bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of NELL2/NICOL-ROS1 lumicrine signaling-related molecules in the human male reproductive tract
Authors: Kiyozumi Daiji 
Published: January 2024

AbstractThe maturation of spermatozoa is a regulated process, influenced by genes expressing essential secreted proteins in the proximal epididymis. Recent genetic studies in rodents have identified the non-sex steroidal molecular signals that regulate gene expression in the proximal epididymis. Germ cells in the testis secrete ligand proteins into the seminiferous tubule lumen The ligand proteins travel through the male reproductive tract lumen to the epididymis, where they bind to receptors, triggering the differentiation of the luminal epithelium for sperm maturation. It is, however, not fully unveiled if such a testis-epididymis trans-luminal signaling mechanism exists in other species, especially humans. In the present study, the rodent-type testis-epididymis trans-luminal signaling in the human male reproductive tract was evaluated in a step-by-step manner by analyzing testis and epididymis gene expression and signaling mediator protein function. There was a significant correlation between the epididymal expressions of mouse genes upregulated by the trans-luminal signaling and those of their human orthologs, as evaluated by the correlation coefficient of 0.604. The transcript expression of NELL2 and NICOL encoding putative ligand proteins was also observed in human testicular cells. In vitro experiments demonstrated that purified recombinant human NELL2 and NICOL formed a molecular complex with similar properties to rodent proteins, which was evaluated by a dissociation equilibrium constant of 110 nM. Recombinant human NELL2 also specifically bound to its putative receptor human ROS1 in vitro. Collectively, these findings suggest that the rodent-type testis-epididymis secreted signaling mechanism is also possible in the human male reproductive tract.
Assessing unConventional Evidence (ACE) tool: development and content of a tool to assess the strengths and limitations of ‘unconventional’ source materials
Authors: Lewin Simon , Langlois Etienne V. , Tunçalp Özge , Portela Anayda 
Published: January 2024

Abstract
Background
When deciding whether to implement an intervention, decision-makers typically have questions on feasibility and acceptability and on factors affecting implementation. Descriptions of programme implementation and of policies and systems are rich sources of information for these questions. However, this information is often not based on empirical data collected using explicit methods. To use the information in unconventional source materials in syntheses or other decision support products, we need methods of assessing their strengths and limitations. This paper describes the development and content of the Assessing unConventional Evidence (ACE) tool, a new tool to assess the strengths and limitations of these sources.

Methods
We developed the ACE tool in four stages: first, we examined existing tools to identify potentially relevant assessment criteria. Second, we drew on these criteria and team discussions to create a first draft of the tool. Third, we obtained feedback on the draft from potential users and methodologists, and through piloting the tool in evidence syntheses. Finally, we used this feedback to iteratively refine the assessment criteria and to improve our guidance for undertaking the assessment.

Results
The tool is made up of 11 criteria including the purpose and context of the source; the completeness of the information presented; and the extent to which evidence is provided to support the findings made. Users are asked to indicate whether each of the criteria have been addressed. On the basis of their judgements for each criterion, users then make an overall assessment of the limitations of the source, ranging from no or very minor concerns to serious concerns. These assessments can then facilitate appropriate use of the evidence in decision support products.

Conclusions
Through focussing on unconventional source materials, the ACE tool fills an important gap in the range of tools for assessing the strengths and limitations of policy-relevant evidence and supporting evidence-informed decision-making.
PIGT promotes cell growth, glycolysis, and metastasis in bladder cancer by modulating GLUT1 glycosylation and membrane trafficking
Authors: Tan Mingyue , Pan Qi , Yu Chao , Zhai Xinyu , Gu Jianyi , Tao Le , Xu Dongliang 
Published: January 2024

Abstract
Background
Bladder cancer is very common worldwide. PIGT is a subunit of the glycosylphosphatidylinositol transamidase which involves in tumorigenesis and invasiveness. m6A modification of mRNA has been linked to cell proliferation, tumor progression and other biological events. However, how PIGT is regulated and what is the function of PIGT in bladder cancer remains to be elucidated.

Methods
PIGT was silenced or overexpressed to study its role in regulating bladder cancer. Cell proliferation and invasion were examined with the Cell Counting Kit-8, colony formation and Transwell assay, respectively. Cellular oxygen consumption rates or extracellular acidification rates were detected by a XF24 Analyzer. Quantitative RT-PCR and immunoblots were performed to detect mRNA and protein levels.

Results
PIGT was overexpressed in bladder cancer. Silencing PIGT inhibited cell proliferation, oxidative phosphorylation, and glycolysis. Overexpressing PIGT promoted cell proliferation, oxidative phosphorylation, glycolysis in vitro and tumor metastasis in vivo by activating glucose transporter 1 (GLUT1). PIGT also promoted GLUT1 glycosylation and membrane trafficking. Wilms’ tumor 1-associated protein (WTAP) mediated PIGT m6A modification, and m6A reader, insulin-like growth factor 2 mRNA-binding protein (IGF2BP2), binds to the methylated PIGT to promote the stability of PIGT, leading to up-regulation of PIGT.

Conclusion
WTAP mediates PIGT m6A modification to increase the stability of PIGT via the IGF2BP2, which enhances cell proliferation, glycolysis, and metastasis in bladder cancer by modulating GLUT1 glycosylation and membrane trafficking.
NCAPG2 promotes prostate cancer malignancy and stemness via STAT3/c-MYC signaling
Authors: Zhang Enchong , Chen Zhengjie , Liu Wangmin , Lin Lin , Wu Lina , Guan Johnny , Wang Jianfeng , Kong Chuize , Bi Jianbin , Zhang Mo 
Published: January 2024

Abstract
Background
Prostate cancer (PCa) is the second leading cause of cancer-related mortality among men worldwide, and its incidence has risen substantially in recent years. Therefore, there is an urgent need to identify novel biomarkers and precise therapeutic targets for managing PCa progression and recurrence.

Methods
We investigated the clinical significance of NCAPG2 in PCa by exploring public datasets and our tissue microarray. Receiver operating characteristic (ROC) curve and survival analyses were performed to evaluate the correlation between NCAPG2 and PCa progression. Cell proliferation, wound healing, transwell, flow cytometry, cell cycle, tumor sphere formation, immunofluorescence (IF), co-immunoprecipitation (co-IP), and chromatin immunoprecipitation (ChIP) assays were conducted to further elucidate the molecular mechanism of NCAPG2 in PCa. Subcutaneous and orthotopic xenograft models were applied to investigate the effects of NCAPG2 on PCa proliferation in vivo. Tandem mass tag (TMT) quantitative proteomics was utilized to detect proteomic changes under NCAPG2 overexpression.

Results
NCAPG2 was significantly upregulated in PCa, and its overexpression was associated with PCa progression and unfavorable prognosis. Knockdown of NCAPG2 inhibited the malignant behavior of PCa cells, whereas its overexpression promoted PCa aggressiveness. NCAPG2 depletion attenuated the development and growth of PCa in vivo. TMT quantitative proteomics analyses indicated that c-MYC activity was strongly correlated with NCAPG2 expression. The malignancy-promoting effect of NCAPG2 in PCa was mediated via c-MYC. NCAPG2 could directly bind to STAT3 and induce STAT3 occupancy on the MYC promoter, thus to transcriptionally activate c-MYC expression. Finally, we identified that NCAPG2 was positively correlated with cancer stem cell (CSC) markers and enhanced self-renewal capacity of PCa cells.

Conclusions
NCAPG2 is highly expressed in PCa, and its level is significantly associated with PCa prognosis. NCAPG2 promotes PCa malignancy and drives cancer stemness via the STAT3/c-MYC signaling axis, highlighting its potential as a therapeutic target for PCa.
Function and mechanism of GBP1 in the development and progression of cervical cancer
Authors: Wang Senyu , Zhang Yajing , Ma Xiumin , Feng Yangchun 
Published: January 2024

AbstractGuanylate binding protein 1 (GBP1) is the most concerned member of the GBP family, which has a series of effects such as anti-infection and anti-angiogenesis. Its role in malignant tumors including cervical cancer is still controversial. We aim to explore the effects of GBP1 on cervical cancer through bioinformatics and related experiments. In this study, we first found that GBP1 was generally expressed in cervical cancer in various online databases and was closely related to immune invasion. Secondly, we used multicolor immunofluorescence technology to verify the expression of GBP1 in cervical cancer tissues and its relationship with immune invasion, and explored its relationship with the prognosis of patients with cervical cancer. Knockdown and overexpression assays of GBP1 in vitro were used to prove GBP1 as a potential oncogene of cervical cancer, and its carcinogenicity was verified by in vivo experiment. In order to explore the potential mechanism of GBP1 in promoting cancer, RNA-seq was performed on GBP1 overexpression and knockdown expression cell lines, and GBP1 knockdown and overexpression were found to be associated with many RNA alternative splicing events, suggesting that GBP1 maybe a RNA binding protein (RBP) which affect the biological characteristics of cervical cancer cells through the alternative splicing pathway. However, the later RNA binding protein immunoprecipitation (RIP) assay proved that GBP1 was not a direct alternative splicing factor, while the co-immunoprecipitation (CoIP)-mass spectroscopy (MS) assay combined with protein protein interaction (PPI) analysis proved that 8 alternative splicing factors including Heterogeneous Nuclear Ribonucleoprotein K (HNRNPK) were interacting proteins of GBP1. Combined with the existing reports and the results of RNA-seq alternative splicing analysis, it is speculated that GBP1 may regulate the alternative splicing of CD44 protein by binding to interacting protein-HNRNPK, and thus play a role in promoting cancer in cervical cancer.
Deficiency of Trex1 leads to spontaneous development of type 1 diabetes
Authors: Zhao Jiang-Man , Su Zhi-Hui , Han Qiu-Ying , Wang Miao , Liu Xin , Li Jing , Huang Shao-Yi , Chen Jing , Li Xiao-Wei , Chen Xia-Ying , Guo Zeng-Lin , Jiang Shuai , Pan Jie , Li Tao , Xue Wen , Zhou Tao 
Published: January 2024

AbstractBackgroundType 1 diabetes is believed to be an autoimmune condition, characterized by destruction of insulin-producing cells, due to the detrimental inflammation in pancreas. Growing evidences have indicated the important role of type I interferon in the development of type 1 diabetes.MethodsTrex1-deficient rats were generated by using CRISPR-Cas9. The fasting blood glucose level of rat was measured by a Roche Accuchek blood glucose monitor. The levels of insulin, islet autoantibodies, and interferon-β were measured using enzyme-linked immunosorbent assay. The inflammatory genes were detected by quantitative PCR and RNA-seq. Hematein-eosin staining was used to detect the pathological changes in pancreas, eye and kidney. The pathological features of kidney were also detected by Masson trichrome and periodic acid-Schiff staining. The distribution of islet cells, immune cells or ssDNA in pancreas was analyzed by immunofluorescent staining.ResultsIn this study, we established aTrex1-deletion Sprague Dawley rat model, and unexpectedly, we found that theTrex1−/−rats spontaneously develop type 1 diabetes. Similar to human diabetes, the hyperglycemia in rats is accompanied by diabetic complications such as diabetic nephropathy and cataract. Mechanistical investigation revealed the accumulation of ssDNA and the excessive production of proinflammatory cytokines, including IFN-β, inTrex1null pancreas. These are likely contributing to the inflammation in pancreas and eventually leading to the decline of pancreatic β cells.ConclusionsOur study links the DNA-induced chronic inflammation to the pathogenesis of type 1 diabetes, and also provides an animal model for type 1 diabetes studies.
Institutionalization for good governance to reach sustainable health development: a framework analysis
Authors: Haghighi Hajar , Takian Amirhossein 
Published: January 2024

Abstract
Background
This article explores the concept of institutionalization, which is the process of transforming ideas into programs and automating actions, in the context of health system governance and sustainable development. Institutionalization is a key mechanism for creating accountable and transparent institutions, which are essential for achieving health system resilience and sustainability. This study identifies the components and dimensions of institutionalization in the health system and its relationship with good governance and sustainable health development.

Main text
We applied a scoping review method in five steps. First, we formulated a question for our research. Then, we concluded a comprehensive literature search in five electronic databases for identifying relevant studies. This review has two phases: identifying the concept of institutional approach and its components in health system, and its relationship with good governance to reach Sustainable Health Development (SHD). The third step was study selection, and the 1st author performed data abstraction. The key issues which are identified in our review, related to the concepts of SDH, its goals, pillars and principles; positive peace; good governance; components of institutional approach components, and their relations. Finally, we summarized and organized our findings in a format of a proposed conceptual framework, to underpin the role of institutionalization in the health system to achieve sustainable development.

Conclusion
Institutionalization is a key concept for achieving positive peace and good governance, which requires meaningful involvement of leaders, politicians, civil society, and public participation. It also depends on the conditions of justice, human rights, transparency, accountability and rule of law. In the wake of COVID-19, institutionalization is more crucial than ever for advancing sustainable development, especially in the context of low and middle-income countries (LMICs).
Surgical aortic valve replacement etiologies, hemodynamics, and outcomes in 1346 patients from the Malaysian heart centre
Authors: Roslan Aslannif , Soon Chong Kee , Sin Tey Yee , Aktifanus Ahmad Tantawi Jauhari , Ling Soh Si , Boon Wong Kian , Rusani Beni I. , Hadi Hafidz Abd , Kolanthaivelu Jayakhanthan , Yahaya Shaiful Azmi , Dillon Jeswant , Yunus Alwi M. 
Published: January 2024

Abstract
Background
This study examined the characteristics and outcomes of surgical aortic valve replacement (SAVR) both isolated and in combination with other cardiac surgery in Malaysia from 2015 to 2021.

Methods
This was a retrospective study of 1346 patients analyzed on the basis of medical records, echocardiograms and surgical reports. The overall sample was both considered as a whole and divided into aortic stenosis (AS)/aortic regurgitation (AR)-predominant and similar-severity subgroups.

Results
The most common diagnosis was severe AS (34.6%), with the 3 most common etiologies being bicuspid valve degeneration (45.3%), trileaflet valve degeneration (36.3%) and rheumatic valve disease (12.2%). The second most common diagnosis was severe AR (25.5%), with the most common etiologies being root dilatation (21.0%), infective endocarditis (IE) (16.6%) and fused prolapse (12.2%). Rheumatic valve disease was the most common mixed disease. A total of 54.5% had AS-predominant pathology (3 most common etiologies: bicuspid valve degeneration valve, degenerative trileaflet valve and rheumatic valve disease), 36.9% had AR-predominant pathology (top etiologies: root dilatation, rheumatic valve disease and IE), and 8.6% had similar severity of AS and AR. Overall, 62.9% of patients had trileaflet valve morphology, 33.3% bicuspid, 0.6% unicuspid and 0.3% quadricuspid. For AS, the majority were high-gradient severe AS (49.9%), followed by normal-flow low-gradient (LG) severe AS (10.0%), paradoxical low-flow (LF)-LG severe AS (6.4%) and classical LF-LG severe AS (6.1%). The overall in-hospital and total 1-year mortality rates were 6.4% and 14.8%, respectively. Pure severe AS had the highest mortality. For AS-predominant pathology, the etiology with the highest mortality was trileaflet valve degeneration; for AR-predominant pathology, it was dissection. The overall survival probability at 5 years was 79.5% in all patients, 75.7% in the AS-predominant subgroup, 83.3% in the AR-predominant subgroup, and 87.3% in the similar-severity subgroup.

Conclusions
The 3 most common causes of AS- predominant patients undergoing SAVR is bicuspid valve degeneration, degenerative trileaflet valve and rheumatic and for AR-predominant is root dilatation, rheumatic and IE. Rheumatic valve disease is an important etiology in our SAVR patients especially in mixed aortic valve disease.
Study registration IJNREC/562/2022.
Pharmacological properties of Polygonatum and its active ingredients for the prevention and treatment of cardiovascular diseases
Authors: Lin Hongyuan , Wang Wenhui , Peng Mengqi , Kong Yifan , Zhang Xiaowei , Wei Xiaohong , Shang Hongcai 
Published: January 2024

AbstractDespite continued advances in prevention and treatment strategies, cardiovascular diseases (CVDs) remain the leading cause of death worldwide, and more effective therapeutic methods are urgently needed. Polygonatum is a traditional Chinese herbal medicine with a variety of pharmacological applications and biological activities, such as antioxidant activity, anti-inflammation, antibacterial effect, immune-enhancing effect, glucose regulation, lipid-lowering and anti-atherosclerotic effects, treatment of diabetes and anticancer effect. There has also been more and more evidence to support the cardioprotective effect of Polygonatum in recent years. However, up to now, there has been a lack of comprehensive studies on the active ingredients and their pharmacotoxicological effects related to cardiovascular diseases. Therefore, the main active components of Polygonatum (including Polysaccharides, Flavonoids, Saponins) and their biological activities were firstly reviewed in this paper. Furthermore, we summarized the pharmacological effects of Polygonatum’s active components in preventing and treating CVDs, and its relevant toxicological investigations. Finally, we emphasize the potential of Polygonatum in the prevention and treatment of CVDs.
3D-printed PCL@BG scaffold integrated with SDF-1α-loaded hydrogel for enhancing local treatment of bone defects
Authors: Wang Chenglong , Dong Jinlei , Liu Fanxiao , Liu Nan , Li Lianxin 
Published: January 2024

Abstract
Background
The long-term nonunion of bone defects is always a difficult problem in orthopaedics treatment. Artificial bone implants made of polymeric materials are expected to solve this problem due to their suitable degradation rate and good biocompatibility. However, the lack of mechanical strength, low osteogenic induction ability and poor hydrophilicity of these synthetic polymeric materials limit their large-scale clinical application.

Results
In this study, we used bioactive glass (BG) (20%, W/W) and polycaprolactone (PCL, 80%, W/W) as raw materials to prepare a bone repair scaffold (PCL@BG20) using fused deposition modelling (FDM) three-dimensional (3D) printing technology. Subsequently, stromal cell-derived factor-1α (SDF-1α) chemokines were loaded into the PCL@BG20 scaffold pores with gelatine methacryloyl (GelMA) hydrogel. The experimental results showed that the prepared scaffold had a porous biomimetic structure mimicking that of cancellous bone, and the compressive strength (44.89 ± 3.45 MPa) of the scaffold was similar to that of cancellous bone. Transwell experiments showed that scaffolds loaded with SDF-1α could promote the recruitment of bone marrow stromal cells (BMSCs). In vivo data showed that treatment with scaffolds containing SDF-1α and BG (PCL@BG-GelMA/SDF-1α) had the best effect on bone defect repair compared to the other groups, with a large amount of new bone and mature collagen forming at the bone defect site. No significant organ toxicity or inflammatory reactions were observed in any of the experimental groups.

Conclusions
The results show that this kind of scaffold containing BG and SDF-1α serves the dual functions of recruiting stem cell migration in vivo and promoting bone repair in situ. We envision that this scaffold may become a new strategy for the clinical treatment of bone defects.
Clinical study protocol on electronic cigarettes and nicotine pouches for smoking cessation in Pakistan: a randomized controlled trial
Authors: Hameed Abdul , Malik Daud 
Published: January 2024

Abstract
Background
Pakistan is one of most vulnerable low- and middle-income countries with 29 million adult active tobacco users. Smoking cessation services are lacking as the tobacco control initiatives have largely failed to address the smoking endemic. Over the last 5 years, Pakistan has witnessed the use of innovative tobacco harm reduction (THR) products such as e-cigarettes and nicotine pouches. However, their use remains limited. THR products are imported legally as consumer goods and are taxable. The lack of sufficient data for THR and its application is a challenge in gauging their effectiveness in assisting smokers quit combustible smoking. Evidence-based studies can help in measuring the effectiveness of e-cigarettes and nicotine pouches as smoking cessation aids.

Method
Keeping in view the study objectives, a sample size of 600 participants will be sufficient to assess the effectiveness of e-cigarettes and nicotine pouches for smoking cessation in Pakistan. Of these, 200 participants each will receive e-cigarettes and nicotine pouches along with basic care counselling, while the remaining 200 participants will only receive basic care counselling for 48 weeks. The association of participants’ characteristics with smoking and health status will be based on the bivariate and multivariate analysis. The simple t-test and variance analysis will assess the differences in intervention indicators between the control and treatment groups. For the inferential analysis, the average treatment impact will be based on the quasi-experimental techniques such as difference in difference (DID) or propensity score matching (PMS).

Discussion
The study will evaluate the participants at the baseline as they decide the quit date. After every 12 weeks, a follow-up survey with the participants will be conducted. Results are anticipated to inform the public, decision-makers, and researchers about the effects of using e-cigarettes and nicotine pouches in the short- and medium-term periods. Critically, the potential of e-cigarettes and other alternative nicotine delivery systems as smoking cessation aid will be assessed.

Trial registration
ClinicalTrials.gov
NCT05715164. Registered on February 6, 2023. Protocol version. Protocol version 1.0, 14-12-2022
Trial in progress and not yet recruiting participants. Estimated primary data collection date—April 2024