bluuebunny/crossref_metadata_2025_split huggingface dataset:
A computational study of the Warburg effect identifies metabolic targets inhibiting cancer migration
Authors: Yizhak Keren , Le Dévédec Sylvia E , Rogkoti Vasiliki Maria , Baenke Franziska , de Boer Vincent C , Frezza Christian , Schulze Almut , van de Water Bob , Ruppin Eytan 
Published: August 2014

AbstractOver the last decade, the field of cancer metabolism has mainly focused on studying the role of tumorigenic metabolic rewiring in supporting cancer proliferation. Here, we perform the first genome‐scale computational study of the metabolic underpinnings of cancer migration. We build genome‐scale metabolic models of the NCI‐60 cell lines that capture the Warburg effect (aerobic glycolysis) typically occurring in cancer cells. The extent of the Warburg effect in each of these cell line models is quantified by the ratio of glycolytic to oxidative ATP flux (AFR), which is found to be highly positively associated with cancer cell migration. We hence predicted that targeting genes that mitigate the Warburg effect by reducing the AFR may specifically inhibit cancer migration. By testing the anti‐migratory effects of silencing such 17 top predicted genes in four breast and lung cancer cell lines, we find that up to 13 of these novel predictions significantly attenuate cell migration either in all or one cell line only, while having almost no effect on cell proliferation. Furthermore, in accordance with the predictions, a significant reduction is observed in the ratio between experimentally measured ECAR and OCR levels following these perturbations. Inhibiting anti‐migratory targets is a promising future avenue in treating cancer since it may decrease cytotoxic‐related side effects that plague current anti‐proliferative treatments. Furthermore, it may reduce cytotoxic‐related clonal selection of more aggressive cancer cells and the likelihood of emerging resistance.
Improving Care for Pediatric Diabetic Ketoacidosis
Authors: Koves Ildiko H. , Leu Michael G. , Spencer Suzanne , Popalisky Jean C. , Drummond Kate , Beardsley Elaine , Klee Kristi , Zimmerman Jerry J. 
Published: August 2014

OBJECTIVE:
We sought to create and implement recommendations from an evidence-based pathway for hospital management of pediatric diabetic ketoacidosis (DKA) and to sustain improvement. We hypothesized that development and utilization of standard work for inpatient care of DKA would lead to reduction in hypokalemia and improvement in outcome measures.

METHODS:
Development involved systematic review of published literature by a multidisciplinary team. Implementation included multidisciplinary feedback, hospital-wide education, daily team huddles, and development of computer decision support and electronic order sets.

RESULTS:
Pathway-based order sets forced clinical pathway adherence; yet, variations in care persisted, requiring ongoing iterative review and pathway tool adjustment. Quality improvement measures have identified barriers and informed subsequent adjustments to interventions. We compared 281 patients treated postimplementation with 172 treated preimplementation. Our most notable findings included the following: (1) monitoring of serum potassium concentrations identified unanticipated hypokalemia episodes, not recognized before standard work implementation, and earlier addition of potassium to fluids resulted in a notable reduction in hypokalemia; (2) improvements in insulin infusion management were associated with reduced duration of ICU stay; and (3) with overall improved DKA management and education, cerebral edema occurrence and bicarbonate use were reduced. We continue to convene quarterly meetings, review cases, and process ongoing issues with system-based elements of implementing the recommendations.

CONCLUSIONS:
Our multidisciplinary development and implementation of an evidence-based pathway for DKA have led to overall improvements in care. We continue to monitor quality improvement metric measures to sustain clinical gains while continuing to identify iterative improvement opportunities.
Incidence, Etiology, and Outcomes of Hazardous Hyperbilirubinemia in Newborns
Authors: Kuzniewicz Michael W. , Wickremasinghe Andrea C. , Wu Yvonne W. , McCulloch Charles E. , Walsh Eileen M. , Wi Soora , Newman Thomas B. 
Published: August 2014

BACKGROUND AND OBJECTIVES:Total serum bilirubin (TSB) levels ≥30 mg/dL are rare but potentially hazardous. A better understanding of their incidence, causes, and outcomes could help inform preventive efforts.METHODS:We identified infants born ≥35 weeks’ gestational age from 1995–2011 in Kaiser Permanente Northern California (n = 525 409) and examined the medical records of infants with a TSB ≥30 mg/dL to determine etiology and the occurrence of acute bilirubin encephalopathy. We reviewed inpatient and outpatient encounters through 2013 for evidence of sensorineural hearing loss (SNHL) or cerebral palsy (CP).RESULTS:We identified 47 infants with TSB ≥30 mg/dL (8.6 per 100 000 births). In 44 infants (94%), the hyperbilirubinemia occurred after the initial birth hospitalization. The etiology was not identified in 33 (70%). Glucose-6-phosphate dehydrogenase (G6PD) activity was measured in only 25 (53%) of whom 10 (40%) were deficient. Four children had acute bilirubin encephalopathy of whom 2 developed both CP and SNHL, and 1 developed isolated SNHL. These 3 infants all had G6PD deficiency and TSB &gt;40 mg/dL. One additional 35-week infant with TSB 38.2 mg/dL had SNHL.CONCLUSIONS:Hazardous (≥30 mg/dL) hyperbilirubinemia is a rare event. No etiology could be identified from the clinical record in most cases. G6PD deficiency was the leading cause of hazardous hyperbilirubinemia when an etiology was identified, but many were not tested. Chronic, bilirubin-induced neurotoxicity was uncommon and occurred only in the setting of additional risk factors and TSB values well over (&gt;15 mg/dL) the American Academy of Pediatrics exchange transfusion thresholds.
Survival and Lifetime Costs Associated With First-Line Bevacizumab Use in Older Patients With Metastatic Colorectal Cancer
Authors: Shankaran Veena , Mummy David , Koepl Lisel , Bansal Aasthaa , Mirick Dana K. , Yu Elaine , Morlock Rob , Ogale Sarika , Ramsey Scott D. 
Published: August 2014

Abstract

Introduction.
The objective of this study was to investigate clinical effectiveness and incremental lifetime costs associated with first-line bevacizumab in older patients with metastatic colorectal cancer (mCRC).

Methods.
Patients diagnosed with mCRC in 2004–2007 were identified from the Surveillance, Epidemiology, and End Results-Medicare database and stratified by first-line treatment (no chemotherapy [CTx], CTx alone, CTx plus bevacizumab). The impact of first-line bevacizumab on survival was investigated using a propensity score adjusted multivariate Cox proportional hazards model. Mean lifetime costs for each cohort were calculated using Medicare claims for all services rendered between diagnosis and end of follow-up, adjusting for death and censoring.

Results.
A total of 4,414 patients (mean age: 77.3 years) were identified, of whom 15% received first-line bevacizumab. Among first-line-treated patients, bevacizumab receipt was associated with improved overall survival (hazard ratio: 0.85 [95% confidence interval: 0.75–0.97]; p = .013), and this benefit was limited to patients who received &gt;1 month of bevacizumab therapy. Median and mean survival were greatest in patients treated with CTx plus bevacizumab relative to CTx alone (CTx plus bevacizumab median 19.4 months [mean 28.0 months] vs. CTx alone median 15.1 months [mean 22.9 months]; p &lt; .001), as were mean lifetime costs (mean per patient cost $143,284 vs. $111,280). Compared with CTx alone, CTx plus bevacizumab was associated with a 5.1-month increase in mean survival and a $32,004 increase in mean lifetime treatment costs, with an incremental cost of $75,303 per life-year gained.

Conclusion.
Bevacizumab use is associated with longer survival than CTx alone in older patients treated in real-world clinical settings, at an incremental cost of $75,303 per life-year gained.
Investigation of Adverse-Event-Related Costs for Patients With Metastatic Breast Cancer in a Real-World Setting
Authors: Hurvitz Sara , Guerin Annie , Brammer Melissa , Guardino Ellie , Zhou Zheng-Yi , Latremouille Viau Dominick , Wu Eric Q. , Lalla Deepa 
Published: August 2014

Abstract

Background.
Existing treatments for metastatic breast cancer (mBC) are often effective but can cause adverse events (AEs). This study aimed to identify AEs associated with chemotherapies commonly used in mBC treatment (phase 1) and to quantify the economic impact of these AEs (phase 2).

Materials and Methods.
Patients in phase 1 had at least one claim for therapy for mBC, with at least one episode with single or multiple agents. The most common chemotherapy-related complications were identified using medical and pharmacy claims data. In phase 2, patients meeting study criteria were divided into four treatment cohorts by the line of treatment and chemotherapy received: first-line taxane-treated patients, second-line taxane-treated patients, first-line capecitabine-treated patients, and second-line capecitabine-treated patients. Average monthly AE-related health care costs per cohort were stratified by cost component. Total monthly costs per number of AEs were also calculated.

Results.
On average, patients in phase 1 (n = 1,551) had 2 episodes of treatment, with a mean duration of 131 days. The most frequently noted complications were anemia (50.7% of mBC treatment episodes), bilirubin elevation (26.4%), and leukopenia (24.8%). In phase 2, costs related to AEs were primarily driven by incremental inpatient, outpatient, and pharmacy costs. Increases in average monthly costs ranged from $854 (9.0%) to $5,320 (69.5%), according to cohort. Overall costs increased with increasing numbers of AEs.

Conclusion.
Chemotherapy-related AEs in patients with mBC are associated with a substantial economic burden that increases with the number of AEs reported.
Past human impact and pollutant loading reconstruction in Lake Engure as a tool for lake basin management
Authors: Kļaviņš Māris , Kokorīte Ilga , Rodinovs Valērijs , Jankevica Maruta 
Published: August 2014

Abstract
Environmental pollution of lakes and rivers is considered as one of the most important environmental problems. Analysis of nutrient and trace element accumulation in sedimentary phases of lakes can reflect the overall regional pollution level, and the observed accumulation patterns of pollutants in sediment profiles can be used to reconstruct the history of anthropogenic impacts. As pollutants in sediments are associated with other substances, it is important not only to study total concentrations of pollutants, but also their speciation forms. The aim of this study was to describe phosphorus (including speciation forms) and trace element concentrations in sediment profiles of Lake Engure and to evaluate human impact on organic matter accumulation and properties in lake sediments. The concentrations of the studied elements in sediments of Lake Engure are at background levels, which is clearly evident when compared with metal concentrations in lake sediments in West European countries. The analysis of element concentration changes in sedimentary profiles provided information about trends in recent accumulation (within the last 100 years) and on the balance between natural and human-induced accumulation processes. Analysis of nutrient concentrations in sediments aided in identifying background values as targets for lake management activities.
Exploring amenity migration towards coastal areas of Latvia: A case study of the Engure coastal area
Authors: Krišjāne Zaiga , Bērziņš Māris , Apsīte-Beriņa Elīna , Rozīte Maija , Sechi Guido 
Published: August 2014

Abstract
Migration has key importance in explaining the spatial distribution of the population in Latvia. The study contributes to an understanding of population shift towards coastal areas affected by amenity-driven migration, beach-oriented tourism and land development. This research explores characteristics of the inhabitants of the Engure coastal area, with special attention to individual attitudes on specific life quality attributes. Using a survey of local residents conducted in 2010, we found statistically significant correlations between groups of the research population. The results show that in-migrants differ from long-term residents with regard to most socio-demographic and attitude variables studied. Similarly, differences were found by out-migration intentions of residents. The area selected for the case study serves as a prominent and instructive laboratory for our analysis due to its suburban location, comparatively stable population growth rates and richness in natural amenities. Moreover, the territory is set as a long-term socio-ecological research platform in Latvia.
Prolonged Clinical Remission in Patients with Systemic Lupus Erythematosus
Authors: Steiman Amanda J. , Urowitz Murray B. , Ibañez Dominique , Papneja Anjali , Gladman Dafna D. 
Published: August 2014

Objective.Systemic lupus erythematosus (SLE) is typically a relapsing/remitting disease. However, some patients experience prolonged remission. These patients may provide further insights into SLE pathophysiology. In this study we characterize their clinical course.Methods.Prolonged remission was defined as Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K) = 0, = 2, or = 4 (based on serology) for ≥ 5 consecutive years, with visits ≤ 18 months apart. The patients could be taking antimalarials, but not corticosteroids or immunosuppressives. Flare was defined as clinical activity on SLEDAI-2K, or by corticosteroid/immunosuppressive initiation. Each patient’s preremission course was classified as monophasic, relapsing/remitting, or chronic active. These patients were compared to matched SLE controls and patients achieving remission on medications.Results.A total of 38/1613 (2.4%) patients achieved prolonged remission while taking no medications. The mean duration was 11.5 ± 6.4 years. Twenty-seven patients (71.0%) had relapsing/remitting disease, 11 (28.9%) had monophasic illness, and none had chronic active disease prior to remission. They differed from matched controls in ethnicity, disease activity at first visit, and cumulative organ damage. There were 34/1613 patients (2.1%) who achieved prolonged remission while taking steroids and/or immunosuppressives, with mean duration 8.5 ± 2.9 years. Twelve patients (35.3%) experienced disease flare. They were younger at diagnosis, with more disease activity prior to remission than patients taking no medications.Conclusion.Prolonged remission is an infrequent outcome among patients and is preceded by an atypically monophasic clinical course in a significant minority. Those taking medications represent a heterogeneous group: those who will tolerate eventual taper, and those whose disease activity was merely suppressed by ongoing immunosuppression. Prolonged remission may reflect unique pathophysiologic mechanisms, and warrants further investigation.
The Role of Depression, Anxiety, Fatigue, and Fibromyalgia on the Evaluation of the Remission Status in Patients with Rheumatoid Arthritis
Authors: Inanc Nevsun , Yilmaz-Oner Sibel , Can Meryem , Sokka Tuulikki , Direskeneli Haner 
Published: August 2014

Objective.To investigate the effect of depression, anxiety, fatigue, and fibromyalgia (FM) on the remission status in patients with rheumatoid arthritis (RA), defined according to the 28-joint count Disease Activity Score (DAS28)-erythrocyte sedimentation rate (ESR) and the Boolean-based new American College of Rheumatology/European League Against Rheumatism remission criteria.Methods.The subjects were patients with RA who participated in a hospital-based observational cohort. Patients who met the DAS28-ESR remission criteria at their latest visit were invited to participate in our study. The patient groups fulfilling or not fulfilling the Boolean remission criteria were identified and compared with each other with regard to the presence of depression, anxiety, fatigue (0–50), and FM. The relationship between psychosocial factors and Simplified Disease Activity Index (SDAI) remission, which is the index-based definition of remission in RA, was also investigated.Results.A total of 87 out of 428 patients (20%) with RA met the DAS28-ESR remission criteria and 32 (37%) of these also met the Boolean remission criteria, while 55 (63%) did not. Forty patients were also in SDAI remission. In the Boolean remission group, 2 patients had depression and 2 had anxiety (p = 0.004). In the Boolean nonremission group, 19 patients had depression and 13 had anxiety (p = 0.04). Continuous scales of anxiety (3.34 ± 3.76 vs 5.83 ± 4.70, p = 0.012) and depression (2.18 ± 2.75 vs 4.63 ± 4.10, p = 0.001) were also lower in the Boolean remission group in comparison with the nonremission group. Though FM syndrome was detected in only 1 patient of the Boolean remission group and in 7 patients of the Boolean nonremission group (p = 0.249), patients’ polysymptomatic distress scores of FM in the Boolean remission group were significantly lower than those of the nonremission group (3.12 ± 3.25 vs 6.27 ± 5.19, p = 0.001). The mean fatigue scores were 9.5 ± 10.6 in the Boolean remission group and 16.8 ± 12.8 in the Boolean nonremission group (p = 0.006). In multivariate analysis, patient’s global assessment (PtGA) and depression were found as the independent discriminators of Boolean-based definition. Similar relationships were also observed between psychosocial factors and SDAI remission.Conclusion.In patients with RA who do not fulfill the Boolean remission criteria, to avoid overtreatment, assessment of anxiety, fatigue, FM, and especially depression must be considered if PtGA scores and disease activity variables are significantly different.
Clinical Characteristics of and Relationship Between Metabolic Components and Renal Function Among Patients with Early-onset Juvenile Tophaceous Gout
Authors: Lu Chuan-Chin , Wu Shyi-Kuen , Chen Han-Yu , Chung Wei-Sheng , Lee Meng-Chih , Yeh Chih-Jung 
Published: August 2014

Objective.Age of onset of gout has recently decreased; however, patients with early-onset gout remain uncommon, and relevant information is scant. We hypothesized that these patients might exhibit differences in serum urates and other comorbidities compared with adult-onset patients.Methods.Early-onset gout patients (i.e., juveniles) with (n = 40) and without tophi (n = 47) were enrolled for study. Their clinical characteristics were compared with those of 353 patients with middle-age-onset tophaceous gout and 64 age-matched healthy participants.Results.Early-onset gout patients with tophi exhibited significantly higher body mass indices and serum urate levels and lower estimated glomerular filtration rates (eGFR) than did those without tophi. Early-onset gout patients with or without tophi demonstrated significantly abnormal lipid profiles and impaired liver or renal function compared with healthy patients. Serum urate levels and gout duration were identified as the principal determinants of tophi development. The presence of tophi might be crucial in decreasing eGFR, which is inversely related to tophi duration or gout duration. Unexpectedly, the most common site of initial gout attacks in early-onset tophaceous gout patients was the ankle, not the toe, which was the most common site in middle-age-onset tophaceous gout patients. The most common site of first tophi occurrence in early-onset patients was a finger, not a toe, which was the most common site in middle-age-onset patients.Conclusion.Early-onset tophaceous gout patients are more likely to exhibit comorbidities and renal dysfunction than middle-age-onset patients and exhibit distinct first sites of gout attack and tophi occurrence patterns.
Adalimumab Significantly Reduces the Recurrence Rate of Anterior Uveitis in Patients with Ankylosing Spondylitis
Authors: van Denderen J. Christiaan , Visman Ingrid M. , Nurmohamed Michael T. , Suttorp-Schulten Maria S.A. , van der Horst-Bruinsma Irene E. 
Published: August 2014

Objective.To investigate whether use of adalimumab decreases the frequency of attacks of anterior uveitis (AU) in patients with ankylosing spondylitis (AS).Methods.Consecutive patients with AS, visiting an outpatient clinic and treated for at least 12 weeks with adalimumab, were enrolled. The number of attacks of AU in the year before start and during treatment were assessed by patient history and ophthalmological controls.Results.In the 77 patients a total of 52 AU attacks occurred in the year before baseline (68 attacks per 100 patient-yrs), whereas during adalimumab treatment 19 attacks were seen (14 per 100 patient-yrs; reduction rate 80%). Twenty-six patients with AU in the year before start of adalimumab treatment had recurrent attacks, with a median number of 2.0 AU attacks per year [interquartile range (IQR) 1.00–3.00], whereas during treatment this decreased to 10 patients with a median number of 0.56 attacks per year (IQR 0.30–0.75). Hence, the number of attacks per year decreased by 72% (p = 0.000).Conclusion.In patients with AS, a significant reduction in the number of AU attacks, as well as in the number of attacks per patient, was observed during adalimumab treatment.
Increased Urinary Interleukin 22 Binding Protein Levels Correlate with Lupus Nephritis Activity
Authors: Yang Xuyan , Gao Yin , Wang Huiying , Zhao Xiaoying , Gong Xubo , Wang Qingqing , Zhang Xiaofei 
Published: August 2014

Objective.Interleukin 22 (IL-22) plays an important role in the promotion of antimicrobial immunity. However, dysregulated IL-22 action leads to inflammation and is involved in autoimmune diseases, including systemic lupus erythematosus (SLE). IL-22 binding protein (IL-22BP) is a soluble inhibitory IL-22 receptor and may represent a crucial regulator of IL-22. We investigated the expression and potential significance of serum and urinary IL-22BP levels in patients with SLE.Methods.A total of 112 patients with SLE and healthy control subjects participated in our study. Patients were classified according to kidney involvement and disease activity based on clinical and laboratory measures such as urinary sediment, proteinuria, kidney function, complement factor 3 (C3), C4, anti-dsDNA, disease activity index, and renal SLE disease activity index. The concentrations of IL-22BP and IL-22 were measured by ELISA. The expression of IL-22BP in the renal tissue was detected by immunohistochemistry.Results.Patients with active renal disease had urinary levels of IL-22BP higher than (1) patients with active SLE but no renal involvement, (2) patients with a history of lupus nephritis in remission with no systemic disease activity and no history of renal involvement, and (3) control subjects. There was no difference in serum levels of IL-22BP among the groups. Urinary levels of IL-22BP in patients with active renal disease were positively correlated with SLE Disease Activity Index, Systemic Lupus International Collaborating Clinics renal activity score, and histological activity index. IL-22BP was highly expressed in renal tissue of patients with active renal disease. After 6 months of treatment, urinary IL-22BP levels decreased significantly in patients with complete response, but remained unchanged in those with partial or no response.Conclusion.Urinary but not serum IL-22BP levels were associated with active renal disease. Urinary levels of IL-22BP might be a potential marker for the presence of renal involvement in patients with SLE.