bluuebunny/crossref_metadata_2025_split huggingface dataset:
Folate Receptor Alpha Expression in Platinum Resistant/Refractory Ovarian Carcinomas and Primary Endocervical Adenocarcinomas
Authors: Rubinsak Lisa A. , Cohen Cynthia , Khanna Namita , Horowitz Ira R. , Hanley Krisztina Z. 
Published: December 2016

Introduction:
Treatment of advanced stage ovarian carcinoma is challenging, and despite surgical treatment and chemotherapy, the 5-year survival rate is estimated around 30%. Early recurrence and resistance to platinum-based chemotherapy are associated with poor prognosis and limited response to available second-line chemotherapy. The relative incidence of endocervical adenocarcinoma (EAC) compared with squamous cell carcinoma is increasing. Although the first-line treatment modality for early stage EAC is surgical resection, for locally advanced disease chemoradiation or neoadjuvant chemotherapy is used. Recently, folate along with its receptor alpha (FRA) has been studied as a potential target in gynecologic malignancy. The objective of this study was to elucidate FRA expression in chemotherapy resistant ovarian cancer and primary EAC.

Methods:
FRA expression was evaluated in tissue samples in an epithelial ovarian tumor microarray and 2 study groups: platinum resistant ovarian cancer and primary EAC. Staining intensity was analyzed with a semiquantitative staining algorithm.

Results:
FRA expression was positive in 32 of 40 (80%) ovarian tumors in the control group. In the platinum resistant ovarian cancer group, FRA was expressed in all 30 samples with moderate to strong staining. None of the EAC samples stained positive for FRA expression.

Conclusions:
FRA expression occurs frequently in epithelial ovarian cancer. Our data supports that FRA expressions are maintained after chemotherapy treatment. Folate targeted therapies may be most useful in patients with chemotherapy resistant disease based on high levels of FRA expression in these tumors. There is likely no benefit to folate therapy as an adjuvant treatment in EAC.
A Systemic Inflammation Mortality Risk Assessment Contingency Table for Severe Sepsis*
Authors: Carcillo Joseph A. , Sward Katherine , Halstead E. Scott , Telford Russell , Jimenez-Bacardi Adria , Shakoory Bita , Simon Dennis , Hall Mark 
Published: December 2016

Objectives:
We tested the hypothesis that a C-reactive protein and ferritin-based systemic inflammation contingency table can track mortality risk in pediatric severe sepsis.

Design:
Prospective cohort study.

Setting:
Tertiary PICU.

Patients:
Children with 100 separate admission episodes of severe sepsis were enrolled.

Interventions:
Blood samples were attained on day 2 of sepsis and bi-weekly for biomarker batch analysis. A 2 × 2 contingency table using C-reactive protein and ferritin thresholds was developed.

Measurements and Main Results:
A C-reactive protein of 4.08 mg/dL and a ferritin of 1,980 ng/mL were found to be optimal cutoffs for outcome prediction at first sampling (n = 100) using the Youden index. PICU mortality was increased in the “high-risk” C-reactive protein greater than or equal to 4.08 mg/dL and ferritin greater than or equal to 1,980 ng/mL category (6/13 [46.15%]) compared with the “intermediate-risk” C-reactive protein greater than or equal to 4.08 mg/dL and ferritin less than 1,980 ng/mL or C-reactive protein less than 4.08 mg/dL and ferritin greater than or equal to 1,980 ng/mL categories (2/43 [4.65%]), and the “low-risk” C-reactive protein less than 4.08 mg/dL and ferritin less than 1,980 ng/mL category (0/44 [0%]) (odds ratio, 36.43 [95% CI, 6.16–215.21]). The high-risk category was also associated with the development of immunoparalysis (odds ratio, 4.47 [95% CI, 1.34–14.96]) and macrophage activation syndrome (odds ratio, 24.20 [95% CI, 5.50–106.54]). Sixty-three children underwent sequential blood sampling; those who were initially in the low-risk category (n = 24) and those who subsequently migrated (n = 19) to the low-risk category all survived, whereas those who remained in the “at-risk” categories had increased mortality (7/20 [35%]; p < 0.05).

Conclusions:
A C-reactive protein- and ferritin-based contingency table effectively assessed mortality risk. Reduction in systemic inflammation below a combined threshold C-reactive protein of 4.08 mg/dL and ferritin of 1,980 ng/mL appeared to be a desired response in children with severe sepsis.
Stress, Illness Perceptions, Behaviors, and Healing in Venous Leg Ulcers: Findings From a Prospective Observational Study
Authors: Walburn Jessica , Weinman John , Norton Sam , Hankins Matthew , Dawe Karen , Banjoko Bolatito , Vedhara Kavita 
Published: December 2016

ABSTRACT

Objective
The aim of the study was to investigate the impact of stress, illness perceptions, and behaviors on healing of venous leg ulcers.

Methods
A prospective observational study of 63 individuals for 24 weeks investigated possible psychosocial predictors of healing. There were two indices of healing: rate of change in ulcer area and number of weeks to heal. Psychological variables were assessed at baseline using self-report measures (Perceived Stress Scale, Hospital Anxiety and Depression Scale, Revised Illness Perception Questionnaire, adapted Summary of Diabetes Self-Care Activities, Adherence Questionnaire, and Short-Form Health Survey).

Results
Controlling for sociodemographic and clinical variables, for the 24 weeks, a slower rate of change in ulcer area was predicted by greater stress (standardized β = −0.61, p = .008), depression (standardized β = −0.51, p = .039), and holding negative perceptions or beliefs about the ulcer (standardized β = −1.4, p = .045). By 24 weeks, 69% of ulcers had closed. A more negative emotional response to the ulcer at baseline (i.e., emotional representation of the ulcer) was associated with a greater number of weeks to heal (hazard ratio [HR] = 0.63, 95% confidence interval [CI] = 0.41-0.95, p = .028). Higher educational attainment (HR = 3.22, 95% CI = 1.37–7.55, p = .007) and better adherence to compression bandaging (HR = 1.41, 95% CI = 1.06–1.88, p = .019) were associated with fewer weeks to heal. No other psychosocial variable (stress, perceptions about the ulcer, health behaviors) predicted weeks to heal.

Conclusions
Alongside ulcer-related predictors, psychological and sociodemographic factors were associated with healing. Future research should explore mediating mechanisms underlying these associations and develop interventions to target these variables.
An Attachment-Based Model of the Relationship Between Childhood Adversity and Somatization in Children and Adults
Authors: Maunder Robert G. , Hunter Jonathan J. , Atkinson Leslie , Steiner Meir , Wazana Ashley , Fleming Alison S. , Moss Ellen , Gaudreau Helene , Meaney Michael J. , Levitan Robert D. 
Published: December 2016

ABSTRACT

Objective
An attachment model was used to understand how maternal sensitivity and adverse childhood experiences are related to somatization.

Methods
We examined maternal sensitivity at 6 and 18 months and somatization at 5 years in 292 children in a longitudinal cohort study. We next examined attachment insecurity and somatization (health anxiety, physical symptoms) in four adult cohorts: healthy primary care patients (AC1, n = 67), ulcerative colitis in remission (AC2, n = 100), hospital workers (AC3, n = 157), and paramedics (AC4, n = 188). Recall of childhood adversity was measured in AC3 and AC4. Attachment insecurity was tested as a possible mediator between childhood adversity and somatization in AC3 and AC4.

Results
In children, there was a significant negative relationship between maternal sensitivity at 18 months and somatization at age 5 years (B = −3.52, standard error = 1.16, t = −3.02, p = .003), whereas maternal sensitivity at 6 months had no significant relationship. In adults, there were consistent, significant relationships between attachment insecurity and somatization, with the strongest findings for attachment anxiety and health anxiety (AC1, β = 0.51; AC2, β = 0.43). There was a significant indirect effect of childhood adversity on physical symptoms mediated by attachment anxiety in AC3 and AC4.

Conclusions
Deficits in maternal sensitivity at 18 months of age are related to the emergence of somatization by age 5 years. Adult attachment insecurity is related to somatization. Insecure attachment may partially mediate the relationship between early adversity and somatization.
Trauma and Autonomic Dysregulation: Episodic—Versus Systemic—Negative Affect Underlying Cardiovascular Risk in Posttraumatic Stress Disorder
Authors: Dennis Paul A. , Kimbrel Nathan A. , Sherwood Andrew , Calhoun Patrick S. , Watkins Lana L. , Dennis Michelle F. , Beckham Jean C. 
Published: December 2016

ABSTRACT

Objective
Posttraumatic stress disorder (PTSD) has been linked to elevated heart rate (HR) and reduced heart rate variability (HRV) in cross-sectional research. Recent evidence suggests that this link may be driven by individual differences in autonomic arousal associated with momentary negative affect (NA). Using ecological momentary assessment (EMA) of NA and minute-to-minute HR/HRV monitoring, we examined whether NA-related HR/HRV mediated the association of PTSD symptom severity with 24-hour HRV and endothelial functioning.

Methods
One hundred ninety-seven young adults (18–39 years), 93 with PTSD, underwent 1 day of Holter monitoring while concurrently reporting NA levels via EMA. Two noninvasive measures of endothelial functioning—flow-mediated dilation and hyperemic flow—were also collected. Multilevel modeling was used to assess the associations of momentary NA with HR and low- and high-frequency HRV during the 5-minute intervals after each EMA reading. Latent variable modeling was then used to determine whether individual differences in these associations mediated the association of PTSD symptom severity with 24-hour HRV, flow-mediated dilation, and hyperemic flow.

Results
PTSD symptom severity was positively associated with NA-related autonomic arousal (β = .21, p < .001), which significantly mediated the association of PTSD symptom severity with 24-hour HRV and hyperemic flow, accounting for 62% and 34% of their associations, respectively, while overshadowing the influence of smoking, lifetime alcohol dependence, sleep duration, mean NA, and episodes of acute NA.

Conclusions
Results suggest that NA-related autonomic arousal is both a primary factor driving cardiovascular risk in PTSD and a potential point of intervention.
Early Life Stress, FKBP5 Polymorphisms, and Quantitative Glycemic Traits
Authors: Suarez Anna , Lahti Jari , Kajantie Eero , Eriksson Johan G. , Räikkönen Katri 
Published: December 2016

ABSTRACT

Objective
Early life stress (ELS) has been shown to influence health later in life. Functioning of the hypothalamic-pituitary-adrenal axis, regulated partly by FKBP5 gene, may moderate these effects. We examined whether FKBP5 single-nucleotide polymorphisms (SNPs) interact with ELS on Type 2 diabetes, cardiovascular disease, and quantitative glycemic traits.

Methods
A total of 1728 Helsinki Birth Cohort Study participants born from 1934 to 1944 were genotyped for FKBP5 SNPs (rs1360780, rs9394309, rs9470080) and were administered a 2-hour (75 g) oral glucose tolerance test and a questionnaire on physician-diagnosed and medication use for chronic diseases at a mean age of 61.5 years. Of the participants, 273 had been exposed to ELS, operationalized as separation from their parents, at a mean age of 4.7 years due to evacuations during World War II.

Results
ELS interacted with FKBP5 SNPs in the analyses of fasting (rs1360780, p = .015), 30-minute (rs1360780, p = .031; rs9394309, p = .041) and incremental insulin (rs1360780, p = .032; rs9394309, p = .028; rs9470080, p = .043), insulin area under the curve (rs1360780, p = .044), and impaired fasting glucose (rs9470080, p = .049); among carriers of at least one copy of minor allele, but not among major allele homozygotes, insulin values were higher, as were the odds for impaired fasting glucose if they had been separated compared with if they had not. Corresponding associations were found with a haplotype formed by minor alleles in all three SNPs for fasting, 30-minute, and incremental insulin (p < .05).

Conclusions

FKBP5 polymorphisms in combination with ELS exposure predict higher insulin and glucose values in midlife. Our findings support the role for hypothalamic-pituitary-adrenal axis dysregulation in health-related metabolic outcomes.
3-D spatial memory and navigation: functions and disorders
Authors: Brandt Thomas , Zwergal Andreas , Glasauer Stefan 
Published: December 2016

Purpose of review
The aim of this review is to report on the specialized neuronal systems mediating spatial orientation and navigation discovered in animal experiments. These findings have important implications for the clinical management of patients with vestibular disorders or dementia and for translational research in these fields.

Recent findings
The following anatomically and functionally separate, but nevertheless cooperative cell types have been characterized: angular head velocity cells and head direction cells, which depend on vestibular input and interact with place cells and grid cells, which represent position and distance. The entire system is thought to encode internal cognitive maps whose spatial data can be utilized for navigation and orientation. Flying and swimming species use spatial orientation and navigation isotropically, i.e., in the earth-horizontal and vertical directions, whereas ground-based species, including humans, perform better in the earth-horizontal plane (anisotropically). Examples of clinical disorders with deficits of spatial orientation and navigation are bilateral peripheral vestibulopathy, mild cognitive impairment, and dementia.

Summary
Testing spatial orientation and navigation should become an integral part of routine neurological examinations, especially in the elderly. Also desirable are the further development and standardization of simple and reliable smart phone-based bedside tests to measure these functions in patients.
Nystagmus and central vestibular disorders
Authors: Choi Jeong-Yoon , Kim Ji-Soo 
Published: December 2016

Purpose of review
This review will cover the recent advances in clinical and laboratory features, pathophysiology, and treatment of central vestibular disorders.

Recent findings
Several features and mechanisms of central nystagmus have been identified over the years. Application of head impulse tests and vestibular evoked myogenic potentials has expanded our understanding of altered processing of canal-driven and otolith-driven vestibular signals in lesions involving the central vestibular structures. Integrated approach based on the symptoms and neurotologic signs enhances the diagnostic accuracy of acute vascular vertigo. Identification of isolated central vestibular syndromes has improved the diagnosis of central vertigo and our understanding of anatomic and functional organization of the central vestibular structures.

Summary
With the developments of clinical and laboratory neurotology, the spectrum of central vestibular disorders has expanded markedly over the years.
Neuroprotection and visual function after optic neuritis
Authors: Petzold Axel 
Published: December 2016

Purpose of review
This article discusses the advantages and pitfalls of testing neuroprotective treatment strategies in patients suffering from optic neuritis.

Recent findings
Spectral domain optical coherence tomography now permits for automated segmentation of individual retinal layers. The peripapillary retinal nerve fibre layer (pRNFL) has been used in 13 of the 15 trials reviewed. Twelve trials also made use of electrophysiology. Overestimation of good visual recovery in the past has recently been recognized. Assessment of low contrast visual acuity and colour vision are now mainstream.

Summary
The availability of highly accurate and robust trial outcome measures has facilitated research on this topic. A single long-term structural outcome measurement of the pRNFL is sufficient. For shorter term, assessments of the ganglion cell/inner plexiform layer and axonal birefringence are promising. Longitudinal blood levels of neurofilament proteins permit to recognize axonal loss at presentation and monitor changes longitudinally. Inner nuclear layer volume changes relate to inflammatory disease activity.
Pitfalls are related to the timing of events. Hyperacute recruitment is needed for future trials. The onset of demyelination is not known, which complicates timing of electrophysiological recordings. Optic disc oedema precludes the use of the pRNFL from the affected eye as a baseline variable. The concomitant use of corticosteroids complicates interpretation of trial data.
Epigallocatechin Gallate Extends Therapeutic Window of Recombinant Tissue Plasminogen Activator Treatment for Brain Ischemic Stroke: A Randomized Double-Blind and Placebo-Controlled Trial
Authors: Wang Xue-Hui , You Yi-Ping 
Published: December 2016

ObjectivesRecombinant tissue plasminogen activator (rt-PA) is a safe and effective treatment for acute brain ischemia stroke, albeit with a narrow therapeutic window. We aimed to assess the effect of epigallocatechin gallate (EGCG) in extending the rt-PA treatment window in this clinical trial among stroke patients.MethodsPatients were randomly assigned according to their onset-to-treatment time (OTT) and were then treated with rt-PA simultaneously with EGCG or placebo. Treatment outcome was assessed by the National Institutes of Health stroke scale (NIHSS) and plasma levels of matrix metalloproteinases (MMP)-2 and 9.ResultsAdministration of EGCG significantly improved treatment outcomes of patients in the delayed OTT strata, as evidenced by improved NIHSS scores. This improved treatment outcome was likely attributed to reduction in plasma levels of both MMP-2 and 9, as indicated by strong linear correlations between both MMPs and NIHSS scores in all patients.ConclusionsEpigallocatechin gallate could potentially be used as a supplement of traditional rt-PA treatment among stroke patients, particularly those with delayed OTT, to extend the otherwise narrow therapeutic window and improve the outcome in late stroke treatment.
Alcohol-Sensitive Generalized Dystonia
Authors: Micheli Federico , Uribe-Roca Claudia , Saenz-Farret Michel 
Published: December 2016

Abstract
We report the case of a 29-year-old male patient with a generalized and progressive dystonia that led him unable to stand. Multiple antidystonic treatments were tried without benefit. Alcohol test was positive with a dramatic improvement. To the best of our knowledge, this is the first reported case of generalized dystonia without other clinical manifestations sensitive to alcohol.
KIF21A influences breast cancer metastasis and survival
Authors: Lucanus Anton J. , King Victoria , Yip George W. 
Published: December 2016

ABSTRACTBreast cancer pathogenesis is known to be propagated by the differential expression of a group of proteins called the Kinesin Superfamily (KIFs), which are instrumental in the intracellular transport of chromosomes along microtubules during mitosis. During mitosis, KIFs are strictly regulated through temporal synthesis so that they are only present when needed. However, their misregulation may contribute to uncontrolled cell growth due to premature sister chromatid separation, highlighting their involvement in tumorigenesis. One particular KIF, KIF21A, was recently found to promote the survival of human breast cancer cellsin vitro. However, how KIF21A influences other cancerous phenotypes is currently unknown. This study therefore aimed to consolidate thein vitrorole of KIF21A in breast cancer metastasis, while also analysing KIF21A expression in human breast cancer tissue to determine its prognostic value. This was achieved by silencing KIF21A in MCF-7 and MDA-MB-231 breast cancer cell lines via siRNA transfection. Migration, invasion, proliferation, and adhesion assays were then performed to measure the effects of KIF21A silencing on oncogenic behaviour. Immunohistochemistry was also conducted in 263 breast cancer tissue samples to compare KIF21A expression levels against various prognostic outcomes and clinicopathological parameters. KIF21A knockdown reduced cell migration (by 42.8% [MCF-7] and 69.7% [MDA-MB-231]) and invasion (by 72.5% [MCF-7] and 42.5% [MDA-MB-231]) in both cell lines, but had no effect on adhesion or proliferation, suggesting that KIF21A plays an important role in the early stages of breast cancer metastasis. Unexpectedly however, KIF21A was shown to negatively correlate with various pro-malignant clinicopathological parameters, including tumour size and histological grade, and high KIF21A expression predicted better breast cancer survival (hazard ratio = 0.45), suggesting that KIF21A is a tumour suppressor. The conflicting outcomes ofin vitroandin vivodata may be due to the possible multi-functionality of KIF21A or study limitations, and means no definitive conclusions can be drawn about the role of KIF21A in breast cancer. This warrants further investigation, which may prove pivotal to the development of novel chemotherapeutic strategies to mediate KIF21A’s function and enhance prognostic outcomes.
The centrosome is a selective phase that nucleates microtubules by concentrating tubulin
Authors: Woodruff Jeffrey B. , Gomes Beatriz Ferreira , Widlund Per O. , Mahamid Julia , Hyman Anthony A. 
Published: December 2016

AbstractCentrosomes are non-membrane-bound compartments that nucleate microtubule arrays. They consist of nanometer-scale centrioles surrounded by a micron-scale, dynamic assembly of protein called the pericentriolar material (PCM). To study how PCM forms a spherical compartment that nucleates microtubules, we reconstituted PCM-dependent microtubule nucleationin vitrousing recombinantC.elegansproteins. We found that macromolecular crowding drives phase separation of the key PCM scaffold protein SPD-5 into spherical droplets that morphologically and dynamically resemblein vivoPCM. These SPD-5 droplets recruited the microtubule polymerase ZYG-9 (XMAP215 homologue) and the microtubule-stabilizing protein TPXL-1 (TPX2 homologue). Together, these three proteins concentrated tubulin ~4- fold over background, which was sufficient to reconstitute nucleation of microtubule astersin vitro.Our results suggest thatin vivoPCM is a selective phase that organizes microtubule arrays through localized concentration of tubulin by microtubule effector proteins.One Sentence SummaryPhase separation ofC. eleganscentrosome proteins drive the formation of micron-sized microtubule organizing centers.