bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lomerizine inhibits LPS-mediated neuroinflammation and tau hyperphosphorylation by modulating NLRP3, DYRK1A, and GSK3α/β
Authors: Park Jin-Hee , Hwang Jeong-Woo , Lee Hyun-ju , Jang Geum Mi , Jeong Yoo Joo , Cho Joonho , Seo Jinsoo , Hoe Hyang-Sook 
Published: June 2023

IntroductionLomerizine is a calcium channel blocker that crosses the blood–brain barrier and is used clinically in the treatment of migraines. However, whether lomerizine is beneficial in modulating neuroinflammatory responses has not been tested yet.MethodsTo assess the potential of lomerizine for repurposing as a treatment for neuroinflammation, we investigated the effects of lomerizine on LPS-induced proinflammatory responses in BV2 microglial cells, Alzheimer’s disease (AD) excitatory neurons differentiated from induced pluripotent stem cells (iPSCs), and in LPS-treated wild type mice.ResultsIn BV2 microglial cells, lomerizine pretreatment significantly reduced LPS-evoked proinflammatory cytokine and NLRP3 mRNA levels. Similarly, lomerizine pretreatment significantly suppressed the increases in Iba-1, GFAP, proinflammatory cytokine and NLRP3 expression induced by LPS in wild-type mice. In addition, lomerizine posttreatment significantly decreased LPS-stimulated proinflammatory cytokine and SOD2 mRNA levels in BV2 microglial cells and/or wild-type mice. In LPS-treated wild-type mice and AD excitatory neurons differentiated from iPSCs, lomerizine pretreatment ameliorated tau hyperphosphorylation. Finally, lomerizine abolished the LPS-mediated activation of GSK3α/β and upregulation of DYRK1A, which is responsible for tau hyperphosphorylation, in wild-type mice.DiscussionThese data suggest that lomerizine attenuates LPS-mediated neuroinflammatory responses and tau hyperphosphorylation and is a potential drug for neuroinflammation- or tauopathy-associated diseases.
Accumulation of plasmacytoid dendritic cell is associated with a treatment response to DNA-damaging treatment and favorable prognosis in lung adenocarcinoma
Authors: Cha Yoon Jin , Kim Eun Young , Choi Yong Jun , Kim Chi Young , Park Min Kyung , Chang Yoon Soo 
Published: June 2023

IntroductionFavorable responses to the treatment including immune checkpoint inhibitors (ICIs) have been consistently reported in lung cancer with smoking history. As the tumor microenvironment (TME) may be involved in the treatment response to ICIs, we aimed to investigate the TME of lung cancer with different smoking status.MethodsLung adenocarcinoma (LUAD) tissue (Tu) and adjacent normal-appearing lung tissue (NL) from current and never smokers were investigated by single-cell RNA sequencing and immunofluorescence and immunohistochemical staining. The clinical implications of identified biomarkers were validated using open-source datasets.ResultsThe lungs of smokers had an increased proportion of innate immune cells in NL tissues, whereas Tu tissues had a lower proportion of these cells than those of non-smokers. Monocyte-derived macrophages (mono-Mc), CD163-LGMN macrophages, monocyte-derived dendritic cells (DCs), and plasmacytoid DCs (pDCs) were significantly enriched in smokers’ Tu. Among these clusters, pDCs, specifically enriched in the Tu of smokers. The expression of representative pDC markers, leukocyte immunoglobulin-like receptor A4 (LILRA4) and Toll-like receptor 9 (TLR9), was increased in the stromal cells of LUAD in patients with a smoking history. In an animal model of lung cancer, ionizing radiation induced robust TLR9 expressing immune cells in peritumoral area. Survival analysis using a TCGA-LUAD dataset indicated that patients overexpressing pDC markers exhibited superior clinical outcomes to age-, sex-, and smoking-matched control groups. Top 25% patients with high TLR9 expression exhibited significantly higher tumor mutational burden than that of low TLR9 expression group (bottom 25% patients) (5.81 mutations/Mb vs 4.36 mutations/Mb; P = 0.0059, Welch’s two-sample t-test).ConclusionThere is an increased pDC in the TME of smokers’ lung cancer, and the response of pDC to DNA damaging treatment would lead a conducive environment to ICIs containing regimens. These findings suggest that R&amp;D that induces an increase in the activated pDC population is continuously required to enhance therapeutic effectiveness of ICIs-containing therapies in lung cancer.
Evaluation of droplet digital qRT-PCR (dd qRT-PCR) for quantification of SARS CoV-2 RNA in stool and urine specimens of COVID-19 patients
Authors: Shinde Manohar , Lavania Mallika , Rawal Jatin , Chavan Nutan , Shinde Pooja 
Published: June 2023

IntroductionThere have been a few reports of viral load detection in stool and urine samples of patients with coronavirus disease 2019 (COVID-19), and the transmission of the virus through faecal oral route. For clinical diagnosis and treatment, the widely used reverse transcription-polymerase chain reaction (qRT-PCR) method has some limitations.MethodsThe aim of our study to assess the presence and concentration of SARS CoV-2 RNA in stool and urine samples from COVID-19 patients with mild, moderate, and severe disease, we compared a traditional qRT-PCR approach with a ddPCR. ddPCR and qRT-PCR-based target gene analysis were performed on 107 COVID-19-confirmed patients paired samples (N1 and N2). The MagMax magnetic beads base method was used to isolate RNA. Real-time qRT-PCR and dd PCR were performed on all patients.Results and DiscussionThe average cycle threshold (Ct) of qRT-PCR was highly correlated with the average copy number of 327.10 copies/l analyzed in ddPCR. In ddPCR, urine samples showed 27.1% positivity while for stool it was 100%.ConclusionThis study’s findings not only show that SARS CoV-2 is present in urine and faeces, but also suggest that low concentrations of the viral target ddPCR make it easier to identify positive samples and help resolve for cases of inconclusive diagnosis.
Triggered episodic vestibular syndrome and transient loss of consciousness due to a retrostyloidal vagal schwannoma: a case report
Authors: Spiegelberg Maritta , Ermiş Ekin , Raabe Andreas , Tarnutzer Alexander Andrea 
Published: June 2023

BackgroundVarious conditions may trigger episodic vertigo or dizziness, with positional changes being the most frequently identified condition. In this study, we describe a rare case of triggered episodic vestibular syndrome (EVS) accompanied by transient loss of consciousness (TLOC) linked to retrostyloidal vagal schwannoma.Case descriptionA 27-year woman with known vestibular migraine presented with a 19-month history of nausea, dysphagia, and odynophagia triggered by swallowing food and followed by recurrent TLOC. These symptoms occurred independently of her body position, resulting in a weight loss of 10 kg within 1 year and in an inability to work. An extensive cardiologic diagnostic work-up undertaken before she presented to the neurologic department was normal. On the fiberoptic endoscopic evaluation of swallowing, she showed a decreased sensitivity, a slight bulging of the right lateral pharyngeal wall, and a pathological pharyngeal squeeze maneuver without any further functional deficits. Quantitative vestibular testing revealed an intact peripheral-vestibular function, and electroencephalography was read as normal. On the brain MRI, a 16 x 15 x 12 mm lesion in the right retrostyloidal space suspicious of a vagal schwannoma was detected. Radiosurgery was preferred over surgical resection, as resection of tumors in the retrostyloid space bears the risk of intraoperative complications and may result in significant morbidity. A single radiosurgical procedure (stereotactic CyberKnife radiosurgery, 1 x 13Gy) accompanied by oral steroids was performed. On follow-up, a cessation of (pre)syncopes was noted 6 months after treatment. Only residual infrequent episodes of mild nausea were triggered by swallowing solid food remained. Brain MRI after 6 months demonstrated no progression of the lesion. In contrast, migraine headaches associated with dizziness remained frequent.DiscussionDistinguishing triggered and spontaneous EVS is important, and identifying specific triggers by structured history-taking is essential. Episodes being elicited by swallowing solid foods and accompanied by (near) TLOC should initiate a thorough search for vagal schwannoma, as symptoms are often disabling, and targeted treatment is available. In the case presented here, cessation of (pre)syncopes and significant reduction of nausea triggered by swallowing was noted with a 6-month delay, illustrating the advantages (no surgical complications) and disadvantages (delayed treatment response) of first-line radiotherapy in vagal schwannoma treatment.
Executive functions and borderline personality features in adolescents with major depressive disorder
Authors: Albermann Mona , Emery Sophie , Baumgartner Noemi , Strumberger Michael , Erb Suzanne , Wöckel Lars , Müller-Knapp Ulrich , Rhiner Bruno , Contin-Waldvogel Brigitte , Bachmann Silke , Schmeck Klaus , Berger Gregor ,   the Omega-3 Study Team, Häberling Isabelle 
Published: June 2023

BackgroundExecutive functions (EF) consolidate during adolescence and are impaired in various emerging psychiatric disorders, such as pediatric Major Depressive Disorder (pMDD) and Borderline Personality Disorder. Previous studies point to a marked heterogeneity of deficits in EF in pMDD. We examined the hypothesis that deficits in EF in adolescents with pMDD might be related to comorbid Borderline Personality features (BPF).MethodsWe examined a sample of 144 adolescents (15.86 ± 1.32) diagnosed with pMDD. Parents rated their child’s EF in everyday life with the Behavior Rating Inventory of Executive Function (BRIEF) and BPF with the Impulsivity and Emotion Dysregulation Scale (IED-27). The adolescents completed equivalent self-rating measures. Self- and parent-ratings of the BRIEF scores were compared with paired t-Tests. Correlation and parallel mediation analyses, ICC, and multiple regression analyses were used to assess symptom overlap, parent-child agreement, and the influence of depression severity.ResultsOver the whole sample, none of the self- or parent-rated BRIEF scales reached a mean score above T &gt; 65, which would indicate clinically impaired functioning. Adolescents tended to report higher impairment in EF than their parents. Depression severity was the strongest predictor for BPF scores, with Emotional Control predicting parent-rated BPF and Inhibit predicting self-rated BPF. Furthermore, the Behavioral Regulation Index, which includes EF closely related to behavioral control, significantly mediated the relationship between depression severity and IED-27 factors emotional dysregulation and relationship difficulties but not non-suicidal self-injuries.ConclusionOn average, adolescents with depression show only subtle deficits in executive functioning. However, increased EF deficits are associated with the occurrence of comorbid borderline personality features, contributing to a more severe overall psychopathology. Therefore, training of executive functioning might have a positive effect on psychosocial functioning in severely depressed adolescents, as it might also improve comorbid BPF.Clinical trial registrationwww.ClinicalTrials.gov, identifier NCT03167307.
Potential candidates for liver resection in liver-confined advanced HCC: a Chinese multicenter observational study
Authors: Bai Tingting , Wang Enxin , Zhao Shoujie , Han Dandan , Zhao Yan , Chen Hui , Zhu Jun , Han Tenghui , Bai Yang , Lou Yanju , Zhang Yongchao , Yang Man , Zuo Luo , Fan Jiahao , Chen Xing , Jia Jia , Wu Wenbin , Ren Weirong , Zhu Yejing , Ma Shouzheng , Xu Fenghua , Tang Yuxin , Du Xilin , Zhao Junlong , Li Jing , Qi Xingshun , Han Ying , Chen Dongfeng , Liu Lei 
Published: June 2023

BackgroundAdvanced hepatocellular carcinoma (HCC) is characterized as symptomatic tumors [performance status (PS) score of 1-2], vascular invasion and extrahepatic spread, but patients with PS1 alone may be eliminated from this stage. Although liver resection is used for liver-confined HCC, its role in patients with PS1 alone remains controversial. Therefore, we aimed to explore its application in such patients and identify potential candidates.MethodsEligible liver-confined HCC patients undergoing liver resection were retrospectively screened in 15 Chinese tertiary hospitals, with limited tumor burden, liver function and PS scores. Cox-regression survival analysis was used to investigate the prognostic factors and develop a risk-scoring system, according to which patients were substratified using fitting curves and the predictive values of PS were explored in each stratification.ResultsFrom January 2010 to October 2021, 1535 consecutive patients were selected. In the whole cohort, PS, AFP, tumor size and albumin were correlated with survival (adjusted P&lt;0.05), based on which risk scores of every patient were calculated and ranged from 0 to 18. Fitting curve analysis demonstrated that the prognostic abilities of PS varied with risk scores and that the patients should be divided into three risk stratifications. Importantly, in the low-risk stratification, PS lost its prognostic value, and patients with PS1 alone achieved a satisfactory 5-year survival rate of 78.0%, which was comparable with that PS0 patients (84.6%).ConclusionSelected patients with PS1 alone and an ideal baseline condition may benefit from liver resection and may migrate forward to BCLC stage A.
Tumor purity–associated genes influence hepatocellular carcinoma prognosis and tumor microenvironment
Authors: Zhao Yan , Xu Xu , Wang Yue , Wu Lin D. , Luo Rui L. , Xia Ren P. 
Published: June 2023

IntroductionTumor purity takes on critical significance to the progression of solid tumors. The aim of this study was at exploring potential prognostic genes correlated with tumor purity in hepatocellular carcinoma (HCC) by bioinformatics analysis.MethodsThe ESTIMATE algorithm was applied for determining the tumor purity of HCC samples from The Cancer Genome Atlas (TCGA). The tumor purity–associated genes with differential expression (DEGs) were identified based on overlap analysis, weighted gene co-expression network analysis (WGCNA), and differential expression analysis. The prognostic genes were identified in terms of the prognostic model construction based on the Kaplan–Meier (K–M) survival analysis and Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses. The expression of the above-described genes was further validated by the GSE105130 dataset from the Gene Expression Omnibus (GEO) database. We also characterized the clinical and immunophenotypes of prognostic genes. Gene set enrichment analysis (GSEA) was carried out for exploring the biological signaling pathway.ResultsA total of 26 tumor purity–associated DEGs were identified, which were involved in biological processes such as immune/inflammatory responses and fatty acid elongation. Ultimately, we identified ADCK3, HK3, and PPT1 as the prognostic genes for HCC. Moreover, HCC patients exhibiting higher ADCK3 expression and lower HK3 and PPT1 expressions had a better prognosis. Furthermore, high HK3 and PPT1 expressions and low ADCK3 expression resulted in high tumor purity, high immune score, high stromal score, and high ESTIMATE score. GSEA showed that the abovementioned prognostic genes showed a significant correlation with immune-inflammatory response, tumor growth, and fatty acid production/degradation.DiscussionIn conclusion, this study identified novel predictive biomarkers (ADCK3, HK3, and PPT1) and studied the underlying molecular mechanisms of HCC pathology initially.
Breast mass as the first sign of metastasis from rectal carcinoma: a case report and review of the literature
Authors: Xu Jiawei , Liu Chao , Yu Chengdong , Yu Tenghua , Fan Fan , Zhang Xiaofang , Huang Chuansheng , Chen Wen , Sun Zhengkui , Zhou Meng 
Published: June 2023

We present a case report of a 41-year-old woman who developed a left breast mass 18 months after undergoing Dixon rectal cancer surgery. The purpose of this case report is to highlight the possibility of breast metastases in patients with colorectal cancer and emphasize the importance of careful evaluation and follow-up as well as timely and accurate diagnosis and management of the metastatic disease. During the physical examination in 2021, we noted that the lower border of the mass was 9 cm from the anal verge and that it occupied approximately one-third of the intestinal lumen. A pathological biopsy revealed the mass in the patient’s intestinal lumen was a rectal adenocarcinoma. The patient underwent Dixon surgery for rectal cancer and received subsequent chemotherapy. The patient had no prior history of breast-related medical conditions or a family history of breast cancer. During the current physical examination, we discovered multiple lymphadenopathies in the patient’s left neck, bilateral axillae, and left inguinal region, but none elsewhere. We observed a large erythema of about 15x10 cm on the patient’s left breast, with scattered hard nodes of varying sizes. Palpation of the area beyond the upper left breast revealed a mass measuring 3x3 cm. We conducted further examinations of the patient, which revealed the breast mass and lymphadenopathy on imaging. However, we did not find any other imaging that had significant diagnostic value. Based on the patient’s conventional pathology and immunohistochemical findings, combined with the patient’s past medical history, we strongly suspected that the patient’s breast mass was of rectal origin. This was confirmed by the abdominal CT performed afterward. The patient was treated with a chemotherapy regimen consisting of irinotecan 260 mg, fluorouracil 2.25 g, and cetuximab 700 mg IV drip, which resulted in a favorable clinical response. This case illustrates that colorectal cancer can metastasize to unusual sites and underscores the importance of thorough evaluation and follow-up, particularly when symptoms are atypical. It also highlights the importance of timely and accurate diagnosis and management of metastatic disease to improve the patient’s prognosis.
Sclerostin decreases in regular swimmers after ice swimming and is associated with meteorin-like protein serum levels
Authors: Mu Shuai , Huang Chongjun , Chen Bobo , Zhao Pengyu , Xu Haoran , Zhang Weihao , Dai Huixu 
Published: June 2023

Introduction: Cold and exercise are two important stimuli affecting the secretion of osteokines and adipomyokines, which often occur simultaneously. However, few studies have investigated the changes in osteokines and adipomyokines induced by exercise during severe cold and their corresponding associations. Therefore, this study aimed to investigate the changes in sclerostin and meteorin-like (metrnl) protein before and after cold exercise (ice swimming [IS]) and observe their correlation.Methods: For this, 56 daily ice swimmers’ data were included in this study. Serum sclerostin and metrnl were measured 30 min before IS and 30 min after. The fat mass, visceral fat area, fat-free mass, skeletal muscle mass, lumbar spine, and femoral neck bone mineral density of the ice swimmers were measured.Results: After IS, sclerostin exhibited significant decreases, whereas metrnl showed no significant change. In addition, the baseline level of sclerostin and the decrease in sclerostin were positively correlated with serum metrnl after adjusting for age, gender, and body composition indicators.Discussion: IS caused a significant decrease in sclerostin but did not affect metrnl. Furthermore, the associations between sclerostin and metrnl suggested a correlation between osteokines and adipomyokines; this encourages future exploration of the interconnection between bone, muscle, and fat, which will be beneficial for identifying potential common therapeutic targets for diseases such as osteoporosis, sarcopenia, and obesity.
Effect of temperature on betacyanins synthesis and the transcriptome of Suaeda salsa
Authors: Li Min , He Peimin , Zhao Zitao , Liu Jinlin , Liu Hongtao , Ma Shaozu , Shen Yifei , Li Bin 
Published: June 2023

IntroductionSuaeda salsa (Linn.) Pall. is an important tourist resource and ecological restoration species in coastal wetlands. Environmental factors such as low temperature, darkness, phytohormone, salt stress and seawater flflooding, and light can induce betalain synthesis in S. salsa, which plays an important role in plant adaptation to abiotic stress processes and in shaping the beautiful “red beach” landscape.MethodsIn this study, Illumina sequencing was used to profifile the transcriptome sequence (RNA-Seq) of S. salsa leaves at different temperatures (5° C, 10°C, 15°C, 20°C, 25°C, and 30°C) and to validate differentially expressed genes (DEGs) indicated by real-time PCR (RT-qPCR).ResultsThe betacyanin content was highest in S. salsa leaves at 15°C. Transcription group data showed that compared to the control group (15°C), the “betacyanin biosynthesis pathway” was signifificantly enriched in the fifive different temperature groups. KEGG analysis showed that the DEGs were mainly involved in pathways of phenylpropanoid biosynthesis, carbon fifixation in photosynthetic organisms, flflavonoid biosynthesis, and betacyanin biosynthesis. Among the key enzymes involved in biosynthesis of betacyanin, genes for tyrosinase, CYP76AD1 and 4,5-DOPA dioxygenase were signifificantly upregulated and most abundantly expressed at 15°C. It is possible that the gene for betacyanin synthesis from S. salsa is primarily regulated by the MYB1R1 and MYB1 transcription factor. Four DEGs were randomly selected for quantitative PCR analysis, and DEG expression was generally consistent with the RNA-Seq data, verifying the validity of the transcriptome sequencing data.DiscussionRelative to other temperatures, 15°C was optimum for S. salsa betacyanin synthesis, and this provides a theoretical reference for coastal wetland ecological remediation, reveals mechanisms of S. salsa discoloration, and further mines its potential application for landscape vegetation.