bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measuring out-of-field dose to the hippocampus in common radiotherapy indications
Authors: Auerbach Hendrik , Dzierma Yvonne , Schürmann Michaela , Rübe Christian , Rübe Claudia E. 
Published: April 2023

AbstractBackgroundThe high susceptibility of the hippocampus region to radiation injury is likely the causal factor of neurocognitive dysfunctions after exposure to ionizing radiation. Repetitive exposures with even low doses have been shown to impact adult neurogenesis and induce neuroinflammation. We address the question whether the out-of-field doses during radiotherapy of common tumour entities may pose a risk for the neuronal stem cell compartment in the hippocampus.MethodsThe dose to the hippocampus was determined for a single fraction according to different treatment plans for the selected tumor entities: Point dose measurements were performed in an anthropomorphic Alderson phantom and the out-of-field dose to the hippocampus was measured using thermoluminescence dosimeters.ResultsFor carcinomas in the head and neck region the dose exposure to the hippocampal region for a single fraction ranged from to 37.4 to 154.8 mGy. The hippocampal dose was clearly different for naso-, oro- and hypopharynx, with maximal values for nasopharynx carcinoma. In contrast, hippocampal dose levels for breast and prostate cancer ranged between 2.7 and 4.1 mGy, and therefore significantly exceeded the background irradiation level.ConclusionThe mean dose to hippocampus for treatment of carcinomas in the head and neck region is high enough to reduce neurocognitive functions. In addition, care must be taken regarding the out of field doses. The mean dose is mainly related to scattering effects, as is confirmed by the data from breast or prostate treatments, with a very different geometrical set-up but similar dosimetric results.
Prophylactic antineoplastic activity of Toxoplasma gondii RH derived antigen against ehrlich solid carcinoma with evidence of shared antigens by comparative immunoblotting
Authors: Eissa Maha M. , Gaafar Maha R. , Younis Layla K. , Ismail Cherine A. , El Skhawy Nahla 
Published: April 2023

Abstract
Background
With cancer cases escalation, an urgent request to develop novel combating strategies arise. Pathogen-based cancer-immunotherapy is getting more consideration. Autoclaved parasitic antigens seem promising candidates, taking steadily their first steps. Our aim was to examine the prophylactic antineoplastic activity of autoclaved Toxoplasma vaccine (ATV) and to test for the shared antigen theory between Toxoplasma gondii and cancer cells.

Methods
Mice were immunized with ATV followed by Ehrlich solid carcinoma (ESC) inoculation. Tumor weight, volume, histopathology, and immunohistochemistry for CD8+ T cells, Treg cells and VEGF were assessed. In addition, the proposed shared antigen theory between parasites and cancer was also verified using SDS-PAGE and immunoblotting.

Results
Results revealed powerful prophylactic activity of ATV with 13.3% inhibition of ESC incidence, significant reduction in tumor weight and volume in ATV vaccinated mice. Immunologically, significantly higher CD8+T cells and lower FOXP3+ Treg cells surrounded and infiltrated ESC in ATV immunized mice with higher CD8+T/Treg cells ratio and significant antiangiogenic effect. Moreover, SDS-PAGE and immunoblotting showed four shared bands between Ehrlich carcinoma and ATV of approximate molecular weights 60, 26, 22 and 12.5 KDa.

Conclusion
Exclusively, we demonstrated a prophylactic antineoplastic activity of autoclaved Toxoplasma vaccine against ESC. Moreover, to the best of our knowledge this is the first report highlighting the existence of cross-reactive antigens between Toxoplasma gondi parasite and cancer cells of Ehrlich carcinoma.
Ablation of microglia does not alter circadian rhythm of locomotor activity
Authors: Matsui Futaba , Yamaguchi Sho T. , Kobayashi Riho , Ito Shiho , Nagashima Sakimi , Zhou Zhiwen , Norimoto Hiroaki 
Published: April 2023

AbstractMicroglia, as macrophages in the brain, are responsible for immune responses and synaptic remodeling. Although the function of microglia is regulated by circadian rhythms, it is still unclear whether microglia are involved in the generation and light entrainment of circadian rhythms of behavior. Here, we report that microglial depletion does not alter behavioral circadian rhythms. We depleted ~ 95% of microglia in the mouse brain by PLX3397, a CSF1R inhibitor, and analyzed the effect on the spontaneous behaviors of mice. We found that neither the free-running period under constant darkness nor light entrainment under jet-lag circumstances were influenced by the ablation of microglia. Our results demonstrate that the circadian rhythms of locomotor activity, an important output of the circadian clock in the brain, are likely a phenomenon not produced by microglia.
CAR-NK cell therapy for hematological malignancies: recent updates from ASH 2022
Authors: Huang Ruihao , Wen Qin , Zhang Xi 
Published: April 2023

AbstractChimeric antigen receptor (CAR)-NK cell therapy has the advantages of a low incidence of side effects and a low cost. However, the clinical outcomes are not satisfactory due to limited antitumor effects and a limited proliferative capacity. Recently, progress in CAR-NK cell therapy has been made in NK cell engineering, target design and combination with other agents to treat relapsed or refractory hematological malignancies, especially acute myeloid leukemia and multiple myeloma. This correspondence summarizes the preclinical and clinical updates for universal CAR-NK cell therapy reported at the ASH 2022 annual meeting.
Timing of bronchoscopy and application of scoring tools in children with severe pneumonia
Authors: Wu Xiangtao , Lu Weihong , Sang Xinquan , Xu Yali , Wang Tuanjie , Zhan Xiaowen , Hao Jie , Ren Ruijuan , Zeng Hanshi , Li Shujun 
Published: April 2023

Abstract
Background
There is still a lack of effective scoring criteria for assessing the severity of pulmonary infection associated with changes in the endobronchial lining of the bronchus in children. This study aimed to ascertain the timing and value of endoscopic scoring of fibreoptic bronchoscopy (FOB) and bronchoalveolar lavage (BAL) in children with severe pneumonia.

Method
The clinical data of 229 children with severe pneumonia treated with BAL in the Pediatric Intensive Care Unit of the First Affiliated Hospital of Xinxiang Medical University between November 2018 and December 2021 were collected. According to the severity of the disease, patients were divided into an invasive ventilation group and a non-invasive ventilation group, as well as an early BAL group (receiving BAL within 1 day of admission) and a late BAL group (receiving BAL 2 days after admission). A Student’s t-test, Chi-square test, receiver operating characteristic (ROC) curve and survival curve were used to analyse the bronchitis score, aetiology of BAL fluid and survival data.

Results
The scores of endoscopic mucosal oedema, erythema and pallor and the total score in the invasive ventilation group were higher than those in the non-invasive ventilation group (P < 0.05), and they were consistent with the Sequential Organ Failure Assessment (SOFA) scores. The secretion colour score was lower in the early BAL group than in the late BAL group (P < 0.05). On the bronchitis scores, which were evaluated using a ROC curve, the difference in the mucosal erythema, pallor, oedema and total score of the invasive and non-invasive groups was statistically significant (P < 0.05), which was consistent with the area under the ROC of the SOFA scores. Acute Physiology and Chronic Health Assessment II and SOFA scores after FOB were lower than those before treatment (P < 0.05). In terms of ICU hospitalisation days and total hospitalisation days, the time of the early FOB patients was shorter than that of the late FOB patients (P < 0.05). A total of 22 patients (9.61%) died. The Kaplan–Meier analysis and log-rank test showed that the survival rate of the non-invasive ventilation group was higher than that of the invasive ventilation group (P < 0.05).

Conclusion
This study found that FOB combined with BAL is an important method for the diagnosis and treatment of severe pneumonia. Early BAL can reduce hospitalisation and ICU time; however, it cannot improve the survival rate. The endoscopic score has a certain role to play in assessing the severity of pulmonary inflammation, but studies with a large sample are still needed to confirm this.
Multilevel interrogation of H3.3 reveals a primordial role in transcription regulation
Authors: Nabeel-Shah Syed , Garg Jyoti , Ashraf Kanwal , Jeyapala Renu , Lee Hyunmin , Petrova Alexandra , Burns James D. , Pu Shuye , Zhang Zhaolei , Greenblatt Jack F. , Pearlman Ronald E. , Lambert Jean-Philippe , Fillingham Jeffrey 
Published: April 2023

Abstract
Background
Eukaryotic cells can rapidly adjust their transcriptional profile in response to molecular needs. Such dynamic regulation is, in part, achieved through epigenetic modifications and selective incorporation of histone variants into chromatin. H3.3 is the ancestral H3 variant with key roles in regulating chromatin states and transcription. Although H3.3 has been well studied in metazoans, information regarding the assembly of H3.3 onto chromatin and its possible role in transcription regulation remain poorly documented outside of Opisthokonts.

Results
We used the nuclear dimorphic ciliate protozoan, Tetrahymena thermophila, to investigate the dynamics of H3 variant function in evolutionarily divergent eukaryotes. Functional proteomics and immunofluorescence analyses of H3.1 and H3.3 revealed a highly conserved role for Nrp1 and Asf1 histone chaperones in nuclear influx of histones. Cac2, a putative subunit of H3.1 deposition complex CAF1, is not required for growth, whereas the expression of the putative ortholog of the H3.3-specific chaperone Hir1 is essential in Tetrahymena. Our results indicate that Cac2 and Hir1 have distinct localization patterns during different stages of the Tetrahymena life cycle and suggest that Cac2 might be dispensable for chromatin assembly. ChIP-seq experiments in growing Tetrahymena show H3.3 enrichment over the promoters, gene bodies, and transcription termination sites of highly transcribed genes. H3.3 knockout followed by RNA-seq reveals large-scale transcriptional alterations in functionally important genes.

Conclusion
Our results provide an evolutionary perspective on H3.3’s conserved role in maintaining the transcriptional landscape of cells and on the emergence of specialized chromatin assembly pathways.
Sperm DNA methylation is predominantly stable in mice offspring born after transplantation of long-term cultured spermatogonial stem cells
Authors: Serrano Joana B. , Tabeling Nils C. , de Winter-Korver Cindy M. , van Daalen Saskia K. M. , van Pelt Ans M. M. , Mulder Callista L. 
Published: April 2023

Abstract
Background
Spermatogonial stem cell transplantation (SSCT) is proposed as a fertility therapy for childhood cancer survivors. SSCT starts with cryopreserving a testicular biopsy prior to gonadotoxic treatments such as cancer treatments. When the childhood cancer survivor reaches adulthood and desires biological children, the biopsy is thawed and SSCs are propagated in vitro and subsequently auto-transplanted back into their testis. However, culturing stress during long-term propagation can result in epigenetic changes in the SSCs, such as DNA methylation alterations, and might be inherited by future generations born after SSCT. Therefore, SSCT requires a detailed preclinical epigenetic assessment of the derived offspring before this novel cell therapy is clinically implemented. With this aim, the DNA methylation status of sperm from SSCT-derived offspring, with in vitro propagated SSCs, was investigated in a multi-generational mouse model using reduced-representation bisulfite sequencing.

Results
Although there were some methylation differences, they represent less than 0.5% of the total CpGs and methylated regions, in all generations. Unsupervised clustering of all samples showed no distinct grouping based on their pattern of methylation differences. After selecting the few single genes that are significantly altered in multiple generations of SSCT offspring compared to control, we validated the results with quantitative Bisulfite Sanger sequencing and RT-qPCRin various organs. Differential methylation was confirmed only for Tal2, being hypomethylated in sperm of SSCT offspring and presenting higher gene expression in ovaries of SSCT F1 offspring compared to control F1.

Conclusions
We found no major differences in DNA methylation between SSCT-derived offspring and control, both in F1 and F2 sperm. The reassuring outcomes from our study are a prerequisite for promising translation of SSCT to the human situation.
Diagnostic reference level quantities for adult chest and abdomen-pelvis CT examinations: correlation with organ doses
Authors: Costa Paulo Roberto , Tomal Alessandra , de Oliveira Castro Jullianna Cristina , Nunes Isabella Paziam Fernandes , Nersissian Denise Yanikian , Sawamura Márcio Valente Yamada , Leão Filho Hilton , Lee Choonsik 
Published: April 2023

Abstract
Objectives
To evaluate correlations between DRL quantities (DRLq) stratified into patient size groups for non-contrast chest and abdomen-pelvis CT examinations in adult patients and the corresponding organ doses.

Methods
This study presents correlations between DRLq (CTDIvol, DLP and SSDE) stratified into patient size ranges and corresponding organ doses shared in four groups: inside, peripheral, distributed and outside. The demographic, technical and dosimetric parameters were used to identify the influence of these quantities in organ doses. A robust statistical method was implemented in order to establish these correlations and its statistical significance.

Results
Median values of the grouped organ doses are presented according to the effective diameter ranges. Organ doses in the regions inside the imaged area are higher than the organ doses in peripheral, distributed and outside regions, excepted to the peripheral doses associated with chest examinations. Different levels of statistical significance between organ doses and the DRLq were presented.

Conclusions
Correlations between DRLq and target-organ doses associated with clinical practice can support guidance’s to the establishment of optimization criteria. SSDE demonstrated to be significant in the evaluation of organ doses is also highlighted. The proposed model allows the design of optimization actions with specific risk-reduction results.
Paraganglioma in pregnancy, a mimic of preeclampsia: a case report
Authors: Lundholm Michelle D. , Marquard Jessica , Rao Pratibha PR 
Published: April 2023

Abstract
Background
The new presentation of pheochromocytoma or paraganglioma in pregnancy is very rare and can be life-threatening for mother and child.

Case presentation
We present the case of a 26-year-old gravida 3 para 2 otherwise healthy Caucasian woman at 34 weeks gestation who presented with new onset hypertension associated with headaches, dry heaves, diaphoresis, and palpitations. She was initially diagnosed with preeclampsia and treated with labetalol and an urgent cesarean section, delivering a healthy baby girl. The diagnosis of preeclampsia came into question when, 6 weeks postpartum, she continued to have hypertension with atypical features. Testing revealed metastatic paraganglioma associated with a succinate dehydrogenase B gene mutation. The patient was then started on alpha-adrenergic blockade and has had close blood pressure monitoring while discussion of advances therapies is ongoing.

Conclusion
This case demonstrates how paraganglioma/pheochromocytoma can be misdiagnosed as preeclampsia due to the overlapping features of new-onset hypertension late in pregnancy accompanied by headache and proteinuria. It is impractical to routinely screen for paraganglioma/pheochromocytoma in all pregnant patients diagnosed with preeclampsia due to the rarity of these tumors and the harm from high false-positive rates. Therefore, it is incumbent on the provider to have a high degree of suspicion for paraganglioma/pheochromocytoma when clinical features are unusual for preeclampsia, such as intermittent palpitations, diaphoresis, orthostatic hypotension, or hyperglycemia. Early detection of paraganglioma/pheochromocytoma with interventions to mitigate the risk of hypertensive crisis greatly reduce maternal and fetal mortality. Fortunately, our patient delivered a healthy baby and did not have any additional pregnancy complications despite the delay in her diagnosis.
Spheroids derived from the stromal vascular fraction of adipose tissue self-organize in complex adipose organoids and secrete leptin
Authors: Robledo Fermín , González-Hodar Lila , Tapia Pablo , Figueroa Ana-María , Ezquer Fernando , Cortés Víctor 
Published: April 2023

Abstract
Background
Adipose tissue-derived stromal vascular fraction (SVF) harbors multipotent cells with potential therapeutic relevance. We developed a method to form adipose spheroids (AS) from the SVF with complex organoid structure and enhanced leptin secretion upon insulin stimulation.

Methods
SVF was generated from the interscapular brown adipose tissue of newborn mice. Immunophenotype and stemness of cultured SVF were determined by flow cytometry and in vitro differentiation, respectively. Spheroids were generated in hanging drops and non-adherent plates and compared by morphometric methods. The adipogenic potential was compared between preadipocyte monolayers and spheroids. Extracellular leptin was quantified by immunoassay. Lipolysis was stimulated with isoprenaline and quantified by colorimetric methods. AS viability and ultrastructure were determined by confocal and transmission electron microscopy analyses.

Results
Cultured SVF contained Sca1 + CD29 + CD44 + CD11b- CD45- CD90- cells with adipogenic and chondrogenic but no osteogenic potential. Culture on non-adherent plates yielded the highest quantity and biggest size of spheroids. Differentiation of AS for 15 days in a culture medium supplemented with insulin and rosiglitazone resulted in greater Pparg, Plin1, and Lep expression compared to differentiated adipocytes monolayers. AS were viable and maintained leptin secretion even in the absence of adipogenic stimulation. Glycerol release after isoprenaline stimulation was higher in AS compared to adipocytes in monolayers. AS were composed of outer layers of unilocular mature adipocytes and an inner structure composed of preadipocytes, immature adipocytes and an abundant loose extracellular matrix.

Conclusion
Newborn mice adipose SVF can be efficiently differentiated into leptin-secreting AS. Prolonged stimulation with insulin and rosiglitazone allows the formation of structurally complex adipose organoids able to respond to adrenergic lipolytic stimulation.
Mesenchymal stromal/stem cell (MSC)-derived exosomes in clinical trials
Authors: Lotfy Ahmed , AboQuella Noha M. , Wang Hongjun 
Published: April 2023

AbstractMesenchymal stromal/stem cells (MSCs) are widely utilized in cell therapy because of their robust immunomodulatory and regenerative properties. Their paracrine activity is one of the most important features that contribute to their efficacy. Recently, it has been demonstrated that the production of various factors via extracellular vesicles, especially exosomes, governs the principal efficacy of MSCs after infusion in experimental models. Compared to MSCs themselves, MSC-derived exosomes (MSC-Exos) have provided significant advantages by efficiently decreasing unfavorable adverse effects, such as infusion-related toxicities. MSC-Exos is becoming a promising cell-free therapeutic tool and an increasing number of clinical studies started to assess the therapeutic effect of MSC-Exos in different diseases. In this review, we summarized the ongoing and completed clinical studies using MSC-Exos for immunomodulation, regenerative medicine, gene delivery, and beyond. Additionally, we summarized MSC-Exos production methods utilized in these studies with an emphasis on MSCs source, MSC-Exos isolation methods, characterization, dosage, and route of administration. Lastly, we discussed the current challenges and future directions of exosome utilization in different clinical studies as a novel therapeutic strategy.
Application of mesenchymal stem cell sheet for regeneration of craniomaxillofacial bone defects
Authors: Banimohamad-Shotorbani Behnaz , Karkan Sonia Fathi , Rahbarghazi Reza , Mehdipour Ahmad , Jarolmasjed Seyedhosein , Saghati Sepideh , Shafaei Hajar 
Published: April 2023

AbstractBone defects are among the most common damages in human medicine. Due to limitations and challenges in the area of bone healing, the research field has turned into a hot topic discipline with direct clinical outcomes. Among several available modalities, scaffold-free cell sheet technology has opened novel avenues to yield efficient osteogenesis. It is suggested that the intact matrix secreted from cells can provide a unique microenvironment for the acceleration of osteoangiogenesis. To the best of our knowledge, cell sheet technology (CST) has been investigated in terms of several skeletal defects with promising outcomes. Here, we highlighted some recent advances associated with the application of CST for the recovery of craniomaxillofacial (CMF) in various preclinical settings. The regenerative properties of both single-layer and multilayer CST were assessed regarding fabrication methods and applications. It has been indicated that different forms of cell sheets are available for CMF engineering like those used for other hard tissues. By tackling current challenges, CST is touted as an effective and alternative therapeutic option for CMF bone regeneration.
Benefits of pre-trained mono- and cross-lingual speech representations for spoken language understanding of Dutch dysarthric speech
Authors: Wang Pu , Van hamme Hugo 
Published: April 2023

AbstractWith the rise of deep learning, spoken language understanding (SLU) for command-and-control applications such as a voice-controlled virtual assistant can offer reliable hands-free operation to physically disabled individuals. However, due to data scarcity, it is still a challenge to process dysarthric speech. Pre-training (part of) the SLU model withsupervisedautomatic speech recognition (ASR) targets or withself-supervisedlearning (SSL) may help to overcome a lack of data, but no research has shown which pre-training strategy performs better for SLU on dysarthric speech and to which extent the SLU task benefits from knowledge transfer from pre-training with dysarthric acoustic tasks. This work aims to compare different mono- or cross-lingual pre-training (supervisedandunsupervised) methodologies and quantitatively investigates the benefits of pre-training for SLU tasks on Dutch dysarthric speech. The designed SLU systems consist of a pre-trained speech representations encoder and a SLU decoder to map encoded features to intents. Four types of pre-trained encoders, a mono-lingual time-delay neural network (TDNN) acoustic model, a mono-lingual transformer acoustic model, a cross-lingual transformer acoustic model (Whisper), and a cross-lingual SSL Wav2Vec2.0 model (XLSR-53), are evaluated complemented with three types of SLU decoders: non-negative matrix factorization (NMF), capsule networks, and long short-term memory (LSTM) networks. The acoustic analysis of the four pre-trained encoders are tested on Dutch dysarthric home-automation data with word error rate (WER) results to investigate the correlations of the dysarthric acoustic task (ASR) and the semantic task (SLU). By introducing the intelligibility score (IS) as a metric of the impairment severity, this paper further quantitatively analyzes dysarthria-severity-dependent models for SLU tasks.