bluuebunny/crossref_metadata_2025_split huggingface dataset:
Guideline documents on caesarean section on maternal request in Sweden: varying usability with a restrictive approach
Authors: Mattebo Magdalena , Holmström Inger K , Höglund Anna T , Fredriksson Mio 
Published: October 2023

Abstract
Background
Globally, studies illustrate different approaches among health care professionals to decision making about caesarean section (CS) and that attitudes regarding the extent to which a CS on maternal request (CSMR) can be granted vary significantly, both between professionals and countries. Absence of proper regulatory frameworks is one potential explanation for high CSMR rates in some countries, but overall, it is unclear how recommendations and guidelines on CSMR relate to CSMR rates. In Sweden, CSMR rates are low by international comparison, but statistics show that the extent to which maternity clinics perform CSMR vary among Sweden’s 21 self-governing regions. These regions are responsible for funding and delivery of healthcare, while national guidelines provide guidance for the professions throughout the country; however, they are not mandatory. To further understand considerations for CSMR requests and existing practice variations, the aim was to analyse guideline documents on CSMR at all local maternity clinics in Sweden.

Methods
All 43 maternity clinics in Sweden were contacted and asked for any guideline documents regarding CSMR. All clinics replied, enabling a total investigation. We used a combined deductive and inductive design, using the framework method for the analysis of qualitative data in multi-disciplinary health research.

Results
Overall, 32 maternity clinics reported guideline documents and 11 denied having any. Among those reporting no guideline documents, one referred to using national guideline document. Based on the Framework method, four theme categories were identified: CSMR is treated as a matter of fear of birth (FOB); How important factors are weighted in the decision-making is unclear; Birth contracts are offered in some regions; and The post-partum care is related to FOB rather than CSMR.

Conclusion
In order to offer women who request CS equal and just care, there is a pressing need to either implement current national guideline document at all maternity clinics or rewrite the guideline documents to enable clinics to adopt a structured approach. The emphasis must be placed on exploring the reasons behind the request and providing unbiased information and support. Our results contribute to the ongoing discussion about CSMR and lay a foundation for further research in which professionals, as well as stakeholders and both women planning pregnancy and pregnant women, can give their views on this issue.
A review of three decades of use of the cattle brucellosis rough vaccine Brucella abortus RB51: myths and facts
Authors: Blasco J. M. , Moreno E. , Muñoz P. M. , Conde-Álvarez R. , Moriyón I. 
Published: October 2023

AbstractCattle brucellosis is a severe zoonosis of worldwide distribution caused byBrucella abortusandB. melitensis. In some countries with appropriate infrastructure, animal tagging and movement control, eradication was possible through efficient diagnosis and vaccination withB. abortusS19, usually combined with test-and-slaughter (T/S). Although S19 elicits anti-smooth lipopolysaccharide antibodies that may interfere in the differentiation of infected and vaccinated animals (DIVA), this issue is minimized using appropriate S19 vaccination protocols and irrelevant when high-prevalence makes mass vaccination necessary or when eradication requisites are not met. However, S19 has been broadly replaced by vaccine RB51 (a rifampin-resistant rough mutant) as it is widely accepted that is DIVA, safe and as protective as S19. These RB51 properties are critically reviewed here using the evidence accumulated in the last 35 years. Controlled experiments and field evidence shows that RB51 interferes in immunosorbent assays (iELISA, cELISA and others) and in complement fixation, issues accentuated by revaccinating animals previously immunized with RB51 or S19. Moreover, contacts with virulent brucellae elicit anti-smooth lipopolysaccharide antibodies in RB51 vaccinated animals. Thus, accepting that RB51 is truly DIVA results in extended diagnostic confusions and, when combined with T/S, unnecessary over-culling. Studies supporting the safety of RB51 are flawed and, on the contrary, there is solid evidence that RB51 is excreted in milk and abortifacient in pregnant animals, thus being released in abortions and vaginal fluids. These problems are accentuated by the RB51 virulence in humans, lack diagnostic serological tests detecting these infections and RB51 rifampicin resistance. In controlled experiments, protection by RB51 compares unfavorably with S19 and lasts less than four years with no evidence that RB51-revaccination bolsters immunity, and field studies reporting its usefulness are flawed. There is no evidence that RB51 protects cattle againstB. melitensis,infection common when raised together with small ruminants. Finally, data acumulated during cattle brucellosis eradication in Spain shows that S19-T/S is far more efficacious than RB51-T/S, which does not differ from T/S alone. We conclude that the assumption that RB51 is DIVA, safe, and efficaceous results from the uncritical repetition of imperfectly examined evidence, and advise against its use.
Interaction, immune infiltration characteristics and prognostic modeling of efferocytosis-related subtypes in glioblastoma
Authors: Zhao Songyun , Wang Qi , Liu Yuankun , Zhang Pengpeng , Ji Wei , Xie Jiaheng , Cheng Chao 
Published: October 2023

Abstract
Background
Efferocytosis is a biological process in which phagocytes remove apoptotic cells and vesicles from tissues. This process is initiated by the release of inflammatory mediators from apoptotic cells and plays a crucial role in resolving inflammation. The signals associated with efferocytosis have been found to regulate the inflammatory response and the tumor microenvironment (TME), which promotes the immune escape of tumor cells. However, the role of efferocytosis in glioblastoma multiforme (GBM) is not well understood and requires further investigation.

Methods
In this study, we conducted a comprehensive analysis of 22 efferocytosis-related genes (ERGs) by searching for studies related to efferocytosis. Using bulk RNA-Seq and single-cell sequencing data, we analyzed the expression and mutational characteristics of these ERGs. By using an unsupervised clustering algorithm, we obtained ERG clusters from 549 GBM patients and evaluated the immune infiltration characteristics of each cluster. We then identified differential genes (DEGs) in the two ERG clusters and classified GBM patients into different gene clusters using univariate cox analysis and unsupervised clustering algorithms. Finally, we utilized the Boruta algorithm to screen for prognostic genes and reduce dimensionality, and the PCA algorithm was applied to create a novel efferocytosis-related scoring system.

Results
Differential expression of ERGs in glioma cell lines and normal cells was analyzed by rt-PCR. Cell function experiments, on the other hand, validated TIMD4 as a tumor risk factor in GBM. We found that different ERG clusters and gene clusters have distinct prognostic and immune infiltration profiles. The ERG signature we developed provides insight into the tumor microenvironment of GBM. Patients with lower ERG scores have a better survival rate and a higher likelihood of benefiting from immunotherapy.

Conclusions
Our novel efferocytosis-related signature has the potential to be used in clinical practice for risk stratification of GBM patients and for selecting individuals who are likely to respond to immunotherapy. This can help clinicians design appropriate targeted therapies before initiating clinical treatment.
Causal relationships between blood lipids and major psychiatric disorders: Univariable and multivariable mendelian randomization analysis
Authors: Li Bozhi , Qu Yue , Fan Zhixin , Gong Xiayu , Xu Hanfang , Wu Lili , Yan Can 
Published: October 2023

Abstract
Background
Whether the positive associations of blood lipids with psychiatric disorders are causal is uncertain. We conducted this two-sample Mendelian randomization (MR) analysis to comprehensively investigate associations of blood lipids with psychiatric disorders.

Methods
Univariable and multivariable models were established for MR analyses. Inverse variance-weighted (IVW) MR was employed as the main approach; weighted median and MR-Egger were used as sensitivity analysis methods. The possibility of violating MR assumptions was evaluated utilizing several sensitivity analyses, including heterogeneity statistics, horizontal pleiotropy statistics, single SNP analysis, leave-one-out analysis and MR-PRESSO analysis. As instrumental variables, we screened 362 independent single-nucleotide polymorphisms (SNP) related to blood lipids from a recent genome-wide association study involving 76,627 individuals of European ancestry, with a genome-wide significance level of p < 5 × 10− 8. Summary-level information for the six psychiatric disorders was extracted from Psychiatric Genomics Consortium and Alzheimer Disease Genetics Consortium.

Results
We observed eight significant associations in univariable MR analysis, four of which were corroborated by multivariable MR (MVMR) analysis modified for the other three lipid traits: high-density lipoprotein cholesterol (HDL-C) level with the risk of PTSD (OR = 0.91, 95% CI = 0.85–0.97, p = 0.002) and AD (OR = 0.79, 95% CI = 0.71–0.88, p < 0.001) and triglycerides (TG) level with the risk of MDD (OR = 1.02, 95% CI = 1.003–1.03, p = 0.01) and panic disorder (OR = 0.83, 95% CI = 0.74–0.92, p < 0.001). In addition, four associations were not significant in MVMR analysis after adjustment for three lipid traits: total cholesterol (TC) level with the risk of PTSD, low-density lipoprotein cholesterol (LDL-C) level with the risk of MDD and AD and TG level with the risk of AD.

Conclusions
Our results show that blood lipids and psychiatric disorders may be related in a causal manner. This shows that abnormal blood lipid levels may act as reliable biomarker of psychiatric disorders and as suitable targets for their prevention and treatment.
Enhanced effect of seasonal malaria chemoprevention when coupled with nutrients supplementation for preventing malaria in children under 5 years old in Burkina Faso: a randomized open label trial
Authors: Sondo Paul , Kaboré Bérenger , Rouamba Toussaint , Compaoré Eulalie , Tibiri Yssimini Nadège Guillène , Kaboré Hyacinthe Abd-El Latif Faïçal , Derra Karim , Tahita Marc Christian , Ilboudo Hamidou , Tougri Gauthier , Bouda Ismaïla , Dakyo Tikanou , Kafando Hyacinthe , Ouédraogo Florence , Rouamba Eli , Hien So-vii Franck , Kazienga Adama , Compaoré Cheick Saïd , Bambara Estelle , Nana Macaire , Dahal Prabin , Garanet Franck , Kaboré William , Léfèvre Thierry , Guerin Philippe , Tinto Halidou 
Published: October 2023

AbstractBackgroundIn rural African settings, most of the children under the coverage of Seasonal Malaria Chemoprevention (SMC) are also undernourished at the time of SMC delivery, justifying the need for packaging malarial and nutritional interventions. This study aimed at assessing the impact of SMC by coupling the intervention with nutrients supplementation for preventing malaria in children less than 5 years old in Burkina Faso.MethodsA randomized trial was carried out between July 2020 and June 2021 in the health district of Nanoro, Burkina Faso. Children (n = 1059) under SMC coverage were randomly assigned to one of the three study arms SMC + Vitamin A (SMC-A, n = 353) or SMC + Vitamin A + Zinc (SMC-AZc, n = 353) or SMC + Vitamin A + PlumpyDoz(tm) (SMC-APd, n = 353)-a medium quantity—lipid-based nutrient supplement (MQ-LNS). Children were followed up for one year that included an active follow-up period of 6 months with scheduled monthly home visits followed by 6 months passive follow-up. At each visit, capillary blood sample was collected for malaria diagnosis by rapid diagnosis test (RDT).ResultsAdding nutritional supplements to SMC had an effect on the incidence of malaria. A reduction of 23% (adjusted IRR = 0.77 (95%CI 0.61–0.97) in the odds of having uncomplicated malaria in SMC-APd arm but not with SMC-AZc arm adjusted IRR = 0.82 (95%CI 0.65–1.04) compare to control arm was observed. A reduction of 52%, adjusted IRR = 0.48 (95%CI 0.23–0.98) in the odds of having severe malaria was observed in SMC-APd arm compared to control arm. Besides the effect on malaria, this combined strategy had an effect on all-cause morbidity. More specifically, a reduction of morbidity odds of 24%, adjusted IRR = 0.76 (95%CI 0.60–0.94) in SMC-APd arm compared to control arm was observed. Unlike clinical episodes, no effect of nutrient supplementation on cross sectional asymptomatic infections was observed.ConclusionAdding nutritional supplements to SMC significantly increases the impact of this intervention for preventing children from malaria and other childhood infections.Trial registration: NCT04238845.
Regulation and signaling pathways in cancer stem cells: implications for targeted therapy for cancer
Authors: Zeng Zhen , Fu Minyang , Hu Yuan , Wei Yuquan , Wei Xiawei , Luo Min 
Published: October 2023

AbstractCancer stem cells (CSCs), initially identified in leukemia in 1994, constitute a distinct subset of tumor cells characterized by surface markers such as CD133, CD44, and ALDH. Their behavior is regulated through a complex interplay of networks, including transcriptional, post-transcriptional, epigenetic, tumor microenvironment (TME), and epithelial-mesenchymal transition (EMT) factors. Numerous signaling pathways were found to be involved in the regulatory network of CSCs. The maintenance of CSC characteristics plays a pivotal role in driving CSC-associated tumor metastasis and conferring resistance to therapy. Consequently, CSCs have emerged as promising targets in cancer treatment. To date, researchers have developed several anticancer agents tailored to specifically target CSCs, with some of these treatment strategies currently undergoing preclinical or clinical trials. In this review, we outline the origin and biological characteristics of CSCs, explore the regulatory networks governing CSCs, discuss the signaling pathways implicated in these networks, and investigate the influential factors contributing to therapy resistance in CSCs. Finally, we offer insights into preclinical and clinical agents designed to eliminate CSCs.
Persistent dyslipidemia increases the longitudinal changes in telomere length
Authors: Liu Xiaowei , Ma Tao , Yang Chan , Li Juan , Zhang Yuhong , Zhao Yi 
Published: October 2023

Abstract
Background and aims
Leukocyte telomere length (LTL) as a ‘biological clock’ of aging is closely related to human health, its association with an aging-related disease, dyslipidemia, has been less studied and mainly focused on cross-sectional investigations.

Methods
Two rounds of information and blood collections were conducted on a cohort of 1624 individuals residing in rural Ningxia, located in northwest China, with an average time gap of 9.8 years. The relative telomere length (RTL) of peripheral blood leukocytes was assessed using real-time quantitative PCR. To investigate the association between dyslipidemia, blood lipid levels, and alterations in RTL, multiple linear regression and generalized linear models were employed.

Results
After conducting the follow-up analysis, it was observed that 83.3% of the participants in the study exhibited a reduction in telomere length, while 16.7% experienced an increase in telomere length. The results suggested that dyslipidemia at baseline or follow-up may increase longitudinal changes in telomere length, but it was more significant in the healthy group, especially in those aged ≥ 60 years. Furthermore, HDL-C levels in baseline and follow-up were found to be associated with longitudinal changes in telomere length, and lower HDL-C levels may be associated with increased longitudinal changes in telomere length.

Conclusions
The change in telomere length is correlated with dyslipidemia and its lipid indicators especially HDL-C. Persistent dyslipidemia and a reduction in HDL-C levels may be associated with elevated longitudinal fluctuations in telomere length.
Exosomes from umbilical cord-derived mesenchymal stem cells combined with gelatin methacryloyl inhibit vein graft restenosis by enhancing endothelial functions
Authors: Deng Yuhang , Li Yiming , Chu Zhuyang , Dai Chun , Ge Jianjun 
Published: October 2023

Abstract
Background
The prevalence of coronary artery disease is increasing. As a common treatment method, coronary artery bypass transplantation surgery can improve heart problems while also causing corresponding complications. Venous graft restenosis is one of the most critical and intractable complications. Stem cell-derived exosomes could have therapeutic promise and value. However, as exosomes alone are prone to inactivation and easy removal, this therapeutic method has not been widely used in clinical practice. Methacrylated gelatin (GelMA) is a polymer with a loose porous structure that maintains the biological activity of the exosome and can control its slow release in vivo. In this study, we combined human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) and GelMA to explore their effects and underlying mechanisms in inhibiting venous graft restenosis.

Results
Human umbilical cord mesenchymal stem cells (hUCMSCs) were appraised using flow cytometry. hUCMSC-Exos were evaluated via transmission electron microscopy and western blotting. hUCMSC-Exos embedded in a photosensitive GelMA hydrogel (GelMA-Exos) were applied topically around venous grafts in a rat model of cervical arteriovenous transplantation, and their effects on graft reendothelialization and restenosis were evaluated through ultrasonic, histological, and immunofluorescence examinations. Additionally, we analyzed the material properties, cellular reactions, and biocompatibility of the hydrogels. We further demonstrated that the topical application of GelMA-Exos could accelerate reendothelialization after autologous vein transplantation and reduce restenosis in the rat model. Notably, GelMA-Exos caused neither damage to major organs in mice nor excessive immune rejection. The uptake of GelMA-Exos by endothelial cells stimulated cell proliferation and migration in vitro. A bioinformatic analysis of existing databases revealed that various cell proliferation and apoptosis pathways, including the mammalian target of rapamycin (mTOR)–phosphoinositide 3-kinase (PI3K)–AKT signaling pathways, might participate in the underlying regulatory mechanism.

Conclusions
Compared with the tail vein injection of hUCMSC-Exos, the local application of a mixture of hUCMSC-Exos and GelMA was more effective in promoting endothelial repair of the vein graft and inhibiting restenosis. Therefore, the proposed biomaterial-based therapeutic approach is a promising treatment for venous graft restenosis.
NF-κB signaling in neoplastic transition from epithelial to mesenchymal phenotype
Authors: Oh Amy , Pardo Makayla , Rodriguez Anaelena , Yu Connie , Nguyen Lisa , Liang Olin , Chorzalska Anna , Dubielecka Patrycja M. 
Published: October 2023

AbstractNF-κB transcription factors are critical regulators of innate and adaptive immunity and major mediators of inflammatory signaling. The NF-κB signaling is dysregulated in a significant number of cancers and drives malignant transformation through maintenance of constitutive pro-survival signaling and downregulation of apoptosis. Overactive NF-κB signaling results in overexpression of pro-inflammatory cytokines, chemokines and/or growth factors leading to accumulation of proliferative signals together with activation of innate and select adaptive immune cells. This state of chronic inflammation is now thought to be linked to induction of malignant transformation, angiogenesis, metastasis, subversion of adaptive immunity, and therapy resistance. Moreover, accumulating evidence indicates the involvement of NF-κB signaling in induction and maintenance of invasive phenotypes linked to epithelial to mesenchymal transition (EMT) and metastasis. In this review we summarize reported links of NF-κB signaling to sequential steps of transition from epithelial to mesenchymal phenotypes. Understanding the involvement of NF-κB in EMT regulation may contribute to formulating optimized therapeutic strategies in cancer.
Single-cell RNA sequencing reveals pro-invasive cancer-associated fibroblasts in hypopharyngeal squamous cell carcinoma
Authors: Cai Zhimou , Chen Lin , Chen Siyu , Fang Ruihua , Chen Xiaolin , Lei Wenbin 
Published: October 2023

Abstract
Background
Hypopharyngeal squamous cell carcinoma (HPSCC) has the worst prognosis among all head-and-neck cancers, and treatment options are limited. Tumor microenvironment (TME) analysis can help identify new therapeutic targets and combined treatment strategies.

Methods
Six primary HPSCC tissues and two adjacent normal mucosae from six treatment-naïve patients with HPSCC were analyzed using scRNA-seq. Cell types were curated in detail, ecosystemic landscapes were mapped, and cell–cell interactions were inferred. Key results were validated with The Cancer Genome Atlas and cell biology experiments.

Results
Malignant HPSCC epithelial cells showed significant intratumor heterogeneity. Different subtypes exhibited distinct histological features, biological behaviors, and spatial localization, all affecting treatment selection and prognosis. Extracellular matrix cancer-associated fibroblasts (mCAFs) expressing fibroblast activation protein were the dominant CAFs in HPSCC tumors. mCAFs, constituting an aggressive CAF subset, promoted tumor cell invasion, activated endothelial cells to trigger angiogenesis, and synergized with SPP1+ tumor associated macrophages to induce tumor progression, ultimately decreasing the overall survival of patients with HPSCC. Moreover, the LAMP3+ dendritic cell subset was identified in HPSCC and formed an immunosuppressive TME by recruiting Tregs and suppressing CD8+ T cell function.

Conclusions
mCAFs, acting as the communication center of the HPSCC TME, enhance the invasion ability of HPSCC cells, mobilizing surrounding cells to construct a tumor-favorable microenvironment. Inhibiting mCAF activation offers a new anti-HPSCC therapeutic strategy.

Graphical Abstract