bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scorpion venom peptide HsTx2 suppressed PTZ-induced seizures in mice via the circ_0001293/miR-8114/TGF-β2 axis
Authors: Hu Yan , Meng Buliang , Yin Saige , Yang Meifeng , Li Yilin , Liu Naixin , Li Shanshan , Liu Yixiang , Sun Dandan , Wang Siyu , Wang Yinglei , Fu Zhe , Wu Yutong , Pang Ailan , Sun Jun , Wang Ying , Yang Xinwang 
Published: December 2022

Abstract
Background
Due to the complexity of the mechanisms involved in epileptogenesis, the available antiseizure drugs (ASDs) do not meet clinical needs; hence, both the discovery of new ASDs and the elucidation of novel molecular mechanisms are very important.

Methods
BALB/c mice were utilized to establish an epilepsy model induced by pentylenetetrazol (PTZ) administration. The peptide HsTx2 was administered for treatment. Primary astrocyte culture, immunofluorescence staining, RNA sequencing, identification and quantification of mouse circRNAs, cell transfection, bioinformatics and luciferase reporter analyses, enzyme-linked immunosorbent assay, RNA extraction and reverse transcription–quantitative PCR, Western blot and cell viability assays were used to explore the potential mechanism of HsTx2 via the circ_0001293/miR-8114/TGF-β2 axis.

Results
The scorpion venom peptide HsTx2 showed an anti-epilepsy effect, reduced the inflammatory response, and improved the circular RNA circ_0001293 expression decrease caused by PTZ in the mouse brain. Mechanistically, in astrocytes, circ_0001293 acted as a sponge of endogenous microRNA-8114 (miR-8114), which targets transforming growth factor-beta 2 (TGF-β2). The knockdown of circ_0001293, overexpression of miR-8114, and downregulation of TGF-β2 all reversed the anti-inflammatory effects and the influence of HsTx2 on the MAPK and NF-κB signaling pathways in astrocytes. Moreover, both circ_0001293 knockdown and miR-8114 overexpression reversed the beneficial effects of HsTx2 on inflammation, epilepsy progression, and the MAPK and NF-κB signaling pathways in vivo.

Conclusions
HsTx2 suppressed PTZ-induced epilepsy by ameliorating inflammation in astrocytes via the circ_0001293/miR-8114/TGF-β2 axis. Our results emphasized that the use of exogenous peptide molecular probes as a novel type of ASD, as well as to explore the novel endogenous noncoding RNA-mediated mechanisms of epilepsy, might be a promising research area.

Graphical Abstract
Role of postoperative radiotherapy in resected adenoid cystic carcinoma of the head and neck
Authors: Choi Seo Hee , Yang Andrew Jihoon , Yoon Sun Och , Kim Hye Ryun , Hong Min Hee , Kim Se-Heon , Choi Eun Chang , Keum Ki Chang , Lee Chang Geol 
Published: December 2022

Abstract
Purpose
Although postoperative radiotherapy (PORT) is demonstrably effective in local control of head and neck adenoid cystic carcinoma (HNACC), its application is controversial and the subset of patients who would benefit most from PORT is unknown. Herein, we analyzed the data of HNACC patients to clarify the role of PORT.

Methods
We retrospectively reviewed 187 patients with nonmetastatic HNACC who underwent surgical resection between 2005 and 2019. The study endpoints were locoregional failure-free survival (LRFFS), progression-free survival (PFS), and overall survival (OS). Subgroup analysis and recursive partitioning analysis (RPA) were performed to identify patients most likely to benefit from PORT.

Results
With a median follow-up of 84.7 months, the 5-year LRFFS, PFS, and OS were 70.0%, 52.6%, and 86.4%, respectively. Survival was significantly shorter in patients who experienced local failure than in those who did not (5-year OS: 88.1% vs. 80.5%, P = 0.001). The local failure rate was significantly lower in patients who underwent PORT (16.9% vs. 31.0%, P = 0.021), despite the high frequency of adverse factors. Especially, significant decreases in local failure and similar OS rates could be obtained after PORT among patients with positive margins, T2-4 stage disease, and minor salivary gland tumors. The RPA model for PFS categorized patients into four groups according to three prognostic factors (T-stage, location, and sex). The RPA model for LRFFS and OS suggested three groups based on two factors (T-stage, margin for LRFFS; T-stage, grade 3 for OS).

Conclusion
PORT could prevent dismal survival, while significantly reducing local failures in high-risk HNACC patients.
Machine learning and experimental validation to construct a metastasis-related gene signature and ceRNA network for predicting osteosarcoma prognosis
Authors: Liao Yong , Liu Qingsong , Xiao Chunxia , Zhou Jihui 
Published: December 2022

Abstract
Objective
Osteosarcoma (OS) is more common in adolescents and significantly harmful, and the survival rate is considerably low, especially in patients with metastatic OS. The identification of effective biomarkers and associated regulatory mechanisms, which predict OS occurrence and development as well as improve prognostic accuracy, will help develop more refined protocols for OS treatment.

Methods
In this study, genes showing differential expression in metastatic and non-metastatic types of OS were identified, and the ones affecting OS prognosis were screened from among these. Following this, the functions and pathways associated with the genes were explored via enrichment analysis, and an effective predictive signature was constructed using Cox regression based on the machine learning algorithm, least absolute shrinkage and selection operator (LASSO). Next, a correlative competing endogenous RNA (ceRNA) regulatory axis was constructed after verification by bioinformatics analysis and luciferase reporter gene experiments conducted based on the prognostic signature.

Results
Overall, 251 differentially expressed genes were identified and screened using bioinformatics and double luciferase reporter gene experiments. An effective prognostic signature was constructed based on 15 genes associated with OS metastasis, and upstream non-coding RNAs were identified to construct the “NBR2/miR-129-5p/FKBP11” regulatory axis based on the ceRNA networks, which helped identify candidate biomarkers for the OS clinical diagnosis and treatment, drug research, and prognostic prediction, among other applications. The findings of this study provide a novel strategy for determining the mechanism underlying OS occurrence and development and the appropriate treatment.
Prevalence of 13 polyomaviruses in actinic keratosis and matched healthy skin samples of immunocompetent individuals
Authors: Donà Maria Gabriella , Gheit Tarik , Chiantore Maria Vincenza , Vescio Maria Fenicia , Luzi Fabiola , Rollo Francesca , Accardi Luisa , Cota Carlo , Galati Luisa , Romeo Giovanna , Giuliani Massimo , Tommasino Massimo , Di Bonito Paola 
Published: December 2022

Abstract
Background
Actinic keratosis (AK) is a precursor of cutaneous squamous cell carcinoma (cSCC). UV radiation is the major risk factor for AK, but certain human papillomaviruses (HPVs) of the beta genus are also involved in its development. Differently, the role of polyomaviruses (PyVs) in skin carcinogenesis is still debated. Fiftheen PyVs have been isolated from human tissues so far, including Merkel cell polyomavirus (MCPyV), the aetiological agent of Merkel cell carcinoma.

Methods
The presence of 13 PyVs was assessed in skin samples from AK patients (n = 342). Matched fresh-frozen scrapings from healthy skin (HS) and AK lesions from 242 patients, and formalin-fixed paraffin-embedded AK biopsies from a different cohort of 100 patients were analyzed by multiplex PyVs genotyping assay.

Results
The most frequent lesion site was the scalp in men (27.3%), and the cheek area in women (29.0%). Differences between men and women were significant for the scalp, the cheek area and the lips. Almost all the scrapings were PyV-positive (HS: 89.7%, AK: 94.6%; p = 0.04). The three most frequent PyVs were MCPyV, HPyV6 and JCPyV (HS: 87.2%, 58.7%, 6.6%, respectively; AK: 88.8%, 51.2%, 9.9%, respectively). HPyV9, TSPyV, BKPyV, HPyV7, LIPyV and SV40 were detected in < 2% of the scrapings. In most cases, matched HS and AK scrapings were both positive (MCPyV: 78.1%, HPyV6: 41.7%), or both negative for the individual genotypes (for the remaining PyVs). PyV prevalence in AK biopsies was 22.0%. Only MCPyV (21.0%) and HPyV6 (3.0%) were detected in these samples.

Conclusions
PyV prevalence in HS and AK scrapings was high, but detection of PyVs exclusively in AK scrapings was rare. PyV positivity rate in AK biopsies was modest. Further research is need to reach firm conclusions regarding the role of these viruses in AK development.
Differences between complex epithelial neoplasms of the ovary and high-grade serous ovarian cancer: a retrospective observational cohort study
Authors: Li Xiaoxue , Ding Yiling , Liu Yang , Yang Mengyuan 
Published: December 2022

Abstract
Background
Complex epithelial neoplasms of the ovary (CENO), an uncommon pathological histotype in ovarian cancer, comprises adenosquamous carcinoma and adenocarcinoma with metaplasia. Owing to the rarity of relevant reports, there are currently no statistics on outcomes based on large samples. Meanwhile high-grade serous ovarian cancer (HGSOC) is the most common histotype in ovarian cancer which has a recognized first-line treatment regimen and poor prognosis. Thus, we aimed to determine the characteristics, prognosis, and independent predictors of survival for CENO, compare them with those of HGSOC and construct prognostic predictive models and nomograms.

Methods
We used the Surveillance, Epidemiology, and End Results (SEER) database to determine patients diagnosed with CENO or HGSOC from 2000 to 2017. Clinical, demographic, and treatment characteristics were compared between these groups. Propensity score matching, Cox risk regression analysis, Kaplan–Meier survival curves, and the Least Absolute Shrinkage and Selection Operator regression analysis were employed for analyzing the data.

Results
Here, 31,567 patients with HGSOC and 216 patients with CENO between 2000 and 2017 in the SEER database were enrolled. Age < 57 years, unmarried, and early-stage diseases were more common in patients with CENO than in those with HGSOC. Women with CENO were less likely to receive adjuvant chemotherapy (65.7% vs. 79.4%) but more likely to receive radiotherapy (6.0% vs. 0.8%; both p < 0.001) than those with HGSOC. Year of diagnosis, surgery status, number of primary tumors, grade, and FIGO stage were independent prognostic factors for overall and cancer-specific survival in CENO. Overall survival rates were significantly lower for CENO than for more malignant HGSOC.

Conclusions
In summary, CENO was rare in ovarian cancer, while the year of diagnosis, surgery status, number of primary tumors, grade, and FIGO stage were independent prognostic factors. Compared with other common malignant ovarian tumors, CENO had a poor prognosis. Prognostic predictive models and nomograms had been determined to predict the individual survival rates of patients with CENO. These methods could improve evaluations of survival and therapeutic decisions for patients.
Predicting disease-free survival in colorectal cancer by circulating tumor DNA methylation markers
Authors: Yang Xin , Wen Xiaofeng , Guo Qin , Zhang Yunfeng , Liang Zhenxing , Wu Qian , Li Zhihao , Ruan Weimei , Ye Zhujia , Wang Hong , Chen Zhiwei , Fan Jian-Bing , Lan Ping , Liu Huashan , Wu Xianrui 
Published: December 2022

Abstract
Background
Recurrence represents a well-known poor prognostic factor for colorectal cancer (CRC) patients. This study aimed to establish an effective prognostic prediction model based on noninvasive circulating tumor DNA methylation markers for CRC patients receiving radical surgery.

Results
Two methylation markers (cg11186405 and cg17296166) were identified by Cox regression and receiver operating characteristics, which could classify CRC patients into high recurrence risk and low recurrence risk group. The 3-year disease-free survival was significantly different between CRC patients with low and high recurrence risk [Training set: hazard ratio (HR) 28.776, 95% confidence interval (CI) 3.594–230.400; P = 0.002; Validation set: HR 7.796, 95% CI 1.425–42.660, P = 0.018]. The nomogram based on the above two methylation markers and TNM stage was established which demonstrated robust prognostic prediction potential, as evidenced by the decision curve analysis result.

Conclusions
A cell-free DNA methylation model consisting of two DNA methylation markers is a promising method for prognostic prediction in CRC patients.
Prequasiideal of the type weighted binomial matrices in the Nakano sequence space of soft functions with some applications
Authors: Alsolmi Meshayil M. , Mustafa Arafa O. , Mohamed Om Kalthum S. K. , Bakery Awad A. 
Published: December 2022

AbstractConsider the space of weighted binomial matrices in the Nakano sequence space of soft functions. We have offered some geometric and topological structures of the multiplication operator acting on this space and its associated operator ideal. The existence of a fixed point of the Kannan contraction operator in this prequasioperator ideal is confirmed. Finally, we discuss many applications of solutions to nonlinear stochastic dynamical matrix systems and illustrative examples of our findings.
Isotope tracing reveals distinct substrate preference in murine melanoma subtypes with differing anti-tumor immunity
Authors: Zhang Xinyi , Halberstam Alexandra A. , Zhu Wanling , Leitner Brooks P. , Thakral Durga , Bosenberg Marcus W. , Perry Rachel J. 
Published: December 2022

Abstract
Background
Research about tumor “metabolic flexibility”—the ability of cells to toggle between preferred nutrients depending on the metabolic context—has largely focused on obesity-associated cancers. However, increasing evidence for a key role for nutrient competition in the tumor microenvironment, as well as for substrate regulation of immune function, suggests that substrate metabolism deserves reconsideration in immunogenic tumors that are not strongly associated with obesity.

Methods
We compare two murine models: immunologically cold YUMM1.7 and immunologically-hot YUMMER1.7. We utilize stable isotope and radioisotope tracer-based metabolic flux studies as well as gas and liquid chromatography-based metabolomics analyses to comprehensively probe substrate preference in YUMM1.7 and YUMMER1.7 cells, with a subset of studies on the impact of available metabolites across a panel of five additional melanoma cell lines. We analyze bulk RNA-seq data and identify increased expression of amino acid and glucose metabolism genes in YUMMER1.7. Finally, we analyze melanoma patient RNA-seq data to identify potential prognostic predictors rooted in metabolism.

Results
We demonstrate using stable isotope tracer-based metabolic flux studies as well as gas and liquid chromatography-based metabolomics that immunologically-hot melanoma utilizes more glutamine than immunologically-cold melanoma in vivo and in vitro. Analyses of human melanoma RNA-seq data demonstrate that glutamine transporter and other anaplerotic gene expression positively correlates with lymphocyte infiltration and function.

Conclusions
Here, we highlight the importance of understanding metabolism in non-obesity-associated cancers, such as melanoma. This work advances the understanding of the correlation between metabolism and immunogenicity in the tumor microenvironment and provides evidence supporting metabolic gene expression as potential prognostic factors of melanoma progression and may inform investigations of adjunctive metabolic therapy in melanoma.

Trial registration
Deidentified data from The Cancer Genome Atlas were analyzed.
A cold high-pressure system over North China hinders the southward migration of Mythimna separata in autumn
Authors: Zhu Jian , Chen Xiao , Liu Jie , Jiang Yuying , Chen Fajun , Lu Jiahao , Chen Hui , Zhai Baoping , Reynolds Don R. , Chapman Jason W. , Hu Gao 
Published: December 2022

AbstractBackgroundIn warm regions or seasons of the year, the planetary boundary layer is occupied by a huge variety and quantity of insects, but the southward migration of insects (in East Asia) in autumn is still poorly understood.MethodsWe collated daily catches of the oriental armyworm (Mythimna separata) moth from 20 searchlight traps from 2014 to 2017 in China. In order to explore the autumn migratory connectivity ofM. separatain East China, we analyzed the autumn climate and simulated the autumn migration process of moths.ResultsThe results confirmed that northward moth migration in spring and summer under the East Asian monsoon system can bring rapid population growth. However, slow southerly wind (blowing towards the north) prevailed over the major summer breeding area in North China (33°–40° N) due to a cold high-pressure system located there, and this severely disrupts the autumn ‘return’ migration of this pest. Less than 8% of moths from the summer breeding area successfully migrated back to their winter-breeding region, resulting in a sharp decline of the population abundance in autumn. As northerly winds (blowing towards the south) predominate at the eastern periphery of a high-pressure system, the westward movement of the high-pressure system leads to more northerlies over North China, increasing the numbers of moths migrating southward successfully. Therefore, an outbreak year ofM. separatalarvae was associated with a more westward position of the high-pressure system during the previous autumn.ConclusionThese results indicate that the southward migration in autumn is crucial for sustaining pest populations ofM. separata, and the position of the cold high-pressure system in September is a key environmental driver of the population size in the next year. This study indicates that the autumn migration of insects in East China is more complex than previously recognized, and that the meteorological conditions in autumn are an important driver of migratory insects’ seasonal and interannual population dynamics.
Long-term outcome of the IMZ implant system: a retrospective clinical study with a follow-up between 23 and 34 years
Authors: Mautsch Christoph , Wolfart Stefan , Mautsch Walter , Rittich Anne Barbara 
Published: December 2022

AbstractPurposeTo evaluate the radiographic and peri-implant outcomes of intramobile cylinder implants (IMZs) and the feasibility of long-term follow-up studies after nearly 30 years.MethodsOf the 94 patients treated with IMZ implants between 1981 and 1995, 39 patients were successfully contacted (contact group, CG), of which 15 patients with a total of 32 implants agreed to participate in the present follow-up study (clinical evaluation group, CEG). The overall implant survival rate was calculated. Information on implant status and oral and general health data was collected. Marginal bone level was evaluated and then compared to the patients’ baseline data. Possible risk factors for peri-implantitis were also identified.ResultsIn total, 16 implants in seven patients were lost, amounting to an overall survival rate of 79.5% after 30 years with a mean follow-up time of 24 ± 10 years (CG). Eight patients were treated with bar-retained mandibular overdentures and seven patients had fixed partial dentures. After a mean observation time of 29 ± 3 years, the surviving implants showed a peri-implantitis rate of 9.4% with a mean marginal bone loss of 2.5 ± 1.8 mm (CEG). No significant correlation between peri-implantitis and possible risk factors could be found.ConclusionsLong-term follow-up studies with acceptable response rates after nearly 30 years are not feasible. Contact was only possible with 41% of the patients. This contact group showed a high implant survival rate. Due to the retrospective study design, additional risk factors could not be considered in a conclusive analysis.Graphical Abstract
Decitabine Versus Hydroxyurea for Advanced Proliferative Chronic Myelomonocytic Leukemia: Results of a Randomized Phase III Trial Within the EMSCO Network
Authors: Itzykson Raphael , Santini Valeria , Thepot Sylvain , Ades Lionel , Chaffaut Cendrine , Giagounidis Aristoteles , Morabito Margot , Droin Nathalie , Lübbert Michael , Sapena Rosa , Nimubona Stanislas , Goasguen Jean , Wattel Eric , Zini Gina , Torregrosa Diaz Jose Miguel , Germing Ulrich , Pelizzari Anna Maria , Park Sophie , Jaekel Nadja , Metzgeroth Georgia , Onida Francesco , Navarro Robert , Patriarca Andrea , Stamatoullas Aspasia , Götze Katharina , Puttrich Martin , Mossuto Sandra , Solary Eric , Gloaguen Silke , Chevret Sylvie , Chermat Fatiha , Platzbecker Uwe , Fenaux Pierre 
Published: December 2022

PURPOSEHydroxyurea (HY) is a reference treatment of advanced myeloproliferative neoplasms. We conducted a randomized phase III trial comparing decitabine (DAC) and HY in advanced myeloproliferative chronic myelomonocytic leukemias (CMML).PATIENTS AND METHODSNewly diagnosed myeloproliferative CMML patients with advanced disease were randomly assigned 1:1 to intravenous DAC (20 mg/m2/d days 1-5) or HY (1-4 g/d) in 28-day cycles. The primary end point was event-free survival (EFS), events being death and acute myelomonocytic leukemia (AML) transformation or progression.RESULTSOne-hundred seventy patients received DAC (n = 84) or HY (n = 86). Median age was 72 and 74 years, and median WBC count 32.5 × 109/L and 31.2 × 109/L in the DAC and HY arms, respectively. Thirty-three percent of DAC and 31% of HY patients had CMML-2. Patients received a median of five DAC and six HY cycles. With a median follow-up of 17.5 months, median EFS was 12.1 months in the DAC arm and 10.3 months in the HY arm (hazard ratio [HR], 0.83; 95% CI, 0.59 to 1.16; P = .27). There was no significant interaction between treatment effect and blast or platelet count, anemia, CMML Prognostic Scoring System, Groupe Francophone des Myelodysplasies, or CMML Prognostic Scoring System–mol risk. Fifty-three (63%) DAC patients achieved a response compared with 30 (35%) HY patients ( P = .0004). Median duration of response was similar in both arms (DAC, 16.3 months; HY, 17.4 months; P = .90). Median overall survival was 18.4 months in the DAC arm and 21.9 months in the HY arm ( P = .67). Compared with HY, DAC significantly reduced the risk of CMML progression or transformation to acute myelomonocytic leukemia (cause-specific HR, 0.62; 95% CI, 0.41 to 0.94; P = .005) at the expense of death without progression or transformation (cause-specific HR, 1.55; 95% CI, 0.82 to 2.9; P = .04).CONCLUSIONCompared with HY, frontline treatment with DAC did not improve EFS in patients with advanced myeloproliferative CMML (ClinicalTrials.gov identifier: NCT02214407 ).