bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunosuppressant exposure confounds gene expression analysis in systemic lupus erythematosus
Authors: Northcott Melissa , Gearing Linden J. , Bonin Julie , Koelmeyer Rachel , Hoi Alberta , Hertzog Paul J. , Morand Eric F. 
Published: August 2022

ObjectivesThe analysis of gene module expression in SLE is emerging as a tool to identify active biological pathways, with the aim of developing targeted therapies for subsets of patients. Detailed information on the effect of immunosuppressants on gene module expression is lacking. We aimed to examine the impact of medication exposure on gene module expression.MethodsA set of commercially available disease-relevant gene modules were measured in 730 whole blood samples from a dedicated lupus clinic on whom prospectively collected, contemporaneous clinical data including medication exposure were available.ResultsCompared to heathy controls, SLE patients showed over-expression of IFN and under-expression of B cell, T cell and pDC modules. Neutrophil module over-expression and under-expression of B and T cell modules were observed in patients with active lupus nephritis or highly active disease (SLEDAI-2K &gt; 8), while Lupus Low Disease Activity State (LLDAS) had inverse associations. Disease activity in other organ domains was not associated with specific gene modules. In contrast, medications were associated with multiple effects. Glucocorticoid use was associated with under-expression of T cell, B cell and plasmablast modules, and over-expression of neutrophil modules. Mycophenolate and azathioprine exposure were associated with plasmablast module and B cell module under-expression respectively. Disease activity associations with neutrophil over-expression and lymphocyte module under-expression were attenuated by multivariable adjustment for medication exposure.ConclusionMedications have significant effect on gene module expression in SLE patients. These findings emphasize the need to control for medications in studies of gene expression in SLE.
Cellular and humoral immune responses and breakthrough infections after three SARS-CoV-2 mRNA vaccine doses
Authors: Almendro-Vázquez Patricia , Chivite-Lacaba Marta , Utrero-Rico Alberto , González-Cuadrado Cecilia , Laguna-Goya Rocio , Moreno-Batanero Miguel , Sánchez-Paz Laura , Luczkowiak Joanna , Labiod Nuria , Folgueira María Dolores , Delgado Rafael , Paz-Artal Estela 
Published: August 2022

BackgroundSARS-CoV-2 vaccination has proven the most effective measure to control the COVID-19 pandemic. Booster doses are being administered with limited knowledge on their need and effect on immunity.ObjectiveTo determine the duration of specific T cells, antibodies and neutralization after 2-dose vaccination, to assess the effect of a third dose on adaptive immunity and to explore correlates of protection against breakthrough infection.Methods12-month longitudinal assessment of SARS-CoV-2-specific T cells, IgG and neutralizing antibodies triggered by 2 BNT162b2 doses followed by a third mRNA-1273 dose in a cohort of 77 healthcare workers: 17 with SARS-CoV-2 infection prior to vaccination (recovered) and 60 naïve.ResultsPeak levels of cellular and humoral response were achieved 2 weeks after the second dose. Antibodies declined thereafter while T cells reached a plateau 3 months after vaccination. The decline in neutralization was specially marked in naïve individuals and it was this group who benefited most from the third dose, which resulted in a 20.9-fold increase in neutralization. Overall, recovered individuals maintained higher levels of T cells, antibodies and neutralization 1 to 6 months post-vaccination than naïve. Seventeen asymptomatic or mild SARS-CoV-2 breakthrough infections were reported during follow-up, only in naïve individuals. This viral exposure boosted adaptive immunity. High peak levels of T cells and neutralizing antibodies 15 days post-vaccination associated with protection from breakthrough infections.ConclusionBooster vaccination in naïve individuals and the inclusion of viral antigens other than spike in future vaccine formulations could be useful strategies to prevent SARS-CoV-2 breakthrough infections.
Sarcoid-like reaction in patients with malignant tumors: Long-term clinical course and outcomes
Authors: Huh Jin-Young , Moon Do Sik , Song Jin Woo 
Published: August 2022

BackgroundThe development of non-caseating epithelioid cell granulomas in cancer patients who do not fulfill the systemic sarcoidosis criteria is termed sarcoid-like reaction (SLR). Little is known about this condition's natural course and impact on the prognosis of malignancy. We aimed to investigate the natural course and prognostic value of cancer-associated SLR.MethodsClinical data were retrospectively analyzed in 32 patients with biopsy-proven cancer-associated SLR. Among patients with non-small cell lung cancer (NSCLC), SLR cases (n = 8) were matched with non-SLR cases (n = 78) for survival analysis.ResultsAmong the included patients, the mean age was 59.7 years, and 68.8% were female. The median follow-up period was 35.6 months [interquartile range (IQR): 14.0–61.4 months]. Of all the included malignancies (n = 32), breast cancer (25.0%) and NSCLC (25.0%) were the most common, with stage I being the most frequent tumor stage (59.4%). During follow-up, SLR progression to overt sarcoidosis was not observed. In the 28 patients with available follow-up computed tomography images (median interval: 24.9 months; IQR: 14.4–41.7), 4 patients received corticosteroids (n = 4), resulting to a decrease of SLR lesions. Meanwhile, among those who did not receive treatment (n = 24), the extent of SLR decreased or did not change in 85.7% of them, whereas 3.6% had increased SLR extent. Furthermore, among patients with NSCLC, SLR was not associated with overall survival [hazard ratio (HR) = 1.28, 95% confidence interval (CI): 0.02–67.71, P = 0.882] and recurrence of malignancy (HR = 1.27, 95% CI 0.21–7.51, P = 0.793) in the Cox proportional hazard regression model.ConclusionsDuring the follow-up of cancer-related SLR, we found no further evidence for systemic sarcoidosis, and most of the lesions decreased or did not change. Development of SLR was also not associated with overall survival or disease-free survival in patients with NSCLC.
Elevated serum TLR4 level as a potential marker for postsurgical chronic pain in pediatric patients with different approaches to analgesia
Authors: Semkovych Yaroslav , Dmytriiev Dmytro 
Published: August 2022

IntroductionThe perioperative period of any surgery is accompanied by immune suppression. The level of Toll-like receptor 4 (TLR4) is known to increase in inflammation and after nerve injury and contributes to the development of neuropathic pain. The interaction of TLRs in response to the effect of opioids results in paradoxical hyperalgesia. Regional anesthesia techniques are the standard of care for perioperative pain management in children.AimThe aim of the study was to determine and evaluate the indicators of TLR4 for different methods of pain relief in anesthetic management of hernia repair in children and their effect on pain chronification.Materials and methodsThere were examined 60 children with inguinal hernia during 2020–2022. Children were divided into 3 groups: Group I included 20 children who underwent surgery under general anesthesia using the block of the anterior abdominal wall—transversalis fascia plane block (TFPB), combined with the quadratus lumborum block (QLB-4) via a single intramuscular injection; Group II included 20 children who underwent surgery under general anesthesia using the TFPB; Group III comprised 20 children who underwent surgery under general anesthesia using opioid analgesics. The levels of TLR4 were evaluated at a discharge from the hospital, 3 and 6 months after surgery.ResultsThere was no difference in age and body weight among all groups. In Group II, boys prevailed. In Group III, the length of hospital stay was the longest (3.28 ± 0.24 days, p &lt; 0.05, t = 4.09) as compared to children of Group II and Group I (3.0 ± 0.30 (p &lt; 0.05, t = 2.647) and 2.1 ± 0.16 days, respectively). While staying in the surgical department, children of Group III demonstrated significantly higher FLACC and VAS scores. The prevalence of chronic pain was the highest among children of Group III (35%) as compared to those in Group II and Group I (20 and 15%, respectively). The highest increase in the level of TLR4 was found in the group of opioid analgesia on the third and sixth months after surgery (68.86 + 10.31 pg/ml and 143.15 + 18.77 pg/ml (p &lt; 0.05, t = 6.33), respectively) as compared to patients who received regional anesthesia.ConclusionsThere were confirmed the following advantages of the transversalis fascia plane block combined with the quadratus lumborum block (QLB + TFPB) via a single intramuscular injection: ease of use; adequate perioperative pain control as evidenced by the FLACC and VAS pain assessment scales; reduced perioperative use of opioid analgesics; shortening the length of hospital stay.
Calculating intraocular lens power in anterior megalophthalmos: A case report
Authors: Mu Jiancheng , Yang Yu , Xiong Tianxu , Fan Wei 
Published: August 2022

IntroductionWe report a case of a man with cataract and anterior megalophthalmos (AM), in which some myopia was retained when calculating intraocular lens (IOL) power using the Haigis formula to avoid postoperative farsightedness.Case descriptionA 59-year-old Chinese man was referred to our clinic for cataract surgery in his right eye. He had strong bilateral megalocornea, and his left eye had undergone surgery four times. After complete preoperative examinations and repeated biometry, the Haigis formula was used, and a 3-piece IOL was implanted with a target power of −1.97 D. At 1-year follow-up, the patient showed the best-corrected distance vision of 20/20 with the refraction of −1.50 DC × 160°, and the IOL was stable.ConclusionOur patient with anterior megalophthalmos showed postoperative hyperopia drift even though the Haigis formula was used as suggested in previous studies. To prevent farsightedness after surgery, some myopia should be retained when calculating IOL power. The Kane, Holladay II with AL adjustment, and Barrett Universal II formulas may be more accurate for calculating IOL power in such patients.
Altered dynamic intrinsic brain activity of the default mode network in Alzheimer’s disease: A resting-state fMRI study
Authors: Liao Zhengluan , Sun Wangdi , Liu Xiaozheng , Guo Zhongwei , Mao Dewang , Yu Enyan , Chen Yan 
Published: August 2022

ObjectiveStatic regional homogeneity (ReHo) based on the resting-state functional magnetic resonance imaging (rs-fMRI) has been used to study intrinsic brain activity (IBA) in Alzheimer’s disease (AD). However, few studies have examined dynamic ReHo (dReHo) in AD. In this study, we used rs-fMRI and dReHo to investigate the alterations in dynamic IBA in patients with AD to uncover dynamic imaging markers of AD.MethodIn total, 111 patients with AD, 29 patients with mild cognitive impairment (MCI), and 73 healthy controls (HCs) were recruited for this study ultimately. After the rs-fMRI scan, we calculated the dReHo values using the sliding window method. ANOVA and post hoc two-sample t-tests were used to detect the differences among the three groups. We used the mini-mental state examination (MMSE) and Montreal Cognitive Assessment (MoCA) to evaluate the cognitive function of the subjects. The associations between the MMSE score, MoCA score, and dReHo were assessed by the Pearson correlation analysis.ResultsSignificant dReHo variability in the right middle frontal gyrus (MFG) and right posterior cingulate gyrus (PCG) was detected in the three groups through ANOVA. In post hoc analysis, the AD group exhibited significantly greater dReHo variability in the right MFG than the MCI group. Compared with the HC group, the AD group exhibited significantly increased dReHo variability in the right PCG. Furthermore, dReHo variability in the right PCG was significantly negatively correlated with the MMSE and MoCA scores of patients with AD.ConclusionDisrupted dynamic IBA in the DMN might be an important characteristic of AD and could be a potential biomarker for the diagnosis or prognosis of AD.
Metabolic protection by the dietary flavonoid 7,8-dihydroxyflavone requires an intact gut microbiome
Authors: Sharma Priyanka , Silva Camila , Pfreundschuh Sarah , Ye Hong , Sampath Harini 
Published: August 2022

Background7,8-dihydroxyflavone (DHF) is a naturally occurring flavonoid found in Godmania, Tridax, and Primula species that confers protection against high-fat diet (HFD) induced metabolic pathologies selectively in female mice. We have previously reported that this metabolic protection is associated with early and stable remodeling of the intestinal microbiome, evident in female but not male DHF-supplemented mice. Early changes in the gut microbiome in female DHF-fed mice were highly predictive of subsequent metabolic protection, suggesting a causative association between the gut microbiome and the metabolic effects of DHF.ObjectiveTo investigate a causal association between the gut microbiome and the metabolic effects of DHF using a model of antibiotic-induced gut microbiome ablation.Materials and methodsAge-matched male and female C57Bl6/J mice were given ad libitum access to HFD and drinking water containing vehicle or DHF for 12 weeks. For antibiotic (Abx) treatment, female mice were given drinking water containing a cocktail of antibiotics for 2 weeks prior to HFD feeding and throughout the feeding period. Metabolic phenotyping consisted of longitudinal assessments of body weights, body composition, food, and water intake, as well as measurement of energy expenditure, glucose tolerance, and plasma and hepatic lipids. Protein markers mediating the cellular effects of DHF were assessed in brown adipose tissue (BAT) and skeletal muscle.ResultsMetabolic protection conferred by DHF in female HFD-fed mice was only apparent in the presence of an intact gut microbiome. Abx-treated mice were not protected from HFD-induced obesity by DHF administration. Further, tissue activation of the tropomyosin-related kinase receptor B (TrkB) receptor, which has been attributed to the biological activity of DHF, was lost upon gut microbiome ablation, indicating a requirement for microbial “activation” of DHF for its systemic effects. In addition, we report for the first time that DHF supplementation significantly activates TrkB in BAT of female, but not male, mice uncovering a novel target tissue of DHF. DHF supplementation also increased uncoupling protein 1 (UCP1) and AMP-activated protein kinase (AMPK) protein in BAT, consistent with protection from diet-induced obesity.ConclusionThese results establish for the first time a requirement for the gut microbiome in mediating the metabolic effects of DHF in female mice and uncover a novel target tissue that may mediate these sexually-dimorphic protective effects.
Evolutions in the management of non-small cell lung cancer: A bibliometric study from the 100 most impactful articles in the field
Authors: Chen Siyuan , Qiao Yu , Chen Juan , Li Yanan , Xie Jianlian , Cui Pengfei , Huang Ziwei , Huang Di , Gao Yiming , Hu Yi , Liu Zhefeng 
Published: August 2022

ObjectiveThe study was designed to explore the evolution of non-small cell lung cancer (NSCLC) management in the last 20 years.MethodsThe top 100 most-cited papers on NSCLC treatment were retrieved from the Web of Science Core Collection database. R and VOSviewer were used to extract bibliographic information, including the year of publication, countries/regions, institutions, authors, journals, keywords, impact factor, and total citations. The topic and type of papers were checked independently by authors. Bibliometric analysis was conducted and visualized with R, CiteSpace, Excel and VOSviewer to identify output dynamics, research forces, topics, hotspots, and frontiers in the field.ResultsThe average citation of each retrieved top 100 most-cited NSCLC management papers was 1,725 (range: 615-7,340). Fifty-seven corresponding authors were from the United States. This country contributed the most papers (n=76), followed by Germany (n=34), France (n=33), and South Korea (n=32). The top contributors were Paz-Ares L. (n=12) and Reck M. (n=12). The Memorial Sloan Kettering Cancer Center published the largest number of papers (n=20). There were two significant citation paths, indicating publications in medicine/medical/clinical journals primarily cited journals in molecular/biology/genetics fields, partly cited health/nursing/medicine fields. Top-cited papers mainly came from the New England Journal of Medicine (n=33, citations=80,427), followed closely by the Journal of Clinical Oncology (n=28, citations=32,408). “Chemotherapy” (n=36) was the keyword with the greatest frequency of co-occurrence. “Open-label” was the keyword with the strongest burst strength (=4.01), followed by “nivolumab” (=3.85), “blockade” (=2.86), and “efficacy” (=2.85).ConclusionsThe United States as a nation and the Memorial Sloan Kettering Cancer Center as an institute contributed the most to this field. The New England Journal of Medicine is the most eye-catching journal. Hotspots of NSCLC management have almost undergone an evolution from chemotherapy and radiotherapy to targeted therapy to immunotherapy. Molecular/biological/genetic fields become the main research base for NSCLC treatment. Immunotherapy and combination therapy are research frontiers.
Machine learning-featured Secretogranin V is a circulating diagnostic biomarker for pancreatic adenocarcinomas associated with adipopenia
Authors: Jo Yunju , Yeo Min-Kyung , Dao Tam , Kwon Jeongho , Yi Hyon‐Seung , Ryu Dongryeol 
Published: August 2022

BackgroundPancreatic cancer is one of the most fatal malignancies of the gastrointestinal cancer, with a challenging early diagnosis due to lack of distinctive symptoms and specific biomarkers. The exact etiology of pancreatic cancer is unknown, making the development of reliable biomarkers difficult. The accumulation of patient-derived omics data along with technological advances in artificial intelligence is giving way to a new era in the discovery of suitable biomarkers.MethodsWe performed machine learning (ML)-based modeling using four independent transcriptomic datasets, including GSE16515, GSE62165, GSE71729, and the pancreatic adenocarcinoma (PAC) dataset of the Cancer Genome Atlas. To find candidates for circulating biomarkers, we exported expression profiles of 1,703 genes encoding secretory proteins. Integrating three transcriptomic datasets into either a training or test set, ML-based modeling distinguishing PAC from normal was carried out. Another ML-model classifying long-lived and short-lived patients with PAC was also built to select prognosis-associated features. Finally, circulating level of SCG5 in the plasma was determined from the independent cohort (non-tumor = 25 and pancreatic cancer = 25). We also investigated the impact of SCG5 on adipocyte biology using recombinant protein.ResultsThree distinctive ML-classifiers selected 29-, 64- and 18-featured genes, recognizing the only common gene, SCG5. As per the prediction of ML-models, the SCG5 transcripts was significantly reduced in PAC and decreased further with the progression of the tumor, indicating its potential as a diagnostic as well as prognostic marker for PAC. External validation of SCG5 using plasma samples from patients with PAC confirmed that SCG5 was reduced significantly in patients with PAC when compared to controls. Interestingly, plasma SCG5 levels were correlated with the body mass index and age of donors, implying pancreas-originated SCG5 could regulate energy metabolism systemically. Additionally, analyses using publicly available Genotype-Tissue Expression datasets, including adipose tissue histology and pancreatic SCG5 expression, further validated the association between pancreatic SCG5 expression and the size of subcutaneous adipocytes in humans. However, we could not observe any definite effect of rSCG5 on the cultured adipocyte, in 2D in vitro culture.ConclusionCirculating SCG5, which may be associated with adipopenia, is a promising diagnostic biomarker for PAC.
Blood neurofilament light chain as a biomarker for monitoring and predicting paclitaxel-induced peripheral neuropathy in patients with gynecological cancers
Authors: Kim Su-Hyun , Kim Ki Hoon , Hyun Jae-Won , Kim Ji Hyun , Seo Sang-Soo , Kim Ho Jin , Park Sang-Yoon , Lim Myong Cheol 
Published: August 2022

ObjectiveWe aimed to evaluate the potential of serum neurofilament light chain (sNfL) and serum brain-derived neurotrophic factor (sBDNF) as reliable biomarkers for paclitaxel-induced peripheral neuropathy (PIPN).MethodsForty-eight patients with gynecologic cancer scheduled to undergo six cycles of paclitaxel-based chemotherapy at the National Cancer Center of Korea between September 2020 and January 2022 were prospectively assessed during and after chemotherapy.ResultsAt the end of the chemotherapy, 12 (25%) patients were classified as having grade 3 PIPN according to the National Cancer Institute-Common Toxicity Criteria. The sNfL levels increased during paclitaxel treatment in all patients. After two, four, and six cycles, patients with grade 3 PIPN exhibited higher mean sNfL levels than those in the 0–2 grade range (p = 0.004, p = 001, and p &lt; 0.001, respectively). For sNfL levels ≥ 124 pg/mL, after two cycles of chemotherapy, the sensitivity and specificity for predicting grade 3 PIPN at the end of treatment were 80% and 79%, respectively. Over the course of paclitaxel-based treatment, sBDNF levels continued to decrease regardless of the severity of PIPN. At the end of treatment and six months after chemotherapy, patients with grade 3 PIPN had lower sBDNF levels than those within the 0–2 grade range (p =0.037 and 0.02, respectively), and the patients in the latter group had better clinical symptoms six months after the end of treatment.ConclusionsThe sNfL levels during paclitaxel-based chemotherapy reflect ongoing neuroaxonal injury and serve as reliable biomarkers of PIPN severity. The sNfL levels during early treatment with paclitaxel might be prognostic indicators for PIPN progression. Low sBDNF levels 6 months after chemotherapy might adversely affect PIPN recovery.