bluuebunny/crossref_metadata_2025_split huggingface dataset:
High levels of memory B cells are associated with response to a first tumor necrosis factor inhibitor in patients with rheumatoid arthritis in a longitudinal prospective study
Authors: Daien Claire I , Gailhac Sarah , Mura Thibault , Combe Bernard , Hahne Michael , Morel Jacques 
Published: April 2014

Abstract
Introduction
Tumor necrosis factor inhibitor (TNFi) therapy is effective for rheumatoid arthritis (RA). Some researchers have suggested that TNFi therapy affects B-cell homeostasis. We studied the effect of TNFi therapy on the distribution of peripheral B-cell subsets to elucidate B-cell–related biomarkers to predict the TNFi response.

Methods
Peripheral B cells were analyzed for expression of CD19, CD27, CD38 and immunoglobulin D in 31 healthy donors and 96 RA patients, including 21 patients who were followed 3 months after TNFi initiation.

Results
Treatment with steroids significantly altered the distribution of B-cell subsets. After we adjusted for age, sex and steroid dose, we found that patients with RA had B-cell subset proportions similar to controls. B-cell subset distributions did not differ upon use of TNFi at baseline or before or after TNFi introduction. TNFi responders (according to European League Against Rheumatism criteria) at 3 months had significantly higher proportions of CD27+ memory B cells at baseline, and ≥26% CD27+ cells at inclusion was associated with a relative risk of 4.9 (1.3 to 18.6) for response to TNFi treatment. CD27+ cells produced three times more TNFα than did TNFi-naïve B cells and were correlated with interferon γ produced from CD4+ cells in patients without TNFi treatment.

Conclusions
In patients with RA, high levels of baseline memory B cells were associated with response to TNFi, which may be related to TNFα-dependent activation of the T helper type 1 cell pathway.
Predicting outcome from subacute unresponsive wakefulness syndrome or vegetative state
Authors: Bodart Olivier , Laureys Steven 
Published: April 2014

AbstractPredicting recovery of consciousness in patients who survive their coma but evolve to a vegetative state (recently coined unresponsive wakefulness syndrome) remains a challenge. Most previous prognostic studies have focused on the acute coma phase. A novel outcome scale (combining behavioural, aetiology, electroencephalographic, sleep electroencephalographic and somatosensory evoked potential data) has been proposed for patients in subacute unresponsive wakefulness syndrome. The scale’s clinical application awaits validation in a larger population.
At the Bedside: Adoptive cell therapy for melanoma—clinical development
Authors: Weber Jeffrey S 
Published: April 2014

AbstractAdoptive cell therapy for melanoma, particularly using TIL, consists of a complex and difficult set of procedures, although it has a strong preclinical background and justification and has been pursued clinically by one small group of investigators over the last 20 years. More recent developments and a better understanding of the molecular basis of the anti-tumor immune response have led to the conduct of clinical trials that use lymphoid depletion with chemotherapy and/or TBI to exploit the favorable immune milieu of homeostatic lymphoid reconstitution during transfer of effector T cells. Improved ways of propagating T cells ex vivo have also simplified and shortened the cell-growth process. Current TIL trials have now been expanded beyond the initial center where it was developed, reproducing excellent objective response rates of 40–50% in previously treated melanoma patients and more importantly, demonstrating that a significant proportion of patients will be alive and free of disease 3–5 years after treatment, raising the possibility that those patients may be cured of their disease. Newer methods for growing the infiltrating T cells using immune-checkpoint antibodies or other agents to condition the tumor before harvest and improved technology to simplify the complex and often cumbersome cell-growth process suggest that this technology may be able to be disseminated to a wide selection of cancer centers and may be a candidate for testing in a randomized Phase III trial to show definitively its benefit in patients with metastatic melanoma. In the accompanying review, the preclinical work that supports the idea of adoptive cell therapy with TIL and expands the concept in promising new ways will be explored.
Phase IIa Trial of Trastuzumab Emtansine With Pertuzumab for Patients With Human Epidermal Growth Factor Receptor 2–Positive, Locally Advanced, or Metastatic Breast Cancer
Authors: Miller Kathy D. , Diéras Véronique , Harbeck Nadia , Andre Fabrice , Mahtani Reshma L. , Gianni Luca , Albain Kathy S. , Crivellari Diana , Fang Liang , Michelson Glenn , de Haas Sanne L. , Burris Howard A. 
Published: April 2014

Purpose Our phase IIa study characterized the safety and efficacy of two human epidermal growth factor receptor 2 (HER2) –targeted agents, trastuzumab emtansine (T-DM1) and pertuzumab, in patients with HER2-positive metastatic breast cancer (MBC). Patients and Methods Patients with HER2-positive locally advanced breast cancer or MBC were treated with 3.6 mg/kg T-DM1 plus pertuzumab (840-mg loading dose, then 420 mg subsequently) once every 3 weeks. The primary efficacy end point was investigator-assessed objective response rate (ORR). Results Sixty-four patients (43 patients in the second-line or greater setting [advanced MBC]; 21 patients in the first-line setting [first-line MBC]) were enrolled. Patients with advanced MBC had received trastuzumab and a median of six prior nonhormonal treatments for MBC; 86% of first-line MBC patients had received trastuzumab in the (neo)adjuvant setting. The ORR was 41% overall, 33% in patients with advanced MBC, and 57% in first-line patients. Median progression-free survival was 6.6, 5.5, and 7.7 months, respectively. The most common adverse events were fatigue (61%), nausea (50%), and diarrhea (39%). The most frequent grade ≥ 3 adverse events were thrombocytopenia (13%), fatigue (11%), and liver enzyme elevations (increased ALT: 9%; increased AST: 9%). One patient had left ventricular ejection fraction of less than 40% after study drug discontinuation. Exploratory biomarker analyses demonstrated that patients with above-median tumor HER2 mRNA levels had a numerically higher ORR than patients with below-median levels (44% v 33%, respectively). Conclusion T-DM1 and pertuzumab can be combined at full doses with no unexpected toxicities. The preliminary efficacy in patients in the first-line and advanced MBC settings warrants further investigation.
Gas-Phase Acidity of Polyfluorinated Hydrocarbons. Effects of Fluorine and the Perfluoroalkyl Group on Acidity
Authors: Zhang Min , Badal Md Mizanur Rahman , Pasikowska Magdalena , Sonoda Takaaki , Mishima Masaaki , Fukaya Haruhiko , Ono Taizo , Siehl Hans-Ullrich , Abboud José-Luis M , Koppel Ilmar A 
Published: April 2014

Abstract
Gas-phase acidities of polyfluorinated hydrocarbons have been determined by measuring proton-transfer equilibria and by computing the free energies of deprotonated carbanions and the corresponding neutrals. An excellent linear relationship between acidities and the accumulated inductive effects of fluorine atoms contained in a molecule was observed for the perfluoroalkyl-substituted neopentanes, (Rf1)(Rf2)(Rf3)CCH3, and polyfluorinated bridgehead carbon acids where the contribution of negative hyperconjugation of the Cβ–F bond to the stability of the conjugate anions is absent or negligibly small. On the basis of this relationship, the extent of β-fluorine negative hyperconjugation involved in acidities of polyfluorinated hydrocarbons could be evaluated quantitatively. The negative hyperconjugation was found to be negligibly small in the stable tertiary polyfluorinated carbanions while in the less stable primary and secondary carbanions the contribution of this effect is present certainly, indicating that the negative fluorine hyperconjugation is complementary to the stabilization by the accumulated inductive effect of fluorine atoms. The extent of negative hyperconjugation was found to increase in order of CF3CH2− &lt; C2F5CH2− ≈ C3F7CH2− &lt; i-C3F7CH2−, being qualitatively consistent with the elongation of the Cβ–F bond by deprotonation. The effect of α-fluorine on acidity was found to change complicatedly with the carbanion, e.g., the α-fluorine substitution in CF3CH3 strengthens acidity, no effect in (CF3)2CH2, and strengthens again acidity in (i-C3F7)2CH2. Such varying effect of α-fluorine in the polyfluorinated hydrocarbons would be caused by a subtle balance of effective electronegativity of an anionic center carbon, a varying p–p lone pair repulsion depending on the net negative charge at the formal charge center carbon, and the change in ability of β-F negative hyperconjugation caused by α-F substitution.
Synthesis and Optical Properties of Flower- and Spiky-Ball-Like Silver–Gold Nanoparticles
Authors: Kumagai Keisuke , Ishida Akito 
Published: April 2014

Abstract
Flower- and spiky-ball-like nanoparticles were selectively obtained by the reduction of H[AuCl4] and AgNO3 with ascorbic acid in the presence and absence of poly(vinylpyrrolidone) with sufficient reproducibility. The morphological switch is attributable to the selective passivation of the crystal facets of the initially grown core particles and growing nanostructures on the surfaces. The characteristic optical properties, which are due to the surface nanostructures, were studied via measurement of the extinction spectra and finite-difference time-domain simulations.
Effect of age on pulmonary embolism
Authors: Beule J. , Coldewey M. , Dippold W. , Balzer J. O. , Keller K. 
Published: April 2014

SummaryBackground: Age is an important and independent risk factor for venous thromboembolism (VTE) and pulmonary embolism (PE). The objectives of this study were to investigate the effects of aging process on PE with regard to the severity of PE, symptoms, inhospital death, history of PE, ECG, echocardiographic, and laboratory findings.Methods: 182 patients with confirmed PE were reviewed retrospectively and subdivided into 4 age groups (<60, 60–69, 70–79 and ≥ 80 years). Analysis of patients’ symptoms, history, echocardiographic, electrocardiographic and laboratory parameters was performed.Results: Proportion of women increased with age (<60 years: 41.5 % vs. 80+ years: 73.1 %, P<0.05). Also percentage of right ventricular dysfunction (RVD) was highest in eldest age group (60–69 years: 42.4 % vs. 80+ years: 75 %, P<0.05). Systolic pulmonary artery pressure (sPAP) was significantly higher in the 80+ years age group. The sPAP was constant from the <60 years group (29.0 ± 17.4 mmHg) to the 60–69 years group (27.4 ± 19.3 mmHg), and increased from the 60–69 years and 70–79 years group (33.8 ± 17.5 mmHg) to the 80+ years groups (44.3 ± 14.3 mmHg) (<60 vs. 80+ and 60–69 vs. 80+ years: respectively P<0.001 and 70–79 vs. 80+ years: P<0.05).Regression model for PE patients 80years showed an association between age 80+ and female gender (OR, 2.53; 95%CI: 1.07–5.99, p<0.05), right bundle branch block (OR, 3.07; 95%CI: 1.05–9.02, p<0.05), RVD (OR, 2.53; 95%CI: 1.07–6.00, p<0.05) and sPAP (OR, 1.05; 95%CI: 1.02–1.08, p<0.001). Pearson correlation matrix revealed a significant correlation between age and sPAP (r=0.30, P<0.001).Conclusions: Right ventricular load at acute PE event, evident from RVD and elevated sPAP, increases with age. RVD is connected with higher mortality in PE patients. High sPAP at acute PE event is one of the well-known risk factors for the development of chronic thromboembolic pulmonary hypertension in long-term. Proportion of female PE patients increases with age.
Curious stories surrounding the discovery and development of conventional antithrombotics
Authors: Haug M. 
Published: April 2014

ZusammenfassungDie Entdeckung eines therapeutischen Effektes war früher meist ein Zufallsereignis. Vielfach war der Weg bis zur Anwendung lang und steinig und nicht selten von merkwürdigen Geschichten begleitet, so bei den Antithrombotika Heparin, Aspirin und Warfarin.Heparin: Wem gebührt die Anerkennung als Entdecker? Dem Studenten Jay McLean, der neben den gesuchten thromboplastisch wirksamen Cephalin-Komponenten zufällig eine gerinnungshemmende Komponente fand? Oder seinem Chef, der die „zufällige Entdeckung“ McLeans später aufgriff und eben-falls gerinnungshemmende Komponenten isolierte, die sich jedoch chemisch von den McLean´schen unterschieden und zur Ausgangssubstanz des heutigen Heparins wurden?Aspirin: Als schmerz- und fiebersenkendes Mittel längst bekannt, erfuhr es eine zweite Karriere in der kardiovaskulären Medizin. Erst 1967 erkannte man, dass die Plättchenaktivität inhibiert wird. Die zweite Karriere begann mit der Zulassung für TIA und Herzinfarkt anfangs 1980. Bis dato unbekannt war die Geschichte des Dr. Craven, der bereits 1950 in „obskuren“ Zeitschriften seine Beobachtung publizierte, dass alle seine unter Aspirin stehenden Patienten von Herzinfarkt verschont blieben.Warfarin:Um 1920 starben tausende Rinder in Nordamerika an inneren Blutungen. Die Ursache fand man im Verzehr des gelagerten „sweet clover“. Erst nach Jahren hatte man die Erklärung: die Umwandlung des ungiftigen Coumarin im Heu in das gerinnungshemmende Dicoumarol durch Pilzinfektion. Bald folgte die Synthese und damit auch der klinische Einsatz als Antithrombotikum. Viel größeren Erfolg aber hatte die Substanz als Rattengift mit dem Namen Warfarin. Die erneute Anwendung beim Menschen erfolgte erst wieder, nachdem ein Soldat seinen Suizidver-such durch Vitamin K-Gabe überstanden hatte.
Infant Self-Regulation and Early Childhood Media Exposure
Authors: Radesky Jenny S. , Silverstein Michael , Zuckerman Barry , Christakis Dimitri A. 
Published: April 2014

OBJECTIVES:
Examine prospective associations between parent-reported early childhood self-regulation problems and media exposure (television and video viewing) at 2 years. We hypothesized that children with poor self-regulation would consume more media, possibly as a parent coping strategy.

METHODS:
We used data from 7450 children in the Early Childhood Longitudinal Study–Birth Cohort. When children were 9 months and 2 years old, parents completed the Infant Toddler Symptom Checklist (ITSC), a validated scale of self-regulation. With daily media use at 2 years as our outcome, we conducted weighted multivariable regression analyses, controlling for child, maternal, and household characteristics.

RESULTS:
Children watched an average of 2.3 hours per day (SD 1.9) of media at age 2 years. Infants with poor self-regulation (9-month ITSC score ≥3) viewed 0.23 hour per day (95% confidence interval [CI] 0.12–0.35) more media at 2 years compared with those with 9-month ITSC score of 0 to 2; this remained significant in adjusted models (0.15 hour per day [95% CI 0.02–0.28]). Children rated as having persistent self-regulation problems (ITSC ≥3 at both 9 months and 2 years) were even more likely to consume media at age 2 (adjusted β 0.21 hour per day [95% CI 0.03–0.39]; adjusted odds ratio for &gt;2 hours per day 1.40 [95% CI 1.14–1.71]). These associations were slightly stronger in low socioeconomic status and English-speaking households.

CONCLUSIONS:
Early childhood self-regulation problems are associated with mildly increased media exposure, even after controlling for important confounding variables. Understanding this relationship may provide insight into helping parents reduce their children’s screen time.
Injury Among Children and Young Adults With Epilepsy
Authors: Prasad Vibhore , Kendrick Denise , Sayal Kapil , Thomas Sara L. , West Joe 
Published: April 2014

OBJECTIVE:
To investigate whether children and young adults with epilepsy are at a greater risk of fracture, thermal injury, or poisoning than those without.

METHODS:
A cohort study was conducted by using the Clinical Practice Research Datalink (1987–2009), a longitudinal database containing primary care records. A total of 11 934 people with epilepsy and 46 598 without, aged between 1 and 24 years at diagnosis, were followed for a median (interquartile range) of 2.6 (0.8–5.9) years. The risk of fractures (including long bone fractures), thermal injuries, and poisonings (including medicinal and nonmedicinal poisonings) was estimated.

RESULTS:
Adjusting for age, gender, Strategic Health Authority region, deprivation, and calendar year at study entry (and, for medicinal poisonings, behavior disorder), people with epilepsy had an 18% increase in risk of fracture (hazard ratio [HR] = 1.18; 95% confidence interval [CI], 1.09–1.27), a 23% increase in risk of long bone fracture (HR = 1.23; 95% CI, 1.10–1.38), a 49% increase in risk of thermal injury (HR = 1.49; 95% CI, 1.27–1.75), and more than twice the risk of poisoning (HR = 2.47; 95% CI, 2.15–2.84), which was limited to poisoning from medicinal products (medicinal HR = 2.54; 95% CI, 2.16–2.99; nonmedicinal HR = 0.96; 95% CI, 0.61–1.52).

CONCLUSIONS:
Children and young adults with epilepsy are at a greater risk of fracture, thermal injury, and poisoning than those without. The greatest risk is from medicinal poisonings. Doctors and other health care professionals should provide injury and poison prevention advice at diagnosis and epilepsy reviews.
Television Viewing, Bedroom Television, and Sleep Duration From Infancy to Mid-Childhood
Authors: Cespedes Elizabeth M. , Gillman Matthew W. , Kleinman Ken , Rifas-Shiman Sheryl L. , Redline Susan , Taveras Elsie M. 
Published: April 2014

BACKGROUND:
Television and insufficient sleep are associated with poor mental and physical health. This study assessed associations of TV viewing and bedroom TV with sleep duration from infancy to midchildhood.

METHOD:
We studied 1864 children in Project Viva. Parents reported children’s average daily TV viewing and sleep (at 6 months and annually from 1–7 years) and the presence of a bedroom TV (annually 4–7 years). We used mixed effects models to assess associations of TV exposures with contemporaneous sleep, adjusting for child age, gender, race/ethnicity, maternal education, and income.

RESULTS:
Six hundred forty-three children (35%) were racial/ethnic minorities; 37% of households had incomes ≤$70 000. From 6 months to 7 years, mean (SD) sleep duration decreased from 12.2 (2.0) hours to 9.8 (0.9) hours per day; TV viewing increased from 0.9 (1.2) hours to 1.6 (1.0) hours per day. At 4 years, 17% had a bedroom TV, rising to 23% at 7 years. Each 1 hour per day increase in lifetime TV viewing was associated with 7 minutes per day (95% confidence interval [CI]: 4 to 10) shorter sleep. The association of bedroom TV varied by race/ethnicity; bedroom TV was associated with 31 minutes per day shorter sleep (95% CI: 16 to 45) among racial/ethnic minority children, but not among white, non-Hispanic children (8 fewer minutes per day [95% CI: −19 to 2]).

CONCLUSIONS:
More TV viewing, and, among racial/ethnic minority children, the presence of a bedroom TV, were associated with shorter sleep from infancy to midchildhood.
Orthodontic Treatment of a Patient with Hypoglossia
Authors: Ogawa Takuya , Sato Chiemi , Kawakubo Naomi , Moriyama Keiji 
Published: April 2014

Objective The aim of this case study was to provide a detailed report of the orthodontic approach used in treating a Japanese patient with congenital hypoglossia. Patient The patient was a 6-year-old girl with hypoglossia, micrognathia, congenital absence of three incisors, and a telescopic occlusion accompanied by an extremely narrow lower arch. She had no limb anomalies, and her speech was normal. Results Bite opening and mandibular widening from the early mixed dentition dramatically improved the extremely constricted mandible and telescopic occlusion. Cephalometric tracings taken from the beginning to the end of active treatment revealed substantial forward and downward growth in the mandible over time, which may have contributed to correction of the intermaxillary relationship. Conclusions Treatment of telescopic occlusion by bite opening and mandibular widening from the early mixed dentition may be effective in facilitating mandibular growth acceleration. An acceptable intermaxillary occlusal relationship and improvement of profile were achieved by an orthodontic approach in this case.
Physical Dysfunction and Nonorganic Signs in Patients With Chronic Neck Pain: Exploratory Study Into Interobserver Reliability and Construct Validity
Authors: Jorritsma Wim , Dijkstra Pieter U. , De Vries Grietje E. , Geertzen Jan H.B. , Reneman Michiel F. 
Published: April 2014

Study Design Repeated-measurement design. Objectives To explore interobserver reliability of the modified physical dysfunction severity (mPDS) as a measure for impairment of the cervical spine and the modified cervical nonorganic signs (mcNOS) as a measure for behavioral signs, and to explore construct validity of the mPDS and mcNOS. Background The PDS has been used for evaluation of treatment efficacy in controlled trials in primary care. The cervical nonorganic signs were developed to assess illness behavior in patients with neck pain. Methods Two observers independently assessed the mPDS and mcNOS in 51 patients with chronic neck pain in an outpatient tertiary rehabilitation setting, with a 3-week interval between assessments. Interobserver reliability for total scores of the mPDS and mcNOS was expressed as an intraclass correlation coefficient. Interobserver agreement for individual mcNOS tests was calculated as absolute agreement and Cohen kappa. Construct validity was expressed as Spearman correlation between the mPDS and mcNOS with the Neck Pain and Disability Scale and numeric pain rating scale for pain. Results The interobserver reliability of the mPDS and mcNOS had intraclass correlation coefficients of 0.72 and 0.78, respectively. Agreement for individual mcNOS tests ranged from 63% to 88%, and kappa values ranged from 0.14 to 0.54. Correlation with the Neck Pain and Disability Scale was 0.26 for the mPDS and 0.49 for the mcNOS, and the correlation with the numeric pain rating scale was 0.32 for the mPDS and 0.37 for the mcNOS. Conclusion Interobserver reliability of both the mPDS and mcNOS was acceptable. The interobserver agreement for the individual mcNOS tests ranged from poor to acceptable. Construct validity of the mPDS and mcNOS appeared satisfactory. J Orthop Sports Phys Ther 2014;44(5):366–376. Epub 14 April 2014. doi:10.2519/jospt.2014.4715
DJ stent - boon or curse?
Authors: Agrawal AS , Rao S , Gupta AO 
Published: April 2014

DJ stent is considered as a boon by the urologist but without proper knowledge it turns to be curse for the patient. We report a case of a 34 year old man who developed vesical calculus secondary to DJ stent in a short span of 6-8 months. He underwent cystolithotomy for removal of the vesical calculus along with the DJ stent. Journal of College of Medical Sciences-Nepal, 2013, Vol-9, No-3, 55-59 DOI: http://dx.doi.org/10.3126/jcmsn.v9i3.10224
Faut-il s'inquiéter de la baisse du niveau des aquifères ?
Authors: Amigues Jean-Pierre , Favard Pascal , Moreaux Michel 
Published: April 2014

Is there Cause for Concern over the Drop in Aquifer Levels ?
by Jean-Pierre Amigues, Pascal Favard and Michel Moreaux
This paper analyses the problems raised when managing continental aquifers replenished by the trickledown of surface water. These aquifers can be regarded as natural wells with a certain amount of regeneration capacity. The theory developed in this paper is that aquifers are gradually depleted due to their being used as wells. This is shown using different assumptions for the cost differences between using ground water reserves and surface water in a model that endogenises the labour supply required to exploit the resource. Our findings are shown to be robust by a thorough analysis of the model’s different parameter configurations (initial level of reserves, importance of replenishment and demand for the resource).