bluuebunny/crossref_metadata_2025_split huggingface dataset:
A randomized phase II study of acyclovir for the prevention of chemotherapy-induced oral mucositis in patients undergoing autologous hematopoietic stem cell transplantation
Authors: Hong Junshik , Park Hee-Kyung , Chang Sung-Ho , Byun Ja Min , Shin Dong-Yeop , Koh Youngil , Yoon Sung-Soo , Choi Youngnim , Kim Inho 
Published: December 2023

Abstract
Objectives
To prove our hypothesis that acyclovir prophylaxis in autologous hematopoietic stem cell transplantation (AHSCT) recipients with hematologic malignancies (HM) reduces the incidence of chemotherapy-induced oral mucositis (CIOM) by inhibiting the intraoral HSV reactivation during the neutropenic period, we conducted a randomized phase II study of acyclovir for the prevention of CIOM in adult HSV sero-positive AHSCT recipients.

Methods
Patients were randomized to either the study group (acyclovir 400 mg PO bid until neutrophil engraftment) or the control group (no prophylaxis) and received AHSCT. Oral examination and sampling for HSV were performed at three timepoints of AHSCT.

Results
In 54 patients who were randomized (for intention-to-analysis), the incidence of CIOM was 16.0% (4/25 patients) and 58.6% (17/29 patients) in the study group and the control group, respectively (P = 0.001). In 49 patients who completed the study (for per-protocol analysis), the incidence of CIOM was 13.0% (3/23 patients) and 61.5% (16/26 patients) in the study group and the control group, respectively (P = 0.001). In addition, HSV-1 PCR positivity in the study group was significantly lower than that the control group (4.3% vs. 46.2%, P = 0.001). A strong association between the HSV-1 reactivation status and CIOM was reconfirmed.

Conclusions
Prophylactic use of oral acyclovir effectively reduced the incidence of CIOM in patients with HM who were undergoing AHSCT.

Trial registrations
This trial was registered at the Clinical Research Information Service in the Republic of Korea under the number KCT0003885 (registration date 03/05/2019).
Effectiveness of using 2D atlas and 3D PDF as a teaching tool in anatomy lectures in initial learners: a randomized controlled trial in a medical school
Authors: Eroğlu Fatma Sıla , Erkan Beyza , Koyuncu Sevil Buket , Komşal Zeynep Rumeysa , Çiçek Feray Ekin , Ülker Müşerref , Toklu Merve Ebrar , Atlan Melike , Kıyak Yavuz Selim , Kula Serdar , Coşkun Özlem , Budakoğlu Işıl İrem 
Published: December 2023

Abstract
Background
Anatomy is a crucial part of medical education, and there have been attempts to improve this field by utilizing various methods. With the advancement of technology, three-dimensional (3D) materials have gained popularity and become a matter of debate about their effectiveness compared to two-dimensional (2D) sources. This research aims to analyze the effectiveness of 3D PDFs compared to 2D atlases.

Methods
This study is a randomized controlled trial involving 87 Year-1 and Year-2 medical students at Gazi University Faculty of Medicine, Turkey. The study was conducted in two steps. In Step-1, students were randomized to watch lecture videos on liver anatomy and male genitalia anatomy supplemented with either a 3D PDF (intervention group) or 2D atlas (control group) images. Following the video lectures, a test (immediate test) was administered. In Step-2, the same test (delayed test) was administered 10 days after the immediate test. The test scores were compared between the intervention and control groups. In addition to the descriptive analyses, Chi-square and Mann-Whitney U tests were performed.

Results
In the immediate test, while there was no significant difference between the groups for the liver test (p > 0.05), 3D PDF group’s scores (Median = 24.50) was significantly higher than the 2D atlas group’s in the genitalia test (Median = 21.00), (p = 0.017). The effect size (Cohen’s d) was 0.57. In the delayed test, there was no significant difference between the groups in the liver and genitalia tests (p > 0.05). However, the effect size in the immediate genitalia test was 0.40. Year-1 students’ immediate test of genitalia performances were significantly higher in the 3D PDF group (Median = 24.00) than the 2D atlas group (Median = 19.00), (p = 0.016). The effect size was 0.76. Also, Year-1 students’ 3D PDF group (Median = 20.50) presented with significantly higher performance than the 2D atlas group (Median = 12.00), (p = 0.044) in the delayed test of genitalia, with the 0.63 effect size.

Conclusion
3D PDF is more effective than 2D atlases in teaching anatomy, especially to initial learners. It is particularly useful for teaching complex anatomical structures, such as male genitalia, compared to the liver. Hence, it may be a valuable tool for medical teachers to utilize during lectures.
The application of artificial intelligence in health policy: a scoping review
Authors: Ramezani Maryam , Takian Amirhossein , Bakhtiari Ahad , Rabiee Hamid R. , Ghazanfari Sadegh , Mostafavi Hakimeh 
Published: December 2023

Abstract
Background
Policymakers require precise and in-time information to make informed decisions in complex environments such as health systems. Artificial intelligence (AI) is a novel approach that makes collecting and analyzing data in complex systems more accessible. This study highlights recent research on AI’s application and capabilities in health policymaking.

Methods
We searched PubMed, Scopus, and the Web of Science databases to find relevant studies from 2000 to 2023, using the keywords “artificial intelligence” and “policymaking.” We used Walt and Gilson’s policy triangle framework for charting the data.

Results
The results revealed that using AI in health policy paved the way for novel analyses and innovative solutions for intelligent decision-making and data collection, potentially enhancing policymaking capacities, particularly in the evaluation phase. It can also be employed to create innovative agendas with fewer political constraints and greater rationality, resulting in evidence-based policies. By creating new platforms and toolkits, AI also offers the chance to make judgments based on solid facts. The majority of the proposed AI solutions for health policy aim to improve decision-making rather than replace experts.

Conclusion
Numerous approaches exist for AI to influence the health policymaking process. Health systems can benefit from AI’s potential to foster the meaningful use of evidence-based policymaking.
Job satisfaction and regulation in the aged care sector: staff perspectives
Authors: Cameron Emilie , Noble Natasha , Bryant Jamie , Norton Grace , Allanson OAM Viv , Sanson-Fisher Rob 
Published: December 2023

Abstract
Background
The quality of care provided in residential aged care facilities is largely dependent on the job satisfaction of employees and the organisational framework and systems that they provide care in. This study aimed to explore aged care staff perceptions of job satisfaction, regulation of the sector and the Royal Commission into Aged Care Quality and Safety.

Methods
A cross-sectional survey conducted in 2019-early 2020 with staff employed in various roles at residential aged care services in Australia. The study specific survey collected views and experiences about working in the aged care sector as well as information about their role.

Results
A total of 167 aged care staff completed the survey of which 71% worked in a direct care role. Most participants indicated they thought they were doing a worthwhile and important job (98%), were proud to work in the sector (94%) and found the job personally rewarding (94%). However, participants also reported feeling emotionally drained by the work (37%) and fatigued by having to face a day of work (30%). 72% of participants felt the Royal Commission would lead to improvements in the care provided to residents.

Conclusion
Aged care staff have an overall positive feeling towards their work. Additional support including increasing skills to deliver high-quality care, creating a supportive work environment to reduce job stressors and changes to the way the sector is regulated, are likely to lead to improved care.
The triglyceride glucose index trajectory is associated with hypertension: a retrospective longitudinal cohort study
Authors: Xin Fengling , He Shuyou , Zhou Yu , Jia Xueni , Zhao Yulong , Zhao Hui 
Published: December 2023

Abstract
Background
Previous studies have found that the triglyceride glucose index (TyG index) trajectories are associated with cardiovascular diseases. However, the association between the patterns of TyG index trajectories and risk for hypertension has not been investigated. In a longitudinal general population, we aimed to identify distinct TyG index trajectories over 12 years and describe their association with incidence of hypertension.

Method
Of the 15,056 adults retrospectively recruited from the Physical Examination Center of the Second Affiliated Hospital of Dalian Medical University in northeast of China from 2011 to 2022. TyG index was calculated as ln (fasting TG [mg/dL] × FPG [mg/dL]/2) and the TyG index trajectories were developed using group-based trajectory modelling. Cox regression analysis was accomplished to assess the association between TyG index and incidence of hypertension.

Results
The median age of the population was 38 years, and 7352 (48.83%) of the participants were men. Three distinct TyG index trajectories were identified: “low increasing” (N = 7241), “moderate increasing” (N = 6448), and “high stable” (N = 1367). Using “low increasing” trajectory as a reference, “moderate increasing” and “high stable” trajectory were associated with increased risk of hypertension (HR = 2.45; 95% CI 2.25–2.67 and HR = 3.88; 95% CI 3.48–4.33). After adjusting for baseline sex, age, diabetes, smoking, systolic blood pressure, diastolic blood pressure, BMI, cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, blood glucose, triglyceride, urea, uric acid, and glomerular filtration rate, the HR were slightly attenuate in “moderate increasing” and “high stable” trajectories to 1.38 (95% CI 1.23–1.54) and 1.69 (95% CI 1.40–2.02) respectively. Meanwhile, similar results were observed in multiple sensitivity analyses. The HR of the “moderate increasing” and “high stable” trajectory groups were 2.63 (95% CI 2.30–3.00) and 4.66 (95% CI 3.66–5.93) in female, and 1.66 (95% CI 1.48–1.86) and 2.33 (95% CI 2.04–2.66) in male.

Conclusions
Elevated TyG index at baseline and long-term TyG index trajectories were associated with the risk of hypertension. Early identification of increasing TyG index could provide insights for preventing hypertension later in life.
Is intimate partner violence vertically transmitted among women in sub-Saharan Africa? Evidence from demographic health surveys between 2010 and 2019
Authors: Alawode Oluwatobi Abel , Bolarinwa Obasanjo Afolabi , Hajjar Julia Marie , Chukwudeh Stephen Okechukwu , Yaya Sanni 
Published: December 2023

Abstract
Background
Violence against women is a major human rights violation, and the continuous occurrence of this can have many implications for women’s social and health outcomes. The experience of violence from an intimate partner could be more intriguing, especially if such women experienced their mother’s intimate partner violence (IPV) issues. Thus, this study examined the vertical transmission of IPV among women in sub-Saharan Africa (SSA).

Methods
A total of 97,542 eligible women were drawn from 27 countries in SSA using a retrospective secondary dataset from Demographic Health Surveys conducted between 2010 and 2019. Multivariable analysis was employed to determine the association between the vertical transmission of IPV from mother to daughter and the covariates associated with IPV in SSA at p < 0.05.

Results
The results showed that 40% of the respondents had experienced lifetime IPV, whilst 25% of those women reported that their mothers experienced it in childhood in SSA. Country-specific variations showed the highest prevalence of IPV experienced in Sierra Leone (60%) and the lowest in Comoros (9%). Results from model 1 showed that women who reported that their mothers experienced IPV were found to be significantly more than two times more likely to have experienced any form of IPV compared to those whose mothers did not (aOR = 2.66; 95% CI: 2.59–2.74), after adjusting for cofounders in Model 2, the result still showed that women who reported that their mothers experienced IPV were found to be significantly more than two times more likely to have experienced any form of IPV compared to those whose mothers did not (aOR = 2.56; 95% CI: 2.48–2.63). On the other hand, women with higher-educated partners, women in rural areas, and those from female-headed households were less likely to experience IPV.

Conclusion
This study concluded that women whose mothers experienced IPV were more likely to have experienced IPV. Our study also identified that education, rural areas, and female-headed households were protective factors against experiencing IPV. To address the groups of women at higher risk for experiencing IPV, we recommend ensuring that girls complete their education to promote greater wealth and resources.
Lonidamine liposomes to enhance photodynamic and photothermal therapy of hepatocellular carcinoma by inhibiting glycolysis
Authors: Lei Lei , Dai Wenbin , Man Jiaping , Hu Haitao , Jin Qiao , Zhang Bo , Tang Zhe 
Published: December 2023

AbstractPhototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), has great promise in the treatment of cancer. However, there are many obstacles that can restrict the therapeutic efficacy of phototherapy. The hypoxic tumor microenvironment can restrict the production of reactive oxygen species (ROS) in PDT. As for PTT, the thermotolerance of cancer cells may lead to ineffective PTT. In this study, IR780 and glycolysis inhibitor lonidamine (LND)-encapsulated liposomes are prepared for photodynamic and photothermal therapy of hepatocellular carcinoma. IR780 can be used as a photosensitizer and photothermal agent for simultaneous PDT and PTT after being irradiated with 808 nm laser. LND can reduce the oxygen consumption of cancer cells by inhibiting glycolysis, which will relieve tumor hypoxia and produce more ROS for PDT. On the other hand, energy supply can be blocked by LND-induced glycolysis inhibition, which will inhibit the production of heat shock proteins (HSPs), reduce the thermotolerance of tumor cells, and finally enhance the therapeutic efficacy of PTT. The enhanced PTT is studied by measuring intracellular HSPs, ATP level, and mitochondrial membrane potential. The antitumor effect of IR780 and LND co-loaded liposomes is extensively investigated by in vitro and in vivo experiments. This research provides an innovative strategy to simultaneously enhance the therapeutic efficacy of PDT and PTT by inhibiting glycolysis, which is promising for future creative approaches to cancer phototherapy.
Recurring EPHB1 mutations in human cancers alter receptor signalling and compartmentalisation of colorectal cancer cells
Authors: Kundu Snehangshu , Nunes Luís , Adler Jeremy , Mathot Lucy , Stoimenov Ivaylo , Sjöblom Tobias 
Published: December 2023

Abstract
Background
Ephrin (EPH) receptors have been implicated in tumorigenesis and metastasis, but the functional understanding of mutations observed in human cancers is limited. We previously demonstrated reduced cell compartmentalisation for somatic EPHB1 mutations found in metastatic colorectal cancer cases. We therefore integrated pan-cancer and pan-EPH mutational data to prioritise recurrent EPHB1 mutations for functional studies to understand their contribution to cancer development and metastasis.

Methods
Here, 79,151 somatic mutations in 9,898 samples of 33 different tumour types were analysed with a bioinformatic pipeline to find 3D-mutated cluster pairs and hotspot mutations in EPH receptors. From these, 15 recurring EPHB1 mutations were stably expressed in colorectal cancer followed by confocal microscopy based in vitro compartmentalisation assays and phospho-proteome analysis.

Results
The 3D-protein structure-based bioinformatics analysis resulted in 63% EPHB1 mutants with compartmentalisation phenotypes vs 43% for hotspot mutations. Whereas the ligand-binding domain mutations C61Y, R90C, and R170W, the fibronectin domain mutation R351L, and the kinase domain mutation D762N displayed reduced to strongly compromised cell compartmentalisation, the kinase domain mutations R743W and G821R enhanced this phenotype. While mutants with reduced compartmentalisation also had reduced ligand induced receptor phosphorylation, the enhanced compartmentalisation was not linked to receptor phosphorylation level. Phosphoproteome mapping pinpointed the PI3K pathway and PIK3C2B phosphorylation in cells harbouring mutants with reduced compartmentalisation.

Conclusions
This is the first integrative study of pan-cancer EPH receptor mutations followed by in vitro validation, a robust way to identify cancer-causing mutations, uncovering EPHB1 mutation phenotypes and demonstrating the utility of protein structure-based mutation analysis in characterization of novel cancer genes.
The role of m6A epigenetic modifications in tumor coding and non-coding RNA processing
Authors: Wen Tongxuan , Li Tong , Xu Yeqiu , Zhang Yuanzhuang , Pan Hai , Wang Yong 
Published: December 2023

Abstract
Background
Epigenetic modifications of RNA significantly contribute to the regulatory processes in tumors and have, thus, received considerable attention. The m6A modification, known as N6-methyladenosine, is the predominant epigenetic alteration found in both eukaryotic mRNAs and ncRNAs.

Main body
m6A methylation modifications are dynamically reversible and are catalyzed, removed, and recognized by the complex of m6A methyltransferase (MTases), m6A demethylase, and m6A methyl recognition proteins (MRPs). Published evidence suggests that dysregulated m6A modification results in abnormal biological behavior of mature mRNA, leading to a variety of abnormal physiological processes, with profound implications for tumor development in particular.

Conclusion
Abnormal RNA processing due to dysregulation of m6A modification plays an important role in tumor pathogenesis and potential mechanisms of action. In this review, we comprehensively explored the mechanisms by which m6A modification regulates mRNA and ncRNA processing, focusing on their roles in tumors, and aiming to understand the important regulatory function of m6A modification, a key RNA epigenetic modification, in tumor cells, with a view to providing theoretical support for tumor diagnosis and treatment.
Inhaled nitric oxide suppresses neuroinflammation in experimental ischemic stroke
Authors: Sienel Rebecca I. , Mamrak Uta , Biller Janina , Roth Stefan , Zellner Andreas , Parakaw Tipparat , Khambata Rayomand S. , Liesz Arthur , Haffner Christof , Ahluwalia Amrita , Seker Burcu F. , Plesnila Nikolaus 
Published: December 2023

AbstractIschemic stroke is a major global health issue and characterized by acute vascular dysfunction and subsequent neuroinflammation. However, the relationship between these processes remains elusive. In the current study, we investigated whether alleviating vascular dysfunction by restoring vascular nitric oxide (NO) reduces post-stroke inflammation. Mice were subjected to experimental stroke and received inhaled NO (iNO; 50 ppm) after reperfusion. iNO normalized vascular cyclic guanosine monophosphate (cGMP) levels, reduced the elevated expression of intercellular adhesion molecule-1 (ICAM-1), and returned leukocyte adhesion to baseline levels. Reduction of vascular pathology significantly reduced the inflammatory cytokines interleukin-1β (Il-1β), interleukin-6 (Il-6), and tumor necrosis factor-α (TNF-α), within the brain parenchyma. These findings suggest that vascular dysfunction is responsible for leukocyte adhesion and that these processes drive parenchymal inflammation. Reversing vascular dysfunction may therefore emerge as a novel approach to diminish neuroinflammation after ischemic stroke and possibly other ischemic disorders.
The inter-link of ageing, cancer and immunity: findings from real-world retrospective study
Authors: Fu Xiaomin , Qin Peng , Li Fanghui , Zhu Huifang , You Hongqin , Zhang Yong , Xu Benling , Li Tiepeng , Zhang Fang , Han Lu , Zhao Lingdi , Ma Baozhen , Wang Zibing , Gao Quanli 
Published: December 2023

Abstract
Background
Although the concept of declined immune function associated with cancer has been accepted extensively, real-world clinical studies focusing on analysis of the peripheral blood immune changes underlying ageing, immunity and cancer are scarce.

Methods
In this case-control study, we retrospectively analysed 1375 cancer patients and enrolled 275 age and gender matched healthy individuals. Flow cytometry was conducted to assess the immune changes. Further analysis was examined by SPSS 17.0 and GraphPad Prism 9 software.

Results
Cancer patients showed obviously decreased CD3+ T, CD3+CD4+ Th, CD3+CD8+ CTL, CD19+ B, CD16+CD56+ NK cell counts and lower percentage of PD-1 (programmed cell death protein-1, PD-1) positive cells than healthy control (P < 0.0001). For cancer patients, the reference range of circulating percentage of PD-1+CD45+ cells, PD-1+CD3+ T cells, PD-1+CD3+CD4+ Th cells and PD-1+CD3+CD8+ CTL (Cytotoxic T Lymphocyte, CTL) were 11.2% (95% CI 10.8%-11.6%), 15.5% (95% CI 14.7%-16.0%), 15.4% (95% CI 14.9%-16.0%) and 14.5% (95% CI 14.0%-15.5%), respectively. Moreover, the reduction of CD3+ T, CD3+CD4+ Th, CD3+CD8+ CTL, CD19+ B cell counts accompanied with age and stage advancing (P < 0.05). CD16+CD56+ NK cells decreased with stage, but elevated in aged and male cancer patients (P < 0.05). Additionally, the percentage of PD-1 positive cells varied across cancer types, raised with age and stage. Head and neck, pancreatic, gynaecological and lung demonstrated a higher level of the percentage of PD-1 positive cells than melanoma, prostate, and breast cancer (P < 0.05).

Conclusions
This study provides the reference range of the percentage of PD-1 positive cells on peripheral blood, confirms the decreased immune cells and a series of immune changes accompanying with cancer, expands our real world evidence to better understand the interactions of ageing, cancer and immunity. Moreover, the circulating percentage of PD-1 positive cells shows similar tumor type distribution with tumor mutational burden (TMB), supports that it maybe a potential predictive biomarker for immune checkpoint inhibitor therapy.
The oral sensory organs in Bathochordaeus stygius (Tunicata Appendicularia) are unique in structure and homologous to the coronal organ
Authors: Le Mai-Lee Van , Müller Lisa-Marie , Stach Thomas 
Published: December 2023

Abstract
Background
Appendicularia consists of approximately 70 purely marine species that belong to Tunicata the probable sister taxon to Craniota. Therefore, Appendicularia plays a pivotal role for our understanding of chordate evolution. In addition, appendicularians are an important part of the epipelagic marine plankton. Nevertheless, little is known about appendicularian species, especially from deeper water.

Results
Using µCT, scanning electron microscopy, and digital 3D-reconstruction techniques we describe three pairs of complex oral sensory organs in the mesopelagic appendicularian Bathochordaeus stygius. The oral sensory organs are situated at the anterior and lateral margin of the mouth and inside the mouth cavity. A single organ consists of 22–90 secondary receptor cells that project apical cilia through a narrow hole in the epidermis. The receptor cells are innervated by branches of the second brain nerve.

Conclusions
Based on position, morphology, and innervation we suggest that the oral sensory organs are homologues of the coronal organs in other tunicates. We discuss the hypothesized homology of coronal organs and the lateral line system of primary aquatic vertebrates. The complex oral sensory organs of B. stygius are unique in tunicates and could be adaptations to the more muffled environment of the mesopelagic.