bluuebunny/crossref_metadata_2025_split huggingface dataset:
DICER1-associated central nervous system sarcoma with neural lineage differentiation: a case report
Authors: Yao Kun , Duan Zejun , Feng Jing , Yan Changxiang , Qi Xueling 
Published: September 2022

Abstract
Background
DICER1-associated central nervous system sarcoma (DCS) without evidence of other cancer-related syndromes is rare. Though the morphology of DCS was highly variable, the immunophenotype was predominant myogenic phenotype. Other lineage markers were consistently negative.

Case presentation
We report a case of DCS with neurogenic differentiation proved by immunohistochemical staining and whole-exome sequencing (WES). An 8-year-old female patient presented with 8-day history of headache, nausea and vomiting. Magnetic resonance imaging (MRI) revealed a heterogeneous mass in the left parietal lobe. The patient underwent the craniotomy via left parietal approach to resect the tumor completely. Histologically, the tumor predominately showed fibrosarcoma-like spindle cells with obvious cytoplasmic eosinophilic globules. Immunohistochemically, the tumor stained positively for DICER1, Desmin, and several neurogenic markers. DICER1 somatic hotspot mutation was confirmed by WES, as well as TP53 and RAF1 mutations which were commonly found in DCS, and other sarcoma-associated genes including AR, AXL and ETV5 mutations. Subsequently, the result of Gene Ontology (GO) analysis showed that the mutated genes in this case were involved in neuron development. All of these findings indicated the diagnosis of DCS with neurogenic differentiation. Postoperatively, the patient received high-dose radiotherapy (60 Gy) and chemotherapy. There was no MRI evidence of tumor recurrence at the 21-month postoperative follow-up.

Conclusions
This unusual DCS case with neuronal differentiation is an important addition to the immuno-phenotypic spectrum of DCS. Although the prognosis for DCS is poor, gross tumor resection with high dose radiotherapy and chemotherapy may assist in prolonging survival.
The genomic stability regulator PTIP is required for proper chromosome segregation in mitosis
Authors: Zhang Fengxia , Wei Mingxuan , Chen Haoran , Ji Liting , Nie Yan , Kang Jungseog 
Published: September 2022

Abstract
Background
The Pax transcription activation domain-interacting protein (PTIP) is a nuclear protein that is an essential component of H3K4 methylation for gene activation in vascular, kidney, B cell, and adipocyte development. Furthermore, it plays a key role in genomic stability in higher eukaryotic cells. It binds to 53BP1 and antagonizes inappropriate homologous recombination for a proper DNA damage response. Interestingly, an early study reported mitotic defects after PTIP inactivation, but it is not clear whether PTIP directly facilitates mitotic processes.

Results
Here, we showed that PTIP is essential for the mitotic integrity of HeLa cells. PTIP inactivation increases cell death during mitotic exit, which appears to result from direct mitotic defects. PTIP inactivation did not affect the G2M DNA damage checkpoint during interphase upon etoposide treatment. However, in mitosis, PTIP inactivation results in prolonged mitotic time, inefficient chromosome alignment, and increased cell death. Furthermore, PTIP localizes to the mitotic centrosome via BRCT domains at the C-terminus.

Conclusion
This study reveals a novel function of PTIP in maintaining the genomic stability of higher eukaryotes during mitosis. Therefore, its deregulation, which occurs in various tumors, may destabilize the genome by introducing an abnormal DNA damage response, as well as erroneous chromosome segregation.
Circ_0051079 functions as an oncogenic regulator in osteosarcoma by leading to MAFB expression upregulation by competitively interacting with miR-1286
Authors: Huang Zhong , Chen Pengcheng , Jia Ruipeng , Liu Yiheng 
Published: September 2022

Abstract
Background
Circular RNAs are involved in various cellular processes of bone diseases by acting as miRNA sponges to regulate gene expression levels, including osteosarcoma (OS). This research concentrated on the molecular mechanism of circ_0051079 in OS progression.

Methods
Reverse transcription-quantitative polymerase chain reaction assay was used for expression detection of circ_0051079, microRNA-1286 (miR-1286), and musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB). Cell Counting Kit-8 assay and Edu assay were used for cell proliferation analysis. Cell apoptosis was evaluated using flow cytometry. Western blot was performed to measure protein levels. Migration and invasion were assessed via transwell assay. Interaction of circ_0051079/miR-1286 or miR-1286/MAFB was explored through a dual-luciferase reporter assay. In vivo research was carried out via tumor xenograft assay and immunohistochemistry staining.

Results
Circ_0051079 expression was upregulated in OS. Downregulation of circ_0051079 reduced OS cell proliferation, migration, invasion, and accelerated apoptosis. Circ_0051079 interacted with miR-1286, and the tumor-inhibitory function of si-circ_0051079 was abolished by miR-1286 inhibition in OS cells. MAFB served as a target for miR-1286. OS cell progression was suppressed by miR-1286 overexpression via downregulating MAFB. Circ_0051079/miR-1286 resulted in expression change of MAFB in OS cells. Silencing circ_0051079 inhibited tumor growth in vivo via regulating the miR-1286/MAFB axis.

Conclusion
The collective results elucidated that circ_0051079 contributed to OS progression via miR-1286-mediated upregulation of MAFB, confirming the interaction of circ_0051079/miR-1286/MAFB axis in OS.
Characterization of a novel polysaccharide from red ginseng and its ameliorative effect on oxidative stress injury in myocardial ischemia
Authors: Lian Yuanpei , Zhu Maomao , Yang Bing , Wang Xianfeng , Zeng Jingqi , Yang Yanjun , Guo Shuchen , Jia Xiaobin , Feng Liang 
Published: September 2022

AbstractBackgroundRed ginseng (RG) was widely used as traditional Chinese medicine (TCM) or dietary supplement. However, few researches had been reported on the red ginseng polysaccharide (RGP).MethodsIn this study, a novel heteropolysaccharide named RGP1-1 was fractionated sequentially by DEAE-52 column and Sephadex G-100 gel column. The primary structure of RGP1-1, including glycosyl linkages, molecular weight, monosaccharide composition, morphology and physicochemical property were conducted by nuclear magnetic resonance (NMR), gas chromatography-mass spectrometer (GC–MS), atomic force microscope (AFM), scanning electron microscope (SEM), differential scanning calorimetry-thermogravimetric analysis (DSC-TG) and so on. The effect of RGP1-1 in preventing and treating myocardial ischemia was evaluated by an animal model isoprenaline (ISO) induced mice.ResultsRGP1-1, with a homogeneous molecular weight of 5655 Da, was composed of Glc and Gal in the ratio of 94.26:4.92. The methylation and NMR analysis indicated the backbone was composed of → 1)-Glcp-(4 → and → 1)-Galp-(4 →, branched partially at O-4 with α-D-Glcp-(1 → residue. Morphology and physicochemical property analysis revealed a triple-helical conformation, flaky and irregular spherical structure with molecule aggregations and stable thermal properties of RGP1-1. And it contained 6.82 mVzetapotential, 117.4 nm partical size and polymerization phenomenon. Furthermore, RGP1-1 possessed strong antioxidant activity in vitro and in vivo, RGP1-1 could decrease cardiomyocyte apoptosis and myocardium fibrosis of mice in histopathology and it could decrease significantly the serum levels of cardiac troponin (cTnI), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), malondialdehyde (MDA). Western blot analysis showed that RGP1-1 can increase the expression of main protein Nuclear factor E2-related factor 2(Nrf2), NAD(P)H:quinone oxidoreductase 1 (NQO1), heme oxygenase-1(HO-1) and kelch-like ECH-associated protein1(keap1) in oxidative stress injure progress, and therefore regulate the pathway of Nrf2/HO-1.ConclusionThe above findings indicated that RGP1-1 had an improving effect on ISO-induced myocardial ischemia injury in mice, as novel natural antioxidant and heart-protecting drugs.
AADAC protects colorectal cancer liver colonization from ferroptosis through SLC7A11-dependent inhibition of lipid peroxidation
Authors: Sun Rongquan , Lin Zhifei , Wang Xiangyu , Liu Lu , Huo Meisi , Zhang Rui , Lin Jing , Xiao Chao , Li Yitong , Zhu Wenwei , Lu Lu , Zhang Jubo , Chen Jinhong 
Published: September 2022

Abstract
Background
Oxidative stress is a highly active metabolic process in the liver, that poses great threats to disseminated tumor cells during their colonization. Here, we aimed to investigate how colorectal cancer (CRC) cells overcome lipid peroxidation to sustain their metastatic colonization in the liver.

Methods
Orthotopic colorectal liver metastasis (CRLM) and CRC liver colonization mouse models were constructed to determine the roles of lipid peroxidation and AADAC in CRC liver colonization. The levels of lipid peroxidation were detected in cells or tissues. AADAC overexpression in LMs and its clinical relevance were analyzed. The oncogenic role of AADAC in CRC liver colonization was evaluated in cell experiments.

Results
Compared with primary tumors (PTs), liver metastases (LMs) showed significantly lower glutathione to oxidized glutathione (GSH/GSSG) ratio and higher malondialdehyde (MDA) levels in CRLM patients and orthotopic mouse models. Inhibition of lipid peroxidation by liproxstatin-1 promoted CRC liver colonization in mouse models. RNA-seq results revealed AADAC as the most significantly upregulated lipid metabolism related gene in LMs compared with PTs. Analyses of datasets and patient and mouse model samples confirmed that AADAC was upregulated in LMs compared with PTs, and was correlated with poor prognosis. AADAC promoted cell proliferation, and facilitated liver colonization in a mouse model by reducing ROS accumulation, which led to lipid peroxidation and ferroptosis. Mechanistically, AADAC upregulated SLC7A11 by activating NRF2 to inhibit lipid peroxidation, thereby protecting metastatic cells from ferroptosis.

Conclusions
AADAC protects metastatic CRC cells from ferroptosis by inhibiting lipid peroxidation in an SLC7A11-dependent manner, thus effectively promoting their metastatic colonization and growth in the liver. Together, our findings suggest that AADAC can act as a prognostic indicator and potential therapeutic target for CRLM.
Gasdermin B over-expression modulates HER2-targeted therapy resistance by inducing protective autophagy through Rab7 activation
Authors: Gámez-Chiachio Manuel , Molina-Crespo Ángela , Ramos-Nebot Carmen , Martinez-Val Jeannette , Martinez Lidia , Gassner Katja , Llobet Francisco J. , Soriano Mario , Hernandez Alberto , Cordani Marco , Bernadó-Morales Cristina , Diaz Eva , Rojo-Sebastian Alejandro , Triviño Juan Carlos , Sanchez Laura , Rodríguez-Barrueco Ruth , Arribas Joaquín , Llobet-Navás David , Sarrió David , Moreno-Bueno Gema 
Published: September 2022

Abstract
Background
Gasdermin B (GSDMB) over-expression promotes poor prognosis and aggressive behavior in HER2 breast cancer by increasing resistance to therapy. Decoding the molecular mechanism of GSDMB-mediated drug resistance is crucial to identify novel effective targeted treatments for HER2/GSDMB aggressive tumors.

Methods
Different in vitro approaches (immunoblot, qRT-PCR, flow cytometry, proteomic analysis, immunoprecipitation, and confocal/electron microscopy) were performed in HER2 breast and gastroesophageal carcinoma cell models. Results were then validated using in vivo preclinical animal models and analyzing human breast and gastric cancer samples.

Results
GSDMB up-regulation renders HER2 cancer cells more resistant to anti-HER2 agents by promoting protective autophagy. Accordingly, the combination of lapatinib with the autophagy inhibitor chloroquine increases the therapeutic response of GSDMB-positive cancers in vitro and in zebrafish and mice tumor xenograft in vivo models. Mechanistically, GSDMB N-terminal domain interacts with the key components of the autophagy machinery LC3B and Rab7, facilitating the Rab7 activation during pro-survival autophagy in response to anti-HER2 therapies. Finally, we validated these results in clinical samples where GSDMB/Rab7/LC3B co-expression associates significantly with relapse in HER2 breast and gastric cancers.

Conclusion
Our findings uncover for the first time a functional link between GSDMB over-expression and protective autophagy in response to HER2-targeted therapies. GSDMB behaves like an autophagy adaptor and plays a pivotal role in modulating autophagosome maturation through Rab7 activation. Finally, our results provide a new and accessible therapeutic approach for HER2/GSDMB + cancers with adverse clinical outcome.
Structured implementation of digital, systematically updated guideline recommendations for enhanced adherence in schizophrenia (SISYPHOS)—protocol of a cluster-randomized trial
Authors: Lorenz Carolin , Gaigl Gabriele , Güler Duygu , Halms Theresa , Khorikian-Ghazari Naiiri , Röh Astrid , Schneider Marco , Wagner Elias , Schneider-Axmann Thomas , Kapfhammer Angelika , Flick Marisa , Pielenz Charline , Salveridou-Hof Eva , Falkai Peter , Gaebel Wolfgang , Hasan Alkomiet , Leucht Stefan 
Published: September 2022

AbstractBackgroundDespite high acceptance rates in the field, the implementation of the 2019 published German evidence and consensus-based S3 guideline is unsatisfactory. This study aims to assess the superiority of an adaptive online version with a better visualization of the recommendations in terms of guideline conformity, application of shared decision making, and digital health expertise compared to the classic pdf print version of the guideline.MethodsThe study is a multicenter, controlled, cluster-randomized trial with two arms: one arm investigating the implementation of the German schizophrenia guideline in form of a digital format (intervention group using the evidence ecosystem MAGICapp), the other arm in form of the classic print pdf version (control group). Physicians and psychologists working in specialized hospitals will be included in the study. The guideline-knowledge before and after the intervention is defined as primary outcome measure. Secondary endpoints include digital health expertise and application of shared decision making.DiscussionThis is the first study evaluating if an adaptive-digital version of the schizophrenia guideline is superior to the classic pdf print version. Therefore, the guideline is digitally prepared in the evidence-ecosystem MAGICapp, which covers the whole process of the development of a living guideline. We intend to use the results of the cluster-randomized trial for developing the German S3 guideline for schizophrenia in form of a living guideline in future.Trial registrationThe study is registered (10 May 2022) in the German Clinical Trials Register (DRKS) and the WHO International Clinical Trials Registry Platform (ICTRP) under registration numberDRKS00028895.
A validated LC–MS/MS method for analysis of Cabergoline in human plasma with its implementation in a bioequivalent study: investigation of method greenness
Authors: Shalaby Khaled , Alghamdi Saleh , Gamal Mohammed , Elhalim Lobna Mohammed Abd , Tony Rehab Moussa 
Published: September 2022

AbstractCabergoline (CAB) is effective prolactin lowering drug. Evaluation of the bioequivalence for the new test product (0.5 mg CAB film-coated tablets) in Egypt is strongly needed for approval of the drug by the official health authority. Therefore, a highly sensitive and rapid (LC–MS/MS) method was validated for CAB analysis in human plasma. CAB was extracted from plasma via diethyl ether using Quetiapine (QUE) as an internal standard. Multiple reaction monitoring (MRM) in positive ion mode was used, m/z 452.3 → 381.2 for CAB and 384.2 → 253.1 for QUE. Separation was accomplished on a reversed-phase C18. FDA procedures for the bio-analytical method were followed. The method was used in the bioequivalence study to compare the test product (0.5 mg CAB) versus Dostinex tablets, on 24 healthy Egyptian volunteers. The total analysis time was 5.5 min for each sample which permits analysis of various samples per day. The linearity range was from 2.00 to 200.00 pg/mL for CAB. LOD and LOQ were found to be 0.5 and 1.6 pg/mL, respectively. The final greenness numerical value was 0.63 using AGREE tool. The results of pharmacokinetic parameter Tmax were 2.17, and 2.33 h; for test and reference products, respectively. The generic formulation of test product is considered bioequivalent to the reference product Dostinex 0.5 mg tablets and satisfies the requirements of the Egyptian market. The merits of the method over the previous published methods are low cost; availability of cheap internal standard; rapidness; use of acetonitrile-free solvents mobile phase.
Spatial and temporal parasite dynamics: microhabitat preferences and infection progression of two co-infecting gyrodactylids
Authors: Twumasi Clement , Jones Owen , Cable Joanne 
Published: September 2022

AbstractBackgroundMathematical modelling of host-parasite systems has seen tremendous developments and broad applications in theoretical and applied ecology. The current study focuses on the infection dynamics of a gyrodactylid-fish system. Previous experimental studies have explored the infrapopulation dynamics of co-infecting ectoparasites,Gyrodactylus turnbulliandG. bullatarudis, on their fish host,Poecilia reticulata, but questions remain about parasite microhabitat preferences, host survival and parasite virulence over time. Here, we use more advanced statistics and a sophisticated mathematical model to investigate these questions based on empirical data to add to our understanding of this gyrodactylid-fish system.MethodsA rank-based multivariate Kruskal-Wallis test coupled with its post-hoc tests and graphical summaries were used to investigate the spatial and temporal parasite distribution of different gyrodactylid strains across different host populations. By adapting a multi-state Markov model that extends the standard survival models, we improved previous estimates of survival probabilities. Finally, we quantified parasite virulence of three different strains as a function of host mortality and recovery across different fish stocks and sexes.ResultsWe confirmed that the captive-bredG. turnbulliand wildG. bullatarudisstrains preferred the caudal and rostral regions respectively across different fish stocks; however, the wildG. turnbullistrain changed microhabitat preference over time, indicating microhabitat preference of gyrodactylids is host and time dependent. The average time of host infection before recovery or death was between 6 and 14 days. For this gyrodactylid-fish system, a longer period of host infection led to a higher chance of host recovery. Parasite-related mortalities are host, sex and time dependent, whereas fish size is confirmed to be the key determinant of host recovery.ConclusionFrom existing empirical data, we provided new insights into the gyrodactylid-fish system. This study could inform the modelling of other host-parasite interactions where the entire infection history of the host is of interest by adapting multi-state Markov models. Such models are under-utilised in parasitological studies and could be expanded to estimate relevant epidemiological traits concerning parasite virulence and host survival.Graphical Abstract
Co-fitness analysis identifies a diversity of signal proteins involved in the utilization of specific c-type cytochromes
Authors: Ding De-wu , Huang Wei-fan , Lei Li-lan , Wu Pu 
Published: September 2022

Abstract
Purpose
c-Type cytochromes are essential for extracellular electron transfer (EET) in electroactive microorganisms. The expression of appropriate c-type cytochromes is an important feature of these microorganisms in response to different extracellular electron acceptors. However, how these diverse c-type cytochromes are tightly regulated is still poorly understood.

Methods
In this study, we identified the high co-fitness genes that potentially work with different c-type cytochromes by using genome-wide co-fitness analysis. We also constructed and studied the co-fitness networks that composed of c-type cytochromes and the top 20 high co-fitness genes of them.

Results
We found that high co-fitness genes of c-type cytochromes were enriched in signal transduction processes in Shewanella oneidensis MR-1 cells. We then checked the top 20 co-fitness proteins for each of the 41 c-type cytochromes and identified the corresponding signal proteins for different c-type cytochromes. In particular, through the analysis of the high co-fitness signal protein for CymA, we further confirmed the cooperation between signal proteins and c-type cytochromes and identified a novel signal protein that is putatively involved in the regulation of CymA. In addition, we showed that these signal proteins form two signal transduction modules.

Conclusion
Taken together, these findings provide novel insights into the coordinated utilization of different c-type cytochromes under diverse conditions.
Recent findings on chimeric antigen receptor (CAR)-engineered immune cell therapy in solid tumors and hematological malignancies
Authors: Keshavarz Ali , Salehi Ali , Khosravi Setareh , Shariati Yasaman , Nasrabadi Navid , Kahrizi Mohammad Saeed , Maghsoodi Sairan , Mardi Amirhossein , Azizi Ramyar , Jamali Samira , Fotovat Farnoush 
Published: September 2022

AbstractAdvancements in adoptive cell therapy over the last four decades have revealed various new therapeutic strategies, such as chimeric antigen receptors (CARs), which are dedicated immune cells that are engineered and administered to eliminate cancer cells. In this context, CAR T-cells have shown significant promise in the treatment of hematological malignancies. However, many obstacles limit the efficacy of CAR T-cell therapy in both solid tumors and hematological malignancies. Consequently, CAR-NK and CAR-M cell therapies have recently emerged as novel therapeutic options for addressing the challenges associated with CAR T-cell therapies. Currently, many CAR immune cell trials are underway in various human malignancies around the world to improve antitumor activity and reduce the toxicity of CAR immune cell therapy. This review will describe the comprehensive literature of recent findings on CAR immune cell therapy in a wide range of human malignancies, as well as the challenges that have emerged in recent years.