bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gestational trophoblastic neoplasia with primary lung cancer and mesenchymal tumor of sigmoid colon: a case report and literature review
Authors: Li HongYe , Sun Meng , Jiang Jing , Shi Bin , Wang BaoHua , Wang Lei , Wu WenXin , Wang WenYan 
Published: February 2023

Abstract
Background
Gestational trophoblastic neoplasia (GTN) is rare, and it is even rarer for GTN to merge with primary malignant tumors in other organs. Herein is described a rare clinical case of GTN combined with primary lung cancer and mesenchymal tumor of the sigmoid colon, followed with literature review.

Case presentation
The patient was hospitalized due to diagnosis of GTN with primary lung cancer. Firstly, two cycles of chemotherapy including 5-fluorouracil (5-FU) and actinomycin-D(Act-D) was given. Laparoscopic total hysterectomy and right salpingo-oophorectomy was performed during the third chemotherapy. During the operation, a 3*2 cm nodule was removed which was protruded from the serous surface of the sigmoid colon, and the nodule was confirmed mesenchymal tumor pathologically, in accord with gastrointestinal stromal tumor. During the treatment of GTN, Icotinib tablets were taken orally to control the progression of lung cancer. After 2 cycles of consolidation chemotherapy of GTN, she received thoracoscopic lower lobe of right lung lobectomy and the mediastinum lymph nodes removal. She undertook gastroscopy and colonoscopy and the tubular adenoma of the descending colon was removed. At present, the regular follow-up is taken and she remains free of tumors.

Conclusions
GTN combined with primary malignant tumors in other organs are extremely rare in clinical practice. When imaging examination reveals a mass in other organs, clinicians should be aware of the possibility of a second primary tumor. It will increase the difficulty of GTN staging and treatment. We emphasis the importance of the collaboration of multidisciplinary teams. Clinicians should choose a reasonable treatment plan according to the priorities of different tumors.
Efficacy and safety of topical 0.1% cannabidiol for managing recurrent aphthous ulcers: a randomized controlled trial
Authors: Umpreecha Chalapinyo , Bhalang Kanokporn , Charnvanich Dusadee , Luckanagul Jittima 
Published: February 2023

Abstract
Background
Although topical steroids constitute the first-line therapy for recurrent aphthous ulcers (RAUs), their long-term use often leads to candidiasis. Although cannabidiol (CBD) can be an alternative for pharmacologically managing RAUs due to its analgesic and anti-inflammatory in vivo effects, there is a lack of clinical and safety trials concerning its use. The aim of this study was to evaluate the clinical safety and efficacy of topical 0.1% CBD for managing RAU.

Methods
A CBD patch test was performed on 100 healthy subjects. CBD was applied on the normal oral mucosa of 50 healthy subjects 3 times/day for 7 days. Oral examination, vital signs, and blood tests were performed pre- and post-CBD use. Another 69 RAU subjects randomly received one of three topical interventions: 0.1% CBD, 0.1% triamcinolone acetonide (TA), or placebo. These were applied on the ulcers 3 times/day for 7 days. The ulcer and erythematous size were measured on day 0, 2, 5, and 7. Pain ratings were recorded daily. The subjects rated their satisfaction with the intervention and completed a quality-of-life questionnaire (OHIP-14).

Results
None of the subjects exhibited allergic reactions or side effects. Their vital signs and blood parameters were stable before and after the 7-day CBD intervention. CBD and TA significantly reduced ulcer size more than placebo at all time points. The erythematous size reduction was higher in the CBD intervention than the placebo on day 2, while TA reduced the erythematous size at all time points. The pain score in the CBD group was lower compared with placebo on day 5, whereas TA reduced pain more than placebo on day 4, 5, and 7. The subjects receiving CBD reported higher satisfaction than placebo. However, the OHIP-14 scores were comparable among the interventions.

Conclusions
Topical 0.1% CBD reduced ulcer size and accelerated ulcer healing without side effects. CBD exerted anti-inflammatory effects in the early stage and an analgesic effect in the late RAU stage. Thus, topical 0.1% CBD might be more appropriate for RAU patients who decline to take topical steroids, except for cases where CBD is contraindicated.

Trial registration
Thai Clinical Trials Registry (TCTR) Number TCTR20220802004. Retrospectively registered on 02/08/2022.
Empathy levels among health professional students at a large midwestern public university - a cross-sectional study
Authors: Wenger Kelsey , Reist Lauren , Achenbach Andrea , Dukes Kimberly , Fravel Michelle , Knockel Laura , Kuehnle Francis , Reist Jeffrey , Suneja Manish , Pendleton Chandler , Xie Xian Jin , Marchini Leonardo 
Published: February 2023

Abstract
Background
Empathic care is considered extremely important by patients and providers alike but there is still an ample need for assessing empathy among healthcare students and professionals and identifying appropriate educational interventions to improve it. This study aims to assess empathy levels and associated factors among students at different healthcare colleges at the University of Iowa.

Methods
An online survey was delivered to healthcare students, including nursing, pharmacy, dental, and medical colleges (IRB ID #202,003,636). The cross-sectional survey included background questions, probing questions, college-specific questions, and the Jefferson Scale of Empathy-Health Professionals Student version (JSPE-HPS). To examine bivariate associations, Kruskal Wallis and Wilcoxon rank sum tests were used. A linear model with no transformation was used in the multivariable analysis.

Results
Three hundred students responded to the survey. Overall JSPE-HPS score was 116 (± 11.7), consistent with other healthcare professional samples. There was no significant difference in JSPE-HPS score among the different colleges (P = 0.532).

Conclusion
Controlling for other variables in the linear model, healthcare students’ view of their faculty’s empathy toward patients and students’ self-reported empathy levels were significantly associated with students’ JSPE-HPS scores.
Factors affecting the transition to adulthood of Korean young adults with spina bifida: a qualitative study
Authors: Choi Eun Kyoung , Park Jisu , Kim Kyua , Bae Eunjeong , Ji Yoonhye , Yang Seung Hyeon , Chinbayar Altantuya , Yun Hyeseon 
Published: February 2023

Abstract
Background
Transition to adulthood to live independently while self-managing health and daily life without parental help is crucial for young adults with chronic conditions. Despite its importance as a precursor to effectively managing lifelong conditions, little is known about the experiences of young adults with spina bifida (SB) in transition to adulthood in Asian countries. This study aimed to explore the experiences of Korean young adults with SB to identify the facilitators or barriers to the transition from adolescence to adulthood from their perspectives.

Methods
This study used a qualitative descriptive design. The data were collected in South Korea through three focus group interviews with 16 young adults with SB, aged 19–26, from August to November 2020. We conducted a qualitative content analysis using a conventional approach to identify the factors that facilitated and hindered the participants’ transition to adulthood.

Results
Two themes emerged as facilitators and barriers to the transition to adulthood. a) Facilitators: understanding and acceptance of SB, acquiring self-management skills, parenting styles encouraging autonomy, parents’ emotional support, school teachers’ thoughtful consideration, and participation in self-help groups. b) Barriers: overprotective parenting style, experience of being bullied by peers, damaged self-concept, concealing one’s chronic condition from others, and the lack of privacy in school restrooms.

Conclusions
Korean young adults with SB shared their experiences of struggling to properly manage their chronic conditions on their own, particularly concerning regular bladder emptying, during the transition from adolescence to adulthood. To facilitate the transition to adulthood, education on the SB and self-management for adolescents with SB and on parenting styles for their parents are important. To eliminate barriers to the transition to adulthood, improving negative perceptions of disability among students and teachers and making school restrooms CIC-friendly are needed.
Monocyte, neutrophil, and whole blood transcriptome dynamics following ischemic stroke
Authors: Carmona-Mora Paulina , Knepp Bodie , Jickling Glen C. , Zhan Xinhua , Hakoupian Marisa , Hull Heather , Alomar Noor , Amini Hajar , Sharp Frank R. , Stamova Boryana , Ander Bradley P. 
Published: February 2023

Abstract
Background
After ischemic stroke (IS), peripheral leukocytes infiltrate the damaged region and modulate the response to injury. Peripheral blood cells display distinctive gene expression signatures post-IS and these transcriptional programs reflect changes in immune responses to IS. Dissecting the temporal dynamics of gene expression after IS improves our understanding of immune and clotting responses at the molecular and cellular level that are involved in acute brain injury and may assist with time-targeted, cell-specific therapy.

Methods
The transcriptomic profiles from peripheral monocytes, neutrophils, and whole blood from 38 ischemic stroke patients and 18 controls were analyzed with RNA-seq as a function of time and etiology after stroke. Differential expression analyses were performed at 0–24 h, 24–48 h, and >48 h following stroke.

Results
Unique patterns of temporal gene expression and pathways were distinguished for monocytes, neutrophils, and whole blood with enrichment of interleukin signaling pathways for different time points and stroke etiologies. Compared to control subjects, gene expression was generally upregulated in neutrophils and generally downregulated in monocytes over all times for cardioembolic, large vessel, and small vessel strokes. Self-organizing maps identified gene clusters with similar trajectories of gene expression over time for different stroke causes and sample types. Weighted Gene Co-expression Network Analyses identified modules of co-expressed genes that significantly varied with time after stroke and included hub genes of immunoglobulin genes in whole blood.

Conclusions
Altogether, the identified genes and pathways are critical for understanding how the immune and clotting systems change over time after stroke. This study identifies potential time- and cell-specific biomarkers and treatment targets.
The hepato-ovarian axis: genetic evidence for a causal association between non-alcoholic fatty liver disease and polycystic ovary syndrome
Authors: Liu Dong , Gao Xue , Pan Xiong-Fei , Zhou Tao , Zhu Cairong , Li Fei , Fan Jian-Gao , Targher Giovanni , Zhao Jian 
Published: February 2023

Abstract
Background
Recent studies found associations between non-alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS), but the causal nature of this association is still uncertain.

Methods
We performed a bidirectional two-sample Mendelian randomization (MR) analysis to test for the causal association between NAFLD and PCOS using data from a large-scale biopsy-confirmed NAFLD genome-wide association study (GWAS) (1483 cases and 17,781 controls) and PCOS GWAS (10,074 cases and 103,164 controls) in European ancestries. Data from glycemic-related traits GWAS (in up to 200,622 individuals) and sex hormones GWAS (in 189,473 women) in the UK Biobank (UKB) were used in the MR mediation analysis to assess potential mediating roles of these molecules in the causal pathway between NAFLD and PCOS. Replication analysis was conducted using two independent datasets from NAFLD and PCOS GWASs in the UKB and a meta-analysis of data from FinnGen and the Estonian Biobank, respectively. A linkage disequilibrium score regression was conducted to assess genetic correlations between NAFLD, PCOS, glycemic-related traits, and sex hormones using full summary statistics.

Results
Individuals with higher genetic liability to NAFLD were more likely to develop PCOS (OR per one-unit log odds increase in NAFLD: 1.10, 95% CI: 1.02–1.18; P = 0.013). Indirect causal effects of NAFLD on PCOS via fasting insulin only (OR: 1.02, 95% CI: 1.01–1.03; P = 0.004) and further a suggestive indirect causal effect via fasting insulin in concert with androgen levels were revealed in MR mediation analyses. However, the conditional F statistics of NAFLD and fasting insulin were less than 10, suggesting likely weak instrument bias in the MVMR and MR mediation analyses.

Conclusions
Our study suggests that genetically predicted NAFLD was associated with a higher risk of developing PCOS but less evidence for vice versa. Fasting insulin and sex hormones might mediate the link between NAFLD and PCOS.
Association between low-density lipoprotein cholesterol and sudden cardiac arrest in people with diabetes mellitus
Authors: Kim Yun Gi , Jeong Joo Hee , Han Kyung-Do , Roh Seung-Young , Min Kyongjin , Lee Hyoung Seok , Choi Yun Young , Shim Jaemin , Choi Jong-Il , Kim Young-Hoon 
Published: February 2023

Abstract
Background
Dyslipidemia measured as low-density lipoprotein (LDL)-cholesterol is an established risk factor of cardiovascular disease, which is more pronounced in diabetes population. Less is known about the association of LDL-cholesterol level and sudden cardiac arrest (SCA) risk in diabetes mellitus patients. This study investigated the association of LDL-cholesterol level and SCA risk in diabetes population.

Methods
This study was based on Korean National Health Insurance Service database. Patients who received general examination from 2009 to 2012 and diagnosed as type 2 diabetes mellitus were analyzed. Primary outcome was defined as SCA event identified with International Classification of Disease code.

Results
A total of 2,602,577 patients were included, with total follow-up duration of 17,851,797 person * year. Mean follow-up duration was 6.86 years, and 26,341 SCA cases were identified. Overall incidence of SCA was highest in the lowest LDL-cholesterol group (< 70 mg/dL) and decreased in a linear manner as LDL-cholesterol rises, till 160 mg/dL. Adjustment of covariates resulted in U-shape association, with highest risk of SCA in the highest LDL-cholesterol group (≥ 160 mg/dL) followed by lowest LDL-cholesterol group (< 70 mg/dL). In subgroup analysis, U-shape association between SCA risk and LDL-cholesterol was more pronounced in male, non-obese people, and those who did not use statins.

Conclusions
In people with diabetes, the association between SCA and LDL-cholesterol level was U-shaped with highest and lowest LDL-cholesterol group having higher risk of SCA than others. Low LDL-cholesterol level can be a surrogate marker for increased risk of SCA in people with diabetes mellitus and this paradoxical association should be recognized and extended to clinical preventive measures.
The role of fatty acid desaturase 2 in multiple tumor types revealed by bulk and single-cell transcriptomes
Authors: Chen Enli , Wang Cong , Lv Hongwei , Yu Jing 
Published: February 2023

Abstract
Background
Previous studies have demonstrated the important role of fatty acid desaturase 2 (FADS2) in governing tumorigenesis and tumor metastasis. Although FADS2 is an essential regulator of fatty acid metabolism, its prognostic and immunotherapeutic value remains uncertain.

Methods
The role of FADS2 was investigated across different types of tumors. Besides, the relationship between FADS2 and survival prognosis, clinicopathologic features, tumor-infiltrating immune cells, immunoregulatory genes, chemokines, chemokines receptor, tumor mutational burden (TMB), and microsatellite instability (MSI) was also explored. FADS2-related genes enrichment analysis was performed to further explore the molecular function of FADS2. Finally, the relationship between FADS2 expression and altered functional states in single-cell levels across different tumor cells was explored.

Results
FADS2 was increased in most tumor tissues. Elevated FADS2 expression was associated with a poor overall survival (OS) and disease-free survival (DFS). FADS2 amplification was germane to worse progress-free survival (PFS). In addition, FADS2 correlated with the majority of tumor-infiltrating immune cells, immunoregulatory genes, and chemokines. Especially, FADS2 expression positively correlated with cancer-associated fibroblast (CAFs) infiltration. Gene Ontology and KEGG analysis demonstrated that FADS2 was involved in the fatty acid metabolic process, arachidonic acid metabolism, RAS, PPAR, and VEGF pathway. FADS2 had a positive relationship with tumor biological behaviors such as inflammation, cell cycle, proliferation, DNA damage, and DNA repair response in single-cell levels.

Conclusions
FADS2 can serve as a potential prognostic and immunotherapeutic biomarker for multiple tumors, revealing new insights and evidence for cancer treatment.
P2RX7 promotes osteosarcoma progression and glucose metabolism by enhancing c-Myc stabilization
Authors: Sheng Gaohong , Gao Yuan , Ding Qing , Zhang Ruizhuo , Wang Tianqi , Jing Shaoze , Zhao Hongqi , Ma Tian , Wu Hua , Yang Yong 
Published: February 2023

Abstract
Background
Osteosarcoma is the most common malignant tumor in bone and its prognosis has reached a plateau in the past few decades. Recently, metabolic reprogramming has attracted increasing attention in the field of cancer research. In our previous study, P2RX7 has been identified as an oncogene in osteosarcoma. However, whether and how P2RX7 promotes osteosarcoma growth and metastasis through metabolic reprogramming remains unexplored.

Methods
We used CRISPR/Cas9 genome editing technology to establish P2RX7 knockout cell lines. Transcriptomics and metabolomics were performed to explore metabolic reprogramming in osteosarcoma. RT-PCR, western blot and immunofluorescence analyses were used to determine gene expression related to glucose metabolism. Cell cycle and apoptosis were examined by flowcytometry. The capacity of glycolysis and oxidative phosphorylation were assessed by seahorse experiments. PET/CT was carried out to assess glucose uptake in vivo.

Results
We demonstrated that P2RX7 significantly promotes glucose metabolism in osteosarcoma via upregulating the expression of genes related to glucose metabolism. Inhibition of glucose metabolism largely abolishes the ability of P2RX7 to promote osteosarcoma progression. Mechanistically, P2RX7 enhances c-Myc stabilization by facilitating nuclear retention and reducing ubiquitination-dependent degradation. Furthermore, P2RX7 promotes osteosarcoma growth and metastasis through metabolic reprogramming in a predominantly c-Myc-dependent manner.

Conclusions
P2RX7 plays a key role in metabolic reprogramming and osteosarcoma progression via increasing c-Myc stability. These findings provide new evidence that P2RX7 might be a potential diagnostic and/or therapeutic target for osteosarcoma. Novel therapeutic strategies targeting metabolic reprogramming appear to hold promise for a breakthrough in the treatment of osteosarcoma.
Amyloid-β accumulation in human astrocytes induces mitochondrial disruption and changed energy metabolism
Authors: Zyśk Marlena , Beretta Chiara , Naia Luana , Dakhel Abdulkhalek , Påvénius Linnea , Brismar Hjalmar , Lindskog Maria , Ankarcrona Maria , Erlandsson Anna 
Published: February 2023

Abstract
Background
Astrocytes play a central role in maintaining brain energy metabolism, but are also tightly connected to the pathogenesis of Alzheimer’s disease (AD). Our previous studies demonstrate that inflammatory astrocytes accumulate large amounts of aggregated amyloid-beta (Aβ). However, in which way these Aβ deposits influence their energy production remain unclear.

Methods
The aim of the present study was to investigate how Aβ pathology in astrocytes affects their mitochondria functionality and overall energy metabolism. For this purpose, human induced pluripotent cell (hiPSC)-derived astrocytes were exposed to sonicated Aβ42 fibrils for 7 days and analyzed over time using different experimental approaches.

Results
Our results show that to maintain stable energy production, the astrocytes initially increased their mitochondrial fusion, but eventually the Aβ-mediated stress led to abnormal mitochondrial swelling and excessive fission. Moreover, we detected increased levels of phosphorylated DRP-1 in the Aβ-exposed astrocytes, which co-localized with lipid droplets. Analysis of ATP levels, when blocking certain stages of the energy pathways, indicated a metabolic shift to peroxisomal-based fatty acid β-oxidation and glycolysis.

Conclusions
Taken together, our data conclude that Aβ pathology profoundly affects human astrocytes and changes their entire energy metabolism, which could result in disturbed brain homeostasis and aggravated disease progression.
Clinicopathological study of pseudomyogenic hemangioendothelioma
Authors: Yang Ningning , Huang Yuchen , Yang Panpan , Yan Wentian , Zhang Shan , Li Nan , Feng Zhenzhong 
Published: February 2023

Abstract
Objectives
Pseudomyogenic hemangioendothelioma (PHE) is a rare intermediate hemangioendothelioma. This article aims to study the clinicopathological features of PHE.

Methods
We collected the clinicopathological features of 10 new PHE, and examined their molecular pathological features by fluorescence in situ hybridization. In addition, we summarized and analyzed the pathological data of 189 reported cases.

Results
The case group consisted of six men and four women aged 12–83 years (median: 41 years). Five instances occurred in the limbs, three in the head and neck, and two in the trunk. Tumor tissues were composed of spindle cells and round or polygonal epithelioid cells, which were either arranged in sheets or interwoven, along with areas of transitional morphology. Scattered or patchy stromal neutrophil infiltration was observed. Tumor cells had abundant cytoplasm, and some contained vacuoles. The nuclei had mild to moderate atypia, with visible nucleoli, and mitosis was rare. PHE tissues diffusely expressed CD31 and ERG, but not CD34, Desmin, SOX-10, HHV8 or S100, while some samples expressed CKpan, FLI-1 and EMA. INI-1 stain is retained. The proliferation index of Ki-67 is 10–35%. Seven samples were detected by fluorescence in situ hybridization, six of which had breakages in FosB proto-oncogene (AP-1 transcription factor subunit). Two patients experienced recurrence; however, no metastasis or death occurred.

Conclusions
PHE is a rare soft tissue vascular tumor, which has biologically borderline malignant potential, local recurrence, little metastasis, and good overall survival and prognosis. Immunomarkers and molecular detection are valuable for diagnosis.