bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insouciance and inexperience: A deadly combination when dealing with COVID‐19
Authors: Paton Calum 
Published: June 2020

SummaryThis article gives key reasons for the UK's tardy and confused attempts to react to the COVID‐19 pandemic. It explains very poor outcomes in the UK (in terms of the spread of the virus and high mortality, already striking at the time of writing), in terms of an initial lack of political will to prioritise public health, itself a product of a strong Prime Minister who made the “wrong call”. It also highlights a failure to “follow the science”, except in so far as the “science” had already accepted some dubious political judgements and the lack of capacity to test as the starting‐point.
Immune phenotype of tumor microenvironment predicts response to bevacizumab in neoadjuvant treatment of ER‐positive breast cancer
Authors: von der Lippe Gythfeldt Hedda , Lien Tonje , Tekpli Xavier , Silwal‐Pandit Laxmi , Borgen Elin , Garred Øystein , Skjerven Helle , Schlichting Ellen , Lundgren Steinar , Wist Erik , Naume Bjørn , Kristensen Vessela , Børresen‐Dale Anne‐Lise , Lingjærde Ole Christian , Engebraaten Olav 
Published: June 2020

AbstractAntiangiogenic drugs are potentially a useful supplement to neoadjuvant chemotherapy for a subgroup of patients with human epidermal growth factor receptor 2 (HER2) negative breast cancer, but reliable biomarkers for improved response are lacking. Here, we report on a randomized phase II clinical trial to study the added effect of bevacizumab in neoadjuvant chemotherapy with FEC100 (5‐fluorouracil, epirubicin and cyclophosphamide) and taxanes (n = 132 patients). Gene expression from the tumors was obtained before neoadjuvant treatment, and treatment response was evaluated by residual cancer burden (RCB) at time of surgery. Bevacizumab increased the proportion of complete responders (RCB class 0) from 5% to 20% among patients with estrogen receptor (ER) positive tumors (P = .02). Treatment with bevacizumab was associated with improved 8‐year disease‐free survival (P = .03) among the good responders (RCB class 0 or I). Patients treated with paclitaxel (n = 45) responded better than those treated with docetaxel (n = 21; P = .03). Improved treatment response was associated with higher proliferation rate and an immune phenotype characterized by high presence of classically activated M1 macrophages, activated NK cells and memory activated CD4 T cells. Treatment with bevacizumab increased the number of adverse events, including hemorrhage, hypertension, infection and febrile neutropenia, but despite this, the ECOG status was not affected.
Harnessing nerve–muscle cell interactions for biomaterials‐based skeletal muscle regeneration
Authors: Narayanan Naagarajan , Lengemann Paul , Kim Kun Ho , Kuang Liangju , Sobreira Tiago , Hedrick Victoria , Aryal Uma K. , Kuang Shihuan , Deng Meng 
Published: June 2020

AbstractNerve cells secrete neurotrophic factors that play a critical role in neuronal survival, proliferation, and regeneration. However, their role in regulating myoblast behavior and skeletal muscle repair remains largely unexplored. In the present study, we investigated the effects of PC12 secreted signaling factors in modulating C2C12 myoblast behavior under physiologically relevant conditions. We showed that PC12 conditioned media modulated myoblast proliferation and differentiation in both 2D culture and 3D aligned electrospun fiber scaffold system in a dose‐dependent manner. We further developed a biomimetic, tunable hydrogel consisting of hyaluronic acid, chondroitin sulfate, and polyethylene glycol as a 3D matrix encapsulating PC12 cells. The hydrogel‐encapsulated PC12 cells promoted survival and proliferation of myoblasts in co‐culture. Further proteomics analysis identified a total of 2,088 proteins from the secretome of the encapsulated PC12 cells and revealed the biological role and overlapping functions of nerve‐secreted proteins for skeletal muscle regeneration, potentially through regulating myoblast behavior, nerve function, and angiogenesis. These experiments provide insights into the nerve–muscle interactions and pave the way for developing advanced biomaterials strategies incorporating nerve cell secretome for accelerated skeletal muscle regeneration.
Increased yield of gelatin coated therapeutic cells through cholesterol insertion
Authors: Davis Kara A. , Peng Hsuan , Chelvarajan Lakshman , Abdel‐Latif Ahmed , Berron Brad J. 
Published: June 2020

AbstractGelatin coatings are effective in increasing the retention of MSCs injected into the heart and minimizing the damage from acute myocardial infarction (AMI), but early studies suffered from low fractions of the MSCs coated with gelatin. Biotinylation of the MSC surface is a critical first step in the gelatin coating process, and in this study, we evaluated the use of biotinylated cholesterol “lipid insertion” anchors as a substitute for the covalent NHS‐biotin anchors to the cell surface. Streptavidin‐eosin molecules, where eosin is our photoinitiator, can then be bound to the cell surface through biotin‐streptavidin affinity. The use of cholesterol anchors increased streptavidin density on the surface of MSCs further driving polymerization and allowing for an increased fraction of MSCs coated with gelatin (83%) when compared to NHS‐biotin (52%). Additionally, the cholesterol anchors increased the uniformity of the coating on the MSC surface and supported greater numbers of coated MSCs even when the streptavidin density was slightly lower than that of an NHS‐biotin anchoring strategy. Critically, this improvement in gelatin coating efficiency did not impact cytokine secretion and other critical MSC functions. Proper selection of the cholesterol anchor and the biotinylation conditions supports cellular function and densities of streptavidin on the MSC surface of up to ~105 streptavidin molecules/μm2. In all, these cholesterol anchors offer an effective path towards the formation of conformal coatings on the majority of MSCs to improve the retention of MSCs in the heart following AMI.
In vitro estimation of reduction in strength and wear resistance of UHMWPE for joint prostheses due to lipid‐induced degradation
Authors: Sakoda Hideyuki , Okamoto Yoshihiro , Haishima Yuji 
Published: June 2020

AbstractUltra‐high molecular weight polyethylene (UHMWPE) is used as a bearing surface of joint prostheses and has been reported to absorb lipids such as squalene (SQ) and cholesterol esters in vivo. These lipids have been suggested by in vitro studies using SQ as a model lipid to have the potential to induce polymer degradation. However, the impact of lipid‐induced degradation on the strength and wear resistance of UHMWPE is unknown. In this study, lipid‐induced degradation was simulated by SQ absorption and subsequent accelerated aging, and its influence on the strength and wear resistance of UHMWPE was investigated using wear, fatigue crack growth, and delamination testing. Lipid‐induced degradation was found to have little impact on fatigue crack growth rates and delamination resistance. These results were consistent with previous reports that lipid‐induced degradation is localized near the surface. However, we also found that lipid‐induced degradation increased the wear rate of both non‐crosslinked and crosslinked UHMWPE by a factor of 2.5 and 14, respectively. These results indicate that lipid‐induced degradation may affect the durability and long‐term clinical outcome of joint replacements due to increased wear of UHMWPE.
Combined approaches for evaluation of xenoestrogen neural toxicity and thyroid dysfunction: Screening of oxido‐nitrosative markers, DNA fragmentation, and biogenic amine degradation
Authors: Taha Mohamed , Marie Abeer M. , Ahmed‐Farid Omar A. 
Published: June 2020

AbstractAnthropogenic chemicals such as parabens and triclosan are used in personal care products. Due to their ability to decrease or prevent bacterial contamination and act as preservatives, these chemicals are used in cosmetic manufacturing processes to increase the shelf life of products. In this study, we assessed the side effects of environmental estrogens (such as the xenoestrogen butylparaben and the antimicrobial agent and preservative triclosan) on thyroid function, brain monoamine levels, and DNA aberration. Forty‐two male albino rats were divided into seven groups with six members each: the first group served as control; the second and the third groups were treated with butylparaben 10 and 50 mg/kg body weight, respectively; the fourth and fifth groups were treated with triclosan 10 and 50 mg/kg body weight, respectively; and the sixth and seventh groups were treated with butylparaben plus triclosan 10 and 50 mg/kg body weight, respectively. After 60 days, blood samples were collected and brain specimens were divided into striatum, midbrain, cortex, and thalamus. Thyroid function and levels of monoamines and monoamine metabolites were determined for each brain area. Comet assay was used for brain tissue analysis. The results showed that butylparaben and triclosan and their combinations induced hypothyroidism and disrupted monoamine levels, leading to a decrease in catecholamine and serotonin levels, and accelerated production of 5‐hydroxyindoleacetic acid. The obtained data indicate that anthropogenic chemicals such as butylparaben and triclosan have harmful effects on thyroid and brain function and accelerate cell destruction and mutation, as evidenced by single‐stranded DNA breaks in the comet assay.
PRKAA1 rs13361707 C/T polymorphism confers decreased susceptibility to esophageal cancer: A case‐control study
Authors: Li Cheng‐Lin , Zhao Jian‐Qiang , Zang Bao 
Published: June 2020

AbstractBackgroundSeveral studies probed into the connection between esophageal cancer (EC) risk and PRKAA1 rs13361707 C/T

polymorphism, but obtained insignificant findings.MethodsIn this study, 814 EC cases and 961

controls from Eastern China were recruited to validate the relationship between this polymorphism and EC susceptibility.ResultsData suggested rs13361707 C/T

polymorphism in PRKAA1 gene was significantly related with a lower risk for EC. Such significant connection was also uncovered in subgroups of males, smokers, drinkers and individuals with age ≥ 60 years. In addition, this polymorphism

was linked with the pathological grading, distant metastasis, and histology of EC.ConclusionIn summary, PRKAA1 rs13361707 C/T

polymorphism is related to the risk and clinical properties of EC patients in East China.
Concomitant blockade of A2AR and CTLA‐4 by siRNA‐loaded polyethylene glycol‐chitosan‐alginate nanoparticles synergistically enhances antitumor T‐cell responses
Authors: Ghasemi‐Chaleshtari Mitra , Kiaie Seyed Hossein , Irandoust Mahzad , Karami Hadis , Nabi Afjadi Mohsen , Ghani Sepideh , Aghaei Vanda Nasimeh , Ghaderi Sede Mohammad Javad , Ahmadi Armin , Masjedi Ali , Hassannia Hadi , Atyabi Fatemeh , Hojjat‐Farsangi Mohammad , Namdar Afshin , Ghalamfarsa Ghasem , Jadidi‐Niaragh Farhad 
Published: June 2020

AbstractInhibitory immune checkpoint (ICP) molecules are important immunosuppressive factors in a tumor microenvironment (TME). They can robustly suppress T‐cell‐mediated antitumor immune responses leading to cancer progression. Among the checkpoint molecules, cytotoxic T‐lymphocyte‐associated protein‐4 (CTLA‐4) is one of the critical inhibitors of anticancer T‐cell responses. Besides, the expression of adenosine receptor (A2AR) on tumor‐infiltrating T cells potently reduces their function. We hypothesized that concomitant silencing of these molecules in T cells might lead to enhanced antitumor responses. To examine this assumption, we purified T cells from the tumor, spleen, and local lymph nodes of CT26 colon cancer‐bearing mice and suppressed the expression of A2AR and CTLA‐4 using the small interfering RNA (siRNA)‐loaded polyethylene glycol‐chitosan‐alginate (PCA) nanoparticles. The appropriate physicochemical properties of the produced nanoparticles (NPs; size of 72 nm, polydispersive index [PDI] < 0.2, and zeta potential of 11 mV) resulted in their high efficiency in transfection and suppression of target gene expression. Following the silencing of checkpoint molecules, various T‐cell functions, including proliferation, apoptosis, cytokine secretion, differentiation, and cytotoxicity were analyzed, ex vivo. The results showed that the generated nanoparticles had optimal physicochemical characteristics and significantly suppressed the expression of target molecules in T cells. Moreover, a concomitant blockade of A2AR and CTLA‐4 in T cells could synergistically enhance antitumor responses through the downregulation of PKA, SHP2, and PP2Aα signaling pathways. Therefore, this combination therapy can be considered as a novel promising anticancer therapeutic strategy, which should be further investigated in subsequent studies.
Selenium deficiency induced necroptosis, Th1/Th2 imbalance, and inflammatory responses in swine ileum
Authors: Zhang Yuan , Zhang Jiuli , Bao Jun , Tang Chaohua , Zhang Ziwei 
Published: June 2020

AbstractSelenium (Se) deficiency has a significant impact on the swine breeding industry by inducing digestive system damage and diarrhea. However, the molecular mechanism remains unclear. Our objectives were to investigate if different amounts of necroptosis, inflammatory responses, and T helper cell 1/T helper cell 2 (Th1/Th2) imbalances were induced by Se deficiency in intestinal porcine jejunal epithelial cells (IPEC‐J2) and swine ileum tissue. Therefore, Se‐deficient models were successfully established both in vitro and in vivo. In the current study, the cell morphological observation results showed that Se deficiency seriously affected the growth and differentiation of IPEC‐J2 cells. Moreover, the necroptosis staining and histomorphology observation results showed that the number of necroptotic cells increased significantly, and the ileal tissue exhibited abnormal structures, including necroptotic features and inflammatory cell infiltration, in the Se‐deficient group. Furthermore, Se deficiency resulted in accelerated cell necroptosis by increasing (p < .05) the expression of genes related to the tumor necrosis factor‐α pathway at both the protein and messenger RNA (mRNA) levels compared to the control group. Moreover, the relative mRNA and protein expression of the inflammatory genes and their responses to dietary Se deficiency were consistent with the resultant Th1/Th2 imbalances in vitro and in vivo. Taken together, the results suggested that Se deficiency caused necroptosis, inflammatory responses, and abnormal expression of cytokines in swine ileum tissue. These findings might help us to explain the damage induced by Se deficiency to the digestive system of swine.
Base promoted regioselective aromatization for the preparation of substituted 3‐hydroxybenzene dicarboxylate
Authors: Guo Weihang , Wang Xianheng , Zhao Changkuo , Wang Yuhe 
Published: June 2020

AbstractA new convenient base promoted aromatization process has been developed to prepare substituted 3‐hydroxybenzene dicarboxylate using commercially available materials. In particular, regioselectivity will occur for substrates with mono‐substitution at 5‐ or 6‐position. This new process provides less reaction steps and moderate yields, and can be used extensively in the synthesis of other substrates to functionalize phenol esters.
Microcredit and Economic Welfare: Experience of Poor Rural Households from Pakistan
Authors: Latif Waqas Umar , Ullah Sana , Ahmed Wasim , Sultan Muhammad Umar , Jafar Rana Muhammad Sohail , Tariq Muhammad , Linping Wang 
Published: June 2020

SummaryThis research article effort to empirically assess the effect of microcredit on household economic welfare consequences, for example income and consumption in rural Pakistan. The valuation is based on the difference‐in‐difference method that is a progressively popular technique of tackling the selection bias issue in measuring the influences of microcredit. This paper uses a 2‐year panel data set, together with both primary and secondary data gained through a household survey in rural Pakistan. Our empirical outcomes favour the full belief in the literature that participates in microcredit programme helps expand households' economic welfare, for example income and consumption. Despite the positive results on how microcredit has improved the rural households' living status, our outcomes display that the huge majority of the program applicants are non‐poor, which casts roughly uncertainties on the social potential (for example poverty alleviation) of Pakistan's microcredit programs. © 2020 John Wiley & Sons, Ltd.
Quantifying lymphocyte vacuolization serves as a measure of CLN3 disease severity
Authors: Kuper Willemijn F. E. , Oostendorp Marlies , van den Broek Brigitte T. A. , van Veghel Karin , Nonkes Lourens J. P. , Nieuwenhuis Edward E. S. , Fuchs Sabine A. , Veenendaal Tineke , Klumperman Judith , Huisman Albert , Nierkens Stefan , van Hasselt Peter M. 
Published: June 2020

AbstractBackgroundThe CLN3 disease spectrum ranges from a childhood‐onset neurodegenerative disorder to a retina‐only disease. Given the lack of metabolic disease severity markers, it may be difficult to provide adequate counseling, particularly when novel genetic variants are identified. In this study, we assessed whether lymphocyte vacuolization, a well‐known yet poorly explored characteristic of CLN3 disease, could serve as a measure of disease severity.MethodsPeripheral blood obtained from healthy controls and CLN3 disease patients was used to assess lymphocyte vacuolization by (a) calculating the degree of vacuolization using light microscopy and (b) quantifying expression of lysosomal‐associated membrane protein 1 (LAMP‐1), using flow cytometry in lymphocyte subsets as well as a qualitative analysis using electron microscopy and ImageStream analysis.ResultsQuantifying lymphocyte vacuolization allowed to differentiate between CLN3 disease phenotypes (P = .0001). On immunofluorescence, classical CLN3 disease lymphocytes exhibited abundant vacuole‐shaped LAMP‐1 expression, suggesting the use of LAMP‐1 as a proxy for lymphocyte vacuolization. Using flow cytometry in lymphocyte subsets, quantifying intracellular LAMP‐1 expression additionally allowed to differentiate between infection and storage and to differentiate between CLN3 phenotypes even more in‐depth revealing that intracellular LAMP‐1 expression was most pronounced in T‐cells of classical‐protracted CLN3 disease while it was most pronounced in B‐cells of “retina‐only” CLN3 disease.ConclusionLymphocyte vacuolization serves as a proxy for CLN3 disease severity. Quantifying vacuolization may help interpretation of novel genetic variants and provide an individualized readout for upcoming therapies.
Successful management of a neonate with OTC deficiency presenting with hyperammonemia and severe cardiac dysfunction with extracorporeal membrane oxygenation support and continuous renal replacement therapy
Authors: Mattke Adrian C. , Shikata Fumiaki , McGill James , Justo Rob , Venugopal Prem 
Published: June 2020

AbstractOrnithine transcarbamylase (OTC) deficiency is an X‐linked urea cycle disorder which—in severe form—results in rapid accumulation of ammonia and glutamine with subsequent irreversible brain injury. We present a case of severe left ventricular dysfunction with hyperammonemic crisis caused by OTC deficiency which was managed with veno‐arterial extracorporeal membrane oxygenation support combined with continuous renal replacement therapy. Aggressive treatment led to normalization of ammonia and full left ventricular recovery.
MRI‐Based Radiomics Signature: A Potential Biomarker for Identifying Glypican 3‐Positive Hepatocellular Carcinoma
Authors: Gu Dongsheng , Xie Yongsheng , Wei Jingwei , Li Wencui , Ye Zhaoxiang , Zhu Zhongyuan , Tian Jie , Li Xubin 
Published: June 2020

BackgroundGlypican 3 (GPC3) expression has proved to be a critical risk factor related to prognosis in hepatocellular carcinoma (HCC) patients.PurposeTo investigate the performance of MRI‐based radiomics signature in identifying GPC3‐positive HCC.Study TypeRetrospective.PopulationAn initial cohort of 293 patients with pathologically confirmed HCC was involved in this study, and patients were randomly divided into training (195) and validation (98) cohorts.Field Strength/SequencesContrast‐enhanced T1‐weight MRI was performed with a 1.5T scanner.AssessmentA total of 853 radiomic features were extracted from the volume imaging. Univariate analysis and Fisher scoring were utilized for feature reduction. Subsequently, forward stepwise feature selection and radiomics signature building were performed based on a support vector machine (SVM). Incorporating independent risk factors, a combined nomogram was developed by multivariable logistic regression modeling.Statistical TestsThe predictive performance of the nomogram was calculated using the area under the receive operating characteristic curve (AUC). Decision curve analysis (DCA) was applied to estimate the clinical usefulness.ResultsThe radiomics signature consisting of 10 selected features achieved good prediction efficacy (training cohort: AUC = 0.879, validation cohort: AUC = 0.871). Additionally, the combined nomogram integrating independent clinical risk factor α‐fetoprotein (AFP) and radiomics signature showed improved calibration and prominent predictive performance with AUCs of 0.926 and 0.914 in the training and validation cohorts, respectively.Data ConclusionThe proposed MR‐based radiomics signature is strongly related to GPC3‐positive. The combined nomogram incorporating AFP and radiomics signature may provide an effective tool for noninvasive and individualized prediction of GPC3‐positive in patients with HCC. J. MAGN. RESON. IMAGING 2020;52:1679–1687.