bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sorafenib in Combination With Capecitabine: An Oral Regimen for Patients With HER2-Negative Locally Advanced or Metastatic Breast Cancer
Authors: Baselga José , Segalla José Getúlio Martins , Roché Henri , del Giglio Auro , Pinczowski Hélio , Ciruelos Eva M. , Filho Sebastião Cabral , Gómez Patricia , Van Eyll Brigitte , Bermejo Begoña , Llombart Antonio , Garicochea Bernardo , Durán Miguel Ángel Climent , Hoff Paulo Marcelo Gehm , Espié Marc , de Moraes Andre Augusto Junior Gemeinder , Ribeiro Ronaldo Albuquerque , Mathias Clarissa , Gil Gil Miguel , Ojeda Belén , Morales Josefa , Kwon Ro Sunhee , Li Shell , Costa Frederico 
Published: March 2012

Purpose Sorafenib is a multikinase inhibitor with antiangiogenic/antiproliferative activity. A randomized, double-blind, placebo-controlled phase IIB trial assessed sorafenib with capecitabine for locally advanced or metastatic human epidermal growth factor receptor 2 (HER2) –negative breast cancer. Patients and Methods Patients were randomly assigned to first- or second-line capecitabine 1,000 mg/m2 orally twice a day for days 1 to 14 of every 21-day cycle with sorafenib 400 mg orally twice a day or placebo. The primary end point was progression-free survival (PFS). Results In total, 229 patients were enrolled. The addition of sorafenib to capecitabine resulted in a significant improvement in PFS versus placebo (median, 6.4 v 4.1 months; hazard ratio [HR], 0.58; 95% CI, 0.41 to 0.81; P = .001) with sorafenib favored across subgroups, including first-line (HR, 0.50; 95% CI, 0.30 to 0.82) and second-line (HR, 0.65; 95% CI, 0.41 to 1.04) treatment. There was no significant improvement for overall survival (median, 22.2 v 20.9 months; HR, 0.86; 95% CI, 0.61 to 1.23; P = .42) and overall response (38% v 31%; P = .25). Toxicities (sorafenib v placebo) of any grade included rash (22% v 8%), diarrhea (58% v 30%), mucosal inflammation (33% v 21%), neutropenia (13% v 4%), hypertension (18% v 12%), and hand-foot skin reaction/hand- foot syndrome (HFSR/HFS; 90% v 66%); grade 3 to 4 toxicities were comparable between treatment arms except HFSR/HFS (44% v 14%). Reasons for discontinuation in the sorafenib and placebo arms included disease progression (63% v 82%, respectively), adverse events (20% v 9%, respectively), and death (0% v 1%, respectively). Conclusion Addition of sorafenib to capecitabine improved PFS in patients with HER2-negative advanced breast cancer. The dose of sorafenib used in this trial resulted in unacceptable toxicity for many patients. A phase III confirmatory trial has been initiated with a reduced sorafenib dose.
Screening for Distress and Unmet Needs in Patients With Cancer: Review and Recommendations
Authors: Carlson Linda E. , Waller Amy , Mitchell Alex J. 
Published: March 2012

Purpose This review summarizes the need for and process of screening for distress and assessing unmet needs of patients with cancer as well as the possible benefits of implementing screening. Methods Three areas of the relevant literature were reviewed and summarized using structured literature searches: psychometric properties of commonly used distress screening tools, psychometric properties of relevant unmet needs assessment tools, and implementation of distress screening programs that assessed patient-reported outcomes (PROs). Results Distress and unmet needs are common problems in cancer settings, and programs that routinely screen for and treat distress are feasible, particularly when staff are supported and links with specialist psychosocial services exist. Many distress screening and unmet need tools have been subject to preliminary validation, but few have been compared head to head in independent centers and in different stages of cancer. Research investigating the overall effectiveness of screening for distress in terms of improved recognition and treatment of distress and associated problems is not yet conclusive, but screening seems to improve communication between patients and clinicians and may enhance psychosocial referrals. Direct effects on quality of life are uncertain, but screening may help improve discussion of quality-of-life issues. Conclusion Involving all stakeholders and frontline clinicians when planning screening for distress programs is recommended. Training frontline staff to deliver screening programs is crucial, and continuing to rigorously evaluate outcomes, including PROs, process of care, referrals, and economic costs and benefits is essential.
Zwischen ‚antemurale‘ und ‚wspólny dom‘: Polen und Europa im Denken Józef Tischners
Authors: Lang Ulrike 
Published: March 2012

Abstract
This article reflects on Józef Tischner’s changing concepts of Europe from the mid 1980s until the late 1990s in the context of Polish discourses on Europe in the second half of the 20th century. It is argued that the Polish adoption of democracy in 1989 had a tremendous impact on the image of Europe as shaped by Tischner. In the 1980s – in the face of social and economic agony – the ‘priest of Solidarność’ draws upon the Romantic and messianistic imagery of Poland as the ‘bulwark of Christianity’. He therefore claims Polish moral and spiritual superiority not only over the Soviet Union but over Central and Western Europe as well. Hence, Tischner does not engage in myths of Central European unity frequently being discussed at the time. Right after the ‘annus mirabilis’ of 1989 Tischner swiftly turns to the new hegemonial paradigm of liberalism and pragmatism. Though maintaining an image of Europe as a community of shared Christian values, Tischner steps up in favour of capitalism and democratic pluralism, hereby following the example set by the ‘West’. Consequently, he became one of the most vehement critics of Polish neo-martyrdom of the 1990s. By applying the metaphor of a ‘common home’ to a unifying Europe, Tischner not only supports Poland’s joining of the EU, but also develops a prospect for a shared European future. Józef Tischner’s ideas of Europe can therefore be traced along the outlines of Polish discourses on Europe evolving from ‘myth’ to ‘metaphor’ as described by Walter Koschmal (2006).
Verbalkomplexe im Bulgarischen
Authors: Pitsch Hagen 
Published: March 2012

Abstract
The paper develops an analysis of verbal complexes in Bulgarian. It is argued that both šte and da are modal markers which become part of the verbal complex in a zone between morphology (lexicon) and syntax. The same is claimed for object clitics. The CP projection is proposed to be the place of existential quantification of the verbal event variable already on the representational level of Semantic Form (SF), going hand in hand with existential presupposition (če‑sentences). Da‑expressions, on the other hand, are construed as mere ModPs from which it follows that there is no existential quantification on SF. The latter is argued to take place only on the extra-grammatical level of Conceptual Structure. The paper also gives a lexical account for the different selectional properties of matrix verbs with respect to da‑expressions and/or če‑sentences.
Methicillin-Resistant and Susceptible Staphylococcus aureus Bacteremia and Meningitis in Preterm Infants
Authors: Shane Andi L. , Hansen Nellie I. , Stoll Barbara J. , Bell Edward F. , Sánchez Pablo J. , Shankaran Seetha , Laptook Abbot R. , Das Abhik , Walsh Michele C. , Hale Ellen C. , Newman Nancy S. , Schrag Stephanie J. , Higgins Rosemary D. ,   for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network
Published: March 2012

BACKGROUND:
Data are limited on the impact of methicillin-resistant Staphylococcus aureus (MRSA) on morbidity and mortality among very low birth weight (VLBW) infants with S aureus (SA) bacteremia and/or meningitis (B/M).

METHODS:
Neonatal data for VLBW infants (birth weight 401–1500 g) born January 1, 2006, to December 31, 2008, who received care at centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network were collected prospectively. Early-onset (≤72 hours after birth) and late-onset (&gt;72 hours) infections were defined by blood or cerebrospinal fluid cultures and antibiotic treatment of ≥5 days (or death &lt;5 days with intent to treat). Outcomes were compared for infants with MRSA versus methicillin-susceptible S aureus (MSSA) B/M.

RESULTS:
Of 8444 infants who survived &gt;3 days, 316 (3.7%) had SA B/M. Eighty-eight had MRSA (1% of all infants, 28% of infants with SA); 228 had MSSA (2.7% of all infants, 72% of infants with SA). No infant had both MRSA and MSSA B/M. Ninety-nine percent of MRSA infections were late-onset. The percent of infants with MRSA varied by center (P &lt; .001) with 9 of 20 centers reporting no cases. Need for mechanical ventilation, diagnosis of respiratory distress syndrome, necrotizing enterocolitis, and other morbidities did not differ between infants with MRSA and MSSA. Mortality was high with both MRSA (23 of 88, 26%) and MSSA (55 of 228, 24%).

CONCLUSIONS:
Few VLBW infants had SA B/M. The 1% with MRSA had morbidity and mortality rates similar to infants with MSSA. Practices should provide equal focus on prevention and management of both MRSA and MSSA infections among VLBW infants.
Stair-Related Injuries to Young Children Treated in US Emergency Departments, 1999–2008
Authors: Zielinski Ashley E. , Rochette Lynne M. , Smith Gary A. 
Published: March 2012

OBJECTIVE:The objective of this study was to investigate the epidemiologic characteristics and secular trends of stair-related injuries among children aged &lt;5 years treated in US emergency departments.METHODS:A retrospective analysis was conducted of data from the National Electronic Injury Surveillance System of the US Consumer Product Safety Commission from 1999 through 2008 by using sample weights to estimate national numbers and rates of stair-related injuries.RESULTS:An estimated 931 886 children aged &lt;5 years were treated for stair-related injuries from 1999 through 2008, averaging 93 189 injuries per year and 46.5 injuries per 10 000 population annually. The number of injuries per year decreased significantly by 11.6% from 1999 to 2008. The rate of stair-related injuries also decreased significantly from 53.0 to 42.4 per 10 000 population from 1999 to 2008. Soft tissue injuries accounted for 34.6% of cases. Approximately three-fourths (76.3%) of children had injuries to the head and neck region, and 2.7% of patients were hospitalized. Children who were being carried at the time of injury accounted for 24.5% of injuries among children &lt;1 year and were more than 3 times more likely to be hospitalized than children injured by other mechanisms.CONCLUSIONS:Stair-related injuries are on the decline but still represent an important source of injury to young children. Increased prevention efforts are needed, including parental education and improved stairway design, to decrease stair-related injuries among young children.
Parental Psychological Well-Being and Behavioral Outcome of Very Low Birth Weight Infants at 3 Years
Authors: Huhtala Mira , Korja Riikka , Lehtonen Liisa , Haataja Leena , Lapinleimu Helena , Rautava Päivi ,   on behalf of the PIPARI Study Group
Published: March 2012

OBJECTIVE:The purpose was to explore whether poor parental psychological well-being is associated with behavioral problems of very low birth weight (VLBW, ≤1500 g) infants at 3 years of age.METHODS:In this prospective cohort study, 189 VLBW preterm infants born between January 2001 and December 2006 at the Turku University Hospital, Finland, were followed. Validated questionnaires (Beck Depression Inventory, Parenting Stress Index, and Sense of Coherence Scale) were mailed to the parents when their children were 2 years corrected age. A total of 140 parents evaluated the behavior of the child at 3 years by filling out the Child Behavior Checklist.RESULTS:There were significant associations between most of the measures of parental symptoms of depression, parenting stress, and sense of coherence and the behavioral outcome of the VLBW infants. The concomitant symptoms of both parents were associated with more problematic child behavior.CONCLUSIONS:Parents report more behavioral and emotional problems in VLBW children at age 3 if they themselves have had symptoms of depression, parenting stress, or weak sense of coherence 1 year earlier. The new finding of this study was to show the significance of the father’s psychological well-being on the behavioral development of a preterm child.
Quantitative Computer-Based Assessment of Lip Symmetry following Cleft Lip Repair
Authors: Mckearney Richard M. , Williams John V. , Mercer Nigel S. 
Published: March 2012

Objective To demonstrate an objective method of measuring lip symmetry after cleft lip repair by comparing patients with unilateral cleft lip (UCL) to non–cleft lip controls using the SymNose computer program. Design Retrospective cohort study comparing several parameters of lip symmetry between UCL cases and controls. Participants were represented by digital photographs that were traced using SymNose. Setting This study was performed at the South West Cleft Unit, Bristol, U.K. Participants Forty-four participants aged 10 years (±1 year) were recruited into and completed the study. A consecutive case series of 22 patients with UCL ± palate had previously undergone primary repair. Twenty-two age-matched controls were recruited from a local primary school. Main Outcome Measures Lip symmetry, expressed as the percentage mismatch of an overlaying of the left upper lip area and upper vermillion border area over the right, horizontal lip tilt, and lateral deviation of the lips. Results A significant increase in labial asymmetry was seen in the UCL group in the following parameters: upper lip mismatch and upper vermillion border mismatch. No significant differences were observed in horizontal lip tilt or lateral lip deviation. Conclusion This study supports the use of SymNose for the objective quantitative assessment of lip symmetry as an outcome measure of surgery following cleft lip repair. It allows comparison of surgical techniques and can be used to perform audits. It is a time-efficient process, relatively inexpensive, and straightforward to use.
Exfoliative Cytology and Titanium Dental Implants: A Pilot Study
Authors: Olmedo Daniel G. , Nalli Gabriela , Verdú Sergio , Paparella María L. , Cabrini Rómulo L. 
Published: March 2012

Background: Oral exfoliative cytology is a diagnostic method that involves the study of cells exfoliated from the oral mucosa. Ions/particles released from metallic implants can remain in the peri‐implant milieu. The aim of the present study is to assess the presence of metal particles in cells exfoliated from peri‐implant oral mucosa around titanium dental implants.Methods: The study comprised 30 patients carrying titanium dental implants, who had neither a metallic prosthesis nor metal restorations in neighboring teeth. Individuals undergoing orthodontic therapy and those who had oral piercing were also excluded from the study. The study sample included patients with and without peri‐implantitis. Cytologic samples of the peri‐implant area were collected. Samples of the marginal gingiva on the contralateral side of the implant were taken from the same individuals to serve as control. Cytologic analysis was performed using light microscopy. Titanium concentration was determined using inductively coupled plasma‐mass spectrophotometry.Results: Metal‐like particles were observed inside and outside epithelial cells and macrophages in cytologic smears of peri‐implant mucosa of both patients with and without peri‐implantitis. No particles were found in the control cytologic samples. The concentration of titanium was higher in the peri‐implantitis group compared with the group without peri‐implantitis; no traces of titanium were observed in controls.Conclusions: Regardless of an inflammatory response, ions/particles are released from the surface of the implant into the biologic milieu. Exfoliative cytology is a simple technique that may be used to detect metal particles in cells exfoliated from the peri‐implant mucosa.
Nano‐Sized Calcium Phosphate Particles for Periodontal Gene Therapy
Authors: Elangovan Satheesh , Jain Shardool , Tsai Pei‐Chin , Margolis Henry C. , Amiji Mansoor 
Published: March 2012

Background: Growth factors such as platelet‐derived growth factor (PDGF) have significantly enhanced periodontal therapy outcomes with a high degree of variability, mostly due to the lack of continual supply for a required period of time. One method to overcome this barrier is gene therapy. The aim of this in vitro study is to evaluate PDGF‐B gene delivery in fibroblasts using nano‐sized calcium phosphate particles (NCaPP) as vectors.Methods: NCaPP incorporating green fluorescent protein (NCaPP‐GFP) and PDGF‐B (NCaPP‐PDGF‐B) plasmids were synthesized using an established precipitation system and characterized using transmission electron microscopy and 1.2% agarose gel electrophoresis. Biocompatibility and transfection of the nanoplexes in fibroblasts were evaluated using cytotoxicity assay and florescence microscopy, respectively. Polymerase chain reaction and enzyme‐linked immunosorbent assay were performed to evaluate PDGF‐B transfection after different time points of treatments, and the functionality of PDGF‐B transfection was evaluated using the cell proliferation assay.Results: Synthesized NCaPP nanoplexes incorporating the genes of GFP and PDGF‐B were spherical in shape and measured about 30 to 50 nm in diameter. Gel electrophoresis confirmed DNA incorporation and stability within the nanoplexes, and 3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H‐tetrazolium reagent assay demonstrated their biocompatibility in fibroblasts. In vitro transfection studies revealed a higher and longer lasting transfection after NCaPP‐PDGF‐B treatment, which lasted up to 96 hours. Significantly enhanced fibroblast proliferation observed in NCaPP‐PDGF‐B–treated cells confirmed the functionality of these nanoplexes.Conclusion: NCaPP demonstrated higher levels of biocompatibility and efficiently transfected PDGF plasmids into fibroblasts under described in vitro conditions.
Significance of Urinary Full-Length and Ectodomain Forms of Megalin in Patients With Type 2 Diabetes
Authors: Ogasawara Shinya , Hosojima Michihiro , Kaseda Ryohei , Kabasawa Hideyuki , Yamamoto-Kabasawa Keiko , Kurosawa Hiroyuki , Sato Hiroyoshi , Iino Noriaki , Takeda Tetsuro , Suzuki Yoshiki , Narita Ichiei , Yamagata Kunihiro , Tomino Yasuhiko , Gejyo Fumitake , Hirayama Yoshiaki , Sekine Sakari , Saito Akihiko 
Published: March 2012

OBJECTIVE
Megalin, an endocytic receptor in proximal tubule cells, is involved in the mechanisms of albuminuria in diabetic nephropathy (DN). To develop efficient novel biomarkers associated with the pathogenesis of DN, we investigated urinary megalin excretion in type 2 diabetes.

RESEARCH DESIGN AND METHODS
Sandwich enzyme-linked immunosorbent assay systems were established with monoclonal antibodies against the NH2 (amino [A]-megalin assay) and COOH (C-megalin assay) termini of megalin to analyze urinary forms of megalin in 68 patients with type 2 diabetes.

RESULTS
The A-megalin assay mainly detected a megalin ectodomain form in the soluble urinary fraction, whereas the C-megalin assay identified a full-length form in both soluble and insoluble fractions. Urinary C-megalin levels were significantly high in patients with normoalbuminuria, were elevated in line with increased albuminuria, and showed a better association with estimated glomerular filtration rate (eGFR) (&lt;60 mL/min/1.73 m2) than did urinary albumin. In contrast, urinary A-megalin levels were increased in patients with normo- and microalbuminuria but not in those with macroalbuminuria. Urinary C-megalin levels were also positively associated with plasma inorganic phosphate and negatively with hemoglobin levels in those showing no features of bleeding and not taking vitamin D analogs, phosphate binders, or erythropoiesis-stimulating agents.

CONCLUSIONS
Urinary full-length megalin excretion as measured by the C-megalin assay is well associated with reduced eGFR and linked to the severity of DN, phosphate dysregulation, and anemia, whereas urinary excretion of megalin ectodomain as measured by the A-megalin assay may be associated with distinctive mechanisms of earlier DN in type 2 diabetes.
Relationship Between Glycosylated Hemoglobin Assessment and Glucose Therapy Intensification in Patients With Diabetes Hospitalized for Acute Myocardial Infarction
Authors: Stolker Joshua M. , Spertus John A. , McGuire Darren K. , Lind Marcus , Tang Fengming , Jones Philip G. , Inzucchi Silvio E. , Rathore Saif S. , Maddox Thomas M. , Masoudi Frederick A. , Kosiborod Mikhail 
Published: March 2012

OBJECTIVE
To evaluate the relationship between A1C and glucose therapy intensification (GTI) in patients with diabetes mellitus (DM) hospitalized for acute myocardial infarction (AMI).

RESEARCH DESIGN AND METHODS
A1C was measured as part of routine care (clinical A1C) or in the core laboratory (laboratory A1C, results unavailable to clinicians). GTI predictors were identified using hierarchical Poisson regression.

RESULTS
Of 1,274 patients, 886 (70%) had clinical A1C and an additional 263 had laboratory A1C measured. Overall, A1C was &lt;7% in 419 (37%), 7–9% in 415 (36%), and &gt;9% in 315 patients (27%). GTI occurred in 31% of patients and was more frequent in those with clinical A1C both before (34 vs. 24%, P &lt; 0.001) and after multivariable adjustment (relative risk 1.34 [95% CI 1.12–1.62] vs. no clinical A1C).

CONCLUSIONS
Long-term glucose control is poor in most AMI patients with DM, but only a minority of patients undergo GTI at discharge. Inpatient A1C assessment is strongly associated with intensification of glucose-lowering therapy.
A peptide uncoupling CRMP-2 from the presynaptic Ca2+ channel complex demonstrates efficacy in animal models of migraine and AIDS therapy-induced neuropathy
Authors: Ripsch Matthew , Ballard Carrie , Khanna May , Hurley Joyce , White Fletcher , Khanna Rajesh 
Published: March 2012

Abstract
Biological, genetic, and clinical data provide compelling proof for N-type voltage-gated calcium channels (CaV2.2) as therapeutic targets for chronic pain. While decreasing channel function is ultimately anti-nociceptive, directly targeting the channel can lead to multiple adverse effects. Targeting regulators of channel activity may facilitate improved analgesic properties associated with channel block and afford a broader therapeutic window. Towards this end, we recently identified a short peptide, designated CBD3, derived from collapsin response mediator protein 2 (CRMP-2) that suppressed inflammatory and neuropathic hypersensitivity by inhibiting CRMP-2 binding to CaV2.2 [Brittain et al., Nature Medicine 17:822–829 (2011)]. Rodents administered CBD3 intraperitoneally, fused to the HIV TAT protein cell penetrating domain, exhibited antinociception lasting ∼4 hours highlighting potential instability, limited oral bioavailability, and/or rapid elimination of peptide. This report focuses on improving upon the parental CBD3 peptide. Using SPOTScan analysis of synthetic versions of the parental CBD3 peptide, we identified peptides harboring single amino acid mutations that bound with greater affinity to CaV2.2. One such peptide, harboring a phenylalanine instead of glycine (G14F), was tested in rodent models of migraine and neuropathic pain. In vivo laser Doppler blood flowmetry measure of capsaicin-induced meningeal vascular responses related to headache pain was almost completely suppressed by dural application of the G14F peptide. The G14F mutant peptide, administered intraperitoneally, also exhibited greater antinociception in Stavudine (2′-3′-didehydro-2′-3′-dideoxythymidine (d4T)/Zerit®) model of AIDS therapy-induced peripheral neuropathy compared to the parent CBD3 peptide. These results demonstrate the patent translational value of small biologic drugs targeting CaV2.2 for management of clinical pain.