bluuebunny/crossref_metadata_2025_split huggingface dataset:
CTLA-4 Blockade with Ipilimumab: Long-term Follow-up of 177 Patients with Metastatic Melanoma
Authors: Prieto Peter A. , Yang James C. , Sherry Richard M. , Hughes Marybeth S. , Kammula Udai S. , White Donald E. , Levy Catherine L. , Rosenberg Steven A. , Phan Giao Q. 
Published: January 2012

Abstract
Purpose: Treatment with ipilimumab can cause objective tumor responses in patients with metastatic melanoma. We have treated 177 evaluable patients in three clinical trials and have long-term follow-up to evaluate the durability of responses.
Experimental Design: Patients with metastatic melanoma were treated in three trials from 2002 to 2005. In protocol 1, 56 patients received ipilimumab with gp100 peptides. In protocol 2, 36 patients received ipilimumab with interleukin-2. In protocol 3, 85 patients received ipilimumab with intrapatient dose-escalation and were randomized to receive gp100 peptides. We have analyzed their long-term follow-up and survival data.
Results: With median follow-up for protocols 1, 2, and 3 being 92, 84, and 71 months, median survival was 14, 16, and 13 months with 5-year survival rates being 13%, 25%, and 23%, respectively. Patients in protocol 2 had a 17% complete response (CR) rate, compared with 7% in protocol 1 and 6% in protocol 3. These CR rates are higher than previously reported for the same trials because some patients who eventually became complete responders had continual tumor regression months to years after therapy. All but one of the 15 complete responders are ongoing at 54+ to 99+ months.
Conclusions: This report provides the longest follow-up of patients with melanoma treated with ipilimumab and shows that ipilimumab can induce durable, potentially curative tumor regression in a small percentage of patients with metastatic melanoma. The combination of ipilimumab and interleukin-2 seems to have an increased CR rate, but this needs to be tested in a randomized trial. Clin Cancer Res; 18(7); 2039–47. ©2012 AACR.
A Phase I Trial of Erlotinib and Concurrent Chemoradiotherapy for Stage III and IV (M0) Squamous Cell Carcinoma of the Head and Neck
Authors: Gilbert Jill , Rudek Michelle A. , Higgins Michaela J. , Zhao Ming , Bienvenu Sara , Tsottles Nancy , Wahl Richard , Forastiere Arlene , Gillison Maura 
Published: January 2012

Abstract
Purpose: Erlotinib, an orally active selective inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, has synergistic activity with radiation and with cisplatin. The EGFR is overexpressed in the majority of head and neck cancers. The primary objective of this phase I study was to determine the maximum-tolerated dose (MTD) of erlotinib in combination with low-dose daily cisplatin and radiotherapy. We also sought evidence of biologic activity of erlotinib alone using serial 18-FDG positron emission tomography (PET) imaging.
Experimental Design: Oral erlotinib was taken daily starting with a 14-day run-in and continued until radiation therapy (RT) was completed. Low-dose daily cisplatin, 6 mg/m2 i.v. was given concurrently with standard fractionation RT to a total dose of 66 to 70 Gy. Dose escalation followed a modified Fibonacci dose escalation design.
Results: Twenty-two patients were enrolled and 18 patients received therapy on protocol. MTD of the combination of erlotinib, cisplatin, and RT was not reached. The recommended phase II dose of erlotinib is 150 mg per day in combination with cisplatin and RT, the highest dose of erlotinib evaluated in this study. 18F-FDG PET showed evidence for metabolic response to single-agent erlotinib. Per PERCIST criteria, the overall metabolic response rate at day 14 was 38.8% (95% CI: 17.3–64.3). On completion of concurrent chemoradiotherapy, overall response rate derived from tumor measurements based on imaging studies was 83% for all dose levels combined.
Conclusions: Erlotinib in combination with low-dose daily cisplatin and RT is well tolerated and shows evidence of clinical efficacy. The combination should be evaluated further. Clin Cancer Res; 18(6); 1735–42. ©2012 AACR.
Ablation of Atrial Fibrillation Under Therapeutic Warfarin Reduces Periprocedural Complications
Authors: Santangeli Pasquale , Di Biase Luigi , Horton Rodney , Burkhardt J. David , Sanchez Javier , Al-Ahmad Amin , Hongo Richard , Beheiry Salwa , Bai Rong , Mohanty Prasant , Lewis William R. , Natale Andrea 
Published: January 2012

Background—
Observational data suggest that performing radiofrequency catheter ablation of atrial fibrillation (AF) under therapeutic warfarin (continuous warfarin [CW]) may reduce the periprocedural risk of complications, such as thromboembolic events, compared to warfarin discontinuation (DW) with periprocedural bridging with heparin. We systematically reviewed the available evidence on the impact of CW compared with DW on periprocedural complications of AF catheter ablation.

Methods and Results—

We searched major Web databases for studies on radiofrequency catheter ablation of AF under CW versus DW with periprocedural bridging with heparin. Data on periprocedural complications were extracted. We identified 9 studies (1 large case series indirectly compared with the latest Worldwide Survey). A total of 27 402 patients were included in the analysis (6400 undergoing ablation with CW). CW was associated with a striking decrease of thromboembolic complications (OR, 0.10; 95% CI, 0.05–0.23;
P
<0.001) and minor bleeding complications (OR, 0.38; 95% CI, 0.21–0.71;
P
=0.002) compared with DW. CW also did not increase the risk of major bleeding (OR, 0.67; 95% CI, 0.31–1.43;
P
=0.30), including cardiac tamponade (OR, 0.69; 95% CI, 0.19–2.47;
P
=0.57).

Conclusions—
There is highly consistent evidence from observational studies that a CW strategy during radiofrequency catheter ablation of AF reduces the risk of thromboembolic complications without increasing the risk of bleeding.
Temperament and its relation to social functioning in schizophrenia
Authors: Jetha Michelle K. , Goldberg Joel O. , Schmidt Louis A. 
Published: January 2012

Background: We previously noted increased shyness in stable community outpatients with schizophrenia compared to healthy controls and that shyness may be a risk factor for social functioning impairment in this population (Goldberg & Schmidt, 2001). Aims: We attempted to replicate and extend these findings by comparing the use of a brief trait measure of shyness and sociability (SS; Cheek, 1983; Cheek & Buss, 1981) with the longer Temperament and Character Inventory (TCI; Cloninger, Przybeck, Svrakic, & Wetzel, 1994) used traditionally in work to measure personality dimensions in this population. Methods: A group of stable outpatients with schizophrenia ( n = 41) and healthy controls ( n = 41) matched on age and gender were compared on the SS and TCI measures. Patients were assessed on clinical symptoms using the Positive and Negative Symptom Scale (PANSS) and on social functioning measures using a Quality of Life Scale (QLS). Results: Patients reported significantly higher shyness, retrospective inhibition and harm avoidance, and lower novelty seeking, self-directedness and cooperativeness than healthy adults, replicating previous findings. Shyness and sociability were related to conceptually linked dimensional sub-scales of the TCI and were predictive of social functioning in the patient group. Importantly, scores on these measures were unrelated to symptom profiles and explained additional variance in social functioning beyond clinical symptoms. Conclusions: These findings suggest that individual differences in trait shyness and sociability may influence social functioning in stable outpatients with schizophrenia. The results also support the use of the brief trait measures of shyness and sociability in this population.
Influence of Parenteral Nutrition Delivery System on the Development of Bloodstream Infections in Critically Ill Patients
Authors: Pontes‐Arruda Alessandro , dos Santos Maria Cecília Freitas Cesarino , Martins Laércia Ferreira , González Eddy René Rodriguez , Kliger Ruben Gustavo , Maia Marcelo , Magnan Gisele Brocco ,   for the EPICOS Study Group
Published: January 2012

Background:Parenteral nutrition (PN) is associated with an increased risk of developing bloodstream infections (BSIs) but the impact of the PN delivery system upon BSI rates remains unclear. This was an international, multicenter, prospective, randomized, open‐label, controlled trial that investigated the differences of BSIs associated with 2 different PN systems.Methods:Patients were randomly allocated in a 2:1:1 ratio to receive either PN delivered by a multichamber bag (MCB group), or by compounded PN made with olive oil (COM1 group) or with MCT/LCT (COM2 group). Blood cultures were performed to evaluate the incidence of BSIs, and catheter use data was collected to calculate CLAB and central venous catheter device use ratio (CVC‐DUR). Secondary outcomes included the development of severe sepsis/septic shock, number of intensive care unit (ICU) and hospital days, and all‐cause mortality at Day 28.Results:406 patients were included: 202 in the MCB group, 103 in the COM1 group, and 101 in the COM2 group. Baseline characteristics were well balanced between the 3 groups, BSIs were significantly higher in patients receiving compounded PN (46 BSIs for COM1+COM2 vs 34 BSIs for MCB; p = 0.03).CLAB was higher in patients receiving compounded PN (13.2 for COM1+COM2 vs 10.3 for MCB; p < 0.0001). No differences were observed for the secondary outcomes.Conclusion:Compounded PN was associated with a higher incidence of BSIs and CLABs, suggesting that the use of MCB PN may play a role in reducing the incidence of BSIs in patients who receive PN. Trial registration number: NCT00798681.
Project Risk Management in Hydropower Plant Projects
Authors: Sudirman Weddy Bernadi , Hardjomuljadi Sarwono 
Published: January 2012

The development of hydroelectric power plant is one of the efforts in utilising water resources for people’s welfare by generating the energy for electricity purpose. Nowadays, the installed capacity of hydro electric power plants is 3,529 MW from the total installed capacity 24,846 MW from various power plants owned by PT PLN (Persero) and the hydropower potential 75,000 MW all over Indonesia. Hydroelectric power plant has complex structures and involves large amounts of capital with a long-running construction period. This situation imposes uncertainty factors with considerably high risks. The construction phase is identified as a critical phase in hydropower projects where many unforeseen factors occur. Failure to manage project risks leads to significant problems for the client such as completion time delays and cost overruns. In order to prevent time delays and cost overruns in hydropower construction in PT PLN (Persero), the study on project risk management in the construction stage of hydropower plant projects had been conducted. The purpose of this study was to identify and measure the importance of construction risks and to determine the level of agreement or disagreement between the client, consultants and contractors on the ranking of construction risk in hydropower projects. The author selected the respondents from the clients, consultants and contractors’ personnel who had work experience in hydropower construction projects in PT PLN (Persero). JEL Classification: L74—Construction
Dual-targeting immunotherapy of lymphoma: potent cytotoxicity of anti-CD20/CD74 bispecific antibodies in mantle cell and other lymphomas
Authors: Gupta Pankaj , Goldenberg David M. , Rossi Edmund A. , Cardillo Thomas M. , Byrd John C. , Muthusamy Natarajan , Furman Richard R. , Chang Chien-Hsing 
Published: January 2012

AbstractWe describe the use of novel bispecific hexavalent Abs (HexAbs) to enhance anticancer immunotherapy. Two bispecific HexAbs [IgG-(Fab)4 constructed from veltuzumab (anti-CD20 IgG) and milatuzumab (anti-CD74 IgG)] show enhanced cytotoxicity in mantle cell lymphoma (MCL) and other lymphoma/leukemia cell lines, as well as patient tumor samples, without a crosslinking Ab, compared with their parental mAb counterparts, alone or in combination. The bispecific HexAbs have different properties from and are more potent than their parental mAbs in vitro. The juxtaposition of CD20 and CD74 on MCL cells by the HexAbs resulted in homotypic adhesion and triggered intracellular changes that include loss of mitochondrial transmembrane potential, production of reactive oxygen species, rapid and sustained phosphorylation of ERKs and JNK, down-regulation of pAkt and Bcl-xL, actin reorganization, and lysosomal membrane permeabilization, culminating in cell death. They also displayed different potencies in depleting lymphoma cells and normal B cells from whole blood ex vivo and significantly extended the survival of nude mice bearing MCL xenografts in a dose-dependent manner, thus indicating stability and antitumor activity in vivo. Such bispecific HexAbs may constitute a new class of therapeutic agents for improved cancer immunotherapy, as shown here for MCL and other CD20+/CD74+ malignancies.
How I treat enteropathy-associated T-cell lymphoma
Authors: Di Sabatino Antonio , Biagi Federico , Gobbi Paolo G. , Corazza Gino R. 
Published: January 2012

Abstract
Enteropathy-associated T-cell lymphoma (EATL) is a complication of celiac disease (CD). This tumor derives from the neoplastic transformation of aberrant intraepithelial T lymphocytes emerging in celiac patients unresponsive to a gluten-free diet. Poor adherence to a gluten-free diet, HLA-DQ2 homozygosity, and late diagnosis of CD are recognized as risk factors for malignant evolution of CD. Recurrence of diarrhea, unexplained weight loss, abdominal pain, fever, and night sweating should alert physicians to this complication. The suspicion of EATL should lead to an extensive diagnostic workup in which magnetic resonance enteroclysis, positron emission tomography scan, and histologic identification of lesions represent the best options. Treatment includes high-dose chemotherapy preceded by surgical resection and followed by autologous stem cell transplantation, although biologic therapies seem to be promising. Strict adherence to a gluten-free diet remains the only way to prevent EATL.
Inhibition of allergic airway responses by heparin derived oligosaccharides: identification of a tetrasaccharide sequence
Authors: Ahmed Tahir , Smith Gregory , Vlahov Iontcho , Abraham William M 
Published: January 2012

AbstractBackgroundPrevious studies showed that heparin's anti-allergic activity is molecular weight dependent and resides in oligosaccharide fractions of <2500 daltons.ObjectiveTo investigate the structural sequence of heparin's anti-allergic domain, we used nitrous acid depolymerization of porcine heparin to prepare an oligosaccharide, and then fractionated it into disaccharide, tetrasaccharide, hexasaccharide, and octasaccharide fractions. The anti-allergic activity of each oligosaccharide fraction was tested in allergic sheep.MethodsAllergic sheep without (acute responder) and with late airway responses (LAR; dual responder) were challenged withAscaris suumantigen with and without inhaled oligosaccharide pretreatment and the effects on specific lung resistance and airway hyperresponsiveness (AHR) to carbachol determined. Additional inflammatory cell recruitment studies were performed in immunized ovalbumin-challenged BALB/C mice with and without treatment.ResultsThe inhaled tetrasaccharide fraction was the minimal effective chain length to show anti-allergic activity. This fraction showed activity in both groups of sheep; it was also effective in inhibiting LAR and AHR, when administered after the antigen challenge. Tetrasaccharide failed to modify the bronchoconstrictor responses to airway smooth muscle agonists (histamine, carbachol and LTD4), and had no effect on antigen-induced histamine release in bronchoalveolar lavage fluid in sheep. In mice, inhaled tetrasaccharide also attenuated the ovalbumin-induced peribronchial inflammatory response and eosinophil influx in the bronchoalveolar lavage fluid. Chemical analysis identified the active structure to be a pentasulfated tetrasaccharide ([IdoU2S (1→4)GlcNS6S (1→4) IdoU2S (1→4) AMan-6S]) which lacked anti-coagulant activity.ConclusionsThese results demonstrate that heparin tetrasaccharide possesses potent anti-allergic and anti-inflammatory properties, and that the domains responsible for anti-allergic and anti-coagulant activity are distinctly different.
Regulation of aggregate size and pattern by adenosine and caffeine in cellular slime molds
Authors: Jaiswal Pundrik , Soldati Thierry , Thewes Sascha , Baskar Ramamurthy 
Published: January 2012

Abstract

Background
Multicellularity in cellular slime molds is achieved by aggregation of several hundreds to thousands of cells. In the model slime mold Dictyostelium discoideum, adenosine is known to increase the aggregate size and its antagonist caffeine reduces the aggregate size. However, it is not clear if the actions of adenosine and caffeine are evolutionarily conserved among other slime molds known to use structurally unrelated chemoattractants. We have examined how the known factors affecting aggregate size are modulated by adenosine and caffeine.

Result
Adenosine and caffeine induced the formation of large and small aggregates respectively, in evolutionarily distinct slime molds known to use diverse chemoattractants for their aggregation. Due to its genetic tractability, we chose D. discoideum to further investigate the factors affecting aggregate size. The changes in aggregate size are caused by the effect of the compounds on several parameters such as cell number and size, cell-cell adhesion, cAMP signal relay and cell counting mechanisms. While some of the effects of these two compounds are opposite to each other, interestingly, both compounds increase the intracellular glucose level and strengthen cell-cell adhesion. These compounds also inhibit the synthesis of cAMP phosphodiesterase (PdsA), weakening the relay of extracellular cAMP signal. Adenosine as well as caffeine rescue mutants impaired in stream formation (pde4

-
and pdiA

-
) and colony size (smlA

-
and ctnA

-
) and restore their parental aggregate size.

Conclusion
Adenosine increased the cell division timings thereby making large number of cells available for aggregation and also it marginally increased the cell size contributing to large aggregate size. Reduced cell division rates and decreased cell size in the presence of caffeine makes the aggregates smaller than controls. Both the compounds altered the speed of the chemotactic amoebae causing a variation in aggregate size. Our data strongly suggests that cytosolic glucose and extracellular cAMP levels are the other major determinants regulating aggregate size and pattern. Importantly, the aggregation process is conserved among different lineages of cellular slime molds despite using unrelated signalling molecules for aggregation.
The core and unique proteins of haloarchaea
Authors: Capes Melinda D , DasSarma Priya , DasSarma Shiladitya 
Published: January 2012

Abstract

Background
Since the first genome of a halophilic archaeon was sequenced in 2000, biologists have been advancing the understanding of genomic characteristics that allow for survival in the harsh natural environments of these organisms. An increase in protein acidity and GC-bias in the genome have been implicated as factors in tolerance to extreme salinity, desiccation, and high solar radiation. However, few previous attempts have been made to identify novel genes that would permit survival in such extreme conditions.

Results
With the recent release of several new complete haloarchaeal genome sequences, we have conducted a comprehensive comparative genomic analysis focusing on the identification of unique haloarchaeal conserved proteins that likely play key roles in environmental adaptation. Using bioinformatic methods, we have clustered 31,312 predicted proteins from nine haloarchaeal genomes into 4,455 haloarchaeal orthologous groups (HOGs). We assigned likely functions by association with established COG and KOG databases in NCBI. After identifying homologs in four additional haloarchaeal genomes, we determined that there were 784 core haloarchaeal protein clusters (cHOGs), of which 83 clusters were found primarily in haloarchaea. Further analysis found that 55 clusters were truly unique (tucHOGs) to haloarchaea and qualify as signature proteins while 28 were nearly unique (nucHOGs), the vast majority of which were coded for on the haloarchaeal chromosomes. Of the signature proteins, only one example with any predicted function, Ral, involved in desiccation/radiation tolerance in Halobacterium sp. NRC-1, was identified. Among the core clusters, 33% was predicted to function in metabolism, 25% in information transfer and storage, 10% in cell processes and signaling, and 22% belong to poorly characterized or general function groups.

Conclusion
Our studies have established conserved groups of nearly 800 protein clusters present in all haloarchaea, with a subset of 55 which are predicted to be accessory proteins that may be critical or essential for success in an extreme environment. These studies support core and signature genes and proteins as valuable concepts for understanding phylogenetic and phenotypic characteristics of coherent groups of organisms.
Lactobacillus rhamnosus GR-1 enhances NF-kappaB activation in Escherichia coli-stimulated urinary bladder cells through TLR4
Authors: Karlsson Mattias , Scherbak Nikolai , Reid Gregor , Jass Jana 
Published: January 2012

AbstractBackgroundEpithelial cells of the urinary tract recognize pathogenic bacteria through pattern recognition receptors on their surface, such as toll-like receptors (TLRs), and mount an immune response through the activation of the NF-kappaB pathway. Some uropathogenic bacteria can subvert these cellular responses, creating problems with how the host eliminates pathogens.Lactobacillusis a genus of lactic acid bacteria that are part of the microbiota and consist of many probiotic strains, some specifically for urogenital infections. Immunomodulation has emerged as an important mode of action of probiotic and commensal lactobacilli and given the importance of epithelial cells, we evaluated the effect of the urogenital probioticLactobacillus rhamnosusGR-1 on epithelial immune activation.ResultsImmune activation through the NF-kappaB pathway was initiated by stimulation of T24 urothelial cells with heat-killedEscherichia coliand this was further potentiated when cells were co-cultured with liveL. rhamnosusGR-1. Heat-killed lactobacilli were poor activators of NF-kappaB. Concomitant stimulation of bladder cells withE. coliandL. rhamnosusGR-1 increased the levels of the pro-inflammatory cytokine TNF, whereas IL-6 and CXCL8 levels were reduced. Another probiotic,L. rhamnosusGG, was also able to potentiate NF-kappaB in these cells although at a significantly reduced level compared to the GR-1 strain. The transcript numbers and protein levels of the lipopolysaccharide receptor TLR4 were significantly increased after co-stimulation withE. coliand lactobacilli compared to controls. Furthermore, inhibition of TLR4 activation by polymixin B completely blocked the lactobacilli potentiation of NF-kappaB.ConclusionsThe immunological outcome ofE. colichallenge of bladder cells was influenced by probioticL. rhamnosusGR-1, by enhancing the activation of NF-kappaB and TNF release. Thus the urogenital probioticL. rhamnosusGR-1 modulated the activation of the NF-kappaB through increased levels of TLR4 on the bladder cells and altered subsequent release of cytokines from urothelial cells. By influencing immunological factors such as TLR4, important in the process of fighting pathogens, lactobacilli could facilitate pathogen recognition and infection clearance.