bluuebunny/crossref_metadata_2025 huggingface dataset:
miR-203a-3p and MMP-2 protein are highly expressed in circulating tumor cells from patients with pancreatic carcinoma
Authors: Tarazona José Gabriel Rodríguez , Abdallah Emne Ali , Flores Bianca C. T. , Coutinho-Camillo Cláudia Malheiros , Marchi Fabio Albuquerque , Chinen Ludmilla Thomé Domingos
Published: May 2021

Objectives: to explore the morphological, molecular and phenotypical characteristics of circulating tumor cells (CTCs) from blood of patients with pancreatic carcinoma, and to correlate the findings with response to treatment, progression-free survival, overall survival (OS) and deep vein thrombosis (DVT). Methods: peripheral blood (10mL) was analyzed before the beginning of treatment, and after 60 and 120 days. CTCs were detected by ISET® and characterized by immunocytochemistry. For miRNAs analysis, peripheral leukocytes from the same patients and healthy individuals (controls) were collected in parallel at baseline. The expression of miRNAs was evaluated (in pool) using TaqMan™ Array Human MicroRNA Cards v2.0. Results: there were included 9 patients. The proteins MMP2 and TGFβ-RI were highly expressed (77.7%) in CTCs at baseline; at the first follow-up, MMP2 was predominant (80%) and at second follow-up, MMP2 and vimentin were predominant (50%). Circulating tumor microemboli (CTM) were found in two patients and both presented DVT. The miR-203a-3p was highly expressed in CTCs. miR-203a-3p is involved in the stimulation of epithelial-to-mesenchymal transition (EMT) and related to worse OS in pancreatic cancer (TCGA data). Conclusion: Due to the low number of patients and short follow-up, we did not observe a correlation between CTCs and response to treatment. However, there was a correlation between CTM and DVT as also miR-203a-3p was highly expressed in CTCs, corroborating the findings of EMT proteins. This study opens perspectives concerning the dynamic change in the pattern of proteins expressed along treatment and the use of miRNAs as new targets in pancreatic carcinoma.
Hypoxia-Responsive Nanoreactors to Amplify Oxidative Damage Through Multiple Cascaded Pathways for Promoting Photodynamic/Ferroptosis-Induced ROS Generation and Simultaneously Disrupting Tumor Antioxidant Defense System
Authors: Wang Xiaoyan , Wu Ming , Zhang Xiaolong , Li Feida , Zeng Yongyi , Lin Xinyi , Liu Xiaolong , Liu Jingfeng
Published: May 2021

Background: Photodynamic therapy (PDT), a typical reactive oxygen species (ROS)-dependent treatment with high controllability, has emerged as an alternative cancer therapy modality but its therapeutic efficacy is still unsatisfactory due to the limited light penetration and constant oxygen consumption. With the development of another ROS-dependent paradigm ferroptosis, several efforts have been made to conquer the poor efficacy by combining these two approaches; however the biocompatibility, tumor-targeting capacity and clinical translation prospect of current systems still exist great concerns. Herein, a novel hypoxia-responsive nanoreactor BCFe@SRF with sorafenib (SRF) loaded inside, constructed by covalently connecting chlorin e6 conjugated bovine serum albumin (BSA-Ce6) and ferritin through azobenzene (Azo) linker, were prepared to offer unmatched opportunities for high-efficient PDT and ferroptosis synergistic therapy.Results: The designed BCFe@SRF exhibited appropriate size distribution, stable dispersity, excellent ROS generation property, controllable drug release capacity, tumor accumulation ability, and outstanding biocompatibility. Importantly, the BCFe@SRF could be degraded under hypoxia environment to release BSA-Ce6 for laser-triggered PDT, ferritin for iron-catalyzed Fenton reaction and SRF for tumor antioxidative defense disruption. Meanwhile, besides PDT effects, it was found that BCFe@SRF mediated treatment upon laser irradiation in hypoxic environment not only could accelerate lipid peroxidation (LPO) generation but also could deplete intracellular glutathione (GSH) and glutathione peroxidase (GPX4) expression, which was believed as three symbolic events during ferroptosis. All in all, the BCFe@SRF nanoreactor, employing multiple cascaded pathways to promote intracellular ROS accumulation, presented remarkably outstanding antitumor effects both in vitro and in vivo.Conclusion: BCFe@SRF could serve as a promising candidate for synergistic PDT and ferroptosis therapy, which is applicable to boost oxidative damage within tumor site and will be informative to future design of ROS-dependent therapeutic nanoplatforms.
Machine learning-based prediction of cognitive trajectories among middle-aged and elderly Chinese adults
Authors: Wu Yafei , Jia Maoni , Xiang Chaoyi , Lin Shaowu , Jiang Zhongquan , Fang Ya
Published: May 2021

Background

Cognition represents heterogeneous in trajectories with increasing age. Early identification of such trend is essential for the prevention of high risk population related to cognition decline. This study aimed to explore the heterogeneity and determinants of cognitive trajectories, and construct prediction models for distinguishing cognitive trajectories among the middle-aged and elderly Chinese people at a community level.
Methods

Data was retrospectively collected from the China Health and Retirement Longitudinal Study with a consecutive survey in 3 waves (2011, 2013, 2015). The Mini-mental State Examination (MMSE) scale was used for cognitive measurement. The heterogeneity of cognitive trajectories was identified through mixed growth model, and the determinants of cognitive trajectories were analyzed by logistic regression. Machine learning (ML) algorithms, namely logistic regression (LR), support vector machine (SVM), and random forest (RF), combined with recursive feature elimination were used to predict cognitive trajectories using epidemiological variables. Area under the receiver operating characteristic curve (AUROC) and brier score were used to assess discrimination and calibration, respectively.
Results

Three cognitive trajectories were identified: “persistently-high” (PH, 83.3%) class with a high cognitive score in baseline and remained high subsequently, “medium-decrease” (MD, 6.6%) class with a medium cognitive score in baseline and a rapid decline subsequently, “low-increase” (LI, 10.1%) with the lowest baseline cognitive score and a rapid growth subsequently. For classification of PH vs. LI and MD vs. LI, the AUROCs of three ML methods were almost larger than 0.90, and brier scores were almost less than 0.10. For PH vs. MD, ML performed less well with the maximum AUROCs close to 0.68, while the calibration was still good. The initial MMSE score was the most significant predictors for distinguishing MD vs. LI and PH vs. LI, while age was the most important predictors in distinguishing MD vs. PH.
Conclusions

Prediction of cognitive trajectories and identification of its key predictors are of great significance for understanding the heterogeneity of cognitive trajectories as well as interventions for cognitive decline.
Machine Learning-Based Direct Solver for One-To-Many Problems on Temporal Shaping of Electron Beams
Authors: Wan Jinyu , Jiao Yi , Wu Juhao
Published: May 2021

To control the temporal profile of an electron beam to meet requirements of various advanced scientific applications, a widely-used technique is to manipulate the dispersion terms which turns out to be one-to-many problems. Due to their intrinsic one-to-many property, current popular stochastic optimization approaches on temporal shaping are not very effective, for being trapped into local optima or suggesting only one solution. Here we propose a real-time solver for one-to-many problems of temporal shaping, with the aid of a semi-supervised machine learning method, the conditional generative adversarial network (CGAN). We demonstrate that the CGAN solver can learn the one-to-many dynamics and is able to accurately and quickly predict the required dispersion terms for different custom temporal profiles. This machine learning-based solver overcomes the limitation of the stochastic optimization methods and is expected to have the potential for wide applications to one-to-many problems in other scientific fields.
Fine Structure Constant derived from Principle Theory.
Authors: Geilhaupt Manfred
Published: May 2021

Derivation of mass (m), charge (e) and fine structure constant (FSC) from theory are unsolved problems in physics up to now. Neither the Standard Model (SM) nor the General theory of Relativity (GR) has provided a complete explanation for the existence of the rest mass, i.e. restmass of the electron. The question “of what is rest mass” is therefore still essentially unanswered. We will show that the combination of two Principle Theories, General Relativity and Thermodynamics (TD), is able to derive the restmass of an electron (m) which surprisingly depends on the (Sommerfeld) FSC. Same to the charge (e).
Efficacy of a New-generation Platelet-rich Fibrin in the Treatment of Periodontal Intrabony Defects: a Randomized Clinical Trial
Authors: Csifo-Nagy Boroka Klara , Solyom Eleonora , Bognar Vera Lili , Nevelits Annamaria , Dori Ferenc
Published: May 2021

Background: The aim of the study was to clinically evaluate the healing of intrabony defects after treatment with a new generation of platelet-rich fibrin (A-PRF+) respect to enamel matrix derivatives (EMD). Methods: Thirty (30) intrabony defects of 18 patients (9 males, 9 females) were randomly treated with A-PRF+ (test, n=15) or EMD (control, n=15). The following clinical parameters were recorded at baseline and 6 months after surgery: pocket depth (PD), gingival recession (GR) and clinical attachment level (CAL). After debridement the intrabony defects were filled with A-PRF+ in the test group, respectively with EMD in the control group, and fixed with sutures to ensure wound closure and stability.Results: Both treatment methods resulted in statistically significant PD reductions, respectively CAL gains six months post-operatively. No statistically significant differences were found between the two groups as the mean CAL gain was 2.33±1.58 mm in the A-PRF+ group, respectively 2.60±1.18 mm in the EMD group (p < 0.001).Conclusion: Within the limits of this study the new-generation platelet-rich fibrin seems to be as clinically effective as EMD in the surgical treatment of intrabony defects. Treatment with A-PRF+ or EMD resulted in reliable clinical outcomes. The use of A-PRF+ as a human autologous product can give a positive impact on periodontal healing.Clinical Relevance: A-PRF+ may be suitable for the treatment of intrabony periodontal defects. Trial registration number (TRN): NCT04404374 (ClinicalTrials.gov ID)Date of registration: 19.05.2020., retrospectively registered
WP-UNet: Weight Pruning U-Net with Depth-wise Separable Convolutions for Semantic Segmentation of Kidney Tumours
Authors: Rao P Kiran , Chatterjee Subarna , Sha M Sreedhar
Published: May 2021

Background

Accurate semantic segmentation of kidney tumours in computed tomography (CT) images is difficult because tumours feature varied forms and, occasionally, look alike. The KiTs19 challenge sets the groundwork for future advances in kidney tumour segmentation.
Methods

We present WP-UNet, a deep network model that is lightweight with a small scale; it involves few parameters with a quick assumption time and a low floating-point computational complexity.
Results

We trained and evaluated the model with CT images from 300 patients. Thefindings implied the dominance of our method on the training Dice score (0.98) for the kidney tumour region. The proposed model only uses 1,297,441 parameters and 7.2e FLOPS, three times lower than those for other network models.
Conclusions

The results confirm that the proposed architecture is smaller than that of U-Net, involves less computational complexity, and yields good accuracy, indicating its potential applicability in kidney tumour imaging.
A Refined Procedure for Esophageal Resection Using a Full Minimally Invasive Approach
Authors: Ashiku Simon , Patel Ashish R. , Horton Brandon H. , Velotta Jeffrey , Ely Sora , Avins Andrew L.
Published: May 2021

Objective: Newer minimally invasive approaches to esophagectomy have brought substantial benefits to esophageal-cancer patients and continue to improve. We report here our experience with a streamlined procedure as part of a comprehensive perioperative-care program that provides additional advances in the continued evolution of this procedure.Methods: All patients with primary esophageal cancer referred for resection to the Oakland Medical Center of the Kaiser-Permanente Northern California health plan who underwent this approach between January 2013 and August 2018 were included. Operative and clinical outcome variables were extracted from the electronic medical record, operating-room files, and manual chart review.Results: 142 patients underwent the new procedure and care program; 121 (85.2%) were men with mean age of 64.5 years. 127 (89.4%) were adenocarcinoma; 117 (82.4%) were clinical stage III or IVA. 115 (81.0%) required no jejunostomy. Median hospital length-of-stay was 3 days and 8 (5.6%) patients required admission to the intensive care unit. Postoperative complications occurred in 22 (15.5%) patients within 30 days of the procedure. There were no inpatient deaths; one patient (0.7%) died within 30 days following discharge and three additional deaths (2.1%) occurred through 90 days of follow-up.Conclusions: This approach resulted in excellent clinical outcomes, including short hospital stays with limited need for the intensive care unit, few perioperative complications, and relatively few patients requiring feeding tubes on discharge. This comprehensive approach to esophagectomy is feasible and provides another clinically meaningful advance in the progress of minimally invasive esophagectomy. Further development and dissemination of this method is warranted.
Study on hyperspectral estimation model of soil organic carbon content in the wheat field under different water treatments
Authors: Yang Chenbo , Feng Meichen , Song Lifang , Wang Chao , Yang Wude , Xie Yongkai , Jing Binghan , Xiao Lujie , Zhang Meijun , Song Xiaoyan , Saleem Muhammad
Published: May 2021

Hyperspectral remote sensing technology can realize the rapid, real-time, and non-destructive monitoring of soil nutrient changes, which is of great significance to promote the development of precision agriculture. In this paper, 225 soil samples were taken as the research object to study the influence of different water treatment on soil organic carbon content, and the relationship between soil organic carbon content and spectral reflectance. After spectral preprocessing, the hyperspectral monitoring models of SOC content were constructed by partial least squares regression(PLSR) with five different sample allocation ratios of calibration to validation sets. The results showed that the effects of drought stress on SOC content were different in different growth stages of winter wheat. Results of correlation analysis showed that the differential transformation can refine the spectral characteristics and improve the correlation between SOC content and spectral reflectance. Results of model construction showed that the models constructed by second-order differential transformation were not effective, but the RPD values of the models were constructed by simple mathematical transformation(T0-T5) and first-order differential transformation(T6-T11) can reach more than 1.4. The simple mathematical transformation(T0-T2, T4-T5) and the first-order differential transformation(T6-T10) resulted in the highest RPD in mode 5 and mode 2, respectively. Among all the models, the model of T7 in mode 2 reach the highest accuracy with a RPD value of 1.9861. Therefore, it is necessary to consider the data preprocessing algorithm and allocation ratio in the construction of SOC hyperspectral monitoring model.
WITHDRAWN: Oral squamous cell carcinomas developing from oral lichen planus: Do they differ in recurrence and metastatic potential?
Authors: Blatt Sebastian , Sagheb Keyvan , Rahimi-Nedjat Roman-Kia , Sagheb Kawe , Lingawi Abdullatif , Schiegnitz Eik , Walter Christian
Published: May 2021

Background:
Due to the low proportion of squamous cell carcinomas of the oral cavity (OSCC) developing from oral lichen planus (OLP-OSCC) there is only little data regarding the frequency of lymph node metastasis and clinical characteristics such as relapse and outcome in this sub-entity. Therefore, a retrospective analysis of OLP- OSCC was performed.
Methods:
In a retrospective monocenter analysis, all consecutive patients with an OSCC treated in the time period 2000 to 2016 were composed. All patients with an OSCC developing from OLP/ OLLs were identified and analyzed for epidemiological data, risk profile, location of primary tumor, pTNM classification, lymph node metastasis, primary therapy, recurrence, and outcome.
Results:
A total of 103 patients (45%♂/ 55%♀) with an average age of 62 ± 14y were included in this study. At the time of initial diagnosis, 17% (n = 18) of patients had cervical metastases (CM) whereas only 11% (11 patients) displayed advanced tumor sizes (T > 2). T-status (p = 0.003) and histopathological grading (p = 0.001) had an impact on the incidence of CM. 39.6% of the patients developed a relapse after an average of 24 months with a mean of two recurrences per patient. Advanced tumor size had a significant impact on the 5-year overall survival and was associated with disease free survival of the patients (p < 0.001, respectively p = 0.004).
Conclusion:
Even if initial lymph node metastases were not found more frequent, more aggressive recurrence patterns compared to OSCC could be demonstrated for OLP-OSCC. Therefore, a modified recall for these patients might be necessary.
Validation of the Efficacy of the NUTRISCORE for Nutritional Screening of Cancer Patients in China
Authors: KANG Junren , LI Hailong , SHI Xiaodong , MA Enling , CHEN Wei
Published: May 2021

Background: Malnutrition is common in cancer patients. The NUTRISCORE was a newly developed cancer-specific nutritional screening tool and validated by reference to the Patient-Generated Subjective Global Assessment (PG-SGA) and Malnutrition Screening Tool (MST) in Spain. We aimed to evaluate the performance of NUTRISCORE, MST, and PG-SGA in estimating the risk of malnutrition in Chinese cancer patients.Methods: Data from an open parallel and multicenter cross-section study in 29 clinical teaching hospitals in 14 Chinese cities were used. Cancer patients were assessed for malnutrition using PG-SGA, NUTRISCORE, and MST. The sensitivity, specificity, and areas under the receiver operating characteristic curve were estimated for NUTRISCORE and MST using PG-SGA as a reference.Results: A total of 1000 cancer patients were included. The mean age was 55.9 (19 to 92 years), and 47.5% were male. 450 patients (45.0%) had PG-SGA B and C, 29 patients (2.9%) had a NUTRISCORE ≥ 5, and 367 patients (36.7%) had MST ≥ 2. With PG-SGA as a reference method, the sensitivity, specificity, and area under the curve values of the NUTRISCORE was 6.2 %, 99.8%, and 0.53, respectively. The sensitivity, specificity, and area under the curve values of the MST were 50.9%, 74.9%, and 0.63, respectively. The kappa index between NUTRISCORE and the PG-SGA were 0.066 and 0.262 between MST and the PG-SGA (P < 0.05).Conclusions: NUTRISCORE was found a higher specificity and lower sensitivity compared with MST using PG-SGA as a reference method in cancer patients in China. Further studies are needed.
Autophagic degradation of CDK2 and CDK4 is responsible for NVP-BEZ235-induced G0/G1 cell cycle arrest in neuroblastoma
Authors: Liu Zhen , Zhang Hong–Liang , Liu Shan-Ling , Zhang Chao , Yue Qing-Xi , Zhang Quan-Wu , Gao Feng-Hou
Published: May 2021

Background

Cyclin-dependent kinases (CDKs) are regarded as promising targets for cancer therapy. CDK2 and CDK4 are the core molecules in the G0 and G1 phases of the cell cycle. Exploring the molecular mechanism of CDK2 and CDK4 protein degradation will provide clues and solutions to control the G0 and G1 phases in tumor cells.
Methods

The expression levels of CDK2 and CDK4 were assessed by Western blotting and qRT-PCR. Cell viability, cell proliferation and growth were evaluated in CCK-8 and flow cytometric analysis. Protein interactions were analysed by immunoprecipitation and immunofluorescence methods.
Results

NVP-BEZ235 induced neuroblastoma cell arrest at the G0/G1 phase, and proliferation inhibition was associated with a significant reduction in the CDK2 and CDK4 proteins in a dose-dependent manner at nanomolar concentrations. Surprisingly, we found that the NVP-BEZ235-induced downregulation of CDK2 and CDK4 was dramatically rescued by autophagy-lysosome inhibitors. Additionally, the blockade of autophagy-related genes contributed to the remarkable rescue of CDK2 and CDK4, which thus strikingly improved NVP-BEZ235-induced G0/G1 arrest and growth inhibition of neuroblastoma cells. Subsequently, we observed the first evidence that NVP-BEZ235 induced the interaction of p62/SQSMT1 with CDK2 or CDK4 and the autophagic degradation of CDK2 and CDK4 in a cathepsin B-dependent manner. Analogous results regarding autophagy and the antiproliferative effects of NVP-BEZ235 were observed in a neuroblastoma xenograft mouse model in vivo.
Conclusions

These results not only established the pivotal role of the autophagy pathway in G0/G1 cell cycle-related protein turnover but also suggest the potential application of NVP-BEZ235 for cancer treatment by modulating elements of the autophagic machinery to promote degradation of G0/G1 cell cycle-related proteins.
A Phase II Study of Talimogene Laherparepvec for Patients With Inoperable Locoregional Recurrence of Breast Cancer
Authors: Kai Megumi , Marx Angela N. , Liu Diane D. , Shen Yu , Reuben James M. , Whitman Gary , Krishnamurthy Savitri , Ross Merrick I. , Litton Jennifer K. , Lim Bora , Ibrahim Nuhad , Kogawa Takahiro , Ueno Naoto T.
Published: May 2021

Purpose: Talimogene laherparepvec (T-VEC) is an immunotherapy that generates local tumor lysis and systemic antitumor immune response. We studied the efficacy of intratumoral administration of T-VEC as monotherapy for inoperable locoregional recurrence of breast cancer.Methods: Patients had to have cutaneous, subcutaneous, or nodal tumors injectable with T-VEC. T-VEC was injected intratumorally at 106 PFU/mL on day 1 (cycle 1), 108 PFU/mL on day 22 (cycle 2), and 108 PFU/mL every 2 weeks thereafter (cycles ≥3). Local lesions were photographed before each cycle.Results: Nine patients were enrolled, 6 with only locoregional disease and 3 with both locoregional and distant disease. No patient completed the planned 10 cycles or achieved complete or partial response. The median number of cycles administered was 4 (range, 3-8). Seven patients withdrew prematurely because of uncontrolled disease progression, 1 withdrew after cycle 3 because of fatigue, and 1 withdrew after cycle 4 for reasons unrelated to study treatment. Median progression-free survival and overall survival were 77 days (95% CI, 63-NA) and 361 days (95% CI, 240-NA). Two patients received 8 cycles with clinically stable disease as the best response. The most common grade 2 or higher adverse event was injection site reaction (n=7, 78%).Conclusion: None of the patients was able to complete the planned 10 cycles due to the disease progression. Future studies could examine whether combining intratumoral T-VEC with concurrent systemic therapy produces better outcomes.Trial registration number and date of registration: ClinicalTrials.gov Identifier: NCT02658812; registered [January 14, 2016]
Recurrent Brain Metastases: The Role of Resection of in a Comprehensive Multidisciplinary Treatment Setting
Authors: Hessler Nadine , Jünger Stephanie T , Meissner Anna-Katharina , kocher Martin , Goldbrunner Roland H , Grau Stefan Josef
Published: May 2021

BackgroundTo evaluate the efficacy of surgical resection for pretreated, recurrent brain metastases (BM) in a comprehensive multidisciplinary treatment setting.MethodsIn a retrospective single center study, patients were analyzed who had undergone surgical resection of recurrent BM between 2007 and 2019. Intracranial event-free survival (EFS) and overall survival (OS) were evaluated by Kaplan-Maier and Cox regression analysis.ResultsIn total, 107 patients with different primary tumor entities and individual previous treatment for BM were included. Primary tumors comprised non-small cell lung cancer (NSCLC) (37.4%), breast cancer (19.6%), melanoma (13.1%), gastro-intestinal cancer (10.3%) and other, rare entities (19.6%). The number of previous treatments of BM ranged from one to four; these comprised: resection only, focal or whole brain radiotherapy, brachytherapy and radiosurgery. BM-related symptoms were present in 73.8% of the patients. Median pre-operative Karnofsky Performance Score (KPS) was 70% (range 40-100) which was improved to 80% (range 0-100) after surgery. The complication rate was 26.2% and two patients died during the perioperative period. Postoperative local radio-oncologic and/or systemic therapy regimens were applied in 67 (62.6%) patients. Median postoperative EFS and OS were 7.1 (95%CI 5.8-8.2) and 11.1 (95%CI 8.4-13.6) months, respectively. The clinical status (postoperative KPS >70 (HR 0.27 95%CI 0.16-0.46; p<0.001) remained the only independent factor for survival in multivariate analysis. Conclusion Surgical resection of recurrent BM may improve the clinical status and thus OS but is associated with a high complication rate; therefore, careful patient selection is crucial.
CD36 Promotes Vasculogenic Mimicry in Melanoma by Mediating Adhesion to the Extracellular Matrix
Authors: Martini Carmela , DeNichilo Mark , King Danielle P. , Cockshell Michaelia P. , Ebert Brenton , Dale Brian , Ebert Lisa M. , Woods Anthony , Bonder Claudine S
Published: May 2021

Background: The formation of blood vessels within solid tumors directly contributes to cancer growth and metastasis. Until recently, tumor vasculature was thought to occur exclusively via endothelial cell (EC) lined structures (i.e. angiogenesis), but a second source of tumor vasculature arises from the cancer cells themselves, a process known as vasculogenic mimicry (VM). While it is generally understood that the function of VM vessels is the same as that of EC-lined vessels (i.e. to supply oxygen and nutrients to the proliferating cancer cells), the molecular mechanisms underpinning VM are yet to be fully elucidated. Methods: Human VM-competent melanoma cell lines were examined for their VM potential using the in vitro angiogenesis assays (Matrigel), together with inhibition studies using small interfering RNA and blocking monoclonal antibodies. Invasion assays and adhesion assays were used to examine cancer cell function. Results: Herein we demonstrate that CD36, a cell surface glycoprotein known to promote angiogenesis by ECs, also supports VM formation by human melanoma cancer cells. In silico analysis of CD36 expression within the melanoma cohort of The Cancer Genome Atlas suggests that melanoma patients with high expression of CD36 have a poorer clinical outcome. Using in vitro ‘angiogenesis’ assays and CD36-knockdown approaches, we reveal that CD36 supports VM formation by human melanoma cells as well as adhesion to, and invasion through, a cancer derived extracellular matrix substrate. Interestingly, thrombospondin-1 (TSP-1), a ligand for CD36 on ECs that inhibits angiogenesis, has no effect on VM formation. Further investigation revealed a role for laminin, but not collagen or fibronectin, as ligands for CD36 expressing melanoma cells. Conclusions: Taken together, this study suggests that CD36 is a novel regulator of VM by melanoma cancer cells that is facilitated, at least in part, via integrin-a3 and laminin. Unlike angiogenesis, VM is not perturbed by the presence of TSP-1, thus providing new information on differences between these two processes of tumor vascularization which may be exploited to combat cancer progression.
Predictor of Atrial Fibrillation Recurrence in Patients who Underwent a Tricuspid Valve Operation with Modified Cox Maze procedure
Authors: Bak Minjung , Park Sung-Ji , Jeong Dong Seop , Park Boram , Seo Jeong Hun , Park Ilkun , Kim Jihoon , Chung Su Ryeun , Kim Eun Kyoung , Sung Kiick
Published: May 2021

Background Recurrence of any atrial arrhythmia after surgical ablation is known as a negative predictor of cardiovascular events and total mortality. However, there have been no focused studies for atrial fibrillation (AF) recurrence prediction in patients with significant tricuspid regurgitation (TR), and the risk-benefit estimation of surgical ablation in tricuspid valve (TV) surgery is not fully established. Objectives In this study, we analyzed predictors of AF recurrence, safety, and efficacy of the modified Cox maze (CM) procedure in patients with AF undergoing TV operation.Method We screened 421 patients who underwent a TV operation between 1994 and 2017. After excluding patients who did not undergo a maze operation, 158 patients were enrolled. Enrolled patients were divided by recurrence of AF.We analyzed the difference between the AF recurrence group and no AF recurrence group, and AF recurrence factors in terms of clinical risk factors and echocardiographic risk factors. The hazard ratio (HR) and 95% confidence intervals (CIs) were presented using a Cox proportional hazard model.ResultS Among 158 patients, AF recurred in 65 patients within 10 years. For AF prediction, age was most the important clinical factor and right atrium (RA) diameter was the most important echocardiographic parameters. In patients with a larger RA diameter over 49.2mm, the prevalence of AF recurrence was higher (HR 4.322, 95% CI [2.185-8.549], log rank p value < 0.001). In clinical outcome, there was no significant difference between the AF recurrence group and the no recurrence group in terms of death, TR recurrence, heart failure and stroke. However, the risk of permanent pacemaker (PPM) insertion was higher in the AF recurrence group (HR 4.706, 95% CI [0.975-22.708], log rank p value 0.034) compared to the no recurrence group. Conclusion Age and RA enlargement are key predictors of AF recurrence after TV operation with the CM procedure in patients with significant TR.
Technology factor as society’s information stock: An elegant proof
Authors: Tao Yong
Published: May 2021

It has been empirically observed that the income structure of the vast majority of populations in market-economy countries follows an exponential distribution. The empirical evidence has covered more than 66 countries, ranging from Europe to Latin America, North America, and Asia. Here, to further support exponential income distribution as a signature of the well-functioning market economy, we empirically show how the income structure of China evolved towards an exponential distribution after the market-oriented economic reformation. In particular, we strictly prove that, if the income structure of an economy obeys an exponential distribution, the income summation over all households leads to a neoclassical aggregate production function, in which the technology factor is exactly equal to society’s information stock. This finding provides an insight into understanding the underlying implication of technological progress.JEL Classification: O33; D31; D83; C46
A nanofluidic device for rapid and multiplexed SARS-CoV-2 serological antibody detection
Authors: Mortelmans Thomas , Kazazis Dimitrios , Padeste Celestino , Berger Philipp , Li Xiaodan , Ekinci Yasin
Published: May 2021

The outbreak of COVID-19 has led to a substantial death toll and has hindered the functioning of modern society, sending the world into a medical and economic crisis1,2. This underlined the importance of point-of-care diagnostics, as well as accurate, cost-effective serological antibody tests as well as point-of-care diagnostics to monitor the viral spread and contain pandemics and endemics. Here, we present a three-dimensional (3D) nanofluidic device for rapid and multiplexed detection of viral antibodies. The device is designed to size-dependently immobilize particles from a multi-particle mixture at predefined positions in nanochannels through capillary forces only, resulting in distinct trapping lines. We show that individual lines can be used as an on-chip fluorescence-linked immunosorbent assay for multiplexed detection of serological immunoglobulin antibodies against viral proteins with high sensitivity. Further device versatility is exhibited by on-bead color multiplexing for simultaneous detection of IgG and IgM antibodies in convalescent human serum and by concurrent detection of anti-spike (SARS-CoV-2) and anti-hemagglutinin (Influenza A) antibodies. The device’s applications can be further extended to detect a plethora of diseases simultaneously in a reliable and straightforward manner.
I-int phenotype among three individuals of a Parsi community from Mumbai, India
Authors: Joshi S.R.
Published: May 2021

The red blood cells (RBCs) of most adult individuals display an I+i– phenotype, whereas those of newborns and some rare adult individuals are typed as I–i+. The phenotype in the latter category, designated as adult i, is under genetic influence as the RBCs of I+i+ individuals display strengths of I and i antigen expression intermediate to that of ordinary adults and ii-adults. As there was no information on the occurrence of adult i phenotype in the Indian population, the present study was undertaken. The RBCs of randomly selected subjects were screened with anti-I and anti-i reagents by a saline tube technique at 22°C. Individuals with unusual I and i antigen reactivity patterns were further tested by a semi-quantitative method with a battery of anti-I and anti-i reagents, followed by family studies. Three of the 5864 donors tested showed an elevated strength of i antigen. Further study revealed an intermediate strength of both I and i antigens compared with those on RBCs from adult and cord blood samples. All three probands came from an ethnic Parsi community. The phenotype (referred to as I-int) was shown to be inherited, being passed through two generations, but none of the members of the families had displayed an adult i phenotype. The I-int phenotype detected showed an ethnic association because all three subjects belonged to an endogamous Parsi community that has migrated to India some centuries ago from Persia, the present-day Iran.
Immunohematology

2014;30:11–13.
Drug-induced immune hemolytic anemia: the last 30 years of changes
Authors: Arndt P.A.
Published: May 2021

Drug-induced immune hemolytic anemia (DIIHA) is a rare condition that occurs primarily as a result of drug-induced antibodies, either drug-dependent or drug-independent. Drug-dependent antibodies can be detected by testing drug-treated red blood cells (RBCs) or untreated RBCs in the presence of a solution of drug. Drug-independent antibodies react with untreated RBCs (no drug added) and cannot be distinguished from warm autoantibodies. Many changes have occurred during the last 30 years, such as which drugs most commonly cause DIIHA, the optimal testing methods for identifying them, and the theories behind the mechanisms by which they react. This article reviews the major changes in DIIHA since the early 1980s involving the immune complex mechanism, cephalosporins, nonimmunologic protein adsorption, and penicillins. Because serologic results associated with DIIHA can mimic those expected with autoimmune hemolytic anemia or hemolytic transfusion reactions, DIIHA may go undetected in some cases.
Immunohematology

2014;30:44–54.
Directed blood donor program decreases donor exposure for children with sickle cell disease requiring chronic transfusion
Authors: Roberts D.O. , Covert B. , Lindsey T. , Edwards V. , McLaughlin L. , Theus J. , Wray R.J. , Jupka K. , Baker D. , Robbins M. , DeBaun M.R.
Published: May 2021

In children with sickle cell disease (SCD), primary and secondary prevention of strokes require indefinite regular blood transfusion therapy. The risks associated with repeated transfusions include alloimmunization and increased donor exposure. The Charles Drew Program is a directed blood donor program designed to lower donor exposure, decreasing the associated complications of transfusion; however, no evidence exists demonstrating the magnitude of the benefit to the recipient. Further, the use of extended red blood cell (RBC) antigen matching for C, E, and K has been well documented in a clinical trial setting but not extensively evaluated in a standard care setting. The goal of this study is to assess the effectiveness in reducing alloimmunization when matching for C, E, and K and the magnitude of the decrease in donor exposure in a directed blood donor program. The rate of alloimmunization and reduction of donor exposure were determined during the course of 1 year in a cohort of children with SCD who received regular directed donor blood transfusions. A total of 24 recipients were in the program, 16 females and 8 males, 4 to 20 years of age. During 2008, alloimmunization was 0 percent and donor exposure was reduced by 20 percent, compared with usual care. Extended RBC antigen matching has the same benefit as in a clinical trial setting for patients with SCD receiving blood transfusion therapy. Despite significant effort, we only achieved a modest decrease in donor exposure and cannot determine the immediate benefit of a directed blood donor program.
Immunohematology

2012;28:7–12.
Cartwright blood group system review
Authors: George M.R.
Published: May 2021

The Cartwright (Yt) blood group system consists of two antigens, Yta and Ytb, that result from point mutations in the acetylcholinesterase gene on chromosome 7q. Yta is a high-incidence antigen, whereas its antithetical antigen, Ytb, shows much lower incidence. Anti-Yta and anti-Ytb are relatively rare. Anti-Yta is more commonly found in individuals of Jewish descent. Cartwright antibodies are rarely clinically significant; however, cases of in vivo hemolysis have been reported, suggesting that clinical significance should be interpreted on a case-by-case basis.
Immunohematology

2012;28:49–54.
Should blood donors be routinely screened for irregular antibodies?
Authors: García M.A. , Bautista L. , Palomino F.
Published: May 2021

Alloantibody reactivity is approximately 0.3 percent in blood donors worldwide. The present study established total alloantibody and clinically significant alloantibody (CSAA) frequencies in all Colombian Red Cross National Blood Bank donors (almost all donors were Colombian). The probability of these alloantibodies reacting with a specific antigen in the general population was also determined, focusing on male CSAA data because routine practice in this blood bank is to discard female plasma components to avoid transfusion-related acute lung syndrome. Total blood donor population between 2007 and 2009 was 60,309 (55.4% male and 44.6% female). Cells I and II were used for alloantibody screening following the Autovue protocol. Positive samples were identified by red blood cell (RBC) panels (Panel A, Panel B, and Panel C, Ortho Clinical Diagnostics, Raritan, NJ). Alloantibody and CSAA frequency were established for both sexes. The database for RBC antigens estimated for the Colombian population was used for calculating the probability of antigen-antibody reaction from donors in this blood bank. Total alloantibodies (438) and CSAA frequency (138) were significantly higher in women than men (p < 0.01). Seventy-four percent of CSAA found in women came from the Rh blood group system. Calculated probability of generating antigen-antibody reaction using plasma only from male donors was estimated as 20.55 episodes for every 100,000 donations, and the probable number of events per year was 1.48. Meanwhile, considering all blood components from male and female origin, the calculated probability of antigen-antibody reaction was 123.54 episodes for every 100,000 donations and 28.67 probable events per year. The data presented here do not represent strong support for the routine screening of alloantibodies in blood donors.
Immunohematology

2012;28:60–6.
Paroxysmal cold hemoglobinuria: a case report
Authors: Wise S.C. , Tinsley S.H. , Cook L.O.
Published: May 2021

A 15-month-old white male child was admitted to the pediatric intensive care unit with symptoms of upper respiratory tract infection, increased somnolence, pallor, jaundice, fever, and decreased activity level. The purpose of this case study is to report the clinical findings associated with the patient’s clinical symptoms and differential laboratory diagnosis.
Immunohematology

2012;28:118–23.
Blood group antigen distribution in Lao blood donors
Authors: Keokhamphoui C. , Urwijitaroon Y. , Kongphaly D. , Thammavong T.
Published: May 2021

Blood group antigens can be distributed differently within different nationalities. Therefore, information about the prevalence of blood group antigens in the Lao population will be useful for providing better blood transfusion services in the Lao People’s Democratic Republic. The purpose of this study was to determine the prevalence of blood group antigens in Lao blood donors. Blood samples from 464 Lao national volunteer blood donors were typed for antigens in various blood group systems including ABO, MNS, P1PK, Rh, Kell, Lewis, Duffy, Kidd, and Diego. The results show similar antigen prevalence to that among Northeast Thais for ABO, MNS, P1PK, Rh, Kell, and Duffy systems. In the ABO system, O was the highest at 37.72 percent, followed by 35.56 percent B, 19.83 percent A1, 6.47 percent A1B, and 0.43 percent A2B. The common phenotypes were D+C+E–c– e+ at 60.43 percent, M+N–S–s+ at 46.55 percent, Fy(a+b–) at 80.82 percent, Jk(a+b+) at 39.44 percent, and kk at 99.72 percent. Interestingly, Le(a–b–) was found at 50.43 percent, which was significantly higher than previous reports in Thais and Taiwanese. The P1 antigen was found in only 18.97 percent, which is much lower than in Whites and Blacks. Rare phenotypes were Fy(a–b+) and Jk(a–b–), found at 0.22 percent and 4.31 percent, respectively. In terms of negative antigens the study shows 0.22 percent Fy(a–), 35.34 percent Jk(a–), 29.53 percent Jk(b–), 3.04 percent C−, 2.39 percent e−, and 5.17 percent M−. The high prevalence of C, e, and Fyaand immunogenicity of these antigens may induce alloimmunization in transfusion-dependent patients, creating difficulties providing blood from Lao donors. The information obtained from this study will be useful for improving transfusion therapy in the country, especially for estimation of the availability of compatible blood for patients who have produced antibodies.
Immunohematology

2012;28:132–6.
Performance characteristics of two automated solid-phase red cell adherence systems for pretransfusion antibody screening: a cautionary tale
Authors: Quillen K. , Caron J. , Murphy K.
Published: May 2021

Our institution has implemented two instruments, the Galileo and the Echo, that use different solid-phase red cell adherence assays for antibody screening in pretransfusion compatibility testing. During the initial implementation of these two instruments, we noticed very different problems: falsely positive results on the Galileo, and falsely negative results and lack of reproducibility on the Echo. Comparison of falsely positive antibody screen results from approximately equivalent numbers of samples run on the Galileo and samples tested by standard manual tube technique using low-ionic-strength saline enhancement showed a false-positive rate of 1.4 percent on the Galileo (defined as a positive screen with a negative panel). Testing using the Echo identified four cases of falsely negative antibody screens, (defined as a negative screen on a patient sample subsequently shown to be positive by the same method). In addition, we note a lack of reproducibility on the Echo, which emphasizes the importance of replicate testing during validation of automated antibody screening platforms.
Immunohematology

2012;28:137–9.
Scianna: the lucky 13th blood group system
Authors: Brunker P.A.R. , Flegel W.A.
Published: May 2021

The Scianna system was named in 1974 when it was appreciated that two antibodies described in 1962 in fact identified antithetical antigens. However, it was not until 2003 that the protein on which antigens of this system are found and the first molecular variants were described. Scianna was the last previously serologically defined, protein-based blood group system to be characterized at the molecular level, marking the end of an era in immunohematology. This story highlights the critical role that availability of laboratory reagents for serologic testing has played in the initial characterization of a blood group and sets the stage for the development of new reagents, such as recombinant proteins, to assist in this process. The central role that genetics has played, both by classical pedigree analysis and by molecular techniques, in the discovery and characterization of this blood group is reviewed.
Immunohematology

2011;27:41–57.
Prevalence of RHD*DOL and RHCE*ce(818T) in two populations
Authors: Halter Hipsky C. , da Costa D.C. , Omoto R. , Zanette A. , Castilho L. , Reid M.E.
Published: May 2021

The alleles RHCE*ceBI (RHCE*ce 48C, 712G, 818T, 1132G) and RHCE*ceSM (RHCE*ce 48C, 712G, 818T) encode the low-prevalence Rh antigen STEM. These alleles frequently travel in cis with RHD*DOL. To estimate the frequency of these alleles, we tested a total of more than 700 samples in two populations. Blood samples were obtained from patients with sickle cell disease and from blood donors of African descent. DNA extractions and analyses were performed by standard methods. In the United States, none of 70 patient samples had the RHCE*818 nucleotide change. Two of 220 donors (frequency of 0.009) were heterozygous for RHCE*818C/T (RHCE*ceBI). One of these samples had RHD/RHD*DOL and the other had RHD/RHD*DOL-2. In these 290 samples, no other RHD*DOL alleles were found. In Brazil, 1 of 244 patients with sickle cell disease (frequency of 0.004) and 1 of 171 donors (frequency of 0.006) were heterozygous for RHCE*818C/T (RHCE*ceBI). Testing of more than 500 additional samples from people of African descent, selected because they had a diverse range of common and variant RHCE alleles, did not reveal a sample with RHD*DOL or RHD/RHD*DOL-2 in the absence of RHCE*ce(818T). Although the numbers are small, our study shows that in the United States, the frequency of RHCE*818T is 0.007 (2 in 290 samples) and in Brazil it is 0.004 (2 in 515 samples). The four RHCE*818T alleles were RHCE*ceBI.

Immunohematology

2011;27:66–67.
The Indian blood group system
Authors: Xu Q.
Published: May 2021

The Indian blood group system (ISBT: IN/023) consists of two antithetical antigens: Ina(IN1), which is present in approximately 10 percent of some Arab populations and in 3 percent of Bombay Indians, and its allelic antigen Inb(IN2), an antigen of high incidence in all populations. In 2007, two new high-incidence antigens were identified as belonging to the IN blood group system, namely IN3 (INFI) and IN4 (INJA). The antigens in this system are located on CD44, a single-pass membrane glycoprotein that is encoded by the CD44gene on chromosome 11 at position p13. The biologic function of CD44 is as a leukocyte homing receptor and cellular adhesion molecule. The Inaand Inbpolymorphism represents a 252G>C substitution of CD44,encoding R46P, and lack of IN3 and IN4 results from homozygosity for mutations encoding H85Q and T163R in the CD44gene. The high-frequency antigen AnWj (901009) has not been assigned to the Indian system, but either is located on an isoform of CD44 or is closely associated with it.
Immunohematology

2011;27:89–93.