bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytogenomic features of Richter transformation
Authors: Woroniecka Renata , Rymkiewicz Grzegorz , Bystydzienski Zbigniew , Pienkowska-Grela Barbara , Rygier Jolanta , Malawska Natalia , Wojtkowska Katarzyna , Goral Nikolina , Blachnio Katarzyna , Chmielewski Marcin , Bartnik-Glaska Magdalena , Grygalewicz Beata 
Published: November 2023

Abstract
Background
Richter transformation (RT) is the development of aggressive lymphoma in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). This rare disease is characterised by dismal prognosis. In recent years, there has been a deeper understanding of RT molecular pathogenesis, and disruptions of apoptosis (TP53) and proliferation (CDKN2A, MYC, NOTCH1) has been described as typical aberrations in RT.

Results
A single-institution cohort of 33 RT patients were investigated by karyotyping, fluorescence in situ hybridization and single nucleotide polymorphism/copy number (CN) arrays. Most of RTs were typically manifested by diffuse large B-cell lymphoma, not otherwise specified, among the remaining cases one was classified as high-grade B-cell lymphoma with 11q aberrations. The most frequent alterations (40–60% of cases) were represented by MYC rearrangement/gain, deletions of TP53 and CDKN2A, IGH rearrangement and 13q14 deletion. Several other frequent lesions included losses of 14q24.1-q32.33, 7q31.33-q36.3, and gain of 5q35.2. Analysis of 13 CLL/SLL-RT pairs showed that RT arised from the CLL/SLL by acquiring of 10 ~ 12 cytogenetic or CN lesions/case, but without acquisition of loss of heterozygosity regions. Our result affirmed the higher genetic complexity in RT than CLL/SLL and confirmed the linear features of RT clonal evolution as predominant.

Conclusions
Cytogenomic profile was concordant with the literature data, however the role of IGH rearrangement, 14q deletion and 5q35.2 gain need to be explored. We anticipate that further characterization of RT lesions will probably facilitate better understanding of the RT clonal evolution.
Transcriptomic and metabolomic analyses reveal the essential nature of Rab1B in Toxoplasma gondii
Authors: He Kai , Wang Qiangqiang , Gao Xuwen , Tang Tao , Ding Huiyong , Long Shaojun 
Published: November 2023

Abstract
Background
The protozoan parasite Toxoplasma gondii encodes a dozen Rab proteins, which are parts of the small GTPase superfamily and regulate intracellular membrane trafficking. Our previous study showed that depletion of Rab1B caused severe defects regarding parasite growth and morphological structure, yet early defects of endocytic trafficking and vesicle sorting to the rhoptry in T. gondii are not expected to have a strong effect. To understand this discrepancy, we performed an integrated analysis at the level of transcriptomics and metabolomics.

Methods
In the study, tetracycline-inducible TATi/Ty-Rab1B parasite line treated with ATc at three different time points (0, 18 and 24 h) was used. We first observed the morphological changes caused by Rab1B depletion via transmission electron technology. Then, high-throughput transcriptome along with non-targeted metabolomics were performed to analyze the RNA expression and metabolite changes in the Rab1B-depleted parasite. The essential nature of Rab1B in the parasite was revealed by the integrated omics approach.

Results
Transmission electron micrographs showed a strong disorganization of endo-membranes in the Rab1B-depleted parasites. Our deep analysis of transcriptome and metabolome identified 2181 and 2374 differentially expressed genes (DEGs) and 30 and 83 differentially expressed metabolites (DEMs) at 18 and 24 h of induction in the tetracycline-inducible parasite line, respectively. These DEGs included key genes associated with crucial organelles that contain the rhoptry, microneme, endoplasmic reticulum and Golgi apparatus. The analysis of qRT-PCR verified some of the key DEGs identified by RNA-Seq, supporting that the key vesicular regulator Rab1B was involved in biogenesis of multiple parasite organelles. Functional enrichment analyses revealed pathways related to central carbon metabolisms and lipid metabolisms, such as the TCA cycle, glycerophospholipid metabolism and fatty acid biosynthesis and elongation. Further correlation analysis of the major DEMs and DEGs supported the role of Rab1B in biogenesis of fatty acids (e.g. myrisoleic acid and oleic acid) (R > 0.95 and P < 0.05), which was consistent with the scavenging role in biotin via the endocytic process.

Conclusions
Rab1B played an important role in parasite growth and morphology, which was supported by the replication assay and transmission electron microscopy observation. Our multi-omics analyses provided detailed insights into the overall impact on the parasite upon depletion of the protein. These analyses reinforced the role of Rab1B in the endocytic process, which has an impact on fatty acid biogenesis and the TCA cycle. Taken together, these findings contribute to our understanding of a key vesicular regulator, Rab1B, on parasite metabolism and morphological formation in T. gondii.

Graphical Abstract
Regenerative effects of platelet-rich plasma releasate injection in rabbit discs degenerated by intradiscal injection of condoliase
Authors: Hasegawa Takahiro , Akeda Koji , Yamada Junichi , Kawaguchi Koki , Takegami Norihiko , Fujiwara Tatsuhiko , Natsume Takahiro , Ide Koichiro , Matsuyama Yukihiro , Sudo Akihiro 
Published: November 2023

Abstract
Background
Intradiscal condoliase injection is an alternative therapeutic option for lumbar disc herniation (LDH). However, it is often associated with disc degeneration. Several in vivo studies have demonstrated the regenerative potential of platelet-rich plasma (PRP) in disc degeneration. Thus, we hypothesized that the intradiscal injection of PRP releasate (PRPr), a soluble releasate isolated from PRP, has the potential to regenerate degenerated intervertebral discs (IVDs) induced by condoliase. This study examined the regenerative effects of PRPr on rabbit IVDs degenerated following condoliase injection.

Methods
Eleven New Zealand white rabbits were used in this study. Condoliase (12.5 mU/10 μl) was injected into two non-contiguous discs (L2-L3 and L4-L5), and L3-L4 disc was left intact as a non-injection control. Saline (20 μl) or PRPr (20 μl) was randomly injected into L2-L3 and L4-L5 discs 4 weeks after the condoliase injection. Disc height (DH) was radiographically monitored biweekly from the day of condoliase injection to 16 weeks post-injection. Changes in DH were expressed as percentage DH (%DH) normalized to the baseline DH. Sixteen weeks after condoliase injection, all rabbits were euthanized, and subjected to MRI and histological analyses.

Results
Intradiscal injection of condoliase induced a significant decrease in %DH (L2-L3 and L4-L5) to 52.0% at week 4. However, the %DH began to return to normal after saline injection and reached 76.3% at week 16. In the PRPr group, %DH began to recover to normal after the PRPr injection and was restored to 95.5% at week 16. The MRI-modified Pfirrmann grade of the PRPr group was significantly lower than that of the saline group (P < 0.01). Histological analyses showed progressive degenerative changes, including reduction of the NP area and condensation of the matrix in the saline and PRPr groups. The histological score of the PRPr group was significantly lower than that of the saline group (P < 0.01).

Conclusions
PRPr has great potential to enhance the regeneration of degenerated rabbit IVDs induced by condoliase. The results of this preclinical study suggest that PRPr injection therapy may be indicated for patients with LDH who have poor recovery from disc degeneration after chemonucleolysis treatment with condoliase.
The role of non-canonical Hippo pathway in regulating immune homeostasis
Authors: Tang Dagang , Xu Huan , Du Xing 
Published: November 2023

AbstractThe Hippo pathway is a crucial signaling pathway that is highly conserved throughout evolution for the regulation of organ size and maintenance of tissue homeostasis. Initial studies have primarily focused on the canonical Hippo pathway, which governs organ development, tissue regeneration, and tumorigenesis. In recent years, extensive research has revealed that the non-canonical Hippo pathway, centered around Mst1/2 as its core molecule, plays a pivotal role in immune response and function by synergistically interacting with other signal transduction pathways. Consequently, the non-canonical Hippo pathway assumes significant importance in maintaining immune system homeostasis. This review concentrates on the research progress of the non-canonical Hippo pathway in regulating innate immune cell anti-infection responses, maintaining redox homeostasis, responding to microenvironmental stiffness, and T-cell differentiation.
Role of macrophage-to-myofibroblast transition in chronic liver injury and liver fibrosis
Authors: Xia Suhong , Huang Yujie , Zhang Yu , Zhang Mingyu , Zhao Kai , Han Ping , Tian Dean , Liao Jiazhi , Liu Jingmei 
Published: November 2023

Abstract
Background
Chronic liver injury contributes to liver fibrosis, which is characterized by the excessive deposition of extracellular matrix (ECM) components. ECM is mainly composed of myofibroblasts. Recently, macrophage-to-myofibroblasts transition (MMT), has been identified as a novel origin for myofibroblasts. However, the potential functions of MMT in chronic liver injury and liver fibrosis remain unknown.

Methods
To clarify the transformation of fibrotic cells in hepatic fibrosis, liver specimens were collected from people at different stages in the progression of hepatic fibrosis and stained with immunofluorescence. Models of hepatic fibrosis such as the CCL4 model, HFD-induced NAFLD model, MCD-induced NAFLD model and ethanol-induced AFLD model were demonstrated and were stained with immunofluorescence.

Results
Here, we uncovered macrophages underwent MMT in clinical liver fibrosis tissue samples and multiple animal models of chronic liver injury. MMT cells were found in specimens from patients with liver fibrosis on the basis of co-expression of macrophage (CD68) and myofibroblast (a-SMA) markers. Moreover, macrophages could transform into myofibroblasts in CCL4-induced liver fibrosis model, high-fat diet (HFD) and methionine-choline-deficient diet (MCD)-induced nonalcoholic fatty liver diseases (NAFLD) model, and ethanol-induced alcoholic fatty liver diseases (AFLD) model. In addition, we highlighted that MMT cells mainly had a predominant M2 phenotype in both human and experimental chronic liver injury.

Conclusions
Taken together, MMT acts a crucial role in chronic liver injury and liver fibrosis.
Hypoglossal canal: an osteological and morphometric study on a collection of dried skulls in an Italian population: clinical implications
Authors: Guarna Massimo , Lorenzoni Paola , Franci Daniela , Aglianò Margherita 
Published: November 2023

Abstract
Background
The hypoglossal canal is a dual bone canal at the cranial base near the occipital condyles. The filaments of the hypoglossal nerve pass through the canal. It also transmits the meningeal branch of the ascending pharyngeal artery, the venous plexus and meningeal branches of the hypoglossal nerve. The hypoglossal nerve innervates all the intrinsic and extrinsic muscles of the tongue except the palatoglossal and is fundamental in physiological functions as phonation and deglutition. A surgical approach to the canal requires knowledge of the main morphometric data by neurosurgeons.

Methods
The present study was carried out on 50 adult dried skulls: 31 males: age range 18–85 years; 19 females: age range 26–79 years. The skulls came from the ''Leonetto Comparini'' Anatomical Museum. The skulls belonged to people from Siena (Italy) and its surroundings (1882–1932) and, therefore, of European ethnicity. The present study reports (a) the osteological variations in hypoglossal canal (b) the morphometry of hypoglossal canal and its relationship with occipital condyles. One skull had both the right and left hypoglossal canals occluded and, therefore, could not be evaluated. None of the skulls had undergone surgery.

Results
We found a double canal in 16% of cases, unilaterally and bilaterally in 2% of cases. The mean length of the right and left hypoglossal canals was 8.46 mm. The mean diameter of the intracranial orifice and extracranial orifice of the right and left hypoglossal canals was 6.12 ± 1426 mm, and 6.39 ± 1495 mm. The mean distance from the intracranial end of the hypoglossal canal to the anterior and posterior ends of occipital condyles was 10,76 mm and 10,81 mm. The mean distance from the intracranial end of the hypoglossal canal to the inferior end of the occipital condyles was 7,65 mm.

Conclusions
The study on the hypoglossal canal adds new osteological and morphometric data to the previous literature, mostly based on studies conducted on different ethnic groups.The data presented is compatible with neuroradiological studies and it can be useful for radiologists and neurosurgeons in planning procedures such as transcondilar surgery. The last purpose of the study is to build an Italian anatomical data base of the dimensions of the hypoglossal canal in dried skulls..
Surgery-induced gut microbial dysbiosis promotes cognitive impairment via regulation of intestinal function and the metabolite palmitic amide
Authors: Pan Cailong , Zhang Huiwen , Zhang Lingyuan , Chen Lu , Xu Lu , Xu Ning , Liu Xue , Meng Qinghai , Wang Xiaoliang , Zhang Zhi-Yuan 
Published: November 2023

Abstract
Background
Perioperative neurocognitive disorders (PND) are the most common postoperative complications with few therapeutic options. Gut microbial dysbiosis is associated with neurological diseases; however, the mechanisms by which the microbiota regulates postoperative gastrointestinal and cognitive function are incompletely understood.

Methods
Behavioral testing, MiSeq 16S rRNA gene sequencing, non-target metabolism, intestinal permeability detection, protein assays, and immunofluorescence staining were employed to discern the impacts of surgery on microbial profiles, intestinal barriers, serum metabolism, and the brain. Interventions in mice included fecal microbiota transplantation, the anti-inflammatory agent dexamethasone, Lactobacillus supplementation, indole propionic acid supplementation, and palmitic amide administration.

Results
Surgery-induced cognitive impairment occurs predominantly in aged mice, and surgery-induced alterations in the microbiota composition profile exacerbate intestinal barrier disruption in aged mice. These adverse effects can be mitigated by transferring microbiota from young donors or by bolstering the intestinal barrier function using dexamethasone, Lactobacillus, or indole propionic acid. Moreover, microbiota composition profiles can be restored by transplanting feces from young mice to aged surgical mice, improving neuropathology and cognitive function, and these effects coincide with increased intestinal permeability. Metabolomic screening identified alterations in metabolites in mouse serum after surgery, especially the increase in palmitic amide. Palmitic amide levels in serum and brain can be decreased by transplanting feces from young mice to aged surgical mice. Oral palmitic amide exacerbates cognitive impairment and neuropathological changes in mice.

Conclusions
Gut microbial dysbiosis in mice after surgery is a key mechanism leading to cognition dysfunction, which disrupts the intestinal barrier and metabolic abnormalities, resulting in neuroinflammation and dendritic spine loss. Intestinal barrier damage and high level of palmitic amide in old mice may be the cause of high incidence of PND in the elderly. Preoperative microbiota regulation and intestinal barrier restoration may be of therapeutic benefit in preventing PND.
Network intrusion detection using feature fusion with deep learning
Authors: Ayantayo Abiodun , Kaur Amrit , Kour Anit , Schmoor Xavier , Shah Fayyaz , Vickers Ian , Kearney Paul , Abdelsamea Mohammed M. 
Published: November 2023

AbstractNetwork intrusion detection systems (NIDSs) are one of the main tools used to defend against cyber-attacks. Deep learning has shown remarkable success in network intrusion detection. However, the effect of feature fusion has yet to be explored in how to boost the performance of the deep learning model and improve its generalisation capability in NIDS. In this paper, we propose novel deep learning architectures with different feature fusion mechanisms aimed at improving the performance of the multi-classification components of NIDS. We propose three different deep learning models, which we call early-fusion, late-fusion, and late-ensemble learning models using feature fusion with fully connected deep networks. Our feature fusion mechanisms were designed to encourage deep learning models to learn relationships between different input features more efficiently and mitigate any potential bias that may occur with a particular feature type. To assess the efficacy of our deep learning solutions and make comparisons with state-of-the-art models, we employ the widely accessible UNSW-NB15 and NSL-KDD datasets specifically designed to enhance the development and evaluation of improved NIDSs. Through quantitative analysis, we demonstrate the resilience of our proposed models in effectively addressing the challenges posed by multi-classification tasks, especially in the presence of class imbalance issues. Moreover, our late-fusion and late-ensemble models showed the best generalisation behaviour (against overfitting) with similar performance on the training and validation sets.
Continuous chest compressions are associated with higher peak inspiratory pressures when compared to 30:2 in an experimental cardiac arrest model
Authors: Mälberg Johan , Marchesi Silvia , Spangler Douglas , Hadziosmanovic Nermin , Smekal David , Rubertsson Sten 
Published: November 2023

Abstract
Background
Ventilation during cardiopulmonary resuscitation (CPR) has long been a part of the standard treatment during cardiac arrests. Ventilation is usually given either during continuous chest compressions (CCC) or during a short pause after every 30 chest compressions (30:2). There is limited knowledge of how ventilation is delivered if it effects the hemodynamics and if it plays a role in the occurrence of lung injuries. The aim of this study was to compare ventilation parameters, hemodynamics, blood gases and lung injuries during experimental CPR given with CCC and 30:2 in a porcine model.

Methods
Sixteen pigs weighing approximately 33 kg were randomized to either receive CPR with CCC or 30:2. Ventricular fibrillation was induced by passing an electrical current through the heart. CPR was started after 3 min and given for 20 min. Chest compressions were provided mechanically with a chest compression device and ventilations were delivered manually with a self-inflating bag and 12 l/min of oxygen. During the experiment, ventilation parameters and hemodynamics were sampled continuously, and arterial blood gases were taken every five minutes. After euthanasia and cessation of CPR, the lungs and heart were removed in block and visually examined followed by sampling of lung tissue which were examined using microscopy.

Results
In the CCC group and the 30:2 group, peak inspiratory pressure (PIP) was 58.6 and 35.1 cmH2O (p < 0.001), minute volume (MV) 2189.6 and 1267.1 ml (p < 0.001), peak expired carbon dioxide (PECO2) 28.6 and 39.4 mmHg (p = 0.020), partial pressure of carbon dioxide (PaCO2) 50.2 and 61.1 mmHg (p = 0.013) and pH 7.3 and 7.2 (p = 0.029), respectively. Central venous pressure (CVP) decreased more over time in the 30:2 group (p = 0.023). All lungs were injured, but there were no differences between the groups.

Conclusions
Ventilation during CCC resulted in a higher PIP, MV and pH and lower PECO2 and PaCO2, showing that ventilation mode during CPR can affect ventilation parameters and blood gases.
Ancient slabs beneath Arctic and surroundings: Izanagi, Farallon, and in-betweens
Authors: Toyokuni Genti , Zhao Dapeng 
Published: November 2023

AbstractA detailed 3-D tomographic model of the whole mantle beneath the northern hemisphere (north of ~ 30°N latitude) is obtained by inverting a large amount of P-wave arrival time data (P, pP, and PP) to investigate transition of subducted slabs beneath Eurasia–Arctic–North America. We apply an updated global tomographic method that can investigate the whole mantle 3-D structure beneath a target area with high resolution comparable to that of regional tomography. The final tomographic model is obtained by performing independent calculations for 12 different target areas and stitching together the results. Our model clearly shows the subducted Izanagi and Farallon slabs penetrating into the lower mantle beneath Eurasia and North America, respectively. In the region from Canada to Greenland, a stagnant slab lying below the 660-km discontinuity is revealed. Because this slab has a texture that seems to be due to subducted oceanic ridges, the slab might be composed of the Farallon and Kula slabs that had subducted during ~60–50 Ma. During that period, a complex rift system represented by division between Canada and Greenland was developed. The oceanic ridge subduction and hot upwelling in the big mantle wedge above the stagnant slab caused a tensional stress field, which might have induced these complex tectonic events.
Caveolin-1 is critical for hepatic iron storage capacity in the development of nonalcoholic fatty liver disease
Authors: Deng Guang-Hui , Wu Chao-Feng , Li Yun-Jia , Shi Hao , Zhong Wei-Chao , Hong Mu-Keng , Li Jun-Jie , Zhao Jia-Min , Liu Chang , Qin Meng-Chen , Zeng Zhi-Yun , Zhang Wei-Min , Yung Ken Kin Lam , Lv Zhi-Ping , Gao Lei 
Published: November 2023

Abstract
Background
Nonalcoholic fatty liver disease (NAFLD) is associated with disordered lipid and iron metabolism. Our previous study has substantiated the pivotal role of Caveolin-1 (Cav-1) in protecting hepatocytes and mediating iron metabolism in the liver. This study aimed to explore the specific mechanisms underlying the regulation of iron metabolism by Cav-1 in NAFLD.

Methods
Hepatocyte-specific Cav-1 overexpression mice and knockout mice were used in this study. Cav-1-knockdown of RAW264.7 cells and mouse primary hepatocytes were performed to verify the changes in vitro. Moreover, a high-fat diet and palmitic acid plus oleic acid treatment were utilized to construct a NAFLD model in vivo and in vitro, respectively, while a high-iron diet was used to construct an in vivo iron overload model. Besides, iron concentration, the expression of Cav-1 and iron metabolism-related proteins in liver tissue or serum were detected using iron assay kit, Prussian blue staining, Western blotting, immunofluorescence staining, immunohistochemical staining and ELISA. The related indicators of lipid metabolism and oxidative stress were evaluated by the corresponding reagent kit and staining.

Results
Significant disorder of lipid and iron metabolism occurred in NAFLD. The expression of Cav-1 was decreased in NAFLD hepatocytes (P < 0.05), accompanied by iron metabolism disorder. Cav-1 enhanced the iron storage capacity of hepatocytes by activating the ferritin light chain/ferritin heavy chain pathway in NAFLD, subsequently alleviating the oxidative stress induced by excess ferrous ions in the liver. Further, CD68+CD163+ macrophages expressing Cav-1 were found to accelerate iron accumulation in the liver, which was contrary to the effect of Cav-1 in hepatocytes. Positive correlations were also observed between the serum Cav-1 concentration and the serum iron-related protein levels in NAFLD patients and healthy volunteers (P < 0.05).

Conclusions
These findings confirm that Cav-1 is an essential target protein that regulates iron and lipid metabolic homeostasis. It is a pivotal molecule for predicting and protecting against the development of NAFLD.