bluuebunny/crossref_metadata_2025 huggingface dataset:
Rice Germosprout Extract Protects Erythrocytes from Hemolysis and the Aorta, Brain, Heart, and Liver Tissues from Oxidative Stress In Vitro
Authors: Hossain Shahdat , Bhowmick Sujan , Sarkar Marzan , Hassan Mehedi , Hussain Jakir , Islam Saiful , Shahjalal Hussain
Published: June 2016

Identifying dietary alternatives for artificial antioxidants capable of boosting antihemolytic and antioxidative defense has been an important endeavor in improving human health. In the present study, we studied antihemolytic and antioxidative effects of germosprout (i.e., the germ part along with sprouted stems plus roots) extract prepared from the pregerminated rice. The extract contained considerable amounts of antioxidant β‐carotene (414 ± 12 ng/g of extract) and phytochemicals such as total polyphenols (12.0 ± 1.1 mg gallic acid equivalent/g of extract) and flavonoids (11.0 ± 1.4 mg catechin equivalent/g of extract). The antioxidant potential of the extract was assessed by its DPPH‐ (2,2‐diphenyl‐1‐picrylhydrazyl‐) free radical scavenging activity where we observed that germosprout extract had considerable antioxidative potentials. To evaluate antihemolytic effect of the extract, freshly prepared erythrocytes were incubated with either peroxynitrite or Fenton’s reagent in the absence or presence of the extract. We observed that erythrocytes pretreated with the extract exhibited reduced degree of in vitro hemolysis. To support the proposition that germosprout extract could act as a good antioxidative agent, we also induced in vitro oxidative stress in erythrocyte membranes and in the aorta, brain, heart, and liver tissue homogenates in the presence of the extract. As expected, germosprout extract decreased oxidative stress almost to the same extent as that of vitamin E, as measured by lipid peroxide levels, in all the mentioned tissues. We conclude that rice germosprout extract could be a good natural source of antioxidants to reduce oxidative stress‐induced hemolysis and damage of blood vessels and other tissues.
The Ubiquitin-like Protein FAT10 Stabilizes eEF1A1 Expression to Promote Tumor Proliferation in a Complex Manner
Authors: Liu Xiuxia , Chen Leifeng , Ge Jin , Yan Chen , Huang Zixi , Hu Junwen , Wen Chongyu , Li Ming , Huang Da , Qiu Yumin , Hao Haibin , Yuan Rongfa , Lei Jun , Yu Xin , Shao Jianghua
Published: June 2016

Human HLA-F adjacent transcript 10 (FAT10) is the only ubiquitin-like protein that can directly target substrates for degradation by proteasomes, but it can also stabilize the expression of certain substrates by antagonizing ubiquitination, through mechanisms as yet uncharacterized. In this study, we show how FAT10 stabilizes the translation elongation factor eEF1A1, which contributes to cancer cell proliferation. FAT10 overexpression increased expression of eEF1A1, which was sufficient to promote proliferation of cancer cells. Mechanistic investigations revealed that FAT10 competed with ubiquitin (Ub) for binding to the same lysines on eEF1A1 to form either FAT10–eEF1A1 or Ub–eEF1A1 complexes, respectively, such that FAT10 overexpression decreased Ub–eEF1A1 levels and increased FAT10–eEF1A1 levels. Overall, our work establishes a novel mechanism through which FAT10 stabilizes its substrates, advancing understanding of the biological function of FAT10 and its role in cancer. Cancer Res; 76(16); 4897–907. ©2016 AACR.
Molecular Landscape of Acquired Resistance to Targeted Therapy Combinations in BRAF-Mutant Colorectal Cancer
Authors: Oddo Daniele , Sennott Erin M. , Barault Ludovic , Valtorta Emanuele , Arena Sabrina , Cassingena Andrea , Filiciotto Genny , Marzolla Giulia , Elez Elena , van Geel Robin M.J.M. , Bartolini Alice , Crisafulli Giovanni , Boscaro Valentina , Godfrey Jason T. , Buscarino Michela , Cancelliere Carlotta , Linnebacher Michael , Corti Giorgio , Truini Mauro , Siravegna Giulia , Grasselli Julieta , Gallicchio Margherita , Bernards René , Schellens Jan H.M. , Tabernero Josep , Engelman Jeffrey A. , Sartore-Bianchi Andrea , Bardelli Alberto , Siena Salvatore , Corcoran Ryan B. , Di Nicolantonio Federica
Published: June 2016

Although recent clinical trials of BRAF inhibitor combinations have demonstrated improved efficacy in BRAF-mutant colorectal cancer, emergence of acquired resistance limits clinical benefit. Here, we undertook a comprehensive effort to define mechanisms underlying drug resistance with the goal of guiding development of therapeutic strategies to overcome this limitation. We generated a broad panel of BRAF-mutant resistant cell line models across seven different clinically relevant drug combinations. Combinatorial drug treatments were able to abrogate ERK1/2 phosphorylation in parental-sensitive cells, but not in their resistant counterparts, indicating that resistant cells escaped drug treatments through one or more mechanisms leading to biochemical reactivation of the MAPK signaling pathway. Genotyping of resistant cells identified gene amplification of EGFR, KRAS, and mutant BRAF, as well as acquired mutations in KRAS, EGFR, and MAP2K1. These mechanisms were clinically relevant, as we identified emergence of a KRAS G12C mutation and increase of mutant BRAF V600E allele frequency in the circulating tumor DNA of a patient at relapse from combined treatment with BRAF and MEK inhibitors. To identify therapeutic combinations capable of overcoming drug resistance, we performed a systematic assessment of candidate therapies across the panel of resistant cell lines. Independent of the molecular alteration acquired upon drug pressure, most resistant cells retained sensitivity to vertical MAPK pathway suppression when combinations of ERK, BRAF, and EGFR inhibitors were applied. These therapeutic combinations represent promising strategies for future clinical trials in BRAF-mutant colorectal cancer. Cancer Res; 76(15); 4504–15. ©2016 AACR.
GON4L Drives Cancer Growth through a YY1–Androgen Receptor–CD24 Axis
Authors: Agarwal Neeraj , Dancik Garrett M. , Goodspeed Andrew , Costello James C. , Owens Charles , Duex Jason E. , Theodorescu Dan
Published: June 2016

In principle, the inhibition of candidate gain-of-function genes defined through genomic analyses of large patient cohorts offers an attractive therapeutic strategy. In this study, we focused on changes in expression of CD24, a well-validated clinical biomarker of poor prognosis and a driver of tumor growth and metastasis, as a benchmark to assess functional relevance. Through this approach, we identified GON4L as a regulator of CD24 from screening a pooled shRNA library of 176 candidate gain-of-function genes. GON4L depletion reduced CD24 expression in human bladder cancer cells and blocked cell proliferation in vitro and tumor xenograft growth in vivo. Mechanistically, GON4L interacted with transcription factor YY1, promoting its association with the androgen receptor to drive CD24 expression and cell growth. In clinical bladder cancer specimens, expression of GON4L, YY1, and CD24 was elevated compared with normal bladder urothelium. This pathway is biologically relevant in other cancer types as well, where CD24 and the androgen receptor are clinically prognostic, given that silencing of GON4L and YY1 suppressed CD24 expression and growth of human lung, prostate, and breast cancer cells. Overall, our results define GON4L as a novel driver of cancer growth, offering new biomarker and therapeutic opportunities. Cancer Res; 76(17); 5175–85. ©2016 AACR.
Durable Complete Response from Metastatic Melanoma after Transfer of Autologous T Cells Recognizing 10 Mutated Tumor Antigens
Authors: Prickett Todd D. , Crystal Jessica S. , Cohen Cyrille J. , Pasetto Anna , Parkhurst Maria R. , Gartner Jared J. , Yao Xin , Wang Rong , Gros Alena , Li Yong F. , El-Gamil Mona , Trebska-McGowan Kasia , Rosenberg Steven A. , Robbins Paul F.
Published: June 2016

Immunotherapy treatment of patients with metastatic cancer has assumed a prominent role in the clinic. Durable complete response rates of 20% to 25% are achieved in patients with metastatic melanoma following adoptive cell transfer of T cells derived from metastatic lesions, responses that appear in some patients to be mediated by T cells that predominantly recognize mutated antigens. Here, we provide a detailed analysis of the reactivity of T cells administered to a patient with metastatic melanoma who exhibited a complete response for over 3 years after treatment. Over 4,000 nonsynonymous somatic mutations were identified by whole-exome sequence analysis of the patient's autologous normal and tumor cell DNA. Autologous B cells transfected with 720 mutated minigenes corresponding to the most highly expressed tumor cell transcripts were then analyzed for their ability to stimulate the administered T cells. Autologous tumor-infiltrating lymphocytes recognized 10 distinct mutated gene products, but not the corresponding wild-type products, each of which was recognized in the context of one of three different MHC class I restriction elements expressed by the patient. Detailed clonal analysis revealed that 9 of the top 20 most prevalent clones present in the infused T cells, comprising approximately 24% of the total cells, recognized mutated antigens. Thus, we have identified and enriched mutation-reactive T cells and suggest that such analyses may lead to the development of more effective therapies for the treatment of patients with metastatic cancer. Cancer Immunol Res; 4(8); 669–78. ©2016 AACR.
Outcome of Patients after Third and Fourth Kidney Transplantation
Authors: Friedersdorff Frank , Patabendhi Supuni , Busch Jonas , Kempkensteffen Carsten , Halleck Fabian , Fuller Tom Florian , Miller Kurt , Peters Robert
Published: June 2016

Introduction: A debate exists whether patients after second graft loss should be considered for a third and subsequent graft. Hence, a retrospective analysis was undertaken to assess outcomes of patients who underwent third and fourth transplantation. Materials and Methods: A total number of 16 kidney transplantations, were included in the present study. Thirteen patients out of them underwent a third kidney transplantation and 3 were fourth graft recipients. Data and variables on patient and graft survival were retrieved and analyzed using Kaplan-Meier statistics. Postoperative complications were assessed and graded based on Clavien-Dindo classification. Results: Patient survival was 92.3% after 1 year and 76.9% after 5 years (third graft). One year censored graft survival was 100% and a 5-year graft survival was 74.1% (third graft), respectively. In the cases of fourth transplantation, graft survivals of 33.3% at 1 and 2 years were noted among 3 patients. All fourth graft recipients have survived during our observation time. The overall rate of postoperative surgical complications among third graft recipients was 46.2 and 66.7% among patients after fourth transplantation. Conclusions: Results on third kidney transplantation showed satisfactory patient and graft survival with acceptable outcome.
Validation of a Preclinical Model of Diethylnitrosamine-Induced Hepatic Neoplasia in Yucatan Miniature Pigs
Authors: Mitchell Jennifer , Tinkey Peggy T. , Avritscher Rony , Van Pelt Carolyn , Eskandari Ghazaleh , Konnath George Suraj , Xiao Lianchun , Cressman Erik , Morris Jeffrey S. , Rashid Asif , Kaseb Ahmed O. , Amin Hesham M. , Uthamanthil Rajesh
Published: June 2016

Objective: The purpose of this study was to reduce the time to tumor onset in a diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) swine model via partial liver embolization (PLE) and to characterize the model for use in translational research. Methods: Eight Yucatan miniature pigs were injected intraperitoneally with either saline (n = 2) or DEN (n = 6) solution weekly for 12 weeks. Three of the DEN-treated pigs underwent PLE. The animals underwent periodic radiological evaluation, liver biopsy, and blood sampling, and full necropsy was performed at study termination (∼29 months). Results: All DEN-treated pigs developed hepatic adenoma and HCC. PLE accelerated the time to adenoma development but not to HCC development. Biomarker analysis results showed that IGF1 levels decreased in all DEN-treated pigs as functional liver capacity decreased with progression of HCC. VEGF and IL-6 levels were positively correlated with disease progression. Immunohistochemical probing of HCC tissues demonstrated the expression of several important survival-promoting proteins. Conclusion: To our knowledge, we are the first to demonstrate an accelerated development of hepatic neoplasia in Yucatan miniature pigs. Our HCC swine model closely mimics the human condition (i.e., progressive disease stages and expression of relevant molecular markers) and is a viable translational model.
Genetic Association of TCF4 and AKT1 Gene Variants with the Age at Onset of Schizophrenia
Authors: Chow Tze Jen , Tee Shiau Foon , Yong Hoi Sen , Tang Pek Yee
Published: June 2016

Background: Age at onset (AAO) is a known prognostic indicator for schizophrenia and is hypothesized to correlate with cognition and symptom severity. TCF4 and AKT1 are schizophrenia risk genes involved in cognitive functions. The current study examined the interactive effects of TCF4 and AKT1 variants with gender, family history of psychiatric disorders and ethnicity on the AAO of schizophrenia. Methods: This study consisted of 322 patients with schizophrenia meeting the DSM-IV criteria. Six single nucleotide polymorphisms (SNPs) of TCF4 (rs12966547, rs8766, rs2958182, rs9960767, rs10401120 and rs17512836) and seven AKT1 SNPs (rs2498804, rs3803304, rs2494732, rs3730358, rs1130214, rs2498784 and rs3803300) were genotyped using the TaqMan® SNP genotyping-based assays method. The relationship of AAO with each variant was investigated using analyses of covariance. Results: Among the TCF4 variants, rs12966547 (p = 0.024) and rs8766 (p = 0.021) were significantly associated with earlier AAO. We found a lower average AAO in patients with the AA genotype of rs12966547, while the CT genotype of rs8766 was demonstrated to have a protective effect on AAO. For rs8766, there was significant gene × gender interaction (p = 0.012) in influencing AAO. However, these results were not significant after false discovery rate correction. Significant gene × ethnicity interactions were observed to influence AAO (p < 0.05). The Kaplan-Meier curve of the minor AA genotype of rs12966547 displayed a significant trend (p = 0.008) for onset after 19 years of age. Similarly, the minor CC genotype of rs8766 showed a significantly (p = 0.034) lower AAO compared to the TT genotype. Conclusion: Our analyses suggest that individual risk genotypes may influence the risk of schizophrenia in an age-specific manner.
Complement-C1q TNF-Related Protein 3 Alleviates Mesangial Cell Activation and Inflammatory Response Stimulated by Secretory IgA
Authors: Zhang Ruicheng , Zhong Liangbao , Zhou Jufeng , Peng Youming
Published: June 2016

Background: Elevated circulating IgA complex deposits in the glomerular mesangium and causes resultant mesangial cell activation, eventually leading to the progression of IgA nephropathy (IgAN). Complement-C1q TNF-related protein 3 (CTRP3) is documented as a potential anti-inflammatory and anti-fibrotic mediator; however, its role in IgAN is unknown. Methods: Serum polymeric IgA (pIgA) was isolated from patients with IgAN and healthy volunteers. Human mesangial cells (HMCs) were incubated with the isolated pIgA. The expression of CTRP3 and its effects on inflammatory cytokines and extracellular matrix were evaluated. Results: Median circulating CTRP3 decreased in patients with IgAN compared to the controls, accompanied by the elevated serum and urine TGF-β and IL-6. While urine CTRP3 in IgAN patients were comparable to that in healthy subjects. pIgA dose-dependently inhibited the expression of CTRP3 and HMC tolerated pIgA at 1.0 mg/ml, for which galactose-deficient IgA might be responsible. pIgA markedly increased IL-6 and TGF-β in HMCs, which were suppressed after Ad-CTRP3 transfection. Additionally, CTRP3 significantly inhibited pIgA-stimulated HMC proliferation, cell cycle progression and synthesis of CTGF and fibronectin. Furthermore, we found that pIgA-treated HMC exhibited higher NF-κB activity as reflected by the increased levels of nuclear p65. Moreover, Src activation and the subsequent Smad3 phosphorylation were significantly elevated in response to the stimulation with pIgA. However, NF-κB activity and Smad3 signaling were inhibited after Ad-CTRP3 transfection in HMC. Conclusion: CTRP3 potentially targeted to NF-κB and TGF-β-Src-Smad3 signaling and exerted anti-inflammatory and anti-fibrotic roles to attenuate the progression of IgAN, which may represent a new strategy for the treatment of IgAN.
Diagnostics and Epidemiology of Colorectal Cancer
Authors: Kolligs Frank T.
Published: June 2016

Colorectal cancer is one of the leading causes of cancer-related morbidity and mortality. Main risk factors include advanced age, family history, male sex, and lifestyle factors. Screening can reduce incidence and death from colorectal cancer. Therefore, prevention and early detection are crucial in order to detect and remove pre-neoplastic adenomas and to detect cancers at early stages. Colonoscopy, flexible sigmoidoscopy, and fecal occult blood tests are established tools for screening. Newer fecal immunochemical tests reveal higher sensitivities for advanced adenoma and cancer than guaiac-based hemoccult tests. Molecular stool and blood tests as well as virtual colonoscopy and colon capsule endoscopy are promising new developments so far not established as routine instruments for the prevention and early detection of colorectal cancer. Colonoscopy is the method of choice for the diagnosis of colorectal cancer and for adenoma removal. Prognosis is essentially dependent on the tumor stage at the time of the initial diagnosis. Proper staging based on imaging prior to therapy is a prerequisite. In rectal cancer, local staging is an essential requirement for the identification of appropriate candidates for neoadjuvant therapy.
Recanalization and Angiographic Reperfusion Are Both Associated with a Favorable Clinical Outcome in the IMS III Trial
Authors: Schmitz Marie L. , Yeatts Sharon D. , Tomsick Thomas A. , Liebeskind David S. , Vagal Achala , Broderick Joseph P. , Khatri Pooja ,   for the IMS III investigators
Published: June 2016

Background: Prompt revascularization is the main goal of acute ischemic stroke treatment. We examined which revascularization scale - reperfusion (modified Treatment in Cerebral Infarctions, mTICI) or recanalization (Arterial Occlusive Lesion, AOL) - better predicted the clinical outcome in ischemic stroke participants treated with endovascular therapy (EVT). Additionally, we determined the optimal thresholds for the predictive accuracy of each scale. Methods: We included participants from the Interventional Management of Stroke (IMS) III trial with complete occlusion in the internal carotid artery terminus or proximal middle cerebral artery (M1 or M2) who completed EVT within 7 h of symptom onset. The abilities of the AOL and mTICI scales to predict a favorable outcome (defined as a modified Rankin Scale score of 0-2 at 3 months) were compared by receiver operating characteristic analyses. The maximal sensitivity and specificity for each revascularization scale were established. Results: Among 240 participants who met the study inclusion criteria, 79 (33%) achieved a favorable outcome. Higher scores of mTICI and AOL increased the likelihood of a favorable outcome (2.7% with mTICI 0 vs. 83.3% with mTICI 3, and 3.0% with AOL 0 vs. 43% with AOL 3). The accuracy of mTICI reperfusion and AOL recanalization for a favorable outcome prediction was similar, with optimal thresholds of mTICI 2b/3 and AOL 3, respectively. Conclusion: Reperfusion (mTICI) and recanalization (AOL) predicted a favorable clinical outcome with comparable accuracy in ischemic stroke participants treated with EVT. Optimal revascularization goals to maximize clinical outcome (modified Rankin Scale score of 0-2) consisted of complete recanalization (AOL 3) and reperfusion of at least 50% of the arterial tree of the symptomatic artery (mTICI 2b/3) in the IMS III trial setting.
Visual Improvement after Intra-Arterial Thrombolysis for Central Retinal Artery Occlusion Does Not Correlate with Time to Treatment
Authors: Page Paul S. , Cambon Alexander C. , James Robert F.
Published: June 2016

Background: Intra-arterial thrombolysis (IAT) for the treatment of acute central retinal artery occlusion (CRAO) has demonstrated variable results for improving visual acuity and remains controversial. Despite limited evidence, time from symptom onset to thrombolysis is believed to be an important factor in predicting visual improvement after IAT. Methods: A comprehensive review of the literature was conducted and individual subject level data were extracted from relevant studies. From these, a secondary analysis was performed. Initial and final logarithm of the minimum angle of resolution (logMAR) scores were either abstracted directly from relevant studies or converted from provided Snellen chart scores. Change in logMAR scores was used to determine overall treatment efficacy. Results: Data on 118 patients undergoing IAT from five studies were evaluated. Median logMAR improvement in visual acuity was -0.400 (p < 0.001). There was no significant association between logMAR change and time to treatment when time (hours) was described as a continuous variable or described categorically [0-4, 4-8, 8-12, 12+ h; or 0-6, 6-12, 12+ h]. Conclusion: The visual improvement observed in this series had no relationship to the time from symptom onset to treatment with IAT. This suggests that patients may have the possibility for improvement even with delayed presentation to the neurointerventionalist. Other factors, such as completeness of retinal occlusion, may be more important than time to treatment. Additional studies to determine optimal patient selection criteria for the endovascular treatment of acute CRAO are needed.
Intrahepatic Size Regulation in a Surgical Model: Liver Resection-Induced Liver Regeneration Counteracts the Local Atrophy following Simultaneous Portal Vein Ligation
Authors: Wei Weiwei , Zhang Tianjiao , Fang Haoshu , Dirsch Olaf , Schenk Andrea , Homeyer André , Gremse Felix , Zafarnia Sara , Settmacher Utz , Dahmen Uta
Published: June 2016

Background/Aim: Liver size regulation is based on the balance between hepatic regeneration and atrophy. To achieve a better understanding of intrahepatic size regulation, we explored the size regulation of a portally deprived liver lobe on a liver subjected to concurrent portal vein ligation (PVL) and partial hepatectomy (PHx). Materials and Methods: Using a surgical rat model consisting of right PVL (rPVL) plus 70% PHx, we evaluated the size regulation of liver lobes 1, 2, 3, and 7 days after the operation in terms of liver weight and hepatocyte proliferation. Portal hyperperfusion was confirmed by measuring portal flow. The portal vascular tree was visualized by injection of a contrast agent followed by CT imaging of explanted livers. Control groups consisted of 70% PHx, rPVL, and sham operation. Results: The size of the ligated right lobe increased to 1.4-fold on postoperative day 7 when subjected to rPVL + 70% PHx. The right lobe increased to 3-fold when subjected to 70% PHx alone and decreased to 0.3-fold when subjected to rPVL only. The small but significant increase in liver weight after the combined procedure was accompanied by a low proliferative response. In contrast, hepatocyte proliferation was undetectable in the right lobe undergoing atrophy after PVL only. The caudate lobe in the rPVL + 70% PHx group increased to 4.6-fold, which is significantly more than in the other groups. This increase in liver weight was paralleled by persisting portal hyperperfusion and a prolonged proliferative phase of 3 days. Conclusions: A discontinued portal blood supply does not always result in atrophy of the ligated lobe. The concurrent regenerative stimulus induced by 70% PHx seemed to counteract the local atrophy after a simultaneously performed rPVL, leading to a low but prolonged regenerative response of the portally deprived liver lobe. This observation supports the conclusion that portal flow is not necessary for liver regeneration. The persisting portal hyperperfusion may be crucial for the specific kinetics of prolonged liver regeneration after rPVL + 70% PHx in the portally supplied caudate lobe. Both observations deserve more attention regarding the underlying mechanism in further studies.
Kidney-Heart Interactions in Acute Kidney Injury
Authors: Doi Kent
Published: June 2016

Acute kidney injury (AKI) is a common complication in critically ill patients treated in intensive care units. Renal replacement therapy (RRT)-requiring AKI occurs in approximately 5-10% patients in intensive care unit and their mortality rate is unacceptably high (50-60%), despite sufficient control of uremia using remarkably advanced modern RRT techniques. This suggests that there are unrecognized organ interactions following AKI that could worsen the outcomes. Cardiorenal syndrome has been defined based on clinical observations that acute and chronic heart failure causes kidney injury and AKI and that chronic kidney disease worsens heart diseases. Possible pathways that connect these 2 organs have been suggested; however, the precise mechanisms are yet to be clarified, particularly in AKI-induced cardiac dysfunction. This review focuses on acute cardiac dysfunction in the setting of AKI. A recent animal study demonstrated the dysregulation of mitochondrial dynamics caused by an increased dynamin-related protein 1 expression and cellular apoptosis of the heart in a renal ischemia reperfusion model. Although the precise mechanisms that induce cardiac mitochondrial injury in AKI remain unclear, cardiac mitochondria injury could be a novel candidate of drug targets against high mortality in severe AKI.
Circulating Proneurotensin Concentrations and Cardiovascular Disease Events in the Community
Authors: Januzzi James L. , Lyass Asya , Liu Yuyin , Gaggin Hanna , Trebnick April , Maisel Alan S. , D’Agostino Ralph B. , Wang Thomas J. , Massaro Joseph , Vasan Ramachandran S.
Published: June 2016

Objective—

Neurotensin is a peptide whose receptor (sortilin receptor 1) is linked to cardiovascular disease (CVD) development. We hypothesized concentrations of proneurotensin (stable profragment of neurotensin) would predict incident cardiovascular events in community-based subjects.

Approach and Results—

Blood samples from 3439 participants in the Framingham Heart Study (FHS) Offspring cohort (mean age 59.2 years, 47.1% male) were tested for proneurotensin. Primary outcome of interest was incident hard CVD (myocardial infarction, stroke, and cardiovascular death); interaction between proneurotensin concentration with sex, low-density lipoprotein concentrations, and sortilin receptor 1 single-nucleotide polymorphisms was sought. At baseline, those in the highest log-proneurotensin quartile were younger and heavier (
P
<0.001); across proneurotensin quartiles, more prevalent hard CVD (from 3% to 7%;
P
<0.001) and diabetes mellitus (from 6% to 14%;
P
<0.001) were present. In age- and sex-adjusted models, log-proneurotensin concentrations predicted incident hard CVD (hazard ratio [HR], 1.24 per SD change in log-proneurotensin; 95% confidence intervals [CIs], 1.11–1.39;
P
<0.001), a finding that remained on adjustment for standard CVD risk factors (HR, 1.13; 95% CI, 1.01–1.27;
P
=0.03). Elevated log-proneurotensin concentrations were associated with shorter time to first event (
P
=0.02). We found no effect modification by sex, low-density lipoprotein concentration, or sortilin receptor 1 single-nucleotide polymorphisms. Concentrations of proneurotensin were modestly associated with left ventricular mass and coronary artery calcium in these subjects.

Conclusions—

Higher concentrations of proneurotensin are associated with a greater risk of incident cardiovascular events in the community. This association did not vary according to sex, baseline low-density lipoprotein, or sortilin receptor 1 genotype.
Medication Adherence Interventions Improve Heart Failure Mortality and Readmission Rates: Systematic Review and Meta‐Analysis of Controlled Trials
Authors: Ruppar Todd M. , Cooper Pamela S. , Mehr David R. , Delgado Janet M. , Dunbar‐Jacob Jacqueline M.
Published: June 2016

Background

Poor adherence to medications is a common problem among heart failure (
HF
) patients. Inadequate adherence leads to increased
HF
exacerbations, reduced physical function, and higher risk for hospital admission and death. Many interventions have been tested to improve adherence to
HF
medications, but the overall impact of such interventions on readmissions and mortality is unknown.

Methods and Results

We conducted a comprehensive search and systematic review of intervention studies testing interventions to improve adherence to
HF
medications. Mortality and readmission outcome effect sizes (
ES
s) were calculated from the reported data.
ES
s were combined using random‐effects model meta‐analysis methods, because differences in true between‐study effects were expected from variation in study populations and interventions.
ES
differences attributed to study design, sample, and intervention characteristics were assessed using moderator analyses when sufficient data were available. We assessed publication bias using funnel plots. Comprehensive searches yielded 6665 individual citations, which ultimately yielded 57 eligible studies. Overall, medication adherence interventions were found to significantly reduce mortality risk among
HF
patients (relative risk, 0.89; 95%
CI
, 0.81, 0.99), and decrease the odds for hospital readmission (odds ratio, 0.79; 95%
CI
, 0.71, 0.89). Heterogeneity was low. Moderator analyses did not detect differences in
ES
from common sources of potential study bias.

Conclusions

Interventions to improve medication adherence among
HF
patients have significant effects on reducing readmissions and decreasing mortality. Medication adherence should be addressed in regular follow‐up visits with
HF
patients, and interventions to improve adherence should be a key part of
HF
self‐care programs.
Intima–Media Thickness Is Linearly and Continuously Associated With Systolic Blood Pressure in a Population‐Based Cohort (STANISLAS Cohort Study)
Authors: Ferreira João Pedro , Girerd Nicolas , Bozec Erwan , Machu Jean Loup , Boivin Jean‐Marc , London Gérard M. , Zannad Faiez , Rossignol Patrick
Published: June 2016

Background

Carotid intima–media thickness (
cIMT
) is a noninvasive marker of cardiovascular risk. The
cIMT
may be increased in patients with harmonisation, but little is known regarding the functional form of the association between blood pressure (
BP
) and
cIMT
in hypertensive and nonhypertensive persons. We aimed to define the shape of the association between
BP
and
cIMT
.

Methods and Results

We studied
cIMT
and ambulatory
BP
monitoring data from a single‐center, cross‐sectional, population‐based study involving 696 adult participants from the
STANISLAS
cohort, a familial longitudinal cohort from the Nancy region of France. Participants with
a
history of hypertension were more likely to have a
cIMT
>900 μm and had higher mean
cIMT
(both
P
<0.001). The risk of
cIMT
>900 μm increased linearly with higher 24‐hour and daytime systolic
BP
in participants both with and without history of hypertension. The relationship between systolic
BP
and the risk of
cIMT
>900 μm was not dependent on
hypertension
status (all
P
for interaction >0.10). In multivariable analysis adjusted on cardiovascular risk factors, each 5‐mm Hg increase in systolic
BP
was associated with an 8‐μm increase in
cIMT
(β=8.249 [95% CI 2.490–14.008],
P
=0.005). In contrast, the association between diastolic
BP
and
cIMT
was weaker and not significant.

Conclusions

Systolic BP is linearly and continuously associated with higher
cIMT
in both hypertensive and nonhypertensive persons, suggesting a detrimental effect of
BP
on the vascular tree prior to overt hypertension. Similarly, it suggests a detrimental effect of
BP
at the higher end of the normal range in treated hypertensive patients.

Clinical Trial Registration

URL
:
https://www.clinicaltrials.gov/
. Unique identifier:
NCT
01391442.
All Mixed Up? Finding the Optimal Feature Set for General Readability Prediction and Its Application to English and Dutch
Authors: De Clercq Orphée , Hoste Véronique
Published: June 2016

Readability research has a long and rich tradition, but there has been too little focus on general readability prediction without targeting a specific audience or text genre. Moreover, although NLP-inspired research has focused on adding more complex readability features, there is still no consensus on which features contribute most to the prediction. In this article, we investigate in close detail the feasibility of constructing a readability prediction system for English and Dutch generic text using supervised machine learning. Based on readability assessments by both experts and crowdsourcing, we implement different types of text characteristics ranging from easy-to-compute superficial text characteristics to features requiring deep linguistic processing, resulting in ten different feature groups. Both a regression and classification set-up are investigated reflecting the two possible readability prediction tasks: scoring individual texts or comparing two texts. We show that going beyond correlation calculations for readability optimization using a wrapper-based genetic algorithm optimization approach is a promising task that provides considerable insights in which feature combinations contribute to the overall readability prediction. Because we also have gold standard information available for those features requiring deep processing, we are able to investigate the true upper bound of our Dutch system. Interestingly, we will observe that the performance of our fully automatic readability prediction pipeline is on par with the pipeline using gold-standard deep syntactic and semantic information.
Coding of Visual, Auditory, Rule, and Response Information in the Brain: 10 Years of Multivoxel Pattern Analysis
Authors: Woolgar Alexandra , Jackson Jade , Duncan John
Published: June 2016

How is the processing of task information organized in the brain? Many views of brain function emphasize modularity, with different regions specialized for processing different types of information. However, recent accounts also highlight flexibility, pointing especially to the highly consistent pattern of frontoparietal activation across many tasks. Although early insights from functional imaging were based on overall activation levels during different cognitive operations, in the last decade many researchers have used multivoxel pattern analyses to interrogate the representational content of activations, mapping out the brain regions that make particular stimulus, rule, or response distinctions. Here, we drew on 100 searchlight decoding analyses from 57 published papers to characterize the information coded in different brain networks. The outcome was highly structured. Visual, auditory, and motor networks predominantly (but not exclusively) coded visual, auditory, and motor information, respectively. By contrast, the frontoparietal multiple-demand network was characterized by domain generality, coding visual, auditory, motor, and rule information. The contribution of the default mode network and voxels elsewhere was minor. The data suggest a balanced picture of brain organization in which sensory and motor networks are relatively specialized for information in their own domain, whereas a specific frontoparietal network acts as a domain-general “core” with the capacity to code many different aspects of a task.
Linking Theoretical Decision-making Mechanisms in the Simon Task with Electrophysiological Data: A Model-based Neuroscience Study in Humans
Authors: Servant Mathieu , White Corey , Montagnini Anna , Burle Borís
Published: June 2016

A current challenge for decision-making research is in extending models of simple decisions to more complex and ecological choice situations. Conflict tasks (e.g., Simon, Stroop, Eriksen flanker) have been the focus of much interest, because they provide a decision-making context representative of everyday life experiences. Modeling efforts have led to an elaborated drift diffusion model for conflict tasks (DMC), which implements a superimposition of automatic and controlled decision activations. The DMC has proven to capture the diversity of behavioral conflict effects across various task contexts. This study combined DMC predictions with EEG and EMG measurements to test a set of linking propositions that specify the relationship between theoretical decision-making mechanisms involved in the Simon task and brain activity. Our results are consistent with a representation of the superimposed decision variable in the primary motor cortices. The decision variable was also observed in the EMG activity of response agonist muscles. These findings provide new insight into the neurophysiology of human decision-making. In return, they provide support for the DMC model framework.
Distinct Neural Suppression and Encoding Effects for Conceptual Novelty and Familiarity
Authors: Reggev Niv , Bein Oded , Maril Anat
Published: June 2016

Like yin and yang, novelty and familiarity are typically described as separate-yet-complementary aspects of an experience, two ends of a single continuum. However, novelty and familiarity are also multifaceted. For instance, novelty can sometimes result in enhanced mnemonic performance, whereas at other times familiarity is better remembered. As previous investigations focused primarily on the experimental aspect of novelty, the mechanisms supporting conceptual novelty (the novel combination of two previously unrelated existing concepts) remain unclear. Importantly, conceptual novelty can be recognized as such only when compared with preexperimental familiar knowledge, regardless of experimental status. Here we applied a combined repetition suppression/subsequent memory fMRI paradigm, focusing on the conceptual aspect of novelty and familiarity as the subject matter. Conceptual novelty was characterized by sustained neural activity; familiarity, on the other hand, exhibited repetition effects in multiple cortical regions, a subset of which was modulated by successful encoding. Subsequent memory of novelty was associated only with activation differences in a distinct set of regions, including the hippocampus and medial cortical regions. These results suggest that conceptual novelty (a) does not (easily) trigger the repetition suppression phenomenon but requires sustained neural recruitment and (b) activates dedicated encoding mechanisms. Conceptual familiarity, in contrast, allows rapid neural processing that depends upon existing neural representations. Overall, these findings challenge the definition of novelty as a unitary concept. Furthermore, they bear important implications for research into the neural bases of knowledge representation and recognition memory.
Semantic Structural Alignment of Neural Representational Spaces Enables Translation between English and Chinese Words
Authors: Zinszer Benjamin D. , Anderson Andrew J. , Kang Olivia , Wheatley Thalia , Raizada Rajeev D. S.
Published: June 2016

Two sets of items can share the same underlying conceptual structure, while appearing unrelated at a surface level. Humans excel at recognizing and using alignments between such underlying structures in many domains of cognition, most notably in analogical reasoning. Here we show that structural alignment reveals how different people's neural representations of word meaning are preserved across different languages, such that patterns of brain activation can be used to translate words from one language to another. Groups of Chinese and English speakers underwent fMRI scanning while reading words in their respective native languages. Simply by aligning structures representing the two groups' neural semantic spaces, we successfully infer all seven Chinese–English word translations. Beyond language translation, conceptual structural alignment underlies many aspects of high-level cognition, and this work opens the door to deriving many such alignments directly from neural representational content.
The Impact of the Rule of Law on Protection of Human Rights in Viet Nam
Authors: Do Minh Khoi
Published: June 2016

Although rule of law and human rights have been mentioned in the documents of the Vietnamese Communist Party since 1997 and were adopted in the 1992 constitution (amended 2001) and the new constitution in 2013, it is hard to be optimistic about their practical application. This research explores influences of the rule of law on the protection of human rights in Viet Nam. The article starts by reviewing concepts of the rule of law, mechanisms of protection of human rights, and the impacts of the rule of law on human rights in general. From analysing the current situation of the rule of law and the impacts of the rule of law on the protection of human rights in Viet Nam, this research offers some solutions for improving constitutional mechanisms to protect human rights.
The Process of Viet Nam’s Preparation of the National Report under the United Nations Human Rights Council’s Universal Periodic Review
Authors: Nguyen Thi Kim Ngan
Published: June 2016

Viet Nam has finished two national reports under the United Nations Human Rights Council’s Universal Periodic Review. The Vietnamese national reports were prepared in accordance with the general guidelines of the Human Rights Council and experience learnt from other countries. However, the process of Viet Nam’s preparation of its national reports reveals some shortcomings that should be considered. In order to fulfill the obligations of international human rights treaties of which Viet Nam is a party, the process of Viet Nam’s preparation of national reports should be continuously improved to further ensure and promote fundamental human rights in Viet Nam.
A refined circumscription of Notobubon striatum and the resurrection of Dregea collina Ecklon & Zeyher (Apiaceae, Apioideae)
Authors: MAGEE ANTHONY R. , CURTIS ODETTE E. , VAN WYK B-E.
Published: June 2016

Extensive field surveys of the Critically Endangered Central and Eastern Rûens Shale Renosterveld have uncovered that Notobubon striatum, as currently circumscribed, comprises two distinct species. Upon careful examination of the type material it has become clear that names exist for both species. The type specimen of N. striatum clearly matches the lesser known species, a large shrub, ca. 1 m. tall, with a powerful anise-scent and which is restricted to the banks of seasonal rivers and watercourses in the Central and Eastern Rûens Shale Renosterveld. The second and better known entity, with a wider distribution, corresponds to the type material of Dregea collina Ecklon & Zeyher. As such, a new combination, Notobubon collinum (Ecklon & Zeyher) Magee, is here made to accommodate this taxon, restricted to dry quartz and silcrete patches or outcrops in Eastern Rûens Shale Renosterveld. In their revised circumscriptions N. striatum and N. collinum are readily distinguished by habit, scent, leaf size and division, as well as leaf lobe shape and sepal size. Comprehensive descriptions of both species are provided, together with notes on their ecology and conservation status, and the existing key to the species of Notobubon updated. This brings the number of recognised species in the genus to thirteen.
Impatiens glabrata (Balsaminaceae)—A new species from southern Western Ghats, India
Authors: PRABHUKUMAR K.M. , HAREESH V.S. , BHASKAR V. , SREEKUMAR V.B. , NIRMESH T.K. , BALACHANDRAN INDIRA
Published: June 2016

Impatiens glabrata, a new species, is described from Muthikulam forest of Palakkad district, Kerala, India. A description and observations on pollen morphology, ecology, distribution and its allied characters between I. henslowiana and I. fruticosa are provided, along with colour photographs.
Eugenia ruschiana (Myrtaceae), a new species from southeastern Brazilian Atlantic forest
Authors: BÜNGER MARIANA DE OLIVEIRA , MAZINE FIORELLA FERNANDA , STEHMANN JOÃO RENATO
Published: June 2016

Eugenia ruschiana, collected in the montane Atlantic forest of Espírito Santo state, is described, illustrated and compared with E. itacarensis, from which it differs mostly through the smaller size and shape of the bracteoles and calyx lobes, as well as, by its distinct geographic distribution. We also assess its conservation status and the species was considered endangered.
Atlas Florae Europaeae notes 30. Resurrection and typification of the name Sorbus semipinnata Borbás (Rosaceae)
Authors: SOMLYAY LAJOS , SENNIKOV ALEXANDER N.
Published: June 2016

The name Sorbus dacica Borbás (1887: 404), which refers to a well-defined species endemic to Romania, is widely accepted (e.g. Jávorka 1924–1925, Nyárády 1939, Kárpáti 1940, 1960, Buia 1956, Warburg & Kárpáti 1968, Dihoru & Pârvu 1987, Ciocârlan 2009, Dihoru & Negrean 2009, Kurtto 2009, Sârbu et al. 2013). This species is supposed to be of hybrid origin between some taxa of S. subgen. Aria Persoon (1806: 38) and S. aucuparia Linnaeus (1753: 477) of S. subgen. Sorbus; such hybrids and stabilized hybridogenous species are currently classified in S. subgen. Soraria Májovský & Bernátová (2001: 21).
New species of Zygoclistron Rehn, 1905 (Insecta: Orthoptera: Acrididae: Copiocerinae) in the central corridor of the Atlantic Forest biome
Authors: SILVA DANIELA SANTOS MARTINS , PEREIRA MARCELO RIBEIRO , DOMENICO FERNANDO CAMPOS DE , SPERBER CARLOS FRANKL
Published: June 2016

Herein we describe a new species of Copiocerinae, Zygoclistron ruschii Silva n. sp., from Atlantic Forest remnants in southeastern Brazil, collected from the Reserva Biológica Augusto Ruschi in the Santa Teresa municipality, Espírito Santo state, Brazil. The diagnosis of this new species is based on phallic complex and terminalia characters.
Neotype designation for Calotes versicolor Daudin, 1802 (Sauria: Agamidae) with notes on its systematics
Authors: GOWANDE GAURANG , MISHRA ANURAG , MIRZA ZEESHAN A.
Published: June 2016

Calotes versicolor Daudin, 1802 is one of the most widespread agamid lizard species which was described without a locality. The type specimen of the species has long been considered lost; however most workers considered Pondicherry as the type locality for the species. Studies by Zug et al. 2006 confirmed that C. versicolor is a complex of multiple species which necessitates fixing type locality and specimen for the species in order to resolve the systematics of the species complex. An adult male from Pondicherry was collected and is here designated as the neotype. A re-description of the species is provided along with notes on systematics of the species.
The Effects of Climate Change on Seasonal Snowpack and the Hydrology of the Northeastern and Upper Midwest United States
Authors: Demaria Eleonora M. C. , Roundy Joshua K. , Wi Sungwook , Palmer Richard N.
Published: June 2016

The potential effects of climate change on the snowpack of the northeastern and upper Midwest United States are assessed using statistically downscaled climate projections from an ensemble of 10 climate models and a macroscale hydrological model. Climate simulations for the region indicate warmer-than-normal temperatures and wetter conditions for the snow season (November–April) during the twenty-first century. However, despite projected increases in seasonal precipitation, statistically significant negative trends in snow water equivalent (SWE) are found for the region. Snow cover is likely to migrate northward in the future as a result of warmer-than-present air temperatures, with higher loss rates in northern latitudes and at high elevation. Decreases in future (2041–95) snow cover in early spring will likely affect the timing of maximum spring peak streamflow, with earlier peaks predicted in more than 80% of the 124 basins studied.