bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microglia and astrocyte activation is region‐dependent in the α‐synuclein mouse model of Parkinson's disease
Authors: Basurco Leyre , Abellanas Miguel Angel , Ayerra Leyre , Conde Enrique , Vinueza‐Gavilanes Rodrigo , Luquin Esther , Vales Africa , Vilas Amaya , Martin‐Uriz Patxi San , Tamayo Ibon , Alonso Marta M. , Hernaez Mikel , Gonzalez‐Aseguinolaza Gloria , Clavero Pedro , Mengual Elisa , Arrasate Montserrat , Hervás‐Stubbs Sandra , Aymerich Maria S. 
Published: November 2022

AbstractInflammation is a common feature in neurodegenerative diseases that contributes to neuronal loss. Previously, we demonstrated that the basal inflammatory tone differed between brain regions and, consequently, the reaction generated to a pro‐inflammatory stimulus was different. In this study, we assessed the innate immune reaction in the midbrain and in the striatum using an experimental model of Parkinson's disease. An adeno‐associated virus serotype 9 expressing the α‐synuclein and mCherry genes or the mCherry gene was administered into the substantia nigra. Myeloid cells (CD11b+) and astrocytes (ACSA2+) were purified from the midbrain and striatum for bulk RNA sequencing. In the parkinsonian midbrain, CD11b+ cells presented a unique anti‐inflammatory transcriptomic profile that differed from degenerative microglia signatures described in experimental models for other neurodegenerative conditions. By contrast, striatal CD11b+ cells showed a pro‐inflammatory state and were similar to disease‐associated microglia. In the midbrain, a prominent increase of infiltrated monocytes/macrophages was observed and, together with microglia, participated actively in the phagocytosis of dopaminergic neuronal bodies. Although striatal microglia presented a phagocytic transcriptomic profile, morphology and cell density was preserved and no active phagocytosis was detected. Interestingly, astrocytes presented a pro‐inflammatory fingerprint in the midbrain and a low number of differentially displayed transcripts in the striatum. During α‐synuclein‐dependent degeneration, microglia and astrocytes experience context‐dependent activation states with a different contribution to the inflammatory reaction. Our results point towards the relevance of selecting appropriate cell targets to design neuroprotective strategies aimed to modulate the innate immune system during the active phase of dopaminergic degeneration.
Ossa cordis and os aorta in the one‐humped camel: Computed tomography, light microscopy and morphometric analysis
Authors: El‐Gendy Samir A.A. , Alsafy Mohamed A.M. , Rutland Catrin S. , Ez Elarab Samar M. , Abd‐Elhafeez Hanan H. , Kamal Basma M. 
Published: November 2022

AbstractThe present study describes the morphological characteristics of the camel heart Ossa cordis, and os aorta using computed tomography soft tissue window (CT) alongside 3D render volume reconstructions and light microscopy. The current study techniques demonstrated the Ossa cordis and os aorta in the cardiac window with more precision than the black and white (ghost), and angiography images. Transverse and sagittal CT images additionally demonstrated the presence of Ossa cordis and os aorta. This study is the first to record two small Ossa cordis sinistrum and one os aorta in the camel heart, in addition to the more commonly observed singular, large, os cordis dextrum. The os cordis dextrum was always located in the upper part of the interventricular septum, near to its junction with the atrium, forming an elongated rectangular shape when observed transversally. The wider cranial part was composed from bone, whereas the caudal aspect was narrow and contained both bone and cartilage. Light microscopy identified that the os cordis dextrum consisted of trabecular bone, marrow spaces, and hyaline cartilage. Two Ossa cordis sinistrum were detected on the left side of the heart, one in the right fibrous ring and another in the interventricular septum, microscopy showed that both contained only trabecular bone with osteocytes, osteoblasts, and osteoclasts. At the level of ascending aorta, there was also trabecular bone containing osteocytes, an os aorta.
Elevated retinal retinol‐binding protein 4 levels in diabetic mice can induce retinal neurodegeneration through microglia
Authors: Xu Zhiwei , Bai Shi , Wu Haijian , Fang Marong 
Published: November 2022

AbstractRetinol‐binding protein 4 (RBP4) is the sole specific transport protein for vitamin A (retinol), but it is also an adipokine with retinol‐independent, proinflammatory activity associated with diabetes and diabetic retinopathy (DR). Most previous studies focused on the relationship between elevated serum RBP4 levels and DR. Since serum RBP4 cannot cross the blood‐retinal barrier, the level of retinal RBP4 is independent of serum RBP4, and the change of retinal RBP4 and its potential pathogenic mechanism in DR has not been studied. We showed that the retinal RBP4 levels were raised in Streptozotocin‐induced diabetic mice though the serum RBP4 levels were decreased. Intravitreal injection of RBP4 protein in mice results in activation of microglia, loss of retinal ganglion cells (RGCs) and bipolar cells. Minocycline (MC) can reverse the activation of microglia induced by RBP4, protecting RGCs and bipolar cells. These findings suggest that retinal RBP4 levels were raised in diabetic mice, and RBP4 can directly induce retinal neurodegeneration in mice through microglia.Research HighlightsWe revealed that the retinal RBP4 levels were raised in diabetes and elevated retinal RBP4 can induce retinal neurodegeneration through microglia. Inhibition of neuroinflammation or reduction of retinal RBP4 level may be a potential therapeutic strategy to prevent diabetic retinal neurodegeration.
Right Ventricular Remodeling Assessed by MRI in Duchenne Muscular Dystrophy
Authors: Brown Nicholas K. , Berhane Haben , Gambetta Katheryn , Markl Michael , Rigsby Cynthia K. , Robinson Joshua D. , Husain Nazia 
Published: November 2022

BackgroundIn Duchenne muscular dystrophy (DMD), the right ventricle (RV) tends to be relatively well preserved, but characterization remains difficult due to its complex architecture. Tissue phase mapping (TPM) is a phase contrast cine MRI technique that allows for multidirectional assessment of myocardial velocities.PurposeTo use TPM to elucidate relationships between myocardial structure, function, and clinical variables in DMD.Study TypeRetrospective.SubjectsA total of 20 patients with muscular dystrophy (median age: 16 years); 18 age‐matched normal controls (median age: 15 years).Field Strength/SequenceThree‐directional velocity encoded cine gradient echo sequence (TPM) at 1.5 T, balanced steady‐state free procession (bSSFP), T1 mapping with extracellular volume (ECV), and late gadolinium enhancement (LGE).AssessmentTPM in basal, mid, and apical short‐axis planes was performed as part of a standard MRI study with collection of clinical data. Radial, circumferential, and longitudinal velocities (Vr, Vφ, and Vz, respectively) and corresponding time to peak (TTP) velocities were quantified from TPM and used to calculate RV twist as well as intraventricular and interventricular dyssynchrony. The correlations between TPM velocities, myocardial structure/function, and clinical variables were assessed.Statistical TestUnpaired t‐test, Wilcoxon rank‐sum test, Bland–Altman analyses were used for comparisons between DMD patients and controls and between DMD subgroups. Pearson's test was used for correlations (r). Significance level: P < 0.05.ResultsCompared to controls, DMD patients had preserved RV ejection fraction (RVEF 53% ± 8%) but significantly increased interventricular dyssynchrony (Vφ: 0.49 ± 0.21 vs. 0.72 ± 0.17). Within the DMD cohort, RV dyssynchrony significantly increased with lower LV ejection fraction (intraventricular Vr and Vz: r = −0.49; interventricular Vz: r = 0.48). In addition, RV intraventricular dyssynchrony significantly increased with older age (Vz: r = 0.67).Data ConclusionRV remodeling in DMD occurs in the context of preserved RVEF. Within DMD, this abnormal RV deformation is associated with older age and decreased LVEF.Evidence Level4.Technical EfficacyStage 2.
Intraoperative blood transfusion does not impact overall and recurrence‐free survival after curative hepatectomy for hepatocellular carcinoma: A propensity‐score‐matched and inverse probability of treatment‐weighted study
Authors: Tan Laura L. Y. , Chew Valerie T. W. , Syn Nicholas , Tan Ek‐Khoon , Koh Ye‐Xin , Teo Jin‐Yao , Cheow Peng‐Chung , Jeyaraj Prema Raj , Chow Pierce K. H. , Chan Chung‐Yip , Chung Alexander Y. F. , Ooi London L. P. J. , Goh Brian K. P. 
Published: November 2022

AbstractIntroductionOur primary objective was to determine if receiving intraoperative blood transfusion was a significant prognostic factor for overall and recurrence‐free survival after curative resection of hepatic cellular carcinoma (HCC).MethodologyBetween 2001 and 2018, 1092 patients with histologically proven primary HCC who underwent curative liver resection were retrospectively reviewed. Primary study endpoints were recurrence‐free survival (RFS) and overall survival (OS). The main analysis was undertaken using propensity‐score matching (PSM) to minimize confounding and selection biases in the comparison of patients with or without transfusion.ResultsThere were 220 patients who received and 666 patients who did not receive intraoperative blood transfusion. The PSM cohort consisted of 163 pairs of patients. After PSM, the only perioperative outcome that appeared to significantly affect whether patients would receive blood transfusion was median blood loss (p = 0.001). In the PSM cohort, whether patients received blood transfusion was neither associated with OS (p = 0.759) nor RFS (p = 0.830). When the volume of blood transfusion was analyzed as a continuous variable, no significant dose–response relationship between blood transfusion volume and HR for OS and RFS was noted.ConclusionIntraoperative blood transfusion had no significant impact on the survival outcomes in patients who receive curative resection in primary HCC.
CST1 promotes the proliferation and migration of PDGF‐BB‐treated airway smooth muscle cells via the PI3K/AKT signaling pathway
Authors: Liu Hong‐Bo , Bai Juan , Wang Wen‐Xiao 
Published: November 2022

AbstractTypically, airway remodeling caused by migration and proliferation of airway smooth muscle cells (ASMCs) plays a crucial role in the pathophysiological characteristics of asthma development. Cystatin 1 (CST1), a protein‐coding gene referred to as Cystatin SN, is highly expressed in asthma patients. However, the role of CST1 and related molecular mechanisms in the development of asthma remains to be explored. This study aims to investigate the role of CST1 in asthma progression and present related molecular mechanisms. To explore these aspects, human ASMCs with platelet‐derived growth factor BB (PDGF‐BB) are initially stimulated and applied as a cellular model of asthma. Further, CST1 is knocked down with small interfering ribose nucleic acid (siRNA) overexpressed with plasmids. Then, 5‐ethynyl‐2′‐deoxyuridine (EdU) and Cell Count Kit (CCK)‐8 assays are applied to assess the cell proliferation rates. Further, Transwell and Western blot analyses for migration of cells and expression of MMP1 and MMP9 proteins are assessed, respectively. Under PDGF‐BB stimulation, human ASMCs showed an increased CST1 expression, enhanced proliferation, and migration abilities, as well as up‐regulated PI3K/AKT signaling pathway. Further, knockdown or overexpression of CST1 presented the declined or enhanced proliferation, migration, and up‐regulation of the PI3K/AKT signaling pathway of human ASMCs. Inhibiting PI3K/AKT signaling pathway displayed the reduced migration and proliferation of human ASMCs. In summary, these findings indicated that CST1 played an essential role in the progression of asthma by activating the PI3K/AKT signaling pathway and promoting the migration and proliferation abilities of human ASMCs treated with PDGF‐BB.
Recovery of macrobenthic communities in tidal flats following the Great East Japan Earthquake
Authors: Yuhara Takeshi , Suzuki Takao , Nishita Tatsuki , Murakami Junichi , Makino Wataru , Kanaya Gen , Kinoshita Kyoko , Yasuno Natsuru , Uchino Takashi , Urabe Jotaro 
Published: November 2022

AbstractThe Great East Japan Earthquake, with a moment magnitude scale of 9.0M on March 11, 2011, caused huge tsunamis that altered aquatic communities in the nearshore ecosystems along the Pacific coastline of Sendai Bay, Japan. However, to understand the ecological implications of the tsunamis' impact, an assessment of the successive changes of the communities and their fate over time is essential. Therefore, we examined eight tidal flat communities of Sendai Bay with the aid of citizen volunteers over 9 years, and compared the microbenthic compositions to those before the earthquake. The results revealed that the differences in the community compositions caused by the tsunamis decreased from year to year and finally disappeared after 7 years except for one flat where the tsunamis largely changed the environmental conditions. The present study indicates that these tidal flat communities are regulated mainly by environmental conditions and are highly resilient to tsunami disturbance.
Laponite–Gelatin Nanofibrous Microsphere Promoting Human Dental Follicle Stem Cells Attachment and Osteogenic Differentiation for Noninvasive Stem Cell Transplantation
Authors: Sarviya Nandini , Basu Suparna Mercy , Induvahi Veernala , Giri Jyotsnendu 
Published: November 2022

AbstractNanofibrous microspheres (NFM) are emerging as prominent next‐generation biomimetic injectable scaffold system for stem cell delivery and different tissue regeneration where nanofibrous topography facilitates ECM‐like stem cells niches. Addition of osteogenic bioactive nanosilicate platelets within NFM can provide osteoconductive cues to facilitate matrix mediated osteogenic differentiation of stem cells and enhance the efficiency of bone tissue regeneration. In this study, gelatin nanofibrous microspheres are prepared containing fluoride‐doped laponite XL21 (LP) using the emulsion mediated thermal induce phase separation (TIPS) technique. Systematic studies are performed to understand the effect of physicochemical properties of biomimicking NFM alone and with different concentrations of LP on human dental follicle stem cells (hDFSCs), their cellular attachment, proliferation, and osteogenic differentiation. The study highlights the effect of LP nanosilicate with biomimicking nanofibrous injectable scaffold system aiding in enhancing stem cell differentiation under normal physiological conditions compared to NFM without LP. The laponite–NFM shows suitability as excellent injectable biomaterials system for stem cell attachment, proliferation and osteogenic differentiation for stem cell transplantation and bone tissue regeneration.
Multicompartment Nanoparticles by Crystallization‐Driven Self‐Assembly of Star Polymers: Combining High Stability and Loading Capacity
Authors: Huo Haohui , Zou Jing , Yang Shu‐Gui , Zhang Jiaqi , Liu Jie , Liu Yutong , Hao Yanyun , Chen Hongfei , Li Hui , Huang Chaobo , Ungar Goran , Liu Feng , Zhang Zhiyue , Zhang Qilu 
Published: November 2022

AbstractHerein novel multicompartment nanoparticles (MCNs) that combine high stability and cargo loading capacity are developed. The MCNs are fabricated by crystallization‐driven self‐assembly (CDSA) of a tailor‐made 21 arm star polymer, poly(L‐lactide)[poly(tert‐butyl acrylate)‐block‐poly(ethylene glycol)]20 [PLLA(PtBA‐b‐PEG)20]. Platelet‐like or spherical MCNs containing a crystalline PLLA core and hydrophobic PtBA subdomains are formed and stabilized by PEG. Hydrophobic cargos, such as Nile Red and chemotherapeutic drug doxorubicin, can be successfully encapsulated into the collapsed PtBA subdomains with loading capacity two orders of magnitude higher than traditional CDSA nanoparticles. Depolarized fluorescence measurements of the Nile Red loaded MCNs suggest that the free volume of the hydrophobic chains in the nanoparticles may be the key for regulating their drug loading capacity. In vitro study of the MCNs suggests excellent cytocompatibility of the blank nanoparticles as well as a dose‐dependent cellular uptake and cytotoxicity of the drug‐loaded MCNs.
VTDCE‐Net: A time invariant deep neural network for direct estimation of pharmacokinetic parameters from undersampled DCE MRI data
Authors: Rastogi Aditya , Dutta Arindam , Yalavarthy Phaneendra Kumar 
Published: November 2022

AbstractPurposeTo propose a robust time and space invariant deep learning (DL) method to directly estimate the pharmacokinetic/tracer kinetic (PK/TK) parameters from undersampled dynamic contrast‐enhanced (DCE) magnetic resonance imaging (MRI) data.MethodsDCE‐MRI consists of 4D (3D‐spatial + temporal) data and has been utilized to estimate 3D (spatial) tracer kinetic maps. Existing DL architecture for this task needs retraining for variation in temporal and/or spatial dimensions. This work proposes a DL algorithm that is invariant to training and testing in both temporal and spatial dimensions. The proposed network was based on a 2.5‐dimensional Unet architecture, where the encoder consists of a 3D convolutional layer and the decoder consists of a 2D convolutional layer. The proposed VTDCE‐Net was evaluated for solving the ill‐posed inverse problem of directly estimating TK parameters from undersampled space data of breast cancer patients, and the results were systematically compared with a total variation (TV) regularization based direct parameter estimation scheme. In the breast dataset, the training was performed on patients with 32 time samples, and testing was carried out on patients with 26 and 32 time samples. Translation of the proposed VTDCE‐Net for brain dataset to show the generalizability was also carried out. Undersampling rates (R) of 8× , 12× , and 20× were utilized with PSNR and SSIM as the figures of merit in this evaluation. TK parameter maps estimated from fully sampled data were utilized as ground truth.ResultsExperiments carried out in this work demonstrate that the proposed VTDCE‐Net outperforms the TV scheme on both breast and brain datasets across all undersampling rates. For and maps, the improvement over TV is as high as 2 and 5 dB, respectively, using the proposed VTDCE‐Net.ConclusionTemporal points invariant DL network that was proposed in this work to estimate the TK‐parameters using DCE‐MRI data has provided state‐of‐the‐art performance compared to standard image reconstruction methods and is shown to work across all undersampling rates.
Explainability and controllability of patient‐specific deep learning with attention‐based augmentation for markerless image‐guided radiotherapy
Authors: Terunuma Toshiyuki , Sakae Takeji , Hu Yachao , Takei Hideyuki , Moriya Shunsuke , Okumura Toshiyuki , Sakurai Hideyuki 
Published: November 2022

AbstractBackgroundWe reported the concept of patient‐specific deep learning (DL) for real‐time markerless tumor segmentation in image‐guided radiotherapy (IGRT). The method was aimed to control the attention of convolutional neural networks (CNNs) by artificial differences in co‐occurrence probability (CoOCP) in training datasets, that is, focusing CNN attention on soft tissues while ignoring bones. However, the effectiveness of this attention‐based data augmentation has not been confirmed by explainable techniques. Furthermore, compared to reasonable ground truths, the feasibility of tumor segmentation in clinical kilovolt (kV) X‐ray fluoroscopic (XF) images has not been confirmed.PurposeThe first aim of this paper was to present evidence that the proposed method provides an explanation and control of DL behavior. The second purpose was to validate the real‐time lung tumor segmentation in clinical kV XF images for IGRT.MethodsThis retrospective study included 10 patients with lung cancer. Patient‐specific and XF angle‐specific image pairs comprising digitally reconstructed radiographs (DRRs) and projected‐clinical‐target‐volume (pCTV) images were calculated from four‐dimensional computer tomographic data and treatment planning information. The training datasets were primarily augmented by random overlay (RO) and noise injection (NI): RO aims to differentiate positional CoOCP in soft tissues and bones, and NI aims to make a difference in the frequency of occurrence of local and global image features. The CNNs for each patient‐and‐angle were automatically optimized in the DL training stage to transform the training DRRs into pCTV images. In the inference stage, the trained CNNs transformed the test XF images into pCTV images, thus identifying target positions and shapes.ResultsThe visual analysis of DL attention heatmaps for a test image demonstrated that our method focused CNN attention on soft tissue and global image features rather than bones and local features. The processing time for each patient‐and‐angle‐specific dataset in the training stage was ∼30 min, whereas that in the inference stage was 8 ms/frame. The estimated three‐dimensional 95 percentile tracking error, Jaccard index, and Hausdorff distance for 10 patients were 1.3–3.9 mm, 0.85–0.94, and 0.6–4.9 mm, respectively.ConclusionsThe proposed attention‐based data augmentation with both RO and NI made the CNN behavior more explainable and more controllable. The results obtained demonstrated the feasibility of real‐time markerless lung tumor segmentation in kV XF images for IGRT.
Granulomatous myopathy: Sarcoidosis and beyond
Authors: Chompoopong Pitcha , Liewluck Teerin 
Published: November 2022

AbstractNon‐necrotizing granulomatous inflammation is a rare but easily recognized histopathological finding in skeletal muscle biopsy. A limited number of diseases are known to be associated with non‐necrotizing granulomatous myopathy. Once identified, a careful evaluation for evidence of extramuscular granulomatosis and other signs suggestive of sarcoidosis is warranted as about half of the patients have sarcoid myopathy. In addition, the presence of granulomatous myopathy should trigger a search for clinical and pathological clues of inclusion body myositis (IBM), which accounts for most of the remaining patients and can coexist with sarcoidosis. Recognizing the features of IBM in patients with granulomatous myopathy can potentially spare the patients from unnecessary exposure to immunosuppressive therapies. In patients whose granulomatous myopathy remain unexplained, further investigations should aim at identifying myasthenia gravis and other autoimmune disorders, especially those known to cause granulomatous inflammation in other organs. Laboratory investigations should include acetylcholine receptor, antimitochondrial, antineutrophil cytoplasmic, thyroglobulin, and thyroid peroxidase autoantibodies. In the appropriate clinical context, exposure to immune checkpoint inhibitors and chronic graft‐vs‐host disease can be causes of granulomatous myopathy. In cases of unexplained granulomatous myopathy, natural killer/T‐cell lymphoma should be considered and careful histopathological examination for atypical cells and appropriate immunostaining is crucial. Identifying the etiology of granulomatous myopathy in each patient can guide appropriate treatment.