bluuebunny/crossref_metadata_2025 huggingface dataset:
Emergent percutaneous therapy for left ventricular assist device retrograde flow
Authors: Wilson Ryan E. , Gurley John C. , Rajagopalan Navin , Tribble Thomas A.
Published: November 2017

With the number of heart transplants being performed each year stagnating due to lack of donors the left ventricular assist device (LVAD) patient population will continue to grow. As more and more patients are living longer with LVADs, either as a bridge to transplant or destination therapy, we will continue to see an increased number of complications related to assist device therapy. One of the common challenges physicians face are patients who suffer from both bleeding and thrombotic complications. When bleeding complications occur anticoagulation is usually reduced or discontinued and then the thrombosis risk increases. Once a pump thrombosis occurs there are limited percutaneous treatment strategies available, especially in the setting of a recent bleeding event. Surgical exchange is the only definitive therapy and that can be a high risk and difficult operation. Turning off an LVAD may become necessary, as it did in our case, but that can lead to significant retrograde flow through the device and rapid patient decline. A prompt percutaneous therapy is needed to stabilize these patients.
Cover Image, Volume 74, Issue 11
Authors: Qadota Hiroshi , Matsunaga Yohei , Nguyen Ken C.Q. , Mattheyses Alexa , Hall David H. , Benian Guy M.
Published: November 2017

The cover image, by Hiroshi Qadota et al., is based on the Research Article High‐resolution imaging of muscle attachment structures in Caenorhabditis elegans, DOI: 10.1002/cm.21410.

image
Effects of temperature and drought on early life stages in three species of butterflies: Mortality of early life stages as a key determinant of vulnerability to climate change?
Authors: Klockmann Michael , Fischer Klaus
Published: November 2017

Anthropogenic climate change poses substantial challenges to biodiversity conservation. Well‐documented responses include phenological and range shifts, and declines in cold but increases in warm‐adapted species. Thus, some species will suffer while others will benefit from ongoing change, although the biological features determining the prospects of a given species under climate change are largely unknown. By comparing three related butterfly species of different vulnerability to climate change, we show that stress tolerance during early development may be of key importance. The arguably most vulnerable species showed the strongest decline in egg hatching success under heat and desiccation stress, and similar pattern also for hatchling mortality. Research, especially on insects, is often focussed on the adult stage only. Thus, collating more data on stress tolerance in different life stages will be of crucial importance for enhancing our abilities to predict the fate of particular species and populations under ongoing climate change.
Ethmoidal adenocarcinoma treated by exclusive endoscopic approach: Focus on learning curve and modification of management
Authors: Oker Natalie , Verillaud Benjamin , Wassef Michel , Froelich Sébastien , Bresson Damien , Kania Romain , Herman Philippe
Published: November 2017

Background

The purpose of this study was to investigate the outcome and recurrences for ethmoidal adenocarcinomas treated by exclusive endoscopic surgery in curative intent and investigate the role of the learning curve.

Methods

We conducted a single‐center retrospective study, including 60 patients separated in 2 groups (2002‐2011 n = 28 and 2012‐2015 n = 32).

Results

The global survival rate at 5 years was 72.6%, and the global and local recurrence rates were 21.6% and 13.3%, respectively. The learning curve had significant impact on global survival at 2 years (93.8% vs 77.8%) and on overall and local recurrences, despite the higher rate of T4 classifications in the latter group. This learning curve could be explained by the evolution toward large endoscopic resection, bilateral, with resection of the cribriform plate, and eventually medial maxillectomy, and started on the healthy side.

Conclusion

For selected cases, exclusive endoscopic resection of ethmoid adenocarcinoma achieves results at least as good as craniofacial resection when performed by an experienced cranial base team and including a large endoscopic resection.
Sensory recovery of myomucosal flap oral cavity reconstructions
Authors: Massarelli Olindo , Vaira Luigi Angelo , Biglio Andrea , Gobbi Roberta , Dell'aversana Orabona Giovanni , De Riu Giacomo
Published: November 2017

Background

Sensory restoration of the oral cavity is a primary aim of reconstructive surgery in posttraumatic or postablative defects. Sensitivity plays a key role in oral function, whose impairment strongly affects the patient's quality of life. Cheek myomucosal flaps provide a reliable and tissue‐like reconstruction of these regions but their sensitive recovery, which we still know little about, deserves thorough assessment.

Methods

In this retrospective study, the myomucosal cheek flaps were tested for different aspects of sensory recovery: touch; 2‐point discrimination; pain; sharp/smooth discrimination; ability to feel hot/cold stimulus; stereognosis; and taste.

Results

Fifty‐two myomucosal flap reconstructions were investigated. All sensitivity tests showed positive results. When comparison was possible, sensitivity seemed significantly close to the contralateral healthy side. Sensory recovery proved to be even better than that reported on reinnervated microvascular free flap reconstructions of the oral cavity.

Conclusion

Myomucosal flap reconstruction demonstrated a high degree of sensory recovery.
Dose‐finding and efficacy confirmation trial of the superselective intra‐arterial infusion of cisplatin and concomitant radiotherapy for locally advanced maxillary sinus cancer (Japan Clinical Oncology Group 1212): Dose‐finding phase
Authors: Homma Akihiro , Onimaru Rikiya , Matsuura Kazuto , Shinomiya Hirotaka , Sakashita Tomohiro , Shiga Kiyoto , Tachibana Hiroyuki , Nakamura Kenichi , Mizusawa Junki , Kitahara Hideaki , Eba Junko , Fukuda Haruhiko , Fujii Masato , Hayashi Ryuichi
Published: November 2017

Background

We are currently undertaking a multi‐institutional prospective trial of the superselective intra‐arterial infusion of high‐dose cisplatin with concomitant radiotherapy for patients with T4aN0M0 or T4bN0M0 locally advanced maxillary sinus squamous cell carcinomas (SCC). We herein report the results of the dose‐finding phase.

Methods

The dose‐finding phase sought to evaluate the incidence of dose‐limiting toxicities and determine the recommended number of cycles of the intra‐arterial infusion of cisplatin. In this phase, 100 mg/m2 of cisplatin was administered intra‐arterially weekly for 7 weeks with concomitant radiotherapy (70 Gy).

Results

All 18 patients received a full dose of radiotherapy. The number of cycles of cisplatin was 7 in 13 patients and 6 in 5 patients. The dose‐limiting toxicities were observed in 5 patients.

Conclusion

These results indicated that this therapy is safe and well‐tolerated at 7 cycles of cisplatin, which was determined to be the recommended number of cycles for locally advanced maxillary sinus SCC.
Effect of general anesthesia and intubation on parathyroid levels in normal patients and those with hyperparathyroidism
Authors: Cinamon Udi , Gavish Doron , Ovnat Tamir Sharon , Goldfarb Abraham , Ezri Tiberiu
Published: November 2017

Background

Induction of general anesthesia and endotracheal intubation may precipitate parathyroid hormone (PTH) elevation in patients with primary hyperparathyroidism (HPT). The purposes of this study were to revisit this observation and to study its impact in healthy patients.

Methods

Patients with primary HPT who underwent parathyroidectomy were retrospectively studied. The PTH was sampled and compared: before, immediately after general anesthesia and endotracheal intubation, and 15 minutes after parathyroidectomy. Healthy adults who underwent elective operations were prospectively studied. The PTH was sampled before general anesthesia and endotracheal intubation, immediately after, and 15 minutes later.

Results

Thirty‐one patients, aged 28‐89 years (mean 60.1 ± 13 years), were retrospectively studied. The PTH was significantly elevated after general anesthesia and endotracheal intubation (P = .014). Fifty patients, aged 21‐86 years (mean 54 ± 15 years), were prospectively studied. The PTH elevation after general anesthesia and endotracheal intubation was not significant.

Conclusion

General anesthesia and endotracheal intubation causes an immediate, steep, and significant PTH elevation in patients with primary HPT but only a minor change in healthy adults. The difference may be attributed to an impaired adrenergic response in patients with primary HPT.
Interaction between the patatin‐like phospholipase domain‐containing protein 3 genotype and coffee drinking and the risk for acute alcoholic hepatitis
Authors: Liangpunsakul Suthat , Beaudoin James J. , Shah Vijay H. , Puri Puneet , Sanyal Arun J. , Kamath Patrick S. , Lourens Spencer G. , Tang Qing , Katz Barry P. , Crabb David W. , Chalasani Naga P.
Published: November 2017

Only a subset of subjects with excessive alcohol consumption develops alcoholic liver disease (ALD). One of the major risk factors for ALD is the genetic variant of the patatin‐like phospholipase domain‐containing protein 3 (PNPLA3) gene. Coffee is one of the most commonly consumed beverages, and coffee consumption has been associated with lower levels of serum alanine aminotransferase. The aim of this study was to investigate the role of coffee drinking and PNPLA3 rs738409 and their association with alcoholic hepatitis (AH) in a well‐characterized cohort of subjects from the Translational Research and Evolving Alcoholic Hepatitis Treatment consortium. AH subjects and heavy drinking controls without a history of liver disease who were enrolled between May 2013 and May 2016 were included (n = 339), and the details of alcohol and coffee consumption were assessed. The PNPLA3 variant was determined among participants of European ancestry (n = 183). Relationships between baseline data and AH status were determined, and multivariable logistic regression modeling was performed. During the study period, 189 cases with AH and 150 heavy drinking controls were prospectively enrolled. The prevalence of regular coffee consumption was significantly lower in patients with AH compared to controls (20% versus 43%; P < 0.0001). The overall minor allele frequency of the PNPLA3 variant was higher in AH cases. Multivariable logistic regression revealed that coffee consumption and PNPLA3 were significantly associated with AH status at baseline after adjusting for relevant patient characteristics. Conclusion: We found a higher prevalence of AH among heavy drinkers with PNPLA3 G/G and G/C genotypes regardless of coffee consumption status and a higher prevalence of AH among heavy drinkers who were not regular coffee drinkers. These findings remained after considering relevant baseline patient characteristics. Further studies are needed to confirm our observation. (Hepatology Communications 2018;2:29–34)
Sofosbuvir induced steven Johnson Syndrome in a patient with hepatitis C virus‐related cirrhosis
Authors: Verma Nipun , Singh Shreya , Sawatkar Gitesh , Singh Virendra
Published: November 2017

Sofosbuvir is an imperative drug used in treatment regimens for hepatitis C virus (HCV). It is considered relatively safe with fewer adverse effects than other treatments. Here, we report a rare and potentially serious, dermatologic, adverse effect following the use of sofosbuvir. A 35‐year‐old man with genotype 3‐related HCV cirrhosis presented with decompensated ascites and jaundice following 7 weeks of therapy with peginterferon alpha‐2a and oral ribavirin. After peginterferon withdrawal and stabilization, oral sofosbuvir and ribavirin were started; 10 days later, he developed itching over the trunk and legs, followed by multiple papules and vesicles over an erythematous base. Over the next 15 days, the rash progressed with the formation of blisters and peeling skin. Simultaneously, the oral mucosa and lips developed crusting and painful erosions. Considering drug‐induced Steven John Syndrome (SJS), sofosbuvir and ribavirin were withdrawn and the patient was treated with topical emollients, steroids, and supportive care. The lesions improved over the next 4 weeks, with some residual hyperpigmentation. Rechallenge with sofosbuvir alone at one eighth the dose resulted in similar skin and mucosal lesions after 2 months; these lesions also improved after sofosbuvir withdrawal. The Algorithm of Drug Causality for Epidermal Necrolysis score was 7, which suggested sofosbuvir as the very probable drug resulting in SJS in our patient. Conclusion: The appearance of SJS following sofosbuvir use is an important and potentially fatal complication from a drug that serves as the backbone of several HCV treatment regimens. Treating physicians must use sofosbuvir with caution and consider withholding or discontinuing this drug in patients with such severe dermatologic manifestations. (Hepatology Communications 2018;2:16–20)
NeXt for neuro‐radiosurgery: A fully automatic approach for necrosis extraction in brain tumor MRI using an unsupervised machine learning technique
Authors: Rundo Leonardo , Militello Carmelo , Tangherloni Andrea , Russo Giorgio , Vitabile Salvatore , Gilardi Maria Carla , Mauri Giancarlo
Published: November 2017

Stereotactic neuro‐radiosurgery is a well‐established therapy for intracranial diseases, especially brain metastases and highly invasive cancers that are difficult to treat with conventional surgery or radiotherapy. Nowadays, magnetic resonance imaging (MRI) is the most used modality in radiation therapy for soft‐tissue anatomical districts, allowing for an accurate gross tumor volume (GTV) segmentation. Investigating also necrotic material within the whole tumor has significant clinical value in treatment planning and cancer progression assessment. These pathological necrotic regions are generally characterized by hypoxia, which is implicated in several aspects of tumor development and growth. Therefore, particular attention must be deserved to these hypoxic areas that could lead to recurrent cancers and resistance to therapeutic damage. This article proposes a novel fully automatic method for necrosis extraction (NeXt), using the Fuzzy C‐Means algorithm, after the GTV segmentation. This unsupervised Machine Learning technique detects and delineates the necrotic regions also in heterogeneous cancers. The overall processing pipeline is an integrated two‐stage segmentation approach useful to support neuro‐radiosurgery.NeXtcan be exploited for dose escalation, allowing for a more selective strategy to increase radiation dose in hypoxic radioresistant areas. Moreover,NeXtanalyzes contrast‐enhanced T1‐weighted MR images alone and does not require multispectral MRI data, representing a clinically feasible solution. This study considers an MRI dataset composed of 32 brain metastatic cancers, wherein 20 tumors present necroses. The segmentation accuracy ofNeXtwas evaluated using both spatial overlap‐based and distance‐based metrics, achieving these average values: Dice similarity coefficient 95.93% ± 4.23% and mean absolute distance 0.225 ± 0.229 (pixels).
Investigating the expression of MMPs and TIMPs in preterm placenta and role of CpG methylation in regulating MMP‐9 expression
Authors: Sundrani Deepali , Narang Ankita , Mehendale Savita , Joshi Sadhana , Chavan‐Gautam Preeti
Published: November 2017

Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) are crucial to the processes of normal labor and parturition. We have previously reported aberrant protein levels of MMPs in placenta of women delivering preterm as compared to term. In this study, we examine the mRNA levels of MMPs (MMP‐1, MMP‐2, and MMP‐9) and TIMPs (TIMP‐1, TIMP‐2) in the placenta from women delivering preterm as compared with term and further study the promoter DNA methylation of the MMP‐9 gene in a sub‐sample of term and preterm placentae. A total of 110 women were included in the study; 56 delivered term and 54 delivered preterm. MMP and TIMP mRNA levels were determined by Taqman‐based qPCR. Promoter CpG methylation of MMP‐9 gene was studied on a subset of 10 term and 8 preterm placenta using Epitect Methyl‐II PCR assay kit. The mRNA levels of MMP‐1,‐2 were higher and those of TIMP‐1,‐2 were lower in the placentae of women delivering preterm. MMP‐9 levels were comparable between the two groups. Among women undergoing spontaneous vaginal deliveries, higher mRNA levels of MMP‐1, ‐2 and ‐9 were seen in the placentae of those delivering preterm as compared to term. Similar results were seen in women undergoing preterm labor as compared to term. MMP‐9 gene promoter was hypomethylated in preterm placenta as compared to term placenta, while the mRNA levels were comparable between the two groups. The observed imbalance between MMP and TIMP expression may have prematurely triggered the signaling cascade leading to preterm birth. © 2017 IUBMB Life, 69(12):985–993, 2017
Acute hypoxic preconditioning prevents palmitic acid‐induced cardiomyocyte apoptosis via switching metabolic GLUT4‐glucose pathway back to CD36‐fatty acid dependent
Authors: Chen Yeh‐Peng , Kuo Wei‐Wen , Baskaran Rathinasamy , Day Cecilia‐Hsuan , Chen Ray‐Jade , Wen Su‐Ying , Ho Tsung‐Jung , Padma Viswanadha Vijaya , Kuo Chia‐Hua , Huang Chih‐Yang
Published: November 2017

Metabolic syndrome is a risk factor for the development of cardiovascular diseases. Myocardial cell damage leads to an imbalance of energy metabolism, and many studies have indicated that short‐term hypoxia during myocardial cell injury has a protective effect. In our previous animal studies, we found that short‐term hypoxia in the heart has a protective effect, but long‐term hypoxia increases myocardial cell injury. Palmitic acid (PA)‐treated H9c2 cardiomyoblasts and neonatal rat ventricle cardiomyocytes were used to simulate hyperlipidemia model, which suppress cluster of differentiation 36 (CD36) and activate glucose transporter type 4 (GLUT4). We exposed the cells to short‐ and long‐term hypoxia and investigated the protective effects of hypoxic preconditioning on PA‐induced lipotoxicity in H9c2 cardiomyoblasts and neonatal rat cardiomyocytes. Preconditioning with short‐term hypoxia enhanced both CD36 and GLUT4 metabolism pathway protein levels. Expression levels of phospho‐PI3K, phospho‐Akt, phospho‐AMPK, SIRT1, PGC1α, PPARα, CD36, and CPT1β induced by PA was reversed by short‐term hypoxia in a time‐dependent manner. PA‐induced increased GLUT4 membrane protein level was reduced in the cells exposed to short‐term hypoxia and si‐PKCζ. Short‐term hypoxia, resveratrol and si‐PKCζ rescue H9c2 cells from apoptosis induced by PA and switch the metabolic pathway from GLUT4 dependent to CD36 dependent. We demonstrate short‐term hypoxic preconditioning as a more efficient way as resveratrol in maintaining the energy metabolism of hearts during hyperlipidemia and can be used as a therapeutic strategy.
Matrine reversed multidrug resistance of breast cancer MCF‐7/ADR cells through PI3K/AKT signaling pathway
Authors: Zhou Bing‐Gang , Wei Chang‐Sheng , Zhang Song , Zhang Zhi , Gao Huan‐min
Published: November 2017

Matrine is an alkaloid extracted from a Chinese herbSophora flavescensAit, and has been used clinically for breast cancer with marked therapeutic efficacy in China. However, the mechanism has not been well known. Thus, the present study was to explore whether Matrine reverses multidrug resistance for breast cancer cells through the regulation of PI3K/AKT signaling pathway. Methyl thiazolyl tetrazolium (MTT) assay was used to detect the inhibitory action; Annexin V to detect apoptosis; fluorospectrophotometry to examine intracellular adriamycin (ADR) accumulation; and Western blot to label the proteins of P‐glycoprotein (P‐gp), MRP1, PTEN, p‐AKT, Bcl‐2, Bax, and Caspase‐3. Matrine (0‐2.5 mg/mL) inhibited MCF‐7/ADR cell growth and induced apoptosis (P < 0.01). A total of 0.2 mg/mL Matrine could increase the intracellular concentration of ADR; the accumulation in MCF‐7/ADR cells increased 3.56 times. Compared with control group, 0.6, 1.2 mg/mL Matrine reduced protein expressions of P‐gp, MRP1, p‐AKT, Bcl‐2, but increased PTEN, Bax, and cleaved caspase‐3 gradually, and unchanged caspase‐3. Matrine was more likely to reduce the expression of P‐gp, MRP1, and p‐AKT at the same inhibition radio of Matrine, (0.6 mg/mL) and MK2206 (0.05 μmol/L). Matrine inhibited MCF‐7/ADR cell growth, induced apoptosis, and reversed multidrug resistance for breast cancer cells through the regulation of downstream apoptosis factors of PI3K/AKT signaling pathway by decreasing cell phosphorylation of AKT level.
ARFHPV E7 oncogene, lncRNA HOTAIR, miR‐331‐3p and its target, NRP2, form a negative feedback loop to regulate the apoptosis in the tumorigenesis in HPV positive cervical cancer
Authors: Zhang Min , Song Yinghui , Zhai Furui
Published: November 2017

The objective of this study was to explore the role of HOTAIR in the development of cervical cancer, as well as its downstream signaling pathway. We conducted computational analysis, luciferase assay to explore downstream of HOTAIR and miR‐331‐3p. Real‐time PCR and Western blot were carried out to detect the relationship among E7, HOTAIR, miR‐331‐3p, NRP2, and P53. Finally, MTT assay and flow cytometry analysis were performed to validate the effect of E7 and miR‐331‐3p on cell apoptosis and proliferation. NRP2 was identified as a virtual target gene of miR‐331‐3p with a binding site of miR‐331‐3p, and HOTAIR was directly sponged to miR‐331‐3p, miR‐331‐3p reduced luciferase activity of wild‐type of NRP2 3′UTR and HOTAIR, but not those of mutant NRP2 3′UTR and HOTAIR. MiR‐331‐3p down‐regulated NRP2 and E7 expression levels, and further promoted cell apoptosis, while inhibited cell proliferation. Cell transfected with HPV16 E7 displayed lower levels of HOTAIR, NRP2 and P53, a higher level of miR‐331‐3p, over‐expression of E7 further repressed cell apoptosis, while improved cell proliferation compared with control. Normal HPV (+) group exhibited a higher miR‐331‐3p, and lower mRNA levels of HOTAIR and NRP2 than HPV (−) group. According to the result of IHC (immunohistochemistry), we found that NRP2 protein was highly expressed in HPV (−) group compared to that in HPV (+) group. E7‐HOTAIR‐miR‐331‐3p‐NRP2‐E7 formed a regulatory loop, and could be involved in the pathogenesis of cervical cancer.
RhoJ promotes hypoxia induced endothelial‐to‐mesenchymal transition by activating WDR5 expression
Authors: Liu Li , Chen Junliang , Sun Lina , Xu Yong
Published: November 2017

Endothelial‐to‐mesenchymal transition (EndMT) contributes to the pathogenesis of a host of human diseases. RhoJ, a small G protein, is abundantly expressed in endothelial cells. In the present study, we investigated the potential role RhoJ plays in EndMT. We report that RhoJ depletion by small interfering RNA attenuated hypoxia induced EndMT in both immortalized endothelial cells and human primary microvascular endothelial cells. RhoJ knockdown blocked the recruitment of TWIST and SNAIL, two transcriptional repressors, to the promoter region of VE‐CADHERIN, a prominent endothelial marker. RhoJ mediated the induction of TWIST and SNAIL expression, under hypoxic conditions, by promoting the binding of HIF‐1α to the gene promoters and by enhancing the accumulation of trimethylated histone H3K4. Further analysis revealed that RhoJ was essential for the up‐regulation of WDR5, a key component of the mammalian H3K4 methyltransferase, by hypoxia thereby leading to the trans‐activation of TWIST and SNAIL. Finally, lentivirus mediated over‐expression of WDR5 compensated for the loss of TWIST and SNAIL and allowed EndMT to proceed despite the absence of RhoJ in hypoxia‐challenged endothelial cells. In conclusion, we propose that RhoJ‐dependent induction of WDR5 may be essential for hypoxia‐induced EndMT.
Mechanism of action of camphoryl‐benzene sulfonamide derivative on glucose uptake in adipose tissue
Authors: Frederico Marisa J. S. , Castro Allisson J. G. , Pinto Veronica A. M. , Ramos Cristiane D. F. , Monteiro Fabíola B. F. , Mascarello Alessandra , Nunes Ricardo J. , Silva Fátima R. M. B.
Published: November 2017

The aim of the present study was to investigate the mechanism of action of a sulfonamide derivative on glucose uptake in adipose tissue, as well as to characterize the effects of this compound on intestinal disaccharidases and advanced glycation end‐products (AGEs) formation. Camphoryl‐benzene sulfonamide (CS) was able to stimulate glucose uptake in isolated adipocytes, adipose tissue, and in soleus muscle. The stimulatory effect of the compound (10 μM) on glucose uptake on adipose tissue was blocked by diazoxide, wortmannin, U73122, colchicine, and N‐ethylmaleimide. On the other hand, the effects of CS were not blocked by glibenclamide, an inhibitor of the K+‐ATP channel, or even by the inhibitor of protein p38 MAPK, SB 203580. In vivo, this compound reduced intestinal disaccharidase activity, while, in vitro, CS reduced the formation of AGEs at 7, 14, and 28 days of incubation. The stimulatory effect of CS on glucose uptake requires the activation of the K+‐ATP channel, translocation, and fusion of GLUT4 vesicles to the plasma membrane on adipocytes for glucose homeostasis. In addition, the inhibition of disaccharidase activity contributes to the glucose homeostasis in a short‐term as well as the remarkable reduction in AGE formation indicates that the CS may prevent of complications of late diabetes.
Identification of gene expression signatures across different types of neural stem cells with the Monte‐Carlo feature selection method
Authors: Chen Lei , Li JiaRui , Zhang Yu‐Hang , Feng KaiYan , Wang ShaoPeng , Zhang YunHua , Huang Tao , Kong Xiangyin , Cai Yu‐Dong
Published: November 2017

Adult neural stem cells (NSCs) are a group of multi‐potent, self‐renewing progenitor cells that contribute to the generation of new neurons and oligodendrocytes. Three subtypes of NSCs can be isolated based on the stages of the NSC lineage, including quiescent neural stem cells (qNSCs), activated neural stem cells (aNSCs) and neural progenitor cells (NPCs). Although it is widely accepted that these three groups of NSCs play different roles in the development of the nervous system, their molecular signatures are poorly understood. In this study, we applied the Monte‐Carlo Feature Selection (MCFS) method to identify the gene expression signatures, which can yield a Matthews correlation coefficient (MCC) value of 0.918 with a support vector machine evaluated by ten‐fold cross‐validation. In addition, some classification rules yielded by the MCFS program for distinguishing above three subtypes were reported. Our results not only demonstrate a high classification capacity and subtype‐specific gene expression patterns but also quantitatively reflect the pattern of the gene expression levels across the NSC lineage, providing insight into deciphering the molecular basis of NSC differentiation.
Breaking the polar‐nonpolar division in solvation free energy prediction
Authors: Wang Bao , Wang Chengzhang , Wu Kedi , Wei Guo‐Wei
Published: November 2017

Implicit solvent models divide solvation free energies into polar and nonpolar additive contributions, whereas polar and nonpolar interactions are inseparable and nonadditive. We present a feature functional theory (FFT) framework to break this ad hoc division. The essential ideas of FFT are as follows: (i) representability assumption: there exists a microscopic feature vector that can uniquely characterize and distinguish one molecule from another; (ii) feature‐function relationship assumption: the macroscopic features, including solvation free energy, of a molecule is a functional of microscopic feature vectors; and (iii) similarity assumption: molecules with similar microscopic features have similar macroscopic properties, such as solvation free energies. Based on these assumptions, solvation free energy prediction is carried out in the following protocol. First, we construct a molecular microscopic feature vector that is efficient in characterizing the solvation process using quantum mechanics and Poisson–Boltzmann theory. Microscopic feature vectors are combined with macroscopic features, that is, physical observable, to form extended feature vectors. Additionally, we partition a solvation dataset into queries according to molecular compositions. Moreover, for each target molecule, we adopt a machine learning algorithm for its nearest neighbor search, based on the selected microscopic feature vectors. Finally, from the extended feature vectors of obtained nearest neighbors, we construct a functional of solvation free energy, which is employed to predict the solvation free energy of the target molecule. The proposed FFT model has been extensively validated via a large dataset of 668 molecules. The leave‐one‐out test gives an optimal root‐mean‐square error (RMSE) of 1.05 kcal/mol. FFT predictions of SAMPL0, SAMPL1, SAMPL2, SAMPL3, and SAMPL4 challenge sets deliver the RMSEs of 0.61, 1.86, 1.64, 0.86, and 1.14 kcal/mol, respectively. Using a test set of 94 molecules and its associated training set, the present approach was carefully compared with a classic solvation model based on weighted solvent accessible surface area. © 2017 Wiley Periodicals, Inc.
Serum lipoprotein and RBC rigidity index to predict cerebral infarction in patients with carotid artery stenosis
Authors: Dong Zhiwu , Guo Qiang , Sun Li , Li Feifei , Zhao Aihong , Liu Jingfan , Qu Peipei , Zhu Qinghua , Xiao Chunhai , Niu Fusheng , Liang Shuang
Published: November 2017

Objective

This study aims to determine the risk factors and to predict the occurrence of cerebral infarction in patients with carotid artery stenosis.

Methods

Two hundred and one subjects with carotid artery stenosis were retrospectively selected from Jinshan Branch of Shanghai Sixth People's Hospital, 115 cases of which with cerebral infarction and 86 without it. Clinical tests were performed including coagulation indices, fasting glucose, serum lipid, and blood rheology. Logistic regression analyses were used to identify the risk factors. Regression model was established, and receiver operating characteristic (ROC) curve was applied to analyze its diagnostic value.

Results

Our data indicated that apolipoprotein AI (OR = 0.051, 95% CI: 0.009‐0.295), lipoprotein (a) (OR = 1.003, 95% CI: 1.001‐1.005), and RBC rigidity index (OR = 0.383, 95% CI: 0.209‐0.702) were independent risk factors. Area under the curve (AUC) of the regression model = 0.78, with the sensitivity of 73.9% (95% CI: 64.9%‐81.7%) and specificity of 69.2% (95% CI: 52.4%‐83.0%). Prediction probability was determined while logistic regression score >0.748 defaulted as high‐risk status. High‐risk ratios were 80% in progressive cerebral infarction and 72% in nonprogressive cerebral infarction (P > .05), respectively, while significant differences were found when both compared with controls (P < .001).

Conclusions

We show herein that the regression model based on apolipoprotein AI, lipoprotein (a), and RBC IR is a promising tool to predict the occurrence of cerebral infarction in patients with carotid artery stenosis. However, identification of novel diagnostic markers for progressive cerebral infarction is still necessary.
Young sexual minority women's definition of community: Toward addressing health disparities in the LGBTQQ community
Authors: Sexton Patrina , Flores Dalmacio , Bauermeister José
Published: November 2017

In accord with Healthy People 2020 goals, the elimination of lesbian, gay, bisexual, transgender, queer, and questioning (LGBTQQ) health disparities will require community‐level strategies to address stigma, discrimination, and prejudice linked to poor health. We explored how young sexual minority women (YSMW) define LGBTQQ community, community connection, community engagement, and community tensions because these concepts have implications for development and evaluation of health disparities interventions. A total of 30 YSMW (aged 18–24 years) from Michigan participated in semistructured, in‐depth interviews. Participants varied by sexual identity, residency, and race/ethnicity. We analyzed transcribed interviews using thematic analysis and compared emergent themes across sexual identity, residency, and race/ethnicity. Women described community connection in terms of organizational involvement, participation in LGBTQQ spaces, and collective social identity. Participants noted how community connections were linked to stigma towards the LGBTQQ community. YSMW highlighted how divisive tensions exist within subgroups constituting the LGBTQQ community, hindering opportunities for social advocacy, unified policy priorities, and community‐level interventions. The heterogeneity of YSMW's experiences identifying with the LGBTQQ community and engaging within LGBTQQ spaces suggest that researchers should attend to the role of community dynamics when developing health disparities interventions and policies. Efforts to reconcile tensions within the LGBTQQ community may strengthen and advance policymakers’ ability to address sexuality‐related disparities.
Resilience and adjustment to widowhood in the Israeli Arab Muslim society: A new perspective
Authors: Yasien Esmael Hend , Eshel Yohanan , Shimshon Rubin Simon
Published: November 2017

Research on bereavement and loss is often concentrated on sustaining meaning in life and maintaining emotional well‐being, despite the psychological impact of loss. However, this research rarely examined empirically what determines the resilience of the bereaved. The present study posits that resilience of widows is a dual construct representing the ratio of their strength and vulnerability (SVR). This ratio of protective factors and risk factors, which was validated in studies of resilience to the effects of war, terrorist attacks, or fire disaster, is presently examined by the balance of posttraumatic growth to distress symptoms of 93 Israeli Arab Muslim widows. Results show that SVR and resilience promoting personality attributes are consistently correlated with beneficial and detrimental responses to a loss of a husband. Results are discussed in terms of cultural effects on mourning, and the validity of the SVR index.
Usefulness of exosome‐encapsulated microRNA‐451a as a minimally invasive biomarker for prediction of recurrence and prognosis in pancreatic ductal adenocarcinoma
Authors: Takahasi Kunihiko , Iinuma Hisae , Wada Keita , Minezaki Shunryo , Kawamura Sachiyo , Kainuma Masahiko , Ikeda Yutaka , Shibuya Makoto , Miura Fumihiko , Sano Keiji
Published: November 2017

Background

MicroRNAs (miRNAs) encapsulated in the exosomes of plasma is of interest as stable and minimally invasive biomarkers for recurrence and prognosis in cancer patients. The aim of this study was to clarify the predictive and prognostic value of plasma exosomal microRNA‐451a (miR‐451a) in patients with pancreatic ductal adenocarcinoma (PDAC).

Methods

Microarray‐based expression profiling of miRNAs derived from exosomes in the plasma of six PDAC patients with UICC stage II was employed to identify a biomarker to distinguish between patients with and without recurrence. For validation analysis, plasma exosome samples of other 50 PDAC patients were measured by TaqMan MicroRNA assays.

Results

In the miRNA microarray analyses, miR‐451a showed the highest upregulation in the stage II patients who showed recurrence after surgery. In the relationship to pathological factors, exosomal miR‐451a showed a significant association with tumor size and stage. The overall survival (OS) and disease‐free survival rates (DFS) of the high exosomal miR‐451a patients were significantly worse than those of the low miR‐451a patients. In Cox proportional hazards model analysis, exsomal miR‐451a showed significance to OS and DFS.

Conclusions

Plasma exosomal miR‐451a levels may be a useful minimally invasive biomarker for the prediction of recurrence and prognosis in PDAC patients.
Distributed decision making in action: diagnostic imaging investigations within the bigger picture
Authors: Makanjee Chandra R. , Bergh Anne‐Marie , Hoffmann Willem A.
Published: November 2017

Introduction

Decision making in the health care system – specifically with regard to diagnostic imaging investigations – occurs at multiple levels. Professional role players from various backgrounds are involved in making these decisions, from the point of referral to the outcomes of the imaging investigation. The aim of this study was to map the decision‐making processes and pathways involved when patients are referred for diagnostic imaging investigations and to explore distributed decision‐making events at the points of contact with patients within a health care system.

Method

A two‐phased qualitative study was conducted in an academic public health complex with the district hospital as entry point. The first phase included case studies of 24 conveniently selected patients, and the second phase involved 12 focus group interviews with health care providers. Data analysis was based on Rapley's interpretation of decision making as being distributed across time, situations and actions, and including different role players and technologies.

Results

Clinical decisions incorporating imaging investigations are distributed across the three vital points of contact or decision‐making events, namely the initial patient consultation, the diagnostic imaging investigation and the post‐investigation consultation. Each of these decision‐making events is made up of a sequence of discrete decision‐making moments based on the transfer of retrospective, current and prospective information and its transformation into knowledge.

Conclusion

This paper contributes to the understanding of the microstructural processes (the ‘when’ and ‘where’) involved in the distribution of decisions related to imaging investigations. It also highlights the interdependency in decision‐making events of medical and non‐medical providers within a single medical encounter.
The maximum standardized uptake value of preoperative positron emission tomography/computed tomography in lung adenocarcinoma with a ground‐glass opacity component of less than 30 mm
Authors: Son Bong Y. , Cho Sukki , Yum Sung W. , Kim Kwhanmien , Jheon Sanghoon
Published: November 2017

Background and Objectives

This study evaluated the relationship between the maximum standardized uptake value (SUVmax) of preoperative positron emission tomography/computed tomography (PET/CT) and the characteristics of lung adenocarcinoma featuring ground‐glass opacity nodules (GGN).

Methods

The association of the SUVmax of preoperative PET/CT with ground‐glass opacity (GGO) proportion on CT, subtypes of adenocarcinoma (minimally invasive adenocarcinoma, invasive adenocarcinoma), predominant types of invasive adenocarcinoma, and size of the total and invasive components of pathology were evaluated in 190 patients who underwent resection for lung adenocarcinoma featuring GGN.

Results

The mean SUVmax of non‐solid GGN and partly solid GGN were 0.53 and 1.32, respectively (P = 0.029). The mean SUVmax of the main masses in 38 patients with MIA and 152 with invasive adenocarcinoma were 0.86 and 1.36, respectively (P = 0.029). The mean SUVmax of acinar, lepidic, papillary, and solid tumors were 1.61, 0.87, 0.98, and 1.60, respectively. The mean SUVmax of invasive components measuring ≤10 mm, 11‐20 mm, and >20 mm were 0.84, 1.66, and 2.09, respectively (P < 0.001).

Conclusions

The SUVmax of lung adenocarcinoma featuring GGN can vary depending on the GGO proportion. A higher SUVmax can be expected in invasive adenocarcinoma than in MIA, and solid and acinar‐predominant invasive adenocarcinoma showed a higher SUVmax.
Historical perspectives and future directions in the surgical management of retroperitoneal sarcoma
Authors: Tseng William W. , Seo Hyun Jae , Pollock Raphael E. , Gronchi Alessandro
Published: November 2017

Retroperitoneal sarcomas (RPS) have fascinated and intrigued physicians both past and present. Operative mortality rates were historically very high and complete resection was not possible for the majority of patients until only the last 2 decades. More recently, changes to the surgical approach and clinical decision‐making in RPS have improved patient outcomes. With select integration of nonsurgical therapies, continued RPS‐specific research, and ongoing collaborative efforts among major referral centers, the future appears promising.
The impact of preoperative magnetic resonance imaging and lumpectomy cavity shavings on re‐excision rate in pure ductal carcinoma in situ—A single institution's experience
Authors: So Alycia , De La Cruz Lucy M. , Williams Austin D. , Bahng Joseph , Liao Geraldine , McDonald Elizabeth S. , Fisher Carla S. , Czerniecki Brian J. , Sataloff Dahlia , Tchou Julia
Published: November 2017

Background and Objectives

The impact of preoperative magnetic resonance imaging (pMRI) and cavity shave margins (CSM) on re‐excision rate (RR) in DCIS is unclear. We investigated whether either modality was associated with RR in DCIS.

Methods

This is a single‐institution retrospective study of 295 women undergoing breast conservation surgery for pure DCIS (2010‐2013). CSM were the systematic resection of 4‐6 margins during lumpectomy whereas selective shave margins (SSM) were the selective resection of 1‐3 margins. Patient demographics and clinical characteristics were abstracted. RR was analyzed according to the use of pMRI, SSM, or CSM with respect to three high‐volume breast surgeons at our institution.

Results

RR was not associated with the use of pMRI (P = 0.87). Any shave margins (P = 0.05), DCIS size (P < 0.001), and DCIS grade (P = 0.14) associated with a lower RR. Of our high‐volume surgeons, RR was lower for Surgeon A (P = 0.02). Multivariate analyses showed larger DCIS (OR 1.35, P = 0.005) and practices specific to surgeons B (OR 3.23, P = 0.04) and C (OR 3.57, P = 0.04) increased re‐excision odds.

Conclusions

SSM/CSM and pMRI use varied among surgeons. Our results suggested the routine use of CSM, not pMRI, could lower re‐excision rate, which highlighted a quality improvement opportunity at our institution.
Management of the “Other” retroperitoneal sarcomas
Authors: Rutkowski Piotr L. , Mullen John T.
Published: November 2017

The focus of this review is on the management of the less common sarcomas occurring in the retroperitoneal space, including solitary fibrous tumor (SFT), malignant peripheral nerve sheath tumor (MPNST), perivascular epithelioid cell tumor (PEComa), and undifferentiated pleomorphic sarcoma (UPS) of the psoas muscle. As for other retroperitoneal sarcomas, surgical resection is the mainstay of curative therapy, and multidisciplinary preoperative assessment, including percutaneous needle biopsy for histologic confirmation, is the basis for personalized management, as the surgical management, and the integration of systemic therapy and radiation therapy is unique to each histologic subtype.
Does neoadjuvant/perioperative chemotherapy improve overall survival for T2N0 gastric adenocarcinoma?
Authors: Gabriel Emmanuel , Attwood Kristopher , Narayanan Sumana , Brady Maureen , Nurkin Steven , Hochwald Steven , Kukar Moshim
Published: November 2017

Background

The purpose of this study was to determine whether neoadjuvant and/or perioperative chemotherapy (NAC) has an overall survival (OS) benefit for patients with T2N0 gastric adenocarcinoma.

Study Design

We performed retrospective analyses using the National Cancer Data Base, 2004‐2013. Patients with T2N0 gastric adenocarcinoma were divided into two treatment groups: (1) NAC plus surgery (NA + S) and (2) surgery alone (S).

Results

Of 1,704 patients included, 277 (16.3%) received NAC, and 1,427 (83.7%) were treated with surgery alone. Patients in the NA + S group were more likely to be younger, have fewer comorbidities, and have larger tumors located in the proximal stomach. Although in an unadjusted analysis of OS, the NA + S group had improved survival compared to the S group (HR = 0.81, 95% CI 0.67‐0.99, P < 0.0001), this was not maintained in a propensity adjusted analysis (HR = 0.89, 95% CI 0.68‐1.18, P = 0.42). Similarly, propensity adjusted analyses accounting for potential bias from clinical misstaging or treatment effect from NAC did not show any OS benefit from NAC.

Conclusion

Based on the largest cohort of clinically staged T2N0 gastric adenocarcinoma, there was no OS benefit derived from NAC compared to surgery alone. For select patients with reliable preoperative staging, NAC may be omitted.
Safety Aspects of the Use of Quercetin as a Dietary Supplement
Authors: Andres Susanne , Pevny Sophie , Ziegenhagen Rainer , Bakhiya Nadiya , Schäfer Bernd , Hirsch‐Ernst Karen Ildico , Lampen Alfonso
Published: November 2017

The flavonoid quercetin is frequently found in low amounts as a secondary plant metabolite in fruits and vegetables. Isolated quercetin is also marketed as a dietary supplement, mostly as the free quercetin aglycone, and frequently in daily doses of up to 1000 mg d–1 exceeding usual dietary intake levels. The present review is dedicated to safety aspects of isolated quercetin used as single compound in dietary supplements. Among the numerous published human intervention studies, adverse effects following supplemental quercetin intake have been rarely reported and any such effects were mild in nature. Published adequate scientific data for safety assessment in regard to the long‐term use (>12 weeks) of high supplemental quercetin doses (≥1000 mg) are currently not available. Based on animal studies involving oral quercetin application some possible critical safety aspects could be identified such as the potential of quercetin to enhance nephrotoxic effects in the predamaged kidney or to promote tumor development especially in estrogen‐dependent cancer. Furthermore, animal and human studies with single time or short‐term supplemental quercetin application revealed interactions between quercetin and certain drugs leading to altered drug bioavailability. Based on these results, some potential risk groups are discussed in the present review.
99Tc NMR determination of the oxygen isotope content in 18O‐enriched water
Authors: Tarasov Valerii P. , Kirakosyan Gayana А. , German Konstantin E.
Published: November 2017

99Tc NMR has been suggested as an original method of evaluating the content of oxygen isotopes in oxygen‐18‐enriched water, a precursor for the production of radioisotope fluorine‐18 used in positron emission tomography. To this end, solutions of NH4TcO4 or NaTcO4 (up to 0.28 mol/L) with natural abundance of oxygen isotopes in virgin or recycled 18O‐enriched water have been studied by 99Tc NMR. The method is based on 16O/17O/18O intrinsic isotope effects in the 99Tc NMR chemical shifts, and the statistical distribution of oxygen isotopes in the coordination sphere of TcO4− and makes it possible to quantify the composition of enriched water by measuring the relative intensities of the 99Tc NMR signals of the Tc16O4−n18On− isotopologues. Because the oxygen exchange between TcO4− and enriched water in neutral and alkaline solutions is characterized by slow kinetics, gaseous HCl was bubbled through a solution for a few seconds to achieve the equilibrium distribution of oxygen isotopes in the Tc coordination sphere without distortion of the oxygen composition of the water. Pertechnetate ion was selected as a probe due to its high stability in solutions and the significant 99Tc NMR shift induced by a single 16O→18O substitution (−0.43 ± 0.01 ppm) in TcO4− and spin coupling constant 1J(99Tc–17O) (131.46 Hz) favourable for the observation of individual signals of Tc16O4−n18On− isotopologues.