bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcranial Direct Current Stimulation of the Dorsolateral Prefrontal Cortex for Treatment of Neuropsychiatric Disorders
Authors: Li Qing , Fu Yu , Liu Chang , Meng Zhiqiang 
Published: June 2022

BackgroundThe dorsolateral prefrontal cortex (DLPFC) is a key node of the frontal cognitive circuit. It is involved in executive control and many cognitive processes. Abnormal activities of DLPFC are likely associated with many psychiatric diseases. Modulation of DLPFC may have potential beneficial effects in many neural and psychiatric diseases. One of the widely used non-invasive neuromodulation technique is called transcranial direct current stimulation (or tDCS), which is a portable and affordable brain stimulation approach that uses direct electrical currents to modulate brain functions.ObjectiveThis review aims to discuss the results from the past two decades which have shown that tDCS can relieve clinical symptoms in various neurological and psychiatric diseases.MethodsHere, we performed searches on PubMed to collect clinical and preclinical studies that using tDCS as neuromodulation technique, DLPFC as the stimulation target in treating neuropsychiatric disorders. We summarized the stimulation sites, stimulation parameters, and the overall effects in these studies.ResultsOverall, tDCS stimulation of DLPFC could alleviate the clinical symptoms of schizophrenia, depression, drug addiction, attention deficit hyperactivity disorder and other mental disorders.ConclusionThe stimulation parameters used in these studies were different from each other. The lasting effect of stimulation was also not consistent. Nevertheless, DLPFC is a promising target for non-invasive stimulation in many psychiatric disorders. TDCS is a safe and affordable neuromodulation approach that has potential clinical uses. Larger clinical studies will be needed to determine the optimal stimulation parameters in each condition.
RETRACTED: Obesity Accelerates Leukocyte Telomere Length Shortening in Apparently Healthy Adults: A Meta-Analysis
Authors: Khosravaniardakani Sheida , Bokov Dmitry Olegovich , Mahmudiono Trias , Hashemi Seyedeh Sedigheh , Nikrad Negin , Rabieemotmaen Shadi , Abbasalizad-Farhangi Mahdieh 
Published: June 2022

BackgroundShorter telomere length is associated with numerous comorbidities. Several studies have investigated the role of obesity in telomere shortening. In the current systematic review and meta-analysis, we summarized the results of studies that evaluated the association between obesity and telomere length.MethodsA systematic search from Scopus, PubMed, Embase, and ProQuest electronic databases up to 19 March 2021 without language restriction was performed and after data extraction and screening, 19 manuscripts were eligible to be included in the final meta-synthesis.ResultsThe highest category of telomere length was associated with an approximate 0.75 kg/m2 reduction in body mass index (BMI; WMD = −0.75 kg/m2; CI = −1.19, −0.31; p &lt; 0.001; I2 = 99.4%). Moreover, overweight/obese individuals had 0.036 kbp shorter telomere length compared with non-overweight/obese adults (WMD = −0.036; CI = −0.05, −0.02; p = 0.030; I2 = 100%). According to the results of subgroupings, continent, age, and sample size could be possible sources of heterogeneity.ConclusionFrom the results, it was clear that obesity was associated with shorter telomere length. Because of the observational design of included studies, the causality inference of results should be done with caution; thus, further longitudinal studies are warranted for better inference of causal association.
Characteristics, Prognosis, and Competing Risk Nomograms of Cutaneous Malignant Melanoma: Evidence for Pigmentary Disorders
Authors: Li Zichao , Li Xinrui , Yi Xiaowei , Li Tian , Huang Xingning , Ren Xiaoya , Ma Tianyuan , Li Kun , Guo Hanfeng , Chen Shengxiu , Ma Yao , Shang Lei , Song Baoqiang , Hu Dahai 
Published: June 2022

PurposeCutaneous malignant melanoma (CMM) always presents as a complex disease process with poor prognosis. The objective of the present study was to explore the influence of solitary or multiple cancers on the prognosis of patients with CMM to better understand the landscape of CMM.MethodsWe reviewed the records of CMM patients between 2004 and 2015 from the Surveillance, Epidemiology, and End Results Program. The cumulative incidence function was used to represent the probabilities of death. A novel causal inference method was leveraged to explore the risk difference to death between different types of CMM, and nomograms were built based on competing risk models.ResultsThe analysis cohort contained 165,043 patients with CMM as the first primary malignancy. Patients with recurrent CMM and multiple primary tumors had similar overall survival status (p = 0.064), while their demographics and cause-specific death demonstrated different characteristics than those of patients with solitary CMM (p &lt; 0.001), whose mean survival times are 75.4 and 77.3 months and 66.2 months, respectively. Causal inference was further applied to unveil the risk difference of solitary and multiple tumors in subgroups, which was significantly different from the total population (p &lt; 0.05), and vulnerable groups with high risk of death were identified. The established competing risk nomograms had a concordance index &gt;0.6 on predicting the probabilities of death of CMM or other cancers individually across types of CMM.ConclusionPatients with different types of CMM had different prognostic characteristics and different risk of cause-specific death. The results of this study are of great significance in identifying the high risk of cause-specific death, enabling targeted intervention in the early period at both the population and individual levels.
Preoperative and Noninvasive Prediction of Gliomas Histopathological Grades and IDH Molecular Types Using Multiple MRI Characteristics
Authors: Du Ningfang , Zhou Xiaotao , Mao Renling , Shu Weiquan , Xiao Li , Ye Yao , Xu Xinxin , Shen Yilang , Lin Guangwu , Fang Xuhao , Li Shihong 
Published: June 2022

Background and PurposeGliomas are one of the most common tumors in the central nervous system. This study aimed to explore the correlation between MRI morphological characteristics, apparent diffusion coefficient (ADC) parameters and pathological grades, as well as IDH gene phenotypes of gliomas.MethodsPreoperative MRI data from 166 glioma patients with pathological confirmation were retrospectively analyzed to compare the differences of MRI characteristics and ADC parameters between the low-grade and high-grade gliomas (LGGs vs. HGGs), IDH mutant and wild-type gliomas (IDHmut vs. IDHwt). Multivariate models were constructed to predict the pathological grades and IDH gene phenotypes of gliomas and the performance was assessed by the receiver operating characteristic (ROC) analysis.ResultsTwo multivariable logistic regression models were developed by incorporating age, ADC parameters, and MRI morphological characteristics to predict pathological grades, and IDH gene phenotypes of gliomas, respectively. The Noninvasive Grading Model classified tumor grades with areas under the ROC curve (AUROC) of 0.934 (95% CI=0.895-0.973), sensitivity of 91.2%, and specificity of 78.6%. The Noninvasive IDH Genotyping Model differentiated IDH types with an AUROC of 0.857 (95% CI=0.787-0.926), sensitivity of 88.2%, and specificity of 63.8%.ConclusionMRI features were correlated with glioma grades and IDH mutation status. Multivariable logistic regression models combined with MRI morphological characteristics and ADC parameters may provide a noninvasive and preoperative approach to predict glioma grades and IDH mutation status.
Patient-Derived Organoid Serves as a Platform for Personalized Chemotherapy in Advanced Colorectal Cancer Patients
Authors: Geevimaan Khamushavalli , Guo Jing-You , Shen Chia-Ning , Jiang Jeng-Kai , Fann Cathy S. J. , Hwang Ming-Jing , Shui Jr-Wen , Lin Hsiu-Ting , Wang Mei-Jung , Shih Hsuan-Cheng , Li Anna Fen-Yau , Chang Shih-Ching , Yang Shung-Haur , Chen Jeou-Yuan 
Published: June 2022

BackgroundAddition of oxaliplatin to adjuvant 5-FU has significantly improved the disease-free survival and served as the first line adjuvant chemotherapy in advanced colorectal cancer (CRC) patients. However, a fraction of patients remains refractory to oxaliplatin-based treatment. It is urgent to establish a preclinical platform to predict the responsiveness toward oxaliplatin in CRC patients as well as to improve the efficacy in the resistant patients.MethodsA living biobank of organoid lines were established from advanced CRC patients. Oxaliplatin sensitivity was assessed in patient-derived tumor organoids (PDOs) in vitro and in PDO-xenografted tumors in mice. Based on in vitro oxaliplatin IC50 values, PDOs were classified into either oxaliplatin-resistant (OR) or oxaliplatin-sensitive (OS) PDOs. The outcomes of patients undergone oxaliplatin-based treatment was followed. RNA-sequencing and bioinformatics tools were performed for molecular profiling of OR and OS PDOs. Oxaliplatin response signatures were submitted to Connectivity Map algorithm to identify perturbagens that may antagonize oxaliplatin resistance.ResultsOxaliplatin sensitivity in PDOs was shown to correlate to oxaliplatin-mediated inhibition on PDO xenograft tumors in mice, and parallelled clinical outcomes of CRC patients who received FOLFOX treatment. Molecular profiling of transcriptomes revealed oxaliplatin-resistant and -sensitive PDOs as two separate entities, each being characterized with distinct hallmarks and gene sets. Using Leave-One-Out Cross Validation algorithm and Logistic Regression model, 18 gene signatures were identified as predictive biomarkers for oxaliplatin response. Candidate drugs identified by oxaliplatin response signature-based strategies, including inhibitors targeting c-ABL and Notch pathway, DNA/RNA synthesis inhibitors, and HDAC inhibitors, were demonstrated to potently and effectively increase oxaliplatin sensitivity in the resistant PDOs.ConclusionsPDOs are useful in informing decision-making on oxaliplatin-based chemotherapy and in designing personalized chemotherapy in CRC patients.
Distinguishing Tumor Admixed in a Radiation Necrosis (RN) Background: 1H and 2H MR With a Novel Mouse Brain-Tumor/RN Model
Authors: Ge Xia , Song Kyu-Ho , Engelbach John A. , Yuan Liya , Gao Feng , Dahiya Sonika , Rich Keith M. , Ackerman Joseph J. H. , Garbow Joel R. 
Published: June 2022

PurposeDistinguishing radiation necrosis (RN) from recurrent tumor remains a vexing clinical problem with important health-care consequences for neuro-oncology patients. Here, mouse models of pure tumor, pure RN, and admixed RN/tumor are employed to evaluate hydrogen (1H) and deuterium (2H) magnetic resonance methods for distinguishing RN vs. tumor. Furthermore, proof-of-principle, range-finding deuterium (2H) metabolic magnetic resonance is employed to assess glycolytic signatures distinguishing RN vs. tumor.Materials and MethodsA pipeline of common quantitative 1H MRI contrasts, including an improved magnetization transfer ratio (MTR) sequence, and 2H magnetic resonance spectroscopy (MRS) following administration of 2H-labeled glucose, was applied to C57BL/6 mouse models of the following: (i) late time-to-onset RN, occurring 4–5 weeks post focal 50-Gy (50% isodose) Gamma Knife irradiation to the left cerebral hemisphere, (ii) glioblastoma, growing ~18–24 days post implantation of 50,000 mouse GL261 tumor cells into the left cerebral hemisphere, and (iii) mixed model, with GL261 tumor growing within a region of radiation necrosis (1H MRI only). Control C57BL/6 mice were also examined by 2H metabolic magnetic resonance.ResultsDifferences in quantitative 1H MRI parametric values of R1, R2, ADC, and MTR comparing pure tumor vs. pure RN were all highly statistically significant. Differences in these parameter values and DCEAUC for tumor vs. RN in the mixed model (tumor growing in an RN background) are also all significant, demonstrating that these contrasts—in particular, MTR—can effectively distinguish tumor vs. RN. Additionally, quantitative 2H MRS showed a highly statistically significant dominance of aerobic glycolysis (glucose ➔ lactate; fermentation, Warburg effect) in the tumor vs. oxidative respiration (glucose ➔ TCA cycle) in the RN and control brain.ConclusionsThese findings, employing a pipeline of quantitative 1H MRI contrasts and 2H MRS following administration of 2H-labeled glucose, suggest a pathway for substantially improving the discrimination of tumor vs. RN in the clinic.
A Novel Model Combining Tumor Length, Tumor Thickness, TNM_Stage, Nutritional Index, and Inflammatory Index Might Be Superior to the 8th TNM Staging Criteria in Predicting the Prognosis of Esophageal Squamous Cell Carcinoma Patients Treated With Definitive Chemoradiotherapy
Authors: Chen Xiaohui , Yu Yilin , Wu Haishan , Qiu Jianjian , Ke Dongmei , Wu Yahua , Lin Mingqiang , Liu Tianxiu , Zheng Qunhao , Zheng Hongying , Yang Jun , Wang Zhiping , Li Hui , Liu Lingyun , Yao Qiwei , Li Jiancheng , Cheng Wenfang 
Published: June 2022

BackgroundWe aimed to determine whether the tumor length and tumor thickness should be used as prognostic factors for esophageal squamous cell carcinoma (ESCC) patients treated with definitive chemoradiotherapy (dCRT).MethodsA retrospective analysis consists of 902 non-operative ESCC patients received dCRT. The nomogram was used to predict the survival. Besides, Restricted Cubic Splines (RCS) was used to examine the relationship between prognostic factors and survival outcomes. Finally, the prognostic index (PI) scores were constructed according to the tumor length and tumor thickness, and the patients were divided into the low-, medium-, and high-risk groups.ResultsThe median follow-up of overall survival (OS) and progression-free survival (PFS) were 23.0 months and 17.5 months. Multivariate Cox regression analysis showed that tumor length and tumor thickness were independent prognostic factors associated with survival. Our novel nomograms for OS and PFS were superior to the TNM classification (p &lt; 0.001). Besides, RCS analysis demonstrated that the death hazard of tumor length and tumor thickness sharply increased at 7.7 cm and 1.6 cm (p &lt; 0.001). Finally, there were significant differences for ESCC patients with clinical TNM stage group of the OS and PFS in different risk groups. The higher risk group was significantly associated with shorter OS and PFS in ESCC patients (both p &lt; 0.001 for all).ConclusionThe study results suggest that the novel models integrating tumor length and tumor thickness may provide a simple and widely available method for evaluating the prognosis of non-operative ESCC patients. The tumor length and tumor thickness should be considered as prognostic factors for ESCC.
Influence of Nanobubble Size Distribution on Ultrasound-Mediated Plasmid DNA and Messenger RNA Gene Delivery
Authors: Kida Hiroshi , Feril Loreto B. , Irie Yutaka , Endo Hitomi , Itaka Keiji , Tachibana Katsuro 
Published: June 2022

The use of nanobubbles (NBs) for ultrasound-mediated gene therapy has recently attracted much attention. However, few studies have evaluated the effect of different NB size distribution to the efficiency of gene delivery into cells. In this study, various size of albumin stabilized sub-micron bubbles were examined in anin vitroultrasound (1 MHz) irradiation setup in the aim to compare and optimize gene transfer efficiency. Results with pDNA showed that gene transfer efficiency in the presence of NB size of 254.7 ± 3.8 nm was 2.5 fold greater than those with 187.3 ± 4.8 nm. Similarly, carrier-free mRNA transfer efficiency increased in the same conditions. It is suggested that NB size greater than 200 nm contributed more to the delivery of genes into the cytoplasm with ultrasound. Although further experiments are needed to understand the underlying mechanism for this phenomenon, the present results offer valuable information in optimizing of NB for future ultrasound-mediate gene therapy.
Recombinant EGFL7 Mitigated Pressure Overload-Induced Cardiac Remodeling by Blocking PI3Kγ/AKT/NFκB Signaling in Macrophages
Authors: Li Lei , Zhao Ying , Hu Ying , Wang Xiaohui , Jin Qun , Zhao Ying 
Published: June 2022

Inflammation and endothelial dysfunction play an essential role in heart failure (HF). Epidermal growth factor-like protein 7 (EGFL7) is upregulated during pathological hypoxia and exerts a protective role. However, it is unclear whether there is a link between abnormal EGFL7 expression and inflammation in overload stress-induced heart failure. Our results showed that EGFL7 transiently increased during the early 4 weeks of TAC and in hypertensive patients without heart failure. However, it decreased to the basal line in the heart tissue 8 weeks post-transverse aortic constriction (TAC) or hypertensive patients with heart failure. Knockdown of EGFL7 with siRNA in vivo accelerated cardiac dysfunction, fibrosis, and macrophage infiltration 4 weeks after TAC. Deletion of macrophages in siRNA-EGFL7-TAC mice rescued that pathological phenotype. In vitro research revealed the mechanism. PI3Kγ/AKT/NFκB signaling in macrophages was activated by the supernatant from endothelial cells stimulated by siRNA-EGFL7+phenylephrine. More macrophages adhered to endothelial cells, but pretreatment of macrophages with PI3Kγ inhibitors decreased the adhesion of macrophages to endothelial cells. Ultimately, treatment with recombinant rmEGFL7 rescued cardiac dysfunction and macrophage infiltration in siRNA-EGFL7-TAC mice. In conclusion, EGFL7 is a potential inhibitor of macrophage adhesion to mouse aortic endothelial cells. The downregulation of EGFL7 combined with increased macrophage infiltration further promoted cardiac dysfunction under pressure overload stress. Mechanistically, EGFL7 reduced endothelial cell adhesion molecule expression and inhibited the PI3Kγ/AKT/NFκB signaling pathway in macrophages.
First Year Real Life Experience With Intravitreal Brolucizumab for Treatment of Refractory Neovascular Age-Related Macular Degeneration
Authors: Abdin Alaa Din , Aljundi Wissam , El Jawhari Khalil , Suffo Shady , Weinstein Isabel , Seitz Berthold 
Published: June 2022

Purpose: To assess the morphological and functional outcomes within the first year of treatment with intravitreal brolucizumab for refractory neovascular age-related macular degeneration (nAMD).Methods: This retrospective study included 21 eyes from 19 patients with refractory nAMD followed for 12 months. All patients were switched to brolucizumab after treatment with at least two other anti-vascular endothelial growth factors (VEGF). All eyes received 3x brolucizumab 6 mg/0.05 ml intravitreal injections (IVI) monthly as an upload phase. Then eyes received an IVI every 8 weeks with interval adjustment to every 12 weeks if disease activity was not present. Main outcome measures: best corrected visual acuity (BCVA), central macular thickness (CMT) and retinal fluid distribution. In addition, we reported the adverse event rate.Results: The number of previous anti-VEGF IVIs/eye was 36 ± 22 before switching to brolucizumab. BCVA (ETDRS) was 51 ± 16 before treatment and 50 ± 19 at week 52 (p = 0.6). CMT was 374 ± 158 μm before treatment and 298 ± 92 μm at week 52 (p = 0.01). The number of IVIs/eye decreased from 9.6 ± 1.9 IVIs in the last year before switching to 6.4 ± 0.9 IVIs in the first year after switching to brolucizumab (p &lt; 0.001). The rate of eyes with subretinal fluid and pigment epithelial detachment decreased at week 52. Finally, two cases of intraocular inflammation were observed as adverse events.Conclusion: In the first year of treatment, intravitreal brolucizumab was able to stabilize visual acuity with significantly less IVIs in patients with refractory nAMD. It also improved anatomic outcomes in these patients, particularly reducing subretinal fluid and pigment epithelial detachment and subsequently central macular thickness. However, two cases of intraocular inflammation were observed as adverse events.
Cost-Effectiveness of Pembrolizumab Plus Chemotherapy as First-Line Therapy for Advanced Oesophageal Cancer
Authors: Wu Meiyu , Qin Shuxia , Wang Liting , Tan Chongqing , Peng Ye , Zeng Xiaohui , Luo Xia , Yi Lidan , Wan Xiaomin 
Published: June 2022

Objective: Pembrolizumab plus chemotherapy is recommended as the first-line treatment for advanced oesophageal cancer. The objective of this study is to evaluate the cost-effectiveness of pembrolizumab plus chemotherapy as first-line therapy for advanced oesophageal cancer from the healthcare system perspective in China.Methods: Based on the KEYNOTE-590 trial, a Markov model was constructed to estimate the cost and effectiveness of pembrolizumab plus chemotherapy and placebo plus chemotherapy, respectively. Total costs, life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated. One-way, probabilistic sensitivity analyses (PSA), and subgroup analyses were adapted to test the model robustness.Result: Compared with the placebo group, pembrolizumab group obtained an additional 1.05 QALY, but the cost was also increased by $121,478.76. The ICER was $115,391.84 per QALY gained, which was higher than the willingness-to-pay (WTP) of $31,304.31. The results of One-way sensitivity analyses showed that the ICER was sensitive to the hazard ratio of PFS and per cycle cost of pembrolizumab. At a WTP threshold of $31,304.31, the probability of pembrolizumab plus chemotherapy being cost-effective was 0%.Conclusion: From the perspective of China healthcare system, pembrolizumab plus chemotherapy as first-line treatment is not cost-effective for patients with advanced oesophageal cancer compared with placebo plus chemotherapy.
In vitro Activity of Repurposed Nitroxoline Against Clinically Isolated Mycobacteria Including Multidrug-Resistant Mycobacterium tuberculosis
Authors: Hoffmann Ada Marie , Wolke Martina , Rybniker Jan , Plum Georg , Fuchs Frieder 
Published: June 2022

Antimicrobial treatment options for mycobacterial infections are limited due to intrinsic resistance and the emergence of acquired resistance in Mycobacterium tuberculosis. Isolates resisting first- and second line drugs are raising concerns about untreatable infections and make the development of new therapeutic strategies more pressing. Nitroxoline is an old oral antimicrobial that is currently repurposed for the treatment of urinary tract infection (UTI). In this study, we report the in vitro activity of nitroxoline against 18 clinical isolates of M. tuberculosis complex (MTBC) (M. tuberculosis N = 16, M. bovis BCG N = 1, M. bovis sp. bovis N = 1). Since nitroxoline achieves high concentrations in the urinary tract, we included all MTBC-isolates from urinary samples sent to our laboratory between 2008 and 2021 (University Hospital of Cologne, Germany). Isolates from other sources (N = 7/18) were added for higher sample size and for inclusion of drug-resistant M. tuberculosis isolates (N = 4/18). Based on our clinical routine the fluorescence-based liquid media system BACTEC MGIT 960 was used for susceptibility testing of nitroxoline and mainstay antitubercular drugs. Nitroxoline yielded a MIC90 of 4 mg/L for MTBC. In all M. tuberculosis isolates nitroxoline MICs were at least two twofold dilutions below the current EUCAST susceptibility breakpoint of ≤16 mg/L (limited to E. coli and uncomplicated UTI). In vitro activity of nitroxoline can be considered excellent, even in multidrug-resistant isolates. Future studies with in vivo models should evaluate a potential role of nitroxoline in the treatment of tuberculosis in the era of drug resistance.