bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study design and baseline description of the BMI2 trial: reducing paediatric obesity in primary care practices
Authors: Resnicow K. , McMaster F. , Woolford S. , Slora E. , Bocian A. , Harris D. , Drehmer J. , Wasserman R. , Schwartz R. , Myers E. , Foster J. , Snetselaar L. , Hollinger D. , Smith K. 
Published: December 2011

SummaryObjectivesThis study will test the efficacy of motivational interviewing (MI) conducted by primary care providers and dieticians among children ages 2‐8 years old with a body mass index (BMI) ≥85th and ≤97th percentile.MethodsForty‐two practices from the American Academy of Pediatrics, Pediatric Research in Office Settings Network were assigned to one of three groups. Group 1 (usual care) measures BMI percentile at baseline, and at 1‐ and 2‐year follow‐ups and receives standard health education materials. Group 2 providers deliver three proactive MI counselling sessions with a parent of the index child in Year 1 and one additional ‘booster’ visit in Year 2. Group 3 adds six MI counselling sessions from a trained dietician. The primary outcome is the child's BMI percentile at 2‐year follow‐up. Secondary outcomes include parent report of the child's screen time, physical activity, intake of fruits and vegetables, and sugar‐sweetened beverages.ResultsWe enrolled 633 eligible children whose mean BMI percentile was 92.0 and mean age of 5.1. The cohort was 57% female. Almost 70% of parents reported a household income of ≥$40 000 per year, and 39% had at least a college education. The cohort was 63% White, 23% Hispanic, 7% Black and 7% Asian. Parent self‐reported confidence that their child will achieve a healthy weight was on average an 8 (out of 10).ConclusionTo date, several aspects of the study can inform similar efforts including our ability to use volunteer clinicians to recruit participants and their willingness to dedicate their time, without pay, to receive training in MI.
Novel Potent Metallocenes against Liver Stage Malaria
Authors: Matos Joana , da Cruz Filipa P. , Cabrita Élia , Gut Jiri , Nogueira Fátima , do Rosário Virgílio E. , Moreira Rui , Rosenthal Philip J. , Prudêncio Miguel , Gomes Paula 
Published: December 2011

ABSTRACT

Novel conjugates of the antimalarial drug primaquine (compound 1) with ferrocene, named primacenes, have been synthesized and screened for their activities against blood stage and liver stage malaria
in vitro
and host-vector transmission
in vivo
. Both transmission-blocking and blood-schizontocidal activities of the parent drug were conserved only in primacenes bearing a basic aliphatic amine group. Liver stage activity did not require this structural feature, and all metallocenes tested were comparable to or better than primaquine in this regard. Remarkably, the replacement of primaquine's aliphatic chain by hexylferrocene, as in compound 7, led to a ∼45-fold-higher level activity against liver stage parasitemia than that of primaquine.
Molecular Identification of Extended-Spectrum-β-Lactamase Genes from Enterobacteriaceae Isolated from Healthy Human Carriers in Switzerland
Authors: Geser Nadine , Stephan Roger , Korczak Bozena M. , Beutin Lothar , Hächler Herbert 
Published: December 2011

ABSTRACT

In this study, fecal samples from 586 healthy humans were investigated to determine the occurrence of extended-spectrum-β-lactamase (ESBL)-producing
Enterobacteriaceae
in Swiss people. A total of 5.8% of the human fecal samples yielded ESBL producers, and all of the 34 isolated strains were
Escherichia coli
. PCR analysis revealed that 14 strains produced CTX-M-15, 10 produced CTX-M-1, 7 strains produced CTX-M-14, and 2 strains produced CTX-M-2 ESBLs. One strain produced SHV-12 ESBL. Of the 34 isolates, 15 produced additional TEM-1 broad-spectrum β-lactamases. By serotyping, a high degree of diversity among the strains was found.
A Novel Carbon Monoxide-Releasing Molecule Fully Protects Mice from Severe Malaria
Authors: Pena Ana C. , Penacho Nuno , Mancio-Silva Liliana , Neres Rita , Seixas João D. , Fernandes Afonso C. , Romão Carlos C. , Mota Maria M. , Bernardes Gonçalo J. L. , Pamplona Ana 
Published: December 2011

ABSTRACTSevere forms of malaria infection, such as cerebral malaria (CM) and acute lung injury (ALI), are mainly caused by the apicomplexan parasitePlasmodium falciparum. Primary therapy with quinine or artemisinin derivatives is generally effective in controllingP. falciparumparasitemia, but mortality from CM and other forms of severe malaria remains unacceptably high. Herein, we report the design and synthesis of a novel carbon monoxide-releasing molecule (CO-RM; ALF492) that fully protects mice against experimental CM (ECM) and ALI. ALF492 enables controlled CO deliveryin vivowithout affecting oxygen transport by hemoglobin, the major limitation in CO inhalation therapy. The protective effect is CO dependent and induces the expression of heme oxygenase-1, which contributes to the observed protection. Importantly, when used in combination with the antimalarial drug artesunate, ALF492 is an effective adjunctive and adjuvant treatment for ECM, conferring protection after the onset of severe disease. This study paves the way for the potential use of CO-RMs, such as ALF492, as adjunctive/adjuvant treatment in severe forms of malaria infection.
High-Level Cefixime- and Ceftriaxone-Resistant Neisseria gonorrhoeae in France: Novel
penA
Mosaic Allele in a Successful International Clone Causes Treatment Failure
Authors: Unemo Magnus , Golparian Daniel , Nicholas Robert , Ohnishi Makoto , Gallay Anne , Sednaoui Patrice 
Published: December 2011

ABSTRACT

Recently, the first
Neisseria gonorrhoeae
strain (H041) highly resistant to the expanded-spectrum cephalosporins (ESCs) ceftriaxone and cefixime, which are the last remaining options for first-line gonorrhea treatment, was isolated in Japan. Here, we confirm and characterize a second strain (F89) with high-level cefixime and ceftriaxone resistance which was isolated in France and most likely caused a treatment failure with cefixime. F89 was examined using six species-confirmatory tests, antibiograms (33 antimicrobials),
porB
sequencing,
N. gonorrhoeae
multiantigen sequence typing (NG-MAST), multilocus sequence typing (MLST), and sequencing of known gonococcal resistance determinants (
penA
,
mtrR
,
penB
,
ponA
, and
pilQ
). F89 was assigned to MLST sequence type 1901 (ST1901) and NG-MAST ST1407, which is a successful gonococcal clone that has spread globally. F89 has high-level resistance to cefixime (MIC = 4 μg/ml) and ceftriaxone (MIC = 1 to 2 μg/ml) and resistance to most other antimicrobials examined. A novel
penA
mosaic allele (
penA-CI
), which was
penA-XXXIV
with an additional A501P alteration in penicillin-binding protein 2, was the primary determinant for high-level ESC resistance, as determined by transformation into a set of recipient strains.
N. gonorrhoeae
appears to be emerging as a superbug, and in certain circumstances and settings, gonorrhea may become untreatable. Investigations of the biological fitness and enhanced understanding and monitoring of the ESC-resistant clones and their international transmission are required. Enhanced disease control activities, antimicrobial resistance control and surveillance worldwide, and public health response plans for global (and national) perspectives are also crucial. Nevertheless, new treatment strategies and/or drugs and, ideally, a vaccine are essential to develop for efficacious gonorrhea management.
Efficacy and Tolerability of Antibiotic Combinations in Neurobrucellosis: Results of the Istanbul Study
Authors: Erdem Hakan , Ulu-Kilic Ayşegül , Kilic Selim , Karahocagil Mustafa , Shehata Ghaydaa , Eren-Tulek Necla , Yetkin Funda , Celen Mustafa Kemal , Ceran Nurgul , Gul Hanefi Cem , Mert Gurkan , Tekin-Koruk Suda , Dizbay Murat , Inal Ayse Seza , Nayman-Alpat Saygın , Bosilkovski Mile , Inan Dilara , Saltoglu Nese , Abdel-Baky Laila , Adeva-Bartolome Maria Teresa , Ceylan Bahadır , Sacar Suzan , Turhan Vedat , Yılmaz Emel , Elaldi Nazif , Kocak-Tufan Zeliha , Uğurlu Kenan , Dokuzoğuz Başak , Yılmaz Hava , Gundes Sibel , Guner Rahmet , Ozgunes Nail , Ulcay Asim , Unal Serhat , Dayan Saim , Gorenek Levent , Karakas Ahmet , Tasova Yesim , Usluer Gaye , Bayindir Yasar , Kurtaran Behice , Sipahi Oguz Resat , Leblebicioglu Hakan 
Published: December 2011

ABSTRACT

No data on whether brucellar meningitis or meningoencephalitis can be treated with oral antibiotics or whether an intravenous extended-spectrum cephalosporin, namely, ceftriaxone, which does not accumulate in phagocytes, should be added to the regimen exist in the literature. The aim of a study conducted in Istanbul, Turkey, was to compare the efficacy and tolerability of ceftriaxone-based antibiotic treatment regimens with those of an oral treatment protocol in patients with these conditions. This retrospective study enrolled 215 adult patients in 28 health care institutions from four different countries. The first protocol (P1) comprised ceftriaxone, rifampin, and doxycycline. The second protocol (P2) consisted of trimethoprim-sulfamethoxazole, rifampin, and doxycycline. In the third protocol (P3), the patients started with P1 and transferred to P2 when ceftriaxone was stopped. The treatment period was shorter with the regimens which included ceftriaxone (4.40 ± 2.47 months in P1, 6.52 ± 4.15 months in P2, and 5.18 ± 2.27 months in P3) (
P
= 0.002). In seven patients, therapy was modified due to antibiotic side effects. When these cases were excluded, therapeutic failure did not differ significantly between ceftriaxone-based regimens (
n
= 5/166, 3.0%) and the oral therapy (
n
= 4/42, 9.5%) (
P
= 0.084). The efficacy of the ceftriaxone-based regimens was found to be better (
n
= 6/166 [3.6%] versus
n
= 6/42 [14.3%];
P
= 0.017) when a composite negative outcome (CNO; relapse plus therapeutic failure) was considered. Accordingly, CNO was greatest in P2 (14.3%,
n
= 6/42) compared to P1 (2.6%,
n
= 3/117) and P3 (6.1%,
n
= 3/49) (
P
= 0.020). Seemingly, ceftriaxone-based regimens are more successful and require shorter therapy than the oral treatment protocol.
Detecting common-cause relationships with directional information transfer
Authors: Hannisdal Bjarte 
Published: December 2011

Abstract
Correlations between sedimentary rock and fossil records may involve a combination of rock-record sampling bias and common response to external forcing. Quantifying their relative importance from incomplete and uncertain proxy data is not trivial given the potential complexity of interactions among the underlying processes. This paper shows how a non-parametric method can be used to detect causal interactions directly from incomplete and irregular time series, by quantifying directional information transfer between variables. A numerical experiment illustrates how estimates of the relative strength, scale, and directionality of coupling can correctly distinguish a common-cause variable from a spurious relationship, even in cases where correlations are misleading. With a joint analysis of Phanerozoic rock and fossil records pending, the method is applied to oxygen, carbon, and sulphur stable isotope records from marine carbonates, identifying complex interactions between climatic changes and the cycling of carbon and sulphur over the Phanerozoic.
Microarchitectural Transformations Using Elasticity
Authors: Galceran-Oms Marc , Gotmanov Alexander , Cortadella Jordi , Kishinevsky Mike 
Published: December 2011

Elasticity is a paradigm that tolerates the variations in computation and communication delays. By applying elastic transformations that allow varying the original timing, circuits can be optimized beyond the conventional rigid transformations that do not modify the external timing.
Pipelining is one of the classical techniques to improve the throughput of a circuit. This article reveals how elasticity can be effectively and practically used to derive pipelined circuits by using correct-by-construction transformations that can be fully automated. Two designs, one of them industrial, are used to demonstrate how the area-performance trade-off can be explored using elasticity.
Nanocarriers Enhance Doxorubicin Uptake in Drug-Resistant Ovarian Cancer Cells
Authors: Arora Hans C. , Jensen Mark P. , Yuan Ye , Wu Aiguo , Vogt Stefan , Paunesku Tatjana , Woloschak Gayle E. 
Published: December 2011

AbstractResistance to anthracyclines and other chemotherapeutics due to P-glycoprotein (pgp)-mediated export is a frequent problem in cancer treatment. Here, we report that iron oxide–titanium dioxide core-shell nanocomposites can serve as efficient carriers for doxorubicin to overcome this common mechanism of drug resistance in cancer cells. Doxorubicin nanocarriers (DNC) increased effective drug uptake in drug-resistant ovarian cells. Mechanistically, doxorubicin bound to the TiO2 surface by a labile bond that was severed upon acidification within cell endosomes. Upon its release, doxorubicin traversed the intracellular milieu and entered the cell nucleus by a route that evaded pgp-mediated drug export. Confocal and X-ray fluorescence microscopy and flow cytometry were used to show the ability of DNCs to modulate transferrin uptake and distribution in cells. Increased transferrin uptake occurred through clathrin-mediated endocytosis, indicating that nanocomposites and DNCs may both interfere with removal of transferrin from cells. Together, our findings show that DNCs not only provide an alternative route of delivery of doxorubicin to pgp-overexpressing cancer cells but also may boost the uptake of transferrin-tagged therapeutic agents. Cancer Res; 72(3); 769–78. ©2011 AACR.
Clinical Effects of Adjuvant Active Specific Immunotherapy Differ between Patients with Microsatellite-Stable and Microsatellite-Instable Colon Cancer
Authors: de Weger Vincent A. , Turksma Annelies W. , Voorham Quirinus J.M. , Euler Zelda , Bril Herman , van den Eertwegh Alfons J. , Bloemena Elisabeth , Pinedo Herbert M. , Vermorken Jan B. , van Tinteren Harm , Meijer Gerrit A. , Hooijberg Erik 
Published: December 2011

Abstract
Purpose: Active specific immunotherapy (ASI) consisting of an autologous tumor cell vaccine given as adjuvant treatment has been shown to improve recurrence-free survival of patients with colon cancer. The aim of the current retrospective study was to investigate whether the beneficial effects of ASI given as adjuvant treatment correlated with microsatellite instability (MSI), which is considered an important biologic determinant of colon cancer.
Experimental Design: Microsatellite status was assessed on archival tumor material from patients with stage II and III colon cancer. Microsatellite status was next associated with clinical outcome in control and ASI treatment groups using Kaplan–Meier analysis.
Results: We identified 162 (83%) microsatellite-stable tumors (MSS) and 34 (17%) MSI tumors. Patients with MSI tumors did well in recurrence-free interval (RFI) as well as disease-specific survival (DSS) irrespective of treatment arm and tumor stage. Patients with MSI tumors had significantly fewer recurrences and prolonged DSS than those with MSS tumors. Patients with MSS Dukes B tumors who received ASI treatment showed a significantly improved recurrence-free survival compared with controls. ASI treatment did not improve recurrence-free interval or DSS for patients with MSS Dukes C tumors.
Conclusion: This retrospective study indicated that patients with MSI tumors did well, irrespective of treatment arm and tumor stage. The data also indicate that the clinical benefit, measured as recurrence-free survival, from adjuvant ASI treatment of patients with colon cancer was restricted to patients with MSS Dukes B tumors. Clin Cancer Res; 18(3); 882–9. ©2011 AACR.
Selective BRAF Inhibitors Induce Marked T-cell Infiltration into Human Metastatic Melanoma
Authors: Wilmott James S. , Long Georgina V. , Howle Julie R. , Haydu Lauren E. , Sharma Raghwa N. , Thompson John F. , Kefford Richard F. , Hersey Peter , Scolyer Richard A. 
Published: December 2011

Abstract
Purpose: To evaluate the effects of treatment with the potent mutant BRAF inhibitors GSK2118436 or vemurafenib (PLX4720) on immune responses to metastatic melanoma in tissues taken before and after treatment.
Experimental Design: Thirty-seven tumor biopsies were collected from 15 patients with unresectable American Joint Committee on Cancer stage III or IV melanoma immediately before and approximately 7 days after the commencement of BRAF inhibitor treatment and at the time of tumor progression. Immunohistochemical staining was carried out on the biopsies using specific antibodies for CD8, CD4, CD20, CD1a, and Granzyme B.
Results: Tumor infiltration by CD4+ and CD8+ lymphocytes increased markedly following BRAF inhibitor treatment (both ρ = 0.015). There was a correlation between the degree of tumor infiltration by CD8+ and Granzyme B–expressing lymphocytes in post–BRAF inhibitor–treated biopsies (r = 0.690 and ρ = 0.013). Increased intratumoral CD8+ lymphocyte expression was correlated with a reduction in tumor size and an increase in necrosis in posttreatment biopsies (r = −0.793, ρ = 0.011; and r = 0.761, ρ = 0.004, respectively).
Conclusions: The increase in tumor-infiltrating lymphocytes induced by treatment with BRAF inhibitors provides strong support for conducting trials that combine BRAF inhibitors with immunotherapy in the hope of prolonging clinical responses. Clin Cancer Res; 18(5); 1386–94. ©2011 AACR.
Blood Cell Origin of Circulating MicroRNAs: A Cautionary Note for Cancer Biomarker Studies
Authors: Pritchard Colin C. , Kroh Evan , Wood Brent , Arroyo Jason D. , Dougherty Katy J. , Miyaji Melanie M. , Tait Jonathan F. , Tewari Muneesh 
Published: December 2011

Abstract
Circulating, cell-free microRNAs (miRNAs) hold great promise as a new class of cancer biomarkers due to their surprisingly high stability in plasma, association with disease states, and ease of sensitive measurement. Yet little is known about the origin of circulating miRNAs in either healthy or sick people or what factors influence levels of circulating miRNA biomarkers. Of 79 solid tumor circulating miRNA biomarkers reported in the literature, we found that 58% (46 of 79) are highly expressed in one or more blood cell type. Plasma levels of miRNA biomarkers expressed by myeloid (e.g., miR-223, miR-197, miR-574-3p, and let-7a) and lymphoid (e.g., miR-150) blood cells tightly correlated with corresponding white blood cell counts. Plasma miRNA biomarkers expressed by red blood cells (e.g., miR-486-5p, miR-451, miR-92a, and miR-16) could not be correlated to red cell counts due to limited variation in hematocrit in the cohort studied but were significantly increased in hemolyzed specimens (20- to 30-fold plasma increase; P &lt; 0.0000001). Finally, in a patient undergoing autologous hematopoietic cell transplantation, plasma levels of myeloid- and lymphoid-expressed miRNAs (miR-223 and miR-150, respectively) tracked closely with changes in corresponding blood counts. We present evidence that blood cells are a major contributor to circulating miRNA and that perturbations in blood cell counts and hemolysis can alter plasma miRNA biomarker levels by up to 50-fold. Given that a majority of reported circulating miRNA cancer biomarkers are highly expressed in blood cells, we suggest caution in interpretation of such results as they may reflect a blood cell-based phenomenon rather than a cancer-specific origin. Cancer Prev Res; 5(3); 492–7. ©2011 AACR.
The preparation and electrical properties of the functionalized graphene/poly (ether sulfone) nanocomposites
Authors: Yin Shangbing , Rong Changru , Zhang Shuling , Huo Pengfei , Wang Guibin 
Published: December 2011

Chemical functionalized graphene (f-G) was obtained by the reaction of the residual epoxide and carboxyl functional groups on the hydrazine-reduced graphene (G) sheets with hydroquinone. The efficacy of the functionalization reaction of graphene was confirmed by X-ray photoelectron spectroscopy and thermogravimetric analysis. Atomic force microscopy and transmission electron microscopy images showed that the functionalized graphene can be easily exfoliated into functionalized graphene nanosheets composed of single or bilayers of graphene sheets. The f-G was used to prepare conductive poly (ether sulfone) (PES) composites (f-G/PES) via the solution casting method and the alternating current (AC) and direct current (DC) properties of f-G/PES composites were investigated. It was observed that good dispersion of f-G nanosheets in PES matrix resulted in a low percolation threshold of 0.355 vol.%. Hopping type of charge transport occurred during the insulator–semiconductor transition of f-G/PES composites. Impedance measurement was carried out to evaluate interfacial capacitance of the composites, and the interfacial capacitance of the composites increased to 1041.9 pF of f-G/PES composites with 5 wt.% f-G from 30.48 pF of f-G/PES composites with 0.5 wt.% f-G.
Surgery for fistula-in-ano in a specialist colorectal unit: a critical appraisal
Authors: Sileri Pierpaolo , Cadeddu Federica , D'Ugo Stefano , Franceschilli Luana , Del Vecchio Blanco Giovanna , De Luca Elisabetta , Calabrese Emma , Capperucci Sara Mara , Fiaschetti Valeria , Milito Giovanni , Gaspari Achille Lucio 
Published: December 2011

Abstract

Background
Several techniques have been described for the management of fistula-in-ano, but all carry their own risks of recurrence and incontinence. We conducted a prospective study to assess type of presentation, treatment strategy and outcome over a 5-year period.

Methods
Between 1st January 2005 and 31st March 2011 247 patients presenting with anal fistulas were treated at the University Hospital Tor Vergata and were included in the present prospective study. Mean age was 47 years (range 16-76 years); minimum follow-up period was 6 months (mean 40, range 6-74 months).
Patients were treated using 4 operative approaches: fistulotomy, fistulectomy, seton placement and rectal advancement flap. Data analyzed included: age, gender, type of fistula, operative intervention, healing rate, postoperative complications, reinterventions and recurrence.

Results
Etiologies of fistulas were cryptoglandular (n = 218), Crohn's disease (n = 26) and Ulcerative Colitis (n = 3). Fistulae were classified as simple -intersphincteric 57 (23%), low transphincteric 28 (11%) and complex -high transphicteric 122 (49%), suprasphincteric 2 (0.8%), extrasphinteric 2 (0.8%), recto-vaginal 7 (2.8%) Crohn 26 (10%) and UC 3 (1.2%).
The most common surgical procedure was the placement of seton (62%), usually applied in case of complex fistulae and Crohn's patients.
Eighty-five patients (34%) underwent fistulotomy, mainly for intersphincteric and mid/low transphincteric tracts. Crohn's patients were submitted to placement of one or more loose setons.
The main treatment successfully eradicated the primary fistula tract in 151/247 patients (61%). Three cases of major incontinence (1.3%) were detected during the follow-up period; Furthermore, three patients complained minor incontinence that was successfully treated by biofeedback and permacol injection into the internal anal sphincter.

Conclusions
This prospective audit demonstrates an high proportion of complex anal fistulae treated by seton placement that was the most common surgical technique adopted to treat our patients as a first line. Nevertheless, a good outcome was achieved in the majority of patients with a limited rate of faecal incontinence (6/247 = 2.4%). New technologies provide promising alternatives to traditional methods of management particularly in case of complex fistulas. There is, however, a real need for high-quality randomized control trials to evaluate the different surgical and non surgical treatment options.