bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of Sodium MRI at 7 Tesla as Predictor of Therapy Response and Survival in Glioblastoma Patients
Authors: Paech Daniel , Regnery Sebastian , Platt Tanja , Behl Nicolas G. R. , Weckesser Nina , Windisch Paul , Deike-Hofmann Katerina , Wick Wolfgang , Bendszus Martin , Rieken Stefan , König Laila , Ladd Mark E. , Schlemmer Heinz-Peter , Debus Jürgen , Adeberg Sebastian
Published: December 2021

The purpose of this work was to prospectively investigate sodium (23Na) MRI at 7 Tesla (T) as predictor of therapy response and survival in patients with glioblastoma (GBM). Thus, 20 GBM patients underwent 23Na MRI at 7T before, immediately after and 6 weeks after chemoradiotherapy (CRT). The median tissue sodium concentration (TSC) inside the whole tumor excluding necrosis was determined. Initial response to CRT was assessed employing the updated response assessment in neuro-oncology working group (RANO) criteria. Clinical parameters, baseline TSC and longitudinal TSC differences were compared between patients with initial progressive disease (PD) and patients with initial stable disease (SD) using Fisher’s exact tests and Mann-Whitney-U-tests. Univariate proportional hazard models for progression free survival (PFS) and overall survival (OS) were calculated using clinical parameters and TSC metrics as predictor variables. The analyses demonstrated that TSC developed heterogeneously over all patients following CRT. None of the TSC metrics differed significantly between cases of initial SD and initial PD. Furthermore, TSC metrics did not yield a significant association with PFS or OS. Conversely, the initial response according to the RANO criteria could significantly predict PFS [univariate HR (95%CI) = 0.02 (0.0001–0.21), p < 0.001] and OS [univariate HR = 0.17 (0.04–0.65), p = 0.005]. In conclusion, TSC showed treatment-related changes in GBM following CRT, but did not significantly correlate with the initial response according to the RANO criteria, PFS or OS. In contrast, the initial response according to the RANO criteria was a significant predictor of PFS and OS. Future investigations need to elucidate the reasons for treatment-related changes in TSC and their clinical value for response prediction in glioblastoma patients receiving CRT.
Electroencephalogram Source Imaging and Brain Network Based Natural Grasps Decoding
Authors: Xu Baoguo , Deng Leying , Zhang Dalin , Xue Muhui , Li Huijun , Zeng Hong , Song Aiguo
Published: December 2021

Studying the decoding process of complex grasping movement is of great significance to the field of motor rehabilitation. This study aims to decode five natural reach-and-grasp types using sources of movement-related cortical potential (MRCP) and investigate their difference in cortical signal characteristics and network structures. Electroencephalogram signals were gathered from 40 channels of eight healthy subjects. In an audio cue-based experiment, subjects were instructed to keep no-movement condition or perform five natural reach-and-grasp movements: palmar, pinch, push, twist and plug. We projected MRCP into source space and used average source amplitudes in 24 regions of interest as classification features. Besides, functional connectivity was calculated using phase locking value. Six-class classification results showed that a similar grand average peak performance of 49.35% can be achieved using source features, with only two-thirds of the number of channel features. Besides, source imaging maps and brain networks presented different patterns between each condition. Grasping pattern analysis indicated that the modules in the execution stage focus more on internal communication than in the planning stage. The former stage was related to the parietal lobe, whereas the latter was associated with the frontal lobe. This study demonstrates the superiority and effectiveness of source imaging technology and reveals the spread mechanism and network structure of five natural reach-and-grasp movements. We believe that our work will contribute to the understanding of the generation mechanism of grasping movement and promote a natural and intuitive control of brain–computer interface.
A Willingness-to-Pay Associated Right Prefrontal Activation During a Single, Real Use of Lipsticks as Assessed Using Functional Near-Infrared Spectroscopy
Authors: Hirabayashi Kazue , Tokuda Tatsuya , Nishinuma Tomomi , Kawabata Duncan Keith , Tagai Keiko , Dan Ippeita
Published: December 2021

Understanding consumer preferences and behavior is a major goal of consumer-oriented companies. The application of neuroscience to this goal is a promising avenue for companies. Previously, we observed a positive correlation during actual cosmetic use between the right dorsolateral prefrontal cortex (dlPFC) activity, measured by functional near-infrared spectroscopy (fNIRS), and the associated willingness-to-pay (WTP) values. However, we were unable to find any consistent group differences in the right dlPFC between different powdery foundations. Thus, the main objective of this study was to replicate the previous study and in addition, we aimed to refine the method of the previous study to increase the chance that a difference in valuation between different products can be detected. Twenty-five frequent lipstick using females were asked to apply six different lipsticks to their lips and to record how much they were willing to pay. To maximize the variation of the subjective experience of the products and the associated brain activity, the most preferred color lipstick and a less preferred color lipstick were chosen for each participant, and each color of lipstick had three different textures (Lo, Mid, and Hi). The time series was analyzed with the general linear model (GLM) and the correlation between the right dlPFC beta scores for the lipsticks and their respective WTP values conducted for each participant. This revealed a significant positive correlation and replicated our previous study. Surprisingly, the lipstick color and the texture manipulations did not result in any consistent differences in WTP and similarly no consistent group differences in brain activations. This study replicates our previous study extending it to a different type of cosmetic. The right dlPFC activity during the use of cosmetics may be a potential brain-based personalization or product selection process biomarker.
Jacob, a Synapto-Nuclear Protein Messenger Linking N-methyl-D-aspartate Receptor Activation to Nuclear Gene Expression
Authors: Grochowska Katarzyna M. , Bär Julia , Gomes Guilherme M. , Kreutz Michael R. , Karpova Anna
Published: December 2021

Pyramidal neurons exhibit a complex dendritic tree that is decorated by a huge number of spine synapses receiving excitatory input. Synaptic signals not only act locally but are also conveyed to the nucleus of the postsynaptic neuron to regulate gene expression. This raises the question of how the spatio-temporal integration of synaptic inputs is accomplished at the genomic level and which molecular mechanisms are involved. Protein transport from synapse to nucleus has been shown in several studies and has the potential to encode synaptic signals at the site of origin and decode them in the nucleus. In this review, we summarize the knowledge about the properties of the synapto-nuclear messenger protein Jacob with special emphasis on a putative role in hippocampal neuronal plasticity. We will elaborate on the interactome of Jacob, the signals that control synapto-nuclear trafficking, the mechanisms of transport, and the potential nuclear function. In addition, we will address the organization of the Jacob/NSMF gene, its origin and we will summarize the evidence for the existence of splice isoforms and their expression pattern.
Dietary Magnesium Intake Affects the Association Between Serum Vitamin D and Type 2 Diabetes: A Cross-Sectional Study
Authors: Huang Weichao , Ma Xiaoman , Liang Hualiang , Li Haojia , Chen Jiayu , Fang Liujia , Yang Qilin , Zhang Zhenhui
Published: December 2021

Introduction: Circulating vitamin D concentrations have been associated with the risk of type 2 diabetes (T2D). Magnesium has also been reported to be associated with lower T2D risk. Besides, magnesium is an essential cofactor for vitamin D activation. However, the effect of dietary magnesium intake on the association between vitamin D and the risk of T2D has not been studied comprehensively. Therefore, we designed this cross-sectional study to assess the effect modification of magnesium intake on the association between vitamin D and risk of T2D.

Research Design and Methods: The present study analyzed data from the National Health and Nutrition Examination Survey (NHANES) continuously from 2007 to 2014, involving 10,249 participants. By having stratified participants based on magnesium intake category (low magnesium intake <267 mg/day; high magnesium intake: ≥267 mg/day), we further evaluated the difference (interaction test) between the relationship of vitamin D with the risk of T2D among low magnesium intake participants and high magnesium intake participants using weighted multivariable logistic regression.

Results: In this cross-sectional study, the association of serum vitamin D with the incidence of T2D appeared to differ between the low magnesium intake group and the high magnesium intake group (OR: 0.968, 95%Cl: 0.919–1.02 vs. OR: 0.925, 95%Cl: 0.883–0.97). Furthermore, there was evidence of interaction between vitamin D levels and magnesium intake on decreasing the incidence of T2D (p-value for interaction = 0.001).

Conclusions: The results of our study indicated that magnesium intake might affect the association of serum vitamin D with the risk of T2D. Such a finding requires further randomized controlled trials to provide more evidence.
Risk Factors Related to Acute Radiation Dermatitis in Breast Cancer Patients After Radiotherapy: A Systematic Review and Meta-Analysis
Authors: Xie Yuxiu , Wang Qiong , Hu Ting , Chen Renwang , Wang Jue , Chang Haiyan , Cheng Jing
Published: December 2021

Background

Acute radiation dermatitis (ARD) is the most common acute response after adjuvant radiotherapy in breast cancer patients and negatively affects patients’ quality of life. Some studies have reported several risk factors that can predict breast cancer patients who are at a high risk of ARD. This study aimed to identify patient- and treatment-related risk factors associated with ARD.

Methods

PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and WanFang literature databases were searched for studies exploring the risk factors in breast cancer patients. The pooled effect sizes, relative risks (RRs), and 95% CIs were calculated using the random-effects model. Potential heterogeneity and sensitivity analyses by study design, ARD evaluation scale, and regions were also performed.

Results

A total of 38 studies composed of 15,623 breast cancer patients were included in the analysis. Of the seven available patient-related risk factors, four factors were significantly associated with ARD: body mass index (BMI) ≥25 kg/m2 (RR = 1.11, 95% CI = 1.06–1.16, I2 = 57.1%), large breast volume (RR = 1.02, 95% CI = 1.01–1.03, I2 = 93.2%), smoking habits (RR = 1.70, 95% CI = 1.24–2.34, I2 = 50.7%), and diabetes (RR = 2.24, 95% CI = 1.53–3.27, I2 = 0%). Of the seven treatment-related risk factors, we found that hypofractionated radiotherapy reduced the risk of ARD in patients with breast cancer compared with that in conventional fractionated radiotherapy (RR = 0.28, 95% CI = 0.19–0.43, I2 = 84.5%). Sequential boost and bolus use was significantly associated with ARD (boost, RR = 1.91, 95% CI = 1.34–2.72, I2 = 92.5%; bolus, RR = 1.94, 95% CI = 1.82–4.76, I2 = 23.8%). However, chemotherapy regimen (RR = 1.17, 95% CI = 0.95–1.45, I2 = 57.2%), hormone therapy (RR = 1.35, 95% CI = 0.94–1.93, I2 = 77.1%), trastuzumab therapy (RR = 1.56, 95% CI = 0.18–1.76, I2 = 91.9%), and nodal irradiation (RR = 1.57, 95% CI = 0.98–2.53, I2 = 72.5%) were not correlated with ARD. Sensitivity analysis results showed that BMI was consistently associated with ARD, while smoking, breast volume, and boost administration were associated with ARD depending on study design, country of study, and toxicity evaluation scale used. Hypofractionation was consistently shown as protective. The differences between study design, toxicity evaluation scale, and regions might explain a little of the sources of heterogeneity.

Conclusion

The results of this systematic review and meta-analysis indicated that BMI ≥ 25 kg/m2 was a significant predictor of ARD and that hypofractionation was consistently protective. Depending on country of study, study design, and toxicity scale used, breast volume, smoking habit, diabetes, and sequential boost and bolus use were also predictive of ARD.
A New Dynamic Response to Therapy Assessment in Postoperative Patients With Low-Risk Differentiated Thyroid Cancer Treated Without Radioactive Iodine
Authors: Dong Ping , Wang Li , Xiao Liu , Yang Liu , Huang Rui , Li Lin
Published: December 2021

Background

Total thyroidectomy (TT) or lobectomy without radioactive iodine (RAI) is becoming a common management for patients with low-risk differentiated thyroid cancer (DTC). However, the assessment of response to therapy for these patients remains controversial. The aim of this study was to propose and validate a new dynamic evaluation strategy to assess the response to therapy in patients with low-risk DTC treated with TT or lobectomy but without RAI.

Methods

We performed a retrospective analysis of 543 adult patients with low-risk DTC who underwent TT or lobectomy without RAI therapy. Follow-up consisted of trends of serum thyroglobulin (Tg), anti-thyroglobulin antibody (TgAb) levels and neck ultrasonography (US) were conducted every 6–24 months. Response to therapy assessments were defined as excellent response, biochemical incomplete response, structural incomplete response, and indeterminate response according to the follow-up findings.

Results

At a median follow-up of 51 months (range 33–66 months), 517 (95%) had excellent response, while the other 26 had either biochemical incomplete response (an increasing trend of suppressed serum Tg levels, n=9; an increasing trend of TgAb levels, n=3) or indeterminate response (a stable or decreasing trend of suppressed serum Tg levels, but a stable positive trend of TgAb levels, n=14). No patients had structural incomplete response or no deaths related to thyroid cancer. The risk of incomplete response was significantly higher in lobectomy than in TT (p<0.001).

Conclusion

Our study proposed and validated a new dynamic response to therapy assessment depending on trends of suppressed serum Tg, TgAb levels, and neck US findings which could be an appropriate tool for postoperative follow-up in low-risk DTC patients without RAI therapy. Our findings provided further evidence to support no routine recommendation of RAI after surgery in low-risk DTC.
Comprehensive Analysis of m6A Regulators Characterized by the Immune Cell Infiltration in Head and Neck Squamous Cell Carcinoma to Aid Immunotherapy and Chemotherapy
Authors: Yang Zhiqiang , Ming Xiaoping , Huang Shuo , Yang Minlan , Zhou Xuhong , Fang Jiayu
Published: December 2021

Background

N6-Methyladenosine (m6A), which is a prevalent regulator of mRNA expression, has gathered increasing study interests. Though the role of m6A as being important in many biological processes (such as growth and proliferation of cancers) has been well documented, its potential role in tumor immune microenvironment (TIME) has rarely been analyzed.

Methods

We downloaded RNA expression, single nucleotide polymorphism (SNP), and copy number variation (CNV) data from The Cancer Genome Atlas (TCGA). We then curated 21 m6A regulators and clustered patients into three m6A subtypes and m6A-related gene subtypes and compared them based on overall survival (OS). The combination of CIBERSORT as well as ssGSEA quantified the infiltration levels of immune cells and immune-related functions. The m6A scores were determined by using principal component analysis (PCA) algorithm. Furthermore, we evaluate the correlation of m6A regulators with immune and response to therapy.

Results

Three m6A clusters were identified based on the TCGA-HNSCC cohort, and there were significant associations among them in overall outcomes and caner-related pathways. We found that three m6A clusters were consistent with three phenotypes: immune-inflamed, immune-dessert, and immune-excluded. HNSCC patients were divided into high– and low–m6A score groups based on the cutoff of m6A score. Patients with lower m6A score had better overall survival outcome. Further analysis indicated that patients with higher m6A score presented higher tumor mutation burden (TMB). In addition, patients in low–m6A score subgroup had high chemotherapeutics sensitivity. GEO cohort confirmed patients with low m6A score demonstrated significant overall survival advantages and clinical benefits. Low m6A score carry an increased neoantigen load, eliciting a response to immunotherapy, and its value in predicting survival outcomes of immunotherapy was also confirmed in three anti-PD-1 cohorts.

Conclusions

Our study demonstrated that m6A regulators are closely related to TIME and the m6A score was an effective prognostic biomarker and predictive indicator for immunotherapy and chemotherapeutics. Comprehensive evaluation of m6A regulators in tumors will extend our understanding of TIME and effectively guide increasing study investigations on immunotherapy and chemotherapy strategies for HNSCC.
A Review on the Role of AFAP1-AS1 in the Pathoetiology of Cancer
Authors: Ghafouri-Fard Soudeh , Khoshbakht Tayybeh , Hussen Bashdar Mahmud , Taheri Mohammad , Mokhtari Majid
Published: December 2021

AFAP1-AS1 is a long non-coding RNA which partakes in the pathoetiology of several cancers. The sense protein coding gene from this locus partakes in the regulation of cytophagy, cell motility, invasive characteristics of cells and metastatic ability. In addition to acting in concert with AFAP1, AFAP1-AS1 can sequester a number of cancer-related miRNAs, thus affecting activity of signaling pathways involved in cancer progression. Most of animal studies have confirmed that AFAP1-AS1 silencing can reduce tumor volume and invasive behavior of tumor cells in the xenograft models. Moreover, statistical analyses in the human subjects have shown strong correlation between expression levels of this lncRNA and clinical outcomes. In the present work, we review the impact of AFAP1-AS1 in the carcinogenesis.
Extraction, Structural Characterization, and Anti-Hepatocellular Carcinoma Activity of Polysaccharides From Panax ginseng Meyer
Authors: Jia Hui , Zhao Bin , Zhang Fangfang , Santhanam Ramesh Kumar , Wang Xinying , Lu Jincai
Published: December 2021

Polysaccharides are the main active ingredients of ginseng. To extract the most effective polysaccharides against hepatocellular carcinoma (HCC), we isolated and characterized the polysaccharides from the mountain cultivated ginseng (MCG) and compared their composition and cytotoxic effect with cultivated ginseng (CG) polysaccharide against HepG2 cell lines for the first time. MCG polysaccharides and CG polysaccharides were fractionated into two fractions such as MTPS-1, MTPS-2 and CTPS-1, CTPS-2 by salting out, respectively. Compared to CG, MCG possessed appreciable cytotoxic effect against HepG2 cells among that MTPS-1 possess fortified effect. Then, MTPS-1 was selected for further isolation process and seven acidic polysaccharides (MCGP-1–MCGP-7) were obtained using ethanol precipitation, ion-exchange, and gel permeation chromatography techniques. Structural characteristics of the polysaccharides (MCGP-1–MCGP-7) were done by adapting methylation/GC-MS and NMR analysis. Overall, MCGP-3 polysaccharide was found to possess significant cytotoxic effect against HepG2 cells with the IC50 value.
Sex Differences of Periaqueductal Grey Matter Functional Connectivity in Migraine
Authors: Gecse Kinga , Baksa Daniel , Dobos Dóra , Aranyi Csaba Sandor , Galambos Attila , Kocsel Natália , Szabó Edina , Kökönyei Gyöngyi , Emri Miklós , Bagdy Gyorgy , Juhasz Gabriella
Published: December 2021

The existence of “sex phenotype” in migraine is a long-standing scientific question. Fluctuations of female sex hormones contribute to migraine attacks, and women also have enhanced brain activity during emotional processing and their functional brain networks seem to be more vulnerable to migraine-induced disruption compared to men. Periaqueductal grey matter (PAG) is a core region of pain processing and modulation networks with possible sex-related implications in migraine. In our study, sex differences of PAG functional resting-state connectivity were investigated in the interictal state in 32 episodic migraines without aura patients (16 women and 16 men). A significant main effect of sex was detected in PAG connectivity with postcentral, precentral, and inferior parietal gyri, and further differences were found between right PAG and visual areas (superior occipital gyrus, calcarine, and cuneus), supplementary motor area, and mid-cingulum connectivity. In all cases, PAG functional connectivity was stronger in female migraineurs compared to males. However, higher average pain intensity of migraine attacks correlated with stronger connectivity of PAG and middle temporal, superior occipital, and parietal gyri in male migraineurs compared to females. Migraine-related disability is also associated with PAG connectivity but without sex differences. Our results indicate that sex differences in PAG connectivity with brain regions involved in sensory and emotional aspects of pain might contribute to the “sex-phenotype” in migraine. The stronger functional connectivity between PAG and pain processing areas may be a sign of increased excitability of pain pathways even in resting-state in females compared to male migraineurs, which could contribute to female vulnerability for migraine. However, pain intensity experienced by male migraineurs correlated with increased connectivity between PAG and regions involved in the subjective experience of pain and pain-related unpleasantness. The demonstrated sex differences of PAG functional connectivity may support the notion that the female and male brain is differently affected by migraine.
NCS Assessments of the Motor, Sensory, and Physical Health Domains
Authors: Clark Jane E. , Pate Russell , Rine Rose Marie , Christy Jennifer , Dalton Pamela , Damiano Diane L. , Daniels Stephen , Holmes Jonathan M. , Katzmarzyk Peter T. , Magasi Susan , McCreery Ryan , McIver Kerry , Newell Karl M. , Sanger Terence , Sugden David , Taveras Elsie , Hirschfeld Steven
Published: December 2021

As part of the National Children's Study (NCS) comprehensive and longitudinal assessment of the health status of the whole child, scientific teams were convened to recommend assessment measures for the NCS. This manuscript documents the work of three scientific teams who focused on the motor, sensory, or the physical health aspects of this assessment. Each domain team offered a value proposition for the importance of their domain to the health outcomes of the developing infant and child. Constructs within each domain were identified and measures of these constructs proposed. Where available extant assessments were identified. Those constructs that were in need of revised or new assessment instruments were identified and described. Recommendations also were made for the age when the assessments should take place.
A Retrospective Analysis of Rituximab Treatment for B Cell Depletion in Different Pediatric Indications
Authors: Wennmann Merlin , Kathemann Simone , Kampmann Kristina , Ohlsson Sinja , Büscher Anja , Holzinger Dirk , Della Marina Adela , Lainka Elke
Published: December 2021

Background: Rituximab (RTX) is used in cancer therapy as well as in the treatment of autoimmune diseases and alloimmune responses after transplantation. It depletes the disease-causing B cells by binding to the CD (cluster of differentiation) 20 antigen. We evaluate different pediatric treatment protocols (via fixed treatment schedule, B cell- or symptom-controlled) and their therapeutic effects.

Methods: Demographic information, clinical and laboratory characteristics, and special laboratory values such as immunoglobulin G (IgG), CD19 positive B cells and Epstein-Barr viral load were retrospectively analyzed in children treated with RTX between 2008 and 2016.

Results: Seventy-six patients aged 1 to 19 (median 13) years were treated with 259 RTX infusions. The spectrum of diseases was very heterogeneous. RTX led to a complete depletion of the B cells. The reconstitution time varied between patients and was dependent on the application schedule (median 11.8 months). Fourteen out of 27 (52%) patients developed hypogammaglobulinaemia. The risk of IgG deficiency was 2.6 times higher in children under 4 years of age than in olderones. In the last group IgG deficiency developed in only 38% of the cases (n = 8). Recurrent and severe infections were observed each in 11/72 (15%) patients. Treatment-related reactions occurred in 24/76 (32%) cases; however, treatment had to be discontinued in only 1 case. In 16/25 (76%), the Epstein-Barr viral load dropped below the detection limit after the first RTX infusion.

Conclusion: RTX is an effective and well-tolerated drug for the treatment of oncological diseases as well as autoimmune and alloimmune conditions in children. B cell depletion and reconstitution varies both intra- und interindividually, suggesting that symptom-oriented and B cell-controlled therapy may be favorable. Treatment-related reactions, IgG deficiency and infections must be taken into account.
Biopsy or Biomarker? Children With Minimal Change Disease Have a Distinct Profile of Urinary Epidermal Growth Factor
Authors: Lodeweyckx Niels , Wouters Kristien , Ledeganck Kristien J. , Trouet Dominique
Published: December 2021

Background: In this study, the profile of urinary EGF excretion (uEGF/uCreat) was mapped in children presenting with prolonged proteinuria or with nephrotic syndrome refractory to or dependent of steroids. We investigated whether uEGF/uCreat could be linked to the underlying biopsy result, taking into account its response to immunosuppressive medication and to ACE inhibition, as well as genetic predisposition.

Methods: Ninety-eight pediatric patients with initial presentation of nephrotic syndrome or prolonged proteinuria were included in this study, along with 49 healthy controls and 20 pediatric Alport patients. All patients had a normal kidney function and were normotensive during the course of the study, whether or not under ACE inhibition. In repeated urine samples, uEGF was measured and concentration was normalized by urine creatinine. In order to compare diagnosis on kidney biopsy, genetic predisposition and response of uEGF/uCreat to immunosuppression and to ACE inhibition, uEGF/uCreat is studied in a linear mixed effects model.

Results: Patients with Minimal Change Disease (MCD) showed a significantly different profile of uEGF/uCreat in comparison to healthy children, as well as compared to patients with Focal Segmental Glomerulosclerosis (FSGS) or another glomerulopathy on kidney biopsy. The response of uEGF/uCreat to ACE inhibition was absent in minimal change disease and contrasted with an impressive beneficial effect of ACE inhibition on uEGF/uCreat in FSGS and other proteinuric glomerulopathies. Absence of a genetic predisposition was also associated with a significantly lower uEGF/uCreat.

Conclusions: Despite preserved kidney function, children with a proteinuric or nephrotic glomerular disease on kidney biopsy show a significantly lower uEGF/uCreat, indicative of early tubulo-interstitial damage, which appears reversible under ACE inhibition in any underlying glomerulopathy except in minimal change disease. In view of the distinct profile of uEGF/uCreat in minimal change disease compared to other glomerulopathies, and the link between genetic predisposition and uEGF/uCreat, our study suggests that uEGF/uCreat can be a helpful tool to decide on the need for a renal biopsy in order to differentiate minimal change disease from other proteinuric glomerular diseases.
Radiofrequency Ablation a Safe and Effective Treatment for Pediatric Benign Nodular Thyroid Goiter
Authors: Lin An-Ni , Lin Wei-Che , Cheng Kai-Lun , Luo Sheng-Dean , Chiang Pi-Ling , Chen Wei-Chih , Chen Yueh-Sheng , Wang Cheng-Kang , Kan Na-Ning , Su Yan-Ye
Published: December 2021

Purpose: To evaluate the effectiveness of radiofrequency ablation (RFA) for benign thyroid nodules in pediatric patients.

Materials and Methods: Twelve pediatric patients (11 female, 1 male; mean age 15.54 ± 2.8 years, range 10–19 years) with benign thyroid nodules (mean longest diameter 4.1 ± 1.4 cm, range 1.5–5.9 cm) treated by RFA from 2017 to 2020 were evaluated. The inclusion criteria for RFA therapy were (i) age < 20 years; (ii) benign cytological confirmation by 2 separate ultrasound guided fine-needle aspiration cytology (FNAC) or core needle biopsies; (iii) pressure symptoms or cosmetic problems caused by thyroid nodules; (iv) absence of any sonographic suspicious feature; and (v) follow-up for >6 months. Under local anesthesia, RFA was performed with the use of an RF generator and an 18-gauge internally cooled electrode. Volume changes in nodules on follow-up ultrasonography (US), changes in symptomatic and cosmetic scores, and complications arising during or after RFA were evaluated.

Results: Mean follow-up period was 24.9 ± 13.9 months (range 6–43 months). At the last follow-up visits, volume of the nodule had decreased significantly (15.34 ± 11.52 mL vs. 4.07 ± 4.99 mL; P < 0.05), whereas volume reduction rate was 74.31% ± 19.59%. Both cosmetic and compressive symptoms were also significantly improved (2.91 ± 0.79 vs. 0.92 ± 0.67 and 1.5 ± 1.93 vs. 0.17 ± 0.39; P < 0.05). The mean number of ablation sessions was 1.4 ± 0.6 (range 1–3 sessions), and one of the patients suffered from transient vocal cord palsy which was spontaneously resolved 53 days later.

Conclusions: RFA is a safe and effective treatment for benign thyroid nodules in pediatric patients, and can thus serve as an alternative treatment for thyroidectomy.
Exposure to an Extended-Interval, High-Dose Gentamicin Regimen in the Neonatal Period Is Not Associated With Long-Term Nephrotoxicity
Authors: Rypdal Veronika , Jørandli Sondre , Hemmingsen Dagny , Solbu Marit Dahl , Klingenberg Claus
Published: December 2021

Objectives: To assess the association between gentamicin exposure and subclinical signs of nephrotoxicity in school children who were exposed to a high-dose gentamicin regimen in the neonatal period.

Methods: Children receiving three or more doses (6 mg/kg) of gentamicin as neonates were invited to a follow-up in school age. We evaluated potential signs of subclinical nephrotoxicity with four validated urine biomarkers: protein-creatinine ratio (PCR), albumin-creatinine ratio (ACR), kidney injury molecule-1 (KIM-1), and N-acetyl-beta-D-glucosaminidase (NAG) normalized for urine creatinine (NAG-Cr). In addition, blood pressure was measured. The measures of gentamicin exposure were cumulative dose (mg/kg) and highest trough plasma concentration (TPC) in mg/L. We used logistic and linear regression and non-parametric kernel regression to analyze the relationship between gentamicin exposure and the urine biomarkers.

Results: A total of 222 gentamicin exposed children were included. As neonates, the children were exposed to a median (interquartile range-IQR) cumulative gentamicin dose of 36 (26–42) mg/kg and the median (IQR) TPC was 1.0 (0.7–1.3) mg/L. At follow-up, 15 children (6.8%) had either one abnormal urine biomarker value (13 children) or two abnormal urine biomarker values (2 children). These 17 biomarker values were all marginally above the suggested upper cutoff, and included the following markers; KIM-1 (n = 2), NAC-Cr (n = 5), ACR (n = 6), and PCR (n = 4). All other 207 children had normal sets of all four urine biomarkers. One child had hypertension. There were no differences in gentamicin exposure, gestational age (GA) at birth or birth weight between the group of 15 children with one or two abnormal urine biomarker values compared to the other 207 children who had normal biomarker values. Using different regression analyses, we did not find any association between gentamicin exposure (cumulative dose and/or TPC) and the urine biomarker values.

Conclusions: Exposure to an extended-interval, high-dose gentamicin regimen in the neonatal period was not associated with signs of subclinical nephrotoxicity in schoolchildren. We therefore suggest that the gentamicin treatment regimen evaluated in this study is safe in terms of long-term nephrotoxicity.

Clinical Trial Registration:ClinicalTrials.gov, identifier: NCT03253614.
Increased Arterial Stiffness Is Associated With Reduced Diastolic Function in Youth With Obesity and Type 2 Diabetes
Authors: Madsen Nicolas L. , Haley Jessica E. , Moore Ryan A. , Khoury Philip R. , Urbina Elaine M.
Published: December 2021

Background: Increased arterial stiffness is associated with diastolic dysfunction in adults. Data in youth are lacking, so we examined the impact of arterial stiffness on diastolic function in youth.

Methods: We obtained diastolic function and augmentation index, pulse wave velocity, brachial artery distensibility, and carotid stiffness on 612 youth [10–24 years, 65% female, 38% normal weight, 36% obese, and 26% with type 2 diabetes mellitus (T2DM)]. Participants were classified as compliant (C) vs. stiff (S) arteries based on seven arterial stiffness parameters [Global Stiffness Index (GSI), S = GSI > 4). Mean differences in covariates were evaluated by Student's t-tests. A stepwise regression analysis was performed to determine if GSI was an independent predictor of diastolic function.

Results: Lower diastolic function and more adverse cardiovascular disease (CVD) risk factors were present in the S group (n = 67) than the C group (n = 545) (p < 0.001). Covariates that were associated with diastolic dysfunction were higher GSI, male sex, higher body mass index (BMI), and systolic blood pressure (SBP) z-score (R2 = 0.18 to 0.25; p ≤ 0.05).

Conclusion: Adverse diastolic function is seen in youth with increased arterial stiffness independent of CVD risk factors. Interventions to improve arterial stiffness prior to clinical onset of diastolic dysfunction are needed to prevent development of heart failure.
Endocan: A Novel Marker for Colchicine Resistance in Familial Mediterranean Fever Patients?
Authors: Omma Ahmet , Armaǧan Berkan , Güven Serdar Can , Sandıkçı Sevinç Can , Çolak Seda , Yücel Çiǧdem , Küçükşahin Orhan , Erden Abdulsamet
Published: December 2021

Introduction: Familial Mediterranean fever (FMF) patients had 5–10% colchicine resistance. Although FMF attacks are characterized by acute phase elevation, there are no biomarkers that can show colchicine resistance yet. The serum endocan levels may elevate in inflammatory and auto-inflammatory diseases.

Objectives: This study aimed to evaluate serum endocan levels in FMF patients according to whether attack and colchicine resistance or not and also compare them with classical acute phase reactants.

Methods: In this single-center and cross-sectional study, a total of 111 FMF patients and 60 healthy individuals were enrolled. All patients' basic demographic and clinical data were recorded and blood samples were collected.

Results: A total of 46 (41.4%) FMF patients had colchicine resistance. In comparison to the FMF patients according to colchicine response, colchicine resistance patients had a significantly higher median (IQR) endocan levels than colchicine responsive patients [36.98 ng/ml (97.41) vs. 13.57 ng/ml (27.87), p = 0.007], but there were no differences between in terms of median ESR and CRP levels. Inversely, serum endocan levels were similar during an attack and attack-free period in FMF patients, although ESR and CRP levels were significantly different. Interestingly, the highest serum endocan levels were in the control group.

Conclusion: In conclusion, serum endocan levels were higher in colchicine resistance than colchicine responsive patients, but attack state had no effect on serum endocan levels in our study. Unlike ESR and CRP, serum endocan may be a novel biomarker for detection of colchicine resistance and distinguish the FMF attacks.
Case Report: Development of Type 1 Autoimmune Pancreatitis in an Adolescent With Ulcerative Colitis Mimicking Pancreatic Cancer
Authors: Choi Sujin , Lee Hae Jeong , Seo An Na , Bae Han Ik , Kwon Hyung Jun , Cho Chang Min , Lee So Mi , Choe Byung-Ho , Kang Ben
Published: December 2021

Introduction: Autoimmune pancreatitis (AIP) is a rare extraintestinal manifestation of inflammatory bowel disease (IBD) which is typically responsive to corticosteroid treatment.

Case Presentation: We report a case of a 17-year-old male diagnosed with ulcerative colitis who subsequently developed acute pancreatitis. Blood tests demonstrated elevated pancreatic enzyme levels of amylase (1319 U/L) and lipase (809 U/L). Abdominal computed tomography revealed peripancreatic fat stranding and the presence of a perisplenic pseudocyst. Azathioprine and mesalazine were stopped as possible causes of drug-induced pancreatitis. However, pancreatic enzymes remained elevated and corticosteroid treatment was started. Despite corticosteroid therapy, amylase and lipase levels continued to increase. Infliximab was started due to a flare in gastrointestinal symptoms of ulcerative colitis. Follow-up abdominal ultrasonography revealed a pancreatic tail mass. Tumor markers, including CA 19-9, were elevated and atypical cells were seen on histological examination of an endoscopic ultrasonography-guided fine needle aspiration biopsy. Surgical pancreaticosplenectomy was performed for suspected pancreatic neoplasm. Surprisingly, histology revealed chronic pancreatitis with storiform fibrosis and infiltration of IgG4-positive cells, compatible with AIP type 1. Thereafter, pancreatic enzymes gradually decreased to normal levels and the patient has been in remission for 9 months on infliximab monotherapy.

Conclusion: Pediatric gastroenterologists should keep in mind that AIP may develop during the natural course of pediatric IBD. Moreover, the development of pancreatic fibrosis may be non-responsive to corticosteroid treatment and mimic pancreatic neoplasia.
Sini San Inhibits Chronic Psychological Stress-Induced Breast Cancer Stemness by Suppressing Cortisol-Mediated GRP78 Activation
Authors: Zheng Yifeng , Zhang Juping , Huang Wanqing , Zhong Linda L. D. , Wang Neng , Wang Shengqi , Yang Bowen , Wang Xuan , Pan Bo , Situ Honglin , Lin Yi , Liu Xiaoyan , Shi Yafei , Wang Zhiyu
Published: December 2021

Chronic psychological stress is closely correlated with breast cancer growth and metastasis. Sini San (SNS) formula is a classical prescription for relieving depression-related symptoms in traditional Chinese medicine (TCM). Current researches have suggested that chronic psychological stress is closely correlated with cancer stem cells (CSCs) and endoplasmic reticulum (ER) stress. This study aimed to investigate the effects of chronic psychological stress on ER stress-mediated breast cancer stemness and the therapeutic implication of SNS. Chronic psychological stress promoted lung metastasis in 4T1 breast tumor-bearing mice and increased the stem cell-like populations and stemness-related gene expression. Meanwhile, GRP78, a marker of ER stress, was significantly increased in the breast tumors and lung metastases under chronic psychological stress. As a biochemical hallmark of chronic psychological stress, cortisol dramatically enhanced the stem cell-like populations and mammospheres formation by activating GRP78 transcriptionally. However, GRP78 inhibitors or shRNA attenuated the stemness enhancement mediated by cortisol. Similarly, SNS inhibited chronic psychological stress-induced lung metastasis and stemness of breast cancer cells, as well as reversed cortisol-induced stem cell-like populations and mammospheres formation by attenuating GRP78 expression. Co-localization and co-immunoprecipitation experiments showed that SNS interrupted the interaction between GRP78 and LRP5 on the cell surface, thus inhibiting the Wnt/β-catenin signaling of breast CSCs. Altogether, this study not only uncovers the biological influence and molecular mechanism of chronic psychological stress on breast CSCs but also highlights SNS as a promising strategy for relieving GRP78-induced breast cancer stemness via inhibiting GRP78 activation.
Pharmacogenetics Based Dose Prediction Model for Initial Tacrolimus Dosing in Renal Transplant Recipients
Authors: Srinivas Lekshmy , Gracious Noble , Nair Radhakrishnan R.
Published: December 2021

Tacrolimus, an immunosuppressant used in solid organ transplantation, has a narrow therapeutic index and exhibits inter-individual pharmacokinetic variability. Achieving and maintaining a therapeutic level of the drug by giving appropriate doses is crucial for successful immunosuppression, especially during the initial post-transplant period. We studied the effect of CYP3A5, CYP3A4, and ABCB1 gene polymorphisms on tacrolimus trough concentrations in South Indian renal transplant recipients from Kerala to formulate a genotype-based dosing equation to calculate the required starting daily dose of tacrolimus to be given to each patient to attain optimal initial post-transplant period drug level. We also investigated the effect of these genes on drug-induced adverse effects and rejection episodes and looked into the global distribution of allele frequencies of these polymorphisms. One hundred forty-five renal transplant recipients on a triple immunosuppressive regimen of tacrolimus, mycophenolate mofetil, and steroid were included in this study. Clinical data including tacrolimus daily doses, trough levels (C0) and dose-adjusted tacrolimus trough concentration (C0/D) in blood at three time points (day 6, 6 months, and 1-year post-transplantation), adverse drug effects, rejection episodes, serum creatinine levels, etc., were recorded. The patients were genotyped for CYP3A5*3, CYP3A4*1B, CYP3A4*1G, ABCB1 G2677T, and ABCB1 C3435T polymorphisms by the PCR-RFLP method. We found that CYP3A5*3 polymorphism was the single most strongly associated factor determining the tacrolimus C0/D in blood at all three time points (p < 0.001). Using multiple linear regression, we formulated a simple and easy to compute equation that will help the clinician calculate the starting tacrolimus dose per kg body weight to be administered to a patient to attain optimal initial post-transplant period tacrolimus level. CYP3A5 expressors had an increased chance of rejection than non-expressors (p = 0.028), while non-expressors had an increased risk for new-onset diabetes mellitus after transplantation (NODAT) than expressors (p = 0.018). Genotype-guided initial tacrolimus dosing would help transplant recipients achieve optimal initial post-transplant period tacrolimus levels and thus prevent the adverse effects due to overdose and rejection due to inadequate dose. We observed inter-population differences in allele frequencies of drug metabolizer and transporter genes, emphasizing the importance of formulating population-specific dose prediction models to draw results of clinical relevance.
Ethnobotanical Survey on Skin Whitening Prescriptions of Traditional Chinese Medicine in Taiwan
Authors: Ko Chien-Yu , Chao Jung , Chen Pei-Yu , Su Shan-Yu , Maeda Tomoji , Lin Chin-Yu , Chiang Hung-Che , Huang Shyh-Shyun
Published: December 2021

The increasing interest and demand for skin whitening products globally, particularly in Asia, have necessitated rapid advances in research on skin whitening products used in traditional Chinese medicine (TCM). Herein, we investigated 74 skin whitening prescriptions sold in TCM pharmacies in Taiwan. Commonly used medicinal materials were defined as those with a relative frequency of citation (RFC) > 0.2 and their characteristics were evaluated. Correlation analysis of commonly used medicinal materials was carried out to identify the core component of the medicinal materials. Of the purchased 74 skin whitening prescriptions, 36 were oral prescriptions, 37 were external prescriptions, and one prescription could be used as an oral or external prescription. After analysis, 90 traditional Chinese medicinal materials were obtained. The Apiaceae (10%; 13%) and Leguminosae (9%; 11%) were the main sources of oral and external medicinal materials, respectively. Oral skin whitening prescriptions were found to be mostly warm (46%) and sweet (53%), while external skin whitening prescriptions included cold (43%) and bitter (29%) medicinal materials. Additionally, mainly tonifying and replenishing effects of the materials were noted. Pharmacological analysis indicated that these medicinal materials may promote wound healing, treat inflammatory skin diseases, or anti-hyperpigmentation. According to the Spearman correlation analysis on interactions among medicinal materials with an RFC > 0.2 in the oral skin whitening prescriptions, Paeonia lactiflora Pall. (white) and Atractylodes macrocephala Koidz. showed the highest correlation (confidence score = 0.93), followed by Ziziphus jujuba Mill. (red) and Astragalus propinquus Schischkin (confidence score = 0.91). Seven medicinal materials in external skin whitening prescriptions with an RFC > 0.2, were classified as Taiwan qī bái sàn (an herbal preparation), including Angelica dahurica (Hoffm.) Benth. & Hook. f. ex Franch. & Sav., Wolfiporia extensa (Peck) Ginns, Bletilla striata (Thunb.) Rchb. f., Atractylodes macrocephala Koidz., Ampelopsis japonica (Thunb.) Makino, Paeonia lactiflora Pall. (white), and Bombyx mori Linnaeus. Skin whitening prescriptions included multiple traditional Chinese medicinal materials. Despite the long history of use, there is a lack of studies concerning skin whitening products, possibly due to the complex composition of traditional Chinese medicine. Further studies are required to assess the efficacy and safety of these traditional Chinese medicinal materials for inclusion in effective, safe, and functional pharmacological products.