bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biomarker-Based Scoring System for Prediction of Tumor Response After Preoperative Chemoradiotherapy in Rectal Cancer by Reverse Transcriptase Polymerase Chain Reaction Analysis
Authors: Hur Hyuk , Tulina Inna , Cho Min Soo , Min Byung Soh , Koom Woong Sub , Lim Joon Seok , Ahn Joong Bae , Kim Nam Kyu 
Published: November 2016

BACKGROUND:
Numerous molecular markers have been investigated to predict tumor response after preoperative chemoradiotherapy for rectal cancer.

OBJECTIVE:
This study aimed to evaluate the predictive value of biomarkers for the prediction of tumor response after preoperative chemoradiotherapy.

DESIGN & SETTING:
Tumor specimens have been collected prospectively from 80 patients with rectal cancer who underwent curative resection at 8 weeks after completing preoperative chemoradiotherapy.

MAIN OUTCOME MEASURES:
With the use of reverse transcriptase polymerase chain reaction analysis, mRNA expression levels of 7 candidate biomarkers (p53, p21, Ki-67, VEGF, CD133, CD24, and CD44) were evaluated from fresh tumor samples collected before preoperative chemoradiotherapy. The correlation between biomarker expression levels and the pathologic response was assessed based on histopathological staging (pTNM) and tumor regression grade.

RESULTS:
The mRNA expression levels of 4 biomarkers (p53, p21, Ki67, and CD133) significantly correlated with tumor regression grade response and pathologic complete response. Patients showing low expression of p53 and/or high expression of p21, Ki67, and CD133 exhibited a significantly greater tumor regression grade response and pathologic complete response rate. A scoring system devised so that 1 point was given for each biomarker whose expression level correlated with pathologic complete response (score range: 0–4) showed that 9 of 62 patients with scores of 0 to 2 achieved pathologic complete response, whereas 15 of 18 patients with scores of 3 to 4 achieved pathologic complete response (14.5% vs 83.3%, p < 0.001). For prediction of pathologic complete response, the scoring system showed 62.5% sensitivity, 94.6% specificity, an 83.3% positive predictive value, and an 85.5% negative predictive value.

LIMITATIONS:
Small patient numbers have limitations related to the reproducibility and ability to provide quantitative information. In addition, this study lacks test and validation sets.

CONCLUSIONS:
The pretreatment mRNA expression levels of 4 biomarkers correlated with pathologic tumor response after intraoperative chemoradiotherapy in rectal cancer. Furthermore, the scoring system combining values of biomarker expression might have predictive power with high positive and negative predictive values.
Sex differences in episodic memory in early midlife: impact of reproductive aging
Authors: Rentz Dorene M. , Weiss Blair K. , Jacobs Emily G. , Cherkerzian Sara , Klibanski Anne , Remington Anne , Aizley Harlyn , Goldstein Jill M. 
Published: November 2016

Abstract

Objective:
Few have characterized cognitive changes with age as a function of menopausal stage relative to men, or sex differences in components of memory in early midlife. The study aim was to investigate variation in memory function in early midlife as a function of sex, sex steroid hormones, and reproductive status.

Methods:
A total of 212 men and women aged 45 to 55 were selected for this cross-sectional study from a prenatal cohort of pregnancies whose mothers were originally recruited in 1959 to 1966. They underwent clinical and cognitive testing and hormonal assessments of menopause status. Multivariate general linear models for multiple memory outcomes were used to test hypotheses controlling for potential confounders. Episodic memory, executive function, semantic processing, and estimated verbal intelligence were assessed. Associative memory and episodic verbal memory were assessed using Face-Name Associative Memory Exam (FNAME) and Selective Reminding Test (SRT), given increased sensitivity to detecting early cognitive decline. Impacts of sex and reproductive stage on performance were tested.

Results:
Women outperformed men on all memory measures including FNAME (β = −0.30, P < 0.0001) and SRT (β = −0.29, P < 0.0001). Furthermore, premenopausal and perimenopausal women outperformed postmenopausal women on FNAME (initial learning, β= 0.32, P = 0.01) and SRT (recall, β= 2.39, P = 0.02). Across all women, higher estradiol was associated with better SRT performance (recall, β = 1.96, P = 0.01) and marginally associated with FNAME (initial learning, β = 0.19, P = 0.06).

Conclusions:
This study demonstrated that, in early midlife, women outperformed age-matched men across all memory measures, but sex differences were attenuated for postmenopausal women. Initial learning and memory retrieval were particularly vulnerable, whereas memory consolidation and storage were preserved. Findings underscore the significance of the decline in ovarian estradiol production in midlife and its role in shaping memory function.
Screening History in 313 Cases of Invasive Cancer: A Retrospective Review of Cervical Cancer Screening in Alberta, Canada
Authors: Mema Silvina C. , Nation Jill , Yang Huiming , Waghray Ranjit , Sun Maggie C. , Xu Linan , Kliewer Gordon 
Published: November 2016

Objective
To examine the screening history of invasive cervical cancer (ICC) cases in Alberta, Canada to identify areas for improvement of the population-based cervical cancer screening program.

Methods
Retrospective review of ICC cases diagnosed in 2 cities in Alberta between 2007 and 2012. Cancer morphology and staging were elicited from the Alberta Cancer Registry; cancer screening history and Pap test results were extracted from the Provincial Cervical Cancer Screening database. Women were classified as adequately screened, underscreened, and unscreened depending on time from last screening Pap test to diagnosis.

Results
Of the 280 cases that occurred in women eligible for screening, 125 (44.6%) were adequately screened, 18 (6.4%) were underscreened, and 137 (49%) were unscreened. Among the adequately screened, 71 (56.8%) had normal Pap test results, but 48 (38%) had less than 3 previous Pap tests (p = .003). Cancer stages I to II were diagnosed in 48.8% and 44.1% of adequately screened and unscreened women and cancer stages III to IV in 30.6% and 66.1% in each group, respectively (p = .0058). Squamous cell carcinoma (SCC) was diagnosed in 189 women (67.5%). The proportion of SCCs was similar in adequately screened and unscreened women.

Conclusions
The proportion of SCCs and advanced stages of ICC seems to be decreased. The results of quality improvement initiatives such as enhanced surveillance of high-grade Pap test results and histology-cytology correlation will be monitored and are expected to result in better outcomes for adequately screened women.
Antipsychotic Selection for Acute Agitation and Time to Repeat Use in a Psychiatric Emergency Department
Authors: GOMEZ SETH , DOPHEIDE JULIE 
Published: November 2016

Background:Early recognition and treatment of agitated patients is essential to avoid violence in the psychiatric emergency department (ED). Antipsychotics have established efficacy in managing agitation, yet little is known about how the choice of initial antipsychotic impacts time to repeat use and length of stay (LOS) in the psychiatric ED.Objective:To describe the impact of initial antipsychotic selection on time to repeat use and LOS in the psychiatric ED.Methods:A chart review identified 388 cases in which patients were administered an antipsychotic for agitation in the psychiatric ED between July 1 and August 31, 2014. Time to repeat use and LOS were compared for intramuscular (IM) haloperidol, other IM antipsychotics, and oral second-generation antipsychotics (SGAs) using the Kruskal-Wallis or Wilcoxon-Mann-Whitney test.Results:Of the 388 cases, 31% (n=122) required repeat medications. Mean time to repeat use for IM haloperidol was 20.1±18.4 hours, which was not significantly different from mean time to repeat use in the groups receiving other IM antipsychotics or oral SGAs (P=0.35). The mean LOS was 29.7±28.7 hours for IM haloperidol, 30.3±36.9 hours for other IM antipsychotics, and 22.6±28.0 hours for oral SGAs. Significant differences in LOS between repeat and nonrepeat users of IM haloperidol and other IM antipsychotics were observed, but not among those who received oral SGAs.Conclusions:Mean time to repeat use ranged from 14 to 20 hours with IM haloperidol, other IM antipsychotics, and oral SGAs without significant differences in time to repeat use in the 3 different groups. Repeat users of IM antipsychotics had a significantly longer LOS in the ED compared with nonrepeat users of IM antipsychotics. However, patients who were initially administered oral SGAs did not have longer LOS in the ED even if a repeat dose was given.
Evaluation of Bipolar Disorder in Children and Adolescents Referred to a Mood Service: Diagnostic Pathways and Manic Dimensions
Authors: FERREIRA-MAIA ANA P. , BORONAT ALEXANDRE C. , BOARATI MIGUEL A. , FU-I LEE , WANG YUAN-PANG 
Published: November 2016

Objectives:
Few studies have examined pediatric mental health services for early-onset bipolar disorder (BD). The goal of this study was to describe diagnostic pathways and manic dimensions in BD among referred children and adolescents.

Methods:
Data were obtained from a review of the charts of 814 subjects, 2 to 17 years of age, with a complaint of mood disturbances who were referred between 2003 and 2012 to a university-based child and adolescent clinic that specializes in mood disorders. After screening, eligible participants (N=494) were systematically assessed and followed to determine diagnoses on the basis of criteria in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision in accordance with the best-estimate approach. Manic symptoms were subjected to principal component analysis to investigate the dimensional bipolar profile of the sample.

Results:
Among the total help-seeking sample, approximately one third of the participants dropped out at intake and, after an average follow-up of 1.7 years, one third had been determined to meet criteria for BD and one third did not fulfill operational criteria for BD. The diagnostic status was changed in 35% of patients: approximately 10% were false positive (going from any bipolar diagnosis to a nonbipolar diagnosis) and approximately 25% were false negative (going from a nonbipolar diagnosis to any bipolar diagnosis). Most patients who converted to a bipolar diagnosis were initially labeled with major depressive disorder or attention-deficit/hyperactivity disorder and had a longer follow-up period. Relevant manic dimensions were elation, grandiosity, and disruption, which explained 41.4% of total variance.

Conclusions:
Regular reappraisal and follow-up of children and adolescents with mood disturbances provides a window for detection of BD (eg, of core manic dimensions). A coordinated and hierarchical connection among pediatric mental health services with different degrees of specialization is recommended.
Small Bowel Gastrointestinal Stromal Tumors: Multidetector Computed Tomography Enhancement Pattern and Risk of Progression
Authors: Verde Franco , Hruban Ralph H. , Fishman Elliot K. 
Published: November 2016

Objective
Small bowel gastrointestinal stromal tumors (SB-GISTs) are rare lesions with a variable appearance on computed tomography (CT). This case series analyzes the CT enhancement pattern with the histologic risk assessment of tumor progression.

Methods
Local institutional pathology database was searched for SB-GISTs from 2000 to 2015. Pathology reports and clinical notes were reviewed. Imaging was qualitatively reviewed for pattern of enhancement categorized into homogeneous or heterogeneous groups. Nonparametric statistical analysis was performed comparing enhancement to segment of bowel involved, presence of necrosis, tumor size, histologic grade (ie, G1 or G2), and histologic risk of progression (ie low, moderate, high). For simplicity, risk of progression was binned into low-risk or non–low-risk groups.

Results
Twenty-six pathology-proven, first presentation, nonmetastatic SB-GISTs were included into study. Seventeen were located in duodenum, 7 in jejunum, and 2 within the ileum. Dual phase (arterial and venous) CT imaging was available for 22 cases. Four cases did not have dual phase (three venous phase and one arterial phase only). Seventeen cases demonstrated heterogeneous enhancement and 9 cases homogeneous enhancement. Statistically significant difference was found between size versus enhancement groups (3.1 cm for homogeneous versus 6.8 cm for heterogeneous) (Mann-Whitney U test, n = 26, P = 0.002). Presence of necrosis versus enhancement group was statistically significant (Pearson χ2, P = 0.001). Low-risk and non–low-risk groups versus enhancement groups was very significant (P = 0.001). Bowel segment involvement and histologic grading versus enhancement group did not reach statistical significance (P = 0.174 and P = 0.07, respectively).

Conclusions
This case series reveals an important significant association between heterogeneous enhancement and non-low risk (ie, moderate/high) SB-GISTs. Beyond just describing the tumor, using enhancing pattern, the interpreting radiologist can preoperatively suggest additional prognostic information, potentially helpful for surgical planning.
Nodal signalling and asymmetry of the nervous system
Authors: Signore Iskra A. , Palma Karina , Concha Miguel L. 
Published: November 2016

The role of Nodal signalling in nervous system asymmetry is still poorly understood. Here, we review and discuss how asymmetric Nodal signalling controls the ontogeny of nervous system asymmetry using a comparative developmental perspective. A detailed analysis of asymmetry in ascidians and fishes reveals a critical context-dependency of Nodal function and emphasizes that bilaterally paired and midline-unpaired structures/organs behave as different entities. We propose a conceptual framework to dissect the developmental function of Nodal as asymmetry inducer and laterality modulator in the nervous system, which can be used to study other types of body and visceral organ asymmetries. Using insights from developmental biology, we also present novel evolutionary hypotheses on how Nodal led the evolution of directional asymmetry in the brain, with a particular focus on the epithalamus. We intend this paper to provide a synthesis on how Nodal signalling controls left–right asymmetry of the nervous system.This article is part of the themed issue ‘Provocative questions in left–right asymmetry’.
Split hand/foot malformation genetics supports the chromosome 7 copy segregation mechanism for human limb development
Authors: Klar Amar J. S. 
Published: November 2016

Genetic aberrations of several unlinked loci cause human congenital split hand/foot malformation (SHFM) development. Mutations of theDLX5(distal-less) transcription factor-encoding gene in chromosome 7 cause SHFM through haploinsufficiency, but the vast majority of cases result from heterozygous chromosomal aberrations of the region without mutating theDLX5gene. To resolve this paradox, we invoke a chromosomal epigenetic mechanism for limb development. It is composed of a monochromatid gene expression phenomenon that we discovered in two fission yeasts with the selective chromosome copy segregation phenomenon that we discovered in mouse cells. Accordingly, one daughter cell inherits both expressedDLX5copies while the other daughter inherits both epigenetically silenced ones from a single deterministic cell of the developing limb. Thus, differentiated daughter cells after further proliferation will correspondingly produce proximal/distal-limb tissues. Published results of a Chr. 7 translocation with a centromere-proximal breakpoint situated over 41 million bases away from theDLXlocus, centromeric andDLX5-region inversions have satisfied key genetic and developmental biology predictions of the mechanism. Further genetic tests of the mechanism are proposed. We propose that the DNA double helical structure itself causes the development of sister cells' gene regulation asymmetry. We also argue against the conventionally invoked morphogen model of development.This article is part of the themed issue ‘Provocative questions in left–right asymmetry’.
Tractography-based connectomes are dominated by false-positive connections
Authors: Maier-Hein Klaus H. , Neher Peter , Houde Jean-Christophe , Côté Marc-Alexandre , Garyfallidis Eleftherios , Zhong Jidan , Chamberland Maxime , Yeh Fang-Cheng , Lin Ying-Chia , Ji Qing , Reddick Wilburn E. , Glass John O. , Chen David Qixiang , Feng Yuanjing , Gao Chengfeng , Wu Ye , Ma Jieyan , Renjie H , Li Qiang , Westin Carl-Fredrik , Deslauriers-Gauthier Samuel , González J. Omar Ocegueda , Paquette Michael , St-Jean Samuel , Girard Gabriel , Rheault François , Sidhu Jasmeen , Tax Chantal M.W. , Guo Fenghua , Mesri Hamed Y. , Dávid Szabolcs , Froeling Martijn , Heemskerk Anneriet M. , Leemans Alexander , Boré Arnaud , Pinsard Basile , Bedetti Christophe , Desrosiers Matthieu , Brambati Simona , Doyon Julien , Sarica Alessia , Vasta Roberta , Cerasa Antonio , Quattrone Aldo , Yeatman Jason , Khan Ali R. , Hodges Wes , Alexander Simon , Romascano David , Barakovic Muhamed , Auría Anna , Esteban Oscar , Lemkaddem Alia , Thiran Jean-Philippe , Cetingul H. Ertan , Odry Benjamin L. , Mailhe Boris , Nadar Mariappan S. , Pizzagalli Fabrizio , Prasad Gautam , Villalon-Reina Julio E. , Galvis Justin , Thompson Paul M. , Requejo Francisco De Santiago , Laguna Pedro Luque , Lacerda Luis Miguel , Barrett Rachel , Dell’Acqua Flavio , Catani Marco , Petit Laurent , Caruyer Emmanuel , Daducci Alessandro , Dyrby Tim B. , Holland-Letz Tim , Hilgetag Claus C. , Stieltjes Bram , Descoteaux Maxime 
Published: November 2016

AbstractFiber tractography based on non-invasive diffusion imaging is at the heart of connectivity studies of the human brain. To date, the approach has not been systematically validated in ground truth studies. Based on a simulated human brain dataset with ground truth white matter tracts, we organized an open international tractography challenge, which resulted in 96 distinct submissions from 20 research groups. While most state-of-the-art algorithms reconstructed 90% of ground truth bundles to at least some extent, on average they produced four times more invalid than valid bundles. About half of the invalid bundles occurred systematically in the majority of submissions. Our results demonstrate fundamental ambiguities inherent to tract reconstruction methods based on diffusion orientation information, with critical consequences for the approach of diffusion tractography in particular and human connectivity studies in general.
EthSEQ: ethnicity annotation from whole exome sequencing data
Authors: Romanel Alessandro , Zhang Tuo , Elemento Olivier , Demichelis Francesca 
Published: November 2016

AbstractWhole exome sequencing (WES) is widely utilized both in translational cancer genomics studies and in the setting of precision medicine. Stratification of individual's ethnicity is fundamental for the correct interpretation of personal genomic variation impact. We implemented EthSEQ to provide reliable and rapid ethnicity annotation from whole exome sequencing individual's data and validated it on 1,000 Genome Project and TCGA data demonstrating high precision (>99%). EthSEQ can be integrated into any WES based processing pipeline and exploits multi-core capabilities. Source code, manual and other data is available athttp://demichelislab.unitn.it/EthSEQ.
Rapid and recent evolution of LTR retrotransposons drives rice genome evolution during the speciation of AA- genomeOryzaspecies
Authors: Zhang Qun-Jie , Gao Li-zhi 
Published: November 2016

ABSTRACTThe dynamics of LTR retrotransposons and their contribution to genome evolution during plant speciation have remained largely unanswered. Here, we perform a genome-wide comparison of all eightOryzaAA- genome species, and identify 3,911 intact LTR retrotransposons classified into 790 families. The top 44 most abundant LTR retrotransposon families show patterns of rapid and distinct diversification since the species split over the last ~4.8 Myr. Phylogenetic and read depth analyses of 11 representative retrotransposon families further provide a comprehensive evolutionary landscape of these changes. Compared with Ty1-copia, independent bursts of Ty3-gypsyretrotransposon expansions have occurred with the three largest showing signatures of lineage-specific evolution. The estimated insertion times of 2,213 complete retrotransposons from the top 23 most abundant families reveal divergent life-histories marked by speedy accumulation, decline and extinction that differed radically between species. We hypothesize that this rapid evolution of LTR retrotransposons not only divergently shaped the architecture of rice genomes but also contributed to the process of speciation and diversification of rice.
Direct estimation of the spontaneous mutation rate by short-term mutation accumulation lines inChironomus riparius
Authors: Oppold Ann-Marie , Pfenninger Markus 
Published: November 2016

AbstractMutations are the ultimate basis of evolution, yet their occurrence rate is known only for few species. We directly estimated the spontaneous mutation rate and the mutational spectrum in the non-biting midgeC. ripariuswith a new approach. Individuals from ten mutation accumulation lines over five generations were deep genome sequenced to countde novomutations (DNMs) that were not present in a pool of F1 individuals, representing parental genotypes. We identified 51 new single site mutations of which 25 were insertions or deletions and 26 single point mutations. This shift in the mutational spectrum compared to other organisms was explained by the high A/T content of the species. We estimated a haploid mutation rate of 2.1 x 10−9(95% confidence interval: 1.4 x 10−9– 3.1 x 10−9) which is in the range of recent estimates for other insects and supports the drift barrier hypothesis. We show that accurate mutation rate estimation from a high number of observed mutations is feasible with moderate effort even for non-model species.
Rapid shift in substrate utilization driven by hypothalamic Agrp neurons
Authors: Cavalcanti-de-Albuquerque João Paulo , Zimmer Marcelo R. , Bober Jeremy , Dietrich Marcelo O. 
Published: November 2016

AbstractAgrp neurons drive feeding. To what extend these neurons participate in the regulation of other homeostatic processes is not well understood. We investigated the role of Agrp neurons in substrate utilization in mice. Activation of Agrp neurons was sufficient to rapidly increase RER and carbohydrate utilization, while decreasing fat utilization. These metabolic changes were linearly correlated with carbohydrates ingested, but not protein or fat ingestion. However, even in the absence of ingestive behaviors, activation of Agrp neurons led to changes in substrate utilization in well-fed mice. These effects were coupled to metabolic shifts towards lipogenesis. Inhibition of fatty acid synthetase (FAS) blunted the effects of Agrp neurons on substrate utilization. Finally, Agrp neurons controlled peripheral metabolism, but not food intake, via ß3-adrenergic receptor signaling in fat tissues. These results reveal a novel component of Agrp neuron-mediate metabolism regulation that involves sympathetic activity on fat compartments to shift metabolism towards lipogenesis.