bluuebunny/crossref_metadata_2025_split huggingface dataset:
Causal relationship between hypothyroidism and temporomandibular disorders: evidence from complementary genetic methods
Authors: Chen Xin , Xu Junyu , Cheng Zheng , Wang Qianyi , Zhao Zhibai , Jiang Qianglin 
Published: February 2024

Abstract
Background
The role of thyroid health in temporomandibular disorders (TMDs) has been emphasized in observational studies. However, whether the causation exists is unclear, and controversy remains about which specific disorder, such as hypothyroidism or hyperthyroidism, is destructive in TMDs. This study aims to investigate the overall and specific causal effects of various thyroid conditions on TMDs.

Methods
Mendelian randomization (MR) studies were performed using genetic instruments for thyrotropin (TSH, N = 119,715), free thyroxine (fT4, N = 49,269), hypothyroidism (N = 410,141), hyperthyroidism (N = 460,499), and TMDs (N = 211,023). We assessed the overall effect of each thyroid factor via inverse-variance weighted (IVW), weighted median, and MR-Egger methods, and performed extensive sensitivity analyses. Additionally, multivariable MR was conducted to evaluate the direct or indirect effects of hypothyroidism on TMDs whilst accounting for TSH, fT4 and hyperthyroidism, and vice versa.

Results
Univariable MR analyses revealed a causal effect of hypothyroidism on an increased risk of TMDs (IVW OR: 1.12, 95% CI: 1.05–1.20, p = 0.001). No significant association between genetically predicted hyperthyroidism, TSH, or fT4 and TMDs. In the multivariable MR analyses, the effects of hypothyroidism on TMDs occurrence remained significant even after adjSusting for TSH, fT4 and hyperthyroidism (multivariable IVW OR: 1.10, 95% CI: 1.03–1.17, p = 0.006). No pleiotropy and heterogeneity were detected in the analyses (p > 0.05).

Conclusions
Hypothyroidism might causally increase the risk of TMDs through a direct pathway, highlighting the critical role of managing thyroid health in the prevention of TMDs. Clinicians should give heightened attention to patients with hypothyroidism when seeking medical advice for temporomandibular discomfort. However, caution is warranted due to the potential confounders, pleiotropy, and selection bias in the MR study.
Evaluating the understanding of the ethical and moral challenges of Big Data and AI among Jordanian medical students, physicians in training, and senior practitioners: a cross-sectional study
Authors: Al-Ani Abdallah , Rayyan Abdallah , Maswadeh Ahmad , Sultan Hala , Alhammouri Ahmed , Asfour Hadeel , Alrawajih Tariq , Al Sharie Sarah , Al Karmi Fahed , Al-Azzam Ahmed Mahmoud , Mansour Asem , Al-Hussaini Maysa 
Published: February 2024

Abstract

Aims
To examine the understanding of the ethical dilemmas associated with Big Data and artificial intelligence (AI) among Jordanian medical students, physicians in training, and senior practitioners.

Methods
We implemented a literature-validated questionnaire to examine the knowledge, attitudes, and practices of the target population during the period between April and August 2023. Themes of ethical debate included privacy breaches, consent, ownership, augmented biases, epistemology, and accountability. Participants’ responses were showcased using descriptive statistics and compared between groups using t-test or ANOVA.

Results
We included 466 participants. The greater majority of respondents were interns and residents (50.2%), followed by medical students (38.0%). Most participants were affiliated with university institutions (62.4%). In terms of privacy, participants acknowledged that Big Data and AI were susceptible to privacy breaches (39.3%); however, 59.0% found such breaches justifiable under certain conditions. For ethical debacles involving informed consent, 41.6% and 44.6% were aware that obtaining informed consent posed an ethical limitation in Big Data and AI applications and denounced the concept of “broad consent”, respectively. In terms of ownership, 49.6% acknowledged that data cannot be owned yet accepted that institutions could hold a quasi-control of such data (59.0%). Less than 50% of participants were aware of Big Data and AI’s abilities to augment or create new biases in healthcare. Furthermore, participants agreed that researchers, institutions, and legislative bodies were responsible for ensuring the ethical implementation of Big Data and AI. Finally, while demonstrating limited experience with using such technology, participants generally had positive views of the role of Big Data and AI in complementing healthcare.

Conclusion
Jordanian medical students, physicians in training and senior practitioners have limited awareness of the ethical risks associated with Big Data and AI. Institutions are responsible for raising awareness, especially with the upsurge of such technology.
A framework for capacity enhancement of Rwandan nurse educators and preceptors facilitating nursing students to learn pediatric pain management
Authors: Uwimana Philomene , Mukamana Donatilla , Babenko-Mould Yolanda , Adejumo Oluyinka 
Published: February 2024

Abstract
Introduction
In low- and middle- income countries like Rwanda, children are most likely to suffer from painful and life-limiting conditions due to various factors predominant in these settings. Adequate pre-licensure pain management training can improve pain relief nursing practices. Educators and nurses in practice have a responsibility to teach the soon-to- be nurses for holistic competent nursing care of children, emphasizing the importance of and addressing child’s suffering, yet inconsistencies were reported in what was taught regarding pediatric pain management from a theoretical perspective by nurse educators as compared to their counterparts in clinical settings in Rwanda.

Design
This study applied a qualitative approach using group discussions based on nominal group technique (NGT) to develop and validate a conceptual framework supporting the capacity enhancement of nurse educators and preceptors facilitating students’ learning about pediatric pain management in Rwanda.

Methods
NGT meetings were conducted with academic nurses (n = 8), nurse clinicians (n = 4), and nursing students (n = 2) during a 2-day workshop to identify strategies, discuss the relevance of each strategy and to agree on key concepts of a framework for improving the ability of nurse educators and preceptors to teach PPM to nursing students. After four weeks another round of NGT meetings were done with nursing faculty (n = 6), academic nurse leaders (n = 3), nurse preceptors (n = 2), clinical nurse leaders (n = 2), a nurse leader from a regulatory body (n = 1), and nursing student (n = 1) to validate the developed framework.

Findings
Four main strategies corresponding to the key concepts were mapped in a framework. Participants had a consensual agreement on the importance of the developed framework, they confirmed its completeness and practicality. In addition, participants found that the developed framework is logical, and confirmed that it is applicable for its purpose.

Conclusion
The developed framework presents an opportunity to respond to the gaps in nursing pain education in the context of limited resources settings such as Rwanda. It can also be applied in nursing practice and nursing research, aligning with the need of improving the quality of care of suffering children. Furthermore, the framework can be adapted and utilized to meet the needs of healthcare professionals other than nurses.

Clinical relevance
Strategies are suggested to improve the ability of nurse educators and preceptors in clinical settings to facilitate the acquisition of pediatric pain management competencies by the next generation of nurses. Future Rwandan nurses could then use the competencies acquired to provide optimal health care to children with pain in the best way possible during their practices.
Association of blood cadmium concentration with chronic obstructive pulmonary disease progression: a prospective cohort study
Authors: Sun Jing , Deng You-Peng , Xu Juan , Zhu Feng-Min , He Qi-Yuan , Tang Min-Min , Liu Ying , Yang Jin , Liu Hong-Yan , Fu Lin , Zhao Hui 
Published: February 2024

Abstract
Background
Prior studies in patients with chronic obstructive pulmonary disease (COPD) had indicated a potential correlation between cadmium (Cd) exposure and reduction in lung function. Nevertheless, the influence of Cd exposure on the progression of COPD remained unknown. Exploring the relationship between Cd exposure and the progression of COPD was the aim of this investigation.

Methods
Stable COPD patients were enrolled. Blood samples were collected and lung function was evaluated. Regular professional follow-ups were conducted through telephone communications, outpatient services, and patients' hospitalization records.

Results
Each additional unit of blood Cd was associated with upward trend in acute exacerbation, hospitalization, longer hospital stay, and death within 2 years. Even after adjusting for potential confounding factors, each 1 unit rise in blood Cd still correlated with a rise in the frequencies of acute exacerbation, longer hospital stay, and death. Moreover, COPD patients with less smoking amount, lower lung function and without comorbidities were more vulnerable to Cd-induced disease deterioration.

Conclusion
Patients with COPD who have higher blood Cd concentration are susceptible to worse disease progression.

Graphical Abstract
Liquid biopsy in T-cell lymphoma: biomarker detection techniques and clinical application
Authors: Huang Zongyao , Fu Yao , Yang Hong , Zhou Yehan , Shi Min , Li Qingyun , Liu Weiping , Liang Junheng , Zhu Liuqing , Qin Sheng , Hong Huangming , Liu Yang 
Published: February 2024

AbstractT-cell lymphoma is a highly invasive tumor with significant heterogeneity. Invasive tissue biopsy is the gold standard for acquiring molecular data and categorizing lymphoma patients into genetic subtypes. However, surgical intervention is unfeasible for patients who are critically ill, have unresectable tumors, or demonstrate low compliance, making tissue biopsies inaccessible to these patients. A critical need for a minimally invasive approach in T-cell lymphoma is evident, particularly in the areas of early diagnosis, prognostic monitoring, treatment response, and drug resistance. Therefore, the clinical application of liquid biopsy techniques has gained significant attention in T-cell lymphoma. Moreover, liquid biopsy requires fewer samples, exhibits good reproducibility, and enables real-time monitoring at molecular levels, thereby facilitating personalized health care. In this review, we provide a comprehensive overview of the current liquid biopsy biomarkers used for T-cell lymphoma, focusing on circulating cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), Epstein-Barr virus (EBV) DNA, antibodies, and cytokines. Additionally, we discuss their clinical application, detection methodologies, ongoing clinical trials, and the challenges faced in the field of liquid biopsy.
CircPCNXL2 promotes tumor growth and metastasis by interacting with STRAP to regulate ERK signaling in intrahepatic cholangiocarcinoma
Authors: Liu Shuochen , Wang Yirui , Wang Tianlin , Shi Kuangheng , Fan Shilong , Li Chang , Chen Ruixiang , Wang Jifei , Jiang Wangjie , Zhang Yaodong , Chen Yananlan , Xu Xiao , Yu Yue , Li Changxian , Li Xiangcheng 
Published: February 2024

Abstract
Background
circular RNAs (circRNAs) have been reported to exert important effects in the progression of numerous cancers. However, the functions of circRNAs in intrahepatic cholangiocarcinoma (ICC) are still unclear.

Methods
circPCNXL2 (has_circ_0016956) were identified in paired ICC by circRNA microarray. Then, we assessed the biological functions of circPCNXL2 by CCK8, EdU, clone formation, transwell, wound healing assays, and xenograft models. RNA pull-down, mass spectrometry, and RNA immunoprecipitation (RIP) were applied to explore the interaction between cirrcPCNXL2 and serine-threonine kinase receptor-associated protein (STRAP). RNA pull-down, RIP and luciferase reporter assays were used to investigate the sponge functions of circPCNXL2. In the end, we explore the effects of circPCNXL2 and trametinib (a MEK1/2 inhibitor) in vivo.

Results
circPCNXL2 was upregulated in ICC tissues and cell lines, which promoted the proliferation and metastasis of ICC in vitro and in vivo. In terms of the mechanisms, circPCNXL2 could directly bind to STRAP and induce the interaction between STRAP and MEK1/2, resulting in the tumor promotion in ICC by activation of ERK/MAPK pathways. Besides, circPCNXL2 could regulate the expression of SRSF1 by sponging miR-766-3p and subsequently facilitated the growth of ICC. Finally, circPCNXL2 could partially inhibit the anti-tumor activity of trametinib in vivo.

Conclusion
circPCNXL2 played a crucial role in the progression of ICC by interacting with STRAP to activate the ERK signaling pathway, as well as by modulating the miR-766-3p/SRSF1 axis. These findings suggest that circPCNXL2 may be a promising biomarker and therapeutic target for ICC.
Adiponectin protects against myocardial ischemia–reperfusion injury: a systematic review and meta-analysis of preclinical animal studies
Authors: Yue Hongyi , Zhang Qunhui , Chang Senhao , Zhao Xinjie , Wang Mengjie , Li Wenhua 
Published: February 2024

Abstract
Background
Myocardial ischemia–reperfusion injury (MIRI) is widespread in the treatment of ischemic heart disease, and its treatment options are currently limited. Adiponectin (APN) is an adipocytokine with cardioprotective properties; however, the mechanisms of APN in MIRI are unclear. Therefore, based on preclinical (animal model) evidence, the cardioprotective effects of APN and the underlying mechanisms were explored.

Methods
The literature was searched for the protective effect of APN on MIRI in six databases until 16 November 2023, and data were extracted according to selection criteria. The outcomes were the size of the myocardial necrosis area and hemodynamics. Markers of oxidation, apoptosis, and inflammation were secondary outcome indicators. The quality evaluation was performed using the animal study evaluation scale recommended by the Systematic Review Center for Laboratory animal Experimentation statement. Stata/MP 14.0 software was used for the summary analysis.

Results
In total, 20 papers with 426 animals were included in this study. The pooled analysis revealed that APN significantly reduced myocardial infarct size [weighted mean difference (WMD) = 16.67 (95% confidence interval (CI) = 13.18 to 20.16, P < 0.001)] and improved hemodynamics compared to the MIRI group [Left ventricular end-diastolic pressure: WMD = 5.96 (95% CI = 4.23 to 7.70, P < 0.001); + dP/dtmax: WMD = 1393.59 (95% CI = 972.57 to 1814.60, P < 0.001); -dP/dtmax: WMD = 850.06 (95% CI = 541.22 to 1158.90, P < 0.001); Left ventricular ejection fraction: WMD = 9.96 (95% CI = 7.29 to 12.63, P < 0.001)]. Apoptosis indicators [caspase-3: standardized mean difference (SMD) = 3.86 (95% CI = 2.97 to 4.76, P < 0.001); TUNEL-positive cells: WMD = 13.10 (95% CI = 8.15 to 18.05, P < 0.001)], inflammatory factor levels [TNF-α: SMD = 4.23 (95% CI = 2.48 to 5.98, P < 0.001)], oxidative stress indicators [Superoxide production: SMD = 4.53 (95% CI = 2.39 to 6.67, P < 0.001)], and lactate dehydrogenase levels [SMD = 2.82 (95% CI = 1.60 to 4.04, P < 0.001)] were significantly reduced. However, the superoxide dismutase content was significantly increased [SMD = 1.91 (95% CI = 1.17 to 2.65, P < 0.001)].

Conclusion
APN protects against MIRI via anti-inflammatory, antiapoptotic, and antioxidant effects, and this effect is achieved by activating different signaling pathways.
A MRI radiomics-based model for prediction of pelvic lymph node metastasis in cervical cancer
Authors: Wang Tao , Li Yan-Yu , Ma Nan-Nan , Wang Pei-An , Zhang Bei 
Published: February 2024

Abstract
Background
Cervical cancer (CC) is a common malignancy of the female reproductive tract, and preoperative prediction of lymph node metastasis (LNM) is essential. This study aims to design and validate a magnetic resonance imaging (MRI) radiomics-based predictive model capable of detecting LNM in patients diagnosed with CC.

Methods
This retrospective analysis incorporated 86 and 38 CC patients into the training and testing groups, respectively. Radiomics features were extracted from MRI T2WI, T2WI-SPAIR, and axial apparent diffusion coefficient (ADC) sequences. Selected features identified in the training group were then used to construct a radiomics scoring model, with relevant LNM-related risk factors having been identified through univariate and multivariate logistic regression analyses. The resultant predictive model was then validated in the testing cohort.

Results
In total, 16 features were selected for the construction of a radiomics scoring model. LNM-related risk factors included worse differentiation (P < 0.001), more advanced International Federation of Gynecology and Obstetrics (FIGO) stages (P = 0.03), and a higher radiomics score from the combined MRI sequences (P = 0.01). The equation for the predictive model was as follows: −0.0493–2.1410 × differentiation level + 7.7203 × radiomics score of combined sequences + 1.6752 × FIGO stage. The respective area under the curve (AUC) values for the T2WI radiomics score, T2WI-SPAIR radiomics score, ADC radiomics score, combined sequence radiomics score, and predictive model were 0.656, 0.664, 0.658, 0.835, and 0.923 in the training cohort, while these corresponding AUC values were 0.643, 0.525, 0.513, 0.826, and 0.82 in the testing cohort.

Conclusions
This MRI radiomics-based model exhibited favorable accuracy when used to predict LNM in patients with CC. Relative to the use of any individual MRI sequence-based radiomics score, this predictive model yielded superior diagnostic accuracy.
Identification of myoferlin as a mitochondria-associated membranes component required for calcium signaling in PDAC cell lines
Authors: Anania Sandy , Farnir Martin , Peiffer Raphaël , Boumahd Yasmine , Thiry Marc , Agirman Ferman , Maloujahmoum Naima , Bellahcène Akeila , Peulen Olivier 
Published: February 2024

Abstract
Background
Pancreatic ductal adenocarcinoma is an aggressive cancer type with one of the lowest survival rates due to late diagnosis and the absence of effective treatments. A better understanding of PDAC biology will help researchers to discover the Achilles’ heel of cancer cells. In that regard, our research team investigated the function of an emerging oncoprotein known as myoferlin. Myoferlin is overexpressed in PDAC and its silencing/targeting has been shown to affect cancer cell proliferation, migration, mitochondrial dynamics and metabolism. Nevertheless, our comprehension of myoferlin functions in cells remains limited. In this study, we aimed to understand the molecular mechanism linking myoferlin silencing to mitochondrial dynamics.

Methods
Experiments were performed on two pancreas cancer cell lines, Panc-1 and MiaPaCa-2. Myoferlin localization on mitochondria was evaluated by immunofluorescence, proximity ligation assay, and cell fractionation. The presence of myoferlin in mitochondria-associated membranes was assessed by cell fractionation and its function in mitochondrial calcium transfer was evaluated using calcium flow experiments, proximity ligation assays, co-immunoprecipitation, and timelapse fluorescence microscopy in living cells.

Results
Myoferlin localization on mitochondria was investigated. Our results suggest that myoferlin is unlikely to be located on mitochondria. Instead, we identified myoferlin as a new component of mitochondria-associated membranes. Its silencing significantly reduces the mitochondrial calcium level upon stimulation, probably through myoferlin interaction with the inositol 1,4,5-triphosphate receptors 3.

Conclusions
For the first time, myoferlin was specifically demonstrated to be located in mitochondria-associated membranes where it participates to calcium flow. We hypothesized that this function explains our previous results on mitochondrial dynamics. This study improves our comprehension of myoferlin localization and function in cancer biology.
Solobacterium moorei promotes the progression of adenomatous polyps by causing inflammation and disrupting the intestinal barrier
Authors: Yu Shoujuan , Wang Xifan , Li Ziyang , Jin Dekui , Yu Mengyang , Li Jingnan , Li Yixuan , Liu Xiaoxue , Zhang Qi , Liu Yinghua , Liu Rong , Wang Xiaoyu , Fang Bing , Zhang Chengying , Wang Ran , Ren Fazheng 
Published: February 2024

Abstract
Background
Adenomatous polyps (APs) with inflammation are risk factors for colorectal cancer. However, the role of inflammation-related gut microbiota in promoting the progression of APs is unknown.

Methods
Sequencing of the 16S rRNA gene was conducted to identify characteristic bacteria in AP tissues and normal mucosa. Then, the roles of inflammation-related bacteria were clarified by Spearman correlation analysis. Furthermore, colorectal HT-29 cells, normal colon NCM460 cells, and azoxymethane-treated mice were used to investigate the effects of the characteristic bacteria on progression of APs.

Results
The expression levels of inflammation-related markers (diamine oxidase, d-lactate, C-reactive protein, tumor necrosis factor-α, interleukin-6 and interleukin-1β) were increased, whereas the expression levels of anti-inflammatory factors (interleukin-4 and interleukin-10) were significantly decreased in AP patients as compared to healthy controls. Solobacterium moorei (S. moorei) was enriched in AP tissues and fecal samples, and significantly positively correlated with serum inflammation-related markers. In vitro, S. moorei preferentially attached to HT-29 cells and stimulated cell proliferation and production of pro-inflammatory factors. In vivo, the incidence of intestinal dysplasia was significantly increased in the S. moorei group. Gavage of mice with S. moorei upregulated production of pro-inflammatory factors, suppressed proliferation of CD4+ and CD8+cells, and disrupted the integrity of the intestinal barrier, thereby accelerating progression of APs.

Conclusions
S. moorei accelerated the progression of AP in mice via activation of the NF-κB signaling pathway, chronic low-grade inflammation, and intestinal barrier disruption. Targeted reduction of S. moorei presents a potential strategy to prevent the progression of APs.
Injection-based hairy root induction and plant regeneration techniques in Brassicaceae
Authors: Jedličková Veronika , Štefková Marie , Mandáková Terezie , Sánchez López Juan Francisco , Sedláček Marek , Lysak Martin A. , Robert Hélène S. 
Published: February 2024

Abstract
Background
Hairy roots constitute a valuable tissue culture system for species that are difficult to propagate through conventional seed-based methods. Moreover, the generation of transgenic plants derived from hairy roots can be facilitated by employing carefully designed hormone-containing media.

Results
We initiated hairy root formation in the rare crucifer species Asperuginoides axillaris via an injection-based protocol using the Agrobacterium strain C58C1 harboring a hairy root-inducing (Ri) plasmid and successfully regenerated plants from established hairy root lines. Our study confirms the genetic stability of both hairy roots and their derived regenerants and highlights their utility as a permanent source of mitotic chromosomes for cytogenetic investigations. Additionally, we have developed an effective embryo rescue protocol to circumvent seed dormancy issues in A. axillaris seeds. By using inflorescence primary stems of Arabidopsis thaliana and Cardamine hirsuta as starting material, we also established hairy root lines that were subsequently used for regeneration studies.

Conclusion
We developed efficient hairy root transformation and regeneration protocols for various crucifers, namely A. axillaris, A. thaliana, and C. hirsuta. Hairy roots and derived regenerants can serve as a continuous source of plant material for molecular and cytogenetic analyses.