bluuebunny/crossref_metadata_2025_split huggingface dataset:
BrcaDx: precise identification of breast cancer from expression data using a minimal set of features
Authors: Muthamilselvan Sangeetha , Palaniappan Ashok 
Published: May 2023

Background: Breast cancer is the foremost cancer in worldwide incidence, surpassing lung cancer notwithstanding the gender bias. One in four cancer cases among women are attributable to cancers of the breast, which are also the leading cause of death in women. Reliable options for early detection of breast cancer are needed.Methods: Using public-domain datasets, we screened transcriptomic profiles of breast cancer samples, and identified progression-significant linear and ordinal model genes using stage-informed models. We then applied a sequence of machine learning techniques, namely, feature selection, principal components analysis, and k-means clustering, to train a learner to discriminate “cancer” from “normal” based on expression levels of identified biomarkers.Results: Our computational pipeline yielded an optimal set of nine biomarker features for training the learner, namely, NEK2, PKMYT1, MMP11, CPA1, COL10A1, HSD17B13, CA4, MYOC, and LYVE1. Validation of the learned model on an independent test dataset yielded a performance of 99.5% accuracy. Blind validation on an out-of-domain external dataset yielded a balanced accuracy of 95.5%, demonstrating that the model has effectively reduced the dimensionality of the problem, and learnt the solution. The model was rebuilt using the full dataset, and then deployed as a web app for non-profit purposes at: https://apalania.shinyapps.io/brcadx/. To our knowledge, this is the best-performing freely available tool for the high-confidence diagnosis of breast cancer, and represents a promising aid to medical diagnosis.
Identifying fibrogenic cells following salivary gland obstructive injury
Authors: Altrieth Amber L. , O’Keefe Kevin J. , Gellatly Victoria A. , Tavarez Joey R. , Feminella Sage M. , Moskwa Nicholas L. , Cordi Carmalena V. , Turrieta Judy C. , Nelson Deirdre A. , Larsen Melinda 
Published: May 2023

Fibrosis results from excess extracellular matrix accumulation, which alters normal tissue architecture and impedes function. In the salivary gland, fibrosis can be induced by irradiation treatment for cancer therapy, Sjögren’s Disease, and other causes; however, it is unclear which stromal cells and signals participate in injury responses and disease progression. As hedgehog signaling has been implicated in fibrosis of the salivary gland and other organs, we examined contributions of the hedgehog effector, Gli1, to fibrotic responses in salivary glands. To experimentally induce a fibrotic response in female murine submandibular salivary glands, we performed ductal ligation surgery. We detected a progressive fibrotic response where both extracellular matrix accumulation and actively remodeled collagen significantly increased at 14 days post-ligation. Macrophages, which participate in extracellular matrix remodeling, and Gli1+ and PDGFRα+ stromal cells, which may deposit extracellular matrix, both increased with injury. Using single-cell RNA-sequencing, Gli1+ cells were not found in discrete clusters at embryonic day 16 but were found in clusters expressing the stromal genes Pdgfra and/or Pdgfrb. In adult mice, Gli1+ cells were similarly heterogeneous but more cells co-expressed PDGFRα and PDGFRβ. Using Gli1-CreERT2; ROSA26tdTomato lineage-tracing mice, we found that Gli1-derived cells expand with ductal ligation injury. Although some of the Gli1 lineage-traced tdTomato+ cells expressed vimentin and PDGFRβ following injury, there was no increase in the classic myofibroblast marker, smooth muscle alpha-actin. Additionally, there was little change in extracellular matrix area, remodeled collagen area, PDGFRα, PDGFRβ, endothelial cells, neurons, or macrophages in Gli1 null salivary glands following injury when compared with controls, suggesting that Gli1 signaling and Gli1+ cells have only a minor contribution to mechanical injury-induced fibrotic changes in the salivary gland. We used scRNA-seq to examine cell populations that expand with ligation and/or showed increased expression of matrisome genes. Some Pdgfra+/Pdgfrb+ stromal cell subpopulations expanded in response to ligation, with two stromal cell subpopulations showing increased expression of Col1a1 and a greater diversity of matrisome genes, consistent with these cells being fibrogenic. However, only a few cells in these subpopulations expressed Gli1, consistent with a minor contribution of these cells to extracellular matrix production. Defining the signaling pathways driving fibrotic responses in stromal cell sub-types could reveal future therapeutic targets.
Number of prior live births is associated with higher arterial stiffness but not its change in older women: the atherosclerosis risk in communities study
Authors: Bonner Alison N. , Jayawickreme Shantal , Malek Angela M. , Vladutiu Catherine J. , Oliver-Williams Clare , Cortés Yamnia I. , Tanaka Hirofumi , Meyer Michelle L. 
Published: May 2023

IntroductionAlthough studies have demonstrated a J-shaped association between parity and cardiovascular disease (CVD), the association with arterial stiffness is not fully understood.MethodsWe examined the association between parity and carotid-femoral pulse wave velocity (cfPWV), a measure of central arterial stiffness. We conducted a longitudinal analysis of 1220 women (mean age 73.7 years) who attended the Atherosclerosis Risk in Communities Study visit 5 (2011-2013). At visit 2 (1990-1992), women self-reported parity (number of prior live births), which we categorized as: 0 (never pregnant or pregnant with no live births); 1-2 (referent); 3-4; and 5+ live births. Technicians measured cfPWV at visit 5 (2011-2013) and visit 6 or 7 (2016-2019). Multivariable linear regression modeled the associations of parity with visit 5 cfPWV and cfPWV change between visit 5 and 6/7 adjusted for demographics and potential confounding factors.ResultsParticipants reported 0 (7.7%), 1-2 (38.7%), 3-4 (40.0%), or 5+ (13.6%) prior live births. In adjusted analyses, women with 5+ live births had a higher visit 5 cfPWV (β=50.6 cm/s, 95% confidence interval: 3.6, 97.7 cm/s) than those with 1-2 live births. No statistically significant associations were observed for other parity groups with visit 5 cfPWV or with cfPWV change.DiscussionIn later life, women with 5+ live births had higher arterial stiffness than those with 1-2 live births, but cfPWV change did not differ by parity, suggesting women with 5+ live births should be targeted for early primary prevention of CVD given their higher arterial stiffness at later-life.
Computed tomography–based pericoronary adipose tissue attenuation in patients undergoing TAVR: a novel method for risk assessment
Authors: Steyer Alexandra , Mas-Peiro Silvia , Leistner David M. , Puntmann Valentina O. , Nagel Eike , Dey Damini , Goeller Markus , Koch Vitali , Booz Christian , Vogl Thomas J. , Martin Simon S. 
Published: May 2023

ObjectivesThis study aims to assess the attenuation of pericoronary adipose tissue (PCAT) surrounding the proximal right coronary artery (RCA) in patients with aortic stenosis (AS) and undergoing transcatheter aortic valve replacement (TAVR). RCA PCAT attenuation is a novel computed tomography (CT)–based marker for evaluating coronary inflammation. Coronary artery disease (CAD) in TAVR patients is common and usually evaluated prior to intervention. The most sensible screening method and consequential treatment approach are unclear and remain a matter of ceaseless discussion. Thus, interest remains for safe and low-demand predictive markers to identify patients at risk for adverse outcomes postaortic valve replacement.MethodsThis single-center retrospective study included patients receiving a standard planning CT scan prior to TAVR. Conventional CAD diagnostic tools, such as coronary artery calcium score and significant stenosis via invasive coronary angiography and coronary computed tomography angiography, were determined in addition to RCA PCAT attenuation using semiautomated software. These were assessed for their relationship with major adverse cardiovascular events (MACE) during a 24-month follow-up period.ResultsFrom a total of 62 patients (mean age: 82 ± 6.7 years), 15 (24.2%) patients experienced an event within the observation period, 10 of which were attributed to cardiovascular death. The mean RCA PCAT attenuation was higher in patients enduring MACE than that in those without an endpoint (−69.8 ± 7.5 vs. −74.6 ± 6.2, P = 0.02). Using a predefined cutoff of &gt;−70.5 HU, 20 patients (32.3%) with high RCA PCAT attenuation were identified, nine (45%) of which met the endpoint within 2 years after TAVR. In a multivariate Cox regression model including conventional CAD diagnostic tools, RCA PCAT attenuation prevailed as the only marker with significant association with MACE (P = 0.02). After dichotomization of patients into high- and low-RCA PCAT attenuation groups, high attenuation was related to greater risk of MACE (hazard ration: 3.82, P = 0.011).ConclusionRCA PCAT attenuation appears to have predictive value also in a setting of concomitant AS in patients receiving TAVR. RCA PCAT attenuation was more reliable than conventional CAD diagnostic tools in identifying patients at risk for MACE .
Spatiotemporal variability of magmatic products under a changing structural and tectonic context: a case study in the Andes of southern Central Chile
Authors: Piquer José , Fischer Tomás , Torres Francisco , Plissart Gaëlle 
Published: May 2023

In a subduction setting, the type of magmatic products which reach the upper crust, and eventually the surface, depends on several variables, among which some of the most relevant are the tectonic regime, and the orientation of magma pathways relative to the predominant stress tensor. To better understand this relationship, we studied in detail an area of the Andes of southern Central Chile in which subduction-related magmatism has been active at least during the last 18 m.y. The relationship between high-angle faults and magmatism was studied, and the spatiotemporal variations on the stress tensor were analyzed. The chemistry of the different magmatic products was used to evaluate the magma “fertility”, understood as its potential to form a giant porphyry-type deposit. The age of the studied units is constrained by new U-Pb zircon ages, complemented with previous geochronological studies. Three main high-angle fault systems are present: ∼NW striking structures control the emplacement of plutonic bodies, while ∼NE–ENE and N–NNE faults, more parallel to the prevailing orientation of σ1 since the middle Miocene, control the emplacement of dike swarms and volcanic alignments. Regarding the geochemical characterization, a transition towards steeper REE patterns and higher fertility indices is observed in the earliest facies of the La Invernada Plutonic Complex (∼15-14 Ma), coincident with a middle Miocene orogenic event described at this latitude by previous authors. The Pliocene La Resolana intrusions show higher magma fertility indices; however, they are still considerably lower than those typical for porphyry-forming magmas in the same Andean region. It is concluded that the contrasting fertility observed in coeval intrusions emplaced under the same tectonic context, cannot be explained by continental-scale processes; instead, they are related to differences in the local pathways of magma ascent through the crust. Fault systems which are miss-oriented relative to the predominant orientation of σ1 appear to favor longer magma residence times, achieving a higher degree of differentiation and fertility in most cases crystalizing within the upper crust, while magmas ascending through more favorably oriented faults are more primitive, and often reach the surface forming stratovolcanoes and alignments of monogenetic vents.
Assessing the scientific value and vulnerability of paleontological sites: a new analytic operational procedure
Authors: Faggi Andrea , Bartolini-Lucenti Saverio , Rook Lorenzo 
Published: May 2023

Introduction:Paleontological heritage rarely receives the same legislative attention as archeological heritage. Part of the problem seems to be, at least in some contexts (e.g., Italy), the difficulty of acknowledging fossils as distinct assets from other cultural heritage objects and the lack of expertise among the administrative functionaries. This study aims to describe and test an objective analytic operational procedure that could allow for the assessment of the relevance of any fossiliferous site and its potential vulnerability in its present state.Methods:The estimations were obtained using several quantitative and qualitative parameters that could describe the probability of fossil recovery for each site (Pr) and the scientific and cultural interest of the locality (In). Each parameter has subcategories for better defining. The product of probability and interest results in the scientific value (S), generally expressed as a percentage (S*). The vulnerability index (V) of productive and active sites considers the use of the land (U) and the natural erosion (E). The parameters were thought to apply to any type of fossil locality. We tested the indexes on 22 localities (7 of which were with paleoichnological records and 15 with direct body-fossil evidence), all different from one another.Results:The results show that the proposed indexes well describe and characterize each locality. Most of the sites are moderately vulnerable (V between 1 and 3) except for large quarry sites (e.g., Pirro Nord, Italy and Solnhofen, Germany) whose vulnerability indexes fell in the maximum degree of risk.Discussion:The operational procedure presented here is a simple, objective, and remotely applicable method allowing paleontologists and non-expert personnel to categorize localities and, therefore, act as a base to plan actions in paleontological heritage management relative to territorial development and land use.
Association between breast cancer and thyroid cancer risk: a two-sample Mendelian randomization study
Authors: Tan Hong , Wang Sisi , Huang Feifei , Tong Zhongyi 
Published: May 2023

BackgroundBreast and thyroid cancer are increasingly prevalent, but it remains unclear whether the observed associations are due to heightened medical surveillance or intrinsic etiological factors. Observational studies are vulnerable to residual confounding, reverse causality, and bias, which can compromise causal inference. In this study, we employed a two-sample Mendelian randomization (MR) analysis to establish a causal link between breast cancer and heightened thyroid cancer risk.MethodsWe obtained the single nucleotide polymorphisms (SNPs) associated with breast cancer from a genome-wide association study (GWAS) conducted by the Breast Cancer Association Consortium (BCAC). The FinnGen consortium’s latest and largest accessible GWAS thyroid cancer data at the summary level. We performed four MR analyses, including the inverse-variance-weighted (IVW), weighted median, MR-Egger regression, and weighted mode, to evaluate the potential causal connection between genetically predicted breast cancer and higher risk for thyroid cancer. Sensitivity analysis, heterogeneity and pleiotropy tests were used to ensure the reliability of our findings.ResultsOur study revealed causal relationship between genetically predicted breast cancer and thyroid cancer (IVW method, odds ratio (OR) = 1.135, 95% confidence interval (CI): 1.006 to 1.279, P = 0.038). However, there was no causal association between genetically predicted triple-negative breast cancer and thyroid cancer (OR = 0.817, 95% CI: 0.610 to 1.095, P = 0.177). There was no directional pleiotropy or horizontal pleiotropy in the present study.ConclusionThis two-sample MR study supports a causal link between ER-positive breast cancer and heightened the risk of thyroid cancer. Our analysis did not reveal a direct correlation between triple-negative breast cancer and thyroid cancer.
Circulating adrenal 11-oxygenated androgens are associated with clinical outcome in endometrial cancer
Authors: Dahmani Cylia , Caron Patrick , Simonyan David , Turcotte Véronique , Grégoire Jean , Plante Marie , Guillemette Chantal 
Published: May 2023

ContextRecent evidence support that androgens play an important role in the etiology of endometrial cancer (EC). Adrenal-derived 11-oxygenated androgens are highly potent agonists of the androgen receptor (AR), comparable to testosterone (T) and dihydrotestosterone (DHT) that have not been studied in the context of EC.MethodologyWe studied a cohort of 272 newly diagnosed postmenopausal EC cases undergoing surgical treatment. Circulating concentrations of seven 11-oxygenated androgens including precursors, potent androgens and their metabolites were established in serum samples collected before and 1 month after surgery using a validated liquid chromatography tandem mass spectrometry method (LC-MS/MS). Free (unconjugated) and total (free + sulfate and glucuronide conjugates following enzymatic hydrolysis) were analyzed in relation to clinicopathological features, recurrence and disease-free survival (DFS).ResultsLevels of 11-oxygenated androgens were weakly correlated to those of canonical androgens such as testosterone (T) and dihydrotestosterone (DHT), with no evidence of their association with clinicopathological features. Levels of 11-oxygenated androgens declined after surgery but remained higher in overweight and obese compared to normal weight cases. Higher levels of preoperative free 11-ketoandrosterone (11KAST) were associated with an increased risk of recurrence (Hazard ratio (HR) of 2.99 (95%CI=1.09-8.18); P=0.03). Postoperative free 11β-hydroxyandrosterone (11OHAST) levels were adversely associated with recurrence and DFS (HR = 3.23 (1.11-9.40); P=0.03 and 3.27 (1.34-8.00); P=0.009, respectively).Conclusion11-oxygenated androgen metabolites emerge as potential prognostic markers of EC.
Comprehensive analysis of endoplasmic reticulum stress-associated genes signature of ulcerative colitis
Authors: Deng Beiying , Liao Fei , Liu Yinghui , He Pengzhan , Wei Shuchun , Liu Chuan , Dong Weiguo 
Published: May 2023

BackgroundEndoplasmic reticulum stress (ERS) is a critical factor in the development of ulcerative colitis (UC); however, the underlying molecular mechanisms remain unclear. This study aims to identify pivotal molecular mechanisms related to ERS in UC pathogenesis and provide novel therapeutic targets for UC.MethodsColon tissue gene expression profiles and clinical information of UC patients and healthy controls were obtained from the Gene Expression Omnibus (GEO) database, and the ERS-related gene set was downloaded from GeneCards for analysis. Weighted gene co-expression network analysis (WGCNA) and differential expression analysis were utilized to identify pivotal modules and genes associated with UC. A consensus clustering algorithm was used to classify UC patients. The CIBERSORT algorithm was employed to evaluate the immune cell infiltration. Gene Set Variation Analysis (GSVA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to explore potential biological mechanisms. The external sets were used to validate and identify the relationship of ERS-related genes with biologics. Small molecule compounds were predicted using the Connectivity Map (CMap) database. Molecular docking was performed to simulate the binding conformation of small molecule compounds and key targets.ResultsThe study identified 915 differentially expressed genes (DEGs) and 11 ERS-related genes (ERSRGs) from the colonic mucosa of UC patients and healthy controls, and these genes had good diagnostic value and were highly correlated. Five potential small-molecule drugs sharing tubulin inhibitors were identified, including albendazole, fenbendazole, flubendazole, griseofulvin, and noscapine, among which noscapine exhibited the highest correlation with a high binding affinity to the targets. Active UC and 10 ERSRGs were associated with a large number of immune cells, and ERS was also associated with colon mucosal invasion of active UC. Significant differences in gene expression patterns and immune cell infiltration abundance were observed among ERS-related subtypes.ConclusionThe results suggest that ERS plays a vital role in UC pathogenesis, and noscapine may be a promising therapeutic agent for UC by affecting ERS.
Akkermansia muciniphila-Nlrp3 is involved in the neuroprotection of phosphoglycerate mutase 5 deficiency in traumatic brain injury mice
Authors: Chen Yuhua , Chen Junhui , Wei Hong , Gong Kai , Meng Jiao , Long Tianlin , Guo Jianfeng , Hong Jun , Yang Lingjian , Qiu Junling , Xiong Kun , Wang Zhanxiang , Xu Quanhua 
Published: May 2023

IntroductionGut-microbiota-brain axis is a potential treatment to decrease the risk of chronic traumatic encephalopathy following traumatic brain injury (TBI). Phosphoglycerate mutase 5 (PGAM5), a mitochondrial serine/threonine protein phosphatase, resides in mitochondrial membrane and regulates mitochondrial homeostasis and metabolism. Mitochondria mediates intestinal barrier and gut microbiome.ObjectivesThis study investigated the association between PGAM5 and gut microbiota in mice with TBI.MethodsThe controlled cortical impact injury was established in mice with genetically-ablated Pgam5 (Pgam5−/−) or wild type, and WT male mice were treated with fecal microbiota transplantation (FMT) from male Pgam5−/− mice or Akkermansia muciniphila (A. muciniphila). Then the gut microbiota abundance, blood metabolites, neurological function, and nerve injury were detected.ResultsTreated with antibiotics for suppressing gut microbiota in Pgam5−/− mice partially relieved the role of Pgam5 deficiency in the improvement of initial inflammatory factors and motor dysfunction post-TBI. Pgam5 knockout exhibited an increased abundance of A. muciniphila in mice. FMT from male Pgam5−/− mice enabled better maintenance of amino acid metabolism and peripherial environment than that in TBI-vehicle mice, which suppressed neuroinflammation and improved neurological deficits, and A. muciniphila was negatively associated with intestinal mucosal injury and neuroinflammation post-TBI. Moreover, A. muciniphila treatment ameliorated neuroinflammation and nerve injury by regulating Nlrp3 inflammasome activation in cerebral cortex with TBI.ConclusionThus, the present study provides evidence that Pgam5 is involved in gut microbiota-mediated neuroinflammation and nerve injury, with A. muciniphila-Nlrp3 contributing to peripheral effects.