bluuebunny/crossref_metadata_2025_split huggingface dataset:
The associations between dysregulation of human blood metabolites and lung cancer risk: evidence from genetic data
Authors: Wu Gujie , Liu Jun , Shi Haochun , Pan Binyang , Li Min , Wang Xiaolin , Li Yao , Cheng Lin , Guo Weigang , Huang Yiwei 
Published: July 2024

Abstract
Background
Metabolic dysregulation is recognized as a significant hallmark of cancer progression. Although numerous studies have linked specific metabolic pathways to cancer incidence, the causal relationship between blood metabolites and lung cancer risk remains unclear.

Methods
Genomic data from 29,266 lung cancer patients and 56,450 control individuals from the Transdisciplinary Research in Cancer of the Lung and the International Lung Cancer Consortium (TRICL-ILCCO) were utilized, and findings were replicated using additional data from the FinnGen consortium. The analysis focused on the associations between 486 blood metabolites and the susceptibility to overall lung cancer and its three major clinical subtypes. Various Mendelian randomization methods, including inverse-variance weighting, weighted median estimation, and MR-Egger regression, were employed to ensure the robustness of our findings.

Results
A total of 19 blood metabolites were identified with significant associations with lung cancer risk. Specifically, oleate (OR per SD = 2.56, 95% CI: 1.51 to 4.36), 1-arachidonoylglyceropholine (OR = 1.79, 95% CI: 1.22 to 2.65), and arachidonate (OR = 1.67, 95% CI: 1.16 to 2.40) were associated with a higher risk of lung cancer. Conversely, 1-linoleoylglycerophosphoethanolamine (OR = 0.57, 95% CI: 0.40 to 0.82), ADpSGEGDFXAEGGGVR, a fibrinogen cleavage peptide (OR = 0.60, 95% CI: 0.47 to 0.77), and isovalerylcarnitine (OR = 0.62, 95% CI: 0.49 to 0.78) were associated with a lower risk of lung cancer. Notably, isoleucine (OR = 9.64, 95% CI: 2.55 to 36.38) was associated with a significantly higher risk of lung squamous cell cancer, while acetyl phosphate (OR = 0.11, 95% CI: 0.01 to 0.89) was associated with a significantly lower risk of small cell lung cancer.

Conclusion
This study reveals the complex relationships between specific blood metabolites and lung cancer risk, highlighting their potential as biomarkers for lung cancer prevention, screening, and treatment. The findings not only deepen our understanding of the metabolic mechanisms of lung cancer but also provide new insights for future treatment strategies.
Metformin induces ZFP36 by mTORC1 inhibition in cervical cancer-derived cell lines
Authors: De la Cruz-López Karen Griselda , Alvarado-Ortiz Eduardo , Valencia-González Heriberto A. , Beltrán-Anaya Fredy Omar , Zamora-Fuentes José María , Hidalgo-Miranda Alfredo , Ortiz-Sánchez Elizabeth , Espinal-Enríquez Jesús , García-Carrancá Alejandro 
Published: July 2024

Abstract
Background
Metformin, a widely prescribed antidiabetic drug, has shown several promising effects for cancer treatment. These effects have been shown to be mediated by dual modulation of the AMPK-mTORC1 axis, where AMPK acts upstream of mTORC1 to decrease its activity. Nevertheless, alternative pathways have been recently discovered suggesting that metformin can act through of different targets regulation.

Methods
We performed a transcriptome screening analysis using HeLa xenograft tumors generated in NOD-SCID mice treated with or without metformin to examine genes regulated by metformin. Western Blot analysis, Immunohistochemical staining, and RT-qPCR were used to confirm alterations in gene expression. The TNMplot and GEPIA2 platform were used for in silico analysis of genes found up-regulated by metformin, in cervical cancer patients. We performed an AMPK knock-down using AMPK-targeted siRNAs and mTOR inhibition with rapamycin to investigate the molecular mechanisms underlying the effect of metformin in cervical cancer cell lines.

Results
We shown that metformin decreases tumor growth and increased the expression of a group of antitumoral genes involved in DNA-binding transcription activator activity, hormonal response, and Dcp1-Dcp2 mRNA-decapping complex. We demonstrated that ZFP36 could act as a new molecular target increased by metformin. mTORC1 inhibition using rapamycin induces ZFP36 expression, which could suggest that metformin increases ZFP36 expression and requires mTORC1 inhibition for such effect. Surprisingly, in HeLa cells AMPK inhibition did not affect ZFP36 expression, suggesting that additional signal transducers related to suppressing mTORC1 activity, could be involved.

Conclusions
These results highlight the importance of ZFP36 activation in response to metformin treatment involving mTORC1 inhibition.

Graphical Abstract
Long noncoding RNA KCNMA1-AS2 regulates the function of colorectal cancer cells and sponges miR-1227-5p
Authors: Miao Xinzhi , Wang Fang , Yunus Muhammad Amir , Ismail Ida Shazrina , Wang Tianyun 
Published: July 2024

Abstract
Background
Many long noncoding RNAs (lncRNAs) with altered expression significantly influence colorectal cancer (CRC) progression and behavior. The functions of many lncRNAs in CRC are not clear yet. This study aimed to discover novel lncRNA entities and comprehensively examine and validate their roles and underlying molecular mechanisms in CRC.

Methods
Tissue samples, both tumourous and non-tumourous, from three CRC patients were submitted for sequencing. Following expression validation in samples from ten patients and four CRC cell lines. The lncRNA KCNMA1-AS2 was synthesized by In-vitro transcription RNA synthesis and the lncRNA was directly transfected into CRC cell lines to overexpress. Functional assays including MTT proliferation assay, Annexin-V/propidium iodide apoptosis assay, wound healing migration assay and cell cycle assays were performed to evaluate the effect of overexpression of KCNMA1-AS2. Furthermore, the binding of KCNMA1-AS2 to miR-1227-5p was confirmed using dual luciferase reporter assays and qPCR analyses. Subsequent bioinformatics analyses identified 58 potential downstream targets of miR-1227-5p across three databases.

Results
In this study, we identified the lncRNA KCNMA1-AS2, the expression of which was down-regulated consistently in cancer tissues and CRC cell lines compared to non-cancerous tissues. The overexpression of lncRNA KCNMA1-AS2 led to significant reduction in CRC cell proliferation and migration, increase in cell apoptosis, and more cells arrested in S phase. Additionally, the interaction between KCNMA1-AS2 and miR-1227-5p was confirmed through dual luciferase reporter assay and qPCR analysis. It is also putatively predicted that MTHFR and ST8SIA2 may be linked to CRC based on bioinformatics analyses.

Conclusions
LncRNA KCNMA1-AS2 exhibited distinct gene expression patterns in both CRC tissue and cell lines, impacting various cellular functions while also acting as a sponge for miR-1227-5p.The findings spotlight lncRNA KCNMA1-AS2 as a potential marker for diagnosis and treatment of CRC.
Clinical analysis of 37 Chinese patients with ocular amyloidosis: a single center study
Authors: Li Jing , Liu Rui , Ren Tingting , Wang Nan , Guo Qihan , Xu Liangyuan , Ma Jianmin 
Published: July 2024

Abstract
Objective
To examine the clinical characteristics, diagnosis and treatment, and prognosis of ocular amyloidosis in a Chinese population.

Methods
A retrospective case series study was conducted. The clinical data of 37 patients with ocular amyloidosis were collected and the clinical characteristics, diagnosis and treatment, and prognosis were summarized and analyzed.

Results
The 37 patients included 12 males and 25 females ranging in age from 22 to 75 years, with median age of 49 years. The clinical signs and symptoms included a conjunctival mass in 37 patients (100%), periorbital discomfort or pain in 29 patients (61.9%), ptosis in 18 patients (23.8%), exophthalmos or eyeball displacement in 3 patients (14.3%), restricted eye movement in 2 patients (9.52%), vision loss in 1 patient (4.76%), and diplopia in 1 patient (4.76%). A total of 29 patients had only conjunctival involvement and 8 patients had concomitant orbital and conjunctival involvement. The main treatment for patients with conjunctival involvement was surgical resection. Thirty-one patients had stable disease, 4 patients progressed or relapsed, and 2 patients were lost to follow-up.

Conclusion
Ocular amyloidosis most commonly presents as an eyelid or conjunctival mass or diffuse thickening and can also present as an orbital mass. Diagnosis is mainly dependent on histopathological examination. Surgery is the main treatment and is done to confirm the diagnosis to guide further treatment, preserve function, and prevent complications that threaten visual acuity. Close postoperative follow-up is necessary.
Quantitative optical coherence tomography angiography assessments in the fellow eyes of those with central serous chorioretinopathy
Authors: Lin Jingjing , Mao Jianbo , Zhao Shixin , Chen Yiqi , Shen Lijun 
Published: July 2024

Abstract
Background
To analyze the vessel density (VD) of the retina and choriocapillaris (CC) layer and the structure of the foveal avascular zone (FAZ) in the fellow eyes of central serous chorioretinopathy (CSC) patients by using optical coherence tomography angiography (OCTA).

Methods
This was a case–control study. Unilateral CSC patients and age-matched healthy subjects were recruited from the Affiliated Eye Hospital of Wenzhou Medical University between July 2016 and July 2021. All eyes were divided into three groups: acute CSC (aCSC), chronic CSC (cCSC), and healthy controls. Both aCSC and cCSC were again divided into two subgroups: the affected eyes and the fellow eyes. In this study, all parameters of VD and FAZ were measured by self-software of OCTA.

Results
A total of 231 eyes of 137 subjects were included, with 47 aCSC patients, 47 cCSC patients, and 43 healthy controls. In the fellow eyes of CSC, the retinal VD was significantly lower (all P < 0.05), and the FAZ was significantly larger (all P < 0.05) in the cCSC group than in healthy controls, while no difference was detected in the CC layer. There was no significant difference between the aCSC group and healthy controls in all OCTA parameters. In the affected eyes of CSC, the superficial retinal vessel density (SRVD) was significantly higher (all P < 0.05) in healthy controls than in the aCSC and cCSC groups, while the deep retinal vessel density (DRVD) was significantly lower (all P < 0.05) and the FAZ was larger (all P < 0.05) in the cCSC group than in the aCSC group and healthy controls. A liner regression equation was established: Y (BCVA, best corrected visual acuity) = 3.692–0.036✱X1 (DRVD-Fovea)-0.031✱X2 (FD-300, vessel density around the 300 μm width of the FAZ), R2 = 0.427.

Conclusion
Based on OCTA measurements, this study revealed that the retinal microvascular network was impaired even in the fellow eyes of those with cCSC, which should arouse attention to the observation of unilateral CSC.
A randomized controlled pilot study of daily intravenous ketamine over three days for treatment-resistant depression
Authors: Pattanaseri Keerati , Lortrakul Juthawadee , Jaisin Kankamol , Srifuengfung Maytinee , Sa-nguanpanich Naratip , Viravan Natee , Pariwatcharakul Pornjira , Makarasara Wattanan , Ratta-apha Woraphat 
Published: July 2024

Abstract
Background
Studies have confirmed the rapid antidepressant action of ketamine in depressive episodes. Nevertheless, a standardized procedure for the delivery of ketamine infusion in individuals suffering from treatment-resistant depression, particularly in terms of infusion frequency and total dosage, remains undetermined. In addition, an efficacious ketamine regimen for persistent pain management involved a continuous 10-day infusion period with no notable adverse effects. Consequently, the primary objective of this study was to evaluate the antidepressant capacity of consecutive ketamine infusions spanning over three successive days, the duration of therapeutic response, and the overall safety profile of the treatment.

Methods
In this randomized controlled trial, participants aged 18–64 with treatment-resistant depression were randomized to receive either intravenous ketamine or midazolam (used as an active placebo) for 40 min daily over three consecutive days. Statistical analysis using repeated measures ANOVA was employed to assess the changes in the total score of the Montgomery–Åsberg Depression Rating Scale (MADRS) and the clinical global impression-Severity from the initial assessment to 10 and 31 days post-infusion. Additionally, the duration of response and remission was evaluated using Kaplan–Meier survival analysis.

Results
Out of 33 randomized participants, 20 underwent the treatment as planned. By day 10th, the ketamine group had a mean reduction in MADRS score of 12.55 (95% CI = 6.70–18.09), whereas the midazolam group had a decrease of 17.22 (95% CI = 11.09–23.36). This pattern continued to day 31, with ketamine showing a mean score decrease of 13.73 (95% CI = 7.54–19.91) and midazolam a fall of 12.44 (95% CI = 5.61–19.28). Both treatments were well tolerated, with dissociative symptoms in the ketamine group being temporary and ceasing by the end of each infusion.

Conclusion
Intravenous ketamine given for three consecutive days did not show a notable antidepressant advantage when compared to the active placebo midazolam, highlighting the need for further research into effective treatments schedules for treatment-resistant depression.

Trial registration
NCT05026203, ClinicalTrials.gov, registered on 24/08/2021.
The association of social isolation and loneliness with sarcopenia among the middle-aged and elderly in China
Authors: Tu Lei , Li Yiqun , Ren Xiao , Jiang Minglan , Han Longyang , Zheng Xiaowei 
Published: July 2024

Abstract
Objectives
This study examined the relationship of social isolation and loneliness on sarcopenia among Chinese middle-aged and elderly people.

Methods
Social isolation, loneliness, and sarcopenia were measured at baseline. Follow-up measures of new-onset sarcopenia were obtained 4 years later. Then used logistic regression to evaluate the association between social isolation, loneliness and sarcopenia.

Results
In cross-sectional analysis, social isolation and loneliness are significantly associated with sarcopenia [OR = 1.88 (95% CI = 1.54–2.28)]. In longitudinal analysis, social isolation and loneliness are significantly associated with sarcopenia [OR = 1.09 (95% CI = 0.71–1.69)]. Social isolation and loneliness have a synergistic effect. Among them, individuals over 60 years old [OR = 2.01 (95% CI = 1.37–2.96)] and those without social support [OR = 2.64 (1.61–4.32), P-for interaction < 0.001] are at higher risk.

Conclusion
Social isolation and loneliness were significantly associated with sarcopenia, and there was a synergistic effect between social isolation and loneliness.
Nasopharyngeal cancer risk assessment by country or region worldwide from 1990 to 2019
Authors: Wei Xian , Chen Biaoyou , Wang Zihao , Zhao Peng , Duan Xuwei 
Published: July 2024

Abstract
Background
Nasopharyngeal carcinoma (NPC) is 22nd most common cancer that occurs all over the world, but the prevalence rate can exhibit significant geographical differences. The Global Burden of Disease (GBD) database provides data related to the incidence, mortality, and disease burden of NPC worldwide from 1990 to 2019. We have designed this study in order to evaluate the potential effectiveness of health care policies and strategies for NPC prevention, diagnosis and treatment in different countries or regions around the world.

Methods
We used for the first time two distinct indicators, EAPC-ASIR and EACP-ASDR, to perform cluster analysis on 200 countries or regions around the world.

Results
200 countries or regions could be divided into five diverse groups. Group 1: The incidence rate showed an increasing trend whereas the mortality rate depicted a decreasing trend. Group 2: Morbidity as well as mortality showed a slight increase; Group 3: Morbidity as well as mortality increased significantly; Group 4: Morbidity and mortality decreased significantly; Group 5: Both morbidity as well as mortality decreased slightly. Moreover, in the context of a global decline in NPC incidence, mortality and disease burden, Group 3 countries, including: “Turkmenistan”, “Bosnia and Herzegovina”, “Dominican Republic”, “Bulgaria”, “Lesotho”, “Cabo Verde”, “Romania”, “Cuba”, “Jamaica”, “Azerbaijan”, “Uzbekistan”, “Chad”, “Belize” and “Ukraine” displayed a significant increase in morbidity, mortality, and disease burden, thus indicating a dangerous trend.

Conclusion
It is suggested that the medical and health policies formulated by the countries in Group 3 for NPC, as well as their capacity for conducting censuses, preventing, diagnosing, and treating diseases, need to be substantially strengthened.
Effect of vaccine hesitancy on female college students’ willingness to receive the HPV vaccine in China: a multicenter cross-sectional study
Authors: Li Xiaoxue , Zhang Fengzhi , Li Manman , Lin Chunhui , Shi Kaige , Yang Fangfang 
Published: July 2024

Abstract
Objective
To analyse the influencing factors of vaccine hesitancy on HPV vaccination willingness of female college students in order to promote the promotion of HPV vaccine in female college student population.

Methods
From September-October 2022, a convenience sampling method was used to conduct a questionnaire survey among freshman female students from four higher vocational colleges in Henan Province, China. The survey comprised a general information questionnaire, as well as inquiries regarding vaccine hesitancy and willingness to receive the human papillomavirus (HPV) vaccine. In PSM analyses, vaccine-hesitant students were matched with non-vaccine-hesitant students at a 1:1 ratio; subsequently, both univariate and multivariatble logistic regression analyses were applied to assess the impact of vaccine hesitancy on female university students’ willingness to receive the HPV vaccine.

Results
The results revealed a vaccine hesitancy rate of 44.75% among female university students, with 82.9% expressing willingness to receive the HPV vaccine. The results of the multivariable ordinal logistic regression analysis indicated vaccine hesitancy is a risk factor for HPV vaccination intentions among female university students [OR = 4.38, 95% CI (2.74, 6.99), P < 0.001]. Furthermore, the field of study (P = 0.01) and independently seeking information about the HPV vaccine (P = 0.04) were identified as factors influencing female university students’ willingness to receive the HPV vaccine.

Conclusions
Non-vaccine-hesitant students were more likely to be willing to receive the HPV vaccine than vaccine-hesitant students. Healthcare providers and educators should focus on vaccine attitudes among female college students to reduce vaccine hesitancy and enhance community education on cervical cancer, HPV infection and prevention through multichannel campaigns.
Comparison of the quadrant method measuring four points and bernard method in femoral tunnel position evaluation on 3-dimensional reconstructed computed tomography after anatomical single-bundle anterior cruciate ligament reconstruction
Authors: Li Jingxin , Yang Jie , Xu Zhaoguang , Wang Weican 
Published: July 2024

Abstract
Purpose
This prospective study aimed to compare the postoperative evaluation of the quadrant method measuring four points and Bernard method in femoral tunnel position evaluation on 3-Dimensional (3D) reconstructed computed tomography (CT) following the arthroscopic single-bundle anterior cruciate ligament (ACL) reconstruction.

Methods
Thirty-eight patients with ACL tears that were reconstructed using single-bundle ACL reconstruction between May 2021 and March 2023 were included in this study. Postoperative 3D CT images were obtained after the operation. The femoral tunnel position was measured by use of the quadrant method measuring four points and Bernard method.

Results
Average mean position of the femoral tunnel insertion center on the 3D CT image was at 26.16 ± 6.27% in the x-coordinate and at 24.36 ± 5.52% in the y-coordinate according to the Bernard method. Meanwhile, the position of the femoral insertion of the ACL measured by the quadrant method measuring four points was 24.2% ± 6.86% in the x-coordinate and 21.16% ± 5.14% in the y-coordinate.

Conclusions
Both the quadrant method measuring four points and Bernard method were effective in femoral tunnel position evaluation on 3D reconstructed CT. Application of the quadrant method measuring four points on 3D CT showed the advantage that measurement can be taken regardless of the shape of the bone tunnel.
Geographical distribution of MTHFR C677T gene polymorphisms among the reproductive-age women in Chinese Han populations: based on migration
Authors: Shen Yifen , Gu Yongchun , Tang Ying , Shen Hao , Liu Chao 
Published: July 2024

Abstract
Background
Methylenetetrahydrofolate reductase (MTHFR) is essential for the metabolism of folic acid and homocysteine. The MTHFR C677T polymorphism is associated with several disorders. Our study aims to explore the geographical distributions of the MTHFR C677T polymorphism of women in China and how migration affected the polymorphism in Suzhou.

Methods
A total of 7188 women of reproductive age were recruited in Suzhou of the study. Subjects were classified according to their native places after data extraction. MTHFR C677T gene polymorphisms were detected by quantitative PCR with genomic DNA isolated from blood samples.

Results
The frequencies of the 677T allele and 677TT genotype were higher in northern China than that in southern China and decreased in geographical gradients from north to south. The frequencies were considerably higher in the migrant population than that in the indigenous population of Suzhou. The migrant population have gradually changed the prevalence in Suzhou.

Conclusions
Our study suggested that the prevalence of MTHFR C677T polymorphisms among women varied across different geographical regions in Chinese Han populations. The 677T allele frequencies of the northern populations were significantly higher than those of the southern populations. The migrant population gradually changed the prevalence of the MTHFR C677T polymorphism in Suzhou.
Broadening placement opportunities for nursing students through an indirect supervision model
Authors: Hay Jonathan , Knight Kate H. , Arnold Mark , Donaghy-Binks Pamela 
Published: July 2024

Abstract
Background
Higher Education Institutions struggle to fill national deficits in student placement capacity, especially in social care and the voluntary sector. The Indirect Placement Supervision and Assessment Model and its holistic focus helps redress this deficit.

Methods
A Microsoft Forms survey was distributed to a self-selecting sample of 50 students, placement providers, and university staff, all of whom had been involved in indirect supervision as either an assessor, student, or supervisor.

Results
Three key themes emerged from the data collected; responses suggested that the model generated greater placement variety, increased placement capacity, and brought about reciprocal gains in the learner-supervisor matrix.

Conclusion
The study’s key implication for healthcare institutions pertains to a strong evidence base that the indirect supervision model provides an efficient means of broadening nursing placement variety and capacity alike.