bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lifestyle changes are burdensome with my body broken by pain and obesity: patients’ perspectives after pain rehabilitation
Authors: Storm Elin , Bendelin Nina , Wessman Kim Bergström , Johansson Maria M , Björk Mathilda , Dong Huan-Ji 
Published: October 2023

Abstract
Background
Despite the existing evidence regarding the interrelated relationship between pain and obesity, knowledge about patients’ perspectives of this relationship is scarce, especially from patients with chronic pain and obesity after completing Interdisciplinary Pain Rehabilitation Program (IPRP).

Aims
This qualitative study expands the understanding of patients’ perspectives on how chronic pain and obesity influence each other and how the two conditions affect the ability to make lifestyle changes.

Method
A purposive sample of patients with Body Mass Index (BMI) ≥ 30 kg/m2 and who had completed an IPRP were recruited for individual semi-structured interviews. The transcribed interviews were analysed using latent content analysis and a pattern of theme and categories was constructed based on the participants’ perspectives.

Results
Sixteen patients (aged 28–63 years, 11 female, BMI 30–43 kg/m2) shared their experiences of chronic pain, obesity and lifestyle changes after IPRP. The analysis revealed one overall theme (lifestyle changes are burdensome with a body broken by both pain and obesity) and four categories (pain disturbing days and nights worsens weight control, pain-related stress makes lifestyle changes harder, a painful and obese body intertwined with negative emotions and the overlooked impact of obesity on chronic pain). Most participants perceived that their pain negatively impacted their obesity, but they were uncertain whether their obesity negatively impacted their pain. Nevertheless, the participants desired and struggled to make lifestyle changes.

Conclusion
After IPRP, patients with chronic pain and obesity perceived difficulties with self-management and struggles with lifestyle changes. They experienced a combined burden of the two conditions. Their perspective on the unilateral relationship between pain and obesity differed from the existing evidence. Future tailored IPRPs should integrate nutritional interventions and address the knowledge gaps as well.
Arthrodesis of the interphalangeal joints of the hand by two-dimensional intraosseous wiring
Authors: Suzuki Tomoaki , Kawamura Daisuke , Matsui Yuichiro , Iwasaki Norimasa 
Published: October 2023

Abstract
Background
Numerous techniques for arthrodesis have been described to fix interphalangeal (IP) joints, and the fixation method should be considered on a case-by-case basis. This study aimed to investigate the availability of IP joint arthrodesis of the hand, using a two-dimensional intraosseous wiring (two-DIOW) method.

Methods
A total of 43 joints (19 thumb IP joints, 9 proximal finger interphalangeal (PIP) joints and 15 distal interphalangeal (DIP) joints in 29 patients with a mean age of 66 years (range, 24–85 y) were retrospectively analyzed. All operations were performed with two-DIOW method. We evaluated the bone union rate, correction loss, presence of any surgical complications, and oral steroid use in cases of joint fixation using the two-DIOW method.

Results
Of these 43 digits, 42 achieved bone union (97.7%). Non-union was seen in a thumb IP joint of mutilans rheumatoid arthritis. Mean correction loss of deviation was 1.0°, and flexion or extension angulation was 1.6° in the direction of extension. Surgical complications included mild nail deformity in 2 digits and wire irritation necessitating wire removal in 2 digits. Oral steroids were used for 18 of the 43 digits, including 2 digits complicated by nail deformities. There was no infection and skin necrosis in all digits with or without steroid use.

Conclusions
The two-DIOW method appears to offer an effective method of IP joint fixation, but caution should be exercised in digits of severe joint destruction and in the treatment of wire knot.
Anti-atherosclerotic effects of naringenin and quercetin from Folium Artemisiae argyi by attenuating Interleukin-1 beta (IL-1β)/ matrix metalloproteinase 9 (MMP9): network pharmacology-based analysis and validation
Authors: Zhang Lei , Yang Zhihui , Li Xinyi , Hua Yunqing , Fan Guanwei , He Feng 
Published: October 2023

AbstractEffective components and related target genes of Folium Artemisiae argyi were screened from Traditional Chinese Medicines for Systems Pharmacology Database and Analysis Platform. The therapeutic targets of atherosclerosis were searched in the MalaCards and OMIM databases. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed in WebGestalt online and verified according to ClueGo and Pedia apps in Cytoscape. Then, the protein-protein interaction network was analyzed using the STRING database and constructed using Cytoscape. Differential expression of target genes was identified in GSE9128 and GSE71226 by GEO2R. And then, molecular docking was performed using the Molecular Operating Environment. Finally, we validated the protein expression of Interleukin-6 (IL-6)/IL-1β /MMP9 by qRT-PCR and Western blot in Raw264.7 which was induced by LPS. A total of 232 potential target genes and 8 ingredients of Folium Artemisiae argyi were identified. Quercetin and naringenin are potential candidate bioactive agents in treating atherosclerosis. Vascular endothelial growth factor (VEGFA), MMP9 and IL-1β could be potential target genes. KEGG analysis demonstrated that the fluid shear stress and atherosclerosis pathway play a crucial role in the anti-atherosclerosis effect of Folium Artemisiae argyi. Gene Expression Omnibus (GEO) validation demonstrated that VEGFA was downregulated, while MMP9 and IL-1β were upregulated in patients with atherosclerosis. Molecular docking suggested that only MMP9 had a good combination with quercetin. The cell experiment results suggested that naringenin and quercetin have strong anti-inflammation effects, and significantly inhibit the expression of MMP9.Practical ApplicationsArtemisiae argyi is a traditional Chinese herbal medicine that has been widely used for its antibacterial and anti-inflammatory effects. This research demonstrated the bioactive ingredients, potential targets, and molecular mechanism of Folium Artemisiae argyi in treating atherosclerosis. It also suggests a reliable approach in investigating the therapeutic effect of traditional Chinese herbal medicine in treating Atherosclerotic cardiovascular disease (ASCVD).
A new histone deacetylase inhibitor remodels the tumor microenvironment by deletion of polymorphonuclear myeloid-derived suppressor cells and sensitizes prostate cancer to immunotherapy
Authors: Chen Zude , Yang Xiaoshuang , Chen Zugen , Li Minzhao , Wang Wei , Yang Riwei , Wang Zuomin , Ma Yuxiang , Xu Yulong , Ao Shan , Liang Leqi , Cai Chao , Wang Changning , Deng Tuo , Gu Di , Zhou Hongqing , Zeng Guohua 
Published: October 2023

Abstract
Background
Prostate cancer (PCa) is the most common malignancy diagnosed in men. Immune checkpoint blockade (ICB) alone showed disappointing results in PCa. It is partly due to the formation of immunosuppressive tumor microenvironment (TME) could not be reversed effectively by ICB alone.

Methods
We used PCa cell lines to evaluate the combined effects of CN133 and anti-PD-1 in the subcutaneous and osseous PCa mice models, as well as the underlying mechanisms.

Results
We found that CN133 could reduce the infiltration of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), and CN133 combination with anti-PD-1 could augment antitumor effects in the subcutaneous PCa of allograft models. However, anti-PD-1 combination with CN133 failed to elicit an anti-tumor response to the bone metastatic PCa mice. Mechanistically, CN133 could inhibit the infiltration of PMN-MDSCs in the TME of soft tissues by downregulation gene expression of PMN-MDSC recruitment but not change the gene expression involved in PMN-MDSC activation in the CN133 and anti-PD-1 co-treatment group relative to the anti-PD-1 alone in the bone metastatic mice model.

Conclusions
Taken together, our work firstly demonstrated that combination of CN133 with anti-PD-1 therapy may increase the therapeutic efficacy to PCa by reactivation of the positive immune microenvironment in the TME of soft tissue PCa.
Anti-cancer effect of palmatine through inhibition of the PI3K/AKT pathway in canine mammary gland tumor CMT-U27 cells
Authors: Yoo Min-Jae , Choi Jawun , Jang Ye-ji , Park Sang-Youel , Seol Jae-Won 
Published: October 2023

AbstractCanine mammary gland tumors (CMTs) are the most common and lethal cancers in female dogs. Dysregulated phosphoinositide 3-kinases (PI3K)/AKT pathway reportedly was involved in the growth and metastasis of CMTs. However, there are few studies on therapeutic strategies for targeting the PI3K pathway in CMTs. In this study, we aimed to determine whether palmatine, a natural isoquinoline alkaloid with anti-cancer properties, could inhibit the growth of CMTs and whether the inhibitory effect was mediated through the PI3K/AKT pathway. Our in vitro experiments on CMT-U27, a CMT cell line, showed that palmatine reduced cell proliferation and induced cell death. Western blotting results revealed that palmatine decreased the protein expression of PI3K, PTEN, AKT, and mechanistic target of rapamycin in the PI3K/AKT pathway, which was supported by the results of immunocytochemistry. Additionally, palmatine suppressed the migration and tube formation of canine aortic endothelial cells as well as the migration of CMT U27 cells. Our in vivo results showed that palmatine inhibited tumor growth in a CMT-U27 mouse xenograft model. We observed a decreased expression of proteins in the PI3K/AKT pathway in tumor tissues, similar to the in vitro results. Furthermore, palmatine significantly disrupted the tumor vasculature and inhibited metastasis to adjacent lymph nodes. In conclusion, our findings demonstrate that palmatine exerts anti-cancer effects against CMTs by inhibiting PI3K/AKT signaling pathway, suggesting that palmatine has potential as a canine-specific PI3K inhibitor for the treatment of CMTs.
Identification of the role of endoplasmic reticulum stress genes in endometrial cancer and their association with tumor immunity
Authors: Zhang Tang ansu , Zhang Qian , Zhang Jun , Zhao Rong , Shi Rui , Wei Sitian , Liu Shuangge , Zhang Qi , Wang Hongbo 
Published: October 2023

Abstract
Background
Endometrial cancer (EC) is one of the worldwide gynecological malignancies. Endoplasmic reticulum (ER) stress is the cellular homeostasis disturbance that participates in cancer progression. However, the mechanisms of ER Stress on EC have not been fully elucidated.

Method
The ER Stress-related genes were obtained from Gene Set Enrichment Analysis (GSEA) and GeneCards, and the RNA-seq and clinical data were downloaded from The Cancer Genome Atlas (TCGA). The risk signature was constructed by the Cox regression and the least absolute shrinkage and selection operator (LASSO) analysis. The significance of the risk signature and clinical factors were tested by time-dependent receiver operating characteristic (ROC) curves, and the selected were to build a nomogram. The immunity correlation was particularly analyzed, including the related immune cells, pathways, and immune checkpoints. Functional enrichment, potential chemotherapies, and in vitro validation were also conducted.

Result
An ER Stress-based risk signature, consisting of TRIB3, CREB3L3, XBP1, and PPP1R15A was established. Patients were randomly divided into training and testing groups with 1:1 ratio for subsequent calculation and validation. Based on risk scores, high- and low-risk subgroups were classified, and low-risk subgroup demonstrated better prognosis. The Area Under Curve (AUC) demonstrated a reliable predictive capability of the risk signature. The majority of significantly different immune cells and pathways were enriched more in low-risk subgroup. Similarly, several typical immune checkpoints, expressed higher in low-risk subgroup. Patients of the two subgroups responded differently to chemotherapies.

Conclusion
We established an ER Stress-based risk signature that could effectively predict EC patients’ prognosis and their immune correlation.
Silencing of CD147 inhibits cell proliferation, migration, invasion, lipid metabolism dysregulation and promotes apoptosis in lung adenocarcinoma via blocking the Rap1 signaling pathway
Authors: Zhang Ning , Liu Zhouzhong , Lai Xuwang , Liu Shubin , Wang Yuli 
Published: October 2023

Abstract
Objective
CD147 is an important glycoprotein that participates in the progression of diverse cancers. This study aims to explore the specific function of CD147 in lung adenocarcinoma (LUAD) and to reveal related downstream molecular mechanisms.

Methods
Followed by silencing of CD147, the viability, migration, invasion, and apoptosis of LUAD cells were measured by CCK8, wound healing, transwell assay, and flow cytometer, respectively. The expression of CD147 and two markers of lipid metabolism (FASN and ACOX1) were detected by qRT-PCR. A xenograft tumor model was constructed to investigate the function of CD147 in vivo. Then transcriptome sequencing was performed to explore the potential mechanisms. After measuring the expression of Rap1 and p-p38 MAPK/p38 MAPK by western blot, the changes of CD147 and lipid metabolism markers (FASN, ACOX1) was detected by Immunohistochemistry. Moreover, a Rap1 activator and a Rap1 inhibitor were applied for feedback functional experiments.

Results
CD147 was up-regulated in LUAD cells, and its silencing inhibited cell proliferation, migration, invasion, lipid metabolism dysregulation and promoted apoptosis, while overexpression of CD147 showed the opposite results. Silencing of CD147 also inhibited the growth of tumor xenografts in mice. Transcriptome sequencing revealed 834 up-regulated differentially expressed genes (DEGs) and 602 down-regulated DEGs. After functional enrichment, the Rap1 signaling pathway was selected as a potential target, which was then verified to be blocked by CD147 silencing. In addition, the treatment of Rap1 activator weakened the inhibiting effects of si-CD147 on the proliferation, migration, invasion, and lipid metabolism in LUAD cells, while the intervention of RAP1 inhibitor showed the opposite results.

Conclusions
Silencing of CD147 inhibited the proliferation, migration, invasion, lipid metabolism dysregulation and promoted apoptosis of LUAD cells through blocking the Rap1 signaling pathway.
Systematic engineering pinpoints a versatile strategy for the expression of functional cytochrome P450 enzymes in Escherichia coli cell factories
Authors: Poborsky Michal , Crocoll Christoph , Motawie Mohammed Saddik , Halkier Barbara Ann 
Published: October 2023

AbstractProduction of plant secondary metabolites in engineered microorganisms provides a scalable and sustainable alternative to their sourcing from nature or through chemical synthesis. However, the biosynthesis of many valuable plant-derived products relies on cytochromes P450 – enzymes notoriously difficult to express in microbes. To improve their expression in Escherichia coli, an arsenal of engineering strategies was developed, often paired with an extensive screening of enzyme variants. Here, attempting to identify a broadly applicable strategy, we systematically evaluated six common cytochrome P450 N-terminal modifications and their effect on in vivo activity of enzymes from the CYP79 and CYP83 families. We found that transmembrane domain truncation was the only modification with a significantly positive effect for all seven tested enzymes, increasing their product titres by 2- to 170-fold. Furthermore, when comparing the changes in the protein titre and product generation, we show that higher protein expression does not directly translate to higher in vivo activity, thus making the protein titre an unreliable screening target in the context of cell factories. We propose the transmembrane domain truncation as a first-line approach that enables the expression of wide range of highly active P450 enzymes in E. coli and circumvents the time-consuming screening process. Our results challenge the notion that the engineering strategy must be tailored for each individual cytochrome P450 enzyme and have the potential to simplify and accelerate the future design of E. coli cell factories.
The role of oncolytic virotherapy and viral oncogenes in the cancer stem cells: a review of virus in cancer stem cells
Authors: Faghihkhorasani Amirhosein , Dalvand Alaleh , Derafsh Ehsan , Tavakoli Farnaz , Younis Nada Khairi , Yasamineh Saman , Gholizadeh Omid , Shokri Pooria 
Published: October 2023

AbstractCancer Stem Cells (CSCs) are the main “seeds” for the initiation, growth, metastasis, and recurrence of tumors. According to many studies, several viral infections, including the human papillomaviruses, hepatitis B virus, Epstein–Barr virus, and hepatitis C virus, promote the aggressiveness of cancer by encouraging the development of CSC features. Therefore, a better method for the targeted elimination of CSCs and knowledge of their regulatory mechanisms in human carcinogenesis may lead to the development of a future tool for the management and treatment of cancer. Oncolytic viruses (OVs), which include the herpes virus, adenovirus, vaccinia, and reovirus, are also a new class of cancer therapeutics that have favorable properties such as selective replication in tumor cells, delivery of numerous eukaryotic transgene payloads, induction of immunogenic cell death and promotion of antitumor immunity, as well as a tolerable safety profile that essentially differs from that of other cancer therapeutics. The effects of viral infection on the development of CSCs and the suppression of CSCs by OV therapy were examined in this paper. The purpose of this review is to investigate the dual role of viruses in CSCs (oncolytic virotherapy and viral oncogenes).
Graphical Abstract
Assessing IRS performance in a gender-integrated vector control programme on Bioko Island, Equatorial Guinea, 2010–2021
Authors: DeBoer Kylie R. , Vaz Liberato Motobe , Ondo Mfumu Teresa Ayingono , Nlang Jose Antonio Mba , Ondo Lucas , Riloha Rivas Matilde , Incardona Sandra , Pollock John , von Fricken Michael E. , Mba Eyono Jeremías Nzamio , Donfack Olivier T. , Guerra Carlos A. , García Guillermo A. 
Published: October 2023

Abstract
Background
Indoor residual spraying (IRS) is a common vector control strategy in countries with high malaria burden. Historically, social norms have prevented women from working in IRS programmes. The Bioko Island Malaria Elimination Project has actively sought to reduce gender inequality in malaria control operations for many years by promoting women’s participation in IRS.

Methods
This study investigated the progress of female engagement and compared spray productivity by gender from 2010 to 2021, using inferential tests and multivariable regression. Spray productivity was measured by rooms sprayed by spray operator per day (RSOD), houses sprayed by spray operator per day (HSOD), and the daily productivity ratio (DPR), defined as the ratio of RSOD to HSOD, which standardized productivity by house size.

Results
The percentage of women participating in IRS has increased over time. The difference in DPR comparing male and female spray operators was only statistically significant (p < 0.05) for two rounds, where the value was higher for women compared to men. Regression analyses showed marginal, significant differences in DPR between men and women, but beta coefficients were extremely small and thus not indicative of a measurable effect of gender on operational performance.

Conclusions
The quantitative analyses of spray productivity are counter to stigmatizing beliefs that women are less capable than male counterparts during IRS spray rounds. The findings from this research support the participation of women in IRS campaigns, and a renewed effort to implement equitable policies and practices that intentionally engage women in vector control activities.
Nonlinear connection between remnant cholesterol and stroke risk: evidence from the China health and retirement longitudinal study
Authors: Wang Yuanqing , Zha Fubing , Han Yong , Cai Ying , Chen Miaoling , Yang Cui , Cai Xiaodong , Hu Haofei , Cao Changchun , Luo Jiao 
Published: October 2023

Abstract
Objective
The evidence on the relationship between remnant cholesterol (RC) and stroke remains controversial. Therefore, this study aimed to explore the relationship between RC and stroke risk in a Chinese population of middle-aged and elderly individuals.

Methods
The present study included 10067 Chinese subjects of middle-aged and elderly individuals. The connection between RC and incident stroke was investigated using the multivariate Cox proportional hazards regression model, several sensitivity analyses, generalized additive models, and smoothed curve fitting.

Results
A total of 1180 participants with stroke were recorded during the follow-up period. The multivariate Cox proportional hazards regression model identified a positive connection between RC and stroke risk (hazard ratio (HR) = 1.087, 95% confidence interval (CI): 1.001–1.180). In addition, the current study discovered a nonlinear connection between RC and incident stroke, and the point of inflection for RC was 1.78 mmol/L. The risk of stroke increased by 25.1% with each unit increase in RC level when RC was < 1.78 mmol/L (HR:1.251, 95%CI: 1.089–1.437, P = 0.0015). The results were not affected by sensitivity tests.

Conclusion
The current study showed a positive and nonlinear connection between RC and stroke risk in a middle-aged and elderly Chinese population. These findings provided new information to help researchers better understand the relationship between RC levels and incident stroke.