bluuebunny/crossref_metadata_2025 huggingface dataset:
Using Writing Process and Product Features to Assess Writing Quality and Explore How Those Features Relate to Other Literacy Tasks
Authors: Deane Paul
Published: April 2014

This paper explores automated methods for measuring features of student writing and determining their relationship to writing quality and other features of literacy, such as reading rest scores. In particular, it uses the e‐rater® automatic essay scoring system to measure product features (measurable traits of the final written text) and features extracted from keystroke logs to measure process features (measurable features of the writing process). These techniques are applied to student essays written during large‐scale pilot administrations of writing assessments developed for ETS's CBAL™ research initiative. The design makes it possible to explore the factor structures of these product and process features and to examine how well they generalize beyond a single test session to predict underlying traits such as writing ability and reading level. Three product factors are identified, connected to fluency, accuracy, and content. The process factors are identified, corresponding to hesitancy behaviors, editing behaviors, and burst span (the extent to which text is produced in long bursts with only short internal pauses). The results suggest that writing process and product features have stable factor structures that generalize to predict writing quality, though there are some genre‐ or task‐specific differences.
Ploidy and clinical characteristics of childhood acute myeloid leukemia: A NOPHO‐AML study
Authors: Sandahl Julie Damgaard , Kjeldsen Eigil , Abrahamsson Jonas , Ha Shau‐Yin , Heldrup Jesper , Jahnukainen Kirsi , Jónsson Ólafur G. , Lausen Birgitte , Palle Josefine , Zeller Bernward , Forestier Erik , Hasle Henrik
Published: April 2014

We report the first large series (n = 596) of pediatric acute myeloid leukemia (AML) focusing on modal numbers (MN) from the population‐based NOPHO‐AML trials. Abnormal karyotypes were present in 452 cases (76%) and numerical aberrations were present in 40% (n = 237) of all pediatric AML. Among patients with an abnormal karyotype, the MN 46 was most common (n = 251; 56%) of which 36 (8%) were pseudodiploid with numerical aberrations, followed by MN 47 (n = 80; 18%) and MN 43–45 (n = 48; 8%). No cases had MN less than 43. Hyperdiploid AML with MN 48–65 comprised 11% of all cases and was associated with early onset (median age 2 years), female sex (57%), and a dominance of acute megakaryoblastic leukemia (AMKL) (29%). Hypodiploidy constituted 8% of all AML and was associated with older age (median age 9 years), male predominance (60%), FAB M2 (56%), and t(8;21)(q22;q22) (56%) with loss of sex chromosomes. Inferior outcome was observed for hypodiploid cases (5‐year event‐free survival 40% and 5‐year overall survival 40%) but did not reach statistical significance. Chromosomes were gained in a nonrandom pattern, where chromosomes 8, 21, 19, and 6 were the most commonly gained. In conclusion, based on MNs, two cytogenetic subgroups with characteristic clinical features are described; hypodiploidy found in 8% and associated with high median age, male sex, t(8;21)(q22;q22), and FAB M2 and possibly associated with inferior outcome (P = 0.13), and hyperdiploidy with MN 48–65 in 11% associated with early onset, female sex, and AMKL. © 2014 Wiley Periodicals, Inc.
Shape analysis, a field in need of careful validation
Authors: Gao Yi , Riklin‐Raviv Tammy , Bouix Sylvain
Published: April 2014

In the last two decades, the statistical analysis of shape has become an actively studied field and finds applications in a wide range of areas. In addition to algorithmic development, many researchers have distributed end‐user orientated toolboxes, which further enable the utilization of the algorithms in an “off the shelf” fashion. However, there is little work on the evaluation and validation of these techniques, which poses a rather serious challenge when interpreting their results. To address this lack of validation, we design a validation framework and then use it to test some of the most widely used toolboxes. Our initial results show inconsistencies and disagreement among four different methods. We believe this type of analysis to be critical not only for the community of algorithm designers but also perhaps more importantly to researchers who use these tools without knowing the algorithm details and seek objective criteria for tool selection. Hum Brain Mapp 35:4965–4978, 2014. © 2014 Wiley Periodicals, Inc.
The influence of group membership and individual differences in psychopathy and perspective taking on neural responses when punishing and rewarding others
Authors: Molenberghs Pascal , Bosworth Rebecca , Nott Zoie , Louis Winnifred R. , Smith Joanne R. , Amiot Catherine E. , Vohs Kathleen D. , Decety Jean
Published: April 2014

Understanding how neural processes involved in punishing and rewarding others are altered by group membership and personality traits is critical in order to gain a better understanding of how socially important phenomena such as racial and group biases develop. Participants in an fMRI study (n = 48) gave rewards (money) or punishments (electroshocks) to in‐group or out‐group members. The results show that when participants rewarded others, greater activation was found in regions typically associated with receiving rewards such as the striatum and medial orbitofrontal cortex, bilaterally. Activation in those regions increased when participants rewarded in‐group compared to out‐group members. Punishment led to increased activation in regions typically associated with Theory of Mind including the medial prefrontal cortex and posterior superior temporal sulcus, as well as regions typically associated with perceiving others in pain such as the dorsal anterior cingulate cortex, anterior insula and lateral orbitofrontal cortex. Interestingly, in contrast to the findings regarding reward, activity in these regions was not moderated by whether the target of the punishment was an in‐ or out‐group member. Additional regression analysis revealed that participants who have low perspective taking skills and higher levels of psychopathy showed less activation in the brain regions identified when punishing others, especially when they were out‐group members. In sum, when an individual is personally responsible for delivering rewards and punishments to others, in‐group bias is stronger for reward allocation than punishments, marking the first neuroscientific evidence of this dissociation. Hum Brain Mapp 35:4989–4999, 2014. © 2014 Wiley Periodicals, Inc.
Feeling safe in the plane: Neural mechanisms underlying superior action control in airplane pilot trainees—A combined EEG/MRS study
Authors: Yildiz Ali , Quetscher Clara , Dharmadhikari Shalmali , Chmielewski Witold , Glaubitz Benjamin , Schmidt‐Wilcke Tobias , Edden Richard , Dydak Ulrike , Beste Christian
Published: April 2014

In day‐to‐day life, we need to apply strategies to cascade different actions for efficient unfolding of behavior. While deficits in action cascading are examined extensively, almost nothing is known about the neuronal mechanisms mediating superior performance above the normal level. To examine this question, we investigate action control in airplane pilot trainees. We use a stop‐change paradigm that is able to estimate the efficiency of action cascading on the basis of mathematical constraints. Behavioral and EEG data is analyzed along these constraints and integrated with neurochemical data obtained using Magnetic Resonance Spectroscopy (MRS) from the striatal gamma‐aminobutyric acid (GABA) ‐ergic system. We show that high performance in action cascading, as exemplified in airplane pilot trainees, can be driven by intensified attentional processes, circumventing response selection processes. The results indicate that the efficiency of action cascading and hence the speed of responding as well as attentional gating functions are modulated by striatal GABA and Glutamate + Glutamine concentrations. In superior performance in action cascading similar increases in the concentrations of GABA and Glutamate + Glutamine lead to stronger neurophysiological and behavioral effects as compared to subjects with normal performance in action cascading. Hum Brain Mapp 35:5040–5051, 2014. © 2014 Wiley Periodicals, Inc.
Multi‐atlas based representations for Alzheimer's disease diagnosis
Authors: Min Rui , Wu Guorong , Cheng Jian , Wang Qian , Shen Dinggang ,   the Alzheimer's Disease Neuroimaging Initiative
Published: April 2014

Brain morphometry based classification from magnetic resonance (MR) acquisitions has been widely investigated in the diagnosis of Alzheimer's disease (AD) and its prodromal stage, i.e., mild cognitive impairment (MCI). In the literature, a morphometric representation of brain structures is obtained by spatial normalization of each image into a common space (i.e., a pre‐defined atlas) via non‐linear registration, thus the corresponding regions in different brains can be compared. However, representations generated from one single atlas may not be sufficient to reveal the underlying anatomical differences between the groups of disease‐affected patients and normal controls (NC). In this article, we propose a different methodology, namely the multi‐atlas based morphometry, which measures morphometric representations of the same image in different spaces of multiple atlases. Representations generated from different atlases can thus provide the complementary information to discriminate different groups, and also reduce the negative impacts from registration errors. Specifically, each studied subject is registered to multiple atlases, where adaptive regional features are extracted. Then, all features from different atlases are jointly selected by a correlation and relevance based scheme, followed by final classification with the support vector machine (SVM). We have evaluated the proposed method on 459 subjects (97 AD, 117 progressive‐MCI (p‐MCI), 117 stable‐MCI (s‐MCI), and 128 NC) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, and achieved 91.64% for AD/NC classification and 72.41% for p‐MCI/s‐MCI classification. Our results clearly demonstrate that the proposed multi‐atlas based method can significantly outperform the previous single‐atlas based methods. Hum Brain Mapp 35:5052–5070, 2014. © 2014 Wiley Periodicals, Inc.
Sigmoid sinus occlusion infiltrated by inflammatory myofibroblastic tumor from mastoid
Authors: Wang Jingye , Sun Zhongwu , Zhuo Shengxia , Wang Kai
Published: April 2014

Background

Inflammatory myofibroblastic tumor (IMT) and some types of immunoglobulin (Ig) G4‐related disease are often involved in the spectrum of inflammatory pseudotumor (IPT) and the concept of IgG4‐related IPT/IMT has recently been proposed.

Methods

A 38‐year‐old man complained of initial symptoms of blurred vision and headache.

Results

A tumor was found in the right mastoid, which caused occlusion of the right sigmoid sinus and intracranial hypertension. A diagnosis of IMT with IgG4+ plasma cell infiltration was established by surgical, pathological, and immunohistochemistry findings. His symptoms were completely relieved after corticosteroid therapy and no recurrence was detected during 22 months of follow‐up.

Conclusion

A case with cerebral venous sinus infiltrated by IMTs in the head and neck has never been reported; corticosteroid therapy proved satisfactory in IMT with IgG4+ plasma cell infiltration. © 2014 Wiley Periodicals, Inc. Head Neck 37: E4–E7, 2015
Hepatocyte nuclear factor 4α-nuclear factor-κB feedback circuit modulates liver cancer progression
Authors: Ning Bei-Fang , Ding Jin , Liu Jiao , Yin Chuan , Xu Wen-Ping , Cong Wen-Ming , Zhang Qing , Chen Fei , Han Tao , Deng Xing , Wang Pei-Qin , Jiang Cai-Feng , Zhang Jun-Ping , Zhang Xin , Wang Hong-Yang , Xie Wei-Fen
Published: April 2014

Hepatocyte nuclear factor 4α (HNF4α) is a liver enriched transcription factor and is indispensable for liver development. However, the role of HNF4α in hepatocellular carcinoma (HCC) progression remains to be elucidated. We report that reduced HNF4α expression correlated well with the aggressive clinicopathological characteristics of HCC and predicted poor prognosis of patients. HNF4α levels were even lower in metastatic HCCs, and ectopic HNF4α expression suppressed the metastasis of hepatoma cells both

in vitro

and

in vivo

. Forced HNF4α expression attenuated the expression and nuclear translocation of RelA (p65) and impaired NF-κB activation through an IKK-independent mechanism. Blockage of RelA robustly attenuated the suppressive effect of HNF4α on hepatoma cell metastasis. MicroRNA (miR)-7 and miR-124 were transcriptionally up-regulated by HNF4α, which repressed RelA expression by way of interaction with RelA-3′ untranslated region (UTR). In addition, nuclear factor kappa B (NF-κB) up-regulated the expression of miR-21 in hepatoma cells, resulting in decreased HNF4α levels through down-regulating HNF4α-3′UTR activity.

Conclusions

: Collectively, an HNF4α-NF-κB feedback circuit including miR-124, miR-7, and miR-21 was identified in HCC, and the combination of HNF4α and NF-κB exhibited more powerful predictive efficiency of patient prognosis. These findings broaden the knowledge of hepatic inflammation and cancer initiation/progression, and also provide novel prognostic biomarkers and therapeutic targets for HCC. (Hepatology 2014;60:1607-1619)
Persistent viremia in human immunodeficiency virus/hepatitis B coinfected patients undergoing long-term tenofovir: Virological and clinical implications
Authors: Boyd Anders , Gozlan Joël , Maylin Sarah , Delaugerre Constance , Peytavin Gilles , Girard Pierre-Marie , Zoulim Fabien , Lacombe Karine
Published: April 2014

Tenofovir (TDF) is considered the ideal treatment for patients coinfected with human immunodeficiency virus (HIV) and hepatitis B virus (HBV). However, certain coinfected patients exhibit incomplete viral suppression, with persistent, and sometimes transient, bouts of HBV replication. The reasons for this, including clinical effect, are unclear. A total of 111 HIV-HBV-infected patients undergoing TDF-containing antiretroviral therapy were prospectively followed. Serum HBV-DNA viral load, hepatitis surface (HBsAg) and e antigen (HBeAg) status were obtained at baseline and every 6-12 months. Amino acid (aa) changes on the polymerase gene were assessed using direct sequencing after nested polymerase chain reaction in patients with persistent viremia (PV). After a median of 74.7 months (interquartile range: 33.4-94.7), virological response (VR; <60 IU/mL) occurred in 96 of 111 (86.5%) patients. Of these, 86 of 96 (89.6%) remained completely undetectable during follow-up (stabilized VR). The remaining 10 of 96 (10.4%) patients had a transient blip of detectable HBV-DNA (transient PV), during which time 9 of 9 (100%) with available samples had detectable plasma TDF. Low-level PV (LL-PV; 61-2,000 IU/mL) was observed in 11 of 111 (9.9%) patients, the majority of which had detectable plasma TDF (8 of 9; 88.9%). High-level PV (>2,000 IU/mL) was rare (4 of 111; 3.6%) and was associated with nonadherence. At TDF initiation, patients with stabilized VR had significantly higher nadir CD4+ count, compared to those with transient PV (P = 0.006) or LL-PV (P = 0.04). No consistent aa changes, other than those associated with lamivudine resistance, were observed in patients with persistent viremia. Importantly, HBeAg loss, HBeAg seroconversion, and HBsAg loss only occurred in patients with stabilized VR. Two patients with stabilized VR developed hepatocellular carcinoma and 2 with LL PV died, 1 of a liver-related cause. Conclusion: Suboptimal HBV control during TDF treatment has a negative effect on serological outcomes, but not necessarily clinical events. Immunoregulation may provide more insight into this phenomenon. (Hepatology 2014;60:497–507)
Hippocampal control of repetition effects for associative stimuli
Authors: Kremers Nico A.W. , Deuker Lorena , Kranz Thorsten A. , Oehrn Carina , Fell Juergen , Axmacher Nikolai
Published: April 2014

Recent findings suggest that repetition effects interact with episodic memory processes that are putatively supported by the hippocampus. Thus, the formation or refinement of episodic memories may be related to a modulating signal from the hippocampus to the neocortex which leads to sparser or more extended stimulus representations (repetition suppression or enhancement), depending on the type of stimulus and the brain site. This framework suggests that hippocampal activity during the initial presentation of a stimulus correlates with the magnitude of repetition effects. Here, we tested this hypothesis in an fMRI study in which associations between faces and buildings were presented twice. BOLD responses showed repetition suppression in fusiform face area (FFA) and parahippocampal place area (PPA), most likely due to a refinement of existing category representations. Hippocampal activity during the first presentations was correlated with the amount of repetition suppression, in particular in the FFA. Repetition enhancement effects were observed on BOLD responses in posterior parietal cortex, possibly related to the formation of new representations of associative stimuli. The magnitude of parietal BOLD repetition effects depended on successful memory formation. These findings suggest that both repetition enhancement and repetition suppression effects are influenced by a modulating signal from the hippocampus. © 2014 Wiley Periodicals, Inc.
Intact CA3 in the hippocampus is only sufficient for contextual behavior based on well‐learned and unaltered visual background
Authors: Ahn Jae‐Rong , Lee Inah
Published: April 2014

Computational models suggest that the dentate gyrus and CA3 subfields of the hippocampus are responsible for discrete memory representations using pattern separation and pattern completion when a modified external stimulus is recognized as an old memory or encoded as a new memory. Experimental evidence of such computational processes in the hippocampus has been obtained mostly from spatial navigational tasks, and little is known about the proposed computational functions of the hippocampal subfields in “nonspatial” memory tasks. We tested whether rats with major damage in the dentate gyrus induced by colchicine lesions could remember patterned visual scene stimuli presented on LCD screens in the background. Rats responded using a touchscreen to indicate the identity of the visual scene. Performance of the lesion group was normal when tested with familiar visual scenes that had been learned prior to surgery. Lesioned rats exhibited severe deficits in learning novel visual scenes, but eventually reached the same level of performance as controls. However, unlike in controls, novel scene‐associated memories formed in the lesion group were unstable and easily disrupted when ambiguous versions of the novel scenes were presented intermixed with the original stimuli. Our findings confirm that the prior computational models can also be applied to the nonspatial memory domain and suggest that the dentate gyrus is not necessary for the retrieval of learned visual scene‐associated behavioral responses but plays a crucial role in forming novel visual scene‐dependent memory and recognizing altered or ambiguous visual scenes in the background. © 2014 Wiley Periodicals, Inc.
Response to O'Reilly et al. (2014)
Authors: Crane Judy L
Published: April 2014

Key Points

O'Reilly et al. (2013) made several errors in their paper regarding environmental forensic techniques for pyrogenic polycyclic aromatic hydrocarbons (PAHs). Their use of alkylated PAHs in forensic evaluations to determine petrogenic (i.e., oil-based) sources of PAHs is limited for urban sediments that are frequently classified as pyrogenic (i.e., combustion sources). O'Reilly et al. (2013) used a small number of samples from multiple sources in their principal components analysis figures and they simply do not have enough data to use this statistical technique. The authors recommended using both the USEPA's chemical mass balance and Unmix models for evaluating the source apportionment of PAHs in sediment data sets; however, this will not be feasible for most studies because the Unmix model requires a large sample size.
Glioma‐associated microglial MMP9 expression is upregulated by TLR2 signaling and sensitive to minocycline
Authors: Hu Feng , Ku Min‐Chi , Markovic Darko , Dzaye Omar , Lehnardt Seija , Synowitz Michael , Wolf Susanne A. , Kettenmann Helmut
Published: April 2014

The invasiveness of malignant gliomas is one of the major obstacles in glioma therapy and the reason for the poor survival of patients. Glioma cells infiltrate into the brain parenchyma and thereby escape surgical resection. Glioma associated microglia/macrophages support glioma infiltration into the brain parenchyma by increased expression and activation of extracellular matrix degrading proteases such as matrix metalloprotease (MMP) 2, MMP9 and membrane‐type 1 MMP. In this work we demonstrate that, MMP9 is predominantly expressed by glioma associated microglia/macrophages in mouse and human glioma tissue but not by the glioma cells. Supernatant from glioma cells induced the expression of MMP9 in cultured microglial cells. Using mice deficient for different Toll‐like receptors we identified Toll‐like receptor 2/6 as the signaling pathway for the glioma induced upregulation of microglial MMP9. Also in an experimental mouse glioma model, Toll‐like receptor 2 deficiency attenuated the upregulation of microglial MMP9. Moreover, glioma supernatant triggered an upregulation of Toll‐like receptor 2 expression in microglia. Both, the upregulation of MMP9 and Toll‐like receptor 2 were attenuated by the antibiotic minocycline and a p38 mitogen‐activated protein kinase antagonist in vitro. Minocycline also extended the survival rate of glioma bearing mice when given to the drinking water. Thus glioma cells change the phenotype of glioma associated microglia/macrophages in a complex fashion using Toll‐like receptor 2 as an important signaling pathway and minocycline further proved to be a potential candidate for adjuvant glioma therapy.
Season of birth and risk of Hodgkin and non‐Hodgkin lymphoma
Authors: Crump Casey , Sundquist Jan , Sieh Weiva , Winkleby Marilyn A. , Sundquist Kristina
Published: April 2014

Infectious etiologies have been hypothesized for Hodgkin and non‐Hodgkin lymphoma (HL and NHL) in early life, but findings to date for specific lymphomas and periods of susceptibility are conflicting. We conducted the first national cohort study to examine whether season of birth, a proxy for infectious exposures in the first few months of life, is associated with HL or NHL in childhood through young adulthood. A total of 3,571,574 persons born in Sweden in 1973–2008 were followed up through 2009 to examine the association between season of birth and incidence of HL (943 cases) or NHL (936 cases). We found a sinusoidal pattern in NHL risk by season of birth (p = 0.04), with peak risk occurring among birthdates in April. Relative to persons born in fall (September–November), odds ratios for NHL by season of birth were 1.25 [95% confidence interval (CI), 1.04–1.50; p = 0.02] for spring (March–May), 1.22 (95% CI, 1.01–1.48; p = 0.04) for summer (June–August) and 1.11 (95% CI, 0.91–1.35; p = 0.29) for winter (December–February). These findings did not vary by sex, age at diagnosis or major subtypes. In contrast, there was no seasonal association between birthdate and risk of HL (p = 0.78). In this large cohort study, birth in spring or summer was associated with increased risk of NHL (but not HL) in childhood through young adulthood, possibly related to immunologic effects of delayed infectious exposures compared with fall or winter birth. These findings suggest that immunologic responses in early infancy may play an important role in the development of NHL.
A multimarker panel for circulating tumor cells detection predicts patient outcome and therapy response in metastatic colorectal cancer
Authors: Barbazán Jorge , Muinelo‐Romay Laura , Vieito María , Candamio Sonia , Díaz‐López Antonio , Cano Amparo , Gómez‐Tato Antonio , de los Ángeles Casares de Cal María , Abal Miguel , López‐López Rafael
Published: April 2014

Circulating tumor cells (CTCs), proposed as major players in cancer dissemination, have demonstrated clinical prognostic significance in several cancer types. However, their predictive value remains unclear. Here we evaluated the clinical utility of six CTC markers (tissue specific and epithelial to mesenchymal transition transcripts) both as prognostic and predictive tools in metastatic colorectal cancer (mCRC) patients. CTCs were immunoisolated from blood in 50 mCRC patients at baseline and at 4 and 16 weeks after treatment onset. Expression levels of GAPDH, VIL1, CLU, TIMP1, LOXL3 and ZEB2 were determined by qualitative polymerase chain reaction and normalized to the unspecific cell isolation marker CD45. At baseline, median progression‐free survival (PFS) and overall survival (OS) for patients with high CTC markers were 6.3 and 12.7 months, respectively, versus 12.7 and 24.2 for patients with low CTC markers (PFS; p = 0.0003; OS; p = 0.044). Concerning response to therapy, PFS and OS for patients with increased CTC markers along treatment were, respectively, 6.6 and 13.1 months, compared with 12.7 and 24.3 for patients presenting CTC markers reduction (PFS; p = 0.004; OS; p = 0.007). Of note, CTC markers identified therapy‐refractory patients not detected by standard image techniques. Patients with increased CTC markers along treatment, but classified as responders by computed tomography, showed significantly shorter survival times (PFS: 7.8 vs. 13.2; OS: 14.4 vs. 24.4; months). In conclusion, we have generated a CTC marker panel for prognosis evaluation and the identification of patients benefiting or not from therapy in mCRC. Our methodology efficiently classified patients earlier than routine computed tomography and from a minimally invasive liquid biopsy.
Connexins in colorectal cancer pathogenesis
Authors: Sirnes Solveig , Lind Guro E. , Bruun Jarle , Fykerud Tone A. , Mesnil Marc , Lothe Ragnhild A. , Rivedal Edgar , Kolberg Matthias , Leithe Edward
Published: April 2014

The connexins constitute a family of integral membrane proteins that form channels between adjacent cells. These channels are assembled in plasma membrane domains known as gap junctions and enable cells to directly exchange ions and small molecules. Intercellular communication via gap junctions plays important roles in regulating cell growth and differentiation and in maintaining tissue homeostasis. This type of cell communication is often impaired during cancer development, and several members of the connexin protein family have been shown to act as tumor suppressors. Emerging evidence suggests that the connexin protein family has important roles in colorectal cancer development. In the normal colonic epithelial tissue, three connexin isoforms, connexin 26 (Cx26), Cx32 and Cx43, have been shown to be expressed at the protein level. Colorectal cancer development is associated with loss of connexin expression or relocalization of connexins from the plasma membrane to intracellular compartments. Downregulation of connexins in colorectal carcinomas at the transcriptional level involves cancer‐specific promoter hypermethylation. Recent studies suggest that Cx43 may constrain growth of colon cancer cells by interfering with the Wnt/β‐catenin pathway. There is also increasing evidence that the connexins may have potential as prognostic markers in colorectal cancer. This review discusses the role of connexins in colorectal cancer pathogenesis, as well as their potential as prognostic markers and targets in the prevention and treatment of the disease.
Anthropometric factors and risk of molecular breast cancer subtypes among postmenopausal Norwegian women
Authors: Horn Julie , Alsaker Mirjam D.K. , Opdahl Signe , Engstrøm Monica J. , Tretli Steinar , Haugen Olav A. , Bofin Anna M. , Vatten Lars J. , Åsvold Bjørn Olav
Published: April 2014

Adult height and body weight are positively associated with breast cancer risk after menopause, but few studies have investigated these factors according to molecular breast cancer subtype. A total of 18,562 postmenopausal Norwegian women who were born between 1886 and 1928 were followed up for breast cancer incidence from the time (between 1963 and 1975) height and weight were measured until 2008. Immunohistochemical and in situ hybridization techniques were used to subtype 734 incident breast cancer cases into Luminal A, Luminal B [human epidermal growth factor receptor 2 (HER2−)], Luminal B (HER2+), HER2 subtype, basal‐like phenotype (BP) and five‐negative phenotype (5NP). We used Cox regression analysis to assess adult height and body mass index (BMI) in relation to risk of these subtypes. We found a positive association of height with risk of Luminal A breast cancer (ptrend, 0.004), but there was no clear association of height with any other subtype. BMI was positively associated with risk of all luminal breast cancer subtypes, including Luminal A (ptrend, 0.002), Luminal B (HER2−) (ptrend, 0.02), Luminal B (HER2+) (ptrend, 0.06), and also for the HER2 subtype (ptrend, 0.04), but BMI was not associated with risk of the BP or 5NP subtypes. Nonetheless, statistical tests for heterogeneity did not provide evidence that associations of height and BMI differed across breast cancer subtypes. This study of breast cancer risk among postmenopausal women suggests that height is positively associated with risk of Luminal A breast cancer. BMI is positively associated with risk of all luminal subtypes and for the HER2 subtype.
SDHB mutations are associated with response to temozolomide in patients with metastatic pheochromocytoma or paraganglioma
Authors: Hadoux Julien , Favier Judith , Scoazec Jean‐Yves , Leboulleux Sophie , Al Ghuzlan Abir , Caramella Caroline , Déandreis Désirée , Borget Isabelle , Loriot Céline , Chougnet Cécile , Letouzé Eric , Young Jacques , Amar Laurence , Bertherat Jérome , Libé Rosella , Dumont Frédéric , Deschamps Frédéric , Schlumberger Martin , Gimenez‐Roqueplo Anne Paule , Baudin Eric
Published: April 2014

Cyclophosphamide–dacarbazine–vincristine regimen is recommended for the treatment of malignant pheochromocytoma and paraganglioma (MPP); however, dacarbazine is the only recognized active drug in neuroendocrine tumours. We investigated the therapeutic benefit of temozolomide (TMZ), an oral alternative to dacarbazine, in patients with MPP. This is a retrospective study of consecutive patients with documented progressive MPP. We examined the correlation between Succinate dehydrogenase B (SDHB) mutation and O(6)‐methylguanine‐DNA methyltransferase (MGMT) promoter methylation and MGMT expression in the French nation‐wide independent cohort of 190 pheochromocytomas or paragangliomas (PP). Progression‐free survival (PFS) according to RECIST 1.1 and PERCIST 1.0 criteria was the primary end point. Fifteen consecutive patients with MPP were enrolled; ten (67%) carried a mutation in SDHB. The mean dose intensity of TMZ was 172 mg/m2/d for 5 days every 28 days. Median PFS was 13.3 months after a median follow‐up of 35 months. There were five partial responses (33%), seven stable (47%) and three progressive diseases (20%). Grade 3 toxicities were lymphopenia in two patients and hypertension in one. Partial responses were observed only in patients with mutation in SDHB. MGMT immunohistochemistry was negative in tumour samples from four patients who responded to treatment. SDHB germline mutation was associated with hypermethylation of the MGMT promoter and low expression of MGMT in 190 samples of the French nation‐wide independent cohort. This study demonstrates that TMZ is an effective antitumour agent in patients with SDHB‐related MPP. The silencing of MGMT expression as a consequence of MGMT promoter hypermethylation in SDHB‐mutated tumours may explain this finding.
Personality dimensions and emotional problems: The mediating role of irrational beliefs in Pakistani adult non‐clinical sample
Authors: Jibeen Tahira
Published: April 2014

This study presents the first examination of the relation between the Big Five personality traits, irrational beliefs and emotional problems in Pakistan, which is an understudied country in the psychological distress literature. A total of 195 participants (aged 25–60 years), employees at COMSATS University, completed a demographic information sheet, the Big Five Personality Questionnaire, the Irrational Belief Inventory and two subscales of the Brief Symptom Inventory including depression and anxiety. Direct effects of neuroticism, openness and conscientiousness were also observed for depression and anxiety. Structural Equation Modelling demonstrated that irrational beliefs played a significant mediating role in the relationship between neuroticism and anxiety and neuroticism and depression. The results highlight the importance of cognitive beliefs in functionally linking personality traits and emotional problems.
Pulsed Electromagnetic Fields Partially Preserve Bone Mass, Microarchitecture, and Strength by Promoting Bone Formation in Hindlimb-Suspended Rats
Authors: Jing Da , Cai Jing , Wu Yan , Shen Guanghao , Li Feijiang , Xu Qiaoling , Xie Kangning , Tang Chi , Liu Juan , Guo Wei , Wu Xiaoming , Jiang Maogang , Luo Erping
Published: April 2014

A large body of evidence indicates that pulsed electromagnetic fields (PEMF), as a safe and noninvasive method, could promote in vivo and in vitro osteogenesis. Thus far, the effects and underlying mechanisms of PEMF on disuse osteopenia and/or osteoporosis remain poorly understood. Herein, the efficiency of PEMF on osteoporotic bone microarchitecture, bone strength, and bone metabolism, together with its associated signaling pathway mechanism, was systematically investigated in hindlimb-unloaded (HU) rats. Thirty young mature (3-month-old), male Sprague-Dawley rats were equally assigned to control, HU, and HU + PEMF groups. The HU + PEMF group was subjected to daily 2-hour PEMF exposure at 15 Hz, 2.4 mT. After 4 weeks, micro–computed tomography (µCT) results showed that PEMF ameliorated the deterioration of trabecular and cortical bone microarchitecture. Three-point bending test showed that PEMF mitigated HU-induced reduction in femoral mechanical properties, including maximum load, stiffness, and elastic modulus. Moreover, PEMF increased serum bone formation markers, including osteocalcin (OC) and N-terminal propeptide of type 1 procollagen (P1NP); nevertheless, PEMF exerted minor inhibitory effects on bone resorption markers, including C-terminal crosslinked telopeptides of type I collagen (CTX-I) and tartrate-resistant acid phosphatase 5b (TRAcP5b). Bone histomorphometric analysis demonstrated that PEMF increased mineral apposition rate, bone formation rate, and osteoblast numbers in cancellous bone, but PEMF caused no obvious changes on osteoclast numbers. Real-time PCR showed that PEMF promoted tibial gene expressions of Wnt1, LRP5, β-catenin, OPG, and OC, but did not alter RANKL, RANK, or Sost mRNA levels. Moreover, the inhibitory effects of PEMF on disuse-induced osteopenia were further confirmed in 8-month-old mature adult HU rats. Together, these results demonstrate that PEMF alleviated disuse-induced bone loss by promoting skeletal anabolic activities, and imply that PEMF might become a potential biophysical treatment modality for disuse osteoporosis. © 2014 American Society for Bone and Mineral Research.
Endogenous Bone Regeneration Is Dependent Upon a Dynamic Oxygen Event
Authors: Sammarco Mimi C , Simkin Jennifer , Fassler Danielle , Cammack Alex J , Wilson Aaron , Van Meter Keith , Muneoka Ken
Published: April 2014

Amputation of the digit tip within the terminal phalangeal bone of rodents, monkeys, and humans results in near-perfect regeneration of bone and surrounding tissues; however, amputations at a more proximal level fail to produce the same regenerative result. Digit regeneration is a coordinated, multifaceted process that incorporates signaling from bioactive growth factors both in the tissue matrix and from several different cell populations. To elucidate the mechanisms involved in bone regeneration we developed a novel multi-tissue slice-culture model that regenerates bone ex vivo via direct ossification. Our study provides an integrated multi-tissue system for bone and digit regeneration and allows us to circumvent experimental limitations that exist in vivo. We used this slice-culture model to evaluate the influence of oxygen on regenerating bone. Micro–computed tomography (µCT) and histological analysis revealed that the regenerative response of the digit is facilitated in part by a dynamic oxygen event, in which mutually exclusive high and low oxygen microenvironments exist and vacillate in a coordinated fashion during regeneration. Areas of increased oxygen are initially seen in the marrow and then surrounding areas of vasculature in the regenerating digit. Major hypoxic events are seen at 7 days postamputation (DPA 7) in the marrow and again at DPA 12 in the blastema, and manipulation of oxygen tensions during these hypoxic phases can shift the dynamics of digit regeneration. Oxygen increased to 21% oxygen tension can either accelerate or attenuate bone mineralization in a stage-specific manner in the regenerative timeline. These studies not only reveal a circumscribed frame of oxygen influence during bone regeneration, but also suggest that oxygen may be one of the primary signaling influences during regeneration. © 2014 American Society for Bone and Mineral Research.
Calcium and Vitamin D in Sarcoidosis: Is Supplementation Safe?
Authors: Kamphuis Lieke S , Bonte-Mineur Femke , van Laar Jan A , van Hagen P Martin , van Daele Paul L
Published: April 2014

Granulomas in sarcoidosis express high levels of 1α-hydroxylase, an enzyme that catalyzes the hydroxylation of 25-OH vitamin D to its active form, 1,25(OH)2 vitamin D. Overproduction of 1α-hydroxylase is held responsible for the development of hypercalcemia in sarcoidosis patients. Corticosteroids are used as first-line treatment in organ-threatening sarcoidosis. In this light, osteoporosis prevention with calcium and vitamin D (CAD) supplementation is often warranted. However, sarcoidosis patients are at risk for hypercalcemia, and CAD supplementation affects the calcium metabolism. We studied calcium and vitamin D disorders in a large cohort of sarcoidosis patients and investigated if CAD supplementation is safe. Retrospectively, data of 301 sarcoidosis patients from July 1986 to June 2009 were analyzed for serum calcium, 25-hydroxy vitamin D (25-(OH)D), 1,25-dihydroxy vitamin D (1,25(OH)2D), and use of CAD supplementation. Disease activity of sarcoidosis was compared with serum levels of vitamin D. Hypercalcemia occurred in 8%. A significant negative correlation was found between 25-(OH)D and disease activity of sarcoidosis measured by somatostatin receptor scintigraphy. In our study, 5 of the 104 CAD-supplemented patients developed hypercalcemia, but CAD supplementation was not the cause of hypercalcemia. Patients without CAD supplementation were at higher risk for developing hypercalcemia. During CAD supplementation, no hypercalcemia developed as a result of supplementation. Hypovitaminosis D seems to be related with more disease activity of sarcoidosis and, therefore, could be a potential risk factor for disease activity of sarcoidosis. Thus, vitamin D–deficient sarcoidosis patients should be supplemented. © 2014 American Society for Bone and Mineral Research.
Widespread Differential Maternal and Paternal Genome Effects on Fetal Bone Phenotype at Mid-Gestation
Authors: Xiang Ruidong , Lee Alice MC , Eindorf Tanja , Javadmanesh Ali , Ghanipoor-Samami Mani , Gugger Madeleine , Fitzsimmons Carolyn J , Kruk Zbigniew A , Pitchford Wayne S , Leviton Alison J , Thomsen Dana A , Beckman Ian , Anderson Gail I , Burns Brian M , Rutley David L , Xian Cory J , Hiendleder Stefan
Published: April 2014

Parent-of-origin–dependent (epi)genetic factors are important determinants of prenatal development that program adult phenotype. However, data on magnitude and specificity of maternal and paternal genome effects on fetal bone are lacking. We used an outbred bovine model to dissect and quantify effects of parental genomes, fetal sex, and nongenetic maternal effects on the fetal skeleton and analyzed phenotypic and molecular relationships between fetal muscle and bone. Analysis of 51 bone morphometric and weight parameters from 72 fetuses recovered at day 153 gestation (54% term) identified six principal components (PC1–6) that explained 80% of the variation in skeletal parameters. Parental genomes accounted for most of the variation in bone wet weight (PC1, 72.1%), limb ossification (PC2, 99.8%), flat bone size (PC4, 99.7%), and axial skeletal growth (PC5, 96.9%). Limb length showed lesser effects of parental genomes (PC3, 40.8%) and a significant nongenetic maternal effect (gestational weight gain, 29%). Fetal sex affected bone wet weight (PC1, p < 0.0001) and limb length (PC3, p < 0.05). Partitioning of variation explained by parental genomes revealed strong maternal genome effects on bone wet weight (74.1%, p < 0.0001) and axial skeletal growth (93.5%, p < 0.001), whereas paternal genome controlled limb ossification (95.1%, p < 0.0001). Histomorphometric data revealed strong maternal genome effects on growth plate height (98.6%, p < 0.0001) and trabecular thickness (85.5%, p < 0.0001) in distal femur. Parental genome effects on fetal bone were mirrored by maternal genome effects on fetal serum 25-hydroxyvitamin D (96.9%, p < 0.001) and paternal genome effects on alkaline phosphatase (90.0%, p < 0.001) and their correlations with maternally controlled bone wet weight and paternally controlled limb ossification, respectively. Bone wet weight and flat bone size correlated positively with muscle weight (r = 0.84 and 0.77, p < 0.0001) and negatively with muscle H19 expression (r = –0.34 and –0.31, p < 0.01). Because imprinted maternally expressed H19 regulates growth factors by miRNA interference, this suggests muscle-bone interaction via epigenetic factors. © 2014 American Society for Bone and Mineral Research.
Toward the understanding of the environmental effects on core ionizations
Authors: Laurent Adèle D. , Glushkov Vitaly N. , Very Thibaut , Assfeld Xavier
Published: April 2014

Experimental X‐ray absorption spectra are extensively used to determine electronic structure of small molecules but remain difficult to exploit for proteins due to the large number of peaks within their spectra. For such complex systems, theoretical tools like quantum mechanics/molecular mechanics methodology can greatly ease the assignment of the spectra. This study presents a systematic methodology to evaluate core‐ionization energies (Eion) in proteins with the help of the asymptotic projection approach (Glushkov and Tsaune, Z. Vichislit. Matem. Mat. Fiz. 1985, 25, 298; Glushkov, Chem. Phys. Lett. 1997, 273, 122; Glushkov, Chem. Phys. Lett. 1998, 287, 189; Glushkov, J. Math. Chem. 2002, 31, 91; Glushkov, Opt. Spectrosc. 2002, 93, 15). An in‐depth inspection of Eion of systems of increasing complexity is considered, going from amino acids to polyglycine and to glycine in human serum albumin (HSA). Computational analysis can help to better understand experimental data and to discriminate environmental effects by tracing them back to individual and collective electrostatic contributions. In the present work, it was found that Eion of alpha carbon of glycine residues in HSA ranges from 285 to 295 eV depending on their surroundings. © 2014 Wiley Periodicals, Inc.
All‐atom polarizable force field for DNA based on the classical drude oscillator model
Authors: Savelyev Alexey , MacKerell Alexander D.
Published: April 2014

Presented is a first generation atomistic force field (FF) for DNA in which electronic polarization is modeled based on the classical Drude oscillator formalism. The DNA model is based on parameters for small molecules representative of nucleic acids, including alkanes, ethers, dimethylphosphate, and the nucleic acid bases and empirical adjustment of key dihedral parameters associated with the phosphodiester backbone, glycosidic linkages, and sugar moiety of DNA. Our optimization strategy is based on achieving a compromise between satisfying the properties of the underlying model compounds in the gas phase targeting quantum mechanical (QM) data and reproducing a number of experimental properties of DNA duplexes in the condensed phase. The resulting Drude FF yields stable DNA duplexes on the 100‐ns time scale and satisfactorily reproduce (1) the equilibrium between A and B forms of DNA and (2) transitions between the BI and BII substates of B form DNA. Consistency with the gas phase QM data for the model compounds is significantly better for the Drude model as compared to the CHARMM36 additive FF, which is suggested to be due to the improved response of the model to changes in the environment associated with the explicit inclusion of polarizability. Analysis of dipole moments associated with the nucleic acid bases shows the Drude model to have significantly larger values than those present in CHARMM36, with the dipoles of individual bases undergoing significant variations during the MD simulations. Additionally, the dipole moment of water was observed to be perturbed in the grooves of DNA. © 2014 Wiley Periodicals, Inc.
Effect of temperature on treating chemical synthesis‐based pharmaceutical wastewater containing 7‐ACA by a novel multi‐stage loop membrane bioreactor
Authors: Chen Zhaobo , He Zhangwei , Hu Dongxue , Cui Yubo , Ran Chunqiu , Ge Hui , Zhang Shunli , Shi Yue , Yang Mengjie , Wang Aijie , Chen Zhiqiang , Ren Nanqi
Published: April 2014

BACKGROUND

7‐amino cephalosporanic acid (7‐ACA) is the most critical intermediate for cephalosporin antibiotics but has caused serious water pollution. In this study, a bench‐scale test was conducted with a novel multi‐stage loop membrane bioreactor (MsLMBR) to treat chemical synthesis‐based pharmaceutical wastewater containing 7‐ACA.

RESULTS

The MsLMBR system comprised a multi‐stage loop aerobic reactor and a separate membrane module operated at different temperatures. Results showed that for MsLMBR1 at 15°C, MsLMBR2 at 25°C and MsLMBR3 at 35°C, the average total chemical oxygen demands (TCODs) of the effluent were all less than 80 mg L−1. For MsLMBR2 and MsLMBR3, the microorganisms had better microbial activities and drug‐resistances, and the biological removal was given priority to TCOD removal. But for MsLMBR1, there was no significant difference between biological removal and physical removal at the early stage. Average 7‐ACA concentration of effluent was less than 40 mg L−1 at 35°C. The laboratory data fitted the simulated data well using a time series analysis model (TSAM) in a MsLMBR system.

CONCLUSION

7‐ACA pharmaceutical wastewater was effectively treated in a MsLMBR system, which also performed well at low temperature. In addition, the TSAM was a valid means to simulate and predict the efficiency of removal of an organic substance. © 2014 Society of Chemical Industry