bluuebunny/crossref_metadata_2025_split huggingface dataset:
ND630 controls ACACA and lipid reprogramming in prostate cancer by regulating the expression of circKIF18B_003
Authors: Wu Yu-Peng , Zheng Wen-Cai , Huang Qi , Huang Xu-Yun , Lin Fei , Ke Zhi-Bin , You Qi , Zheng Qing-Shui , Wei Yong , Xue Xue-Yi , Xu Ning 
Published: December 2023

Abstract
Background
ND630 is believed to be a new therapy pharmacologic molecule in targeting the expression of ACACA and regulating the lipid metabolism. However, the function of ND630 in prostate cancer remains unknown. KIF18B, as an oncogene, plays a vital role in prostate cancer progression. circKIF18B_003 was derived from oncogene KIF18B and was markedly overexpressed in prostate cancer tissues. We speculated that oncoprotein KIF18B-derived circRNA circKIF18B_003 might have roles in prostate cancer promotion. The aim of this study was to validate whether ND630 could control ACACA and lipid reprogramming in prostate cancer by regulating the expression of circKIF18B_003.

Methods
RT-qPCR was used to analyze the expression of circKIF18B_003 in prostate cancer cell lines and prostate cancer samples. circKIF18B_003 expression was modulated in prostate cancer cells using circKIF18B_003 interference or overexpression plasmid. We examined the function and effects of circKIF18B_003 in prostate cancer cells using CCK-8, colony formation, wound healing, and Transwell invasion assays and xenograft models. Fluorescence in situ hybridization (FISH) was performed to evaluate the localization of circKIF18B_003. RNA immunoprecipitation (RIP), RNA pull down, and luciferase reporter assay were performed to explore the potential mechanism of circKIF18B_003.

Results
The function of ND630 was determined in this study. circKIF18B_003 was overexpressed in prostate cancer tissues, and overexpression of circKIF18B_003 was associated with poor survival outcome of prostate cancer patients. The proliferation, migration, and invasion of prostate cancer cells were enhanced after up-regulation of circKIF18B_003. circKIF18B_003 is mainly located in the cytoplasm of prostate cancer cells, and the RIP and RNA pull down assays confirmed that circKIF18B_003 could act as a sponge for miR-370-3p. Further study demonstrated that up-regulation of circKIF18B_003 increased the expression of ACACA by sponging miR-370-3p. The malignant ability of prostate cancer cells enhanced by overexpression of circKIF18B_003 was reversed by the down-regulation of ACACA. We found that overexpression of circKIF18B_003 was associated with lipid metabolism, and a combination of ND-630 and docetaxel markedly attenuated tumor growth.

Conclusion
ND630 could control ACACA and lipid reprogramming in prostate cancer by regulating the expression of circKIF18B_003. ND630 and circKIF18B_003 may represent a novel target for prostate cancer.
Bioinformatics analysis of immune characteristics in tumors with alternative carcinogenesis pathways induced by human papillomaviruses
Authors: Smahel Michal , Nunvar Jaroslav 
Published: December 2023

Abstract
Background
Human papillomaviruses (HPVs) induce a subset of head and neck squamous cell carcinomas (HNSCC) and anogenital cancers, particularly cervical cancer (CC). The major viral proteins that contribute to tumorigenesis are the E6 and E7 oncoproteins, whose expression is usually enhanced after the integration of viral DNA into the host genome. Recently, an alternative tumorigenesis pathway has been suggested in approximately half of HNSCC and CC cases associated with HPV infection. This pathway is characterized by extrachromosomal HPV persistence and increased expression of the viral E2, E4, and E5 genes. The E6, E7, E5, and E2 proteins have been shown to modify the expression of numerous cellular immune-related genes. The antitumor immune response is a critical factor in the prognosis of HPV-driven cancers, and its characterization may contribute to the prediction and personalization of the increasingly used cancer immunotherapy.

Methods
We analyzed the immune characteristics of HPV-dependent tumors and their association with carcinogenesis types. Transcriptomic HNSCC and CC datasets from The Cancer Genome Atlas were used for this analysis.

Results
Clustering with immune-related genes resulted in two clusters of HPV16-positive squamous cell carcinomas in both tumor types: cluster 1 had higher activation of immune responses, including stimulation of the antigen processing and presentation pathway, which was associated with higher immune cell infiltration and better overall survival, and cluster 2 was characterized by keratinization. In CC, the distribution of tumor samples into clusters 1 and 2 did not depend on the level of E2/E5 expression, but in HNSCC, most E2/E5-high tumors were localized in cluster 1 and E2/E5-low tumors in cluster 2. Further analysis did not reveal any association between the E2/E5 levels and the expression of immune-related genes.

Conclusions
Our results suggest that while the detection of immune responses associated with preserved expression of genes encoding components of antigen processing and presentation machinery in HPV-driven tumors may be markers of better prognosis and an important factor in therapy selection, the type of carcinogenesis does not seem to play a decisive role in the induction of antitumor immunity.
A metabolomics study in aqueous humor discloses altered arginine metabolism in Parkinson’s disease
Authors: Serrano-Marín Joan , Marin Silvia , Bernal-Casas David , Lillo Alejandro , González-Subías Marc , Navarro Gemma , Cascante Marta , Sánchez-Navés Juan , Franco Rafael 
Published: December 2023

Abstract
Background
The lack of accessible and informative biomarkers results in a delayed diagnosis of Parkinson’s disease (PD), whose symptoms appear when a significant number of dopaminergic neurons have already disappeared. The retina, a historically overlooked part of the central nervous system (CNS), has gained recent attention. It has been discovered that the composition of cerebrospinal fluid influences the aqueous humor composition through microfluidic circulation. In addition, alterations found in the brain of patients with PD have a correlate in the retina. This new paradigm highlights the potential of the aqueous humor as a sample for identifying differentially concentrated metabolites that could, eventually, become biomarkers if also found altered in blood or CSF of patients. In this research we aim at analyzing the composition of the aqueous humor from healthy controls and PD patients.

Methods
A targeted metabolomics approach with concentration determination by mass spectrometry was used. Statistical methods including principal component analysis and linear discriminants were used to select differentially concentrated metabolites that allow distinguishing patients from controls.

Results
In this first metabolomics study in the aqueous humor of PD patients, elevated levels of 16 compounds were found; molecules differentially concentrated grouped into biogenic amines, amino acids, and acylcarnitines. A biogenic amine, putrescine, alone could be a metabolite capable of differentiating between PD and control samples. The altered levels of the metabolites were correlated, suggesting that the elevations stem from a common mechanism involving arginine metabolism.

Conclusions
A combination of three metabolites, putrescine, tyrosine, and carnitine was able to correctly classify healthy participants from PD patients. Altered metabolite levels suggest altered arginine metabolism. The pattern of metabolomic disturbances was not due to the levodopa-based dopamine replacement medication because one of the patients was not yet taking levodopa but a dopamine receptor agonist.
The optimisation of public health emergency governance: a simulation study based on COVID-19 pandemic control policy
Authors: Yang Keng , Qi Hanying 
Published: December 2023

Abstract
Background
The outbreak of the COVID-19 pandemic sparked numerous studies on policy options for managing public health emergencies, especially regarding how to choose the intensity of prevention and control to maintain a balance between economic development and disease prevention.

Methods
We constructed a cost-benefit model of COVID-19 pandemic prevention and control policies based on an epidemic transmission model. On this basis, numerical simulations were performed for different economies to analyse the dynamic evolution of prevention and control policies. These economies include areas with high control costs, as seen in high-income economies, and areas with relatively low control costs, exhibited in upper-middle-income economies.

Results
The simulation results indicate that, at the outset of the COVID-19 pandemic, both high-and low-cost economies tended to enforce intensive interventions. However, as the virus evolved, particularly in circumstances with relatively rates of reproduction, short incubation periods, short spans of infection and low mortality rates, high-cost economies became inclined to ease restrictions, while low-cost economies took the opposite approach. However, the consideration of additional costs incurred by the non-infected population means that a low-cost economy is likely to lift restrictions as well.

Conclusions
This study concludes that variations in prevention and control policies among nations with varying income levels stem from variances in virus transmission characteristics, economic development, and control costs. This study can help researchers and policymakers better understand the differences in policy choice among various economies as well as the changing trends of dynamic policy choices, thus providing a certain reference value for the policy direction of global public health emergencies.
Retrospective analysis of the 18F-FDG PET/CT cutoff value for metabolic parameters was performed as a prediction model to evaluate risk factors for endometrial cancer
Authors: Yang Ye , Pan Yu-Qin , Wang Min , Gu Song , Bao Wei 
Published: December 2023

Abstract
Purpose
The study retrospectively analyzed the accuracy and predictive ability of preoperative integrated whole-body 18F-FDG PET/CT for the assessment of high-risk factors in patients with endometrial carcinoma (EC).

Materials and methods
A total of 205 patients with endometrial cancer who underwent preoperative PET/CT at Shanghai General Hospital from January 2018 to December 2021 were retrospectively evaluated and last follow-up was June 2023. Our study evaluated the ability and optimal cutoff values of three metabolic and volumetric parameters—standardized uptake value (SUV), metabolic tumor volume (MTV) and total lesion glycolysis (TLG)—to predict deep myometrial invasion (DMI), endocervical stroma invasion (ESI) and lymph node metastases (LNM) in endometrial cancer. The accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PET/CT were used to assess the diagnostic performance for the prediction.

Results
Our study demonstrated a significant relationship between SUVmax (11.29, 17.38, 9.47), SUVmean (5.20, 6.12, 4.49), MTV (38.15, 36.28, 33.79 ml), and TLG (199.30, 225.10, 156.40 g) on PET/CT and histologically confirmed DMI, ESI and LNM in endometrial carcinoma (EC), with sensitivity, specificity, accuracy, PPV, and NPV of 100%/100%/100%, 96.53%/98.89%/87.14%, 97.56%/99.02%/91.22%, 92.42%/92.85%/78.31%, and 100%/100%/100%, respectively. Our study showed a risk model based on optimal cutoff values for MTV and TLG of 19.6 ml/126.3 g, 20.54 ml/84.80 g and 24 ml/49.83 g to preoperatively predict DMI, ESI, and LNM, respectively, in endometrial carcinoma. The 4-year OS (HR) for Stage IA, IB, II, III and IV according to 2009 FIGO was 98.00% (0.22), 95.20% (0.04), 83.90% (0.18), 90.50% (0.09) and 60% (0.51). Accordingly, estimated 4-year DFS (HR) for the stage IA-III was 98% (0.02), 95.20% (0.05), 76.90% (0.27) and 76.30% (0.35), all the patients in stage IV occurred recurrence and progression.

Conclusion
The present study showed patients with MTV > = 19.6 ml of MI and PET- positive LN with MTV cutoff > = 24 ml tended to predict poor OS and PFS in endometrial carcinoma. The cutoff of MTV and TLG in PET/CT assessment could be an independent prognostic factors to predict aggressive forms of EC.

Graphic Abstract
The potentially dangerous zone of the dorsomedial cutaneous nerve in minimally invasive surgery for hallux valgus: a cadaveric study
Authors: Teng Zhaolin , Geng Xiang , Song Jiafeng , Chen Li , Zhang Chao , Huang Jiazhang , Wang Xu , Ma Xin 
Published: December 2023

Abstract
Background
This study aims to describe the distribution of the dorsomedial cutaneous nerve (DMCN) in the middle and proximal parts of the metatarsal from a lateral view. The purpose is to provide guidance to surgeons in protecting the nerve during the 3rd and 4th generation minimally invasive surgery (MIS) for hallux valgus (HV).

Methods
A total of 20 cadaveric feet were dissected to expose the course of the DMCN and sentinel vein. Measurements of the distances between the nerve/vein and the upper border of the metatarsal, as well as the height of the metatarsal, were taken from a lateral view. The distribution area was then described in proportion.

Results
At the base of the metatarsal, the DMCN was distributed in the upper 25.7% of the area. When it reached the middle of the metatarsal, the DMCN was distributed in the upper 13.2–47.2% of the area. As for the sentinel vein, it was distributed in the upper 23.5–71.9% and upper 4.1–52.7%, respectively, at these two positions.

Conclusions
The area, which is above the line connecting the upper 1/4 point at the base of the first metatarsal and the 1/2 point at the middle of the first metatarsal, is a dangerous zone for the DMCN. Avoiding the zone is recommended during MIS for HV.
Remimazolam besylate versus propofol for deep sedation in critically ill patients: a randomized pilot study
Authors: Tang Yun , Gao Xuehui , Xu Jiqian , Ren Lehao , Qi Hong , Li Ruiting , Shu Huaqing , Zou Xiaojing , Yuan Shiying , Yang Xiaobo , Shang You 
Published: December 2023

Abstract
Objective
To compare the efficacy and safety of remimazolam besylate and propofol for deep sedation in critically ill patients.

Methods
In this single-center, prospective, randomized, controlled pilot study, patients in the intensive care unit (ICU) requiring deep sedation were randomized to receive remimazolam besylate or propofol intravenously. Deep sedation was defined as a Richmond Agitation and Sedation Scale (RASS) score of − 4 or − 5. Sedation depth was monitored using RASS and Narcotrend Index (NI). The primary outcome was the percentage of time within the target sedation range without rescue sedation. The secondary outcomes included ventilator-free hours within 7 days, successful extubation, length of ICU stay, and 28-day mortality. Adverse events during the interventional period were also recorded.

Results
Thirty patients were assigned to each group. The median (IQR) RASS score was − 5.0 (− 5.0, − 4.0), and the median (IQR) NI value was 29.0 (21.0, 37.0) during the intervention period. Target RASS was reached a median of 100% of the sedation time in the two groups. No significant differences were observed in ventilator-free hours within 7 days, successful extubation, length of ICU stay, or 28-day mortality among groups. Hypotension occurred in 16 (53.3%) patients of remimazolam group and 18 (60.0%) patients of propofol group (p > 0.05). No patient experienced bradycardia.

Conclusions
Remimazolam besylate appears to be an effective and safe agent for short-term deep sedation in critically ill patients. Our findings warrant large sample-sized randomized clinical trials.
A prospective, single-centre, randomized, double-blind controlled study protocol to study whether long-term oral metronidazole can effectively reduce the incidence of postoperative liver metastasis in patients with colorectal cancer
Authors: Gao Rui Qi , Mo Zhen Chang , Zhou Hai Kun , Yu Peng Fei , Wang Wei Dong , Dong Dan Hong , Yang Xi Sheng , Li Xiao Hua , Ji Gang 
Published: December 2023

Abstract
Introduction
Fifteen to 25% of patients with colorectal cancer have combined liver metastases at the time of diagnosis, whereas an additional 15 to 25% will develop liver metastases after curative resection of primary colorectal cancer, with the vast majority (80–90%) of liver metastases unresponsive to curative resection at first. Colorectal cancer liver metastasis is also the leading cause of death in patients with colorectal cancer. In recent years, several studies have demonstrated that intestinal flora, especially Fusobacterium nucleatum, plays a crucial role in the development of colorectal cancer liver metastasis, so we hypothesized that long-term metronidazole use could effectively reduce the incidence of postoperative liver metastasis in colorectal cancer patients.

Methods/design
This study is a prospective, single-centre, randomized, double-blind controlled study in which 300 patients will be randomly assigned to the test group or the control group in a 1:1 allocation ratio. The aim of this trial is to demonstrate that long-term oral antibiotics can effectively reduce the incidence of postoperative liver metastasis in patients with colorectal cancer.

Ethics and dissemination
Ethics approval was obtained from the Ethics Committee at the Chinese Ethics Committee of Registering Clinical Trials (ChiECRCT20210229). The results of this study will be disseminated at several research conferences and as published articles in peer-reviewed journals.

Trial registration
Chinese Clinical Trial Registry ChiCTR2100046201. Registered on July 05, 2021.
The effect of eye movement desensitization and reprocessing (EMDR) on abdominal pain in patients with irritable bowel syndrome (IBS): a study protocol for a randomized controlled trial (EMDR4IBS)
Authors: Wertheim B. , Aarts E. E. , de Roos C. , van Rood Y. R. 
Published: December 2023

Abstract
Background
Irritable bowel syndrome (IBS) is a highly prevalent disorder for which treatment options such as medication, diets, and hypnotherapy either have shown limited effect or relieve symptoms in only a limited subset of patients. Abdominal pain is the key criterion for the diagnosis and is deemed the most distressing IBS symptom, and the most disruptive of everyday life. A growing body of research demonstrates the effect of Eye Movement Desensitization and Reprocessing (EMDR) on chronic pain. EMDR is known as a safe and successful treatment for disorders in which unresolved traumatic memories play a role in the cause or maintenance of symptoms. In IBS, activated memories may increase pain through pain flashbacks and the stress generated by unresolved memories. The aim of this study is to ascertain whether applying EMDR to traumatic memories including pain memories will reduce abdominal pain in IBS patients.

Methods
This study is a randomized controlled trial which will be conducted at a city hospital in the Netherlands. Adult patients with considerable IBS pain (pain intensity at least 60/100 during at least 5/10 days) will be randomly assigned to either EMDR therapy or the wait list. We aim to include 34 participants. The EMDR condition comprises seven sessions, around 90 min in length delivered weekly, the first of which is a case conceptualization session. All participants will be assessed at baseline, post-treatment, and at 3 months follow-up. The primary outcome measure is pain intensity on a Likert scale which is self-reported daily during a 2-week period. Secondary outcomes include similar daily ratings on other IBS symptoms and reported hindrance of valued activities, and also standardized questionnaires on IBS symptoms and Quality of Life. Data will be analyzed by a Linear Mixed Effects Model for repeated measures.

Discussion
The results are expected to gain insight into the effectiveness of EMDR treatment on abdominal pain in IBS. As there are very few effective treatment options for IBS-related abdominal pain, this study could have important implications for clinical practice.

Trial registration
Human ethics committee MEC-U NL71740.100.20. International Clinical Trial Registry Platform: NL8894. Prospectively registered on 28 January 2020.
Borrelia puertoricensis in opossums (Didelphis marsupialis) from Colombia
Authors: López Yesica , Faccini-Martínez Álvaro A. , Muñoz-Leal Sebastián , Contreras Verónica , Calderón Alfonso , Rivero Ricardo , Muñoz Marina , Ramírez Juan David , Mattar Salim 
Published: December 2023

Abstract
Background
The genus Borrelia comprises pathogenic species of bacteria that pose a significant risk to public health. Borrelia spp. are emerging or reemerging infectious agents worldwide with complex transmission cycles, and many species use rodents as vertebrate reservoir hosts. Spirochetes morphologically compatible with Borrelia have been recurrently observed in opossums; however, there is currently a lack of genetic evidence confirming infection or supporting that these marsupials are hosts of Borrelia spirochetes.

Methods
During 2017, 53 serum samples of Didelphis marsupialis from the municipality of Colosó (department of Sucre, Colombia) were collected and allocated in a serum bank. DNA extracted from the serum samples was submitted to a Borrelia genus-specific real-time PCR targeting the 16S rRNA gene. Positive samples were subsequently derived from semi-nested PCR protocols to obtain large fragments of the 16S rRNA and flaB genes. Obtained amplicons were subjected to Sanger sequencing. One positive sample was randomly selected for next-generation sequencing (NGS). Obtained reads were mapped to genomes of Borrelia spp. and sequences of two genes used in a multilocus sequence typing scheme retrieved for taxonomic assignment and phylogenetic analyses.

Results
Overall, 18.8% (10/53) of the samples were positive by qPCR. Of them, 80% (8/10) and 60% (6/10) were positive for the 16S rRNA and flaB genes after semi-nested PCRs, respectively. Bioinformatic analysis of one sample sequenced with NGS yielded 22 reads of genus Borrelia with different sizes. Two housekeeping genes, rplB and pyrG, were recovered. Nucleotide pairwise comparisons and phylogenetic analyses of 16S rRNA, flaB, rplB and pyrG genes showed that the Borrelia sp. found in opossums from Colosó corresponded to Borrelia puertoricensis.

Conclusions
We describe the first molecular evidence to our knowledge of B. puertoricensis in Colombia, specifically in opossums, and the first detection of this spirochete in a vertebrate host since its isolation from Ornithodoros puertoricensis in Panama. This detection is also relevant because of the epidemiological importance of opossums as reservoirs of zoonotic diseases to humans.

Graphical abstract
Disease aggravation following surgery in a rare patient suspected to Fibrodysplasia (Myositis) ossificans progressiva: a case report
Authors: Zarei Amir , Rahimi Foad , Khadem Mehryar , Moradi Mansour , Rahmani Khaled 
Published: December 2023

Abstract
Background
Fibrodysplasia ossificans progressiva (FOP) as a rare and heritable disorder with the infrequent genetic transmission of the condition is a catastrophic disorder of heterotopic ossification (HO) and a cause of extraskeletal bone formation in humans. Given the lack of effective treatment for this disease, the important point is to avoid aggravating factors such as bone biopsy, surgery, and intramuscular injection.

Case presentation
In this report, we present a 52-year-old female patient, Kurdish ethnic, suspected to FOP who had a surgical intervention on the second toe of the right foot, which subsequently, it caused further deterioration of the disease in the person including necrosis and amputation of the distal phalanx of the second toe.

Conclusions
Although, based on our investigation and the available scientific evidence, surgery may a cause for faster progression and worsening of the FOP disorder, but its proof requires further studies.