bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of noninvasive quantitative decline in liver fat content on MRI with histologic response in nonalcoholic steatohepatitis
Authors: Patel Janki , Bettencourt Ricki , Cui Jeffrey , Salotti Joanie , Hooker Jonathan , Bhatt Archana , Hernandez Carolyn , Nguyen Phirum , Aryafar Hamed , Valasek Mark , Haufe William , Hooker Catherine , Richards Lisa , Sirlin Claude B. , Loomba Rohit 
Published: July 2016

Background: Magnetic resonance imaging-estimated proton-density-fat-fraction (MRI-PDFF) has been shown to be a noninvasive, accurate and reproducible imaging-based biomarker for assessing steatosis and treatment response in nonalcoholic steatohepatitis (NASH) clinical trials. However, there are no data on the magnitude of MRI-PDFF reduction corresponding to histologic response in the setting of a NASH clinical trial. The aim of this study was to quantitatively compare the magnitude of MRI-PDFF reduction between histologic responders versus histologic nonresponders in NASH patients. Methods: This study is a secondary analysis of the MOZART trial, which included 50 patients with biopsy-proven NASH randomized to ezetimibe 10 mg/day orally or placebo for 24 weeks. The primary aim was to perform a head-to-head comparative analysis of histologic responders [defined as a ⩾2-point reduction in the nonalcoholic fatty liver disease (NAFLD) Activity Score (NAS) without worsening fibrosis] versus nonresponders, and the corresponding quantitative change in liver fat content measured via MRI-PDFF. Results: Of the 35 patients who underwent paired liver biopsy and MRI-PDFF assessment at the beginning and end of treatment, 10 demonstrated a histologic response. Compared with histologic nonresponders, histologic responders had a statistically significant reduction in MRI-PDFF of −4.1% ± 4.9 versus −0.6 ± 4.1 ( p < 0.04) with a mean relative percent change of −29.3% ± 33.0 versus +2.0% ± 24.0 ( p < 0.004), respectively. Conclusions: Utilizing paired MRI-PDFF and liver histology data, we demonstrate that a relative reduction of 29% in liver fat on MRI-PDFF is associated with a histologic response in NASH. After external validation by independent research groups, these results can be incorporated into designing future NASH clinical trials, especially those utilizing change in hepatic fat quantified by MRI-PDFF, as a treatment endpoint.
Safety of long-term exposure to abiraterone acetate in patients with castration-resistant prostate cancer and concomitant cardiovascular risk factors
Authors: Verzoni Elena , Grassi Paolo , Ratta Raffaele , Niger Monica , De Braud Filippo , Valdagni Riccardo , Procopio Giuseppe 
Published: July 2016

Background: We aimed to evaluate the long-term safety profile of abiraterone in patients with metastatic castration-resistant prostate cancer (mCRPC) with controlled cardiovascular comorbidities or risk factors. Methods: We retrospectively analysed the clinical charts of consecutive mCRPC patients with cardiac disorders/risk factors who had been treated with abiraterone 1000 mg once daily plus prednisone 5 mg twice daily for a median duration of 16 months at an oncology referral centre between April 2011 and July 2015. Patients underwent an electrocardiogram (ECG) and echocardiographic assessments, including measurement of left ventricular ejection fraction (LVEF) at baseline and at the end of treatment. Blood pressure (BP) was measured daily at home. During follow up (median 24 months), all adverse events were recorded. Cardiac events (CEs) were defined, according to Common Terminology Criteria for Adverse Events version 4.0, as the appearance of a symptomatic CE that required medical intervention. Results: A total of 51 patients (median age 71 years) were evaluated. Pre-existing cardiovascular conditions included hypertension (41%), cardiac ischaemia (12%), stroke (9%), dyslipidaemia (18%) and type 2 diabetes mellitus (12%). No CEs were recorded and no changes in LVEF were observed. The most frequently reported adverse events were Grade 1–2 fluid retention (18%), hypertension (16%) and asthenia (16%). No patients permanently discontinued abiraterone due to cardiac events. Conclusions: Long-term abiraterone treatment was well tolerated in mCRPC patients with controlled cardiovascular comorbidities/risk factors, with no apparent worsening of cardiovascular conditions from baseline over an extended observation period.
Long noncoding RNAs in B-cell development and activation
Authors: Brazão Tiago F. , Johnson Jethro S. , Müller Jennifer , Heger Andreas , Ponting Chris P. , Tybulewicz Victor L. J. 
Published: July 2016

AbstractLong noncoding RNAs (lncRNAs) are potentially important regulators of cell differentiation and development, but little is known about their roles in B lymphocytes. Using RNA-seq and de novo transcript assembly, we identified 4516 lncRNAs expressed in 11 stages of B-cell development and activation. Most of these lncRNAs have not been previously detected, even in the closely related T-cell lineage. Comparison with lncRNAs previously described in human B cells identified 185 mouse lncRNAs that have human orthologs. Using chromatin immunoprecipitation-seq, we classified 20% of the lncRNAs as either enhancer-associated (eRNA) or promoter-associated RNAs. We identified 126 eRNAs whose expression closely correlated with the nearest coding gene, thereby indicating the likely location of numerous enhancers active in the B-cell lineage. Furthermore, using this catalog of newly discovered lncRNAs, we show that PAX5, a transcription factor required to specify the B-cell lineage, bound to and regulated the expression of 109 lncRNAs in pro-B and mature B cells and 184 lncRNAs in acute lymphoblastic leukemia.
VIP impairs acquisition of the macrophage proinflammatory polarization profile
Authors: Carrión Mar , Pérez-García Selene , Martínez Carmen , Juarranz Yasmina , Estrada-Capetillo Lizbeth , Puig-Kröger Amaya , Gomariz Rosa P , Gutiérrez-Cañas Irene 
Published: July 2016

Abstract
This study tested the hypothesis that vasoactive intestinal peptide (VIP) is able to modify the macrophage inflammatory profile, thus supporting its therapeutic role in autoimmune diseases. Macrophages are innate immune cells that display a variety of functions and inflammatory profiles in response to the environment that critically controls their polarization. Deregulation between the pro- and anti-inflammatory phenotypes has been involved in different pathologies. Rheumatoid arthritis (RA) is an autoimmune disease, in which macrophages are considered central effectors of synovial inflammation, displaying a proinflammatory profile. VIP is a pleiotropic neuropeptide with proven anti-inflammatory actions. As modulation of the macrophage phenotype has been implicated in the resolution of inflammatory diseases, we evaluated whether VIP is able to modulate human macrophage polarization. In vitro-polarized macrophages by GM-CSF (GM-MØ), with a proinflammatory profile, expressed higher levels of VIP receptors, vasoactive intestinal polypeptide receptors 1 and 2 (VPAC1 and VPAC2, respectively), than macrophages polarized by M-CSF (M-MØ) with anti-inflammatory activities. RA synovial macrophages, according to their GM-CSF-like polarization state, expressed both VPAC1 and VPAC2. In vitro-generated GM-MØ exposed to VIP exhibited an up-regulation of M-MØ gene marker expression, whereas their proinflammatory cytokine profile was reduced in favor of an anti-inflammatory function. Likewise, in GM-MØ, generated in the presence of VIP, VIP somehow changes the macrophages physiology profile to a less-damaging phenotype. Therefore, these results add new value to VIP as an immunomodulatory agent on inflammatory diseases.
How Eye-Preserving Therapy Affects Long-Term Overall Survival in Heritable Retinoblastoma Survivors
Authors: Temming Petra , Arendt Marina , Viehmann Anja , Eisele Lewin , Le Guin Claudia H.D. , Schündeln Michael M. , Biewald Eva , Mäusert Jennifer , Wieland Regina , Bornfeld Norbert , Sauerwein Wolfgang , Eggert Angelika , Lohmann Dietmar R. , Jöckel Karl-Heinz 
Published: July 2016

PurposeIntraocular retinoblastoma is curable, but survivors with a heritable predisposition are at high risk for second malignancies. Because second malignancies are associated with high mortality, prognostic factors for second malignancy influence long-term overall survival. This study investigates the impact of all types of eye-preserving therapies on long-term survival in the complete German cohort of patients with heritable retinoblastoma.Patients and MethodsOverall survival, disease staging using international scales, time period of diagnosis, and treatment type were analyzed in the 633 German children treated at the national reference center for heritable retinoblastoma.ResultsThe 5-year overall survival of children diagnosed in Germany with heritable retinoblastoma between 1940 and 2008 was 93.2% (95% CI, 91.2% to 95.1%), but long-term mortality was increased compared with patients with nonheritable disease. Overall survival correlated with tumor staging, and 92% of patients were diagnosed with a favorable tumor stage (International Retinoblastoma Staging System stage 0 or I). Despite a 5-year overall survival of 97.4% (95% CI, 96.0% to 98.8%) in patients with stage 0 or I, only 79.5% (95% CI, 74.2% to 84.8%) of these patients survived 40 years after diagnosis. Long-term overall survival was reduced in children treated with eye-preserving radiotherapy compared with enucleation alone, and adding chemotherapy aggravated this effect.ConclusionThe benefits of preserving vision must be balanced with the impact of eye-preserving treatments on long-term survival in heritable retinoblastoma, and the genetic background of the patient influences choice of eye-preserving treatment. Germline RB1 genetic analysis is important to identify heritable retinoblastoma among unilateral retinoblastoma cases. Eye-preserving radiotherapy should be carefully considered in patients with germline RB1 mutations. Life-long oncologic follow-up is crucial for all retinoblastoma survivors, and less detrimental eye-preserving therapies must be developed.
CALGB 80403 (Alliance)/E1206: A Randomized Phase II Study of Three Chemotherapy Regimens Plus Cetuximab in Metastatic Esophageal and Gastroesophageal Junction Cancers
Authors: Enzinger Peter C. , Burtness Barbara Ann , Niedzwiecki Donna , Ye Xing , Douglas Kathe , Ilson David H. , Villaflor Victoria Meucci , Cohen Steven J. , Mayer Robert J. , Venook Alan , Benson Al Bowen , Goldberg Richard M. 
Published: July 2016

Purpose To determine the optimal chemotherapy backbone for testing in future US cooperative group studies for metastatic esophageal and gastroesophageal junction cancers. Cetuximab was added to each treatment arm based on promising preclinical data. Patients and Methods Patients with previously untreated metastatic esophageal or gastroesophageal junction cancer were randomly assigned at a one-to-one-to-one ratio to epirubicin, cisplatin, and continuous-infusion fluorouracil (ECF), irinotecan plus cisplatin (IC), or FOLFOX (oxaliplatin, leucovorin, and bolus and infusional fluorouracil). All treatment programs included cetuximab once per week. The primary end point was response rate. Secondary outcomes included overall survival, progression-free survival, time to treatment failure, and safety. As prespecified, primary and secondary analyses were conducted only among patients with adenocarcinoma. Results This study randomly assigned 245 patients, including 222 with adenocarcinoma. Among patients with adenocarcinoma, response rate was 60.9% (95% CI, 47.9 to 72.8) for ECF plus cetuximab, 45.0% (95% CI, 33.0 to 57.0) for IC plus cetuximab, and 54.3% (95% CI, 42.0 to 66.2) for FOLFOX plus cetuximab. Median overall survival was 11.6, 8.6, and 11.8 months; median progression-free survival was 7.1, 4.9, and 6.8 months; and median time to treatment failure was 5.6, 4.3, and 6.7 months for each of these arms, respectively. FOLFOX plus cetuximab required fewer treatment modifications compared with ECF plus cetuximab and IC plus cetuximab (P = .013), and fewer patients were removed from treatment because of an adverse event or experienced treatment-related death. Conclusion In combination with cetuximab, ECF and FOLFOX had similar efficacy, but FOLFOX was better tolerated. Although differences were nonsignificant, IC plus cetuximab seemed to be the least effective and most toxic of the three regimens tested.
Considering Bone Marrow Blasts From Nonerythroid Cellularity Improves the Prognostic Evaluation of Myelodysplastic Syndromes
Authors: Arenillas Leonor , Calvo Xavier , Luño Elisa , Senent Leonor , Alonso Esther , Ramos Fernando , Ardanaz María Teresa , Pedro Carme , Tormo Mar , Marco Víctor , Montoro Julia , Díez-Campelo María , Brunet Salut , Arrizabalaga Beatriz , Xicoy Blanca , Andreu Rafael , Bonanad Santiago , Jerez Andrés , Nomdedeu Benet , Ferrer Ana , Sanz Guillermo F. , Florensa Lourdes 
Published: July 2016

Purpose WHO classification of myeloid malignancies is based mainly on the percentage of bone marrow (BM) blasts. This is considered from total nucleated cells (TNCs), unless there is erythroid-hyperplasia (erythroblasts ≥ 50%), calculated from nonerythroid cells (NECs). In these instances, when BM blasts are ≥ 20%, the disorder is classified as erythroleukemia, and when BM blasts are < 20%, as myelodysplastic syndrome (MDS). In the latter, the percentage of blasts is considered from TNCs. Patients and Methods We assessed the percentage of BM blasts from TNCs and NECs in 3,692 patients with MDS from the Grupo Español de Síndromes Mielodisplásicos, 465 patients with erythroid hyperplasia (MDS-E) and 3,227 patients without erythroid hyperplasia. We evaluated the relevance of both quantifications on classification and prognostication. Results By enumerating blasts systematically from NECs, 22% of patients with MDS-E and 12% with MDS from the whole series diagnosed within WHO categories with < 5% BM blasts, were reclassified into higher-risk categories and showed a poorer overall survival than did those who remained in initial categories (P = .006 and P = .001, respectively). Following WHO recommendations, refractory anemia with excess blasts (RAEB)-2 diagnosis is not possible in MDS-E, as patients with 10% to < 20% BM blasts from TNCs fulfill erythroleukemia criteria; however, by considering blasts from NECs, 72 patients were recoded as RAEB-2 and showed an inferior overall survival than did patients with RAEB-1 without erythroid hyperplasia. Recalculating the International Prognostic Scoring System by enumerating blasts from NECs in MDS-E and in the overall MDS population reclassified approximately 9% of lower-risk patients into higher-risk categories, which indicated the survival expected for higher-risk patients. Conclusion Regardless of the presence of erythroid hyperplasia, calculating the percentage of BM blasts from NECs improves prognostic assessment of MDS. This fact should be considered in future WHO classification reviews.
Non-Lethal Type VIII Osteogenesis Imperfecta Has Elevated Bone Matrix Mineralization
Authors: Fratzl-Zelman Nadja , Barnes Aileen M. , Weis MaryAnn , Carter Erin , Hefferan Theresa E. , Perino Giorgio , Chang Weizhong , Smith Peter A. , Roschger Paul , Klaushofer Klaus , Glorieux Francis H. , Eyre David R. , Raggio Cathleen , Rauch Frank , Marini Joan C. 
Published: July 2016

Abstract

Context:
Type VIII osteogenesis imperfecta (OI; OMIM 601915) is a recessive form of lethal or severe OI caused by null mutations in P3H1, which encodes prolyl 3-hydroxylase 1.

Objectives:
Clinical and bone material description of non-lethal type VIII OI.

Design:
Natural history study of type VIII OI.

Setting:
Pediatric academic research centers.

Patients:
Five patients with non-lethal type VIII OI, and one patient with lethal type VIII OI.

Interventions:
None.

Main Outcome Measures:
Clinical examinations included bone mineral density, radiographs, and serum and urinary metabolites. Bone biopsy samples were analyzed for histomorphometry and bone mineral density distribution by quantitative backscattered electron imaging microscopy. Collagen biochemistry was examined by mass spectrometry, and collagen fibrils were examined by transmission electron microscopy.

Results:
Type VIII OI patients have extreme growth deficiency, an L1–L4 areal bone mineral density Z-score of −5 to −6, and normal bone formation markers. Collagen from bone and skin tissue and cultured osteoblasts and fibroblasts have nearly absent 3-hydroxylation (1–4%). Collagen fibrils showed abnormal diameters and irregular borders. Bone histomorphometry revealed decreased cortical width and very thin trabeculae with patches of increased osteoid, although the overall osteoid surface was normal. Quantitative backscattered electron imaging showed increased matrix mineralization of cortical and trabecular bone, typical of other OI types. However, the proportion of bone with low mineralization was increased in type VIII OI bone, compared to type VII OI.

Conclusions:
P3H1 is the unique enzyme responsible for collagen 3-hydroxylation in skin and bone. Bone from non-lethal type VIII OI children is similar to type VII, especially bone matrix hypermineralization, but it has distinctive features including extremely thin trabeculae, focal osteoid accumulation, and an increased proportion of low mineralized bone.
The temperature dependence of electrical excitability in fish hearts
Authors: Vornanen Matti 
Published: July 2016

ABSTRACT
Environmental temperature has pervasive effects on the rate of life processes in ectothermic animals. Animal performance is affected by temperature, but there are finite thermal limits for vital body functions, including contraction of the heart. This Review discusses the electrical excitation that initiates and controls the rate and rhythm of fish cardiac contraction and is therefore a central factor in the temperature-dependent modulation of fish cardiac function. The control of cardiac electrical excitability should be sensitive enough to respond to temperature changes but simultaneously robust enough to protect against cardiac arrhythmia; therefore, the thermal resilience and plasticity of electrical excitation are physiological qualities that may affect the ability of fishes to adjust to climate change. Acute changes in temperature alter the frequency of the heartbeat and the duration of atrial and ventricular action potentials (APs). Prolonged exposure to new thermal conditions induces compensatory changes in ion channel expression and function, which usually partially alleviate the direct effects of temperature on cardiac APs and heart rate. The most heat-sensitive molecular components contributing to the electrical excitation of the fish heart seem to be Na+ channels, which may set the upper thermal limit for the cardiac excitability by compromising the initiation of the cardiac AP at high temperatures. In cardiac and other excitable cells, the different temperature dependencies of the outward K+ current and inward Na+ current may compromise electrical excitability at temperature extremes, a hypothesis termed the temperature-dependent depression of electrical excitation.
Lubricating the swordfish head
Authors: Videler John J. , Haydar Deniz , Snoek Roelant , Hoving Henk-Jan T. , Szabo Ben G. 
Published: July 2016

ABSTRACT
The swordfish is reputedly the fastest swimmer on Earth. The concave head and iconic sword are unique characteristics, but how they contribute to its speed is still unknown. Recent computed tomography scans revealed a poorly mineralised area near the base of the rostrum. Here we report, using magnetic resonance imaging and electron microscopy scanning, the discovery of a complex organ consisting of an oil-producing gland connected to capillaries that communicate with oil-excreting pores in the skin of the head. The capillary vessels transport oil to abundant tiny circular pores that are surrounded by denticles. The oil is distributed from the pores over the front part of the head. The oil inside the gland is identical to that found on the skin and is a mixture of methyl esters. We hypothesize that the oil layer, in combination with the denticles, creates a super-hydrophobic layer that reduces streamwise friction drag and increases swimming efficiency.
Jumping mechanisms and performance in beetles. I. Flea beetles (Coleoptera: Chrysomelidae: Alticini)
Authors: Nadein Konstantin , Betz Oliver 
Published: July 2016

ABSTRACTThe present study analyses the anatomy, mechanics and functional morphology of the jumping apparatus, the performance and the kinematics of the natural jump of flea beetles (Coleoptera: Chrysomelidae: Galerucinae: Alticini). The kinematic parameters of the initial phase of the jump were calculated for five species from five genera (average values from minimum to maximum): acceleration 0.91–2.25 (×103) m s−2, velocity 1.48–2.80 m s−1, time to take-off 1.35–2.25 ms, kinetic energy 2.43–16.5 µJ, g-force 93–230. The jumping apparatus is localized in the hind legs and formed by the femur, tibia, femoro-tibial joint, modified metafemoral extensor tendon, extensor ligament, tibial flexor sclerite, and extensor and flexor muscles. The primary role of the metafemoral extensor tendon is seen in the formation of an increased attachment site for the extensor muscles. The rubber-like protein resilin was detected in the extensor ligament, i.e. a short, elastic element connecting the extensor tendon with the tibial base. The calculated specific joint power (max. 0.714 W g−1) of the femoro-tibial joint during the jumping movement and the fast full extension of the hind tibia (1–3 ms) suggest that jumping is performed via a catapult mechanism releasing energy that has beforehand been stored in the extensor ligament during its stretching by the extensor muscles. In addition, the morphology of the femoro-tibial joint suggests that the co-contraction of the flexor and the extensor muscles in the femur of the jumping leg is involved in this process.
School Subjects Work Program Requirements and Assessment Criterion Development
Authors: ��������  , Kuznetsov A. 
Published: July 2016

The article considers the development of structure and contents of program components requirements for school subjects in accordance with the new
Federal State Education Standard, connection between the requirements and assessment criteria of the programs, improvement of program structure,
development of the educational results requirements, levels of acquisition of learning material, requirements to the explanatory notes to the program,
development of the intersubject communications and content-related course lines.
Readiness Criteria of Medical Students for Professionally Oriented Oral Communication in Foreign Language
Authors: �������  , Petrova E. , ������  , Ilina Nina 
Published: July 2016

In the article approaches to determination of students� readiness to professionally oriented oral communication in foreign language are considered. The
formation of students� readiness to professionally oriented oral communication in foreign language depends on the level of mastering by them theoretical
components of psychology, linguistics and practical skills, including special sciences. Students� readiness to professionally oriented oral communication
in foreign language is a professionally signifi cant quality and is considered, as unity of personal, theoretical and practical readiness. According
to structural components of readiness the criteria refl ecting specifi cs of readiness to professionally oriented oral communication in foreign language
are developed as means and conditions of preparation for it: motivation and profession, activity and speech, interpersonal communication, result and
competitiveness. When developing criteria the main parameters are determined and levels of students� readiness to professionally oriented oral communication
in foreign language are characterized.