bluuebunny/crossref_metadata_2025_split huggingface dataset:
Presence of TMD-related pain and symptoms associated with anxiety in Peruvian students in their final years of dental education: an analytical cross-sectional study under a multivariable regression model
Authors: Angeles-García Karen , Ladera-Castañeda Marysela , Castro-Ramirez Leonor , Paucar-Rodríguez Elizabeth , Castro-Rojas Miriam , Cervantes-Ganoza Luis , Cayo-Rojas César 
Published: February 2025

Abstract

Background
Temporomandibular disorders (TMD) are frequently associated with anxiety, as this can increase the hyperactivity of the masticatory muscles, resulting in TMD-related pain and symptoms. The aim of this study was to assess the presence of TMD-related pain and symptoms associated with anxiety levels in Peruvian students in their final years of dental education.

Methods
This analytical cross-sectional study of 273 Peruvian students in the final two years of dental education was conducted from October to December 2023. The Zung test was employed to diagnose anxiety, while the TMD-Pain Screener questionnaire was utilized to diagnose painful temporomandibular disorders (TMD). A Poisson regression model with robust variance using Adjusted Prevalence Ratio (APR) was employed to assess the prevalence of TMD-related pain and symptoms. The following variables were considered in the analysis: anxiety, sex, age, academic year, marital status, area of residence, type of housing, living with parents, and occupation. All statistical tests were conducted with a significance level of p < 0.05.

Results
The prevalence of TMD-related pain and symptoms was 24.5%. The 0.7% of the sample exhibited very extreme levels of anxiety; 8.1% demonstrated severe anxiety; and 39.9% exhibited mild to moderate anxiety. Furthermore, dental students with severe to very extreme anxiety and with mild to moderate anxiety were 8.2 times and 3.8 times, respectively, more likely to present TMD-related pain and symptoms (APR = 8.18, 95% CI: 4.62–14.47 and APR = 3.84, 95% CI: 2.18–6.75, respectively), compared to those who did not have anxiety. Conversely, no significant association was observed between the presence of TMD-related pain and symptoms and sex, age, academic year, marital status, area of residence, type of housing, living with parents, or occupation (p > 0.05).

Conclusion
Almost a quarter of the students in their final years of dental education had TMD-related pain and symptoms. It was found that as the level of anxiety increased, from mild to moderate and from severe to very extreme, the likelihood of experiencing TMD-related pain and symptoms also increased significantly. On the other hand, gender, age, academic year, marital status, area of residence, type of housing, living with parents or occupation were not found to be influential factors in the presence of TMD-related pain and symptoms.
A whole-body atlas of BMP signaling activity in an adult sea anemone
Authors: Knabl Paul , Mörsdorf David , Genikhovich Grigory 
Published: February 2025

Abstract

Background
BMP signaling is responsible for the second body axis patterning in Bilateria and in the bilaterally symmetric members of the bilaterian sister clade Cnidaria—corals and sea anemones. However, medusozoan cnidarians (jellyfish, hydroids) are radially symmetric, and yet their genomes contain BMP signaling components. This evolutionary conservation suggests that BMP signaling must have other functions not related to axial patterning, which keeps BMP signaling components under selective pressure.

Results
To find out what these functions might be, we generated a detailed whole-body atlas of BMP activity in the sea anemone Nematostella. In the adult polyp, we discover an unexpected diversity of domains with BMP signaling activity, which is especially prominent in the head, as well as across the neuro-muscular and reproductive parts of the gastrodermis. In accordance, analysis of two medusozoan species, the true jellyfish Aurelia and the box jellyfish Tripedalia, revealed similarly broad and diverse BMP activity.

Conclusions
Our study reveals multiple, distinct domains of BMP signaling in Anthozoa and Medusozoa, supporting the versatile nature of the BMP pathway across Cnidaria. Most prominently, BMP signaling appears to be involved in tentacle formation, neuronal development, and gameto- or gonadogenesis.
The extracellular matrix protein type I collagen and fibronectin are regulated by β-arrestin-1/endothelin axis in human ovarian fibroblasts
Authors: Masi Ilenia , Ottavi Flavia , Caprara Valentina , Rio Danila Del , Kunkl Martina , Spadaro Francesca , Licursi Valerio , Tuosto Loretta , Bagnato Anna , Rosano’ Laura 
Published: February 2025

Abstract

Background
The invasive and metastatic spread of serous ovarian cancer (SOC) results from the cooperative interactions between cancer and stroma, which include extracellular matrix (ECM) and cellular components, including cancer-associated fibroblasts (CAFs). Soluble factors secreted by cancer and stromal cells contribute to stroma remodeling through the secretion of ECM proteins, providing a favorable environment for cancer cell dissemination. The peptide endothelin-1 (ET-1), through two G protein-coupled receptors (GPCR), endothelin receptor type A (ETAR) and B (ETBR), acts on both cancer and stromal cells, engaging the protein β-arrestin1 (β-arr1), to bolster SOC progression. However, its role in the regulation of the ECM proteins by ovarian fibroblasts is not understood. This study delves into the role of ET-1 as a regulator of type I collagen (Col1) and fibronectin (FN).

Methods
We used human primary ovarian fibroblasts (HOFs) and CAFs. The expression of Col1 (COL1A1) and FN (FN1) were detected by western blotting (WB), quantitative real time-polymerase chain reaction (qRT-PCR), immunofluorescence (IF), and confocal laser scanning microscopy (CLSM) in cells and tumor tissue sections from mice xenografts, while the transcription of COL1A1 was detected by luciferase reporter gene assay. The nuclear function of β-arr1 was evaluated by silencing and rescue expression with wild-type (WT) and nuclear mutant plasmid constructs, RNA seq and differential gene expression and gene sets enrichment analyses. The prognostic role of COL1A1, FN1, EDN1 (ET-1) and ARRB1 (β-arr1) gene expression was evaluated using the Kaplan–Meier plotter database and clinical ovarian cancer tissue samples.

Results
We demonstrated that ET-1 boosts Col1 and FN expression in HOFs, akin to ovarian CAF levels. Both receptors are implicated, evident from inhibitory effects after ETAR or ETBR antagonist treatments and notably with bosentan, a dual antagonist, in vitro and in vivo. At the molecular level, ET-1 triggers the activation of COL1A1 promoter activity and its enhanced expression via β-arr1 nuclear function. Transcriptome analysis of β-arr1-silenced HOFs confirms the nuclear role of β-arr1 in collagen and ECM remodeling-related protein transcriptional regulation. Accordingly, a high level of EDN1/ARRB1 expression in combination with either COL1A1 or FN1 is associated with the poor prognosis of SOC patients.

Conclusions
These findings hint at ET-1 involvement in ECM remodeling and early SOC stages by modulating the expression of Col1 and FN. Targeting ET-1 signaling with ETAR/ETBR antagonists might interfere with the ability of CAFs to produce key ECM proteins in this tumor.
A blue blood toddler– a case report of methemoglobinemia and literature review
Authors: Pjetraj Dorina , Mechri Madiha El , Bacelli Silvia , Fabiani Elisabetta , Caponi Laura , Gatti Simona , Lionetti Elena 
Published: February 2025

Abstract

Background
Methemoglobinemia (MetHb) is a rare and potentially life-threatening condition caused by oxidation of ferrous hemoglobin (Fe2+) to the ferric (Fe3+) state, making it incapable of binding oxygen and resulting in cyanosis and tissue ischemia.

Case presentation
This case presentation describes a 1-year-old boy who developed sudden cyanosis and reduced consciousness disorder. An initial assessment showed decreased oxygen saturation (SpO2 85%) despite oxygen therapy, while point-of-care venous blood gas (VBG) analysis assessed high rates of MetHb (72.7%). Methylene blue and ascorbic acid were administered, resulting in in rapid clinical recovery and normalized VBG test results. The trigger for this condition was not identified, however the most likely cause of poisoning was attributed to food oxidants.

Conclusion
Starting from the description of a clinical case, this paper discusses the causes and mechanisms of possible poisoning and reviews recent guidelines for methemoglobinemia management.
Establishment and validation of risk prediction model to predict intravenous immunoglobulin-resistance in Kawasaki disease based on meta-analysis of 15 cohorts
Authors: Wang Shuhui , Sun Na , Liu PanPan , Qian Weiguo , Xu Qiuqin , Yang DaoPing , Zhang Mingyang , Hou Miao , Chen Ye , Qian Guanghui , Gao Chunmei , Sun Ling , Lv Haitao 
Published: February 2025

Abstract

Background
Pediatric Kawasaki disease (KD) patients showing resistance to intravenous immunoglobulin (IVIG) are at risk of coronary artery lesions; thus, early prediction of IVIG resistance is particularly important. Herein, we aimed to develop and verify a novel predictive risk model for IVIG resistance in KD based on meta-analyses.

Methods
PubMed, Embase, and Web of Science databases were searched for cohort studies on the risk factors for IVIG resistance from January 2006 to December 2022. Data were extracted from the screened literature, followed by quality assessment using the Newcastle-Ottawa scale. meta-analyses used Stata 17.0 software to extract the risk factors with significant combined effect sizes and combined risk values, followed by logistic regression prediction model construction. The model was prospective validated using data from 1007 pediatric KD cases attending the Children’s Hospital of Soochow University. The model’s predictive ability was assessed using the Hosmer–Lemeshow test and area under the receiver operating characteristic curve (AUC) and the clinical utility was assessed using decision curve analysis(DCA).

Results
Fifteen cohort studies reporting 4273 patients with IVIG resistance were included. The incidence of IVIG resistance was 16.2%. Six risk factors were reported ≥ 3 times with significant results for the combined effect size: male sex, rash, cervical lymphadenopathy, % neutrophils ≥ 80%, Age ≤ 12 months and platelet count ≤ 300 × 109/L. The logistic scoring model had 83.8% specificity, 70.4% sensitivity, and an optimal cut-off value of 23.500.

Conclusion
The risk prediction model for IVIG resistance in KD showed a good predictive performance, and pediatricians should pay high attention to these high-risk patients and develop an appropriate individual regimens to prevent coronary complications.
Analysis of informed consent forms of patients undergoing cancer genetic testing in the era of next-generation sequencing
Authors: Kerševan Tina , Kogovšek Tina , Blatnik Ana , Krajc Mateja 
Published: February 2025

Abstract

Background
The Department of Clinical Cancer Genetics at the Institute of Oncology Ljubljana offers genetic counselling and testing to cancer patients and their relatives. Before undergoing genetic testing, patients sign the informed consent form. In addition to giving consent for collection of biological material and genetic testing, patients decide about storage of biological material and participation in international databases. Furthermore, patients decide whether the information regarding their test results may be revealed to their blood relatives and whether they want to be informed about secondary findings.

Methods
Using the signed consent forms, we investigated the effect of selected factors on patients’ decisions. Using different statistical methods, we tried to determine the proportion of patients who opted for different items and the effect of gender, age and cancer diagnoses on their decisions.

Results
Nearly all (99.6%) patients, regardless of gender, age, and presence of oncological diagnosis, consented to the storage of their biological material, 98.4% of patients, regardless of gender, age, and presence of oncological diagnosis, wanted to be included in international databases in a pseudo-anonymised form, 98.8% of patients, irrespective of gender, age, and presence of oncological diagnosis, allowed blood relatives to see their results, and 98.4% of patients, irrespective of gender, age and presence of oncological diagnosis, wanted to know whether secondary findings were detected when genetic analysis of their biological material was performed. Men are, on average, more likely to consent but the difference between genders is not statistically significant. Patients without oncological disease were more likely to agree to be included in international databases than patients with a confirmed oncological diagnosis.

Conclusions
Our results show that the vast majority of patients were in favour of the options they were offered. Most importantly, the majority of them allow their genetic test results be revealed to their blood relatives when needed and would participate in international databases. Research in rare diseases, including rare cancer genetic predisposition syndromes, is crucial for optimal diagnostic, prevention and treatment options for patients with rare genetic disorders. The results are also important for refining the approach to pre-and post-test cancer genetic counselling.
Timing of menarche and menopause and epigenetic aging among U.S. adults: results from the National Health and Nutrition Examination Survey 1999–2002
Authors: Daredia Saher , Khodasevich Dennis , Gladish Nicole , Shen Hanyang , Nwanaji-Enwerem Jamaji C. , Bozack Anne K. , Needham Belinda L. , Rehkopf David H. , Deardorff Julianna , Cardenas Andres 
Published: February 2025

Abstract
Reproductive aging, including timing of menarche and menopause, influences long-term morbidity and mortality in women, yet underlying biological mechanisms remain poorly understood. Using DNA methylation-based biomarkers, we assessed associations of age at menarche (N = 1,033) and menopause (N = 658) with epigenetic aging in a nationally representative sample of women ≥ 50 years. Later age at menopause was associated with lower GrimAge epigenetic age deviation (

$$B$$

B

= − 0.10 years, 95% CI: − 0.19, − 0.02). No associations were observed for menarche timing. This suggests a connection between earlier menopause and biological aging, with potential clinical implications for identifying those at high risk for age-related disease.
Hereditary multiple exostoses: an educational review
Authors: Rueda-de-Eusebio Alvaro , Gomez-Pena Sara , Moreno-Casado María José , Marquina Gloria , Arrazola Juan , Crespo-Rodríguez Ana María 
Published: February 2025

Abstract
Hereditary multiple exostoses (HME), an autosomal dominant disorder with an incidence of 1:50,000 to 1:100,000, is characterised by the formation of multiple osteochondromas arising from the metaphyses of long and flat bones. These osteochondromas often present as painless palpable lumps, though some cases are symptomatic due to mechanical compression or bursitis. Diagnosis of HME is typically clinical and radiological. WHO diagnostic criteria include ≥ 2 radiological osteochondromas in the juxta-epiphyseal region of the long bones. Genetic testing is reserved for ambiguous cases. HME is associated with mutations in the EXT-1 (exostosin-1) and EXT-2 (exostosin-2) genes. Imaging techniques, including conventional radiography, CT, MRI, ultrasound, and nuclear medicine, play a crucial role in diagnosing and assessing HME, with each modality offering distinct advantages in visualising the lesions and associated complications. Common complications include skeletal deformities, fractures, bursitis, as well as neural and vascular abnormalities. Notably, there is a 10% risk of malignant transformation into secondary chondrosarcoma in HME patients, compared to only a 1% risk in those with solitary osteochondromas. Malignant transformation should be suspected in patients with new-onset pain or specific imaging features in an osteochondroma, such as growth of de cartilaginous cap. In these cases, an MRI should be performed to assess the cartilage cap thickness. Advances in imaging techniques and genetic understanding have improved the management and prognosis of HME. Follow-up is essential to rule out malignant transformation. This review summarises current knowledge on the clinical presentation, pathogenesis, imaging characteristics, complications, and treatment of HME.

Critical relevance statement
HME is a disorder characterised by the formation of osteochondromas arising from long and flat bones. Multi-modality imaging characteristics, clinical presentation, complications, and treatment are highlighted to familiarise the readers with this entity and offer optimal patient care.

Key Points

HME is characterised by multiple osteochondromas on long and flat bones.

Imaging for HME includes radiography, CT, MRI, ultrasound, and nuclear medicine studies.

Complications include non-malignant complications, such as bone deformities and malignant transformation.

Cartilage-cap measurement with MRI or US is key to exclude malignancy.

Follow-up is essential to rule out malignant transformation of the osteochondromas.

Graphical Abstract
Gain of 20q11.21 in human pluripotent stem cells enhances differentiation to retinal pigment epithelium
Authors: Vitillo Loriana , Anjum Fabiha , Hewitt Zoe , Laing Owen , Ababneh Nidaa A. , Baker Duncan , Barbaric Ivana , Coffey Peter J. 
Published: February 2025

Abstract

Background
Cell therapies based on human pluripotent stem cells (hPSCs) are in clinical trials with the aim of restoring vision in people with age-related macular degeneration. The final cell therapy product consists of retinal pigment epithelium (RPE) cells differentiated from hPSCs. However, hPSCs recurrently acquire genetic abnormalities that give them an advantage in culture with unknown effects to the clinically-relevant cell progeny. One of the most common genetic abnormalities in hPSCs is the sub-karyotype 20q11.21 copy number variant, known to carry oncogenes. Understanding the impact of this variant on RPE differentiation and its potential for malignant transformation is crucial for the development of safe and effective cell therapies.

Methods
We monitored the RPE differentiation efficiency of hPSCs with or without the 20q11.21 variant. We then phenotyped the purified RPE cells for functionality, purity and tumorigenicity potential.

Results
We observed that 20q11.21 clones exhibited an enhanced differentiation capacity, developing pigmented foci at a higher rate and yield compared to normal clones. Gene expression analysis confirmed the upregulation of key RPE markers in 20q11.21 clones. The enhanced differentiation capacity of 20q11.21 clones was found to be dependent on the activity of BCL-XL, located within the amplicon. Furthermore, we demonstrated that 20q11.21-containing RPE cells displayed a mature phenotype, maintained long-term stability, and exhibited no malignant transformation capacity in vitro.

Conclusion
We demonstrated that gain of 20q11.21 enhances the speed and yield of RPE differentiation without compromising the phenotype of the derivatives. Finally, we discovered that 20q11.21-localised BCL-XL is important for RPE differentiation with potential non-canonical roles in retinal biology.
Implementing intranasal povidone-iodine in the orthopedic trauma surgery setting to prevent surgical site infections: a qualitative study of healthcare provider perspectives
Authors: Racila AM , Balkenende Erin C. , Herwaldt Loreen A. , Willey Michael C. , Boyken Linda D. , Pottinger Jean G. , Ayers Brennan S. , Dukes Kimberly C. , Ward Melissa A. , Schweizer Marin L. 
Published: February 2025

Abstract

Background
Surgical site infections (SSIs) are associated with morbidity, mortality, and increased costs. Staphylococcus aureus is the most common cause of SSIs and approximately 30% of hemodialysis patients carry this organism in their nares. Unlike mupirocin, intranasal povidone-iodine (PVI) is applied only the day of surgery to prevent surgical site infections. Thus, intranasal PVI could be valuable in orthopedic trauma surgery settings where time to prepare a patient for surgery is limited.

Methods
We conducted a small phase IV post-marketing study from 2020 to 2021 in an academically affiliated hospital wherein staff administered intranasal PVI pre- and post-operatively to consenting patients undergoing orthopedic fixation procedures for traumatic fractures. Before implementing the PVI intervention, we conducted a human factors task analysis to determine the optimal time and hospital location to perform PVI decolonization for patients receiving these orthopedic fixation procedures. After the post-marketing study was completed, we conducted qualitative interviews with healthcare staff to determine barriers and facilitators that could affect staff members’ likelihood of administering PVI to patients. We aligned our inductive interview findings with strategies defined in Powell and colleagues’ Expert Recommendations for Implementing Change (ERIC) framework to facilitate generalizability and standardized reporting of implementation strategies.

Results
Our human factors task analysis identified the Day of Surgery Admissions (DOSA) as the appropriate context for PVI administration within surgical workflow, as there was downtime during this period and direct patient-provider communication could occur. Two DOSA nurses, one postoperative nurse, and one orthopedic trauma surgeon agreed to be interviewed. Facilitators of intranasal PVI administration included emphasizing the non-invasiveness of PVI nasal swabs to patients and emphasizing intranasal PVI efficacy to staff and patients. While the nurse participants felt that having PVI orders with other medication orders in the EMR helped them identify patients enrolled in the study and who required PVI, entering these orders increased the surgeon’s workflow and presented a time barrier.

Conclusions
Macro- and micro-level contextual factors should be considered when tailoring implementation to healthcare settings. Our findings reinforce prior work demonstrating the value of incorporating human factors engineering methodologies into infection control and prevention implementation approaches.