PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (716)
 

Clipboard (0)
None

Select a Filter Below

Journals
more »
Year of Publication
more »
1.  Genome-wide association analysis identifies new lung cancer susceptibility loci in never-smoking women in Asia 
Lan, Qing | Hsiung, Chao A | Matsuo, Keitaro | Hong, Yun-Chul | Seow, Adeline | Wang, Zhaoming | Hosgood, H Dean | Chen, Kexin | Wang, Jiu-Cun | Chatterjee, Nilanjan | Hu, Wei | Wong, Maria Pik | Zheng, Wei | Caporaso, Neil | Park, Jae Yong | Chen, Chien-Jen | Kim, Yeul Hong | Kim, Young Tae | Landi, Maria Teresa | Shen, Hongbing | Lawrence, Charles | Burdett, Laurie | Yeager, Meredith | Yuenger, Jeffrey | Jacobs, Kevin B | Chang, I-Shou | Mitsudomi, Tetsuya | Kim, Hee Nam | Chang, Gee-Chen | Bassig, Bryan A | Tucker, Margaret | Wei, Fusheng | Yin, Zhihua | Wu, Chen | An, She-Juan | Qian, Biyun | Lee, Victor Ho Fun | Lu, Daru | Liu, Jianjun | Jeon, Hyo-Sung | Hsiao, Chin-Fu | Sung, Jae Sook | Kim, Jin Hee | Gao, Yu-Tang | Tsai, Ying-Huang | Jung, Yoo Jin | Guo, Huan | Hu, Zhibin | Hutchinson, Amy | Wang, Wen-Chang | Klein, Robert | Chung, Charles C | Oh, In-Jae | Chen, Kuan-Yu | Berndt, Sonja I | He, Xingzhou | Wu, Wei | Chang, Jiang | Zhang, Xu-Chao | Huang, Ming-Shyan | Zheng, Hong | Wang, Junwen | Zhao, Xueying | Li, Yuqing | Choi, Jin Eun | Su, Wu-Chou | Park, Kyong Hwa | Sung, Sook Whan | Shu, Xiao-Ou | Chen, Yuh-Min | Liu, Li | Kang, Chang Hyun | Hu, Lingmin | Chen, Chung-Hsing | Pao, William | Kim, Young-Chul | Yang, Tsung-Ying | Xu, Jun | Guan, Peng | Tan, Wen | Su, Jian | Wang, Chih-Liang | Li, Haixin | Sihoe, Alan Dart Loon | Zhao, Zhenhong | Chen, Ying | Choi, Yi Young | Hung, Jen-Yu | Kim, Jun Suk | Yoon, Ho-Il | Cai, Qiuyin | Lin, Chien-Chung | Park, In Kyu | Xu, Ping | Dong, Jing | Kim, Christopher | He, Qincheng | Perng, Reury-Perng | Kohno, Takashi | Kweon, Sun-Seog | Chen, Chih-Yi | Vermeulen, Roel | Wu, Junjie | Lim, Wei-Yen | Chen, Kun-Chieh | Chow, Wong-Ho | Ji, Bu-Tian | Chan, John K C | Chu, Minjie | Li1, Yao-Jen | Yokota, Jun | Li, Jihua | Chen, Hongyan | Xiang, Yong-Bing | Yu, Chong-Jen | Kunitoh, Hideo | Wu, Guoping | Jin, Li | Lo, Yen-Li | Shiraishi, Kouya | Chen, Ying-Hsiang | Lin, Hsien-Chih | Wu, Tangchun | Wu, Yi-Long | Yang, Pan-Chyr | Zhou, Baosen | Shin, Min-Ho | Fraumeni, Joseph F | Lin, Dongxin | Chanock, Stephen J | Rothman, Nathaniel
Nature genetics  2012;44(12):1330-1335.
To identify common genetic variants that contribute to lung cancer susceptibility, we conducted a multistage genome-wide association study of lung cancer in Asian women who never smoked. We scanned 5,510 never-smoking female lung cancer cases and 4,544 controls drawn from 14 studies from mainland China, South Korea, Japan, Singapore, Taiwan, and Hong Kong. We genotyped the most promising variants (associated at P < 5 × 10-6) in an additional 1,099 cases and 2,913 controls. We identified three new susceptibility loci at 10q25.2 (rs7086803, P = 3.54 × 10-18), 6q22.2 (rs9387478, P = 4.14 × 10-10) and 6p21.32 (rs2395185, P = 9.51 × 10-9). We also confirmed associations reported for loci at 5p15.33 and 3q28 and a recently reported finding at 17q24.3. We observed no evidence of association for lung cancer at 15q25 in never-smoking women in Asia, providing strong evidence that this locus is not associated with lung cancer independent of smoking.
doi:10.1038/ng.2456
PMCID: PMC4169232  PMID: 23143601
2.  Genetic variant in TP63 on locus 3q28 is associated with risk of lung adenocarcinoma among never-smoking females in Asia 
Hosgood, H. Dean | Wang, Wen-Chang | Hong, Yun-Chul | Wang, Jiu-Cun | Chen, Kexin | Chang, I-Shou | Chen, Chien-Jen | Lu, Daru | Yin, Zhihua | Wu, Chen | Zheng, Wei | Qian, Biyun | Park, Jae Yong | Kim, Yeul Hong | Chatterjee, Nilanjan | Chen, Ying | Chang, Gee-Chen | Hsiao, Chin-Fu | Yeager, Meredith | Tsai, Ying-Huang | Wei, Hu | Kim, Young Tae | Wu, Wei | Zhao, Zhenhong | Chow, Wong-Ho | Zhu, Xiaoling | Lo, Yen-Li | Sung, Sook Whan | Chen, Kuan-Yu | Yuenger, Jeff | Kim, Joo Hyun | Huang, Liming | Chen, Ying-Hsiang | Gao, Yu-Tang | Kim, Jin Hee | Huang, Ming-Shyan | Jung, Tae Hoon | Caporaso, Neil | Zhao, Xueying | Huan, Zhang | Yu, Dianke | Kim, Chang Ho | Su, Wu-Chou | Shu, Xiao-Ou | Kim, In-San | Bassig, Bryan | Chen, Yuh-Min | Cha, Sung Ick | Tan, Wen | Chen, Hongyan | Yang, Tsung-Ying | Sung, Jae Sook | Wang, Chih-Liang | Li, Xuelian | Park, Kyong Hwa | Yu, Chong-Jen | Ryu, Jeong-Seon | Xiang, Yongbing | Hutchinson, Amy | Kim, Jun Suk | Cai, Qiuyin | Landi, Maria Teresa | Lee, Kyoung-Mu | Hung, Jen-Yu | Park, Ju-Yeon | Tucker, Margaret | Lin, Chien-Chung | Ren, Yangwu | Perng, Reury-Perng | Chen, Chih-Yi | Jin, Li | Chen, Kun-Chieh | Li, Yao-Jen | Chiu, Yu-Fang | Tsai, Fang-Yu | Yang, Pan-Chyr | Fraumeni, Joseph F. | Seow, Adeline | Lin, Dongxin | Zhou, Baosen | Chanock, Stephen | Hsiung, Chao Agnes | Rothman, Nathaniel | Lan, Qing
Human genetics  2012;131(7):10.1007/s00439-012-1144-8.
A recent genome-wide association study (GWAS) of subjects from Japan and South Korea reported a novel association between the TP63 locus on chromosome 3q28 and risk of lung adenocarcinoma (p = 7.3 × 10−12); however, this association did not achieve genome-wide significance (p < 10−7) among never-smoking males or females. To determine if this association with lung cancer risk is independent of tobacco use, we genotyped the TP63 SNPs reported by the previous GWAS (rs10937405 and rs4488809) in 3,467 never-smoking female lung cancer cases and 3,787 never-smoking female controls from 10 studies conducted in Taiwan, Mainland China, South Korea, and Singapore. Genetic variation in rs10937405 was associated with risk of lung adenocarcinoma [n = 2,529 cases; p = 7.1 × 10−8; allelic risk = 0.80, 95% confidence interval (CI) = 0.74–0.87]. There was also evidence of association with squamous cell carcinoma of the lung (n = 302 cases; p = 0.037; allelic risk = 0.82, 95% CI = 0.67–0.99). Our findings provide strong evidence that genetic variation in TP63 is associated with the risk of lung adenocarcinoma among Asian females in the absence of tobacco smoking.
doi:10.1007/s00439-012-1144-8
PMCID: PMC3875137  PMID: 22367405
3.  Antigenic Divergence of Bordetella pertussis Isolates in Taiwan 
Journal of Clinical Microbiology  2005;43(11):5457-5461.
In recent studies, antigenic divergence has been observed in Bordetella pertussis circulating isolates. We collected 80 Bordetella pertussis isolates in Taiwan from 1998 to 2004 and analyzed them using a combination of pulsed-field gel electrophoresis (PFGE) and sequencing of the ptxS1 and prn genes. The incidence of pertussis increases every 3 years, and most of the isolates prevalent since 1998 have expressed nonvaccine ptxS1A and prn2 alleles. Through PFGE analysis, all isolates could be classified into four major groups, and the incidence of these groups exhibited a correlation with the prn allele expressed by the isolates. We found that PFGE is more discriminative than gene sequencing, since it could divide the isolates expressing the prn2 allele into two groups: one group circulating from 1998 to 2001 and another group circulating from 2001 to 2004. The transition between the two groups in 2000 coincided with an outbreak of 326 cases. This research indicates that the antigenic divergence of B. pertussis circulating isolates has evolved over time in Taiwan. Such information will have implications for vaccine policy in Taiwan.
doi:10.1128/JCM.43.11.5457-5461.2005
PMCID: PMC1287815  PMID: 16272470
4.  T cell Ig and mucin-1 and -3 in Plasmodium berghei ANKA infection 
Parasitology research  2013;112(7):2713-2719.
Cerebral malaria (CM) is a serious and often fatal complication of Plasmodium falciparum infections; however, the precise mechanisms leading to CM is poorly understood. Mouse malaria models have provided insight into the key events in pathogenesis of CM. T cell immune response is known to play an important role in malaria infection, and members of the T-cell immunoglobulin– and mucin–domain–containing molecule (TIM) family have roles in T-cell–mediated immune responses. Tim-1 and Tim-3 are expressed on terminally differentiated Th2 and Th1 cells, respectively, and participate in the regulation of Th immune response. Until now, the role of Tim family proteins in Plasmodium infection remains unclear. In the present study, the mRNA levels of Tim-1, Tim-3, and some key Th1 and Th2 cytokines in the spleen of female Kunming outbred mice infected with P. berghei ANKA (PbANKA) were determined using real-time polymerase chain reaction (qRT-PCR). Tim-1 expression was significantly decreased at day 10 postinfection (p.i.) in infected mice with CM, and significantly increased at day 22 p.i. in infected mice with non-CM, compared with uninfected controls (P < 0.01); in contrast, Tim-3 expression was significantly increased in both CM and non-CM infected mice at days 10 and 22 p.i., respectively. Furthermore, the expression of Tim-1 and Tim-3 mRNA in spleen was significantly positively correlated with the level of Th2 and Th1 cytokine mRNA in the spleens, respectively. PbANKA infection could inhibit the differentiation of T lymphocytes toward Th2 cells, promote the Th1 cell differentiation, and induce Th1-biased immune response in the early infective stage in infected mice with CM; whereas the infection could promote Th2 cell differentiation, and induce Th2-biased immune response in the late infective stage, in infected mice with non-CM. Our data suggest that both Tim-1 and Tim-3 may play an important role in the pathogenesis of P. berghei infection, which may represent a potential therapeutic target.
doi:10.1007/s00436-013-3442-z
PMCID: PMC4521769  PMID: 23653017
Cerebral malaria; Plasmodium berghei; rodent; immune response; Tim gene expression
5.  The significance of NTR1 expression and its correlation with β-catenin and EGFR in gastric cancer 
Diagnostic Pathology  2015;10:128.
Background
Several reports indicate the high-affinity receptor of NT (neurotensin), NTR1 (neurotensin receptor 1), in numerous detrimental functions linked to neoplastic progression of several cancer types. Recently, it has also been shown that NTR1 gene is a target of the Wnt/APC oncogenic pathways connected with the β-catenin/Tcf transcriptional complex and NT can stimulate cancer proliferation in an EGFR-dependent mechanism. In this study, we explored NTR1, β-catenin and EGFR expression in gastric cancer. The possible associations of NTR1 expression with clinicopathological factors, prognosis, β-catenin and EGFR were analyzed.
Methods
NTR1, β-catenin and EGFR expression in gastric cancer tissues and the adjacent normal tissues of 210 cases was detected by Immunohistochemistry. The possible associations of NTR1 expression with clinicopathological data, prognosis, β-catenin and EGFR were analyzed.
Results
1. NTR1 expression in tumor tissues was significantly higher than that in adjacent normal tissues (P <0 .01). 2. Its expression was positively correlated with pathological grade, T stage, N stage and TNM stage and was not correlated with sex, age, tumor size and Lauren’s classification. 3. A co-expression of NTR1 and nuclear β-catenin was in 53 (25.2 %) of cases and NTR1 expression was positively correlated with β-catenin nuclear translocation. NTR1 expression was not correlated with EGFR expression, but at a critical value (P = 0.05). 4. By log-rank test, higher expression of NTR1, higher pathological grade, diffusion Lauren’s classification and advanced TNM stage showed worse prognosis (P <0 .05). Age, sex, tumor size, β-catenin and EGFR had no prognostic significance. Multivariate Cox analysis showed that NTR1 expression and TNM clinical stage (P <0 .05) were the independent prognostic factors for patients with GC.
Conclusion
By immunohistochemistry, we found that a high expression of NTR1 in GC specimens, which showed a bad prognosis, besides, NTR1 expression was related to invasion and migration of GC. These findings provide new and important information on the progression of GC. This study indicated that NTR1 may play an important role in tumor progression of GC and have its potential to be a predictive biomarker or a therapeutic molecular target in GC. The interaction between NTR1 and β-catenin may participate in the development of GC. However, the relationship between NTR1 and EGFR needs to be further investigated.
doi:10.1186/s13000-015-0356-3
PMCID: PMC4517349  PMID: 26215716
Gastric cancer, NTR1; β-catenin, EGFR, Clinical pathology, Prognosis
6.  Biliary tract external drainage increases the expression levels of heme oxygenase-1 in rat livers 
Background
Heme oxygenase-1 (HO-1) protects cells by anti-oxidation, maintaining normal microcirculation and anti-inflammatory under stress. This study investigated the effects of biliary tract external drainage (BTED) on the expression levels of HO-1 in rat livers.
Methods
Biliary tract external drainage was performed by inserting a cannula into the bile duct. Sixty Sprague–Dawley rats were randomized to the following groups: sham 1 h group; BTED 1 h group; bile duct ligation (BDL) 1 h group; sham 6 h group and BTED 6 h group. The expression levels of HO-1 mRNA were analyzed using real-time RT-PCR. The expression levels of HO-1 were analyzed using immunohistochemistry.
Results
The expression levels of HO-1 mRNA in the liver of the BTED group increased significantly compared with the sham group 1 and 6 h after surgery (p < 0.05).The expression levels of HO-1 in the BTED group increased significantly compared with the sham group 1 and 6 h after surgery. The expression levels of HO-1 mRNA in the liver in the BDL group decreased significantly compared with the sham group 1 h after surgery (p < 0.05).The expression levels of HO-1 in the BDL group decreased significantly compared with the sham group at this time.
Conclusion
Biliary tract external drainages increase the expression levels of HO-1 in the liver.
doi:10.1186/s40001-015-0152-2
PMCID: PMC4511237  PMID: 26199001
Biliary tract external drainage; Heme oxygenase-1
7.  Performance of genetic risk factors in prediction of trichloroethylene induced hypersensitivity syndrome 
Scientific Reports  2015;5:12169.
Trichloroethylene induced hypersensitivity syndrome is dose-independent and potentially life threatening disease, which has become one of the serious occupational health issues and requires intensive treatment. To discover the genetic risk factors and evaluate the performance of risk prediction model for the disease, we conducted genomewide association study and replication study with total of 174 cases and 1761 trichloroethylene-tolerant controls. Fifty seven SNPs that exceeded the threshold for genome-wide significance (P < 5 × 10−8) were screened to relate with the disease, among which two independent SNPs were identified, that is rs2857281 at MICA (odds ratio, 11.92; Pmeta = 1.33 × 10−37) and rs2523557 between HLA-B and MICA (odds ratio, 7.33; Pmeta = 8.79 × 10−35). The genetic risk score with these two SNPs explains at least 20.9% of the disease variance and up to 32.5-fold variation in inter-individual risk. Combining of two SNPs as predictors for the disease would have accuracy of 80.73%, the area under receiver operator characteristic curves (AUC) scores was 0.82 with sensitivity of 74% and specificity of 85%, which was considered to have excellent discrimination for the disease, and could be considered for translational application for screening employees before exposure.
doi:10.1038/srep12169
PMCID: PMC4507183  PMID: 26190474
8.  Early treatment of minocycline alleviates white matter and cognitive impairments after chronic cerebral hypoperfusion 
Scientific Reports  2015;5:12079.
Subcortical ischemic vascular dementia (SIVD) caused by chronic cerebral hypoperfusion develops with progressive white matter and cognitive impairments, yet no effective therapy is available. We investigated the temporal effects of minocycline on an experimental SIVD exerted by right unilateral common carotid arteries occlusion (rUCCAO). Minocycline treated at the early stage (day 0–3), but not the late stage after rUCCAO (day 4–32) alleviated the white matter and cognitive impairments, and promoted remyelination. The actions of minocycline may not involve the inhibition of microglia activation, based on the effects after the application of a microglial activation inhibitor, macrophage migration inhibitory factor, and co-treatment with lipopolysaccharides. Furthermore, minocycline treatment at the early stage promoted the proliferation of oligodendrocyte progenitor cells (OPCs) in subventricular zone, increased OPC number and alleviated apoptosis of mature oligodendrocytes in white matter. In vitro, minocycline promoted OPC proliferation and increased the percentage of OPCs in S and G2/M phases. We provided direct evidence that early treatment is critical for minocycline to alleviate white matter and cognitive impairments after chronic cerebral hypoperfusion, which may be due to its robust effects on OPC proliferation and mature oligodendrocyte loss. So, early therapeutic time window may be crucial for its application in SIVD.
doi:10.1038/srep12079
PMCID: PMC4502604  PMID: 26174710
9.  Differential Incorporation of Glucose into Biomass during Warburg Metabolism 
Biochemistry  2014;53(29):4755-4757.
It is well established that most cancer cells take up an increased amount of glucose relative to that taken up by normal differentiated cells. The majority of this glucose carbon is secreted from the cell as lactate. The fate of the remaining glucose carbon, however, has not been well-characterized. Here we apply a novel combination of metabolomic technologies to track uniformly labeled glucose in HeLa cancer cells. We provide a list of specific intracellular metabolites that become enriched after being labeled for 48 h and quantitate the fraction of consumed glucose that ends up in proteins, peptides, sugars/glycerol, and lipids.
doi:10.1021/bi500763u
PMCID: PMC4116146  PMID: 25010499
10.  Focal segmental glomerulosclerosis: molecular genetics and targeted therapies 
BMC Nephrology  2015;16:101.
Recent advances show that human focal segmental glomerulosclerosis (FSGS) is a primary podocytopathy caused by podocyte-specific gene mutations including NPHS1, NPHS2, WT-1, LAMB2, CD2AP, TRPC6, ACTN4 and INF2. This review focuses on genes discovered in the investigation of complex FSGS pathomechanisms that may have implications for the current FSGS classification scheme. It also recounts recent recommendations for clinical management of FSGS based on translational studies and clinical trials. The advent of next-generation sequencing promises to provide nephrologists with rapid and novel approaches for the diagnosis and treatment of FSGS. A stratified and targeted approach based on the underlying molecular defects is evolving.
doi:10.1186/s12882-015-0090-9
PMCID: PMC4496884  PMID: 26156092
Focal segmental glomerulosclerosis; Podocyte gene mutation; Proteinuria; Next-generation sequencing
11.  Evaluation of the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry Bruker Biotyper for identification of Penicillium marneffei, Paecilomyces species, Fusarium solani, Rhizopus species, and Pseudallescheria boydii 
We evaluated the performance of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), the MALDI Bruker Biotyper system (microflex LT; Bruker Daltonik GmbH, Bremen, Germany), on the identification of 50 isolates of clinically encountered molds, including Penicillium marneffei (n = 28), Paecilomyces species (n = 12), Fusarium solani (n = 6), Rhizopus species (n = 3), and Pseudallescheria boydii (n = 1). The isolates were identified to species levels by sequence analysis of the internal transcribed spacer (ITS) regions using primers ITS1 and ITS4. None of the 28 genetically well characterized isolates of P. marneffei were identified as P. marneffei by MALDI-TOF MS, because P. marneffei was not present in either Bruker general library (DB 5627) or Bruker filamentous fungi library V1.0. However, the rate of accurate identification as P. marneffei (score value ≥ 2.000) was 85.7% based on newly created database from one P. marneffei strain (NTUH-3370) by MALDI Biotyper system. Sequencing analysis of these 22 non-P. marneffei isolates of molds revealed seven Paecilomyces variotii, six F. solani, four Paecilomyces lilacinus, and one each of Paecilomyces sinensis, Rhizopus arrhizus, R. oryzae, R. microspores, and P. boydii. Although all the seven P. variotii isolates, four of the six F. solani, two of the four P. lilacinus, and two of the three isolates of Rhizopus species, and the P. boydii isolate had concordant identification results between MALDI-TOF MS and sequencing analysis, the score values of these isolates were all of <1.700. This study indicated that the MALDI Bruker Biotyper is ineffective for identifying P. marneffei and other unusual molds because of the current database limitations. Therefore, it is necessary to continuously update the MALDI-TOF MS databases.
doi:10.3389/fmicb.2015.00679
PMCID: PMC4495555  PMID: 26217315
matrix-assisted laser desorption/ionization time-of-flight mass spectrometry; Penicillium marneffei; Paecilomyces species; Fusarium solani; Rhizopus species; Pseudallescheria boydii
12.  Metabolic regulator LKB1 plays a crucial role in Schwann cell-mediated axon maintenance 
Nature neuroscience  2014;17(10):1351-1361.
Summary
Schwann cells (SCs) promote axonal integrity independently of myelination by poorly understood mechanisms. Current models suggest that SC metabolism is critical for this support function and that SC metabolic deficits may lead to axonal demise. The LKB1-AMPK kinase pathway targets multiple downstream effectors including mTOR and is a key metabolic regulator implicated in metabolic diseases. We show through integrative molecular, structural, and behavioral characterization of SC-specific mutant mice that LKB1 activity is central to axon stability, whereas AMPK and mTOR in SCs are largely dispensable. The degeneration of axons in LKB1-mutants is most dramatic in unmyelinated small sensory fibers, whereas motor axons are relatively spared. LKB1 deletion in SCs leads to abnormalities in nerve energy and lipid homeostasis, and increased lactate release. The latter acts in a compensatory manner to support distressed axons. LKB1 signaling is essential for SC-mediated axon support, a function that may be dysregulated in diabetic neuropathy.
doi:10.1038/nn.3809
PMCID: PMC4494117  PMID: 25195104
13.  Spectrum of diverse genomic alterations define non–clear cell renal carcinoma subtypes 
Nature genetics  2014;47(1):13-21.
To further understand the molecular distinctions between kidney cancer subtypes, we analyzed exome, transcriptome and copy number alteration data from 167 primary human tumors that included renal oncocytomas and non–clear cell renal cell carcinomas (nccRCCs), consisting of papillary (pRCC), chromophobe (chRCC) and translocation (tRCC) subtypes. We identified ten significantly mutated genes in pRCC, including MET, NF2, SLC5A3, PNKD and CPQ. MET mutations occurred in 15% (10/65) of pRCC samples and included previously unreported recurrent activating mutations. In chRCC, we found TP53, PTEN, FAAH2, PDHB, PDXDC1 and ZNF765 to be significantly mutated. Gene expression analysis identified a five-gene set that enabled the molecular classification of chRCC, renal oncocytoma and pRCC. Using RNA sequencing, we identified previously unreported gene fusions, including ACTG1-MITF fusion. Ectopic expression of the ACTG1-MITF fusion led to cellular transformation and induced the expression of downstream target genes. Finally, we observed upregulation of the anti-apoptotic factor BIRC7 in MiTF-high RCC tumors, suggesting a potential therapeutic role for BIRC7 inhibitors.
doi:10.1038/ng.3146
PMCID: PMC4489427  PMID: 25401301
14.  Co-expression of three opsins in cone photoreceptors of the salamander, Ambystoma tigrinum 
The Journal of comparative neurology  2014;522(10):2249-2265.
Whereas more than one type of visual opsin is present in the retina of most vertebrates, it was thought that each type of photoreceptor expressed only one opsin. However, evidence has accumulated that some photoreceptors contain more than one opsin, in many cases as a result of a developmental transition from the expression of one opsin to another. The salamander UV-sensitive (UV) cone is particularly notable because it contains three opsins (Makino and Dodd, 1996; J Gen Physiol 108:27–34). Two opsin types are expressed at levels more than a hundred times lower than that of the primary opsin. Here, immunohistochemical experiments identified the primary component as a UV cone opsin and the two minor components as the short wavelength-sensitive (S) and long wavelength-sensitive (L) cone opsins. Based on single cell recordings of 156 photoreceptors, the presence of three components in UV cones of hatchlings and terrestrial adults ruled out a developmental transition. There was no evidence for multiple opsin types within rods or S cones. But immunohistochemistry and partial bleaching in conjunction with single cell recording revealed that both single and double L cones contained low levels of short wavelength-sensitive pigments in addition to the main L visual pigment. These results raise the possibility that co-expression of multiple opsins in other vertebrates was overlooked because a minor component absorbing at short wavelengths was masked by the main visual pigment or because the expression level of a component absorbing at long wavelengths was exceedingly low.
doi:10.1002/cne.23531
PMCID: PMC3997598  PMID: 24374736
electrophysiology; immunocytochemistry; phototransduction; retina; visual pigment
15.  Performance of Goodness-of-Fit Tests for the Cox Proportional Hazards Model with Time-Varying Covariates 
Lifetime data analysis  2013;20(3):355-368.
There are few readily-implemented tests for goodness-of-fit for the Cox proportional hazards model with time-varying covariates. Through simulations, we assess the power of tests by Cox (1972), Grambsch and Therneau (1994), and Lin et al (2006). Results show that power is highly variable depending on the time to violation of proportional hazards, the magnitude of the change in hazard ratio, and the direction of the change. Because these characteristics are unknown outside of simulation studies, none of the tests examined is expected to have high power in real applications. While all of these tests are theoretically interesting, they appear to be of limited practical value.
doi:10.1007/s10985-013-9277-1
PMCID: PMC3918489  PMID: 23925703
Survival analysis; Lack of fit; Time-dependent covariates
17.  Microstructural abnormalities of the brain white matter in attention-deficit/hyperactivity disorder 
Background
Attention-deficit/hyperactivity disorder (ADHD) is an early-onset neurodevelopmental disorder with multiple behavioural problems and executive dysfunctions for which neuroimaging studies have reported a variety of abnormalities, with inconsistencies partly owing to confounding by medication and concurrent psychiatric disease. We aimed to investigate the microstructural abnormalities of white matter in unmedicated children and adolescents with pure ADHD and to explore the association between these abnormalities and behavioural symptoms and executive functions.
Methods
We assessed children and adolescents with ADHD and healthy controls using psychiatric interviews. Behavioural problems were rated using the revised Conners’ Parent Rating Scale, and executive functions were measured using the Stroop Colour-Word Test and the Wisconsin Card Sorting test. We acquired diffusion tensor imaging data using a 3 T MRI system, and we compared diffusion parameters, including fractional anisotropy (FA) and mean, axial and radial diffusivities, between the 2 groups.
Results
Thirty-three children and adolescents with ADHD and 35 healthy controls were included in our study. In patients compared with controls, FA was increased in the left posterior cingulum bundle as a result of both increased axial diffusivity and decreased radial diffusivity. In addition, the averaged FA of the cluster in this region correlated with behavioural measures as well as executive function in patients with ADHD.
Limitations
This study was limited by its cross-sectional design and small sample size. The cluster size of the significant result was small.
Conclusion
Our findings suggest that white matter abnormalities within the limbic network could be part of the neural underpinning of behavioural problems and executive dysfunction in patients with ADHD.
doi:10.1503/jpn.140199
PMCID: PMC4478061  PMID: 25853285
18.  Resection of the main trunk of the superior mesenteric vein without reconstruction during surgery for giant pancreatic mucinous cystadenoma: A case report 
Pancreatic tumors, with peri-pancreatic main vascular invasion, especially the superior mesenteric vein (SMV) or the portal vein, are very common. In some cases, vascular resection and reconstruction are required for complete resection of pancreatic tumors. However, the optimum surgical method for venous management is controversial. Resection of the SMV without reconstruction during surgery for pancreatic tumors is rarely reported. Here we present the case of a 58-year-old woman with a giant pancreatic mucinous cystadenoma adhering to the SMV, who underwent an en bloc tumor resection, including the main trunk of the SMV and the spleen. No venous reconstruction was performed during surgery. No ischemic changes occurred in the bowel. The presence of several well-developed collateral vessels was shown by 3-dimensional computed tomography examination. The patient had an uneventful postoperative period and was discharged. This case indicated that the main trunk of the SMV can be resected without venous reconstruction if adequate collateralization has formed.
doi:10.3748/wjg.v21.i24.7604
PMCID: PMC4481460  PMID: 26140011
Superior mesenteric vein; Pancreatic mucinous cystadenoma; Collateral vessel; Main trunk; Reconstruction
19.  Lung cancer risk among bricklayers in a pooled analysis of case–control studies 
Bricklayers may be exposed to several lung carcinogens, including crystalline silica and asbestos. Previous studies that analyzed lung cancer risk among these workers had several study design limitations. We examined lung cancer risk among bricklayers within SYNERGY, a large international pooled analysis of case–control studies on lung cancer and the joint effects of occupational carcinogens. For men ever employed as bricklayers we estimated odds ratios (OR) and 95% confidence intervals (CI) adjusted for study center, age, lifetime smoking history and employment in occupations with exposures to known or suspected lung carcinogens. Among 15,608 cases and 18,531 controls, there were 695 cases and 469 controls who had ever worked as bricklayers (OR: 1.47; 95% CI: 1.28–1.68). In studies using population controls the OR was 1.55 (95% CI: 1.32–1.81, 540/349 cases/controls), while it was 1.24 (95% CI: 0.93–1.64, 155/120 cases/controls) in hospital-based studies. There was a clear positive trend with length of employment (p < 0.001). The relative risk was higher for squamous (OR: 1.68, 95% CI: 1.42–1.98, 309 cases) and small cell carcinomas (OR: 1.78, 95% CI: 1.44–2.20, 140 cases), than for adenocarcinoma (OR: 1.17, 95% CI: 0.95–1.43, 150 cases) (p-homogeneity: 0.0007). ORs were still elevated after additional adjustment for education and in analyses using blue collar workers as referents. This study provided robust evidence of increased lung cancer risk in bricklayers. Although non-causal explanations cannot be completely ruled out, the association is plausible in view of the potential for exposure to several carcinogens, notably crystalline silica and to a lesser extent asbestos.
What's new?
In their work, bricklayers can be exposed to various airborne carcinogens, including crystalline silica and asbestos. Previous studies of cancer risk have not accounted for full employment history or smoking status, and failed to establish a firm relationship between bricklaying and lung cancer. In this study, the authors used data from the largest collection of case-control studies on lung cancer with complete occupational and smoking history existing today, the SYNERGY project. They found clear evidence that lung cancer risk increases in proportion to the length of time spent working as a bricklayer, paving the way for better protection and compensation for those in this occupation.
doi:10.1002/ijc.28986
PMCID: PMC4477910  PMID: 24861979
lung neoplasms; case–control studies; bricklayers; occupational health; epidemiology
20.  Fabrication of nanoscale Ga balls via a Coulomb explosion of microscale silica-covered Ga balls by TEM electron-beam irradiation 
Scientific Reports  2015;5:11313.
Nanoscale Ga particles down to 5 nm were fabricated by an explosion via an in situ electron-beam irradiation on microscale silica-covered Ga balls in a transmission electron microscope. The explosion is confirmed to be a Coulomb explosion because it occurs on the surface rather than in the whole body of the insulating silica-covered Ga micro–balls, and on the pure Ga nano-balls on the edge of carbon film. The ejected particles in the explosion increase their sizes with increasing irradiation time until the stop of the explosion, but decrease their sizes with increasing distance from the original ball. The Coulomb explosion suggests a novel method to fabricate nanoscale metal particles with low melting point.
doi:10.1038/srep11313
PMCID: PMC4477366  PMID: 26100238
21.  Amniotic fluid stem cells provide considerable advantages in epidermal regeneration: B7H4 creates a moderate inflammation microenvironment to promote wound repair 
Scientific Reports  2015;5:11560.
The current treatments for severe skin injury all involve skin grafting. However, there is a worldwide shortage of donor skin tissue. In this study, we examined the advantages of using human amniotic fluid stem (hAFS) cells in skin wound healing. In vitro, hAFS cells differentiate into keratinocytes (termed hAFS-K). Like keratinocytes, hAFS-K cells express the markers K5, K14, K10 and involucrin; display typical cellular structure, including a tonofibril-rich cytoplasm; and construct a completely pluristratified epithelium in 3D culture. In vivo, in a mouse excisional wound model, GFP-positive hAFS cells participate in wound repair. Co-localization of GFP/K14 and GFP/K10 in the repaired epidermis demonstrated that hAFS cells can differentiate into keratinocytes. Real-time PCR results confirmed that hAFS cells can initiate and promote early-stage repair of skin damage. During wound repair, hAFS cells did not directly secrete repair-related factors, such as bFGF, VEGF, CXCL12, TGF-β1 and KGF, and provided a moderate inflammation reaction with lower expression of IL-1β, IL-6, TNF-α, Cox2 and Mac3. In hAFS cells, the negative co-stimulatory molecule B7H4 regulates low immunogenicity, which can provide a modest inflammatory reaction microenvironment for wound repair. Furthermore, with their uniquely high proliferation rate, hAFS cells offer a promising alternative for epidermal regeneration.
doi:10.1038/srep11560
PMCID: PMC4477371  PMID: 26101181
22.  Age and CHADS2 Score Predict the Effectiveness of Renin-Angiotensin System Blockers on Primary Prevention of Atrial Fibrillation 
Scientific Reports  2015;5:11442.
Renin-angiotensin system (RAS) blockers have potential protective effects against atrial fibrillation (AF). The purpose of this study was to determine if patient characteristics and underlying co-morbidities could predict the efficacy of RAS blockers in AF prevention. Patients aged ≥ 45 years with hypertension were identified from the Taiwan National Health Insurance Research Database. After propensity-score matching, a total of 22,324 patients were included in this study. Risk of new-onset AF in RAS blockers users and non-users was estimated. During up to 10 years of follow-up, 1,475 patients experienced new-onset AF. Overall, RAS blockers reduced the risk of AF by 36% (adjusted HR 0.64; 95% CI 0.58 to 0.71; p < 0.001). Subgroup analysis showed that RAS blockers use was beneficial for AF prevention in patients aged ≥ 55 years or with a CHADS2 score of 1, 2, or 3. The therapy provided no obvious beneficial effect for AF prevention in those aged less than 55 years or with a CHADS2 score ≥ 4. In conclusion, RAS blockers reduced the risk of new-onset AF in patients aged ≥ 55 years or with a CHADS2 score of 1, 2, or 3, but not in patients aged less than 55 years or with a CHADS2 score ≥ 4.
doi:10.1038/srep11442
PMCID: PMC4476091  PMID: 26094981
23.  Breathable and Stretchable Temperature Sensors Inspired by Skin 
Scientific Reports  2015;5:11505.
Flexible electronics attached to skin for healthcare, such as epidermal electronics, has to struggle with biocompatibility and adapt to specified environment of skin with respect to breath and perspiration. Here, we report a strategy for biocompatible flexible temperature sensors, inspired by skin, possessing the excellent permeability of air and high quality of water-proof by using semipermeable film with porous structures as substrate. We attach such temperature sensors to underarm and forearm to measure the axillary temperature and body surface temperature respectively. The volunteer wears such sensors for 24 hours with two times of shower and the in vitro test shows no sign of maceration or stimulation to the skin. Especially, precise temperature changes on skin surface caused by flowing air and water dropping are also measured to validate the accuracy and dynamical response. The results show that the biocompatible temperature sensor is soft and breathable on the human skin and has the excellent accuracy compared to mercury thermometer. This demonstrates the possibility and feasibility of fully using the sensors in long term body temperature sensing for medical use as well as sensing function of artificial skin for robots or prosthesis.
doi:10.1038/srep11505
PMCID: PMC4476093  PMID: 26095941
24.  Impact of body mass index on complications following pancreatectomy: Ten-year experience at National Cancer Center in China 
AIM: To examine the impact of body mass index (BMI) on outcomes following pancreatic resection in the Chinese population.
METHODS: A retrospective cohort study using prospectively collected data was conducted at the Cancer Hospital of the Chinese Academy of Medical Sciences, China National Cancer Center. Individuals who underwent pancreatic resection between January 2004 and December 2013 were identified and included in the study. Persons were classified as having a normal weight if their BMI was < 24 kg/m2 and overweight/obese if their BMI was ≥ 24 kg/m2 as defined by the International Life Sciences Institute Focal Point in China. A χ2 test (for categorical variables) or a t test (for continuous variables) was used to examine the differences in patients’ characteristics between normal weight and overweight/obese groups. Multiple logistic regression models were used to assess the associations of postoperative complications, operative difficulty, length of hospital stay, and cost with BMI, adjusting for age, sex, and type of surgery procedures.
RESULTS: A total of 362 consecutive patients with data available for BMI calculation underwent pancreatic resection for benign or malignant disease from January 1, 2004 to December 31, 2013. Of the 362 patients, 156 were overweight or obese and 206 were of normal weight. One or more postoperative complications occurred in 35.4% of the patients following pancreatic resection. Among patients who were overweight or obese, 42.9% experienced one or more complications, significantly higher than normal weight (29.6%) individuals (P = 0.0086). Compared with individuals who had normal weight, those with a BMI ≥ 24.0 kg/m2 had higher delayed gastric emptying (19.9% vs 5.8%, P < 0.0001) and bile leak (7.7% vs 1.9%, P = 0.0068). There were no significant differences seen in pancreatic fistula, gastrointestinal hemorrhage, reoperation, readmission, or other complications. BMI did not show a significant association with intraoperative blood loss, operative time, length of hospital stay, or cost.
CONCLUSION: Higher BMI increases the risk for postoperative complications after pancreatectomy in the Chinese population. The findings require replication in future studies with larger sample sizes.
doi:10.3748/wjg.v21.i23.7218
PMCID: PMC4476883  PMID: 26109808
Body mass index; China; Pancreatectomy; Pancreatic cancer; Postoperative complications
25.  Corneal endothelial cell density and morphology and central corneal thickness in Guangxi Maonan and Han adolescent students of China 
AIM
To investigate the corneal endothelial cell density and morphology and central corneal thickness in the Guangxi Maonan and Han adolescent students of China.
METHODS
Noncontact specular microscope (Topcon SP3000P, Tokyo, Japan) was performed in 133 adolescent students of Maonan nationality (M:F 54:79) and 105 adolescent students of Han nationality (M:F 50:55), 5 to 20y of age, who were randomly selected from 3 schools in Huanjiang Maonan Autonomous County of Guangxi Zhuang Autonomous Region of China. Parameters studied included endothelial cell density, mean cell area, coefficient of variation in cell size, percentage hexagonality and central corneal thickness.
RESULTS
Endothelial cell density, mean cell area, coefficient of variation in cell size, percentage hexagonality and central corneal thickness in the study population were (2969.50±253.93) cells/mm2, (339.23±29.44) µm2, (29.96±4.07) %, (64.58±9.41) % and (523.71±32.82) µm in Maonan and (2998.26±262.65) cells/mm2, (336.11±30.07) µm2, (29.89±5.03) %, (64.91±11.64) % and (524.39±33.15) µm in Han, respectively. No significant differences were observed in endothelial cell density, mean cell area, coefficient of variation in cell size, percentage hexagonality and central corneal thickness between Maonan and Han (P=0.615, 0.659, 0.528, 0.551, 0.999). In Maonan and Han, we found age was negatively correlated with endothelial cell density and percentage hexagonality and positively correlated with mean cell area and coefficient of variation in cell size. Negative correlation was also found between central corneal thickness and age in Han, whereas no correlation was found in Maonan.
CONCLUSION
There were no differences between Maonan and Han in corneal endothelial cell density and morphology and central corneal thickness. In these two nationalities, there were statistically significant decrease in endothelial cell density and percentage hexagonality with increasing age and statistically significant increase in cell area and coefficient of variation in cell size with increasing age. Central corneal thinned with increasing age in Han, whereas difference did not attain statistical significance in Maonan.
doi:10.3980/j.issn.2222-3959.2015.03.31
PMCID: PMC4458672  PMID: 26086017
endothelial cell density; morphology; central corneal thickness; Maonan

Results 1-25 (716)