bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduction of Regulatory T Cells by Mogamulizumab, a Defucosylated Anti-CC Chemokine Receptor 4 Antibody, in Patients with Aggressive/Refractory Mycosis Fungoides and Sézary Syndrome
Authors: Ni Xiao , Jorgensen Jeffrey L. , Goswami Meghali , Challagundla Pramoda , Decker William K. , Kim Youn H. , Duvic Madeleine A. 
Published: November 2014

AbstractPurpose: The CC chemokine receptor 4 (CCR4) is expressed on malignant T cells in cutaneous T-cell lymphoma (CTCL) as well as on regulatory T cells (Treg). When mogamulizumab, a defucosylated monoclonal antibody, binds to CCR4, it induces antibody-dependent cellular cytotoxicity against CCR4+ malignant T cells. The goal of this study was to determine the effect of mogamulizumab on CCR4+ Tregs in patients with CTCL.Experimental Design: Peripheral blood of 24 patients with CTCL participating in a phase I/II trial was analyzed for CCR4 expression on different T-cell subsets by flow cytometry, before and after one course of mogamulizumab. The number and function of natural killer (NK) cells were also analyzed. Lesional biopsies were examined for CCR4, Foxp3, and CD16 expression by immunohistochemistry.Results: Malignant T cells in peripheral blood were 20.8%–100% positive for CCR4 at baseline. Fourteen patients who achieved a response in blood had high baseline CCR4 expression on malignant T cells. Tregs in blood were 58.6% to 100% positive for CCR4 at baseline and showed decreased numbers and CCR4 expression after treatment. CD8+ T cells in blood were 3.2% to 23.2% positive for CCR4 at baseline and showed limited reduction of CCR4 expression with increased percentages of CD8+ T cells after treatment. Of 14 patients tested for NK cells in blood, 10 showed increased percentages after treatment. Four of 6 patients tested showed increased NK cell cytotoxicity. Sixteen of 18 patients who had CCR4+ lymphocytes in baseline lesions showed decreased numbers after treatment.Conclusions: Mogamulizumab reduces levels of CCR4+ malignant T cells and also CCR4+ Tregs in patients with CTCL, which may in turn improve immune profiles. Clin Cancer Res; 21(2); 274–85. ©2014 AACR.
Preclinical Pharmacokinetics, Tolerability, and Pharmacodynamics of Metuzumab, a Novel CD147 Human–Mouse Chimeric and Glycoengineered Antibody
Authors: Zhang Zheng , Zhang Yang , Sun Qian , Feng Fei , Huhe Muren , Mi Li , Chen Zhinan 
Published: November 2014

Abstract
Metuzumab is an affinity-optimized and nonfucosylated anti-CD147 human–mouse chimeric IgG1 monoclonal antibody with enhanced antibody-dependent cellular cytotoxicity (ADCC). The purpose of this study was to characterize the pharmacokinetics, safety, and antitumor activities of metuzumab in mouse, rat, and monkey. The ADCC activity was assessed by a lactate dehydrogenase release assay. The pharmacokinetics of metuzumab were determined in Sprague–Dawley rats and in cynomolgus monkeys. Single- and repeat-dose toxicology studies of the i.v. administration of high-dose metuzumab were conducted in cynomolgus monkeys. Mice bearing human tumor xenografts were used to evaluate the antitumor efficacy of metuzumab. The ADCC potency of metuzumab was enhanced compared with the nonglycoengineered parental antibody. Metuzumab also effectively inhibited tumor growth in A549 and NCI-H520 xenograft models. In the monkey model, the total clearance of metuzumab decreased with increasing dose. The nonspecific clearance in monkeys was estimated to be 0.53 to 0.92 mL/h/kg. In single- and repeat-dose toxicology studies in cynomolgus monkeys, metuzumab did not induce any distinct or novel adverse findings and was well tolerated at all tested doses. These preclinical safety data facilitated the initiation of an ongoing clinical trial of metuzumab for the treatment of non–small cell lung cancer (NSCLC) in China. Mol Cancer Ther; 14(1); 162–73. ©2014 AACR.
Idiopathic Accelerated Idioventricular Rhythm or Ventricular Tachycardia Originating From the Right Bundle Branch
Authors: Chen Minglong , Gu Kai , Yang Bing , Chen Hongwu , Ju Weizhu , Zhang Fengxiang , Yang Gang , Li Mingfang , Lu Xinzheng , Cao Kejiang , Ouyang Feifan 
Published: November 2014

Background—
Accelerated idioventricular rhythm (AIVR) or ventricular tachycardia (VT) originating from the right bundle branch (RBB) is rare and published clinical data on such arrhythmia are scarce. In this study, we will describe the clinical manifestations, diagnosis, and management of a cohort of patients with this novel arrhythmia.

Methods and Results—
Eight patients (5 men; median age, 25 years) with RBB-AIVR/VT were consecutively enrolled in the study. Pharmacological testing, exercise treadmill testing, electrophysiological study, and catheter ablation were performed in the study patients, and ECG features were characterized. All RBB-AIVR/VTs were of typical left bundle-branch block morphology with atrioventricular dissociation. The arrhythmias, which demonstrated chronotropic variability, were often isorhythmic with sinus rhythm and were accelerated by physical exercise, stress, and intravenous isoprenaline infusion. The rate of RBB-AIVR/VT varied from 45 to 200 beats per minute. Two patients experienced syncope, and 3 had impaired left ventricular function. Metoprolol was proven to be the most effective drug to decelerate the arrhythmia rate and relieve symptoms. Electrophysiology study was performed in 5 patients and the earliest activation with a sharp RBB potential was localized in the mid or distal RBB area. Catheter ablation terminated the arrhythmia with subsequent RBB block morphology during sinus rhythm. During follow-up, patients’ symptoms were controlled with normalization of left ventricular function either on metoprolol or by catheter ablation.

Conclusions—
RBB-AIVR/VT is an unusual type of ventricular arrhythmia. It can result in significant symptoms and depressed ventricular function and can be successfully treated with catheter ablation.
Embolic Strokes of Undetermined Source in the Athens Stroke Registry
Authors: Ntaios George , Papavasileiou Vasileios , Milionis Haralambos , Makaritsis Konstantinos , Manios Efstathios , Spengos Konstantinos , Michel Patrik , Vemmos Konstantinos 
Published: November 2014

Background and Purpose—
A new clinical construct termed embolic stroke of undetermined source (ESUS) was recently introduced, but no such population has been described yet. Our aim is to provide a detailed descriptive analysis of an ESUS population derived from a large prospective ischemic stroke registry using the proposed diagnostic criteria.

Methods—
The criteria proposed by the Cryptogenic Stroke/ESUS International Working Group were applied to the Athens Stroke Registry to identify all ESUS patients. ESUS was defined as a radiologically confirmed nonlacunar brain infarct in the absence of (a) extracranial or intracranial atherosclerosis causing ≥50% luminal stenosis in arteries supplying the ischemic area, (b) major-risk cardioembolic source, and (c) any other specific cause of stroke.

Results—
Among 2735 patients admitted between 1992 and 2011, 275 (10.0%) were classified as ESUS. In the majority of ESUS (74.2%), symptoms were maximal at onset. ESUS were of moderate severity (median National Institute Health Stroke Scale score, 5). The most prevalent risk factor was arterial hypertension (64.7%), and 50.9% of patients were dyslipidemic. Among potential causes of the ESUS, covert atrial fibrillation (AF) was the most prevalent: in 30 (10.9%) patients, AF was diagnosed during hospitalization for stroke recurrence, whereas in 50 (18.2%) patients AF was detected after repeated ECG monitoring during follow-up. Also, covert AF was strongly suggested in 38 patients (13.8%) but never recorded.

Conclusions—
About 10% of patients with first-ever ischemic stroke met criteria for ESUS; covert paroxysmal AF seems to be a frequent cause of ESUS.
Graph Degree Sequence Solely Determines the Expected Hopfield Network Pattern Stability
Authors: Berend Daniel , Dolev Shlomi , Hanemann Ariel 
Published: November 2014

We analyze the effect of network topology on the pattern stability of the Hopfield neural network in the case of general graphs. The patterns are randomly selected from a uniform distribution. We start the Hopfield procedure from some pattern v. An error in an entry e of v is the situation where, if the procedure is started at e, the value of e flips. Such an entry is an instability point. Note that we disregard the value at e by the end of the procedure, as well as what happens if we start the procedure from another pattern [Formula: see text] or another entry [Formula: see text] of v. We measure the instability of the system by the expected total number of instability points of all the patterns. Our main result is that the instability of the system does not depend on the exact topology of the underlying graph, but rather only on its degree sequence. Moreover, for a large number of nodes, the instability can be approximated by [Formula: see text], where [Formula: see text] is the standard normal distribution function and [Formula: see text] are the degrees of the nodes.
Two new species of Dichorisandra (Commelinaceae) from Rio de Janeiro and comments on the two species included in Vellozo’s “Flora Fluminensis”
Authors: Aona Lidyanne Yuriko Saleme , BITTRICH VOLKER , AMARAL Maria DO CARMO E. 
Published: November 2014

Two new species of Dichorisandra collected in Rio de Janeiro state are described based on studies in the field, herbarium specimens and cultivated plants. Dichorisandra odorata can be distinguished by its small stature, leaves congested at the apex of the stems, with the lamina densely pilose on both sides, fragrant flowers (unusual for the genus), six anthers with pilose connectives and dehiscent by an apical pore; Dichorisandra nana resembles D. thyrsiflora by the presence of six yellow anthers dehiscent by apical pores, however it differs being smaller, reaching only 30 cm tall, and by the position of the stamens in relation to the petals. Illustrations of the species, comparisons with species looking morphologically similar, discussion of the diagnostic characters, as well as their conservation status are presented. Vellozo´s Flora Fluminensis includes two names that belong to Dichorisandra, both treated under the genus Convallaria. The first one, C. diffusa, is a synonym of D. hexandra while the other, thought by Vellozo to be C. racemosa (= Maianthemum racemosum), is in fact D. thyrsiflora.
Future Hydrological Regimes in the Upper Indus Basin: A Case Study from a High-Altitude Glacierized Catchment
Authors: Soncini Andrea , Bocchiola Daniele , Confortola Gabriele , Bianchi Alberto , Rosso Renzo , Mayer Christoph , Lambrecht Astrid , Palazzi Elisa , Smiraglia Claudio , Diolaiuti Guglielmina 
Published: November 2014

Abstract
The mountain regions of the Hindu Kush, Karakoram, and Himalayas (HKH) are considered Earth’s “third pole,” and water from there plays an essential role for downstream populations. The dynamics of glaciers in Karakoram are complex, and in recent decades the area has experienced unchanged ice cover, despite rapid decline elsewhere in the world (the Karakoram anomaly). Assessment of future water resources and hydrological variability under climate change in this area is greatly needed, but the hydrology of these high-altitude catchments is still poorly studied and little understood. This study focuses on a particular watershed, the Shigar River with the control section at Shigar (about 7000 km2), nested within the upper Indus basin and fed by seasonal melt from two major glaciers (Baltoro and Biafo). Hydrological, meteorological, and glaciological data gathered during 3 years of field campaigns (2011–13) are used to set up a hydrological model, providing a depiction of instream flows, snowmelt, and ice cover thickness. The model is used to assess changes of the hydrological cycle until 2100, via climate projections provided by three state-of-the-art global climate models used in the recent IPCC Fifth Assessment Report under the representative concentration pathway (RCP) emission scenarios RCP2.6, RCP4.5, and RCP8.5. Under all RCPs, future flows are predicted to increase until midcentury and then to decrease, but remaining mostly higher than control run values. Snowmelt is projected to occur earlier, while the ice melt component is expected to increase, with ice thinning considerably and even disappearing below 4000 m MSL until 2100.
Quantifying and Interpreting Striations in a Subtropical Gyre: A Spectral Perspective
Authors: Chen Ru , Flierl Glenn R. , Wunsch Carl 
Published: November 2014

AbstractThe amplitude, origin, and direction of striations in the subtropical gyre are investigated using simulated and analytical multidimensional spectra. Striations, defined as banded structures in the low-frequency motions, account for a noticeable percentage of zonal velocity variability in the east North Pacific (ENP: 25°–42°N, 150°–130°W) and central North Pacific (CNP: 10°–22°N, 132°E–162°W) regions in an eddying global ocean model. Thus, they likely are nonnegligible in mixing and transport processes. Striations in the ENP region are nonzonal and are embedded in the nonzonal gyre flow, whereas striations in the CNP region are more zonal, as are the mean gyre flows. An idealized 1.5-layer model shows the gyre flow partially determines their directions, which qualitatively resemble those in the global eddying model. In the linear limit, structures are quasi-stationary (frequency ω → 0) linear Rossby waves and the gyre flow influences the direction by influencing the nature of the zero Rossby wave frequency curve. In the nonlinear regime, striations are consistent with the nondispersively propagating eddies, whose low-frequency component has banded structures. The gyre flow influences the striation direction by changing the eddy propagation direction. Their origin in the nonlinear regime is consistent with the existence of a nondispersive line in the frequency–wavenumber spectra. This study does not exclude other striation mechanisms from literature, considering that the interpretations here are based on an idealized model and only from a spectral perspective.
Oceanic Boundary Conditions for Jakobshavn Glacier. Part II: Provenance and Sources of Variability of Disko Bay and Ilulissat Icefjord Waters, 1990–2011
Authors: Gladish Carl V. , Holland David M. , Lee Craig M. 
Published: November 2014

AbstractJakobshavn Glacier, west Greenland, has responded to temperature changes in Ilulissat Icefjord, into which it terminates. Basin waters in this fjord exchange with neighboring Disko Bay waters of a particular density at least once per year. This study determined the provenance of this isopycnic layer for 1990–2011 using hydrographic data from Cape Farewell to Baffin Bay. The warm Atlantic-origin core of the West Greenland Current never filled deep Disko Bay or entered the fjord basin because of bathymetric impediments on the west Greenland shelf. Instead, equal parts of Atlantic water and less-saline polar water filled the fjord basin and bathed Jakobshavn Glacier. The polar water fraction was often traceable to the East/West Greenland Current but sometimes to the colder Baffin Current. The huge annual temperature cycle on West Greenland Current isopycnals did not propagate into deep Disko Bay or the fjord basin because isopycnals over the west Greenland shelf were depressed during the warm autumn/winter phase of the cycle.Ilulissat Icefjord basin waters were anomalously cool in summer 2010. This was not because of the record low NAO index winter of 2009/10 or atmospheric anomalies over Baffin Bay but, possibly, because of high freshwater flux through the Canadian Arctic and a weak West Greenland Current in early 2010. Together, this caused cold Baffin Current water to flood the west Greenland shelf. Subpolar gyre warming associated with the NAO anomaly in winter 2009/10 was more likely responsible for the record warm Disko Bay and Ilulissat Icefjord basin waters of 2011/12.
Postoperative Observation of Children after Endoscopic Type 1 Posterior Laryngeal Cleft Repair
Authors: Alexander Nathan S. , Liu Judy Z. , Bhushan Bharat , Holinger Lauren D. , Schroeder James W. 
Published: November 2014

ObjectivesTo report the perioperative management and surgical outcomes in a large series of pediatric patients with endoscopically repaired type 1 posterior laryngeal cleft (PLC).Study DesignCase series with chart review.SettingUrban, tertiary care, free‐standing pediatric hospital.Subjects and MethodsPatients who underwent endoscopic carbon dioxide laser–assisted repair of type 1 posterior laryngeal clefts between January 2006 and December 2012. Medical records were reviewed.ResultsFifty‐four patients (34 male) underwent repair of type 1 PLC. Median age was 25.5 months (range, 2‐120 months). Indications for repair included aspiration (n = 39; 72%), chronic bronchitis (n = 13; 24%), and stridor with feeds (n = 2; 4%). No children remained intubated postoperatively. Thirty‐three patients (61%) stayed in overnight observation (“Obs PLC”) and 21 patients (39%) stayed in the pediatric intensive care unit (“PICU PLC”) postoperatively. Between Obs PLC and PICU PLC groups, there was no significant difference in age (mean 22 vs 30 months, respectively; P =. 28). Comorbidities were similar between the groups. Symptoms improved in 41 of the 54 patients (76%). No postoperative complications were noted. Two patients required revision PLC repair. The cost of admitting a patient to a lower acuity location was estimated to be 60% less per day than cost of a PICU admission.ConclusionsThe endoscopic surgical repair of a type 1 PLC is successful and has a low morbidity and complication rate. Patients may be safely managed in an observation unit and without postoperative intubation. This approach achieved a marked cost reduction in postoperative care.
The impact of the peritoneal glucose load index on hydration status and inflammation in peritoneal dialysis patients
Authors: Hassan Kamal , Hassan Fadi , Edgem Rabia , Moshe Smadar , Hassan Shadi 
Published: November 2014

Objective To evaluate the impact of the peritoneal glucose load (PGL) on hydration status and inflammation in peritoneal dialysis (PD) patients. Methods This cross-sectional study evaluated stable PD patients using a novel PGL index (PGLI), which was calculated as the net glucose content (g) in the PD solutions administered in the daily PD prescription divided by the dry body weight (kg) assessed by whole-body bioimpedance spectroscopy. The relationship between PGLI and glycosylated haemoglobin (HbA1c), fluid overload (FO), and inflammatory markers was investigated. Results A total of 43 stable PD patients participated in the study. Significant positive correlations were found between PGLI and HbA1c, FO, plasma high sensitivity C-reactive protein (hsCRP), and plasma interleukin-6 (IL-6) levels. HbA1c, FO, plasma hsCRP and plasma IL-6 levels were significantly higher in patients with PGLI >3 g/kg/day compared with those with PGLI ≤3 g/kg/day. Conclusions PGLI values >3 g/kg/day may be associated with poor glycaemic control, over hydration and augmented inflammation. PGLI might be a useful tool for the quantitative assessment of the PGL and could be applied when managing PD patients.
Pretreatment With Caffeine Citrate to Increase Seizure Duration During Electroconvulsive Therapy
Authors: Pinkhasov Aaron , Biglow Michael , Chandra Subhash , Pica Tiffany 
Published: November 2014

Objective: Due to the shortage of parenteral caffeine and sodium benzoate, patients were pretreated with caffeine citrate to increase therapeutic seizure duration during electroconvulsive therapy (ECT). To date, no data are available on the use of caffeine citrate during ECT. This retrospective case series was done to demonstrate utilization of caffeine citrate as a substitute for caffeine and sodium benzoate in optimizing ECT. Method: Medical records were reviewed to identify patients who received ECT and caffeine citrate. Physician notes were reviewed to determine the parameters of the ECT procedure, the seizure length, and the dose of caffeine citrate. Each chart was thoroughly studied to find the relationship between seizure duration and dose of caffeine citrate. Results: Of the 12 ECT treatments utilizing caffeine citrate, 9 achieved at least 1 session lasting >30 seconds with an average seizure duration of 35 seconds. Increase in seizure duration ranged from −41% to 276% with an average increase of 48%. Only 3 treatment sessions utilizing caffeine citrate showed no increase in seizure duration. Doses ranged from 120 to 600 mg of both oral and parenteral caffeine citrate. Although increase in seizure duration was achieved for the majority of the ECT sessions, no dose–response correlation could be made. No significant adverse reactions were noted with the use of caffeine citrate during ECT. Conclusion: It was determined that, much like caffeine and sodium benzoate, caffeine citrate does increase the seizure duration. However, this response did vary due to many reasons including small sample size, concomitant medications, duration of illness, and number of ECTs they received in the past and how long ago they received the last ECT. Further research is required to elucidate the effect of these variables on seizure duration.
The Effects of Social Service Contact on Teenagers in England
Authors: Henderson Morag , Scourfield Jonathan , Cheung Sin Yi , Sharland Elaine , Sloan Luke 
Published: November 2014

Objective: This study investigated outcomes of social service contact during teenage years. Method: Secondary analysis was conducted of the Longitudinal Survey of Young People in England ( N = 15,770), using data on reported contact with social services resulting from teenagers’ behavior. Outcomes considered were educational achievement and aspiration, mental health, and locus of control. Inverse-probability-weighted regression adjustment was used to estimate the effect of social service contact. Results: There was no significant difference between those who received social service contact and those who did not for mental health outcome or aspiration to apply to university. Those with contact had lower odds of achieving good exam results or of being confident in university acceptance if sought. Results for locus of control were mixed. Conclusions: Attention is needed to the role of social services in supporting the education of young people in difficulty. Further research is needed on the outcomes of social services contact.
Nursing Staff’s Perception of Barriers in Providing End-of-Life Care to Terminally Ill Pediatric Patients in Southeast Iran
Authors: Iranmanesh Sedigheh , Banazadeh Marjan , Forozy Mansoure Azizzadeh 
Published: November 2014

Objective: To determine pediatric nurses’ perceptions of intensity, frequency occurrence, and magnitude score of selected barriers in providing pediatric end-of-life (EOL) care. Method: A translated modified version of National Survey of critical care Nurses’ s Regarding End-of-Life Care questionnaire was used to assess 151 nurses’ perceptions of intensity and frequency occurrence of barriers in caring for dying children. Results: The highest/lowest perceived barriers magnitude scores were “families not accepting poor child prognosis” (5.04) and “continuing to provide advanced treatment to dying child because of financial benefits to the hospital” (2.19). Conclusion: More high perceived barriers by nurses were family-related issues. One of the possible causes of such deficiencies was lack of palliative care (PC) education/PC units in Iran. Thus, developing EOL/PC education may enhance nurses’ knowledge/skill to face EOL care challenges.