bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of immunotherapy mediated by apoptotic bodies, microvesicles and exosomes: apoptotic bodies’ unique anti-inflammatory potential
Authors: Wen Jing , Creaven Dale , Luan Xiangshu , Wang Jiemin 
Published: July 2023

AbstractImmunotherapy, including immunostimulation and immunosuppression, has seen significant development in the last 10 years. Immunostimulation has been verified as effective in anti-cancer treatment, while immunosuppression is used in the treatment of autoimmune disease and inflammation. Currently, with the update of newly-invented simplified isolation methods and the findings of potent triggered immune responses, extracellular vesicle-based immunotherapy is very eye-catching. However, the research on three main types of extracellular vesicles, exosomes, microvesicles and apoptotic bodies, needs to be more balanced. These three subtypes share a certain level of similarity, and at the same time, they have their own properties caused by the different methods of biogensis. Herein, we summarized respectively the status of immunotherapy based on each kind of vesicle and discuss the possible involved mechanisms. In conclusion, we highlighted that the effect of the apoptotic body is clear and strong. Apoptotic bodies have an excellent potential in immunosuppressive and anti-inflammatory therapies .
IL-1RA promotes oral squamous cell carcinoma malignancy through mitochondrial metabolism-mediated EGFR/JNK/SOX2 pathway
Authors: Yuan Shyng-Shiou F. , Wang Yun-Ming , Chan Leong-Perng , Hung Amos C. , Nguyen Hieu D. H. , Chen Yuk-Kwan , Hu Stephen Chu‐Sung , Lo Steven , Wang Yen-Yun 
Published: July 2023

Abstract
Background
Interleukin-1 receptor antagonist (IL-1RA), a member of the IL-1 family, has diverse roles in cancer development. However, the role of IL-1RA in oral squamous cell carcinoma (OSCC), in particular the underlying mechanisms, remains to be elucidated.

Methods
Tumor tissues from OSCC patients were assessed for protein expression by immunohistochemistry. Patient survival was evaluated by Kaplan–Meier curve analysis. Impact of differential IL-1RA expression on cultured OSCC cell lines was assessed in vitro by clonogenic survival, tumorsphere formation, soft agar colony formation, and transwell cell migration and invasion assays. Oxygen consumption rate was measured by Seahorse analyzer or multi-mode plate reader. PCR array was applied to screen human cancer stem cell-related genes, proteome array for phosphorylation status of kinases, and Western blot for protein expression in cultured cells. In vivo tumor growth was investigated by orthotopic xenograft in mice, and protein expression in xenograft tumors assessed by immunohistochemistry.

Results
Clinical analysis revealed that elevated IL-1RA expression in OSCC tumor tissues was associated with increased tumor size and cancer stage, and reduced survival in the patient group receiving adjuvant radiotherapy compared to the patient group without adjuvant radiotherapy. In vitro data supported these observations, showing that overexpression of IL-1RA increased OSCC cell growth, migration/invasion abilities, and resistance to ionizing radiation, whereas knockdown of IL-1RA had largely the opposite effects. Additionally, we identified that EGFR/JNK activation and SOX2 expression were modulated by differential IL-1RA expression downstream of mitochondrial metabolism, with application of mitochondrial complex inhibitors suppressing these pathways. Furthermore, in vivo data revealed that treatment with cisplatin or metformin—a mitochondrial complex inhibitor and conventional therapy for type 2 diabetes—reduced IL-1RA-associated xenograft tumor growth as well as EGFR/JNK activation and SOX2 expression. This inhibitory effect was further augmented by combination treatment with cisplatin and metformin.

Conclusions
The current study suggests that IL-1RA promoted OSCC malignancy through mitochondrial metabolism-mediated EGFR/JNK activation and SOX2 expression. Inhibition of this mitochondrial metabolic pathway may present a potential therapeutic strategy in OSCC.
Transcriptional activity of the long control region in human papillomavirus type 33 intratype variants
Authors: Gyöngyösi Eszter , László Brigitta , Szalmás Anita , Kónya József , Veress György 
Published: July 2023

Abstract
Background
High-risk human papillomaviruses (HPVs) are responsible for the development of cervical and other anogenital cancers. Intratype sequence variants of certain high-risk HPV types (e.g. 16, 18 and 31) are thought to have different oncogenic potential, partly due to nucleotide sequence variation in the viral long control region (LCR). The LCR has an important role in the regulation of viral replication and transcription. The purpose of this study was to explore sequence variation in the LCR of HPV 33 intratype variants in Hungary and to see whether there are differences in the transcriptional activities of the variants.

Methods
The complete HPV 33 LCR was amplified from HPV 33 positive cervical samples. After sequencing the LCR variants, multiple sequence alignment and phylogenetic analyses were carried out. Representative HPV 33 LCR sequence variants were selected for cloning and functional analysis. After transient transfection of HeLa cells, luciferase reporter assays were used to analyse the transcriptional activities of different LCR variants.

Results
Altogether 10 different variants were identified by sequence analysis of the HPV 33 LCR. The results of phylogenetic analysis showed that 3 variants belonged to sublineage A1, while the other 7 variants clustered with sublineage A2. Variants belonging to sublineage A2 had significantly lower transcriptional activities than variants belonging to sublineage A1. Within sublineage A2, the two variants analysed had significantly different transcriptional activities, which was shown to be caused by the A7879G variation.

Conclusions
Nucleotide variation in the HPV 33 LCR can result in altered transcriptional activity of the intratype variants. Our results can help to understand the correlation between LCR polymorphism and the oncogenic potential of HPV 33 variants.
The incidence and severity of open gingival embrasures in adults treated with clear aligners and fixed appliances: a retrospective cohort study
Authors: Yang Tianrui , Jiang Lishan , Sun Weiman , Zhu Meng , Jiang Ke , Li Houxuan , Lei Lang 
Published: July 2023

AbstractBackgroundTo evaluate the incidence and severity of open gingival embrasures (OGEs) in adult patients treated with clear aligners and fixed appliances.MethodsTwo hundred non-extraction adult subjects with less than 5 mm of crowding (mean age, 24.6 ± 3.8 years) were enrolled in this retrospective study. The subjects were divided into the clear aligner (n = 100) and fixed appliance group (n = 100). The intraoral photographs were utilized to determine the incidence of OGEs in the upper arch between maxillary central incisors, as well as the lower arch between mandibular central incisors. Crown overlap, crown shape, posttreatment root angulation, the distance from the interproximal contact point (ICP) to the alveolar bone crest (ABC) after treatment and interproximal enamel reduction (IPR) were determined in the two groups.ResultsThe incidence of OGEs between maxillary and mandibular central incisors after orthodontic treatment was 35.0% and 38.0% in the clear aligner group, respectively, significantly higher than that (18.0% and 24.0%) in the fixed appliance group (P < 0.05). The average area of an OGE after clear aligner treatment was larger both in the maxilla (0.16 ± 0.12mm2) and mandible (0.21 ± 0.24mm2) compared with that (0.05 ± 0.03mm2and 0.05 ± 0.06mm2) after fixed appliance treatment (P < 0.05). No difference was found regarding pretreatment crown overlap, crown shape, treatment duration, posttreatment root angulation, amount and distribution of IPR and the distance from ICP to ABC.ConclusionsThe incidence and severity of OGEs were higher in adults treated with clear aligners. Clinicians should be aware of the risk of OGEs during treatment with clear aligners.
Three-dimensional design custom-made uncemented stem for revision of cemented distal femoral endoprosthesis due to aseptic loosening
Authors: Li Zhuangzhuang , Lu Minxun , Zhou Yong , Min Li , Tu Chongqi 
Published: July 2023

Abstract
Background
Revision of cemented distal femoral replacement (DFR) due to aseptic loosening is challenging because of the resultant femoral bone loss. This paper aims to examine the outcomes of three-dimensional (3D) design custom-made uncemented stems for revision.

Methods
Between January 2014 and December 2020, 17 patients received 3D design uncemented stems for revision of loosed cemented DFR. The femoral bone loss was classified into four Grades, and four types of uncemented stems were designed correspondingly. The revision stems were custom-made for each patient by measuring the diameter of the medullary cavity and the anterior curvature of the femur.

Results
The patient counts with their corresponding Grades of femoral bone loss were as follows: Grade I, 8 patients; Grade II, 5 patients; Grade III, 3 patients; and Grade IV, 1 patient. During the mean follow-up of 80 months, no revision failure was detected. The postoperative radiographic showed that the stem matched the femoral anterior curvature well. The femoral bone defect was completely filled by the 3D design stem in 10 of the 17 cases postoperatively. In the remaining cases, the persistent peri-stem defect was filled or partially restored during the follow-up.

Conclusion
3D design custom-made uncemented stem created precise, stable, and durable fixation and provided satisfactory clinical outcomes, which seems to be a viable method for cemented DFR revision.
Energy stress-induced circZFR enhances oxidative phosphorylation in lung adenocarcinoma via regulating alternative splicing
Authors: Ma Zhifei , Chen Hao , Xia Zhijun , You Jing , Han Chencheng , Wang Siwei , Xia Wenjia , Bai Yongkang , Liu Tongyan , Xu Lin , Zhou Guoren , Xu Youtao , Yin Rong 
Published: July 2023

Abstract
Background
Circular RNAs (circRNAs) contribute to multiple biological functions and are also involved in pathological conditions such as cancer. However, the role of circRNAs in metabolic reprogramming, especially upon energy stress in lung adenocarcinoma (LUAD), remains largely unknown.

Methods
Energy stress-induced circRNA was screened by circRNA profiling and glucose deprivation assays. RNA-seq, real-time cell analyzer system (RTCA) and measurement of oxygen consumption rate (OCR) were performed to explore the biological functions of circZFR in LUAD. The underlying mechanisms were investigated using circRNA pull-down, RNA immunoprecipitation, immunoprecipitation and bioinformatics analysis of alternative splicing. Clinical implications of circZFR were assessed in 92 pairs of LUAD tissues and adjacent non-tumor tissues, validated in established patient-derived tumor xenograft (PDTX) model.

Results
CircZFR is induced by glucose deprivation and is significantly upregulated in LUAD compared to adjacent non-tumor tissues, enhancing oxidative phosphorylation (OXPHOS) for adaptation to energy stress. CircZFR is strongly associated with higher T stage and poor prognosis in patients with LUAD. Mechanistically, circZFR protects heterogeneous nuclear ribonucleoprotein L-like (HNRNPLL) from degradation by ubiquitination to regulate alternative splicing, such as myosin IB (MYO1B), and subsequently activates the AKT-mTOR pathway to facilitate OXPHOS.

Conclusion
Our study provides new insights into the role of circRNAs in anticancer metabolic therapies and expands our understanding of alternative splicing.
RAGE inhibition blunts insulin-induced oncogenic signals in breast cancer
Authors: Muoio M. G. , Pellegrino M. , Rapicavoli V. , Talia M. , Scavo G. , Sergi V. , Vella V. , Pettinato S. , Galasso M. G. , Lappano R. , Scordamaglia D. , Cirillo F. , Pulvirenti A. , Rigiracciolo D. C. , Maggiolini M. , Belfiore A. , De Francesco E. M. 
Published: July 2023

AbstractThe receptor for advanced glycation end products (RAGE) is implicated in diabetes and obesity complications, as well as in breast cancer (BC). Herein, we evaluated whether RAGE contributes to the oncogenic actions of Insulin, which plays a key role in BC progression particularly in obese and diabetic patients. Analysis of the publicly available METABRIC study, which collects gene expression and clinical data from a large cohort (n = 1904) of BC patients, revealed that RAGE and the Insulin Receptor (IR) are co-expressed and associated with negative prognostic parameters. In MCF-7, ZR75 and 4T1 BC cells, as well as in patient-derived Cancer-Associated Fibroblasts, the pharmacological inhibition of RAGE as well as its genetic depletion interfered with Insulin-induced activation of the oncogenic pathway IR/IRS1/AKT/CD1. Mechanistically, IR and RAGE directly interacted upon Insulin stimulation, as shown by in situ proximity ligation assays and coimmunoprecipitation studies. Of note, RAGE inhibition halted the activation of both IR and insulin like growth factor 1 receptor (IGF-1R), as demonstrated in MCF-7 cells KO for the IR and the IGF-1R gene via CRISPR-cas9 technology. An unbiased label-free proteomic analysis uncovered proteins and predicted pathways affected by RAGE inhibition in Insulin-stimulated BC cells. Biologically, RAGE inhibition reduced cell proliferation, migration, and patient-derived mammosphere formation triggered by Insulin. In vivo, the pharmacological inhibition of RAGE halted Insulin-induced tumor growth, without affecting blood glucose homeostasis. Together, our findings suggest that targeting RAGE may represent an appealing opportunity to blunt Insulin-induced oncogenic signaling in BC.
Identifying and quantifying isoforms from accurate full-length transcriptome sequencing reads with Mandalorion
Authors: Volden Roger , Schimke Kayla D. , Byrne Ashley , Dubocanin Danilo , Adams Matthew , Vollmers Christopher 
Published: July 2023

AbstractIn this manuscript, we introduce and benchmark Mandalorion v4.1 for the identification and quantification of full-length transcriptome sequencing reads. It further improves upon the already strong performance of Mandalorion v3.6 used in the LRGASP consortium challenge. By processing real and simulated data, we show three main features of Mandalorion: first, Mandalorion-based isoform identification has very high precision and maintains high recall even in the absence of any genome annotation. Second, isoform read counts as quantified by Mandalorion show a high correlation with simulated read counts. Third, isoforms identified by Mandalorion closely reflect the full-length transcriptome sequencing data sets they are based on.
LILRB4 regulates the function of decidual MDSCs via the SHP-2/STAT6 pathway during Toxoplasma gondii infection
Authors: Li Yuantao , Guo Jingjing , Zhang Haixia , Li Zhidan , Ren Yushan , Jiang Yuzhu , Liu Xianbing , Hu Xuemei 
Published: July 2023

Abstract
Background
Toxoplasma gondii infection can cause adverse pregnancy outcomes, such as recurrent abortion, fetal growth restriction and infants with malformations, among others. Decidual myeloid-derived suppressor cells (dMDSCs) are a novel immunosuppressive cell type at the fetal-maternal interface which play an important role in sustaining normal pregnancy that is related to their high expression of the inhibitory molecule leukocyte immunoglobulin-like receptor B4 (LILRB4). It has been reported that the expression of LILRB4 is downregulated on decidual macrophages after T. gondii infection, but it remains unknown whether T. gondii infection can induce dMDSC dysfunction resulting from the change in LILRB4 expression.

Methods
LILRB4-deficient (LILRB4−/−) pregnant mice infected with T. gondii with associated adverse pregnancy outcomes, and anti-LILRB4 neutralized antibodies-treated infected human dMDSCs were used in vivo and in vitro experiments, respectively. The aim was to investigate the effect of LILRB4 expression on dMDSC dysfunction induced by T. gondii infection.

Results
Toxoplasma gondii infection was observed to reduce STAT3 phosphorylation, resulting in decreased LILRB4 expression on dMDSCs. The levels of the main functional molecules (arginase-1 [Arg-1], interleukin-10 [IL-10]) and main signaling molecules (phosphorylated Src-homology 2 domain-containing protein tyrosine phosphatase [p-SHP2], phosphorylated signal transducer and activator of transcription 6 [p-STAT6]) in dMDSCs were all significantly reduced in human and mouse dMDSCs due to the decrease of LILRB4 expression induced by T. gondii infection. SHP-2 was found to directly bind to STAT6 and STAT6 to bind to the promoter of the Arg-1 and IL-10 genes during T. gondii infection.

Conclusions
The downregulation of LILRB4 expression on dMDSCs induced by T. gondii infection could regulate the expression of Arg-1 and IL-10 via the SHP-2/STAT6 pathway, resulting in the dysfunction of dMDSCs, which might contribute to adverse outcomes during pregnancy by T. gondii infection.

Graphical abstract
Ancestry-driven metabolite variation provides insights into disease states in admixed populations
Authors: Reynolds Kaylia M. , Horimoto Andrea R. V. R. , Lin Bridget M. , Zhang Ying , Kurniansyah Nuzulul , Yu Bing , Boerwinkle Eric , Qi Qibin , Kaplan Robert , Daviglus Martha , Hou Lifang , Zhou Laura Y. , Cai Jianwen , Shaikh Saame Raza , Sofer Tamar , Browning Sharon R. , Franceschini Nora 
Published: July 2023

Abstract
Background
Metabolic pathways are related to physiological functions and disease states and are influenced by genetic variation and environmental factors. Hispanics/Latino individuals have ancestry-derived genomic regions (local ancestry) from their recent admixture that have been less characterized for associations with metabolite abundance and disease risk.

Methods
We performed admixture mapping of 640 circulating metabolites in 3887 Hispanic/Latino individuals from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Metabolites were quantified in fasting serum through non-targeted mass spectrometry (MS) analysis using ultra-performance liquid chromatography-MS/MS. Replication was performed in 1856 nonoverlapping HCHS/SOL participants with metabolomic data.

Results
By leveraging local ancestry, this study identified significant ancestry-enriched associations for 78 circulating metabolites at 484 independent regions, including 116 novel metabolite-genomic region associations that replicated in an independent sample. Among the main findings, we identified Native American enriched genomic regions at chromosomes 11 and 15, mapping to FADS1/FADS2 and LIPC, respectively, associated with reduced long-chain polyunsaturated fatty acid metabolites implicated in metabolic and inflammatory pathways. An African-derived genomic region at chromosome 2 was associated with N-acetylated amino acid metabolites. This region, mapped to ALMS1, is associated with chronic kidney disease, a disease that disproportionately burdens individuals of African descent.

Conclusions
Our findings provide important insights into differences in metabolite quantities related to ancestry in admixed populations including metabolites related to regulation of lipid polyunsaturated fatty acids and N-acetylated amino acids, which may have implications for common diseases in populations.
Tuberculosis and Takayasu arteritis: a case report
Authors: Ferjani Maryem , El Euch Mounira , Boumediene Mariem , Jrad Mariem , Hamida Fethi Ben , Turki Sami , Gargah Tahar 
Published: July 2023

Abstract
Background
Takayasu arteritis is a rare and chronic granulomatous vasculitis that affects the large vessels. Takayasu arteritis targets the aorta and its branches and is still of unknown etiology. It often affects female patients under 50 years of age. A relationship between Takayasu arteritis and tuberculosis has been suggested for a long time.

Case presentation
We report a severe case of Takayasu arteritis in a 10-year-old Tunisian child revealed by renovascular hypertension with concomitant pulmonary tuberculosis.

Conclusions
Our patient is among only a few cases of Takayasu arteritis published worldwide affecting young infants and adolescents, which underlines the strong relationship between Takayasu arteritis and tuberculosis.
E-mental health in Germany — what is the current use and what are experiences of different types of health care providers for patients with mental illnesses?
Authors: Weitzel Elena Caroline , Schwenke Maria , Schomerus Georg , Schönknecht Peter , Bleckwenn Markus , Mehnert-Theuerkauf Anja , Riedel-Heller Steffi G. , Löbner Margrit 
Published: July 2023

Abstract
Background
As a new and effective support option, e-mental health interventions can be useful in complementing treatment in mental health care. To date, little is known about how health care providers use these programs to treat patients with mental illnesses in Germany. The present study aims to examine the use of and experiences with e-mental health interventions from the point of view of different types of health care providers for patients with mental illnesses.

Methods
Data from a cross-sectional survey of routine care health care providers in Germany in 2021 were analysed. In this survey, data were collected from n = 107 general practitioners (GPs), n = 114 specialist doctors, n = 102 psychotherapists, and n = 102 inpatient clinicians. Assessments included professional use of digital media, as well as knowledge, use and experiences regarding e-mental health interventions in care of people with mental illness.

Results
In the total sample of n = 425, 65.6% (n = 279) were female. The study participants had an average age of 47.7 years (SD = 11.0) and their average work experience was 20.0 years (SD = 11.1). Overall, the majority (83.8%, n = 353) had heard of e-mental health interventions, but few felt well informed. Only 28.5% (n = 121) had already used e-mental health interventions for treatment support. The most commonly recommended e-mental health interventions in the sample were deprexis (39.7%, n = 48), moodgym (24.8%, n = 30), and iFightDepression (22.3%, n = 27). The use was predominantly considered to be helpful and satisfactory. Insufficient knowledge about e-mental health interventions and lack of informational materials for patients were reported as relevant barriers to the use of e-mental health interventions.

Conclusions
E-mental health interventions can be a useful support option, but they are rarely used in the treatment of patients with mental illnesses. There is a need to disseminate information specific to the various types of health care providers. Tailored implementation strategies need to be developed in order to capitalize on the potential of effective e-mental health interventions and to improve health care for patients with mental illnesses.