bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional Contribution and Clinical Implication of Cancer-Associated Fibroblasts in Glioblastoma
Authors: Galbo Phillip M. , Madsen Anne Tranberg , Liu Yang , Peng Mou , Wei Yao , Ciesielski Michael J. , Fenstermaker Robert A. , Graff Sarah , Montagna Cristina , Segall Jeffrey E. , Sidoli Simone , Zang Xingxing , Zheng Deyou 
Published: December 2023

Abstract

Purpose:
The abundance and biological contribution of cancer-associated fibroblasts (CAF) in glioblastoma (GBM) are poorly understood. Here, we aim to uncover its molecular signature, cellular roles, and potential tumorigenesis implications.

Experimental Design:
We first applied single-cell RNA sequencing (RNA-seq) and bioinformatics analysis to identify and characterize stromal cells with CAF transcriptomic features in human GBM tumors. Then, we performed functional enrichment analysis and in vitro assays to investigate their interactions with malignant GBM cells.

Results:
We found that CAF abundance was low but significantly correlated with tumor grade, poor clinical outcome, and activation of extracellular matrix remodeling using three large cohorts containing bulk RNA-seq data and clinical information. Proteomic analysis of a GBM-derived CAF line and its secretome revealed fibronectin (FN1) as a critical candidate factor mediating CAF functions. This was validated using in vitro cellular models, which demonstrated that CAF-conditioned media and recombinant FN1 could facilitate the migration and invasion of GBM cells. In addition, we showed that CAFs were more abundant in the mesenchymal-like state (or subtype) than in other states of GBMs. Interestingly, cell lines resembling the proneural state responded to the CAF signaling better for the migratory and invasive phenotypes.

Conclusions:
Overall, this study characterized the molecular features and functional impacts of CAFs in GBM, alluding to novel cell interactions mediated by CAFs in the GBM microenvironment.
TAS0313 plus Pembrolizumab for Post-Chemotherapy Immune Checkpoint Inhibitor—Naïve Locally Advanced or Metastatic Urothelial Carcinoma
Authors: Nishiyama Hiroyuki , Yonese Junji , Kawahara Takashi , Matsumoto Ryuji , Miyake Hideaki , Matsubara Nobuaki , Uemura Hiroji , Eto Masatoshi , Azuma Haruhito , Obara Wataru , Terai Akito , Fukasawa Satoshi , Suekane Shigetaka 
Published: December 2023

AbstractWe evaluated the efficacy and safety of TAS0313, a multi-epitope long peptide vaccine, plus pembrolizumab in post-chemotherapy immune checkpoint inhibitor—naïve patients with locally advanced/metastatic urothelial carcinoma (la/mUC). TAS0313 9 mg was administered subcutaneously followed by pembrolizumab 200 mg on Day 1, and as monotherapy on Day 8 and 15 of Cycles 1 and 2, and Day 1 of subsequent cycles in 21-day cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Biomarkers of response were assessed. In 36 patients enrolled, the ORR was 33.3% (complete response: 7 patients; partial response: 5 patients). Median PFS was 5.0 months; 6- and 12-month progression-free rates were 46.4% and 36.5%, respectively. Median OS was not reached; 6-, 12-, and 24-month OS rates were 83.3%, 72.2%, and 55.1%, respectively. In post hoc analysis, patients with a tumor infiltrating CD8+ lymphocyte (CD8+ TIL) count ≥99 and/or programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥50 and lymphocyte count &gt;1,380 cells/μL had higher ORRs and prolonged PFS versus patients with a CD8+ TIL count &lt;99, PD-L1 CPS &lt;50, and lymphocyte count ≤1,380 cells/μL. Thirty-four (94.4%) patients receiving combination therapy experienced treatment-related adverse events (AE), with pyrexia (n = 15, 41.7%), injection-site reactions (n = 15, 41.7%), injection-site induration (n = 6, 16.7%), and malaise (n = 6, 16.7%) the most common. No grade ≥3 treatment-related AEs occurred in ≥10% of patients. TAS0313 plus pembrolizumab combination therapy showed promising efficacy and manageable safety in la/mUC.Clinical Trial Registration: JapicCTI-183824.
Signaling Pathway Alterations Driven by BRCA1 and BRCA2 Germline Mutations are Sufficient to Initiate Breast Tumorigenesis by the PIK3CAH1047R Oncogene
Authors: Bhat-Nakshatri Poornima , Khatpe Aditi S. , Chen Duojiao , Batic Katie , Mang Henry , Herodotou Christopher , McGuire Patrick C. , Xuei Xiaoling , Erdogan Cihat , Gao Hongyu , Liu Yunlong , Sandusky George , Storniolo Anna Maria , Nakshatri Harikrishna 
Published: December 2023

Abstract

Single-cell transcriptomics studies have begun to identify breast epithelial cell and stromal cell specific transcriptome differences between BRCA1/2 mutation carriers and non-carriers. We generated a single-cell transcriptome atlas of breast tissues from BRCA1, BRCA2 mutation carriers and compared this single-cell atlas of mutation carriers with our previously described single-cell breast atlas of healthy non-carriers. We observed that BRCA1 but not BRCA2 mutations altered the ratio between basal (basal-myoepithelial), luminal progenitor (luminal adaptive secretory precursor, LASP), and mature luminal (luminal hormone sensing) cells in breast tissues. A unique subcluster of cells within LASP cells is underrepresented in case of BRCA1 and BRCA2 mutation carriers compared with non-carriers. Both BRCA1 and BRCA2 mutations specifically altered transcriptomes in epithelial cells which are an integral part of NFκB, LARP1, and MYC signaling. Signaling pathway alterations in epithelial cells unique to BRCA1 mutations included STAT3, BRD4, SMARCA4, HIF2A/EPAS1, and Inhibin A signaling. BRCA2 mutations were associated with upregulation of IL6, PDK1, FOXO3, and TNFSF11 signaling. These signaling pathway alterations are sufficient to alter sensitivity of BRCA1/BRCA2-mutant breast epithelial cells to transformation as epithelial cells from BRCA1 mutation carriers overexpressing hTERT + PIK3CAH1047R generated adenocarcinomas, whereas similarly modified mutant BRCA2 cells generated basal carcinomas in NSG mice. Thus, our studies provide a high-resolution transcriptome atlas of breast epithelial cells of BRCA1 and BRCA2 mutation carriers and reveal their susceptibility to PIK3CA mutation-driven transformation.

Significance:
This study provides a single-cell atlas of breast tissues of BRCA1/2 mutation carriers and demonstrates that aberrant signaling due to BRCA1/2 mutations is sufficient to initiate breast cancer by mutant PIK3CA.
A Randomized Phase III Study of Arfolitixorin versus Leucovorin with 5-Fluorouracil, Oxaliplatin, and Bevacizumab for First-Line Treatment of Metastatic Colorectal Cancer: The AGENT Trial
Authors: Tabernero Josep , Yoshino Takayuki , Stintzing Sebastian , de Gramont Aimery , Gibbs Peter , Jonker Derek J. , Nygren Peter , Papadimitriou Christos , Prager Gerald W. , Tell Roger , Lenz Heinz-Josef 
Published: December 2023

Abstract

Purpose:
Suboptimal treatment outcomes with 5-fluorouracil (5-FU)/folate, the standard of care for metastatic colorectal cancer (mCRC), have generated interest in optimizing the folate. Arfolitixorin ([6R]-5,10-methylene-tetrahydrofolate) is an immediately active folate and may improve outcomes over the existing standard of care (leucovorin).

Experimental Design:
AGENT was a randomized, phase III study (NCT03750786). Patients with mCRC were randomized to arfolitixorin (120 mg/m2 given as two intravenous bolus doses of 60 mg/m2) or leucovorin (400 mg/m2 given as a single intravenous infusion) plus 5-FU, oxaliplatin, and bevacizumab. Assessments were performed every 8 weeks. The primary endpoint was the superiority of arfolitixorin for overall response rate (ORR).

Results:
Between February 2019 and April 2021, 490 patients were randomized (245 to each arm). After a median follow-up of 266 days, the primary endpoint of superiority for ORR was not achieved (48.2% for arfolitixorin vs. 49.4% for leucovorin, Psuperiority = 0.57). Outcomes were not achieved for median progression-free survival (PFS; 12.8 and 11.6 months, P = 0.38), median duration of response (12.2 and 12.9 months, P = 0.40), and median overall survival (23.8 and 28.0 months, P = 0.78). The proportion of patients with an adverse event of grade ≥3 severity was similar between arms (68.7% and 67.2%, respectively), as was quality of life. BRAF mutations and MTHFD2 expression were both associated with a lower PFS with arfolitixorin.

Conclusions:
The study failed to demonstrate clinical benefit of arfolitixorin (120 mg/m2) over leucovorin. However, it provides some useful insights from the first-line treatment setting, including the effect of gene expression on outcomes.

Significance:
This phase III study compared arfolitixorin, a direct-acting folate, with leucovorin in FOLFOX plus bevacizumab in mCRC. Arfolitixorin (120 mg/m2) did not improve the ORR, potentially indicating a suboptimal dose.
Bone impairment assessed by lumbar spine trabecular bone score (TBS) and HR-pQCT in male ankylosing spondylitis patients
Authors: Furlam Pedro Luis , Caparbo Valéria de Falco , Saad Carla Gonçalves Schahin , Pereira Rosa Maria Rodrigues 
Published: December 2023

Objectives. Low bone mineral density (BMD) and osteoporosis diagnosis in AS patients is based on data using dual-energy X-ray absorptiometry (DXA), which may be difficult to interpret due to the presence of syndesmophytes. The objective of this study is to evaluate bone mass and quality using areal (a) BMD, lumbar spine trabecular bone score (TBS) and HR-pQCT parameters in AS patients compared with healthy controls (HC). Methods. TBS and aBMD were evaluated using DXA. Volumetric bone mineral density (vBMD), bone microarchitecture and stiffness were analyzed at the distal tibia and radius using HR-pQCT. Seventy-three AS male patients and 52 agematched HC were evaluated. Results. Lower TBS values were observed in AS patients compared with HC (1.314 ± 0.121 vs. 1.396 ± 0.070, p<0.001); however, no difference was observed in lumbar spine aBMD between these two groups (1.080 ± 0.193 vs. 1.041 ± 0.118 g/cm2 , p=0.11). Lower trabecular vBMD (162.1 ± 39.6 vs. 186.8 ± 39.9 mg HA/cm3 , p<0.001), lower structural parameters Tb.Th (0.074 ± 0.012 vs. 0.080 ± 0.013 mm, p=0,044) and Tb.Sp (0.497 ± 0.110 vs. 0.448 ± 0.086 mm, p=0,039) and lower strength parameters stiffness (254250.8 ± 48477.7 vs. 291770.3 ± 52858.4 N/mm, p<0.001) and F.Load (12098.6 ± 2240. vs 13770.2 ± 2388.1 N, p=0,001) were observed in the trabecular compartment at the distal tibia in AS patients compared to HC. Conclusion. The lumbar spine TBS and HR-pQCT imaging measurements are superior technologies to detect impairment of bone mass and quality in AS patients compared to healthy subjects.
HDL preserves mitochondrial complex I activity during myocardial reperfusion injury
Authors: Barreto Joaquim , Bonilha Isabella , Busanello Estela , Petrucci Orlando , Vercesi Anibal , Sposito Andrei Carvalho 
Published: December 2023

Introduction. Myocardial reperfusion injury answers for half of final infarct size following myocardial infarction, although no effective therapy has yet been discovered. Modulation of mitochondrial activity stands as an attractive target, as its impairment following reperfusion impairs ATP generation and henceforth turns cardiac recovery less prone to occur. HDL reduced final infarct size in different ischemia-reperfusion injury models for unknown mechanisms. Whether this effect involves mitochondrial activity modulation is unknown. Hypothesis. HDL post-conditioning preserves mitochondrial activity. Methods. Hearts extracted from male adult Wistar rats were subjected to 35min of regional ischemia, followed by 90min of reperfusion in a Langendorff apparatus. HDL (200ug/mL) or saline solution (PBS) was administered during the 7 first minutes of reperfusion. Infarct size was determined as percentage of total ventricular area, considering area at risk (AAR) as the delineated by Evans Blue. Cardiac samples underwent high-resolution oxygraph, and maximal oxygen consumption rate was calculated after the addition of saturating concentrations of ADP (1mM). Mitochondrial viability and complex I activity were assessed by colorimetric assays. Statistical analysis. Data are mean ± standard error. Means were compared by Student`s t test and p value < 0,05 was considered significant. Results. Treatment with HDL improved cardiac recovery, as indicated by better recovery of LVDP and dP/dT, and reduction of coronary artery resistance in comparison to control group (30,5 vs. 46,7%, 26 vs. 54,7% and 144±30 Vs. 98±14mmHg/mL, respectively; p<0.01). Treatment with HDL reduced final infarct size by 30% in comparison to control (69.2±3.7% Vs. 49.2±13%; p<0.001). The HDL group showed higher ADP-stimulated oxygen consumption rate (7.1±2.2 Vs. 33.8±6.6pmol/s.mg; p<0.05; n=6) and greater complex I activity (12.7±4.2 vs. 30.7±4.4mOD/min; p<0.05; n=3 per group) compared to control, though mitochondrial content was comparable (1.1±0.8 vs. 1.1±0.8AU; n=3; ns). Conclusions. Ischemic postconditioning with HDL reduces infarct size and preserves complex I activity, improving myocardial recovery following reperfusion injury.
Exclusive abdominal lymphadenopathy as a rare presentation of sarcoidosis
Authors: Santos Matheus de Carvalho , Carvalho Ana Júlia Araujo de , Santos Helena Telles Furtado dos , Gomes Matheus Heringer , Rezende Thiago Arruda 
Published: December 2023

Introduction: Sarcoidosis is a systemic granulomatous disease. The disease’s immunopathogenic mechanism is the activation of a cell mediated immune response. Lung is the most affected organ, but up to 30% of patients can have extrapulmonary manifestations.Case report: A 21-year-old male presented with a history of nausea, vomiting after meals, epigastric and periumbilical pain for approximately 6 months. Hyporexia and loss of 35 kilograms in 7 months were present, in addition to intermittent low nocturnal fever. His computed tomography (CT) scan (Figure 1) of the abdomen showed the presence of multiple, enlarged mesenteric lymph nodes with homogenous shape, measuring up to 2.0 cm in diameter, extending from the upper abdomen to the pelvis. Histopathologic findings of these lymph nodes showed a sarcoid appearance (Figure 2). Lymphoma,tuberculosis and other infections were excluded through immunohistochemical analysis. Treatment with prednisone was started initially at a dose of 40mg a day and after 5 weeks the patient was asymptomatic. One year and three months after the onset of treatment, corticosteroid dose reduction was attempted 3 times, with all of them leading to disease relapses. Treatment was optimized with 60mg of prednisone (for 2 weeks) plus 100mg of azathioprine daily.Discussion: The prevalence of gastrointestinal system involvement with clinical manifestations is 0,1 to 0,9%. However, the incidence of subclinical involvement can be higher. Enlarged lymph nodes are present in approximately 30% of cases. Treatment is indicated in sarcoidosis for patients with damage organ function or symptomatic disease and the first-line therapy is corticosteroids
Hepatic angiosarcoma: a transdisciplinary case study
Authors: Arruda Vivian Nunes , Andrade Melissa de , Gonçalves Rhafir 
Published: December 2023

Hepatic Angiosarcoma is a rare malignancy of endothelial cell origin that is generally idiopathic and presents non-specific clinical manifestations. Hemoperitoneum can occur in 17-27% of cases and is a result of tumor rupture, which has a devastating prognosis. We present a 79-year-old female patient with history of diffuse right upper quadrant abdominal pain associated with syncope episodes and unintentional weight loss. Physical examination was unremarkable except for painful palpation of the right upper quadrant. Laboratory exams indicated chronic disease anemia, a 2.7 INR, decreased albumin,increased C-Reactive Protein and GGT, and normal AST, ALT, Alkaline Phosphatase and Bilirubin. Viral hepatitis serologies were negative. Abdominal ultrasonography revealed hepatomegaly and solid liver lesions of heterogeneous echogenicity and imprecise limits. Three-phase abdominal CT showed multiple liver masses of heterogeneous pattern of enhancement suggestive of atypical hemangioma associated with ascites. Chest CT revealed bilateral pulmonary nodules suggestive of metastasis. During hospital stay, the patient developed a massive hemoperitoneum that required emergency laparotomy. Inthis circumstance, liver and omentum biopsies were performed and the pathology reports ultimately indicated the possibility of hepatic angiosarcoma. The patient developed refractory hemoperitoneum and hemorrhagic shock and ultimately passed away, 48 days after hospital admission. Definitive diagnosis was only available posteriorly, with immunohistochemistry positivity for ERG, CD34 and Factor VIII-related antigen on both omentum and lung samples. This case study provides valuable clinical discussion and emphasizes how a transdisciplinary approach is essential to correctly diagnose and manage such complex cases.
How Society Anxiety Influences Attention Control in College Students: The Moderated Mediation Effect of Cognitive Flexibility and Resting-state Electroencephalography Activity
Authors: Wang Li , Sheng Jing , Duan Shumin , Lin Shuang , Li Yongjian , Li Zhe , Li Shuzhen , Sataer Yifutihaer , Chen Jun 
Published: December 2023

Abstract
Social anxiety is a prevalent issue among college students, adversely affecting their overall well-being. Drawing from the cognitive model of social anxiety and attention control theory, heightened levels of social anxiety may correspond to poorer attention control ability. However, little is known about the underlying cognitive mechanisms of the relationship between social anxiety and attention control. To address this research gap, the current study recruited a sample of 156 college students (56 women) who underwent self-report measures of social anxiety, cognitive flexibility, and attention control, followed by a resting-state EEG recording. The results revealed a significant negative predictive effect of social anxiety on attention control, with cognitive flexibility partially mediating this relationship. Furthermore, resting-state theta power emerged as a significant moderator, accentuating the negative impact of social anxiety on cognitive flexibility among individuals with lower theta power. In addition, frontal alpha asymmetry (FAA) demonstrated a moderating effect, with lower FAA intensifying the predictive influence of cognitive flexibility on attention control. Taken together, these results suggested that social anxiety can predict attention control either directly or indirectly via the mediating role of cognitive flexibility, and lower theta power and FAA has a risk amplification effect, which provide novel insights into the treatment and prevention of social anxiety and its negative impact on college students.
Sociocultural factors and academic openness of world countries
Authors: Khosrowjerdi Mahmood , Linhart Silje Hernæs 
Published: December 2023

Abstract
Academic openness (i.e., the extent of collaborative academic activities of nations with external actors in the science communication system) has been regarded as a major contributor to strong science. We used several nation-level data sets to explore the associations of sociocultural factors with the academic openness of world nations. To check the robustness of relationships, two distinct data sets for academic openness of nations were used in this research. Our findings showed the strong relationships of some dimensions of national culture and (economic and human) resources with both academic openness indicators. The findings were discussed considering Schwartz’s national culture theory, and the implications were presented in conclusion.
Scope and limitations of library metrics for the assessment of ebook usage: COUNTER R5 and link resolver
Authors: Echeverria Mercedes , Bustamante Yacelli 
Published: December 2023

Abstract
Data are at the heart of electronic resource management in academic libraries. Assessing the usage data of electronic resources has become a prevalent approach to demonstrate the value of digital collections, justify library expenditures, and gain insights into how users interact with library materials. This study analyzes the usage statistics of electronic books (ebooks) generated locally by the OpenURL link resolver in an academic library, and statistics collected by platform vendors based on Release 5 of the Counting Online Usage of Networked Electronic Resource (COUNTER R5). Three content provider platforms (Cambridge Core, EBSCOhost, and ScienceDirect) were analyzed as data sources. The COUNTER and link resolver statistics were examined to determine the degree of association between these two metrics. The Spearman correlation coefficient was moderate (rs &gt; 0.561 and &lt; 0.678) and statistically significant (p &lt; .01). This suggests that these metrics capture different aspects of the usage of ebooks in different contexts. Other factors, such as the types of access to electronic resources and the units of content delivered, were also examined. The study concludes with a discussion regarding the scope and limitations of link resolver and COUNTER R5 as library metrics for measuring the usage of ebooks.
Uncovering Risk Factors and Outcomes of Pulmonary Embolism in a Nationwide Cohort of Hospitalized Children
Authors: Huerta Carlos Theodore , Ramsey Walter A. , Rodriguez Cindy , Parreco Joshua P. , Thorson Chad M. , Sola Juan E. , Perez Eduardo A. 
Published: December 2023

Purpose The incidence of pulmonary embolism (PE) in hospitalized children has increased in recent years. This study sought to characterize factors and outcomes associated with PE using a national pediatric cohort. Methods The Nationwide Readmissions Database was queried (2016-2018) for patients (<18 years) with a diagnosis of PE. Index and prior hospitalizations (PHs) within 1 year were analyzed. A binary logistic regression utilizing 37 covariates (demographics, procedures, comorbidities, etc.) was constructed to examine a primary outcome of in-hospital mortality. Results 3440 patients were identified (57% female) with the majority >12 years old (77%). One-third had a known deep vein thrombosis (69% lower and 31% upper extremity). Nineteen percent underwent central venous catheter (CVC) placement. Twenty-one percent had a PH within 1 year. Nine percent underwent an operation with the majority being cardiothoracic (5%). Overall mortality was 5%. Neurocranial surgery, cardiothoracic surgery, and CVC placement were associated with the highest odds of inpatient mortality after logistic regression. Conclusion Pediatric patients with PE have a high rate of PHs, CVC placement, and inpatient operations, which may be associated with higher mortality. This information can be utilized to improve screening measures and clinical suspicion for PE in hospitalized children.