bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional pathway mapping analysis for hypoxia-inducible factors
Authors: Chuang Chia-Sheng , Pai Tun-Wen , Hu Chin-Hua , Tzou Wen-Shyong , Dah-Tsyr Chang Margaret , Chang Hao-Teng , Chen Chih-Chia 
Published: August 2011

Abstract

Background
Hypoxia-inducible factors (HIFs) are transcription factors that play a crucial role in response to hypoxic stress in living organisms. The HIF pathway is activated by changes in cellular oxygen levels and has significant impacts on the regulation of gene expression patterns in cancer cells. Identifying functional conservation across species and discovering conserved regulatory motifs can facilitate the selection of reference species for empirical tests. This paper describes a cross-species functional pathway mapping strategy based on evidence of homologous relationships that employs matrix-based searching techniques for identifying transcription factor-binding sites on all retrieved HIF target genes.

Results
HIF-related orthologous and paralogous genes were mapped onto the conserved pathways to indicate functional conservation across species. Quantitatively measured HIF pathways are depicted in order to illustrate the extent of functional conservation. The results show that in spite of the evolutionary process of speciation, distantly related species may exhibit functional conservation owing to conservative pathways. The novel terms OrthRate and ParaRate are proposed to quantitatively indicate the flexibility of a homologous pathway and reveal the alternative regulation of functional genes.

Conclusion
The developed functional pathway mapping strategy provides a bioinformatics approach for constructing biological pathways by highlighting the homologous relationships between various model species. The mapped HIF pathways were quantitatively illustrated and evaluated by statistically analyzing their conserved transcription factor-binding elements.

Keywords
hypoxia-inducible factor (HIF), hypoxia-response element (HRE), transcription factor (TF), transcription factor binding site (TFBS), KEGG (Kyoto Encyclopedia of Genes and Genomes), cross-species comparison, orthology, paralogy, functional pathway
Increased midgestational IFN-γ, IL-4 and IL-5 in women bearing a child with autism: A case-control study
Authors: Goines Paula E , Croen Lisa A , Braunschweig Daniel , Yoshida Cathleen K , Grether Judith , Hansen Robin , Kharrazi Martin , Ashwood Paul , Van de Water Judy 
Published: August 2011

Abstract

Background
Immune anomalies have been documented in individuals with autism spectrum disorders (ASDs) and their family members. It is unknown whether the maternal immune profile during pregnancy is associated with the risk of bearing a child with ASD or other neurodevelopmental disorders.

Methods
Using Luminex technology, levels of 17 cytokines and chemokines were measured in banked serum collected from women at 15 to 19 weeks of gestation who gave birth to a child ultimately diagnosed with (1) ASD (n = 84), (2) a developmental delay (DD) but not autism (n = 49) or (3) no known developmental disability (general population (GP); n = 159). ASD and DD risk associated with maternal cytokine and chemokine levels was estimated by using multivariable logistic regression analysis.

Results
Elevated concentrations of IFN-γ, IL-4 and IL-5 in midgestation maternal serum were significantly associated with a 50% increased risk of ASD, regardless of ASD onset type and the presence of intellectual disability. By contrast, elevated concentrations of IL-2, IL-4 and IL-6 were significantly associated with an increased risk of DD without autism.

Conclusion
The profile of elevated serum IFN-γ, IL-4 and IL-5 was more common in women who gave birth to a child subsequently diagnosed with ASD. An alternative profile of increased IL-2, IL-4 and IL-6 was more common for women who gave birth to a child subsequently diagnosed with DD without autism. Further investigation is needed to characterize the relationship between these divergent maternal immunological phenotypes and to evaluate their effect on neurodevelopment.
Role of neutrophils in the activation of trypsinogen in severe acute pancreatitis
Authors: Abdulla Aree , Awla Darbaz , Thorlacius Henrik , Regnér Sara 
Published: August 2011

ABSTRACTThe relationship between inflammation and proteolytic activation in pancreatitis is an unresolved issue in pancreatology. The purpose of this study was to define the influence of neutrophils on trypsinogen activation in severe AP. Pancreatitis was induced by infusion of taurocholate into the pancreatic duct in C57BL/6 mice. For neutrophil depletion, an anti-Gr-1 antibody was administered before pancreatitis induction. Administration of the anti-Gr-1 antibody reduced circulating neutrophils by 97%. Pancreatic TAP and serum amylase levels increased 2 h and 24 h after induction of pancreatitis. Neutrophil depletion reduced pancreatic TAP and serum amylase levels at 24 h but not at 2 h after pancreatitis induction. Pancreatic MPO and infiltration of neutrophils, as well as MIP-2 levels, were increased 24 h after taurocholate infusion. Two hours after taurocholate administration, no significant pancreatic infiltration of neutrophils was observed. Injection of the anti-Gr-1 antibody abolished MPO activity, neutrophil accumulation, and MIP-2 levels, as well as acinar cell necrosis, hemorrhage, and edema in the pancreas at 24 h. Moreover, taurocholate-provoked tissue damage and MPO activity in the lung were normalized by neutrophil depletion. Intravital fluorescence microscopy revealed a 97% reduction of leukocytes in the pancreatic microcirculation after administration of the anti-Gr-1 antibody. Our data demonstrate that initial trypsinogen activation is independent of neutrophils, whereas later activation is dependent on neutrophils in the pancreas. Neutrophils are critical in mediating pancreatic and lung tissue damage in severe AP.
Bortezomib, Bendamustine, and Rituximab in Patients With Relapsed or Refractory Follicular Lymphoma: The Phase II VERTICAL Study
Authors: Fowler Nathan , Kahl Brad S. , Lee Peter , Matous Jeffrey V. , Cashen Amanda F. , Jacobs Samuel A. , Letzer Jeffrey , Amin Bipinkumar , Williams Michael E. , Smith Sonali , Saleh Alfred , Rosen Peter , Shi Hongliang , Parasuraman Sudha , Cheson Bruce D. 
Published: August 2011

PurposeThe aims of this multicenter study were to evaluate the response rate, progression-free survival, and toxicity of the combination of bortezomib, bendamustine, and rituximab in patients with follicular lymphoma whose disease was relapsed or refractory to prior treatment.Patients and MethodsPatients received five 35-day cycles of bortezomib, bendamustine, and rituximab: bortezomib administered intravenously (IV) at a dose of 1.6 mg/m2on days 1, 8, 15, and 22, cycles one to five; bendamustine 50, 70, or 90 mg/m2IV over a 60-minute infusion on days 1 and 2, cycles one to five; and rituximab 375 mg/m2on days 1, 8, 15, and 22 of cycle one and day 1 of subsequent cycles. Patients were assessed using the International Workshop Response Criteria, with the primary end point of 60% complete response rate.ResultsSeventy-three patients were enrolled. During the dose-escalation phase, the maximum-tolerated dose for bendamustine was not reached; the 90 mg/m2dose level was expanded for the efficacy assessment, and a total of 63 patients received bendamustine 90 mg/m2. In these 63 patients, the overall response rate was 88% (including 53% complete response). Median duration of response was 11.7 months (95% CI, 9.2 to 13.3). Median progression-free survival was 14.9 months (95% CI, 11.1 to 23.7). Toxicities were manageable; myelosuppression was the main toxicity (25% and 14% of patients experienced grade 3 to 4 neutropenia and grade 3 to 4 thrombocytopenia, respectively). Transient grade 3 to 4 neuropathy occurred in 11% of patients.ConclusionThe combination of bortezomib, bendamustine, and rituximab is highly active in patients with follicular lymphoma who have received previous treatment.
Incidence and Risk of Congestive Heart Failure in Patients With Renal and Nonrenal Cell Carcinoma Treated With Sunitinib
Authors: Richards Christopher J. , Je Youjin , Schutz Fabio A.B. , Heng Daniel Y.C. , Dallabrida Susan M. , Moslehi Javid J. , Choueiri Toni K. 
Published: August 2011

Purpose Sunitinib is a multitargeted receptor tyrosine kinase inhibitor approved for treatment of renal cell carcinoma (RCC) and GI stromal tumor. Congestive heart failure (CHF) is an important adverse effect that has been reported with sunitinib, but overall incidence and relative risk (RR) remain undefined. We performed an up-to-date meta-analysis to determine the risk of developing CHF in patients with both RCC and non-RCC tumors treated with sunitinib. Methods Medline databases were searched for articles published between January 1966 and February 2011. Eligible studies were limited to phase II and III trials of sunitinib with adequate safety reporting in patients with cancer of any tumor type. Summary incidence, RR, and 95% CIs were calculated using random- or fixed-effects models based on the heterogeneity of included studies. Results A total of 6,935 patients were included. Overall incidence for all- and high-grade CHF in sunitinib-treated patients was 4.1% (95% CI, 1.5% to 10.6%) and 1.5% (95% CI, 0.8% to 3.0%), respectively. RR of all- and high-grade CHF in sunitinib-treated patients compared with placebo-treated patients was 1.81 (95% CI, 1.30 to 2.50; P < .001) and 3.30 (95% CI, 1.29 to 8.45; P = .01), respectively. On subgroup analysis, there was no difference observed in CHF incidence for patients with RCC versus non-RCC or in trials with or without cardiac monitoring. No evidence of publication bias was observed. Conclusion Sunitinib use is associated with increased risk of CHF in patients with cancer.
Physician Characteristics and Variability of Erythropoiesis-Stimulating Agent Use Among Medicare Patients With Cancer
Authors: Wright Jason D. , Neugut Alfred I. , Wilde Elizabeth T. , Buono Donna L. , Malin Jennifer , Tsai Wei Y. , Hershman Dawn L. 
Published: August 2011

Purpose Drugs are usually approved for a specific indication on the basis of randomized trials. However, once approved, these treatments are often used differently than as tested in trials. We performed an analysis to determine the patterns of use of erythropoiesis-stimulating agents (ESAs). Methods We used the Surveillance, Epidemiology, and End Results–Medicare database to identify patients age 65 years or older with breast, lung, or colon cancer diagnosed between 1995 and 2005 who had one ESA and chemotherapy claim. Associations of patient, tumor, and physician-related factors with receipt of ESAs were analyzed. Results Of 21,091 patients analyzed, 5,099 (24.2%) received ESAs for 1 week or less (misuse), and 1,601 (7.6%) received ESAs for more than 14 weeks (prolonged use). Receipt of ESAs while not actively receiving chemotherapy (off label) occurred in 2,876 patients (13.6%). In a multivariable analysis, ESA misuse was associated with MD degree, female sex of physician, and earlier year of medical school graduation. Private practice physicians (odds ratio [OR], 0.78; 95% CI, 0.72 to 0.84) and high-volume physicians (OR, 0.78; 95% CI, 0.72 to 0.85) were less likely to use 1 week or less of ESA treatment. Treatment by high-volume oncologists (OR, 1.33; 95% CI, 1.14 to 1.55) and by oncologists who graduated from US medical schools (OR, 1.26; 95% CI, 1.12 to 1.42) predicted prolonged-duration ESA use, whereas female oncologists (OR, 0.79; 95% CI, 0.68 to 0.93) were less likely to prescribe prolonged ESA treatment. Private practice physicians (OR, 1.18; 95% CI, 1.02 to 1.38) and high-volume providers (OR, 1.58; 95% CI, 1.33 to 1.87) were more likely to prescribe more than 24 weeks of ESA treatment. Conclusion Our study demonstrated widespread variability in the use of ESAs. Physician characteristics exerted substantial influence on ESA use. Policies to discourage inappropriate use of cancer therapies are needed.
Tumescent anaesthesia in combination with femoral nerve block for surgery of varicose veins: prilocaine 0.1% versus 0.2%
Authors: Hillermann T , Dullenkopf A , Joechle W , Traber J 
Published: August 2011

Objective Results of a prospective, randomized, double-blinded study about tumescent anaesthesia (TA) in combination with femoral nerve block (FNB) for surgery of varicose veins are reported. The aim is to compare two different concentrations of prilocaine in TA. Method With approval of the ethical committee and informed consent, FNB (nerve stimulation, 20 mL prilocaine 0.75%) was performed followed by TA using prilocaine 0.1% versus 0.2% (groups P0.1 and P0.2). Further medication was standardized. Overall amount of prilocaine was recorded, plasma levels of 20 patients measured regularly. Side-effects, patient satisfaction and pain scores were compared ( P < 0.05). Results Ninety patients were included. In one patient (P0.1), general anaesthesia was necessary. There was no difference in pain scores, need for rescue medication or patient satisfaction. More prilocaine was administered in P0.2 ( P < 0.0001) with higher but far below toxic plasma levels. In three patients (P0.2) mild met-haemoglobinaemia was confirmed. Conclusion TA with prilocaine 0.1% in combination with FNB is sufficient to provide high patient satisfaction during varicosis surgery.
Effect of multilayer high-compression bandaging on ankle range of motion and oxygen cost of walking
Authors: Roaldsen K S , Elfving B , Stanghelle J K , Mattsson E 
Published: August 2011

Objective To evaluate the effects of multilayer high-compression bandaging on ankle range of motion, oxygen consumption and subjective walking ability in healthy subjects. Method A volunteer sample of 22 healthy subjects (10 women and 12 men; aged 67 [63–83] years) were studied. The intervention included treadmill-walking at self-selected speed with and without multilayer high-compression bandaging (Proforeº), randomly selected. The primary outcome variables were ankle range of motion, oxygen consumption and subjective walking ability. Results Total ankle range of motion decreased 4% with compression. No change in oxygen cost of walking was observed. Less than half the subjects reported that walking-shoe comfort or walking distance was negatively affected. Conclusion Ankle range of motion decreased with compression but could probably be counteracted with a regular exercise programme. There were no indications that walking with compression was more exhausting than walking without. Appropriate walking shoes could seem important to secure gait efficiency when using compression garments.
Quality of optometry referrals to neovascular age-related macular degeneration clinic: a prospective study
Authors: Muen Wisam J , Hewick Simon A 
Published: August 2011

Objectives To evaluate the quality of referrals to a neovascular age-related macular degeneration clinic from optometrists using the standard Rapid Access Referral Form (RARF) from the Royal College of Ophthalmologists. Design A prospective study. Prospective data were gathered from all optometry referrals using the RARF, between the periods of December 2006 to August 2009. These were assessed for accuracy of history, clinical signs and final diagnosis as compared to a macula expert. Setting Highlands NHS Trust. Participants All patients referred to the eye department at NHS Highlands Trust using the RARF. Main outcome measures The symptoms of neovascular age-related macular degeneration correctly identified by optometrists, and the signs of neovascular age-related macular degeneration correctly identified by optometrists. Results Fifty-four RARFs were received during this period, there was an overall agreement with symptomatology in 57.4% of cases. Optometrists scored less well in recognizing the clinical signs of neovascular age-related macular degeneration, with the poorest scores for recognizing macular oedema (44.4%) and drusen (51.9%). Twenty (37%) patients referred had neovascular age-related macular degeneration. Conclusions RARFs make up the minority of referrals to the neovascular age-related macular degeneration clinic. Optometrists find it difficult to accurately elicit the signs of macula disease.
Maintenance Immunosuppression with Intermittent Intravenous IL-2 Receptor Antibody Therapy in Renal Transplant Recipients
Authors: Gabardi Steven , Catella Jennifer , Martin Spencer T , Perrone Ronald , Chandraker Anil , Magee Colm C , McDevitt-Potter Lisa M 
Published: August 2011

Objective: To report what we believe to be the first 2 cases of long-term (>24 months) intermittent intravenous interleukin-2 receptor antibody (IL-2RA) therapy for maintenance immunosuppression following renal transplantation. Case Summary: The first patient is a 52-year-old female with a history of intolerance to calcineurin inhibitors (CNIs) and sirolimus. Following her second transplant, the patient received mycophenolate mofetil 100 mg twice daily, a tapering corticosteroid regimen (initial dose of methylprednisoIona 500 mg tapered over 1 week to prednisone 30 mg/day), and biweekly intravenous daclizumab 1-1.2 mg/kg/dose; 33 months after transplant the IL-2RA was changed to intravenous basiliximab 40 mg once a month. At 40 months after transplant, the patient continued to have stable renal function (estimated glomerular filtration rate 48 mL/min/1.73 m2) with excellent tolerability. The second patient is a 59-year-old female also intolerant to CNIs and sirolimus who required intermittent maintenance therapy with intravenous basiliximab 20 mg/dose. Despite an initial rejection episode, the patient tolerated more than 2 years of basiliximab therapy with good renal function (estimated glomerular filtration rate 103 months after transplant 69 mL/min/1.73 m2) and no adverse events. Discussion: The IL-2RAs basiliximab and daclizumab possess several characteristics of ideal maintenance immunosuppressive agents (ie, nondepleting long half-lives, limited adverse events). Based on a MEDLINE search (through December 31, 2010) using the search terms basiliximab, daclizumab, organ transplant, immunosuppression, and/or maintenance immunosuppression, and an advanced search in the published abstracts from the American Transplant Congress and World Transplant Congress (2000-2010), it appears that IL-2RAS have been used successfully as short-term therapy in both renal and extrarenal transplant recipients to allow for renal recovery following CNI-induced nephrotoxicity. In heart transplant recipients, the IL-2RAs have been used for <24 months as maintenance immunosuppression in patients intolerant of CNIs or sirolimus. Conclusions: To the best of our knowledge, these 2 cases are the first to demonstrate that IL-2RAs can be used as an alternative to a CNI in a de novo immunosuppressive regimen. Also, this is the first report to illustrate successful long-term use of IL-2RAS in renal transplant recipients. This alternative approach was well tolerated by our patients, with no apparent adverse events. Although the efficacy of such regimens cannot be determined with 2 case reports, the fact that intermittent intravenous IL-2RA administration was successfully accomplished in these patients provides impetus to evaluate this treatment modality in prospective studies.
A series of tetranuclear [2 × 2] grid complexes derived from an asymmetric ligand: Structural differences based on metal ion affinities
Authors: Shiga Takuya , Noguchi Mao , Matsumoto Takuto , Sato Hiroki , Tahira Hirotaka , Newton Graham N. , Oshio Hiroki 
Published: August 2011

A series of tetranuclear grid-type complexes were prepared by the reaction of the asymmetric multidentate ligand HL (HL = 2-[3-(2-hydroxyphenyl)-1H-pyrazol-5-yl]-6-pyridine carboxylic acid ethylester) with different metal sources. The tetranuclear copper complex, [Cu4(L1)4(NO3)4(H2O)4]·Et2O·2MeOH (1, HL1 = 2-[3-(2-hydroxyphenyl)-1H-pyrazol-5-yl]-6-pyridine carboxylic acid methyl ester) consists of four ligands, four copper ions, four nitrate ions and four water molecules, forming a [2 × 2] grid structure, in which all four copper ions have the same coordination environment. On the other hand, the corresponding nickel and cobalt complexes, [M4(L2)4(H2O)4]·4MeOH·6H2O (M = Ni (2) and Co (3), (H2L2 = 6-[1,3-dioxo-3-(2-phenyl)propionyl]pyridine-2-carboxylic acid)), have a similar grid core structure to the copper complex with four metal ions, four ligand molecules, and four water molecules, however, in these clusters there are two kinds of coordination site for the metal ions. Temperature-dependent magnetic susceptibility measurements for all complexes demonstrated that antiferromagnetic interactions between the metal ions were in operation. The magnetic susceptibility data of the copper and nickel complexes were analyzed using a tetranuclear model based on H = –2J(S1S2+S2S3+S3S4+S4S1) to give best-fit parameters of g = 2.11(1), J = –1.39(3) cm–1 and g = 2.19(1), J = –0.44(2) cm–1, respectively.
A Poem of Philes to Makarios Chrysokephalos? The Case of Poem Florentinus 58
Authors: Bazzani Marina 
Published: August 2011

Abstract
Manuel Philes dedicated countless occasional poems to his many benefactors to praise their qualities and ask for all sorts of assistance, both spiritual and material. This article analyses one of these compositions, namely poem Flor. 58, and offers a commentary of its language and content. On the basis of the imagery, repetitions and allusions present in the text, it is argued that this untitled poem was in fact dedicated to the scholar and metropolitan of Philadelphia Makarios Chrysokephalos to request the gift of a hat. The detailed reading of the text aims at showing the presence of several layers of meaning which characterise the whole poem, as well as illustrating Philes' sophisticated poetic technique.
ProcopiusDe aedificiis4.2.1–22 on the Thermopylae Frontier
Authors: Cherf William J. 
Published: August 2011

AbstractThis article compares topographical and archaeological remains of the Thermopylae frontier with the ancient testimonia of the sixth century historian Procopius of Caesareia (De aedificiis4.2.1.–22). It was revealed that: many of the frontier fortifications described were initially built before the sixth century; the fortified κλεισούρα mentioned should be equated with the Dhéma Pass; and the commercial settlement of Myropóles is best identified with the modern village of Káto Dhió Vouná. Written in Attic prose, this passage represents a rhetorical exercise, the climax of which turned not on the ancient battlefield of Thermopylae, but rather on a mountain pass and it's highway that neutralized the Thermopylae defenses if they were ever controlled by the enemy. We were told that only the Emperor Justinian's wisdom could grasp this critical fact. Additionally, Procopius employed many rhetorical devices in this narrative: τóπος, χρóνος,, ἄγαλμα, ἔκφρασις, πανηγρικóς and employed imperial propaganda, praise, and exaggeration as well. In short, the passage is a classic example of selective story telling that may have found its inspiration in the Hunnic raid of 539/540 and the Herodotean account of the Persian invasion of 480 BC. While Procopius' account remains our best topographical description of the late antique Thermopylae frontier, one can only say that more archaeological questions were left unanswered than were resolved. In short, as an archaeological source, theDe aedificiisis a disappointing and vexing resource filled with equivocations. Finally, one may doubt that Procopius ever did visit the Thermopylae frontier, even though during his career he certainly had ample opportunity to do so. His account, therefore, must have been based upon secondary sources, whether imperial archival material, itineraries, or military staff reports and were not the result of personal autopsy.