bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein disulfide isomerase family member 4 promotes triple-negative breast cancer tumorigenesis and radiotherapy resistance through JNK pathway
Authors: Tao Jinqiu , Xue Cailin , Cao Meng , Ye Jiahui , Sun Yulu , Chen Hao , Guan Yinan , Zhang Wenjie , Zhang Weijie , Yao Yongzhong 
Published: January 2024

Abstract
Background
Despite radiotherapy ability to significantly improve treatment outcomes and survival in triple-negative breast cancer (TNBC) patients, acquired resistance to radiotherapy poses a serious clinical challenge. Protein disulfide isomerase exists in endoplasmic reticulum and plays an important role in promoting protein folding and post-translational modification. However, little is known about the role of protein disulfide isomerase family member 4 (PDIA4) in TNBC, especially in the context of radiotherapy resistance.

Methods
We detected the presence of PDIA4 in TNBC tissues and paracancerous tissues, then examined the proliferation and apoptosis of TNBC cells with/without radiotherapy. As part of the validation process, xenograft tumor mouse model was used. Mass spectrometry and western blot analysis were used to identify PDIA4-mediated molecular signaling pathway.

Results
Based on paired clinical specimens of TNBC patients, we found that PDIA4 expression was significantly higher in tumor tissues compared to adjacent normal tissues. In vitro, PDIA4 knockdown not only increased apoptosis of tumor cells with/without radiotherapy, but also decreased the ability of proliferation. In contrast, overexpression of PDIA4 induced the opposite effects on apoptosis and proliferation. According to Co-IP/MS results, PDIA4 prevented Tax1 binding protein 1 (TAX1BP1) degradation by binding to TAX1BP1, which inhibited c-Jun N-terminal kinase (JNK) activation. Moreover, PDIA4 knockdown suppressed tumor growth xenograft model in vivo, which was accompanied by an increase in apoptosis and promoted tumor growth inhibition after radiotherapy.

Conclusions
The results of this study indicate that PDIA4 is an oncoprotein that promotes TNBC progression, and targeted therapy may represent a new and effective anti-tumor strategy, especially for patients with radiotherapy resistance.
Tissue-specific RNA Polymerase II promoter-proximal pause release and burst kinetics in a Drosophila embryonic patterning network
Authors: Hunt George , Vaid Roshan , Pirogov Sergei , Pfab Alexander , Ziegenhain Christoph , Sandberg Rickard , Reimegård Johan , Mannervik Mattias 
Published: January 2024

AbstractBackgroundFormation of tissue-specific transcriptional programs underlies multicellular development, including dorsoventral (DV) patterning of theDrosophilaembryo. This involves interactions between transcriptional enhancers and promoters in a chromatin context, but how the chromatin landscape influences transcription is not fully understood.ResultsHere we comprehensively resolve differential transcriptional and chromatin states duringDrosophilaDV patterning. We find that RNA Polymerase II pausing is established at DV promoters prior to zygotic genome activation (ZGA), that pausing persists irrespective of cell fate, but that release into productive elongation is tightly regulated and accompanied by tissue-specific P-TEFb recruitment. DV enhancers acquire distinct tissue-specific chromatin states through CBP-mediated histone acetylation that predict the transcriptional output of target genes, whereas promoter states are more tissue-invariant. Transcriptome-wide inference of burst kinetics in different cell types revealed that while DV genes are generally characterized by a high burst size, either burst size or frequency can differ between tissues.ConclusionsThe data suggest that pausing is established by pioneer transcription factors prior to ZGA and that release from pausing is imparted by enhancer chromatin state to regulate bursting in a tissue-specific manner in the early embryo. Our results uncover how developmental patterning is orchestrated by tissue-specific bursts of transcription from Pol II primed promoters in response to enhancer regulatory cues.
Circ_MAPK9 promotes STAT3 and LDHA expression by silencing miR-642b-3p and affects the progression of hepatocellular carcinoma
Authors: Wang Kunyuan , Lu Qianting , Luo Yufeng , Yu Ganxiang , Wang Zhilei , Lin Jiaen , Tan Zhenlin , Lao Yueqiong , Liu Shiming , Yang Hui 
Published: January 2024

Abstract
Background
Aberrant expression and activation of circular RNAs (circRNAs) are closely associated with various cancers. The role of circ_MAPK9 (hsa_circ_0001566) in cancer progression remains unknown. This study aims to investigate the function, mechanism and clinical significance of circ_MAPK9 in hepatocellular carcinoma (HCC).

Methods
Circ_MAPK9 expression on the microarray of tumor from clinical HCC patients was detected by in situ hybridization (ISH). Circ_MAPK9 knockdown was achieved with siRNAs in SMMC-7721 and SK-Hep1 HCC cell lines. The biological function of circ_MAPK9 was verified in vitro by CCK8 test, colony formation assay, transwell assay, PI-Annexin V staining, and in vivo by xenograft tumor in nude mice. Fluorescent in situ hybridization (FISH), subcellular fractionation assay, a dual-luciferase reporter assay and rescue experiments were employed for further mechanistic investigation.

Results
The expression of circ_MAPK9 was significantly up-regulated in HCC tissues and cells, which was found to be associated with poor prognosis. Patients with high expression of circ_MAPK9 had a shorter overall survival and disease-free survival in comparison to those with low circ_MAPK9 expression. Functional assays showed that circ_MAPK9 knockdown suppressed cellular proliferation, migration, invasion and tumor growth in vivo, and promoted apoptosis in HCC cells. Moreover, we found that circ_MAPK9 knockdown could inhibit aerobic glycolysis by decreasing the production of adenosine triphosphate (ATP) and lactic acid, which was mediated by lactate dehydrogenase (LDHA). Mechanistically, circ_MAPK9 functioned as ceRNA via sponging miR-642b-3p and alleviated the inhibitory effect of miR-642b-3p on its target signal transducer and activator of transcription 3 (STAT3) and LDHA, thereby leading to STAT3 activation and LDHA expression.

Conclusions
Circ_MAPK9, as an oncogene, promotes HCC growth and metastasis through miR-642b-3p/STAT3-LDHA axis. Circ_MAPK9 could serve as a potential biomarker for HCC poor prognosis and diagnosis.
The oncogenic role and regulatory mechanism of PGK1 in human non-small cell lung cancer
Authors: Tian Tian , Leng Yahui , Tang Bingbing , Dong Xiaoxia , Ren Qiulei , Liang Jingyin , Liu Tianhui , Liu Yanni , Feng Wenxiao , Liu Song , Zhou Yang , Zhao Hongyan , Shen Li 
Published: January 2024

Abstract
Background
Phosphoglycerate kinase 1 (PGK1) is a metabolic enzyme that participates in various biological and pathological processes. Dysregulated PGK1 has been observed in numerous malignancies. However, whether and how PGK1 affects non-small cell lung cancer (NSCLC) is not yet fully elucidated.

Methods
Herein, the non-metabolic function of PGK1 in NSCLC was explored by integrating bioinformatics analyses, cellular experiments, and nude mouse xenograft models. The upstream regulators and downstream targets of PGK1 were examined using multiple techniques such as RNA sequencing, a dual-luciferase reporter assay, Co-immunoprecipitation, and Western blotting.

Results
We confirmed that PGK1 was upregulated in NSCLC and this upregulation was associated with poor prognosis. Further in vitro and in vivo experiments demonstrated the promoting effects of PGK1 on NSCLC cell growth and metastasis. Additionally, we discovered that PGK1 interacted with and could be O-GlcNAcylated by OGT. The inhibition of PGK1 O-GlcNAcylation through OGT silencing or mutation at the T255 O-GlcNAcylation site could weaken PGK1-mediated NSCLC cell proliferation, colony formation, migration, and invasion. We also found that a low miR-24-3p level led to an increase in OGT expression. Additionally, PGK1 exerted its oncogenic properties by augmenting ERK phosphorylation and MCM4 expression.

Conclusions
PGK1 acted as a crucial mediator in controlling NSCLC progression. The miR-24-3p/OGT axis was responsible for PGK1 O-GlcNAcylation, and ERK/MCM4 were the downstream effectors of PGK1. It appears that PGK1 might be an attractive therapeutic target for the treatment of NSCLC.
GPR137 inactivates Hippo signaling to promote gastric cancer cell malignancy
Authors: Li Lin , Tang Jinlong , Cao Bin , Xu Qiang , Xu Shouying , Lin Chao , Tang Chao 
Published: January 2024

AbstractAs the fifth most common cancer in the world, gastric cancer (GC) ranks as the third major cause of cancer-related death globally. Although surgical resection and chemotherapy still remains the mainstay of potentially curative treatment for GC, chemotherapy resistance and adverse side effects limit their clinical applications. Thus, further investigation of the mechanisms of carcinogenesis in GC and discovery of novel biomarkers is of great concern. We herein report that the elevated expression of GPR137 is correlated with GC. Overexpression of GPR137 potentiates human gastric cancer AGS cell malignancy, including proliferation, migration, invasion, colony formation and xenograft growth in nude mice in vivo, whereas knockout of GPR137 by CRISPR/Cas9 gene editing exerts the opposite effects. Mechanistically, GPR137 could bind to MST, the upstream kinases in Hippo pathway, which disrupts the association of MST with LATS, subsequently activating the transcriptional co-activators, YAP and TAZ, and thereby triggering the target transcription and the alterations in GC cell biological actions consequently. Therefore, our findings may provide with the evidence of developing a potentially novel treatment method with specific target for GC.
Risk assessment of transgender people: implementation of a demasculinizing–feminizing rodent model including the evaluation of thyroid homeostasis
Authors: Tammaro Alessia , Lori Gabriele , Martinelli Andrea , Cancemi Luigia , Tassinari Roberta , Maranghi Francesca 
Published: January 2024

Abstract
Background
Individuals whose gender identity differs from the biological sex and the social norms are defined as transgender. Sometimes transgender undergo gender affirming hormone therapy, which lasts for the entire life making essential to evaluate its potential long-term effects. Moreover, transgender can represent a susceptible sub-group of population and specific attention is needed in risk assessment, including the development of targeted animal models. Aim of the study is the implementation of a rodent demasculinizing–feminizing model through the setting of appropriate dose of hormone therapy and the selection of specific biomarkers to evaluate the sex transition. Specific attention is paid to thyroid homeostasis due to the close link with reproductive functions. Four male adult rats/group were subcutaneously exposed to three doses plus control of β-estradiol valerate plus cyproterone acetate at: 0.045 + 0.2 (low), 0.09 + 0.2 (medium) and 0.18 + 0.2 (high) mg/dose, five times/week. The doses were selected considering the most recent recommendations for transgender woman. Sperm count, histopathological analysis (testis, liver, thyroid), testosterone, estradiol, triiodothyronine and thyroid-stimulating hormone serum levels and gene expression of sex dimorphic CYP450 were evaluated.

Results
The doses induced feminizing–demasculinizing effects: decreased testosterone serum levels at the corresponding cisgender, increased estradiol, impairment of male reproductive function and reversal of sex-specific CYP liver expression. However, the medium and high doses induced marked liver toxicity and the low dose is considered the best choice, also for long-term studies in risk assessment. The alterations of thyroid indicated follicular cell hypertrophy supported by increased thyroid-stimulating hormone serum levels at the higher doses.

Conclusions
The implementation of animal models that mimic the effects of gender affirming hormone therapy is essential for supporting clinical studies in transgender people and filling data gap in order to ensure an appropriate risk assessment and a more accurate, personalized care for transgender people.
Comparison between the mesenteric fixation method (MEFIX) and conventional methods at preventing the occurrence of Petersen’s hernia: a study protocol for a multicenter randomized controlled trial
Authors: Park Jae Kyun , Kim Dae Hwan , Jeon Tae-Yong , Jeong Sang-Ho , Kim Tae Han , Min Jae-Seok , Kim Rock Bum , Lee Young Joon , Park Ji Ho , Son Young Gil , Yoon Ki Young , Seo Kyung Won , Kim Ki Hyun , Kim Yoonhong , Chae Hyun Dong , Hwang Sun Hwi , Lee Si-Hak , Chung Jae Hun , Kim Hyoung-Il , Park Dong Jin , Kim Kwang Hee , Seo Sang Hyuk , Oh Sung Jin , Lee Woo Yong , In Choi Chang 
Published: January 2024

Abstract
Background
Petersen’s hernia, which occurs after Billroth-II (B-II) or Roux-en-Y (REY) anastomosis, can be reduced by defect closure. This study aims to compare the incidence of bowel obstruction above Clavien–Dindo classification grade III due to Petersen’s hernia between the mesenteric fixation method and the conventional methods after laparoscopic or robotic gastrectomy.

Methods
This study was designed as prospective, single-blind, non-inferiority randomized controlled multicenter trial in Korea. Patients with histologically diagnosed gastric cancer of clinical stages I, II, or III who underwent B-II or REY anastomosis after laparoscopic or robotic gastrectomy are enrolled in this study. Participants who meet the inclusion criteria are randomly assigned to two groups: a CLOSURE group that underwent conventional Petersen’s defect closure method and a MEFIX group that underwent the mesenteric fixation method. The primary endpoint is the number of patients who underwent surgery for bowel obstruction caused by Petersen’s hernia within 3 years after laparoscopic or robotic gastrectomy.

Discussion
This trial is expected to provide high-level evidence showing that the MEFIX method can quickly and easily close Petersen’s defect without increased postoperative complications compared to the conventional method.

Trial registration
ClinicalTrials.gov NCT05105360. Registered on November 3, 2021.
Internet-based transdiagnostic treatment for emotional disorders in Arabic- and Farsi-speaking refugees: study protocol of a randomized controlled trial
Authors: Boettcher Johanna , Heinrich Manuel , Boettche Maria , Burchert Sebastian , Glaesmer Heide , Gouzoulis-Mayfrank Euphrosyne , Heeke Carina , Hernek Martina , Knaevelsrud Christine , Konnopka Alexander , Muntendorf Louisa , Nilles Hannah , Nohr Laura , Pohl Steffi , Paskuy Sophia , Reinhardt Isabelle , Sierau Susan , Stammel Nadine , Wirz Christina , Renneberg Babette , Wagner Birgit 
Published: January 2024

Abstract
Background
Refugee populations have an increased risk for mental disorders, such as depression, anxiety, and posttraumatic stress disorders. Comorbidity is common. At the same time, refugees face multiple barriers to accessing mental health treatment. Only a minority of them receive adequate help. The planned trial evaluates a low-threshold, transdiagnostic Internet-based treatment. The trial aims at establishing its efficacy and cost-effectiveness compared with no treatment.

Methods
N = 131 treatment-seeking Arabic- or Farsi-speaking patients, meeting diagnostic criteria for a depressive, anxiety, and/or posttraumatic stress disorder will be randomized to either the intervention or the waitlist control group. The intervention group receives an Internet-based treatment with weekly written guidance provided by Arabic- or Farsi-speaking professionals. The treatment is based on the Common Elements Treatment Approach (CETA), is tailored to the individual patient, and takes 6–16 weeks. The control group will wait for 3 months and then receive the Internet-based treatment.

Discussion
The planned trial will result in an estimate of the efficacy of a low-threshold and scalable treatment option for the most common mental disorders in refugees.

Trial registration
German Registry for Clinical Trials DRKS00024154. Registered on February 1, 2021.
Randomized study of two different consent procedures on recall: a study within a digital alcohol intervention trial
Authors: Ulfsdotter Gunnarsson Katarina , Collier Elizabeth S. , McCambridge Jim , Bendtsen Marcus 
Published: January 2024

Abstract
Introduction
Individuals’ comprehension of the information provided in consent forms should fundamentally influence whether to participate initially in a study and later whether to remain a participant. Existing evidence, however, suggests that participants do not thoroughly read, comprehend, or recall the information in consent forms. This study aimed to better understand how well participants recalled trial procedure information in the consent materials they received prior to taking part in a trial of a digital alcohol intervention.

Method
This study was nested within an online effectiveness trial. The study included a contrast between two layout approaches to present the trial procedure information: one where all materials were shown on the same page (One page) and one where participants had to click on links to get materials for certain parts of the study information (Active request). Recall of trial procedures was measured 2 months post-randomization with four questions. Participants were also asked to leave a comment after each question.

Result
Of the 2437 individuals who registered interest in the parent trial, 1197 were randomized to One page and 1240 were randomized to Active request. Approximately 90% consented to participate and 53% of the participants responded to the recall questionnaire. Contrasting the consent layout showed no marked differences between groups in three out of the four questions on recall of trial procedures. There was, however, evidence that recall of aspects of how personal data would be handled during the trial did differ between the two groups, with the Active request group reporting less recall than the One page group. Free-text comments were used to give nuance to the quantitative analysis.

Conclusion
Participants exposed to different layouts of trial procedure information exhibited varying levels of information recall 2 months after consenting. The findings highlight the influence of the presentation of consent forms, which should be given attention when designing trials.

Trial registration
ISRCTN ISRCTN48317451. Registered 6 December 2018, https://www.isrctn.com/ISRCTN48317451
PeRsOnaliSed care Planning for oldER people with frailty (PROSPER): protocol for a randomised controlled trial
Authors: Heaven Anne , Bower Peter , Day Florence , Farrin Amanda , Fernadez Catherine , Foster Marilyn , Foy Robbie , Hawkins Rebecca , Hulme Claire , Humphrey Sara , Lawton Rebecca , Parker Catriona , Thompson Ellen , West Robert , Clegg Andrew 
Published: January 2024

Abstract
Background
Frailty is common in older age and is characterised by loss of biological reserves across multiple organ systems. These changes associated with frailty mean older people can be vulnerable to sudden, dramatic changes in health because of relatively small problems. Older people with frailty are at increased risk of adverse outcomes including disability, hospitalisation, and care home admission, with associated reduction in quality of life and increased NHS and social care costs. Personalised Care Planning offers an anticipatory, preventative approach to supporting older adults to live independently for longer, but it has not been robustly evaluated in a population of older adults with frailty.

Methods
Following an initial feasibility study, this multi-centre, individually randomised controlled trial aims to establish whether personalised care planning for older people improves health-related quality of life. It will recruit 1337 participants from general practices across Yorkshire and Humber and Mid-Mersey in the North of England. Eligible patients will be aged 65 and over with an electronic frailty index score of 0.21 or above, living in their own homes, without severe cognitive impairment and not in receipt of end-of-life care. Following confirmation of eligibility, informed consent and baseline data collection, participants will be individually randomised to the PeRsOnaliSed care Planning for oldER people with frailty (PROSPER) intervention or usual care in a 2.6:1 allocation ratio. Participants will not be blinded to allocation, but data collection and analysis will be blinded. The intervention will be delivered over 12 weeks by a Personal Independence Co-ordinator worker based within a voluntary sector organisation, Age UK. The primary outcomes are health-related quality of life, measured using both the physical and mental components of the Short-Form 12 Item Health Questionnaire at 12 months after randomisation. Secondary outcomes comprise activities of daily living, self-management capabilities and loneliness, admission to care homes, hospitalisations, and health and social care resource use at 12 months post randomisation. Parallel cost-effectiveness and process evaluations will be conducted alongside the trial.

Discussion
The PROSPER study will evaluate the effectiveness and cost-effectiveness of a personalised care planning approach for older people with frailty and inform the process of its implementation.

Trial registration
mailto:ISRCTN16123291. Registered on 28 August 2020.
A randomized, controlled clinical study of low-molecular-weight heparin improving pregnancy outcomes in PCOS women undergoing IVF: study protocol
Authors: Huang Ou , Ding Haixia , Wu Dandan , Zhang Qing , Li Wen 
Published: January 2024

Abstract
Background
Polycystic ovary syndrome (PCOS), an incidence of 10–15% in women of reproductive age, shows sex hormone disorders, luteal insufficiency, and the tendency of placental villus space thrombus. The incidence of early pregnancy loss in women with PCOS is three to eight times higher than that in non-PCOS women. PCOS women were reported in a pre-thrombotic state, which was manifested by accelerated thrombin production, increased PAI-1 activity, and fibrinogen. Other research also found an over-activated state of women with PCOS in immune system. Therefore, changing the prethrombotic state of PCOS through anticoagulation may be a new way to improve the adverse pregnancy outcome of PCOS. Low-molecular-weight heparin (LMWH) is the most common used anticoagulant drug in pregnancy, and it also was proposed for the prevention of recurrent abortion, although the application of LMWH in PCOS population during early pregnancy has not been reported. The objective of this study is to investigate the effect of LMWH on pregnancy outcomes after invitro fertilization-frozen embryo transfer (IVF-FET) in patients with polycystic ovary syndrome.

Methods
A total of 356 PCOS women aged between 20 and 38 years which prepared for IVF followed with FET will be enrolled in the study. The patients, from four different hospitals stratified by age and body mass index (BMI), will be randomly divided into the study group who will be treated with LMWH started on the day of progesterone transformation (hormone therapy) during FET cycle and the control group without additional medicine. Serum or urine hCG test will be given 14 days after embryo transfer to confirm biochemical pregnancy. If pregnancy is positive, LMWH+ hormone therapy/hormone therapy will be continued for another 2 weeks. Transvaginal ultrasonography will be performed 14 days later to confirm intrauterine pregnancy. The primary outcome is the ongoing pregnancy, which is defined as intrauterine live fetus with ultrasound after 12 weeks of gestation.

Discussion
This is the first study protocol to investigate the efficacy of LMWH as an adjuvant drug for IVF-FET outcomes in PCOS women, by comparing differences in ongoing pregnancy rate, clinical pregnancy rate, live birth rate, and early pregnancy loss rate between LMWH group and the control group.

Trial registration
ClinicalTrials.gov ChiCTR2000036527. Registered on August 24, 2020