bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-coding RNAs/DNMT3B axis in human cancers: from pathogenesis to clinical significance
Authors: Huang Chunjie , Azizi Paniz , Vazirzadeh Masoud , Aghaei-Zarch Seyed Mohsen , Aghaei-Zarch Fatemehsadat , Ghanavi Jalaledin , Farnia Poopak 
Published: September 2023

AbstractCancer is a complex disease with many contributing factors, and researchers have gained extensive knowledge that has helped them understand the diverse and varied nature of cancer. The altered patterns of DNA methylation found in numerous types of cancer imply that they may play a part in the disease’s progression. The human cancer condition involves dysregulation of the DNA methyltransferase 3 beta (DNMT3B) gene, a prominent de novo DNA methyltransferase, and its abnormal behavior serves as an indicator for tumor prognosis and staging. The expression of non-coding RNAs (ncRNAs), which include microRNAs (miRNA), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), is critical in controlling targeted gene expression and protein translation and their dysregulation correlates with the onset of tumors. NcRNAs dysregulation of is a critical factor that influences the modulation of several cellular characteristics in cancerous cells. These characteristics include but are not limited to, drug responsiveness, angiogenesis, metastasis, apoptosis, proliferation, and properties of tumor stem cell. The reciprocal regulation of ncRNAs and DNMT3B can act in synergy to influence the destiny of tumor cells. Thus, a critical avenue for advancing cancer prevention and treatment is an inquiry into the interplay between DNMT3B and ncRNAs. In this review, we present a comprehensive overview of the ncRNAs/DNMT3B axis in cancer pathogenesis. This brings about valuable insights into the intricate mechanisms of tumorigenesis and provides a foundation for developing effective therapeutic interventions.
Vitamin D status in hospitalized COVID‑19 patients is associated with disease severity and IL-5 production
Authors: Qiu Yali , Bao Wuping , Tian Xue , Zhang Yingying , Pan Yilin , Xie Guogang , Bao Aihua , Yin Dongning , Zhang Min , Zhou Yan 
Published: September 2023

Abstract
Background
There are many studies on the relationship between vitamin D and coronavirus disease 2019 (COVID-19), while the results are matters of debate and the mechanisms remain unknown. The present study was performed to assess the impact of serum 25-hydroxyvitamin D [25(OH)D] levels on the severity of disease in hospitalized COVID-19 patients and identify potential mechanisms of 25(OH)D alterations.

Methods
A total of 399 hospitalized COVID-19 patients were recruited from three centers between December 19, 2022, and February 1, 2023. Medical history, laboratory examination, and radiologic data were retrospectively collected. The patients were divided into four groups based on disease severity. Serum 25(OH)D levels in the patients were determined by the electrochemiluminescence method and cytokines were detected by flow cytometry. The relationship between serum 25(OH)D status and the severity of COVID-19, and the correlation between 25(OH)D levels and cytokines in COVID-19 patients were assessed.

Results
Levels of 25(OH)D were significantly lower in the deceased group than in the other three groups (P < 0.05), and lower in the critical group than in the general group (P < 0.05). There were no significant differences in the 25(OH)D levels between the general and severe groups (P > 0.05). The levels of 25(OH)D (odds ratio = 0.986, 95% confidence interval: 0.973–0.998, P = 0.024) and IL-5 (odds ratio = 1.239, 95% confidence interval: 1.104–1.391, P = 0.04) were independent risk factors for the severity of COVID-19 disease upon admission. Serum 25(OH)D levels were able to predict the mortality of patients with COVID-19, and the predictive value was even higher when combined with IL-5 levels and eosinophil (Eos) count. Circulating 25(OH)D status correlated negatively with the expression of IL-5 (r=-0.262, P < 0.001) and was positively linked with CD8+ T cell counts (r=-0.121, P < 0.05) in patients with COVID-19.

Conclusions
This study found that the serum 25(OH)D status combined with IL-5 levels and Eos counts could be identified as a predictive factor for recognizing the risk of COVID-19 mortality. The serum 25(OH)D status in COVID-19 patients correlated negatively with the expression of IL-5. The potential mechanism for this relationship is worth further exploration.
Proteomic alterations in the brain and blood–brain barrier during brain Aβ accumulation in an APP knock-in mouse model of Alzheimer’s disease
Authors: Ito Shingo , Yagi Ryotaro , Ogata Seiryo , Masuda Takeshi , Saito Takashi , Saido Takaomi , Ohtsuki Sumio 
Published: September 2023

Abstract
Background
Blood–brain barrier (BBB) dysfunction is supposed to be an early event in the development of Alzheimer’s disease (AD). This study aimed to investigate the relationship between BBB alterations and AD progression in terms of amyloid-β peptide (Aβ) accumulation in the brains of humanized amyloid precursor protein knock-in (APP-KI) mice.

Methods
Brain Aβ accumulation was examined using immunohistochemical analysis. Alterations in differentially expressed proteins were determined using sequential window acquisition of all theoretical fragment ion mass spectroscopy (SWATH-MS)-based quantitative proteomics, and Metascape, STRING, Gene Ontology, and KEGG were used for network analyses of altered biological pathways and processes. Statistical significance was determined using the unpaired two-tailed Student’s t-test and Welch’s t-test for two groups and one-way analysis of variance followed by Tukey’s test for more than two groups. Correlations between two groups were determined using Pearson’s correlation analysis.

Results
Brain Aβ accumulation in APP-KI mice was detectable at 2 months, increased significantly at 5 months, and remained elevated at 12 months of age. The levels of differentially expressed proteins in isolated brain capillaries were higher in younger mice, whereas those in the brain were higher in older mice. Network analyses indicated changes in basement membrane-associated and ribosomal proteins in the brain capillaries. There were no significant changes in key proteins involved in drug or Aβ transport at the BBB. In contrast, solute carrier transporter levels in astrocytes, microglia, and neurons were altered in the brain of older mice. Moreover, the levels of the lipid transporters Apoe and Apoj were upregulated in both the brain and isolated brain capillaries after Aβ accumulation.

Conclusions
Our results suggest that changes in the brain occurred after advanced Aβ accumulation, whereas initial Aβ accumulation was sufficient to cause alterations in the BBB. These findings may help elucidate the role of BBB alterations in AD progression and predict the distribution of drugs across the BBB in the brain of patients with AD.
Implementing contingency management for stimulant use in opioid treatment programs: protocol of a type III hybrid effectiveness-stepped-wedge trial
Authors: Becker Sara J. , DiClemente-Bosco Kira , Scott Kelli , Janssen Tim , Salino Sarah M. , Hasan Fariha N. , Yap Kimberly R. , Garner Bryan R. 
Published: September 2023

Abstract
Background
Contingency management (CM) is an evidence-based intervention for stimulant use and is highly effective in combination with medication for opioid use disorder. Yet, uptake of CM in opioid treatment programs that provide medication for opioid use disorder remains low. This paradox in which CM is one of the most effective interventions, yet one of the least available, represents one of the greatest research-to-practice gaps in the addiction health services field. Multi-level implementation strategies are needed to address barriers to CM implementation at both the provider- and organization-level. This type III hybrid effectiveness-implementation trial was funded by the National Institute on Drug Abuse to evaluate whether a multi-level implementation strategy, the Science of Service Laboratory (SSL), can effectively promote CM implementation in opioid treatment programs. Specific aims will test the effectiveness of the SSL on implementation outcomes (primary aim) and patient outcomes (secondary aim), as well as test putative mediators of implementation outcomes (exploratory aim).

Methods
Utilizing a fully powered type III hybrid effectiveness-implementation trial with a stepped wedge design, we propose to randomize a cohort of 10 opioid treatment programs to receive the SSL across four steps. Each step, an additional 2–3 opioid treatment programs will receive the SSL implementation strategy, which has three core components: didactic training, performance feedback, and external facilitation. At six intervals, each of the 10 opioid treatment programs will provide de-identified electronic medical record data from all available patient charts on CM delivery and patient outcomes. Staff from each opioid treatment program will provide feedback on contextual determinants influencing implementation at three timepoints.

Discussion
Between planning of this protocol and receipt of funding, the landscape for CM in the USA changed dramatically, with multiple Departments of Health launching state-wide CM initiatives. We therefore accelerated the protocol timeline and offered some cursory training resources to all sites as a preparation activity. We also began partnering with multiple Departments of Health to evaluate their rollout of CM using the measures outlined in this protocol.

Trial registration
This study protocol is registered via ClinicalTrials.gov Identifier: NCT05702021. Date of registration: January 27, 2023.
Is punctate palmoplantar keratoderma type 1 associated with malignancy? A systematic review of the literature
Authors: Gram S. B. , Bjerrelund J. , Jelsig A. M. , Bygum A. , Leboeuf-Yde C. , Ousager L. B. 
Published: September 2023

Abstract
Background
An association between punctate palmoplantar keratoderma type 1 (PPPK1) and malignancy has been proposed for decades. Some authors suggest that individuals with PPPK1 should undergo screening for various types of malignancies while others caution that an association is not well-established. In this systematic review, we summarized and evaluated the current evidence for a possible association between PPPK1 and malignancy.

Methods
The review was conducted along PRISMA guidelines. The search used Embase, MEDLINE, Scopus, and the Human Gene Mutation Database up to March 2022. All studies reporting on individuals with the diagnosis of PPPK1 with or without history of malignancy were included. Two authors screened for eligible studies, extracted predefined data, and performed a quality assessment.

Results
Of 773 studies identified, 45 were included. Most studies were reports on single families (24 of 45 studies) or multiple families (10 of 45 studies). The number of index cases with PPPK1 across all included studies was 280, and when family members reported with PPPK1 were added, a total of 817 individuals were identified. Overall, 23 studies reported on individuals with PPPK1 with a history of malignancy, whereas 22 studies reported on individuals with PPPK1 without a history of malignancy. Although the extracted data were not considered to be of sufficient quality to synthesize and answer our research question, the review did not confirm an association between PPPK1 and malignancy.

Conclusion
This review shows that there is a lack of well-designed studies on this topic to conclude whether individuals with PPPK1 have an increased risk of malignancy. Based on the present literature, however, we could not confirm an association between PPPK1 and malignancy and find it highly questionable if patients with PPPK1 should be offered surveillance for malignancies.
Circ-RAPGEF5 promotes intrahepatic cholangiocarcinoma progression by stabilizing SAE1 to facilitate SUMOylation
Authors: Zheng Junhao , Wang Yali , Tao Liye , Cai Jingwei , Shen Zefeng , Liu Yang , Pan Haoyu , Li Shihao , Ruan Yeling , Chen Tianyi , Ye Zhengtao , Lin Kainan , Sun Yin , Xu Junjie , Liang Xiao 
Published: September 2023

Abstract
Background
Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy with a poor prognosis. The underlying functions and mechanisms of circular RNA and SUMOylation in the development of ICC remain poorly understood.

Methods
Circular RNA hsa_circ_0001681 (termed Circ-RAPGEF5 hereafter) was identified by circular RNA sequencing from 19 pairs of ICC and adjacent tissue samples. The biological function of Circ-RAPGEF5 in tumor proliferation and metastasis was examined by a series of in vitro assays. A preclinical model was used to validate the therapeutic effect of targeting Circ-RAPGEF5. RNA pull-down and dual-luciferase reporter assays were used to access the RNA interactions. Western blot and Co-IP assays were used to detect SUMOylation levels.

Results
Circ-RAPGEF5, which is generated from exons 2 to 6 of the host gene RAPGEF5, was upregulated in ICC. In vitro and in vivo assays showed that Circ-RAPGEF5 promoted ICC tumor proliferation and metastasis, and inhibited apoptosis. Additionally, high Circ-RAPGEF5 expression was significantly correlated with a poor prognosis. Further investigation showed that SAE1, a potential target of Circ-RAPGEF5, was also associated with poor oncological outcomes. RNA pull-down and dual-luciferase reporter assays showed an interaction of miR-3185 with Circ-RAPGEF5 and SAE1. Co-IP and western blot assays showed that Circ-RAPGEF5 is capable of regulating SUMOylation.

Conclusion
Circ-RAPGEF5 promotes ICC tumor progression and SUMOylation by acting as a sponge for miR-3185 to stabilize SAE1. Targeting Circ-RAPGEF5 or SAE1 might be a novel diagnostic and therapeutic strategy in ICC.
Influenza viruses circulation in a tertiary care children hospital in Rome: a comparison between 2022 and the previous 5 years
Authors: Ranno Stefania , Coltella Luana , Linardos Giulia , Di Maio Velia Chiara , Colagrossi Luna , Gentile Leonarda , Galeno Eugenia , Ciofi degli Atti Marta Luisa , Cristaldi Sebastian , Villani Alberto , Raponi Massimiliano , Perno Carlo Federico , Russo Cristina 
Published: September 2023

Abstract
Background
Influenza surveillance aims to determine onset, duration and intensity of the seasonal Influence-like Illness (ILI); data collection begins in the week 42 of a year and ends in the week 17 of the following year. In this observational study, we report the experience of a tertiary care children hospital in Rome about Influenza viruses circulation during the calendar year 2022 (January-December) in comparison with the previous five years (2017–2021), with a special focus on the weeks 18–41, usually not under surveillance.

Methods
This retrospective study involved 36782 respiratory samples referred to 21354 patients (pts), median age 2.63 years, admitted with respiratory symptoms at Bambino Gesù Children’s Hospital in the years 2017–2022. Respiratory viruses were detected by molecular Allplex™ Respiratory Panel Assays (Seegene, Korea).

Results
Regarding the pre pandemic years, 2017–2019, distribution of Flu positive patients focused in the first weeks of the year (weeks 1–17). During the pandemic period, Flu was not detected. In 2022, 239 Flu viruses were identified: 37 FluA (weeks 1–17), 29 FluA (weeks 18–41) and 168 FluA and 5 FluB (weeks 42–52). For the year 2022, during the non-epidemic period, the number of Flu viruses detected corresponded to 12.1% of total Flu detected, respect to 0-1.7% for the previous five years (p < 0.001).

Conclusions
When compared with pre SARS-CoV-2 pandemic years, our data show a significant increase in Influenza cases during weeks 18–41/2022 and reveal an unexpected summer circulation of these viruses: just weeks 26–30 showed to be influenza virus free. A national year-round Flu surveillance could be useful to understand if changing in influenza epidemiology is transitional or likely to persist in the following years.
Reduction in the duration of postoperative fever following NUSS surgery during the COVID-19 pandemic
Authors: Jia An , Qiang Wang , Zhuoga Deqin , Di Yu , Zhaocong Yang , Xuming Mo 
Published: September 2023

Abstract
Background
Our study aimed to compare the prevalence of postoperative fever during the COVID-19 pandemic period with that of the preceding non-pandemic period.

Methods
A retrospective analysis was conducted on patients with pectus excavatum (PE) undergoing minimally invasive repair (also called NUSS procedure) at Nanjing Children’s Hospital from January 1, 2017 to March 1, 2019 (Group 2019), and from January 1, 2020 to March 1, 2021 (Group 2021). Data from a total of 284 patients, consisting of 200 (70.4%) males and 84 (29.6%) females with an average age of 9.73 ± 3.41 (range, 4 to 17) years, were collected. The presence of post-operative fever (defined as a forehead temperature of 37.5℃ or above within 72 h post-surgery), as well as the time of operation, duration of postoperative mechanical ventilator and urinary catheter use, and length of hospitalization were all assessed in admitted patients from Group 2019 (n = 144) and Group 2021 (n = 140). Postoperative white blood cell (WBC), C-reactive protein (CRP) levels, and prevalence of postoperative complications (i.e., pneumothorax, pulmonary atelectasis, pneumonia, wound infection, and dehiscence) were also determined.

Result
Our results showed a statistically significant decrease in the incidence of postoperative fever within 24 to 72 h of surgery in patients admitted from Group 2019 as compared to Group 2021 (p < 0.001), as well as a decrease in peak body temperature within 72 h (p < 0.05). Meanwhile, no significant differences were observed in age and body mass index (BMI), time of operation, or duration of postoperative mechanical ventilator and urinary catheter use between the two groups (p > 0.05). The average hospitalization length of Group 2021 was significantly shorter than Group 2019 (12.49 ± 2.57 vs. 11.85 ± 2.19 days, p < 0.05). Furthermore, while the WBC count between the two groups 24 h after surgery showed a statistical difference (p < 0.05), no differences in CRP levels or the incidence of postoperative complications were observed (p > 0.05).

Conclusion
The prevalence of postoperative fever within 72 h of surgery and the length of hospital stay for patients with PE undergoing NUSS surgery were both decreased in Group 2021. We propose that the above phenomenon may be related to increased used of personal protection equipment (such as surgical masks and filtering facepiece respirators (FFRs)) by physicians, nurses, and the patients themselves.
Receptor conversion and survival in breast cancer liver metastases
Authors: Sundén Marcus , Norgren Sofia , Lundqvist Robert , Andersson Anne , Sund Malin , Hemmingsson Oskar 
Published: September 2023

Abstract
Background
Breast cancer liver metastases (BCLM) is a common cause of breast cancer-related death. The prognostic and predictive value of receptor expression and St Gallen classification is challenged by receptor status discordance in distant metastases. The aim of this study was to determine the rate of receptor conversion from breast cancer to BCLM and the impact on survival.

Method
Patients registered with BCLM in two Swedish national cancer registers were recruited retrospectively. Data on receptor expression in primary breast cancer and BCLM were collected, as well as information about predictive factors for survival. The rate of receptor and subtype conversion was analyzed. A Cox regression model was used to investigate predictive factors for survival.

Results
A cohort of 132 patients with BCLM was identified. Estrogen receptor (ER), progesterone receptor (PgR) and HER2 converted in 17, 33 and 10%, respectively. PgR was lost in BCLM while 8/10 HER2 conversions went from negative to positive. The BC subtype was re-classified in 21% of the BCLM. Median survival after BCLM was 13 months and HER2 amplification was associated with improved survival (HR 0.28 CI 0.085–0.90). The highest predictive value (Harrell´s C-index) was obtained when including both BC and BCLM status.

Conclusions
Receptor and subtype conversions are common in BCLM, and a liver biopsy is warranted to tailor BCLM treatment. HER2 amplification is associated with improved survival in a BCLM cohort.
MicroRNA-989 targets 5-hydroxytryptamine receptor1 to regulate ovarian development and eggs production in Culex pipiens pallens
Authors: Zheng Junnan , Xu Jingwei , Zhang Ruiming , Du Jiajia , Wang Huan , Li Jinze , Zhou Dan , Sun Yan , Shen Bo 
Published: September 2023

AbstractBackgroundFemale mosquitoes need a blood meal after mating for their eggs to develop, and this behavior leads to the spread of pathogens. Therefore, understanding the molecular regulation of reproduction in female mosquitoes is essential to control mosquito vector populations. In this study, we reported that microRNA-989 (miR-989), which targets5-HTR1(encoding secreted5-hydroxytryptamine receptor1), is essential for mosquito reproduction.MethodsThe spatiotemporal expression profile of miR-989 was detected using quantitative real-time reverse transcription PCR (RT-qPCR). miR-989 antagomirs and antagomir-negative control (NC) were designed and synthesized to knock down the expression of endogenous miR-989 in female mosquitoes. RNA sequencing was used to analyze the ovarian response to miR-989 deletion. The targets of miR-989 were predicted and confirmed using RNAhybrid and dual-luciferase assays.ResultsmiR-989 is exclusively expressed in female mosquito ovaries and responds to blood feeding. Injection of the miR-989 antagomir resulted in smaller ovaries and reduced egg production.5-HTR1was demonstrated as a target of miR-989. The deletion of miR-989 contributed to the upregulation of5-HTR1expression. Knockdown of5-HTR1rescued the adverse egg production caused by miR-989 silencing. Thus, miR-989 might play an essential role in female reproduction by targeting5-HTR1.ConclusionsWe found that miR-989 targets5-HTR1and participates in the regulation of reproduction in female mosquitoes. These findings expand our understanding of reproduction-related miRNAs and promote new control strategies for mosquitoes.Graphical Abstract
Modelling porcine NAFLD by deletion of leptin and defining the role of AMPK in hepatic fibrosis
Authors: Tan Tan , Song Zhiyuan , Li Wenya , Wang Runming , Zhu Mingli , Liang Zuoxiang , Bai Yilina , Wang Qi , Wu Hanyu , Hu Xiaoxiang , Xing Yiming 
Published: September 2023

Abstract
Background
Non-alcoholic fatty liver disease (NAFLD) is the most prevalent cause of chronic hepatic disease and results in non-alcoholic steatohepatitis (NASH), which progresses to fibrosis and cirrhosis. Although the Leptin deficient rodent models are widely used in study of metabolic syndrome and obesity, they fail to develop liver injuries as in patients.

Methods
Due to the high similarity with humans, we generated Leptin-deficient (Leptin−/−) pigs to investigate the mechanisms and clinical trials of obesity and NAFLD caused by Leptin.

Results
The Leptin−/− pigs showed increased body fat and significant insulin resistance at the age of 12 months. Moreover, Leptin−/− pig developed fatty liver, non-alcoholic steatohepatitis and hepatic fibrosis with age. Absence of Leptin in pig reduced the phosphorylation of JAK2-STAT3 and AMPK. The inactivation of JAK2-STAT3 and AMPK enhanced fatty acid β-oxidation and leaded to mitochondrial autophagy respectively, and both contributed to increased oxidative stress in liver cells. In contrast with Leptin−/− pig, although Leptin deletion in rat liver inhibited JAK2-STAT3 phosphorylation, the activation of AMPK pathway might prevent liver injury. Therefore, β-oxidation, mitochondrial autophagy and hepatic fibrosis did not occurred in Leptin−/− rat livers.

Conclusions
The Leptin-deficient pigs presents an ideal model to illustrate the full spectrum of human NAFLD. The activity of AMPK signaling pathway suggests a potential target to develop new strategy for the diagnosis and treatment of NAFLD.