bluuebunny/crossref_metadata_2025_split huggingface dataset:
BMI1 fine-tunes gene repression and activation to safeguard undifferentiated spermatogonia fate
Authors: Liu Ruiqi , Peng Yonglin , Du Wenfei , Wu Yunqiang , Zhang Wen , Hu Congxia , Liu Min , Liu Xinhua , Wu Ji , Sun Jielin , Zhao Xiaodong 
Published: April 2023

Introduction: Spermatogenesis is sustained by the homeostasis of self-renewal and differentiation of undifferentiated spermatogonia throughout life, which is regulated by transcriptional and posttranscriptional mechanisms. B cell-specific Moloney murine leukemia virus integration site 1 (BMI1), one of spermatogonial stem cell markers, is a member of Polycomb repressive complex 1 (PRC1) and important to spermatogenesis. However, the mechanistic underpinnings of how BMI1 regulates spermatogonia fate remain elusive.Methods: We knocked down BMI1 by siRNA to investigate the role of BMI1 in undifferentiated spermatogonia. Differentially expressed genes were identified by RNA-seq and used for KEGG pathway analysis. We performed ChIP-seq analysis in wild type and BMI1 knockdown cells to explore the underlying molecular mechanisms exerted by BMI1. BMI1-associated alterations in repressive histone modifications were detected via Western blotting and ChIP-seq. Furthermore, we performed mass spectrometry and Co-immunoprecipitation assays to investigate BMI1 co-factors. Finally, we demonstrated the genomic regions occupied by both BMI1 and its co-factor.Results: BMI1 is required for undifferentiated spermatogonia maintenance by both repressing and activating target genes. BMI1 preserves PI3K-Akt signaling pathway for spermatogonia proliferation. Decrease of BMI1 affects the deposition of repressive histone modifications H2AK119ub1 and H3K27me3. BMI also positively regulates H3K27ac deposited genes which are associated with proliferation. Moreover, we demonstrate that BMI1 interacts with Sal-like 4 (SALL4), the transcription factor critical for spermatogonia function, to co-regulate gene expression.Discussion: Overall, our study reveals that BMI1 safeguards undifferentiated spermatogonia fate through multi-functional roles in regulating gene expression programs of undifferentiated spermatogonia.
Case report: Diagnosis of apical hypertrophic cardiomyopathy that escaped clinical and echocardiographic investigations for twenty years: Reasons and clinical implications
Authors: Caiati Carlo , Stanca Alessandro , Lepera Mario Erminio 
Published: April 2023

BackgroundApical hypertrophic cardiomyopathy (ApHCM) is a rare form of hypertrophic cardiomyopathy which predominantly affects the apex of the left ventricle. The diagnosis can be challenging due to several factors, ranging from no typical clinical and electrocardiogram (EKG) findings to potential difficulties in executing and interpreting the echocardiographic examination.Case presentationWe report the case of an 84-year-old woman who came to our echo-lab to undergo a routine echocardiogram. She had a history of permanent atrial fibrillation, paced rhythm and previous episodes of heart failure (HF), allegedly explained by a diagnosis of hypertensive heart disease that had been confirmed many times over the previous 20 years. The clinical examination and the EKG were unremarkable. The echocardiographic images were poor quality. But a senior cardiologist, expert in imaging and echocardiography, noted the lack of delineation of the endocardial border of the left ventricular (LV) apex region. Contrast echocardiography was performed and severe apical hypertrophy discovered.ConclusionApHCM can be a challenging diagnosis. Contrast echocardiography must always be applied in cases of poor delineation of the LV apical endocardial border at baseline echocardiography. Timely detection and appropriate lifestyle intervention might slow the development of LV hypertrophy, and possibly minimize and delay heart failure (HF) related symptoms and arrhythmias. The prognosis remains relatively benign during long term follow-up.
Overview of distinct 5-methylcytosine profiles of messenger RNA in normal and knock-down NSUN2 colorectal cancer cells
Authors: Lin Yu , Zhao Zhifang , Nie Wenqiang , Huang Manting , Cai Jiazhong , Wang Yadong , Wang Hesong , Huang Yongmei , Bai Yang 
Published: April 2023

Background: Colorectal cancer (CRC) is a harmful cancer with high morbidity and poor prognosis. There is growing evidence that RNA methylation is closely related to the occurrence of cancer and its malignant biological behavior. N6-methyladenosine (m6A) methylation is the most common RNA modification in eukaryotes, and its multiple regulatory mechanisms in CRC have been elucidated from multiple perspectives. At the same time, the role of 5-methylcytosine (m5C), another important and widely distributed methylation modification, in CRC is far from being elucidated.Methods: In this study, we used RNA immunoprecipitation sequencing combined with bioinformatics methods to identify the m5C peaks on messenger RNA (mRNA) in HCT15 cells and sh-NSUN2 HCT15 cells, understand which transcripts are modified by m5C, and characterize the distribution of m5C modifications. In addition, we performed further bioinformatics analysis of the detected data to initially clarify the potential function of these m5C-modified transcripts.Results: We found significant differences in the distribution of m5C between HCT15 cells and sh-NSUN2 HCT15 cells, suggesting that m5C is likely to play a key role in the occurrence and development of CRC. Furthermore, Gene Ontology (GO) enrichment analysis showed that genes altered by m5C were mainly enriched in phylogeny, synaptic membrane, and transcription factor binding. The Kyoto Encyclopedia of Genes and Genomes (KEGG)pathway analysis showed that the genes altered by m5C are enriched in ECM receptor interaction pathway, the circadian pathway, and the cAMP signaling pathway.Conclusion: Here, our study preliminarily revealed the different distribution patterns of m5C between HCT15 cell and sh-NSUN2 HCT15 cell. Our results open a new window to understand the role of m5C RNA methylation of mRNA in the development of CRC.
Outcomes with chimeric antigen receptor t-cell therapy in relapsed or refractory acute myeloid leukemia: a systematic review and meta-analysis
Authors: Shahzad Moazzam , Nguyen Andrea , Hussain Ali , Ammad-Ud-Din Mohammad , Faisal Muhammad Salman , Tariq Ezza , Ali Fatima , Butt Atif , Anwar Iqra , Chaudhary Sibgha Gull , Lutfi Forat , Ahmed Nausheen , Singh Anurag K. , Hematti Peiman , McGuirk Joseph P. , Mushtaq Muhammad Umair 
Published: April 2023

BackgroundWe conducted a systematic review and meta-analysis to evaluate outcomes following chimeric antigen receptor T cell (CAR-T) therapy in relapsed/refractory acute myeloid leukemia (RR-AML).MethodsWe performed a literature search on PubMed, Cochrane Library, and Clinicaltrials.gov. After screening 677 manuscripts, 13 studies were included. Data was extracted following PRISMA guidelines. Pooled analysis was done using the meta-package by Schwarzer et al. Proportions with 95% confidence intervals (CI) were computed.ResultsWe analyzed 57 patients from 10 clinical trials and 3 case reports. The pooled complete and overall response rates were 49.5% (95% CI 0.18-0.81, I2 =65%) and 65.2% (95% CI 0.36-0.91, I2 =57%). The pooled incidence of cytokine release syndrome, immune-effector cell associated neurotoxicity syndrome, and graft-versus-host disease was estimated as 54.4% (95% CI 0.17-0.90, I2 =77%), 3.9% (95% CI 0.00-0.19, I2 =22%), and 1.6% (95%CI 0.00-0.21, I2 =33%), respectively.ConclusionCAR-T therapy has demonstrated modest efficacy in RR-AML. Major challenges include heterogeneous disease biology, lack of a unique targetable antigen, and immune exhaustion.
Physiological fibrin hydrogel modulates immune cells and molecules and accelerates mouse skin wound healing
Authors: Pereira Rafaela Vaz Sousa , EzEldeen Mostafa , Ugarte-Berzal Estefania , Martens Erik , Malengier-Devlies Bert , Vandooren Jennifer , Vranckx Jan Jeroen , Matthys Patrick , Opdenakker Ghislain 
Published: April 2023

IntroductionWound healing is a complex process to restore homeostasis after injury and insufficient skin wound healing is a considerable problem in medicine. Whereas many attempts of regenerative medicine have been made for wound healing with growth factors and cell therapies, simple pharmacological and immunological studies are lagging behind. We investigated how fibrin hydrogels modulate immune cells and molecules in skin wound healing in mice.MethodsPhysiological fibrin hydrogels (3.5 mg/mL fibrinogen) were generated, biophysically analyzed for stiffness and protein contents and were structurally studied by scanning electron microscopy. Physiological fibrin hydrogels were applied to full thickness skin wounds and, after 3 days, cells and molecules in wound tissues were analyzed. Leukocytes, endothelial cells, fibroblasts and keratinocytes were explored with the use of Flow Cytometry, whereas cytokines and matrix metalloproteinases were analyzed with the use of qPCR, ELISAs and zymography. Skin wound healing was analyzed microscopically at day 3, macroscopically followed daily during repair in mice and compared with commercially available fibrin sealant Tisseel.ResultsExogenous fibrin at physiological concentrations decreased neutrophil and increased non-classical Ly6Clow monocyte and resolutive macrophage (CD206+ and CX3CR1+) populations, at day 3 after injury. Fibrin hydrogel reduced the expression of pro-inflammatory cytokines and increased IL-10 levels. In line with these findings, gelatinase B/MMP-9 was decreased, whereas gelatinase A/MMP-2 levels remained unaltered. Frequencies of dermal endothelial cells, fibroblasts and keratinocytes were increased and keratinocyte migration was enhanced by fibrin hydrogel. Importantly, physiological fibrin accelerated the healing of skin wounds in contrast to the highly concentrated fibrin sealant Tisseel, which delayed wound repair and possessed a higher fiber density.ConclusionCollectively, we show that adding a tailored fibrin hydrogel scaffold to a wound bed positively influences the healing process, modulating leukocyte populations and inflammatory responses towards a faster wound repair.
Students' and lecturers' perspectives on the implementation of online learning in medical education due to COVID-19 in Germany: a cross-sectional pilot study
Authors: Hertling Stefan F. , Back David A. , Kaiser Mario , Loos Franziska M. , Schleußner Ekkehard , Graul Isabel 
Published: April 2023

BackgroundDuring the coronavirus disease 2019 (COVID-19) crisis, many things changed in universities around the world. In-person learning was not possible. Instead, courses were offered in digital form. The sudden change posed enormous challenges to universities, students, and teachers. The aim of this study was to investigate the disadvantages as well as the advantages and opportunities of digital learning.ObjectiveThis study investigated the evaluation of an elective module by medical students and teachers in the traditional in-person and virtual teaching forms during the COVID-19 pandemic.MethodsUsing the elective module “Sports Medicine,” which includes both lectures and practical units, the opinions of the medical students about conventional teaching compared to digital instruction were evaluated. In the winter semester of 2019/2020, all classes were taught face-to-face but had to be switched to virtual teaching in the summer semester of 2020 on an ad hoc basis due to the pandemic. The students were asked to answer questions on general conditions, participant behavior, instructor evaluation, skill acquisition, topic selection, and overall evaluation after both forms of teaching. Likewise, the lecturers of both courses were queried in semiqualitative interviews about the same topics. Descriptive data analysis was performed to process the data.ResultsThe students perceived digital teaching to be superior in most subareas compared to in-person teaching in terms of framework, instructor evaluation, skill acquisition, topic selection, and overall rating. Medical students seemed to feel better with digital teaching in most areas of evaluation. The lecturers found the new form of teaching rather unsettling and criticized the lack of verbal and especially nonverbal communication as well as the short preparation time for the new challenge. The instructors were uncomfortable with some aspects of the virtual teaching format.ConclusionIn the wake of the COVID-19 pandemic, medical schools should rapidly digitize their teaching offerings and support faculty members in their computer-based competence with continuing education opportunities and time resources.
A prediction model for short-term neurodevelopmental impairment in preterm infants with gestational age less than 32 weeks
Authors: Li Yan , Zhang Zhihui , Mo Yan , Wei Qiufen , Jing Lianfang , Li Wei , Luo Mengmeng , Zou Linxia , Liu Xin , Meng Danhua , Shi Yuan 
Published: April 2023

IntroductionEarly identification and intervention of neurodevelopmental impairment in preterm infants may significantly improve their outcomes. This study aimed to build a prediction model for short-term neurodevelopmental impairment in preterm infants using machine learning method.MethodsPreterm infants with gestational age  &lt; 32 weeks who were hospitalized in The Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, and were followed-up to 18 months corrected age were included to build the prediction model. The training set and test set are divided according to 8:2 randomly by Microsoft Excel. We firstly established a logistic regression model to screen out the indicators that have a significant effect on predicting neurodevelopmental impairment. The normalized weights of each indicator were obtained by building a Support Vector Machine, in order to measure the importance of each predictor, then the dimension of the indicators was further reduced by principal component analysis methods. Both discrimination and calibration were assessed with a bootstrap of 505 resamples.ResultsIn total, 387 eligible cases were collected, 78 were randomly selected for external validation. Multivariate logistic regression demonstrated that gestational age(p = 0.0004), extrauterine growth restriction (p = 0.0367), vaginal delivery (p = 0.0009), and hyperbilirubinemia (0.0015) were more important to predict the occurrence of neurodevelopmental impairment in preterm infants. The Support Vector Machine had an area under the curve of 0.9800 on the training set. The results of the model were exported based on 10-fold cross-validation. In addition, the area under the curve on the test set is 0.70. The external validation proves the reliability of the prediction model.ConclusionA support vector machine based on perinatal factors was developed to predict the occurrence of neurodevelopmental impairment in preterm infants with gestational age  &lt; 32 weeks. The prediction model provides clinicians with an accurate and effective tool for the prevention and early intervention of neurodevelopmental impairment in this population.
In situ spatiotemporal mapping of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) inhibitor in pineapple (Ananas comosus) fruit tissue by MALDI mass spectrometry imaging
Authors: Suarez Angelica Faith L. , Juanillo Angel Ann B. , Sison Dave Clark D. , Orajay Joey I. , Javier Maria Bella B. , Baladjay Diane Monique S. , Yang Yu-Liang , Saludes Jonel P. , Dalisay Doralyn S. 
Published: April 2023

Pineapple (Ananas comosus) fruit is a functional food that has become a part of healthy diets worldwide due to its nutrition and health benefits. Given this concept, the potential anti-hypercholesterolemic activity of pineapple fruit was assessed using in vitro HMG-CoA reductase (HMGCR) inhibition assay. Our findings show that pineapple fruit (PAF) extract showed HMGCR inhibition activity. These findings led to partial purification of PAF extract by gel filtration chromatography (GFC) whereby fraction PAF 06 exhibited 100.00% HMGCR inhibition at 10 mg/mL. Matrix assisted laser desorption ionization (MALDI) mass spectrometry profiling, HRMS, MS/MS, and dereplication identified N1, N10-diferuloylspermidine as potential HMGCR inhibitor in pineapple fruit. The MALDI mass spectrometry imaging (MSI) enabled the in situ spatiotemporal mapping of the HMGCR inhibitor, N1, N10-diferuloylspermidine, in the pineapple fruit tissue, with localization concentrated mainly in the tissue near the peel/shell and a gradual decrease towards the flesh and ovary. The MALDI MSI provided the first evidence of in situ spatial localization of N1, N10-diferuloylspermidine, a potential HMGCR inhibitor in pineapple while maintaining the cellular and structural features of the fruit tissues.
CCNF is a potential pancancer biomarker and immunotherapy target
Authors: Wei Lifang , Li Huiming , Xiao Mengjun , Zhou Cuiling , Liu Jiliang , Weng Shilian , Wei Ruda 
Published: April 2023

BackgroundCCNF catalyzes the transfer of ubiquitin molecules from E2 ubiquitin-conjugating enzymes to target proteins, thereby regulating the G1/S or G2/M transition of tumor cells. Thus far, CCNF expression and its potential as a pancancer biomarker and immunotherapy target have not been reported.MethodsTCGA datasets and the R language were used to analyze the pancancer gene expression, protein expression, and methylation levels of CCNF; the relationship of CCNF expression with overall survival (OS), recurrence-free survival (RFS), immune matrix scores, sex and race; and the mechanisms for posttranscriptional regulation of CCNF.ResultsCCNF expression analysis showed that CCNF mRNA expression was higher in cancer tissues than in normal tissues in the BRCA, CHOL, COAD, ESCA, HNSC, LUAD, LUSC, READ, STAD, and UCEC; CCNF protein expression was also high in many cancer tissues, indicating that it could be an important predictive factor for OS and RFS. CCNF overexpression may be caused by CCNF hypomethylation. CCNF expression was also found to be significantly different between patients grouped based on sex and race. Overexpression of CCNF reduces immune and stromal cell infiltration in many cancers. Posttranscriptional regulation analysis showed that miR-98-5p negatively regulates the expression of the CCNF gene.ConclusionCCNF is overexpressed across cancers and is an adverse prognostic factor in terms of OS and RFS in many cancers; this phenomenon may be related to hypomethylation of the CCNF gene, which could lead to cancer progression and worsen prognosis. In addition, CCNF expression patterns were significantly different among patients grouped by sex and race. Its overexpression reduces immune and stromal cell infiltration. miR-98-5p negatively regulates CCNF gene expression. Hence, CCNF is a potential pancancer biomarker and immunotherapy target.
Predicting hypercapnia and hypoxia by the ventilator's built-in software in children on long-term non-invasive ventilation: A pilot study
Authors: Mentens Xante , Vanhees Janne , Paulussen Jolien , Installé Sophie , Van Ostaeyen Anse , Ides Kris , Jouret Nathalie , Van Hoorenbeeck Kim , Verhulst Stijn 
Published: April 2023

IntroductionFollow-up of children on long-term non-invasive ventilation (NIV) could be improved by telemonitoring, using the ventilator's built-in software (BIS) parameters as alternative for in-hospital sleep studies to reduce costs, enhance patient independence and contribute to early detection of infections. This pilot study investigated whether analysis of BIS parameters can predict abnormal nocturnal transcutaneous CO2 (TcCO2) and saturation (SpO2) measurements in children on long-term NIV.MethodsChildren on long-term NIV in follow-up at the Antwerp University Hospital were retrospectively included. Nocturnal TcCO2 and SpO2 measurements were collected together with BIS parameters at three different time points: the night of the sleep study (BIS1), mean values from 48 h (BIS2) and 72 h (BIS3) before the sleep study. Predictions were calculated for following outcome measures: % recording time TcCO2 &gt; 46.9 mmHg (%RT TcCO2; abnormal if ≥2%), recording time SpO2 &lt; 93% (RT SpO2; abnormal if &gt;1 h), abnormal TcCO2 or SpO2, mean TcCO2, mean SpO2.Results69 patients were included. %RT TcCO2 was separately predicted by reached tidal volume2 [OR 0.97 (0.93; 1.00); p = 0.051; AUC = 30%] and reached IPAP1 [OR 1.05 (1.00; 1.10); p = 0.050; AUC = 66%]. Leak1 predicted RT SpO2 [OR 1.21 (1.02; 1.43); p = 0.025; AUC = 84%]. Mean TcCO2 correlated with reached tidal volume2 (R2 0.10, p = 0.033).DiscussionCertain BIS parameters can predict nocturnal hypercapnia and desaturation in children on long-term NIV. Future studies with larger sample sizes are warranted to further investigate the predictive value of the identified BIS parameters.
Biological effects of sub-lethal doses of glyphosate and AMPA on cardiac myoblasts
Authors: Arrigo Elisa , Gilardi Sara , Muratori Luisa , Raimondo Stefania , Mancardi Daniele 
Published: April 2023

Introduction: Glyphosate is the active compound of different non-selective herbicides, being the most used agriculture pesticide worldwide. Glyphosate and AMPA (one of its main metabolites) are common pollutants of water, soil, and food sources such as crops. They can be detected in biological samples from both exposed workers and general population. Despite glyphosate acts as inhibitor of the shikimate pathway, present only in plants and some microorganisms, its safety in mammals is still debated. Acute glyphosate intoxications are correlated to cardiovascular/neuronal damages, but little is known about the effects of the chronic exposure.Methods: We evaluated the direct biological effects of different concentrations of pure glyphosate/AMPA on a rat-derived cell line of cardiomyoblasts (H9c2) in acute (1–2 h) or sub-chronic (24–48 h) settings. We analyzed cell viability/morphology, ROS production and mitochondrial dynamics.Results: Acute exposure to high doses (above 10 mM) of glyphosate and AMPA triggers immediate cytotoxic effects: reduction in cell viability, increased ROS production, morphological alterations and mitochondrial function. When exposed to lower glyphosate concentrations (1 μM—1 mM), H9c2 cells showed only a slight variation in cell viability and ROS production, while mitochondrial dynamic was unvaried. Moreover, the phenotype was completely restored after 48 h of treatment. Surprisingly, the sub-chronic (48 h) treatment with low concentrations (1 μM—1 mM) of AMPA led to a late cytotoxic response, reflected in a reduction in H9c2 viability.Conclusion: The comprehension of the extent of human exposure to these molecules remains pivotal to have a better critical view of the available data.