractDespite many differences, autism spectrum disorder and schizophrenia spectrum disorder share environmental risk factors, genetic predispositions as well as neuronal abnormalities, and show similar cognitive deficits in working memory, perspective taking, or response inhibition. These shared abnormalities are already present in subclinical traits of these disorders. The literature proposes that changes in the inhibitory GABAergic and the excitatory glutamatergic system could explain underlying neuronal commonalities and differences. Using magnetic resonance spectroscopy (1H-MRS), we investigated the associations between glutamate concentrations in the anterior cingulate cortex (ACC), the left/right putamen, and left/right dorsolateral prefrontal cortex and psychotic-like experiences (Schizotypal Personality Questionnaire) and autistic traits (Autism Spectrum Quotient) in 53 healthy individuals (26 women). To investigate the contributions of glutamate concentrations in different cortical regions to symptom expression and their interactions, we used linear regression analyses. We found that only glutamate concentration in the ACC predicted psychotic-like experiences, but not autistic traits. Supporting this finding, a binomial logistic regression predicting median-split high and low risk groups for psychotic-like experiences revealed ACC glutamate levels as a significant predictor for group membership. Taken together, this study provides evidence that glutamate levels in the ACC are specifically linked to the expression of psychotic-like experiences, and may be a potential candidate in identifying early risk individuals prone to developing psychotic-like experiences.
Particulate matter impairs immune system function by up-regulating inflammatory pathways and decreasing pathogen response gene expression
Authors: Marín-Palma Damariz , Fernandez Geysson Javier , Ruiz-Saenz Julian , Taborda Natalia A. , Rugeles Maria T. , Hernandez Juan C. 
Published: August 2023

AbstractAirborne particulate matter produced by industrial sources and automobiles has been linked to increased susceptibility to infectious diseases and it is known to be recognized by cells of the immune system. The molecular mechanisms and changes in gene expression profiles induced in immune cells by PM have not been fully mapped out or systematically integrated. Here, we use RNA-seq to analyze mRNA profiles of human peripheral blood mononuclear cells after exposure to coarse particulate matter (PM10). Our analyses showed that PM10 was able to reprogram the expression of 1,196 genes in immune cells, including activation of a proinflammatory state with an increase in cytokines and chemokines. Activation of the IL-36 signaling pathway and upregulation of chemokines involved in neutrophil and monocyte recruitment suggest mechanisms for inflammation upon PM exposure, while NK cell-recruiting chemokines are repressed. PM exposure also increases transcription factors associated with inflammatory pathways (e.g., JUN, RELB, NFKB2, etc.) and reduces expression of RNases and pathogen response genes CAMP, DEFAs, AZU1, APOBEC3A and LYZ. Our analysis across gene regulatory and signaling pathways suggests that PM plays a role in the dysregulation of immune cell functions, relevant for antiviral responses and general host defense against pathogens.
Linking aberrant glycosylation of plasma glycoproteins with progression of myelodysplastic syndromes: a study based on plasmonic biosensor and lectin array
Authors: Chrastinová Leona , Pastva Ondřej , Bocková Markéta , Kovářová Hana , Ceznerová Eliška , Kotlín Roman , Pecherková Pavla , Štikarová Jana , Hlaváčková Alžběta , Havlíček Marek , Válka Jan , Homola Jiří , Suttnar Jiří 
Published: August 2023

AbstractAberrant glycosylation of glycoproteins has been linked with various pathologies. Therefore, understanding the relationship between aberrant glycosylation patterns and the onset and progression of the disease is an important research goal that may provide insights into cancer diagnosis and new therapy development. In this study, we use a surface plasmon resonance imaging biosensor and a lectin array to investigate aberrant glycosylation patterns associated with oncohematological disease—myelodysplastic syndromes (MDS). In particular, we detected the interaction between the lectins and glycoproteins present in the blood plasma of patients (three MDS subgroups with different risks of progression to acute myeloid leukemia (AML) and AML patients) and healthy controls. The interaction with lectins from Aleuria aurantia (AAL) and Erythrina cristagalli was more pronounced for plasma samples of the MDS and AML patients, and there was a significant difference between the sensor response to the interaction of AAL with blood plasma from low and medium-risk MDS patients and healthy controls. Our data also suggest that progression from MDS to AML is accompanied by sialylation of glycoproteins and increased levels of truncated O-glycans and that the number of lectins that allow discriminating different stages of disease increases as the disease progresses.
Long-term surgical results of trabeculectomy for secondary glaucoma in Val30Met hereditary transthyretin amyloidosis
Authors: Kitahara Junya , Kakihara Shinji , Mukawa Shuji , Hirano Takao , Imai Akira , Miyahara Teruyoshi , Murata Toshinori 
Published: August 2023

AbstractThis study reports the long-term results of trabeculectomy (LEC) for secondary glaucoma in hereditary transthyretin (ATTRv) amyloidosis patients and its correlation with prior vitrectomy. A retrospective case series was conducted involving 31 consecutive eyes of 20 ATTRv amyloidosis patients who underwent LEC between 2007 and 2020. The mean follow-up period was 73.2 ± 37.0 months (range: 20–181 months). Postoperative intraocular pressures (IOPs) were evaluated based on the following criteria: (a) IOP between 6 and 21 mmHg without additional glaucoma surgeries, except for laser suture lysis, (b) IOP between 6 and 15 mmHg without additional glaucoma surgeries, except for laser suture lysis, and (c) IOP between 6 and 21 mmHg without additional glaucoma surgeries, except for needling and laser suture lysis. Kaplan–Meier analysis revealed survival rates after LEC of 0.52 at 36 months, 0.42 at 60 months, and 0.25 at 84 months under criterion (a); 0.49 at 36 months, 0.27 at 60 months, and 0.11 at 84 months under criterion (b); and 0.76 at 36 months, 0.71 at 60 months, and 0.65 at 84 months under criterion (c). Eyes with a history of small gauge transconjunctival vitrectomy (SGTV) exhibited a tendency towards lower survival rates, although no statistically significant difference was observed (log-rank test; p = 0.193 under criterion (a) and p = 0.0553 under criterion (b)). Our findings suggest that LEC and additional needling procedures can provide some control over IOP; however, the overall postoperative outcomes of LEC for ATTRv amyloidosis remain unsatisfactory, even in the era of SGTV with reduced conjunctival scarring.
Associations between obstructive sleep apnea and dental pain and chewing discomfort in Korean adults: a nationwide cross-sectional study
Authors: Lee Jae-Hyun , Han Kyungdo , Lee Su Young 
Published: August 2023

AbstractObstructive sleep apnea (OSA) may be linked with oral health issues. This study evaluated the associations between OSA, dental pain, and chewing discomfort. Big data from a nationwide survey involving 6984 participants aged ≥ 40 years were analyzed. The STOP-Bang questionnaire was used to assess the OSA risk, categorizing the participants into low-, intermediate-, and high-risk groups. The associations of OSA risk with dental pain and chewing discomfort were evaluated using multivariate logistic regression analyses (α = 0.05). Results revealed that 50.33%, 37.50%, and 12.17% of the population belonged to the low-, intermediate-, and high-risk groups, respectively. After adjusting for covariates, a significant association emerged between OSA risk and dental pain, with adjusted odds ratios (95% confidence intervals) of 1 (reference), 1.208 (1.003–1.455), and 1.472 (1.131–1.916) for the low-, intermediate-, and high-risk groups, respectively (p = 0.0156). The adjusted odds ratio for chewing discomfort in the high-risk OSA group was 1.307 (0.977–1.748), although not significantly different from that of the low-risk group (p > 0.05). A high risk of OSA was associated with 1.472-fold increased risk of dental pain compared to those at low risk, implicating OSA as a potential risk indicator of poor oral health.
Effects of metformin and donepezil on the prevention of doxorubicin-induced cardiotoxicity in breast cancer: a randomized controlled trial
Authors: Osataphan Nichanan , Phrommintikul Arintaya , Leemasawat Krit , Somwangprasert Areewan , Apaijai Nattayaporn , Suksai Supanai , Sirikul Wachiranun , Gunaparn Siriluck , Chattipakorn Siriporn C. , Chattipakorn Nipon 
Published: August 2023

AbstractDoxorubicin (DOX) causes deleterious cardiotoxicity. We aimed to investigate the protective roles of metformin and donepezil against DOX-induced cardiotoxicity. In this randomized-controlled trial, 143 female breast cancer patients were enrolled. Metformin (n = 43), donepezil (n = 52), or placebo (n = 48) were prescribed during DOX treatment. The primary endpoint was a proportion of patients with high sensitivity troponin-I (hsTnI) more than the 99th percentile value (> 15.6 ng/L) after DOX treatment. The secondary outcomes were the changes in the hsTnI, N-terminal pro-B-type natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), global longitudinal strain (GLS) and peripheral blood mononuclear cells analysis for mitochondrial respiration. Baseline characteristics were similar between the groups. The primary endpoint occurred in 58.54% of metformin group, 76.92% in donepezil group, and 69.77% in placebo group (p = 0.215). The level of hsTnI increased after receiving DOX with subsequent decline in LVEF and GLS. Metformin and donepezil did not attenuate hsTnI elevation, LVEF or GLS reduction. There was no significant change in NT-proBNP level. Mitochondrial respiratory dysfunction was observed in the placebo and donepezil groups. However, metformin preserved mitochondrial respiration during DOX therapy. In conclusion, co-treatment with metformin or donepezil did not prevent myocardial injury. Metformin had a favorable mitochondrial outcome and warranted future studies.
Exploration of key ferroptosis-related genes and immune infiltration in Crohn’s disease using bioinformatics
Authors: Tang Xiaoting , Hu Weitao , You Wei , Fang Taiyong 
Published: August 2023

AbstractCrohn's disease (CD) is a type of inflammatory bowel disease (IBD) that manifests mainly as chronic inflammation in different parts of the gastrointestinal tract, and its incidence has come to be increasing in recent years. Ferroptosis, a novel type of programmed cell death, it seems the role of ferroptosis-related biomarkers in CD has not been mentioned. Thus, the role of ferroptosis in CD and its relationship with immune infiltration were explored in this study. The CD dataset was downloaded from the Gene Expression Omnibus database. The validated ferroptosis genes (FRGs) were retrieved from the public FerrDb database. The gene expression matrix of the CD dataset was analyzed with the “limma” package in R language to obtain differentially expressed genes (DEGs) between diseased and healthy samples. Then, intersecting genes between DEGs and FRGs were identified as differentially expressed ferroptosis-associated genes (DE-FRGs). Protein–protein interaction (PPI) network analysis and visualization were carried out with STRING and Cytoscape, and key CD ferroptosis-related genes (CD-FRGs) were identified along with their Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways using the clusterProfiler package. Immune cell infiltration was analyzed with CIBERSORT. The correlation between key CD-FRGs and immune-infiltrated cells in CD was studied by Spearman's correlation method. A total of 37 DE-FRGs and 6 key CD-FRGs (CAV1, CD44, HIF1A, IFNG, TIMP1 and TLR4) were identified. GO and KEGG functional analysis indicated these genes enrichment in programmed cell death and apoptotic process, HIF-1 signaling pathway and IBD. Infiltration matrix analysis of immune cells showed abundant T cells CD4 memory activated, M1 macrophages, M2 macrophages, Mast cells activated and Neutrophils in CD intestinal tissues. The 6 key CD-FRGs were correlated with immune-infiltrated cells in CD based on correlation analysis. Taken together, immune cells with abnormal infiltration can be implicated in CD due to ferroptosis. This study identified 6 key CD-FRGs that may be key biomarkers of ferroptosis in CD; they include CAV1, CD44, HIF1A, IFNG, TIMP1 and TLR4. These findings suggest that the immune response is critical in CD caused by ferroptosis through the interaction between key CD-FRGs and immune infiltrating cells.
Cognitive behavioral therapy for lifestyle changes in patients with obesity and type 2 diabetes: a systematic review and meta-analysis
Authors: Kurnik Mesarič Katja , Pajek Jernej , Logar Zakrajšek Bernarda , Bogataj Špela , Kodrič Jana 
Published: August 2023

AbstractThe aim of this systematic review and meta-analysis was to examine the contribution of cognitive behavioral therapy (CBT) to the implementation of lifestyle changes, considering health-related and behavioral outcomes. A systematic literature review was performed using multiple databases (PsycInfo, PubMed and MEDLINE). The inclusion criteria comprised randomised controlled trials of CBT for lifestyle changes in patients with obesity and/or type 2 diabetes. The quality of study reporting was assessed with the revised Cochrane Collaboration’s risk of bias tool. A meta-analysis was conducted on studies with appropriate outcomes. Nine randomised controlled trials, with a total sample size of 902 participants, met the inclusion criteria. The meta-analysis has shown a medium, significant effect size of CBT interventions for weight loss and weight maintenance, and a low, non-significant effect size of CBT interventions for reducing glycated hemoglobin (HbA1c) levels. A separate, combined, meta-analysis for all nine calculated effect sizes has yielded a medium and significant overall effect size for the model. Our review of the studies about the effectiveness of CBT in implementing lifestyle changes has, in comparison to usual control groups, proven the efficacy of CBT interventions in implementing lifestyle changes, especially for weight loss and weight maintenance.
Asparagine restriction enhances CD8+ T cell metabolic fitness and antitumoral functionality through an NRF2-dependent stress response
Authors: Gnanaprakasam J. N. Rashida , Kushwaha Bhavana , Liu Lingling , Chen Xuyong , Kang Siwen , Wang Tingting , Cassel Teresa A. , Adams Christopher M. , Higashi Richard M. , Scott David A. , Xin Gang , Li Zihai , Yang Jun , Lane Andrew N. , Fan Teresa W.-M. , Zhang Ji , Wang Ruoning 
Published: August 2023

AbstractRobust and effective T cell immune surveillance and cancer immunotherapy require proper allocation of metabolic resources to sustain energetically costly processes, including growth and cytokine production. Here, we show that asparagine (Asn) restriction on CD8+ T cells exerted opposing effects during activation (early phase) and differentiation (late phase) following T cell activation. Asn restriction suppressed activation and cell cycle entry in the early phase while rapidly engaging the nuclear factor erythroid 2-related factor 2 (NRF2)-dependent stress response, conferring robust proliferation and effector function on CD8+ T cells during differentiation. Mechanistically, NRF2 activation in CD8+ T cells conferred by Asn restriction rewired the metabolic program by reducing the overall glucose and glutamine consumption but increasing intracellular nucleotides to promote proliferation. Accordingly, Asn restriction or NRF2 activation potentiated the T cell-mediated antitumoral response in preclinical animal models, suggesting that Asn restriction is a promising and clinically relevant strategy to enhance cancer immunotherapy. Our study revealed Asn as a critical metabolic node in directing the stress signaling to shape T cell metabolic fitness and effector functions.
Different niches for stem cells carrying the same oncogenic driver affect pathogenesis and therapy response in myeloproliferative neoplasms
Authors: Grockowiak Elodie , Korn Claudia , Rak Justyna , Lysenko Veronika , Hallou Adrien , Panvini Francesca M. , Williams Matthew , Fielding Claire , Fang Zijian , Khatib-Massalha Eman , García-García Andrés , Li Juan , Khorshed Reema A. , González-Antón Sara , Baxter E. Joanna , Kusumbe Anjali , Wilkins Bridget S. , Green Anna , Simons Benjamin D. , Harrison Claire N. , Green Anthony R. , Lo Celso Cristina , Theocharides Alexandre P. A. , Méndez-Ferrer Simón 
Published: August 2023

AbstractAging facilitates the expansion of hematopoietic stem cells (HSCs) carrying clonal hematopoiesis-related somatic mutations and the development of myeloid malignancies, such as myeloproliferative neoplasms (MPNs). While cooperating mutations can cause transformation, it is unclear whether distinct bone marrow (BM) HSC-niches can influence the growth and therapy response of HSCs carrying the same oncogenic driver. Here we found different BM niches for HSCs in MPN subtypes. JAK–STAT signaling differentially regulates CDC42-dependent HSC polarity, niche interaction and mutant cell expansion. Asymmetric HSC distribution causes differential BM niche remodeling: sinusoidal dilation in polycythemia vera and endosteal niche expansion in essential thrombocythemia. MPN development accelerates in a prematurely aged BM microenvironment, suggesting that the specialized niche can modulate mutant cell expansion. Finally, dissimilar HSC-niche interactions underpin variable clinical response to JAK inhibitor. Therefore, HSC-niche interactions influence the expansion rate and therapy response of cells carrying the same clonal hematopoiesis oncogenic driver.
How Australian environmental non-governmental organisations frame and enact climate justice
Authors: Gulliver Robyn E. , Vachette Astrid , Boddington Sarah 
Published: August 2023

AbstractThis paper seeks to examine how Australian environmental non-governmental organisations (ENGOs) communicate about and mobilise their supporters for climate justice. ENGOs play an important role in raising awareness and changing values, attitudes and behaviours related to climate justice. However, while many Australian ENGOs have begun incorporating language around climate justice in their communications, it remains unclear how this concept is framed and enacted in practice. Using data collected from 619 ENGO websites and 149 grant applications, we examine how ENGOs describe climate justice and the collective action frames they use to mobilise action. We found that while few ENGOs provided detailed explanations of climate justice on their websites, they primarily framed climate injustice as a procedural and distributive problem. The fossil fuel sector was most commonly identified as the cause of climate injustice, and First Nations communities most commonly affected. ENGOs linked different climate justice dimensions to diverse causes, issues and actions, indicating a nuanced understanding of how climate justice can be enacted in different contexts. However, they primarily proposed incremental tactics involving education, solidarity and allyship behaviours rather than radical actions through which to drive a transformative agenda of social, political or economic change. We conclude the paper with a discussion of applied implications for ENGOs and suggestions for future research.