bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cystine/glutamate antiporter xCT deficiency reduces metastasis without impairing immune system function in breast cancer mouse models
Authors: Ruiu Roberto , Cossu Chiara , Iacoviello Antonella , Conti Laura , Bolli Elisabetta , Ponzone Luca , Magri Jolanda , Rumandla Alekya , Calautti Enzo , Cavallo Federica 
Published: September 2023

Abstract
Background
The upregulation of antioxidant mechanisms is a common occurrence in cancer cells, as they strive to maintain balanced redox state and prevent oxidative damage. This includes the upregulation of the cystine/glutamate antiporter xCT, which plays a crucial role in protecting cancer cells from oxidative stress. Consequently, targeting xCT has become an attractive strategy for cancer treatment. However, xCT is also expressed by several types of immune cells where it has a role in proliferation and effector functions. In light of these observations, a comprehensive understanding of the specific role of xCT in the initiation and progression of cancer, as well as its potential impact on the immune system within the tumor microenvironment and the anti-tumor response, require further investigation.

Methods
We generated xCTnull BALB/c mice to investigate the role of xCT in the immune system and xCTnull/Erbb2-transgenic BALB-neuT mice to study the role of xCT in a mammary cancer-prone model. We also used mammary cancer cells derived from BALB-neuT/xCTnull mice and xCTKO 4T1 cells to test the contribution of xCT to malignant properties in vitro and in vivo.

Results
xCT depletion in BALB-neuT/xCTnull mice does not alter autochthonous tumor initiation, but tumor cells isolated from these mice display proliferation and redox balance defects in vitro. Although xCT disruption sensitizes 4T1 cells to oxidative stress, it does not prevent transplantable tumor growth, but reduces cell migration in vitro and lung metastasis in vivo. This is accompanied by an altered immune cell recruitment in the pre-metastatic niche. Finally, systemic depletion of xCT in host mice does not affect transplantable tumor growth and metastasis nor impair the proper mounting of both humoral and cellular immune responses in vivo.

Conclusions
xCT is dispensable for proper immune system function, thus supporting the safety of xCT targeting in oncology. Nevertheless, xCT is involved in several processes required for the metastatic seeding of mammary cancer cells, thus broadening the scope of xCT-targeting approaches.
Chronic stress induces pulmonary epithelial cells to produce acetylcholine that remodels lung pre-metastatic niche of breast cancer by enhancing NETosis
Authors: Pan Jun , Zhang Leyi , Wang Xiaomei , Li Lili , Yang Chenghui , Wang Zhen , Su Ke , Hu Xiaoxiao , Zhang Yi , Ren Guohong , Jiang Jiahuan , Li Peng , Huang Jian 
Published: September 2023

Abstract
Background
Chronic stress promotes most hallmarks of cancer through impacting the malignant tissues, their microenvironment, immunity, lymphatic flow, etc. Existing studies mainly focused on the roles of stress-induced activation of systemic sympathetic nervous system and other stress-induced hormones, the organ specificity of chronic stress in shaping the pre-metastatic niche remains largely unknown. This study investigated the role of chronic stress in remodeling lung pre-metastatic niche of breast cancer.

Methods
Breast cancer mouse models with chronic stress were constructed by restraint or unpredictable stress. Expressions of tyrosine hydroxylase, vesicular acetylcholine transporter (VAChT), EpCAM and NETosis were examined by immunofluorescence and confocal microscopy. mRNA and protein levels of choline acetyltransferase (ChAT), VAChT, and peptidylarginine deiminase 4 were detected by qRT-PCR and Western blotting, respectively. Immune cell subsets were analyzed by flow cytometry. Acetylcholine (ACh) and chemokines were detected by ELISA and multi chemokine array, respectively. ChAT in lung tissues from patients was examined by immunohistochemistry.

Results
Breast cancer-bearing mice suffered chronic stress metastasized earlier and showed more severe lung metastasis than did mice in control group. VAChT, ChAT and ChAT+ epithelial cells were increased significantly in lung of model mice undergone chronic stress. ACh and chemokines especially CXCL2 in lung culture supernatants from model mice with chronic stress were profoundly increased. Chronic stress remodeled lung immune cell subsets with striking increase of neutrophils, enhanced NETosis in lung and promoted NETotic neutrophils to capture cancer cells. ACh treatment resulted in enhanced NETosis of neutrophils. The expression of ChAT in lung tissues from breast cancer patients with lung metastasis was significantly higher than that in patients with non-tumor pulmonary diseases.

Conclusions
Chronic stress promotes production of CXCL2 that recruits neutrophils into lung, and induces pulmonary epithelial cells to produce ACh that enhances NETosis of neutrophils. Our findings demonstrate for the first time that chronic stress induced epithelial cell derived ACh plays a key role in remodeling lung pre-metastatic niche of breast cancer.
Leading reasons for antibiotic prescriptions in pediatric respiratory infections: influence of fever in a primary care setting
Authors: Picca Marina , Carrozzo Romeo , Milani Gregorio Paolo , Corsello Antonio , Macchi Marina , Buzzetti Roberto , Marchisio Paola , Mameli Chiara 
Published: September 2023

Abstract
Background
Antibiotic overuse in children is a significant public health concern, as it can lead to the emergence and spread of antibiotic-resistant bacteria. Although respiratory infections account for most antibiotic prescriptions in children, many of these infections are viral and do not require antibiotics. In this study, we aimed to investigate the use of antibiotics in children with respiratory infections in a primary care setting and to explore the possible role of fever on antibiotic prescription.

Methods
We conducted a prospective observational study that evaluated preschool children aged 0–5 years who were assessed by their primary care pediatricians for respiratory infectious diseases between October 2019 and March 2021. The study involved 69 public primary care pediatricians and a total of 678 pediatric episodes for respiratory infections.

Results
Amoxicillin/clavulanate was the most frequently prescribed drug. Bronchitis accounted for most of inappropriate antibiotic prescriptions (73%). Furthermore, the presence of fever was associated with a ~ 300% increase in the likelihood of prescribing antibiotics for respiratory infections that do not typically require antibiotics.

Conclusion
Our findings emphasize the need for adherence to international guidelines and recommendations in the primary care of children to reduce unnecessary antibiotic use and prevent the development of antibiotic resistance. This study also underscores the potential relevance of new studies to evaluate antibiotic prescription attitudes in other clinical settings and geographical areas.
Year 2022: exploring COVID-19 pandemic in children
Authors: Bozzola Elena , Caffarelli Carlo , Santamaria Francesca , Corsello Giovanni 
Published: September 2023

AbstractCOVID-19 pandemics is rapidly changing. In this article, we review progresses published in the Italian Journal of Pediatrics in 2022. More data on clinical pictures, prevention strategies and active management in children have been provided. The continued evolution of knowledge has driven transformations in the clinical approach to the disease and allowed key advancements in the care of children with COVID-19.
Tamoxifen-predictive value of gene expression signatures in premenopausal breast cancer: data from the randomized SBII:2 trial
Authors: Lundgren Christine , Tutzauer Julia , Church Sarah E. , Stål Olle , Ekholm Maria , Forsare Carina , Nordenskjöld Bo , Fernö Mårten , Bendahl Pär-Ola , Rydén Lisa 
Published: September 2023

AbstractBackgroundGene expression (GEX) signatures in breast cancer provide prognostic information, but little is known about their predictive value for tamoxifen treatment. We examined the tamoxifen-predictive value and prognostic effects of different GEX signatures in premenopausal women with early breast cancer.MethodsRNA from formalin-fixed paraffin-embedded tumor tissue from premenopausal women randomized between two years of tamoxifen treatment and no systemic treatment was extracted and successfully subjected to GEX profiling (n = 437, NanoString Breast Cancer 360™ panel). The median follow-up periods for a recurrence-free interval (RFi) and overall survival (OS) were 28 and 33 years, respectively. Associations between GEX signatures and tamoxifen effect were assessed in patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+ /HER2−) tumors using Kaplan–Meier estimates and Cox regression. The prognostic effects of GEX signatures were studied in the entire cohort. False discovery rate adjustments (q-values) were applied to account for multiple hypothesis testing.ResultsIn patients with ER+/HER2− tumors,FOXA1expression below the median was associated with an improved effect of tamoxifen after 10 years with regard to RFi (hazard ratio [HR]FOXA1(high) = 1.04, 95% CI = 0.61–1.76, HRFOXA1(low) = 0.30, 95% CI = 0.14–0.67,qinteraction = 0.0013), and a resembling trend was observed forAR(HRAR(high) = 1.15, 95% CI = 0.60–2.20, HRAR(low) = 0.42, 95% CI = 0.24–0.75,qinteraction = 0.87). Similar patterns were observed for OS. Tamoxifen was in the same subgroup most beneficial for RFi in patients with lowESR1expression (HRRFiESR1(high) = 0.76, 95% CI = 0.43–1.35, HRRFi,ESR1(low) = 0.56, 95% CI = 0.29–1.06,qinteraction = 0.37). Irrespective of molecular subtype, higher levels ofESR1, Mast cells, andPGRon a continuous scale were correlated with improved 10 years RFi (HRESR1 = 0.80, 95% CI = 0.69–0.92,q = 0.005; HRMast cells = 0.74, 95% CI = 0.65–0.85,q < 0.0001; and HRPGR = 0.78, 95% CI = 0.68–0.89,q = 0.002). For BC proliferation and Hypoxia, higher scores associated with worse outcomes (HRBCproliferation = 1.54, 95% CI = 1.33–1.79,q < 0.0001; HRHypoxia = 1.38, 95% CI = 1.20–1.58,q < 0.0001). The results were similar for OS.ConclusionsExpression ofFOXA1is a promising predictive biomarker for tamoxifen effect in ER+/HER2− premenopausal breast cancer. In addition, each of the signatures BC proliferation, Hypoxia, Mast cells, and the GEX ofAR,ESR1,andPGRhad prognostic value, also after adjusting for established prognostic factors.Trial registrationThis trial was retrospectively registered in the ISRCTN database the 6th of December 2019, trial ID:https://clinicaltrials.gov/ct2/show/ISRCTN12474687.
happi: a hierarchical approach to pangenomics inference
Authors: Trinh Pauline , Clausen David S. , Willis Amy D. 
Published: September 2023

AbstractRecovering metagenome-assembled genomes (MAGs) from shotgun sequencing data is an increasingly common task in microbiome studies, as MAGs provide deeper insight into the functional potential of both culturable and non-culturable microorganisms. However, metagenome-assembled genomes vary in quality and may contain omissions and contamination. These errors present challenges for detecting genes and comparing gene enrichment across sample types. To address this, we propose , an approach to testing hypotheses about gene enrichment that accounts for genome quality. We illustrate the advantages of over existing approaches using published Saccharibacteria MAGs,Streptococcus thermophilusMAGs, and via simulation.
Exosomes secreted by endothelial cells derived from human induced pluripotent stem cells improve recovery from myocardial infarction in mice
Authors: Li Hao , Wang Lu , Ma Teng , Liu Zhongmin , Gao Ling 
Published: September 2023

AbstractBackgroundHuman induced pluripotent stem cell-derived endothelial cells (hiPSC-ECs) exhibit the potential to repair the injured heart after myocardial infarction (MI) by promoting neovascularization and cardiomyocyte survival. However, because of the low cellular retention and poor engraftment efficacy, cell therapy of MI is partly mediated by exosomes secreted from the transplanted cells. In this study, we investigated whether exosomes secreted from hiPSC-ECs could become a promising acellular approach to repair the infarcted heart after MI and elucidated the underlying protective mechanism.MethodsThe hiPSC-ECs were differentiated, and exosomes were isolated in vitro. Then, hiPSC-EC exosomes were delivered by intramyocardial injection in a murine MI model in vivo. Echocardiography, combined with hemodynamic measurement, histological examination, Ca2+transient and cell shortening assessment, and Western blot, was used to determine the protective effects of hiPSC-EC exosomes on the infarcted heart. Furthermore, microRNA sequencing, luciferase activity assay, and microRNA gain–loss function experiments were performed to investigate the enriched microRNA and its role in exosome-mediated effects.ResultsIn vitro, the hiPSC-EC exosomes enhanced intracellular Ca2+transients, increased ATP content, and improved cell survival to protect cardiomyocytes from oxygen–glucose deprivation injury. Congruously, hiPSC-EC exosome administration in vivo improved the myocardial contractile function and attenuated the harmful left ventricular remodeling after MI without increasing the frequency of arrhythmias. Mechanistically, the hiPSC-EC exosomes notably rescued the protein expression and function of the sarcoplasmic reticulum Ca2+ATPase 2a (SERCA-2a) and ryanodine receptor 2 (RyR-2) to maintain intracellular Ca2+homeostasis and increase cardiomyocyte contraction after MI. The microRNA sequencing showed that miR-100-5p was the most abundant microRNA in exosomes. miR-100-5p could target protein phosphatase 1β (PP-1β) to enhance phospholamban (PLB) phosphorylation at Ser16and subsequent SERCA activity, which contributes to the hiPSC-EC exosome-exerted cytoprotective effects on maintaining intracellular Ca2+homeostasis and promoting cardiomyocyte survival.ConclusionThe hiPSC-EC exosomes maintain cardiomyocyte Ca2+homeostasis to improve myocardial recovery after MI, which may provide an acellular therapeutic option for myocardial injury.
CD73 mediates the therapeutic effects of endometrial regenerative cells in concanavalin A-induced hepatitis by regulating CD4+ T cells
Authors: Qin Hong , Sun Chenglu , Kong Dejun , Zhu Yanglin , Shao Bo , Ren Shaohua , Wang Hongda , Zhang Jingyi , Xu Yini , Wang Hao 
Published: September 2023

Abstract
Background
As a kind of mesenchymal-like stromal cells, endometrial regenerative cells (ERCs) have been demonstrated effective in the treatment of Concanavalin A (Con A)-induced hepatitis. However, the therapeutic mechanism of ERCs is not fully understood. Ecto-5`-nucleotidase (CD73), an enzyme that could convert immune-stimulative adenosine monophosphate (AMP) to immune-suppressive adenosine (ADO), was identified highly expressed on ERCs. The present study was conducted to investigate whether the expression of CD73 on ERCs is critical for its therapeutic effects in Con A-induced hepatitis.

Methods
ERCs knocking out CD73 were generated with lentivirus-mediated CRISPR-Cas9 technology and identified by flow cytometry, western blot and AMPase activity assay. CD73-mediated immunomodulatory effects of ERCs were investigated by CD4+ T cell co-culture assay in vitro. Besides, Con A-induced hepatitis mice were randomly assigned to the phosphate-buffered saline treated (untreated), ERC-treated, negative lentiviral control ERC (NC-ERC)-treated, and CD73-knockout-ERC (CD73-KO-ERC)-treated groups, and used to assess the CD73-mediated therapeutic efficiency of ERCs. Hepatic histopathological analysis, serum transaminase concentrations, and the proportion of CD4+ T cell subsets in the liver and spleen were performed to assess the progression degree of hepatitis.

Results
Expression of CD73 on ERCs could effectively metabolize AMP to ADO, thereby inhibiting the activation and function of conventional CD4+ T cells was identified in vitro. In addition, ERCs could markedly reduce levels of serum and liver transaminase and attenuate liver damage, while the deletion of CD73 on ERCs dampens these effects. Furthermore, ERC-based treatment achieved less infiltration of CD4+ T and Th1 cells in the liver and reduced the population of systemic Th1 and Th17 cells and the levels of pro-inflammatory cytokines such as IFN-γ and TNF-α, while promoting the generation of Tregs in the liver and spleen, while deletion of CD73 on ERCs significantly impaired their immunomodulatory effects locally and systemically.

Conclusion
Taken together, it is concluded that CD73 is critical for the therapeutic efficiency of ERCs in the treatment of Con A-induced hepatitis.
Role of YAP in hematopoietic differentiation and erythroid lineage specification of human-induced pluripotent stem cells
Authors: Laowtammathron Chuti , Lorthongpanich Chanchao , Jiamvoraphong Nittaya , Srisook Pimonwan , Klaihmon Phatchanat , Kheolamai Pakpoom , Luanpitpong Sudjit , Issaragrisil Surapol 
Published: September 2023

Abstract
Background
In vitro production of hematopoietic stem/progenitor cells (HSPCs) from human-induced pluripotent stem cells (hiPSCs) provides opportunities for fundamental research, disease modeling, and large-scale production of HLA-matched HSPCs for therapeutic applications. However, a comprehensive understanding of the signaling mechanisms that regulate human hematopoiesis is needed to develop a more effective procedure for deriving HSPCs from hiPSCs.

Methods
In this study, we investigate the role of YAP during the hematopoietic differentiation of hiPSCs to HSPCs and erythrocytes using the isogenic YAP-overexpressing (YAP-S5A) and YAP-depleting (YAP-KD) hiPSCs to eliminate the effects of a genetic background variation.

Results
Although YAP is dispensable for maintaining the self-renewal and pluripotency of these hiPSCs, it affects the early cell-fate determination and hematopoietic differentiation of hiPSCs. Depleting YAP enhances the derivation efficiency of HSPCs from hiPSCs by inducing the mesodermal lineage commitment, promoting hematopoietic differentiation, and preventing the differentiation toward endothelial lineage. On the contrary, the overexpression of YAP reduced HSPCs yield by inducing the endodermal lineage commitment, suppressing hematopoietic differentiation, and promoting the differentiation toward endothelial lineage.

Conclusions
Expression of YAP is crucial for the differentiation of hiPSC-derived HSPCs toward mature erythrocytes. We believe that by manipulating YAP activity using small molecules, the efficiency of the large-scale in vitro production system for generating hematopoietic stem/progenitor cells for future therapeutic use could be improved.
Pampean megamammals in Europe: the fossil collections from Santiago Roth
Authors: Voglino Damián , Carrillo-Briceño Jorge D. , Furrer Heinz , Balcarcel Ana , Rangel-de Lazaro Gizeh , Aguirre Fernández Gabriel , Forasiepi Analía M. 
Published: September 2023

AbstractSantiago Roth was a Swiss fossil finder, naturalist, and paleontologist that emigrated to Argentina in 1866. His work largely influenced the discipline in the country at the end of the twentieth century, particularly the stratigraphy of the Pampean region. Some of his collections of Pampean fossils were sold to museums and private collectors in Europe and were accompanied by elaborated catalogues. Fossils in the Roth’s catalogues N° 2 and 3 are housed today in the Natural History Museum of Denmark, fossils from catalogues N° 4 to 6, were sold to Swiss museums, with Catalogue N° 5 currently housed at the Department of Paleontology, Universität Zürich. Here, we provide a general framework on the stratigraphy from the Roth’s Pampean fossil sites, summarize the history of the Pampean fossils in Europe originally collected by Roth, and provide historical and curatorial details of the Roth’s collection at the Department of Paleontology, Universität Zürich.
On fractional biparameterized Newton-type inequalities
Authors: Saleh Wedad , Lakhdari Abdelghani , Abdeljawad Thabet , Meftah Badreddine 
Published: September 2023

AbstractIn this work, we present a novel biparameterized identity that yields a family of one-, two-, three-, and four-point Newton-type formulas. Subsequently, we establish some new Newton-type inequalities for functions whose first derivatives are α-convex. The investigation is concluded with numerical examples accompanied by graphical representations to substantiate the accuracy of the obtained results.
Some estimates for commutators of the fractional maximal function on stratified Lie groups
Authors: Wu Jianglong , Zhao Wenjiao 
Published: September 2023

AbstractIn this paper, the main aim is to consider the boundedness of the nonlinear commutator $[b, M_{\alpha}]$
[
b
,

M
α

]
and the maximal commutator $M_{\alpha ,b}$

M

α
,
b

on the Lebesgue spaces over some stratified Lie group $\mathbb{G}$
G
when the symbol b belongs to the Lipschitz space. As a result, some new characterizations of the Lipschitz spaces on Lie group via $[b, M_{\alpha}]$
[
b
,

M
α

]
and $M_{\alpha ,b}$

M

α
,
b

are given.
Relationship between cortisol and diabetic microvascular complications: a retrospective study
Authors: Sun Shengnan , Wang Yangang 
Published: September 2023

Abstract
Objective
We aimed to investigate whether serum cortisol associate with diabetic microvascular compliments in patients with type 2 diabetes mellitus (T2DM).

Materials and methods
The subjects were recruited from hospitalized patients with T2DM from 2019 to 2021. The odds ratios (OR) and corresponding 95% confidence intervals (CI) in relation to cortisol quartiles were obtained by multiple logistic regression analysis.

Results
(1) Cortisol level was positively correlated with the severity of microalbuminuria. The OR (95% CI) of microalbuminuria and macroalbuminuria in the last quartile were 3.396 (2.030, 5.682) and 8.407 (3.726, 18.971) compared with the first quartile (p < 0.001). (2) Cortisol level was positively correlated with the severity of diabetic retinopathy (DR). The OR (95% CI) of non-proliferative diabetic retinopathy group (NPDR) and proliferative diabetic retinopathy group (PDR) in the last quartile were 2.007 (1.401, 2.875) and 7.122 (2.525, 20.090) compared with the first quartile. (3) Elevated cortisol level was associated with diabetic peripheral neuropathy. The OR (95% CI) of diabetic peripheral neuropathy (DPN) in the last quartile was 1.956 (1.371, 2.792) and that in the third quartile was 1.854 (1.319, 2.608).

Conclusions
High serum cortisol levels were significantly associated with diabetic microvascular compliments in inpatients. Its causality remains to be further studied.
Clinical trial registration number: ChiCTR2100051749.