bluuebunny/crossref_metadata_2025_split huggingface dataset:
Noninvasive tests maintain high accuracy for advanced fibrosis in chronic hepatitis B patients with different nomenclatures of steatotic liver disease
Authors: Chen Lin , Tao Xuemei , Zeng Minghui , Li Yuqin , Han Jiaxin , Wang Yuekui , Liu Yonggang , Shi Ruifang , Su Rui , Xu Liang , Mi Yuqiang 
Published: April 2024

AbstractMetabolic dysfunction‐associated steatotic liver disease (MASLD) is a new nomenclature proposed in 2023. We aimed to compare the diagnostic efficacy of noninvasive tests (NITs) for advanced fibrosis under different nomenclatures in patients with chronic hepatitis B (CHB). A total of 844 patients diagnosed with CHB and concurrent steatotic liver disease (SLD) by liver biopsy were retrospectively enrolled and divided into four groups. The performances of fibrosis‐4 (FIB‐4), gamma‐glutamyl transpeptidase to platelet ratio index (GPRI), aspartate aminotransferase to platelet ratio index (APRI), and liver stiffness measurement (LSM) were compared among the four groups. The four NITs showed similar diagnostic efficacy for nonalcoholic fatty liver disease (NAFLD), MASLD, and metabolic dysfunction‐associated fatty liver disease (MAFLD) in patients with CHB with advanced fibrosis. LSM showed the most stable accuracy for NAFLD (AUC = 0.842), MASLD (AUC = 0.846), and MAFLD (AUC = 0.863) compared with other NITs (p < 0.05). Among the four NITs, APRI (AUC = 0.841) and GPRI (AUC = 0.844) performed best in patients with CHB & MetALD (p < 0.05). The cutoff value for GPRI in patients with CHB & MetALD was higher than that in the other three groups, while further comparisons of NITs at different fibrosis stages showed that the median GPRI of CHB & MetALD (1.113) at F3‐4 was higher than that in the CHB & MASLD group (0.508) (p < 0.05). Current NITs perform adequately in patients with CHB and SLD; however, alterations in cutoff values for CHB & MetALD need to be noted.
Changing respiratory pathogens infection patterns after COVID‐19 pandemic in Shanghai, China
Authors: Wei Muyun , Li Shuangshuang , Lu Xinhua , Hu Kaiming , Li Zhilan , Li Min 
Published: April 2024

AbstractTo assess the positive rate of 11 respiratory pathogens in 2023, providing a comprehensive summary and analysis of the respiratory infection patterns after COVID‐19 pandemic. The study comprised 7544 inpatients suspected of respiratory infections who underwent respiratory pathogen multiplex polymerase chain reaction tests from July 2022 to December 31, 2023. We analyzed the positive rate of 11 pathogens over 18 months and the characterization of infection patterns among different age groups and immune states. Among 7544 patients (age range 4 months to 104 years, 44.99% female), the incidence of infected by at least one of the 11 pathogens was 26.07%. Children (55.18%, p < 0.05) experienced a significantly higher infection probability than adults (20.88%) and old (20.66%). Influenza A virus (8.63%), Mycoplasma pneumoniae (5.47%), and human rhinovirus (5.12%) were the most common pathogens. In children, M. pneumoniae (35.96%) replaced the predominant role of human respiratory syncytial virus (HRSV) (5.91%) in the pathogen spectrum. Age, immunosuppressed state, and respiratory chronic conditions were associated with a significantly higher risk of mixed infection. Immunosuppressed patients were more vulnerable to human coronavirus (4.64% vs. 1.65%, p < 0.05), human parainfluenza virus (3.46% vs. 1.69%, p < 0.05), and HRSV (2.27% vs. 0.55%, p < 0.05). Patterns in respiratory infections changed following regional epidemic control measures and the COVID‐19 pandemic.
Antibiotics administered as continuous intravenous infusion over 24 hours by elastomeric devices to patients treated at home: a study of infusion efficiency
Authors: Docherty Toni , David Michael , Schneider Jennifer , O'Kane Gabrielle , Morris Joni , Paavola Catherine , Sawers Janelle , O'Mahony Deirdre , Cooper Joyce 
Published: April 2024

AbstractBackgroundElastomeric infusion devices or ‘Infusors’ are commonly used to administer 24‐h continuous intravenous infusions to hospital patients at home, a service which can increase hospital capacity.AimThis study sought to determine Infusor efficiency by measuring infusion lengths administered by Infusors to patients in the community setting and reviewing any impacting factors on varying infusion rates, if observed.MethodPatients and nurses completed data collection forms daily over a 12‐month period. The following information was recorded: time Infusor attached to patient, time Infusor emptied, Infusor ‘empty’ or ‘not empty’ when removed, volume of antibiotic solution remaining, Infusor storage details, antibiotic solution and dose, indication for treatment, and date (season). Statistical analyses was conducted using Stata. Data were analysed using descriptive statistics, including median and range for continuous variables, and frequency counts and percentages for categorical variables. Ethical approval was granted by Northern Sydney Local Health District (NSLHD) Research Office (Reference no: RESP/14/184), the Human Research Ethics Committee (HREC) (Reference no: LNR/14/HAWKE/265) and the study conforms to the Australian National Statement on Ethical Conduct in Human Research. Informed consent was obtained from all participants via a study information leaflet that was provided with the patient questionnaire and patients were informed that their participation in the study was optional. Patients indicated their consent by completing the data collection form for each day of treatment.ResultsA significant number of Infusors (27%) emptied outside the expected infusion duration of 24 h ± 10% (21.6–26.4 h) and Infusors were removed ‘not empty’ when the nurse visited >24 h on 35% of occasions. Infusors were more likely to empty >24 h if they contained piperacillin‐tazobactam 13.5 g (predicted probability = 1.0), in winter (predicted probability = 0.83), and in cooler overnight storage locations (predicted probability = 0.64). Infusors were more likely to empty <24 h if they contained vancomycin (predicted probability = 0.12).ConclusionInfusors delivering 24‐h continuous intravenous infusions in the home setting may empty at unpredictable times and may be affected by temperature or solutions with varying doses. Outpatient parenteral antimicrobial therapy clinicians should be aware of possible unfinished infusions from Infusors.
Prediction model for pheochromocytoma/paraganglioma using nCounter assay
Authors: Oh Young Lyun , Byeon Sun‐Ju , Suh Yong Joon 
Published: April 2024

AbstractBackgroundWorld Health Organization defined pheochromocytomas/paragangliomas (PPGL) as malignant tumors in 2017 because the existing classification system could not reflect locally aggressive behavior sufficiently. However, predicting the likelihood of metastasis remains a crucial part of the treatment strategy.MethodsFrom one tertiary care hospital and one secondary hospital, 97 PPGL cases were selected. Medical records of PPGL cases with the presence of formalin‐fixed and paraffin‐embedded (FFPE) tissue of primary lesion were reviewed. For FFPE tissues, a nCounter assay was conducted to determine differently expressed genes between metastatic and non‐metastatic PPGL groups. Performances of prediction models for the likelihood of metastasis were calculated.ResultsOf a total of 97 PPGL cases, 39, 20, and 38 were classified as benign, malignant, and validation, respectively. In the nCounter assay, CDK1, TYMS, and TOP2A genes showed significant differences in expression. Tumor size was positively correlated with CDK1 expression level. The Lasso regression model showed supreme performance of sensitivity 91.7% and specificity 95.5% when those significant factors were considered.ConclusionMachine learning of multi‐modal classifiers can be used to create a prediction model for metastasis of PPGL with high sensitivity and specificity using nCounter assay. Moreover, CDK1 inhibitors could be considered for developing drug treatment.
Activation of ASIC3/ERK pathway by paeoniflorin improves intestinal fluid metabolism and visceral sensitivity in slow transit constipated rats
Authors: Deng Yuan , Zhao Qiong , Zhou Hong‐Yun , Zhang Zi‐Qi , Zhan Yu 
Published: April 2024

AbstractSlow transit constipation (STC) is one of the most common gastrointestinal disorders in children and adults worldwide. Paeoniflorin (PF), a monoterpene glycoside compound extracted from the dried root of Paeonia lactiflora, has been found to alleviate STC, but the mechanisms of its effect remain unclear. The present study aimed to investigate the effects and mechanisms of PF on intestinal fluid metabolism and visceral sensitization in rats with compound diphenoxylate‐induced STC. Based on the evaluation of the laxative effect, the abdominal withdrawal reflex test, enzyme‐linked immunosorbent assay, quantitative real‐time polymerase chain reaction, western blot, and immunohistochemistry were used to detect the visceral sensitivity, fluid metabolism‐related proteins, and acid‐sensitive ion channel 3/extracellular signal‐regulated kinase (ASIC3/ERK) pathway‐related molecules. PF treatment not only attenuated compound diphenoxylate‐induced constipation symptoms and colonic pathological damage in rats but also ameliorated colonic fluid metabolic disorders and visceral sensitization abnormalities, as manifested by increased colonic goblet cell counts and mucin2 protein expression, decreased aquaporin3 protein expression, improved abdominal withdrawal reflex scores, reduced visceral pain threshold, upregulated serum 5‐hydroxytryptamine, and downregulated vasoactive intestinal peptide levels. Furthermore, PF activated the colonic ASIC3/ERK pathway in STC rats, and ASIC3 inhibition partially counteracted PF's modulatory effects on intestinal fluid and visceral sensation. In conclusion, PF alleviated impaired intestinal fluid metabolism and abnormal visceral sensitization in STC rats and thus relieved their symptoms through activation of the ASIC3/ERK pathway.
Hypoxia‐mediated attenuation of EGLN2 inhibition of the NF‐κB signaling pathway leads to the formation of a loop between HIF‐1α and MUC1‐C promoting chemoresistance in bladder cancer
Authors: Qing Liangliang , Li Qingchao , Yang Yongjin , Xu Wenbo , Wang Yanan , Li Rongxing , You Chengyu , Dong Zhilong 
Published: April 2024

AbstractThe expression pattern of MUC1‐C in tumors is closely linked to tumor progression; however, its specific mechanism remains unclear. The expression of MUC1‐C in cancer and adjacent normal tissues was detected using immunohistochemistry and Western blot. The IC50 of cells to gemcitabine was determined using the CCK8 assay. The effects of hypoxia and MUC1‐C on the behavioral and metabolic characteristics of bladder cancer cells were investigated. Gene expression was assessed through Western blot and polymerase chain reaction. The relationship between the genes was analyzed by co‐immunoprecipitation, immunofluorescence and Western blot. Finally, the role of the EGLN2 and NF‐κB signaling pathways in the interaction between MUC1‐C and hypoxia‐inducible factor‐1α (HIF‐1α) was investigated. MUC1‐C expression is significantly higher in bladder cancer tissues than in adjacent normal tissues, particularly in large‐volume tumors, and is closely correlated with clinical features such as tumor grade. Tumor volume‐mediated hypoxia resulted in increased expression of MUC1‐C and HIF‐1α in bladder cancer cells. Under stimulation of hypoxia, the inhibitory effect of EGLN2 on the NF‐κB signaling pathway was weakened, allowing NF‐κB to promote the positive feedback formation of MUC1‐C and HIF‐1α. Simultaneously, EGLN2‐mediated degradation of HIF‐1α was reduced. This ultimately led to elevated HIF‐1α‐mediated downstream gene expression, promoting increased glucose uptake and glycolysis, and ultimately resulting in heightened chemotherapy resistance and malignancy.
Diversity, equity, and inclusion in natural science education: A review of literature
Authors: Goodwin Catlin M. , McKendree Robert Bud 
Published: April 2024

AbstractDiversity, equity, and inclusion (DEI) are relevant in societal discourse and have implications for educators in natural sciences disciplines. A synthesis of DEI research in these disciplines is necessary to identify opportunities to strengthen initiatives and identify future research needs. The purpose of this study was to introduce a review of current literature related to DEI in natural sciences education, exploring the frameworks, methods, and focal areas of current literature as well as synthesizing findings, and recommendations for practice and research. Key findings indicate that while conversations and interventions surrounding issues of DEI are occurring, inequities across various scales of the education system still exist. Recommendations center on the need for critical reflexivity on the part of individuals, programs, and the larger education system to identify inequities and opportunities for change.
Somatic GNA11/GNAQ variants in a cohort of Chinese children with phakomatosis pigmentovascularis
Authors: Zhang Bin , He Rui , Wu Riga , Yang Zhou , Hu Man , Zhang Nan , Guo Wu , Xu Zigang , Ma Lin 
Published: April 2024

ABSTRACTImportancePostzygotic mutations in the GNAQ/GNA11 genes, which encode the G‐protein nucleotide binding protein alpha subunits, have been identified in patients with phakomatosis pigmentovascularis (PPV). However, little is known about the Chinese population.ObjectiveTo identify pathogenic mutations in pediatric patients with PPV within the Chinese population.MethodsWe performed whole‐exome sequencing (WES) using skin lesion tissues from pediatric patients diagnosed with PPV. Additionally, ultradeep‐targeted sequencing was conducted to validate the somatic mutations. A genotype‐phenotype correlation was analyzed by integrating data from previous reports with the findings of the present study.ResultsThirteen patients were enrolled, all diagnosed with the cesioflammea type of PPV, except for one patient with an unclassifiable type. We identified somatic GNA11 c.547C>T (p.R183C) variant in seven patients and GNAQ c.548G>A (p.R183Q) in four patients, with low allelic fractions ranging from 2.1% to 8.6% through ultradeep sequencing. Besides, a GNAQ c.548G>A (p.R183Q) variant was detected through targeted sequencing in one of two patients who did not exhibit detectable variants via WES. The genotype‐phenotype correlation analysis, involving 15 patients with a GNA11 variant and 10 with a GNAQ variant, revealed that facial capillary malformation (87% vs. 50%, P = 0.075) and ocular melanocytosis (80% vs. 40%, P = 0.087) appeared to be more frequent in patients with GNA11 mutation compared to those with GNAQ mutations. All four patients diagnosed with cesiomarmorata type or overlapping cesioflammea and cesiomarmorata type PPV carried the GNA11 variant.InterpretationOur study demonstrated that the majority of PPV patients in the Chinese population carried a postzygotic variant of GNAQ/GNA11, thus further confirming the pathogenic role of GNAQ/GNA11 mosaicism in the development of PPV cesioflammea type.
Primary ciliary dyskinesia in Egypt: First report of cilia ultrastructural defects and novel genetic variants
Authors: Shoman Walaa , Elbanna Amr G. , Fassad Mahmoud R. , Elheneidy Moushira A. R. , Petrarca Laura , 3billion Consortium  , Elsawy Ihab , Fasseeh Nader 
Published: April 2024

AbstractBackgroundPrimary ciliary dyskinesia (PCD) is a genetic disorder that follows several inheritance patterns predominately autosomal recessive. It is caused by aberrant motile cilia structure and/or function. Diagnosis of PCD is challenging, involving complex technical steps and requiring special expertise. Here, we report the first attempt to employ transmission electron microscopy (TEM) to precisely diagnose PCD in Egypt. The study aims to outline the findings of diagnostic procedures, including TEM and genetic analysis, carried out on a cohort of Egyptian patients clinically suspected of having PCD.MethodsA cohort of 48 individuals underwent testing to determine their PCD status. The diagnostic modalities used included genetic and TEM analysis. Clinical features and diagnostic test outcomes were described.ResultsPCD was confirmed in 27 of the 48 participating cases. Class 1 hallmark defects were the most commonly detected TEM findings. Outer dynein arm defect in addition to microtubular disorganization with inner dynein arm loss was found equally to be the most common diagnostic defects in the confirmed cases. A highly heterogeneous genetic background was found with 14 different affected genes. Of these, CCDC39 was the most commonly mutated one. The variants, c.430‐1G>A in DNAAF6, c.8099C>T in DNAH11, c.263T>C in DNAL1, c.1154dup in NEK10, c.487C>T in HYDIN, and c.90+1G>C in CCDC39 gene were detected novel variants.ConclusionDiagnosis of PCD is challenging especially in low‐ and middle‐income countries. As there is no single reference diagnostic test, integrating diagnostic modalities, such as TEM and genetics, can enhance diagnosis.
FOXA1 regulates ribosomal RNA transcription in prostate cancer
Authors: Jia Tianwei , Liu Chenxu , Guo Ping , Xu Yaning , Wang Wenzheng , Liu Xiaoyu , Wang Song , Zhang Xianglin , Guo Haiyang 
Published: April 2024

AbstractBackgroundRibosome biogenesis is excessively activated in tumor cells, yet it is little known whether oncogenic transcription factors (TFs) are involved in the ribosomal RNA (rRNA) transactivation.MethodsNucleolar proteomics data and large‐scale immunofluorescence were re‐analyzed to jointly identify the proteins localized at nucleolus. RNA‐Seq data of five prostate cancer (PCa) cohorts were combined and integrated with multi‐dimensional data to define the upregulated nucleolar TFs in PCa tissues. Then, ChIP‐Seq data of PCa cell lines and two PCa clinical cohorts were re‐analyzed to reveal the TF binding patterns at ribosomal DNA (rDNA) repeats. The TF binding at rDNA was validated by ChIP‐qPCR. The effect of the TF on rRNA transcription was determined by rDNA luciferase reporter, nascent RNA synthesis, and global protein translation assays.ResultsIn this study, we reveal the role of oncogenic TF FOXA1 in regulating rRNA transcription within nucleolar organization regions. By analyzing human TFs in prostate cancer clinical datasets and nucleolar proteomics data, we identified that FOXA1 is partially localized in the nucleolus and correlated with global protein translation. Our extensive FOXA1 ChIP‐Seq analysis provides robust evidence of FOXA1 binding across rDNA repeats in prostate cancer cell lines, primary tumors, and castration‐resistant variants. Notably, FOXA1 occupancy at rDNA repeats correlates with histone modifications associated with active transcription, namely H3K27ac and H3K4me3. Reducing FOXA1 expression results in decreased transactivation at rDNA, subsequently diminishing global protein synthesis.ConclusionsOur results suggest FOXA1 regulates aberrant ribosome biogenesis downstream of oncogenic signaling in prostate cancer.
Coadministration of fluconazole to boost subtherapeutic sirolimus concentrations: A case report
Authors: Scherkl Camilo , Meid Andreas D. , Cuntz Sven E. , Classen Laura , Weiss Johanna , Czock David , Haefeli Walter E. 
Published: April 2024

AbstractIndividual sirolimus whole blood concentrations are highly variable, critically influenced by the concomitant use of cytochrome P450 (CYP) 3A inducers or inhibitors, and also modulated by food. Therapeutic drug monitoring is therefore recommended, especially at treatment start or in circumstances that can influence sirolimus exposure. In this case report, we highlight the challenge of achieving therapeutic sirolimus concentrations and present pragmatic solutions with regimen adaptions, pharmacokinetic enhancement (use of a drug–drug interaction), concentration monitoring, and subsequent modeling of population pharmacokinetics to support treatment decisions. In a 69‐year‐old female patient with allogeneic hematopoietic stem cell transplantation, sirolimus concentrations were stable until she developed cerebral toxoplasmosis with tonic–clonic seizures. During treatment of this acute infection, sirolimus concentrations dropped to subtherapeutic levels and remained largely unaffected by dose increases. [Correction added on 4 May 2024, after first online publication: The word “tacrolimus concentrations” has been changed to “sirolimus concentrations” in the preceding sentence.] Only the simultaneous administration of the CYP3A4 inhibitor fluconazole and a shortening of the sirolimus dosing intervals to a (non‐approved) twice‐daily administration led to successful control of the concentrations, which ultimately even made a dose reduction possible. This intervention resulted in an increase of sirolimus mean trough concentration to 5.85 ng/mL, i.e., into the desired target range. Additionally, a higher ratio of sirolimus trough levels/daily dose from 26.9 to 109 ng/mL/mg/kg/day was achieved with the initiation of fluconazole. Thus, this case report describes the use of clinical pharmacological concepts and pharmacokinetic modeling to optimize treatment strategies in an individual patient. This strategy could be generalized to other CYP inhibitors and other treatment regimens.
Experimental study on the explosion‐resistant performance of blast walls and doors of gas facilities
Authors: Ryu Young Jo , Lee Yong Gil , Park Dal Jae 
Published: April 2024

AbstractThis study aims to provide experimental data necessary for the validation of the test conditions given in the current standard for high‐pressure gas facility KGS FU111. A series of experiments were conducted in a shock tube on 15 specimens (walls and doors) constructed according to the design recommendations in KGS FP112. The design elements of 12 walls are the materials, the thickness, and the holder positions, while the 3 doors were made of steel plates with different types and structures. The shock tube tester used in dividual specimens were exposed to blast overpressure of 0.11 or 0.17 MPa. From the acquired data and visual inspection, we conclude that the current designs of blast mitigation for high‐pressure gas‐storage facilities in KGS FP112 are acceptable for an accidental overpressure of up to 0.17 MPa, provided that both sides of the wall are supported by auxiliary structures such as adjacent barriers. Furthermore, the walls and doors as in KGS FP112 show comparable protection performances. Nevertheless, recommendations for doors are as follows: it may require additional latches and remain closed, and when designing the facility, the doorway may be located in a place with less possibility of direct exposure to the overpressure.