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1.  Overexpression of Brain-Derived Neurotrophic Factor Protects Large Retinal Ganglion Cells After Optic Nerve Crush in Mice 
eNeuro  2017;4(1):ENEURO.0331-16.2016.
Abstract
Brain-derived neurotrophic factor (BDNF), a neurotrophin essential for neuron survival and function, plays an important role in neuroprotection during neurodegenerative diseases. In this study, we examined whether a modest increase of retinal BDNF promotes retinal ganglion cell (RGC) survival after acute injury of the optic nerve in mice. We adopted an inducible Cre-recombinase transgenic system to up-regulate BDNF in the mouse retina and then examined RGC survival after optic nerve crush by in vivo imaging. We focused on one subtype of RGC with large soma expressing yellow fluorescent protein transgene that accounts for ∼11% of the total SMI-32–positive RGCs. The median survival time of this subgroup of SMI-32 cells was 1 week after nerve injury in control mice but 2 weeks when BDNF was up-regulated. Interestingly, we found that the survival time for RGCs taken as a whole was 2 weeks, suggesting that these large-soma RGCs are especially vulnerable to optic nerve crush injury. We also studied changes in axon number using confocal imaging, confirming first the progressive loss reported previously for wild-type mice and demonstrating that BDNF up-regulation extended axon survival. Together, our results demonstrate that the time course of RGC loss induced by optic nerve injury is type specific and that overexpression of BDNF prolongs the survival of one subgroup of SMI-32–positive RGCs.
doi:10.1523/ENEURO.0331-16.2016
PMCID: PMC5240030
brain-derived neurotrophic factor (BDNF); in vivo imaging; neuroprotection; optic nerve crush; retinal ganglion cells (RGCs)
2.  Residential exposure to chlorinated hydrocarbons from groundwater contamination and the impairment of renal function-An ecological study 
Scientific Reports  2017;7:40283.
Groundwater pollution from the petrochemical industry causes serious deterioration of soil and groundwater quality and impacts on human health worldwide. However, few studies have examined the effect of residential exposure to petrochemical chlorinated hydrocarbon-contaminated groundwater on renal function impairment in humans. We conducted an ecological study to investigate the two. A polyvinyl chloride (PVC) plant was located in one of the six villages, the study area, in Kaohsiung city of southwestern Taiwan. Based on the direction of groundwater flow and previous groundwater measurements of chlorinated hydrocarbons from Taiwan Environmental Protection Bureau, we divided the six villages into highly-polluted villages, moderately-polluted villages, and a non-polluted village. All inhabitants in those six villages were invited to receive free health examinations between May-June, 2010. In total, 4,432 study subjects ≥18 yrs old were analyzed. Compared to those in the non-polluted village, subjects in highly-polluted villages had 1.89- and 1.46-fold the risk of impaired estimated glomerular filtration rate (eGFR) and proteinuria (95% CI = 1.15–1.85 and 1.09–3.28, respectively) after adjusting for other covariates. Given this relative large sample size, we found that groundwater chlorinated hydrocarbon pollution can cause kidney damage in adults.
doi:10.1038/srep40283
PMCID: PMC5220340  PMID: 28067285
3.  Multi-antigen avian influenza a (H7N9) virus-like particles: particulate characterizations and immunogenicity evaluation in murine and avian models 
BMC Biotechnology  2017;17:2.
Background
Human infection with avian influenza A virus (H7N9) was first reported in China in March 2013. Since then, hundreds of cases have been confirmed showing severe symptoms with a high mortality rate. The virus was transmitted from avian species to humans and has spread to many neighboring areas, raising serious concerns over its pandemic potential. Towards containing the disease, the goal of this study is to prepare a virus-like particle (VLP) that consists of hemagglutinin (HA), neuraminidase (NA) and matrix protein 1 (M1) derived from the human isolate A/Taiwan/S02076/2013(H7N9) for potential vaccine development.
Results
Full length HA, NA, and M1 protein genes were cloned and expressed using a baculoviral expression system, and the VLPs were generated by co-infecting insect cells with three respective recombinant baculoviruses. Nanoparticle tracking analysis and transmission electron microscopy were applied to verify the VLPs’ structure and antigenicity, and the multiplicity of infection of the recombinant baculoviruses was adjusted to achieve the highest hemagglutination activity. In animal experiments, BALB/c mice and specific-pathogen-free chickens receiving the VLP immunization showed elevated hemagglutination inhibition serum titer and antibodies against NA and M1 proteins. In addition, examination of cellular immunity showed the VLP-immunized mice and chickens exhibited an increased splenic antigen-specific cytokines production.
Conclusions
The H7N9 VLPs possess desirable immunogenicity in vivo and may serve as a candidate for vaccine development against avian influenza A (H7N9) infection.
Electronic supplementary material
The online version of this article (doi:10.1186/s12896-016-0321-6) contains supplementary material, which is available to authorized users.
doi:10.1186/s12896-016-0321-6
PMCID: PMC5219756  PMID: 28061848
Avian influenza virus A (H7N9); Virus-like particles; Vaccine
4.  Long-Term Protection of Retinal Ganglion Cells and Visual Function by Brain-Derived Neurotrophic Factor in Mice With Ocular Hypertension 
Purpose
Glaucoma, frequently associated with elevated intraocular pressure (IOP), is characterized by progressive retinal ganglion cell (RGC) death and vision loss. Brain-derived neurotrophic factor (BDNF) has been studied as a candidate for neuroprotection in rodent models of experimental glaucoma, yet it remains to be determined whether BDNF exerts long-term protection for subtype RGCs and vision against chronic IOP elevation.
Methods
We induced modest and sustained IOP elevation by laser illumination and microbead injection in mice. Using a tamoxifen-induced Cre recombinase system, BDNF was upregulated in the mouse retina when sustained IOP elevation was induced. We then examined whether overexpression of BDNF protected RGCs and vision during the period of ocular hypertension. Given that BDNF modulates axon growth and dendritic formation in a subtype-dependent manner, we tested whether BDNF protects RGC dendritic structure against the hypertensive insult also in a subtype-dependent manner.
Results
Sustained IOP elevation was induced and lasted up to 6 months. Overexpression of BDNF delayed progressive RGC and axon loss in hypertensive eyes. Brain-derived neurotrophic factor overexpression also helped to preserve acuity against the chronic hypertensive insult. We classified RGCs into ON and ON–OFF subtypes based on their dendritic lamination pattern in the inner plexiform layer and found that BDNF prevented ON–RGC dendritic degeneration in mice with sustained ocular hypertension.
Conclusions
Our data demonstrated that BDNF can protect the dendritic fields of ON RGCs and reduce RGC and vision loss in mice with sustained ocular hypertension.
doi:10.1167/iovs.16-19825
PMCID: PMC4961002  PMID: 27421068
retinal ganglion cells (RGCs); brain-derived neurotrophic factor (BDNF); neuroprotection; visual acuity; experimental glaucoma
5.  Factors influencing exclusive breastfeeding among Iranian mothers: A longitudinal population-based study 
Health Promotion Perspectives  2016;7(1):34-41.
Background: Exclusive breastfeeding (EBF) contributes to the health and survival of the newborns. Many factors influence the EBF behavior. This study aimed to identify the determinant factors in order to improve the practice of EBF among Iranian mothers.
Methods: A longitudinal study was carried out in 1445 mothers with newborns in Qazvin city, Iran (September 2015-March 2016). Demographic variables as well as the constructs of theory of planned behavior (TBP) were measured by questionnaires. Bivariate analysis using Pearson and Spearman correlation tests with analysis of variance were used to investigate the associations among the variables. Both hierarchal multiple regression and logistic regression were applied to identify potential determinative factors for the EBF.
Results: Nearly, 80% (CI: 77.97-82.63%) of the participants had the intention of EBF. All TPB constructs, moral norms, and self-identity were significantly correlated with each other (r: 0.09- 0.40, P < 0.01). Some demographic variables such as age, income, employment and primiparity were also correlated with the EBF (r: 0.11-0.15, P < 0.05). The constructs of the TPB were able to predict the EBF behavior, which account for 49% of the variance in the predicting factors (df = 8, F = 7.70). The self-identity and moral norms accounted for an additional 15% of the variance (df = 10, F = 3.16). Younger mothers with lower socio-economic status were at higher risk of EBF cessation. The intention has a greater impact on the initiation of EBF than perceived behavioral control (PBC) but not for the maintenance of EBF (OR, 2.88 [CI: 2.38-3.48] & 1.13 [CI:1.03- 1.23] vs. OR, 1.27 [CI:1.15-1.39] & 2.66 [CI: 2.02-3.49]).
Conclusion: The interventions to promote knowledge, attitude and behavioral control towards the EBF should be considered especially in the young mothers with low socio-economic status.
doi:10.15171/hpp.2017.07
PMCID: PMC5209648  PMID: 28058240
Exclusive breastfeeding; Mothers; Theory of planned behavior
6.  Chronic Olanzapine Treatment Induces Disorders of Plasma Fatty Acid Profile in Balb/c Mice: A Potential Mechanism for Olanzapine-Induced Insulin Resistance 
PLoS ONE  2016;11(12):e0167930.
Background
Atypical antipsychotics such as olanzapine cause metabolic side effects leading to obesity and insulin resistance. The underlying mechanisms remain elusive. In this study we investigated the effects of chronic treatment of olanzapine on the fatty acid composition of plasma in mice.
Methods
Twenty 8-week female Balb/c mice were randomly assigned to two groups: the OLA group and the control group. After treatment with olanzapine (10 mg/kg/day) or vehicle intraperitoneally for 8 weeks, fasting glucose, insulin levels and oral glucose tolerance test were determined. Effects on plasma fatty acid profile and plasma indices of D5 desaturase, D6 desaturase and SCD1 activity were also investigated.
Results
Chronic administration of olanzapine significantly elevated fasting glucose and insulin levels, impaired glucose tolerance, but did not increase body weight. Total saturated fatty acids and n-6 polyunsaturated fatty acids were significantly increased and total monounsaturated fatty acids were significantly decreased, while total n-3 polyunsaturated fatty acids showed no prominent changes. Chronic olanzapine treatment significantly up-regulated D6 desaturase activity while down-regulating D5 desaturase activity. Palmitic acid (C16:0), dihomo-γ-linolenic acid (C20:3n-6) and D6 desaturase were associated with an increase probability of insulin resistance, whereas nervonic acid (C24:1) and SCD1 were significantly associated with a lower insulin resistance probability.
Conclusions
All results indicated that such drug-induced effects on fatty acid profile in plasma were relevant for the metabolic adverse effects associated with olanzapine and possibly other antipsychotics. Further studies are needed to investigate geneticand other mechanisms to explain how plasma fatty acids regulate glucose metabolism and affect the risk of insulin resistance.
doi:10.1371/journal.pone.0167930
PMCID: PMC5156395  PMID: 27973621
7.  An update on the Pauwels classification 
Background
Femoral neck fractures typically occur as a result of high-energy mechanisms among non-geriatric patients. Complications, including femoral neck shortening, non-union, and avascular necrosis, are relatively common after the internal fixation of this fracture pattern. These complications have serious effects on young patients. The Pauwels classification, which is the first biomechanical classification for femoral neck fractures, is still frequently used to determine and prescribe the appropriate treatment for femoral neck fractures. However, we lack a unified standard for measuring the Pauwels angle, which may make the classification unreliable. Understanding the relationship between the Pauwels classification and the complications arising from the internal fixation of femoral neck fractures is necessary. Meanwhile, a Pauwels type III femoral neck fracture among young adults, which involves a high shear load at the fracture site, is difficult to treat successfully. In addition, the recognized internal fixation for this fracture pattern remains uncertain.
Main body
This review aims to provide an update on the viewpoint on the Pauwels classification including the measurement of the Pauwels angle and to present evidence to prove the aforementioned relationship. Moreover, this article also discusses the optimal internal fixation for femoral neck fractures based on the Pauwels classification.
Conclusion
A unified standard of measurement should be established for the Pauwels classification, which is still frequently used in the literature and in determining appropriate treatment for femoral neck fractures, to achieve a credible classification. In addition, more randomized, multicentric, and prospective trials should be conducted in the future to clearly understand the relationship between the Pauwels classification and complications arising from the internal fixation of femoral neck fractures and, consequently, to explore ideal fixations for a Pauwels type III femoral neck fracture.
doi:10.1186/s13018-016-0498-3
PMCID: PMC5154085  PMID: 27955672
Femoral neck fracture; Pauwels classification; Measurement of Pauwels angle; Post-operative complications; Therapeutic guideline
8.  Protocol of a prospective study for the combination treatment of Shu-Gan-jian-Pi decoction and steroid standard therapy in autoimmune hepatitis patients 
Background
Prednisone plus azathioprine is considered the mainstay of therapy in the current recommendations for autoimmune hepatitis (AIH). However, it does not provide good benefits for AIH patients because of its serious side effects. Therefore, more and more AIH patients prefer to seek for traditional Chinese medicine (TCM) to manage their symptoms and reduce the side effects of steroids in China. Shu-Gan-Jian-Pi Decoction is a popular used Chinese herbal formula in Guangdong province of China, which has demonstrated the effect of improving efficacy and reducing side effects of corticosteroids in AIH patients. The aim of this study is to evaluate the effects of Shu-Gan-Jian-Pi Decoction combined with steroid in AIH patients. So, this study aims to explore whether the combination treatment of Shu-Gan-Jian-Pi Decoction and steroid standard therapy could improve the clinical management of AIH.
Methods
A prospective non-randomized study on AIH will be conducted between October 2015 and June 2017 in Guangdong Provincial hospital of Chinese medicine. Eligible AIH patients will be classified as the case group (n = 66) and the control group (n = 66) based on the interventions. Patients taking Shu-Gan-Jian-Pi Decoction combined with prednisone and azathioprine will be in the case group and those taking prednisone and azathioprine will be in the control group. The whole study will last 48 weeks, including a 24-week observation period and a 24-week follow-up period. The primary outcome was complete response to therapy, defined as complete biochemical remission at the patient’s last visit of observation period and the absence of predefined steroid-specific side effects throughout treatment.
Discussion
This trial will evaluate the efficacy and safety of Shu-Gan-Jian-Pi Decoction combined with prednisone and azathioprine on AIH patients. The achievement of this trial will provide evidence-based data for Shu-Gan-Jian-Pi Decoction, which could provide good benefits for AIH patients.
Trial registration
Chinese Clinical Trial Registry: ChiCTR-OOC-15006155.
Registration date: 28 March 2015
doi:10.1186/s12906-016-1486-1
PMCID: PMC5142150  PMID: 27923369
Autoimmune Hepatitis; Steroid; Side effects; Shu-Gan-Jian-Pi Decoction
9.  Global Deletion of TSPO Does Not Affect the Viability and Gene Expression Profile 
PLoS ONE  2016;11(12):e0167307.
Translocator Protein (18kDa, TSPO) is a mitochondrial outer membrane transmembrane protein. Its expression is elevated during inflammation and injury. However, the function of TSPO in vivo is still controversial. Here, we constructed a TSPO global knockout (KO) mouse with a Cre-LoxP system that abolished TSPO protein expression in all tissues and showed normal phenotypes in the physiological condition. The birth rates of TSPO heterozygote (Het) x Het or KO x KO breeding were consistent with Mendel’s Law, suggesting a normal viability of TSPO KO mice at birth. RNA-seq analysis showed no significant difference in the gene expression profile of lung tissues from TSPO KO mice compared with wild type mice, including the genes associated with bronchial alveoli immune homeostasis. The alveolar macrophage population was not affected by TSPO deletion in the physiological condition. Our findings contradict the results of Papadopoulos, but confirmed Selvaraj’s findings. This study confirms TSPO deficiency does not affect viability and bronchial alveolar immune homeostasis.
doi:10.1371/journal.pone.0167307
PMCID: PMC5131929  PMID: 27907096
10.  Impact of CYP2C19 Variants on Clinical Efficacy of Clopidogrel and 1-Year Clinical Outcomes in Coronary Heart Patients Undergoing Percutaneous Coronary Intervention 
The impact of pharmacogenetic variants of cytochrome P450 2C19 (CYP2C19) on clopidogrel-mediated effects on platelet inhibition, inflammatory response and endothelial function, as well as risk of major adverse cardiovascular events (MACE), in coronary heart patients undergoing percutaneous coronary intervention (PCI) was investigated. To this end, we assessed the residual platelet aggregation rate (RPA), maximal aggregation rate (MAR) and plasma levels of sCD40L, sP-selectin, MMP-9, sVCAM-1 and sE-selectin after 24 h of PCI in 559 patients treated with clopidogrel and followed up for 1 year for evidence of MACE. CYP2C19 *2 and *3 variants were identified using a clopidogrel-sensitive gene detection kit. Our results showed higher RPA and MAR as well as increased sE-selectin, sCD40L, sP-selectin, MMP-9, and sVCAM-1 levels in CYP2C19 intermediate metabolizer (IM, CYP2C19*1/*2, or *1/*3), poor metabolizer (PM, CYP2C19*2/*2, *2/*3, or *3/*3) and combined IM+PM groups, relative to those in extensive metabolizers (EM, CYP2C19*1/*1). In total, 519 patients completed 1 year of follow-up, among which 69 (13.3%) experienced MACE. The risk of MACE in CYP2C19 IM+PM patients was 2.664 times higher than that in CYP2C19 EM patients (OR = 2.664 (1.397–5.193), P = 0.004). The data suggest that CYP2C19*2 and *3 variants modulate the drug efficacy of clopidogrel in coronary heart patients undergoing PCI and further enhance the risk of MACE. Accordingly, CYP2C19 pharmacogenetic profiling may be beneficial for coronary heart patients undergoing PCI to predict the efficacy of treatment with clopidogrel. We propose that IM and PM patients should benefit from treatment with higher clopidogrel doses to improve efficacy and reduce the incidence of MACE.
doi:10.3389/fphar.2016.00453
PMCID: PMC5121225  PMID: 27932982
CYP2C19; clopidogrel; PCI; antiplatelet therapy; metabolizers
11.  Identification of an infectious bronchitis coronavirus strain exhibiting a classical genotype but altered antigenicity, pathogenicity, and innate immunity profile 
Scientific Reports  2016;6:37725.
Avian coronavirus infectious bronchitis virus (IBV) poses economic threat to the poultry industry worldwide. Pathogenic IBV 3575/08 was isolated from broilers vaccinated with the attenuated viral vaccine derived from a Taiwan strain 2575/98. In this study, extensive investigations were conducted on the genome sequences, antigenicity, pathogenicity, and host immune responses of several IBV strains in specific-pathogen-free chickens. Sequence analyses revealed that 3575/08 and 2575/98 shared high homology in their structural genes, but not in non-structural accessory proteins such as 3a, 3b and 5b. Despite a high degree of homology in their spike protein genes, cross neutralization test showed low cross protection between 3575/08 and 2575/98, suggesting distinct antigenicity for the two strains. Animal challenge experiments exhibited strong respiratory and renal pathogenicity for 3575/08. In addition, early and prolonged viral shedding and rapid viral dissemination were observed. Immune gene expression profiling by PCR array showed chickens infected with 3575/08 had delayed expression of a subset of early innate immune genes, whereas chickens infected with the wild-type or attenuated-type 2575/08 revealed quick gene induction and efficient virus control. In summary, this study reveals a new IBV strain, which harbors a known local genotype but displays remarkably altered antigenicity, pathogenicity and host defenses.
doi:10.1038/srep37725
PMCID: PMC5120290  PMID: 27876864
12.  Ovarian thecoma-fibroma groups: clinical and sonographic features with pathological comparison 
Background
Ovarian thecoma-fibroma groups (OTFG) are uncommon sex cord-stromal neoplasms. The objective of the study was to demonstrate clinical and sonographic features of OTFG and compare with surgical histopathology.
Methods
A total of 61 patients with surgically proven OTFG were enrolled in this retrospective study to demonstrate its clinical and sonographic features and to compare with pathological findings. Gray scale and color Doppler sonography were performed presurgically with either transabdominal or transvaginal approach to image pelvic structures and lesions. The clinical findings and sonographic appearances were compared with the types of the OTFG tumors based on the histopathological diagnosis.
Results
The mean patient age was 53.57 (range, 26–86) years. There were 63.93% (39/61) patients in postmenopausal and 63.93% (39/61) patients with no clinical symptoms. Ultrasound findings of OTFG revealed as solid tumors with a typical feature of well-demarcated hypoechoic masses in 70.49% (43/61), among which 74.41% (32/43) tumors were smaller than 5 cm in diameter. There were 17 mixed echogenic masses with calcification, hemorrhage, or cyst, among which 70.59% (12/17) lesions were larger than 5 cm in diameter. Acoustic attenuation of the tumor was presented in 44.26% (27/61) of the cases. Doppler flow signals within the tumors were found in 20 cases (32.79%), in which 80% (16/20) had minimal or moderate flow signals. Ascites was detected in 32.79% (20/61) of the cases, Megi’s syndrome was found in 1 case. Final pathology revealed 41 (67.21%) thecoma-fibromas, 15 (24.59%) fibromas, 4 (6.56%) thecomas and 1 (1.64%) fibrosarcoma. There were 58 patients underwent cancer antigen 125 (CA125) test, and 20.69% (12/58) showed an elevated level. The diameter of tumors was found to be significantly correlated with CA125 level (p < 0.01) and the amount of ascites fluid (p < 0.05).
Conclusions
The typical sonographic features of OTFG include adnexal hypoechoic masses with clear border and acoustic attenuation as well as minimal Doppler flow signals. All the aforementioned features could make ultrasound imaging as a assistent tool improve the preoperative diagnostic accuracy.
doi:10.1186/s13048-016-0291-2
PMCID: PMC5120502  PMID: 27876070
Thecoma; Fibroma; Ovarian neoplasms; Ultrasound; Pathology
13.  MicroRNA-455-3p Inhibits Tumor Cell Proliferation and Induces Apoptosis in HCT116 Human Colon Cancer Cells 
Background
MicroRNAs have been reported to play significant roles in pathogenesis of colorectal cancer (CRC). In the present study, we aimed to investigate the functional role of microRNA-455-3p (miR-455-3p) in CRC, as well as its underlying mechanisms.
Material/Methods
Human colon cancer cell line HCT116 cells were transfected with miR-455-3p mimics, inhibitors, or controls. After transfection, the effects of miR-455-3p mimics or inhibitors on cell proliferation were analyzed by 3-(4, 5-dimethyl-2- thiazolyl)-2, 5-diphenyl -2-H-tetrazolium bromide (MTT) assay and BrdU assay, and the effects of miR-455-3p mimics or inhibitors on cell apoptosis were determined. In addition, the underlying mechanisms of cell proliferation and apoptosis were explored by assessing the protein levels of cell cycle regulators and apoptosis-related protein.
Results
The results showed that overexpression of miR-455-3p significantly inhibited the cell proliferation (P<0.05 or <0.01) in HCT116 cells compared with the control group, but significantly increased the apoptosis (P<0.01). On the contrary, suppression of miR-455-3p significantly increased the cell proliferation but decreased the apoptosis. Moreover, we found that overexpression of miR-455-3p significantly elevated the protein levels of p27 kinase inhibition protein (KIP) 1, Bax, pro-caspase-3, and active caspase-3, and markedly downregulated the levels of B-cell lymphoma-2 (Bcl-2). Contrary results were found by suppression of miR-455-3p. However, there were no significant differences in p21 expression.
Conclusions
MiRNA-455-3p functions as an anti-oncogene in HCT116 cells by inhibiting cell proliferation and inducing of apoptosis.
doi:10.12659/MSM.898452
PMCID: PMC5117242  PMID: 27861461
Apoptosis; Cell Proliferation; Colorectal Neoplasms; MicroRNAs
14.  31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part one 
Lundqvist, Andreas | van Hoef, Vincent | Zhang, Xiaonan | Wennerberg, Erik | Lorent, Julie | Witt, Kristina | Sanz, Laia Masvidal | Liang, Shuo | Murray, Shannon | Larsson, Ola | Kiessling, Rolf | Mao, Yumeng | Sidhom, John-William | Bessell, Catherine A. | Havel, Jonathan | Schneck, Jonathan | Chan, Timothy A. | Sachsenmeier, Eliot | Woods, David | Berglund, Anders | Ramakrishnan, Rupal | Sodre, Andressa | Weber, Jeffrey | Zappasodi, Roberta | Li, Yanyun | Qi, Jingjing | Wong, Philip | Sirard, Cynthia | Postow, Michael | Newman, Walter | Koon, Henry | Velcheti, Vamsidhar | Callahan, Margaret K. | Wolchok, Jedd D. | Merghoub, Taha | Lum, Lawrence G. | Choi, Minsig | Thakur, Archana | Deol, Abhinav | Dyson, Gregory | Shields, Anthony | Haymaker, Cara | Uemura, Marc | Murthy, Ravi | James, Marihella | Wang, Daqing | Brevard, Julie | Monaghan, Catherine | Swann, Suzanne | Geib, James | Cornfeld, Mark | Chunduru, Srinivas | Agrawal, Sudhir | Yee, Cassian | Wargo, Jennifer | Patel, Sapna P. | Amaria, Rodabe | Tawbi, Hussein | Glitza, Isabella | Woodman, Scott | Hwu, Wen-Jen | Davies, Michael A. | Hwu, Patrick | Overwijk, Willem W. | Bernatchez, Chantale | Diab, Adi | Massarelli, Erminia | Segal, Neil H. | Ribrag, Vincent | Melero, Ignacio | Gangadhar, Tara C. | Urba, Walter | Schadendorf, Dirk | Ferris, Robert L. | Houot, Roch | Morschhauser, Franck | Logan, Theodore | Luke, Jason J. | Sharfman, William | Barlesi, Fabrice | Ott, Patrick A. | Mansi, Laura | Kummar, Shivaani | Salles, Gilles | Carpio, Cecilia | Meier, Roland | Krishnan, Suba | McDonald, Dan | Maurer, Matthew | Gu, Xuemin | Neely, Jaclyn | Suryawanshi, Satyendra | Levy, Ronald | Khushalani, Nikhil | Wu, Jennifer | Zhang, Jinyu | Basher, Fahmin | Rubinstein, Mark | Bucsek, Mark | Qiao, Guanxi | MacDonald, Cameron | Hylander, Bonnie | Repasky, Elizabeth | Chatterjee, Shilpak | Daenthanasanmak, Anusara | Chakraborty, Paramita | Toth, Kyle | Meek, Megan | Garrett-Mayer, Elizabeth | Nishimura, Michael | Paulos, Chrystal | Beeson, Craig | Yu, Xuezhong | Mehrotra, Shikhar | Zhao, Fei | Evans, Kathy | Xiao, Christine | Holtzhausen, Alisha | Hanks, Brent A. | Scharping, Nicole | Menk, Ashley V. | Moreci, Rebecca | Whetstone, Ryan | Dadey, Rebekah | Watkins, Simon | Ferris, Robert | Delgoffe, Greg M. | Peled, Jonathan | Devlin, Sean | Staffas, Anna | Lumish, Melissa | Rodriguez, Kori Porosnicu | Ahr, Katya | Perales, Miguel | Giralt, Sergio | Taur, Ying | Pamer, Eric | van den Brink, Marcel R. M. | Jenq, Robert | Annels, Nicola | Pandha, Hardev | Simpson, Guy | Mostafid, Hugh | Harrington, Kevin | Melcher, Alan | Grose, Mark | Davies, Bronwyn | Au, Gough | Karpathy, Roberta | Shafren, Darren | Ricca, Jacob | Merghoub, Taha | Wolchok, Jedd D. | Zamarin, Dmitriy | Batista, Luciana | Marliot, Florence | Vasaturo, Angela | Carpentier, Sabrina | Poggionovo, Cécile | Frayssinet, Véronique | Fieschi, Jacques | Van den Eynde, Marc | Pagès, Franck | Galon, Jérôme | Hermitte, Fabienne | Smith, Sean G. | Nguyen, Khue | Ravindranathan, Sruthi | Koppolu, Bhanu | Zaharoff, David | Schvartsman, Gustavo | Bassett, Roland | McQuade, Jennifer L. | Haydu, Lauren E. | Davies, Michael A. | Tawbi, Hussein | Glitza, Isabella | Kline, Douglas | Chen, Xiufen | Fosco, Dominick | Kline, Justin | Overacre, Abigail | Chikina, Maria | Brunazzi, Erin | Shayan, Gulidanna | Horne, William | Kolls, Jay | Ferris, Robert L. | Delgoffe, Greg M. | Bruno, Tullia C. | Workman, Creg | Vignali, Dario | Adusumilli, Prasad S. | Ansa-Addo, Ephraim A | Li, Zihai | Gerry, Andrew | Sanderson, Joseph P. | Howe, Karen | Docta, Roslin | Gao, Qian | Bagg, Eleanor A. L. | Tribble, Nicholas | Maroto, Miguel | Betts, Gareth | Bath, Natalie | Melchiori, Luca | Lowther, Daniel E. | Ramachandran, Indu | Kari, Gabor | Basu, Samik | Binder-Scholl, Gwendolyn | Chagin, Karen | Pandite, Lini | Holdich, Tom | Amado, Rafael | Zhang, Hua | Glod, John | Bernstein, Donna | Jakobsen, Bent | Mackall, Crystal | Wong, Ryan | Silk, Jonathan D. | Adams, Katherine | Hamilton, Garth | Bennett, Alan D. | Brett, Sara | Jing, Junping | Quattrini, Adriano | Saini, Manoj | Wiedermann, Guy | Gerry, Andrew | Jakobsen, Bent | Binder-Scholl, Gwendolyn | Brewer, Joanna | Duong, MyLinh | Lu, An | Chang, Peter | Mahendravada, Aruna | Shinners, Nicholas | Slawin, Kevin | Spencer, David M. | Foster, Aaron E. | Bayle, J. Henri | Bergamaschi, Cristina | Ng, Sinnie Sin Man | Nagy, Bethany | Jensen, Shawn | Hu, Xintao | Alicea, Candido | Fox, Bernard | Felber, Barbara | Pavlakis, George | Chacon, Jessica | Yamamoto, Tori | Garrabrant, Thomas | Cortina, Luis | Powell, Daniel J. | Donia, Marco | Kjeldsen, Julie Westerlin | Andersen, Rikke | Westergaard, Marie Christine Wulff | Bianchi, Valentina | Legut, Mateusz | Attaf, Meriem | Dolton, Garry | Szomolay, Barbara | Ott, Sascha | Lyngaa, Rikke | Hadrup, Sine Reker | Sewell, Andrew Kelvin | Svane, Inge Marie | Fan, Aaron | Kumai, Takumi | Celis, Esteban | Frank, Ian | Stramer, Amanda | Blaskovich, Michelle A. | Wardell, Seth | Fardis, Maria | Bender, James | Lotze, Michael T. | Goff, Stephanie L. | Zacharakis, Nikolaos | Assadipour, Yasmine | Prickett, Todd D. | Gartner, Jared J. | Somerville, Robert | Black, Mary | Xu, Hui | Chinnasamy, Harshini | Kriley, Isaac | Lu, Lily | Wunderlich, John | Robbins, Paul F. | Rosenberg, Steven | Feldman, Steven A. | Trebska-McGowan, Kasia | Kriley, Isaac | Malekzadeh, Parisa | Payabyab, Eden | Sherry, Richard | Rosenberg, Steven | Goff, Stephanie L. | Gokuldass, Aishwarya | Blaskovich, Michelle A. | Kopits, Charlene | Rabinovich, Brian | Lotze, Michael T. | Green, Daniel S. | Kamenyeva, Olena | Zoon, Kathryn C. | Annunziata, Christina M. | Hammill, Joanne | Helsen, Christopher | Aarts, Craig | Bramson, Jonathan | Harada, Yui | Yonemitsu, Yoshikazu | Helsen, Christopher | Hammill, Joanne | Mwawasi, Kenneth | Denisova, Galina | Bramson, Jonathan | Giri, Rajanish | Jin, Benjamin | Campbell, Tracy | Draper, Lindsey M. | Stevanovic, Sanja | Yu, Zhiya | Weissbrich, Bianca | Restifo, Nicholas P. | Trimble, Cornelia L. | Rosenberg, Steven | Hinrichs, Christian S. | Tsang, Kwong | Fantini, Massimo | Hodge, James W. | Fujii, Rika | Fernando, Ingrid | Jochems, Caroline | Heery, Christopher | Gulley, James | Soon-Shiong, Patrick | Schlom, Jeffrey | Jing, Weiqing | Gershan, Jill | Blitzer, Grace | Weber, James | McOlash, Laura | Johnson, Bryon D. | Kiany, Simin | Gangxiong, Huang | Kleinerman, Eugenie S. | Klichinsky, Michael | Ruella, Marco | Shestova, Olga | Kenderian, Saad | Kim, Miriam | Scholler, John | June, Carl H. | Gill, Saar | Moogk, Duane | Zhong, Shi | Yu, Zhiya | Liadi, Ivan | Rittase, William | Fang, Victoria | Dougherty, Janna | Perez-Garcia, Arianne | Osman, Iman | Zhu, Cheng | Varadarajan, Navin | Restifo, Nicholas P. | Frey, Alan | Krogsgaard, Michelle | Landi, Daniel | Fousek, Kristen | Mukherjee, Malini | Shree, Ankita | Joseph, Sujith | Bielamowicz, Kevin | Byrd, Tiara | Ahmed, Nabil | Hegde, Meenakshi | Lee, Sylvia | Byrd, David | Thompson, John | Bhatia, Shailender | Tykodi, Scott | Delismon, Judy | Chu, Liz | Abdul-Alim, Siddiq | Ohanian, Arpy | DeVito, Anna Marie | Riddell, Stanley | Margolin, Kim | Magalhaes, Isabelle | Mattsson, Jonas | Uhlin, Michael | Nemoto, Satoshi | Villarroel, Patricio Pérez | Nakagawa, Ryosuke | Mule, James J. | Mailloux, Adam W. | Mata, Melinda | Nguyen, Phuong | Gerken, Claudia | DeRenzo, Christopher | Spencer, David M. | Gottschalk, Stephen | Mathieu, Mélissa | Pelletier, Sandy | Stagg, John | Turcotte, Simon | Minutolo, Nicholas | Sharma, Prannda | Tsourkas, Andrew | Powell, Daniel J. | Mockel-Tenbrinck, Nadine | Mauer, Daniela | Drechsel, Katharina | Barth, Carola | Freese, Katharina | Kolrep, Ulrike | Schult, Silke | Assenmacher, Mario | Kaiser, Andrew | Mullinax, John | Hall, MacLean | Le, Julie | Kodumudi, Krithika | Royster, Erica | Richards, Allison | Gonzalez, Ricardo | Sarnaik, Amod | Pilon-Thomas, Shari | Nielsen, Morten | Krarup-Hansen, Anders | Hovgaard, Dorrit | Petersen, Michael Mørk | Loya, Anand Chainsukh | Junker, Niels | Svane, Inge Marie | Rivas, Charlotte | Parihar, Robin | Gottschalk, Stephen | Rooney, Cliona M. | Qin, Haiying | Nguyen, Sang | Su, Paul | Burk, Chad | Duncan, Brynn | Kim, Bong-Hyun | Kohler, M. Eric | Fry, Terry | Rao, Arjun A. | Teyssier, Noam | Pfeil, Jacob | Sgourakis, Nikolaos | Salama, Sofie | Haussler, David | Richman, Sarah A. | Nunez-Cruz, Selene | Gershenson, Zack | Mourelatos, Zissimos | Barrett, David | Grupp, Stephan | Milone, Michael | Rodriguez-Garcia, Alba | Robinson, Matthew K. | Adams, Gregory P. | Powell, Daniel J. | Santos, João | Havunen, Riikka | Siurala, Mikko | Cervera-Carrascón, Víctor | Parviainen, Suvi | Antilla, Marjukka | Hemminki, Akseli | Sethuraman, Jyothi | Santiago, Laurelis | Chen, Jie Qing | Dai, Zhimin | Wardell, Seth | Bender, James | Lotze, Michael T. | Sha, Huizi | Su, Shu | Ding, Naiqing | Liu, Baorui | Stevanovic, Sanja | Pasetto, Anna | Helman, Sarah R. | Gartner, Jared J. | Prickett, Todd D. | Robbins, Paul F. | Rosenberg, Steven A. | Hinrichs, Christian S. | Bhatia, Shailender | Burgess, Melissa | Zhang, Hui | Lee, Tien | Klingemann, Hans | Soon-Shiong, Patrick | Nghiem, Paul | Kirkwood, John M. | Rossi, John M. | Sherman, Marika | Xue, Allen | Shen, Yueh-wei | Navale, Lynn | Rosenberg, Steven A. | Kochenderfer, James N. | Bot, Adrian | Veerapathran, Anandaraman | Gokuldass, Aishwarya | Stramer, Amanda | Sethuraman, Jyothi | Blaskovich, Michelle A. | Wiener, Doris | Frank, Ian | Santiago, Laurelis | Rabinovich, Brian | Fardis, Maria | Bender, James | Lotze, Michael T. | Waller, Edmund K. | Li, Jian-Ming | Petersen, Christopher | Blazar, Bruce R. | Li, Jingxia | Giver, Cynthia R. | Wang, Ziming | Grossenbacher, Steven K. | Sturgill, Ian | Canter, Robert J. | Murphy, William J. | Zhang, Congcong | Burger, Michael C. | Jennewein, Lukas | Waldmann, Anja | Mittelbronn, Michel | Tonn, Torsten | Steinbach, Joachim P. | Wels, Winfried S. | Williams, Jason B. | Zha, Yuanyuan | Gajewski, Thomas F. | Williams, LaTerrica C. | Krenciute, Giedre | Kalra, Mamta | Louis, Chrystal | Gottschalk, Stephen | Xin, Gang | Schauder, David | Jiang, Aimin | Joshi, Nikhil | Cui, Weiguo | Zeng, Xue | Menk, Ashley V. | Scharping, Nicole | Delgoffe, Greg M. | Zhao, Zeguo | Hamieh, Mohamad | Eyquem, Justin | Gunset, Gertrude | Bander, Neil | Sadelain, Michel | Askmyr, David | Abolhalaj, Milad | Lundberg, Kristina | Greiff, Lennart | Lindstedt, Malin | Angell, Helen K. | Kim, Kyoung-Mee | Kim, Seung-Tae | Kim, Sung | Sharpe, Alan D. | Ogden, Julia | Davenport, Anna | Hodgson, Darren R. | Barrett, Carl | Lee, Jeeyun | Kilgour, Elaine | Hanson, Jodi | Caspell, Richard | Karulin, Alexey | Lehmann, Paul | Ansari, Tameem | Schiller, Annemarie | Sundararaman, Srividya | Lehmann, Paul | Hanson, Jodi | Roen, Diana | Karulin, Alexey | Lehmann, Paul | Ayers, Mark | Levitan, Diane | Arreaza, Gladys | Liu, Fang | Mogg, Robin | Bang, Yung-Jue | O’Neil, Bert | Cristescu, Razvan | Friedlander, Philip | Wassman, Karl | Kyi, Chrisann | Oh, William | Bhardwaj, Nina | Bornschlegl, Svetlana | Gustafson, Michael P. | Gastineau, Dennis A. | Parney, Ian F. | Dietz, Allan B. | Carvajal-Hausdorf, Daniel | Mani, Nikita | Velcheti, Vamsidhar | Schalper, Kurt | Rimm, David | Chang, Serena | Levy, Ronald | Kurland, John | Krishnan, Suba | Ahlers, Christoph Matthias | Jure-Kunkel, Maria | Cohen, Lewis | Maecker, Holden | Kohrt, Holbrook | Chen, Shuming | Crabill, George | Pritchard, Theresa | McMiller, Tracee | Pardoll, Drew | Pan, Fan | Topalian, Suzanne | Danaher, Patrick | Warren, Sarah | Dennis, Lucas | White, Andrew M. | D’Amico, Leonard | Geller, Melissa | Disis, Mary L. | Beechem, Joseph | Odunsi, Kunle | Fling, Steven | Derakhshandeh, Roshanak | Webb, Tonya J. | Dubois, Sigrid | Conlon, Kevin | Bryant, Bonita | Hsu, Jennifer | Beltran, Nancy | Müller, Jürgen | Waldmann, Thomas | Duhen, Rebekka | Duhen, Thomas | Thompson, Lucas | Montler, Ryan | Weinberg, Andrew | Kates, Max | Early, Brandon | Yusko, Erik | Schreiber, Taylor H. | Bivalacqua, Trinity J. | Ayers, Mark | Lunceford, Jared | Nebozhyn, Michael | Murphy, Erin | Loboda, Andrey | Kaufman, David R. | Albright, Andrew | Cheng, Jonathan | Kang, S. Peter | Shankaran, Veena | Piha-Paul, Sarina A. | Yearley, Jennifer | Seiwert, Tanguy | Ribas, Antoni | McClanahan, Terrill K. | Cristescu, Razvan | Mogg, Robin | Ayers, Mark | Albright, Andrew | Murphy, Erin | Yearley, Jennifer | Sher, Xinwei | Liu, Xiao Qiao | Nebozhyn, Michael | Lunceford, Jared | Joe, Andrew | Cheng, Jonathan | Plimack, Elizabeth | Ott, Patrick A. | McClanahan, Terrill K. | Loboda, Andrey | Kaufman, David R. | Forrest-Hay, Alex | Guyre, Cheryl A. | Narumiya, Kohei | Delcommenne, Marc | Hirsch, Heather A. | Deshpande, Amit | Reeves, Jason | Shu, Jenny | Zi, Tong | Michaelson, Jennifer | Law, Debbie | Trehu, Elizabeth | Sathyanaryanan, Sriram | Hodkinson, Brendan P. | Hutnick, Natalie A. | Schaffer, Michael E. | Gormley, Michael | Hulett, Tyler | Jensen, Shawn | Ballesteros-Merino, Carmen | Dubay, Christopher | Afentoulis, Michael | Reddy, Ashok | David, Larry | Fox, Bernard | Jayant, Kumar | Agrawal, Swati | Agrawal, Rajendra | Jeyakumar, Ghayathri | Kim, Seongho | Kim, Heejin | Silski, Cynthia | Suisham, Stacey | Heath, Elisabeth | Vaishampayan, Ulka | Vandeven, Natalie | Viller, Natasja Nielsen | O’Connor, Alison | Chen, Hui | Bossen, Bolette | Sievers, Eric | Uger, Robert | Nghiem, Paul | Johnson, Lisa | Kao, Hsiang-Fong | Hsiao, Chin-Fu | Lai, Shu-Chuan | Wang, Chun-Wei | Ko, Jenq-Yuh | Lou, Pei-Jen | Lee, Tsai-Jan | Liu, Tsang-Wu | Hong, Ruey-Long | Kearney, Staci J. | Black, Joshua C. | Landis, Benjamin J. | Koegler, Sally | Hirsch, Brooke | Gianani, Roberto | Kim, Jeffrey | He, Ming-Xiao | Zhang, Bingqing | Su, Nan | Luo, Yuling | Ma, Xiao-Jun | Park, Emily | Kim, Dae Won | Copploa, Domenico | Kothari, Nishi | doo Chang, Young | Kim, Richard | Kim, Namyong | Lye, Melvin | Wan, Ee | Kim, Namyong | Lye, Melvin | Wan, Ee | Kim, Namyong | Lye, Melvin | Wan, Ee | Knaus, Hanna A. | Berglund, Sofia | Hackl, Hubert | Karp, Judith E. | Gojo, Ivana | Luznik, Leo | Hong, Henoch S. | Koch, Sven D. | Scheel, Birgit | Gnad-Vogt, Ulrike | Kallen, Karl-Josef | Wiegand, Volker | Backert, Linus | Kohlbacher, Oliver | Hoerr, Ingmar | Fotin-Mleczek, Mariola | Billingsley, James M. | Koguchi, Yoshinobu | Conrad, Valerie | Miller, William | Gonzalez, Iliana | Poplonski, Tomasz | Meeuwsen, Tanisha | Howells-Ferreira, Ana | Rattray, Rogan | Campbell, Mary | Bifulco, Carlo | Dubay, Christopher | Bahjat, Keith | Curti, Brendan | Urba, Walter | Vetsika, E-K | Kallergi, G. | Aggouraki, Despoina | Lyristi, Z. | Katsarlinos, P. | Koinis, Filippos | Georgoulias, V. | Kotsakis, Athanasios | Martin, Nathan T. | Aeffner, Famke | Kearney, Staci J. | Black, Joshua C. | Cerkovnik, Logan | Pratte, Luke | Kim, Rebecca | Hirsch, Brooke | Krueger, Joseph | Gianani, Roberto | Martínez-Usatorre, Amaia | Jandus, Camilla | Donda, Alena | Carretero-Iglesia, Laura | Speiser, Daniel E. | Zehn, Dietmar | Rufer, Nathalie | Romero, Pedro | Panda, Anshuman | Mehnert, Janice | Hirshfield, Kim M. | Riedlinger, Greg | Damare, Sherri | Saunders, Tracie | Sokol, Levi | Stein, Mark | Poplin, Elizabeth | Rodriguez-Rodriguez, Lorna | Silk, Ann | Chan, Nancy | Frankel, Melissa | Kane, Michael | Malhotra, Jyoti | Aisner, Joseph | Kaufman, Howard L. | Ali, Siraj | Ross, Jeffrey | White, Eileen | Bhanot, Gyan | Ganesan, Shridar | Monette, Anne | Bergeron, Derek | Amor, Amira Ben | Meunier, Liliane | Caron, Christine | Morou, Antigoni | Kaufmann, Daniel | Liberman, Moishe | Jurisica, Igor | Mes-Masson, Anne-Marie | Hamzaoui, Kamel | Lapointe, Rejean | Mongan, Ann | Ku, Yuan-Chieh | Tom, Warren | Sun, Yongming | Pankov, Alex | Looney, Tim | Au-Young, Janice | Hyland, Fiona | Conroy, Jeff | Morrison, Carl | Glenn, Sean | Burgher, Blake | Ji, He | Gardner, Mark | Mongan, Ann | Omilian, Angela R. | Conroy, Jeff | Bshara, Wiam | Angela, Omilian | Burgher, Blake | Ji, He | Glenn, Sean | Morrison, Carl | Mongan, Ann | Obeid, Joseph M. | Erdag, Gulsun | Smolkin, Mark E. | Deacon, Donna H. | Patterson, James W. | Chen, Lieping | Bullock, Timothy N. | Slingluff, Craig L. | Obeid, Joseph M. | Erdag, Gulsun | Deacon, Donna H. | Slingluff, Craig L. | Bullock, Timothy N. | Loffredo, John T. | Vuyyuru, Raja | Beyer, Sophie | Spires, Vanessa M. | Fox, Maxine | Ehrmann, Jon M. | Taylor, Katrina A. | Korman, Alan J. | Graziano, Robert F. | Page, David | Sanchez, Katherine | Ballesteros-Merino, Carmen | Martel, Maritza | Bifulco, Carlo | Urba, Walter | Fox, Bernard | Patel, Sapna P. | De Macedo, Mariana Petaccia | Qin, Yong | Reuben, Alex | Spencer, Christine | Guindani, Michele | Bassett, Roland | Wargo, Jennifer | Racolta, Adriana | Kelly, Brian | Jones, Tobin | Polaske, Nathan | Theiss, Noah | Robida, Mark | Meridew, Jeffrey | Habensus, Iva | Zhang, Liping | Pestic-Dragovich, Lidija | Tang, Lei | Sullivan, Ryan J. | Logan, Theodore | Khushalani, Nikhil | Margolin, Kim | Koon, Henry | Olencki, Thomas | Hutson, Thomas | Curti, Brendan | Roder, Joanna | Blackmon, Shauna | Roder, Heinrich | Stewart, John | Amin, Asim | Ernstoff, Marc S. | Clark, Joseph I. | Atkins, Michael B. | Kaufman, Howard L. | Sosman, Jeffrey | Weber, Jeffrey | McDermott, David F. | Weber, Jeffrey | Kluger, Harriet | Halaban, Ruth | Snzol, Mario | Roder, Heinrich | Roder, Joanna | Asmellash, Senait | Steingrimsson, Arni | Blackmon, Shauna | Sullivan, Ryan J. | Wang, Chichung | Roman, Kristin | Clement, Amanda | Downing, Sean | Hoyt, Clifford | Harder, Nathalie | Schmidt, Guenter | Schoenmeyer, Ralf | Brieu, Nicolas | Yigitsoy, Mehmet | Madonna, Gabriele | Botti, Gerardo | Grimaldi, Antonio | Ascierto, Paolo A. | Huss, Ralf | Athelogou, Maria | Hessel, Harald | Harder, Nathalie | Buchner, Alexander | Schmidt, Guenter | Stief, Christian | Huss, Ralf | Binnig, Gerd | Kirchner, Thomas | Sellappan, Shankar | Thyparambil, Sheeno | Schwartz, Sarit | Cecchi, Fabiola | Nguyen, Andrew | Vaske, Charles | Hembrough, Todd
Journal for Immunotherapy of Cancer  2016;4(Suppl 1):1-106.
doi:10.1186/s40425-016-0172-7
PMCID: PMC5123387
15.  Validation of Taiwan Performance-Based Instrumental Activities of Daily Living (TPIADL), a Performance- Based Measurement of Instrumental Activities of Daily Living for Patients with Vascular Cognitive Impairment 
PLoS ONE  2016;11(11):e0166546.
Objective
Patients with cerebrovascular diseases often presented both cognitive and physical impairment. Disability in everyday functioning involving cognitive impairment among patients may be hard to completely rely on informants’ reports, as their reports may be confounded with physical impairment. The aim of this study was to validate a performance-based measure of functional assessment, the Taiwan Performance-Based Instrumental Activities of Daily Living (TPIADL), for vascular cognitive impairment (VCI) by examining its psychometric properties and diagnostic accuracy.
Methods
Ninety-seven patients with cerebrovascular diseases, including 30 with vascular dementia (VaD), 28 with mild cognitive impairment and 39 with no cognitive impairment, and 49 healthy control adults were recruited during study period. The TPIADL, as well as the Mini Mental State Examination (MMSE), Lawton-IADL and Barthel Index (BI), were performed. The internal consistency, convergent and criteria validity of the TPIADL were examined.
Results
Cronbach’s alpha of the TPIADL test was 0.84. The TPIADL scores were significantly correlated with the Lawton IADL (r = –0.587, p <0.01). Notably, the TPIADL had a higher correlation coefficient with the cognitive domain of Lawton IADL (r = –0.663) than with physical domain of Lawton IADL (r = –0.541). The area under the relative operating characteristic curve was 0.888 (95% CI = 0.812–0.965) to differentiate VaD from other groups. The optimal cut-off point of the TPIADL for detecting VaD was 6/7, which gives a sensitivity of 73.3% and a specificity of 84.5%.
Conclusion
The TPIADL is a brief and sensitive tool for the detection of IADL impairment in patients with VaD.
doi:10.1371/journal.pone.0166546
PMCID: PMC5113008  PMID: 27851810
16.  Cytokine cascade and networks among MSM HIV seroconverters: implications for early immunotherapy 
Scientific Reports  2016;6:36234.
The timing, intensity and duration of the cytokine cascade and reorganized interrelations in cytokine networks are not fully understood during acute HIV-1 infection (AHI). Using sequential plasma samples collected over three years post-infection in a cohort of MSM HIV-1 seroconvertors, we determined the early kinetics of cytokine levels during FiebigI-IV stages using Luminex-based multiplex assays. Cytokines were quantified and relationships between cytokines were assessed by Spearman correlation. Compared with HIV-negative MSM, HIV-infected individuals had significantly increased multiple plasma cytokines, including GM-CSF, IFN-α2, IL-12p70, IP-10 and VEGF, during both acute and chronic stages of infection. Furthermore, rapid disease progressors (RDPs) had earlier and more robust cytokine storms, compared with slow disease progressors (SDPs) (49.6 days vs. 74.9 days, respectively; 6.7-fold vs. 3.7-fold change of cytokines, respectively), suggesting the faster and stronger cytokine storm during AHI could promote disease progression. On the other hand, HIV-1 infection induced more interlocked cytokines network, establishing new strong correlations and imposing a higher rigidity. There were, respectively, 146 (44.9%) statistically significant correlations of cytokines in RDPs and 241 (74.2%) in SDPs (p < 0.001). This study suggests that immunomodulatory interventions aimed at controlling cytokine storm in AHI may be beneficial to slow eventual disease progression.
doi:10.1038/srep36234
PMCID: PMC5103227  PMID: 27830756
17.  Effect of Splenectomy Combined with Resection for Gastric Carcinoma on Patient Prognosis 
Background
For patients with stage IV gastric cancer, it is unclear whether splenectomy combined with palliative surgery is needed to reduce tumor load and relieve symptoms. The objective of the present study was to investigate the effect of splenectomy combined with palliative resection for stage IV gastric carcinoma on immunological dysfunction and patient prognosis.
Material/Methods
We retrospectively analyzed medical records of 106 stage IV gastric cancer patients who underwent palliative surgery; of these, 49 patients were treated with palliative resection for gastric carcinoma combined with splenectomy, while the other 57 patients retained their spleens. The immunologic function and prognosis in these 2 groups were examined and compared.
Results
The immune function of patients in the group that retained their spleens was better later in the postoperative course than in the resection group. The groups did not show statistically significant differences in postoperative infectious complications, median survival time, and survival rate; however, the average postoperative hospitalization time of patients in the retained group was significantly shorter.
Conclusions
Splenectomy combined with gastric cancer resection did not improve the prognosis of the patients; patients who retained their spleens had faster recovery and improved immune function. However, whether retaining the spleen is an independent factor improving the prognosis needs further investigation.
doi:10.12659/MSM.897842
PMCID: PMC5100834  PMID: 27816984
Prognosis; Splenectomy; Stomach Neoplasms
18.  Quantification of IGF-1 Receptor May Be Useful in Diagnosing Polycythemia Vera–Suggestion to Be Added to Be One of the Minor Criterion 
PLoS ONE  2016;11(11):e0165299.
Endogenous erythroid colony (EEC) formation is one of the minor criteria for diagnosing polycythemia vera (PV) according to 2008 WHO diagnostic criteria. But EEC requires bone marrow aspiration and sophisticated laboratory procedures; therefore, practically it is rarely used to diagnose PV. Insulin-like growth factor 1 receptor (IGF-1R) was found to be constitutively phosphorylated and was responsible for the EEC formation in PV; therefore, we measured IGF-1R levels in the peripheral blood of 26 PV patients and compared them with those of 33 patients with secondary polycythemia and 29 normal controls. Among the PV patients, 16 were treated with only phlebotomy, 9 received hydroxyurea, and 1 was treated with ruxolinitinib. We found that PV patients treated with only phlebotomy had significantly higher IGF-1R levels than did those PV patients treated with hydroxyurea or ruxolinitinib. None of the secondary PV patients or normal controls had elevated IGR-1R levels, while 14 of 16 (87%) PV patients had significantly elevated IGF-1R levels. The new 2016 WHO has eliminated EEC as a minor criterion for diagnosing PV, but there are still some cases that cannot be definitively diagnosed by the current criteria. Therefore, we suggest that quantifying the IGF-1R level in peripheral blood by flow cytometry to replace EEC as the minor criterion for diagnosing PV.
doi:10.1371/journal.pone.0165299
PMCID: PMC5094699  PMID: 27812134
19.  Coenzyme Engineering of a Hyperthermophilic 6-Phosphogluconate Dehydrogenase from NADP+ to NAD+ with Its Application to Biobatteries 
Scientific Reports  2016;6:36311.
Engineering the coenzyme specificity of redox enzymes plays an important role in metabolic engineering, synthetic biology, and biocatalysis, but it has rarely been applied to bioelectrochemistry. Here we develop a rational design strategy to change the coenzyme specificity of 6-phosphogluconate dehydrogenase (6PGDH) from a hyperthermophilic bacterium Thermotoga maritima from its natural coenzyme NADP+ to NAD+. Through amino acid-sequence alignment of NADP+- and NAD+-preferred 6PGDH enzymes and computer-aided substrate-coenzyme docking, the key amino acid residues responsible for binding the phosphate group of NADP+ were identified. Four mutants were obtained via site-directed mutagenesis. The best mutant N32E/R33I/T34I exhibited a ~6.4 × 104-fold reversal of the coenzyme selectivity from NADP+ to NAD+. The maximum power density and current density of the biobattery catalyzed by the mutant were 0.135 mW cm−2 and 0.255 mA cm−2, ~25% higher than those obtained from the wide-type 6PGDH-based biobattery at the room temperature. By using this 6PGDH mutant, the optimal temperature of running the biobattery was as high as 65 °C, leading to a high power density of 1.75 mW cm−2. This study demonstrates coenzyme engineering of a hyperthermophilic 6PGDH and its application to high-temperature biobatteries.
doi:10.1038/srep36311
PMCID: PMC5090862  PMID: 27805055
20.  E2f8 mediates tumor suppression in postnatal liver development 
The Journal of Clinical Investigation  null;126(8):2955-2969.
E2F-mediated transcriptional repression of cell cycle–dependent gene expression is critical for the control of cellular proliferation, survival, and development. E2F signaling also interacts with transcriptional programs that are downstream of genetic predictors for cancer development, including hepatocellular carcinoma (HCC). Here, we evaluated the function of the atypical repressor genes E2f7 and E2f8 in adult liver physiology. Using several loss-of-function alleles in mice, we determined that combined deletion of E2f7 and E2f8 in hepatocytes leads to HCC. Temporal-specific ablation strategies revealed that E2f8’s tumor suppressor role is critical during the first 2 weeks of life, which correspond to a highly proliferative stage of postnatal liver development. Disruption of E2F8’s DNA binding activity phenocopied the effects of an E2f8 null allele and led to HCC. Finally, a profile of chromatin occupancy and gene expression in young and tumor-bearing mice identified a set of shared targets for E2F7 and E2F8 whose increased expression during early postnatal liver development is associated with HCC progression in mice. Increased expression of E2F8-specific target genes was also observed in human liver biopsies from HCC patients compared to healthy patients. In summary, these studies suggest that E2F8-mediated transcriptional repression is a critical tumor suppressor mechanism during postnatal liver development.
doi:10.1172/JCI85506
PMCID: PMC4966321  PMID: 27454291
21.  Energy-Efficient Heterogeneous Wireless Sensor Deployment with Multiple Objectives for Structural Health Monitoring 
Sensors (Basel, Switzerland)  2016;16(11):1865.
Heterogeneous wireless sensor networks (HWSNs) are widely adopted in structural health monitoring systems due to their potential for implementing sophisticated algorithms by integrating a diverse set of devices and improving a network’s sensing performance. However, deploying such a HWSN is still in a challenge due to the heterogeneous nature of the data and the energy constraints of the network. To respond to these challenges, an optimal deployment framework in terms of both modal information quality and energy consumption is proposed in this study. This framework generates a multi-objective function aimed at maximizing the quality of the modal information identified from heterogeneous data while minimizing the consumption of energy within the network at the same time. Particle swarm optimization algorithm is then implemented to seek solutions to the function effectively. After laying out the proposed sensor-optimization framework, a methodology is present to determine the clustering of the sensors to further conserve energy. Finally, a numerical verification is performed on a four-span pre-stressed reinforced concrete box-girder bridge. Results show that a set of strategically positioned heterogeneous sensors can maintain a balanced trade-off between the modal information accuracy and energy consumption. It is also observed that an appropriate cluster-tree network topology can further achieve energy saving in HWSNs.
doi:10.3390/s16111865
PMCID: PMC5134524  PMID: 27827975
heterogeneous wireless sensor networks; modal information quality; energy consumption; clustering
22.  Association of Fluid Status and Body Composition with Physical Function in Patients with Chronic Kidney Disease 
PLoS ONE  2016;11(10):e0165400.
Background
Impairment of physical function and abnormal body composition are the major presentations in patients with chronic kidney disease (CKD). The aim of this study is to investigate the relationship between body composition and physical function in CKD patients.
Methods
This cross-sectional study enrolled 172 of CKD stages 1–5 from February 2013 to September 2013. Handgrip strength (upper extremity muscle endurance), 30-second chair-stand test (lower extremity muscle endurance) and 2-minute step test (cardiorespiratory endurance) were used as indices of physical function. Body composition, including fluid status (extracellular water/total body water, ECW/TBW), lean tissue index (LTI), and fat tissue index (FTI), was measured using a bioimpedance spectroscopy method.
Results
All patients with high ECW/TBW had lower handgrip strength and 30-second chair-stand than those with low ECW/TBW (P<0.001 and P = 0.002). CKD patients with high FTI had lower handgrip strength and 30-second chair-stand than those with low FTI (P<0.001 and P = 0.002). These patients with low LTI had lower handgrip strength than those with high LTI (P = 0.04). In multivariate analysis, high ECW/TBW was positively associated with decreased handgrip strength (β = -41.17, P = 0.03) in CKD patients. High FTI was significantly correlated with decreased times of 30-second chair-stand (β = -0.13, P = 0.01). There was no significant relationship between body composition and 2-minute step test.
Conclusions
Our results show a significant association of impaired upper and lower extremity muscle endurance with high fluid status and fat tissue. Evaluation of body composition may assist in indentifying physical dysfunction earlier in CKD patients.
doi:10.1371/journal.pone.0165400
PMCID: PMC5087878  PMID: 27798648
23.  Comorbidity in Adult Patients Hospitalized with Type 2 Diabetes in Northeast China: An Analysis of Hospital Discharge Data from 2002 to 2013 
BioMed Research International  2016;2016:1671965.
This study aims to evaluate the comorbidity burden and patterns among adult patients hospitalized with a diagnosis of type 2 diabetes mellitus (T2DM) in Northeast China using hospital discharge data derived from the electronic medical record database between 2002 and 2013. 12.8% of 4,400,892 inpatients aged ≥18 had a diagnosis of T2DM. Sex differences in prevalence varied among those aged <50, 50–59, and ≥60. Twenty-seven diseases were determined as major comorbidities of T2DM. Essential hypertension was the most common comorbidity of T2DM (absolute cooccurrence risk, 58.4%), while T2DM was also the most popular comorbidity of essential hypertension. Peripheral and visceral atherosclerosis showed the strongest association (relative cooccurrence risk, RCoR 4.206). For five leading comorbidities among patients aged ≥40, male patients had a stronger association with disorders of lipid metabolism than female patients (RCoR 2.779 versus 2.099), and female patients had a stronger association with chronic renal failure than male patients (RCoR 2.461 versus 2.155). Leading comorbidities, except chronic renal failure, had declining associations with T2DM with increased age. Collectively, hospital discharge data can be used to estimate disease prevalence and identify comorbidities. The findings provided comprehensive information on comorbidity patterns, helping policy makers and programs in public health domains to estimate and evaluate the epidemic of chronic diseases.
doi:10.1155/2016/1671965
PMCID: PMC5099493  PMID: 27847807
24.  Discovery of the molecular mechanisms of the novel chalcone-based Magnaporthe oryzae inhibitor C1 using transcriptomic profiling and co-expression network analysis 
SpringerPlus  2016;5(1):1851.
Background
In our previous studies, we discovered a series of chalcone-based phytopathogenic fungus inhibitors. However, knowledge of their effects, detailed targets and molecular mechanisms in Magnaporthe oryzae (M. oryzae) remained limited.
Methods
To explore the expression and function of differentially expressed genes in M. oryzae after treatment with compound C1, we analyzed the expression profile of mRNAs using a microarray analysis and GO, KEGG and WGCNA analysis, followed by qRT-PCR and Western blots to validate our findings.
Results
A total of 1013 up-regulated and 995 down-regulated mRNAs were differentially expressed after M. oryzae was treated with C1 compared to those of the control samples. Among these, cytochrome P450, glycylpeptide N-myristoyltransferase (NMT) and peroxisomal membrane protein 4 were identified as the most significant DEGs and were validated by experiments.
Conclusion
In conclusion, our study suggests that the combination of transcriptomic microarray, bioinformatics analysis and weighted gene co-expression networks can be used to predict potential therapeutic targets and to map the pathways regulated by small molecular natural product-like drugs.
Electronic supplementary material
The online version of this article (doi:10.1186/s40064-016-3385-9) contains supplementary material, which is available to authorized users.
doi:10.1186/s40064-016-3385-9
PMCID: PMC5075332  PMID: 27818889
Magnaporthe oryzae; Transcriptome; Gene co-expression network; Molecular docking
25.  Molecular epidemiology of hepatitis C infections in Ningxia, China: genotype, phylogeny and mutation analysis 
Virology Journal  2016;13:172.
Background
Current prevalence and genotype distribution of hepatitis C virus (HCV) infection remain unknown in Ningxia, northwest China.
Methods
From June to December 2013, 13,022 individuals were screened in Ningxia HIV/AIDS Sentinel Surveillance System, with their demographic features collected and serum samples tested for HCV antibody. Sero-positive drug users were further subjected to sequencing of NS5B and Core regions of HCV.
Results
The anti-HCV prevalence was 0.34 % among individuals without history of drug use, while it was 15.80 % among drug users. Of 79 NS5B sequences amplified from drug users, 64 (81.0 %) were male and 51 (64.0 %) were injection drug users (IDUs). Subtype 3a (40.5 %) and 1b (25.3 %) were the most predominant subtypes, followed in frequency by 3b (10.1 %) and 2a (7.6 %). Subtype distribution has no significant difference between injection and non-injection drug users. Based on phylogeographic analysis, HCV strains in Ningxia IDUs were mainly originated from two sites, Yunnan province (in southwest China bordering Myanmar, also known as Burma) and Xinjiang Autonomous Region (in northwest China on the border of Central Asia), which are the two major drug trafficking originates in China. Previously reported drug-resistance mutations were also scanned in this treatment-naïve population. Amino acid substitutions (C316N) associated with direct anti-viral agents (DAA) resistance were identified in the NS5B region in seven samples.
Conclusion
This study is the first to reveal the existence of multiple genotypes of HCV in Ningxia, an inland province in northwest China, suggesting the rapid spreading of the virus.
Electronic supplementary material
The online version of this article (doi:10.1186/s12985-016-0635-y) contains supplementary material, which is available to authorized users.
doi:10.1186/s12985-016-0635-y
PMCID: PMC5070218  PMID: 27756381
Hepatitis C virus; Prevalence; Genotype; Phylogenetic; Genetic diversity

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