bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of alfaxalone and dexmedetomidine for intramuscular restraint in European hedgehogs (Erinaceus europaeus)
Authors: Bellini Luca , Pagani Gaia , Mollo Antonio , Contiero Barbara , Loretti Enrico , Gelli Donatella 
Published: July 2019

The European hedgehogs may require the use of chemical restraint for clinical examination because of their tendency to roll up as a defensive behaviour. This study evaluated the effects of alfaxalone combined with dexmedetomidine for restraint of hedgehogs undergoing pre‐release health checks and atipamezole for recovery.Twenty hedgehogs received alfaxalone 2 mg/kg and dexmedetomidine 0.05 mg/kg intramuscularly in the quadriceps. If the righting reflex was still present, both drugs were administered at half of the initial doses. A semiquantitative scale scored sedation; clinical variables evaluated included pulse rate, respiratory rate, arterial haemoglobin oxygen saturation, end‐tidal CO2 and body temperature.The righting reflex disappeared between 141 and 880 seconds. Overweight animals required one additional injection to achieve adequate relaxation. Pulse rate decreased during the procedure and increased after atipamezole administration. Respiratory rate and end‐tidal CO2 did not change statistically throughout the procedure but one hedgehog showed haemoglobin oxygen saturation lower than 90%. Recovery after atipamezole was smooth and complete. Body temperature decreased over time.The sedation protocol may represent an effective combination to restrain European hedgehogs and atipamezole provides a rapid antagonism. Additional sedatives administration may be required in overweight animals and an external source of oxygen should be available.
Comparative effects of low zinc oxide dose with or without probiotics relative to high zinc oxide dose on the performance, nutrient digestibility, blood metabolites, and noxious gases emission in weaned piglets
Authors: Shi Huan , Upadhaya Santi Devi , Kim In Ho 
Published: July 2019

The objective of this study was to assess the effects of low-dose zinc oxide (ZnO) supplemented with or without probiotic complex compared with pharmacological ZnO (3000 mg kg−1) on the performance, digestibility, blood metabolites, fecal Lactobacillus and enterobacteria counts of weaned piglets. One-hundred and twenty crossbred piglets were randomly allocated to three treatments based on their initial body weight (BW). Treatments consisted of corn–soybean-meal-based basal diet supplemented with 3000 mg kg−1 ZnO as positive control (ZH), basal diet supplemented with 300 mg kg−1 ZnO as negative control (ZL), and ZL + 0.1% probiotic complex (ZLP). At the end of the experiment, fecal samples were collected by direct rectal massage to determine nutrient digestibility, Lactobacillus and enterobacteria counts, and gas emission, whereas blood samples were taken via jugular venipuncture for determination of blood metabolites. The BW of piglets at week 6, and the average daily gain (ADG) at week 6 and during overall period were higher (P < 0.05) in pigs fed ZH diet compared with those fed ZL diet. The supplementation of ZLP increased the ADG during week 6 and overall making it comparable with ZH diet (P < 0.05). However, other parameters described above were comparable with ZH in pigs fed ZLP diet.
Influence of crop residues and nitrogen fertilizer on soil water repellency and soil hydrophobicity under long-term no-till
Authors: Miller J.J. , Owen M.L. , Ellert B.H. , Yang X.M. , Drury C.F. , Chanasyk D.S. 
Published: July 2019

Crop residues and N fertilizer under no-till may increase soil water repellency (SWR) and soil hydrophobicity, but few studies have examined these two treatment factors and their interaction. A laboratory study was conducted using a long-term (since 1999) field experiment on a clay loam soil to determine the effect of three crop residues and two N fertilizer levels on SWR and soil hydrophobicity under no-till within the Dark Brown soil zone of the semi-arid Canadian prairies. The three residue treatments were residues removed from soil (Rx0), residues returned to soil (Rx1), and residues supplemented to soil (Rx2). The two fertilizer N treatments were 0 (N0) and 45 kg N ha−1 (N1). Surface (0–10 cm) soil samples were taken in the spring of 2017 after 17 yr. Laboratory measurements were conducted on air-dried and sieved (<2 mm) soil to determine SWR using the repellency index method (RI), soil organic C, hydrophobic CH and hydrophilic CO functional groups, and soil hydrophobicity (CH/CO ratio). Mean RI values ranged from 2.19 to 2.75, indicating subcritical (RI > 1.95) SWR. Similar (P > 0.05) RI values were found for the three residue and two N fertilizer treatments, but the trend was for greater RI with increased residue addition (by 12%–26%) and N fertilizer (by 8%). Soil hydrophobicity was significantly greater by 47%–82% for straw returned or supplemented than straw removed treatments, and by 33% for fertilized than unfertilized treatments. Overall, greater residues and N fertilizer had no effect on SWR, but significantly increased soil hydrophobicity.
Differential activation of lumbar and sacral motor pools during walking at different speeds and slopes
Authors: Dewolf A. H. , Ivanenko Y. P. , Zelik K. E. , Lacquaniti F. , Willems P. A. 
Published: July 2019

Organization of spinal motor output has become of interest for investigating differential activation of lumbar and sacral motor pools during locomotor tasks. Motor pools are associated with functional grouping of motoneurons of the lower limb muscles. Here we examined how the spatiotemporal organization of lumbar and sacral motor pool activity during walking is orchestrated with slope of terrain and speed of progression. Ten subjects walked on an instrumented treadmill at different slopes and imposed speeds. Kinetics, kinematics, and electromyography of 16 lower limb muscles were recorded. The spinal locomotor output was assessed by decomposing the coordinated muscle activation profiles into a small set of common factors and by mapping them onto the rostrocaudal location of the motoneuron pools. Our results show that lumbar and sacral motor pool activity depend on slope and speed. Compared with level walking, sacral motor pools decrease their activity at negative slopes and increase at positive slopes, whereas lumbar motor pools increase their engagement when both positive and negative slope increase. These findings are consistent with a differential involvement of the lumbar and the sacral motor pools in relation to changes in positive and negative center of body mass mechanical power production due to slope and speed.NEW & NOTEWORTHY In this study, the spatiotemporal maps of motoneuron activity in the spinal cord were assessed during walking at different slopes and speeds. We found differential involvement of lumbar and sacral motor pools in relation to changes in positive and negative center of body mass power production due to slope and speed. The results are consistent with recent findings about the specialization of neuronal networks located at different segments of the spinal cord for performing specific locomotor tasks.
Heterosynaptic facilitation of mechanical nociceptive input is dependent on the frequency of conditioning stimulation
Authors: van den Broeke E. N. , Gousset S. , Bouvy J. , Stouffs A. , Lebrun L. , van Neerven S. G. A. , Mouraux A. 
Published: July 2019

High-frequency burstlike electrical conditioning stimulation (HFS) applied to human skin induces an increase in mechanical pinprick sensitivity of the surrounding unconditioned skin (a phenomenon known as secondary hyperalgesia). The present study assessed the effect of frequency of conditioning stimulation on the development of this increased pinprick sensitivity in humans. In a first experiment, we compared the increase in pinprick sensitivity induced by HFS, using monophasic non-charge-compensated pulses and biphasic charge-compensated pulses. High-frequency stimulation, traditionally delivered with non-charge-compensated square-wave pulses, may induce a cumulative depolarization of primary afferents and/or changes in pH at the electrode-tissue interface due to the accumulation of a net residue charge after each pulse. Both could contribute to the development of the increased pinprick sensitivity in a frequency-dependent fashion. We found no significant difference in the increase in pinprick sensitivity between HFS delivered with charge-compensated and non-charge-compensated pulses, indicating that the possible contribution of charge accumulation when non-charge-compensated pulses are used is negligible. In a second experiment, we assessed the effect of different frequencies of conditioning stimulation (5, 20, 42, and 100 Hz) using charge-compensated pulses on the development of increased pinprick sensitivity. The maximal increase in pinprick sensitivity was observed at intermediate frequencies of stimulation (20 and 42 Hz). It is hypothesized that the stronger increase in pinprick sensitivity at intermediate frequencies may be related to the stronger release of substance P and/or neurokinin-1 receptor activation expressed at lamina I neurons after C-fiber stimulation. NEW & NOTEWORTHY Burstlike electrical conditioning stimulation applied to human skin induces an increase in pinprick sensitivity in the surrounding unconditioned skin (a phenomenon referred to as secondary hyperalgesia). Here we show that the development of the increase in pinprick sensitivity is dependent on the frequency of the burstlike electrical conditioning stimulation.
The amnestic agent anisomycin disrupts intrinsic membrane properties of hippocampal neurons via a loss of cellular energetics
Authors: Scavuzzo C. J. , LeBlancq M. J. , Nargang F. , Lemieux H. , Hamilton T. J. , Dickson C. T. 
Published: July 2019

The nearly axiomatic idea that de novo protein synthesis is necessary for long-term memory consolidation is based heavily on behavioral studies using translational inhibitors such as anisomycin. Although inhibiting protein synthesis has been shown to disrupt the expression of memory, translational inhibitors also have been found to profoundly disrupt basic neurobiological functions, including the suppression of ongoing neural activity in vivo. In the present study, using transverse hippocampal brain slices, we monitored the passive and active membrane properties of hippocampal CA1 pyramidal neurons using intracellular whole cell recordings during a brief ~30-min exposure to fast-bath-perfused anisomycin. Anisomycin suppressed protein synthesis to 46% of control levels as measured using incorporation of radiolabeled amino acids and autoradiography. During its application, anisomycin caused a significant depolarization of the membrane potential, without any changes in apparent input resistance or membrane time constant. Anisomycin-treated neurons also showed significant decreases in firing frequencies and spike amplitudes, and showed increases in spike width across spike trains, without changes in spike threshold. Because these changes indicated a loss of cellular energetics contributing to maintenance of ionic gradients across the membrane, we confirmed that anisomycin impaired mitochondrial function by reduced staining with 2,3,5-triphenyltetrazolium chloride and also impaired cytochrome c oxidase (complex IV) activity as indicated through high-resolution respirometry. These findings emphasize that anisomycin-induced alterations in neural activity and metabolism are a likely consequence of cell-wide translational inhibition. Critical reevaluation of studies using translational inhibitors to promote the protein synthesis dependent idea of long-term memory is absolutely necessary. NEW & NOTEWORTHY Memory consolidation is thought to be dependent on the synthesis of new proteins because translational inhibitors produce amnesia when administered just after learning. However, these agents also disrupt basic neurobiological functions. We show that blocking protein synthesis disrupts basic membrane properties of hippocampal neurons that correspond to induced disruptions of mitochondrial function. It is likely that translational inhibitors cause amnesia through their disruption of neural activity as a result of dysfunction of intracellular energetics.
Evaluation of Residual Disease and TKI Duration Are Critical Predictive Factors for Molecular Recurrence after Stopping Imatinib First-line in Chronic Phase CML Patients
Authors: Nicolini Franck Emmanuel , Dulucq Stéphanie , Boureau Lisa , Cony-Makhoul Pascale , Charbonnier Aude , Escoffre-Barbe Martine , Rigal-Huguet Françoise , Coiteux Valérie , Varet Bruno , Dubruille Viviane , Lenain Pascal , Rousselot Philippe , Rea Delphine , Guerci-Bresler Agnès , Legros Laurence , Liu Jixing , Gardembas Martine , Ianotto Jean-Christophe , Turlure Pascal , Johnson-Ansah Hyacinthe , Martiniuc Juliana , Jardel Henry , Joly Bertrand , Zunic Patricia , Henni Tawfiq , Villemagne Bruno , Berger Marc G. , Cayssials Emilie , Guilhot François , Larosa Fabrice , Guilhot Joëlle , Etienne Gabriel , Mahon François-Xavier 
Published: July 2019

Abstract

Purpose:
Tyrosine kinase inhibitor (TKI) discontinuation is an emerging goal in chronic myelogenous leukemia (CML) management and several studies have demonstrated the feasibility of safely stopping imatinib. A sustained deep molecular response on long-term TKI is critical prior to attempting treatment-free remission. Reproducible results from several studies reported recently, failed to identify robust and reproducible predictive factors for the selection of the best candidates for successful TKI cessation.

Patients and Methods:
We conducted a prospective national phase II study evaluating the cessation of imatinib after at least 2 years of MR4.5 obtained on imatinib first-line in patients with chronic phase CML.

Results:
A total of 218 patients with de novo chronic phase CML were involved in the study. The median follow-up after imatinib cessation was 23.5 (1–64) months, 2 patients died from unrelated causes, and 107 experienced a confirmed increase in BCR-ABL1 levels defined as molecular recurrence. The molecular recurrence-free survival was 52% [95% confidence interval (CI), 45%–59%] at 6 months, and 50% (95% CI, 43%–57%) at 24 months. Droplet digital PCR (ddPCR) was used to evaluate more accurately low levels of BCR-ABL1 in 175 of 218 patients at imatinib cessation. To apply positive BCR-ABL1/ABL1 ratios on the international scale (IS), a conversion factor was calculated for ddPCR and the significant cut-off point was established at 0.0023%IS. In a multivariate analysis, the duration of TKI (≥74.8 months) and ddPCR (≥0.0023%IS) were the two identified predictive factors of molecular recurrence, with P = 0.0366 (HR, 0.635; 95% CI, 0.415–0.972] and P = 0.008 (HR, 0.556; 95% CI, 0.360–0.858), respectively.

Conclusions:
We conclude that the duration of TKI and residual leukemic cell load as determined by ddPCR are key factors for predicting successful treatment-free remission for patients with de novo chronic phase CML.
See related commentary by Yan et al., p. 6561
A Novel Anti-HER2 Antibody–Drug Conjugate XMT-1522 for HER2-Positive Breast and Gastric Cancers Resistant to Trastuzumab Emtansine
Authors: Le Joncour Vadim , Martins Ana , Puhka Maija , Isola Jorma , Salmikangas Marko , Laakkonen Pirjo , Joensuu Heikki , Barok Mark 
Published: July 2019

Abstract
Most patients with HER2-positive breast or gastric cancer exhibit primary or acquired resistance to trastuzumab emtansine (T-DM1), and such patients may have limited therapeutic options. XMT-1522 is a novel anti-HER2 antibody–drug conjugate. We compared XMT-1522 to T-DM1 in preclinical models. The effects of XMT-1522 and T-DM1 on cell survival and apoptosis were compared in six HER2-positive breast cancer or gastric cancer cell lines, of which three lines were T-DM1–sensitive (N-87, OE-19, JIMT-1) and three T-DM1–resistant (RN-87, ROE-19, SNU-216). We compared these agents also in the HER2-negative breast cancer cell line MCF-7, and in mouse RN-87 and JIMT-1 xenograft models. Cell survival was assessed using the AlamarBlue method and apoptosis with the Caspase-Glo 3/7 method. XMT-1522 inhibited the growth of all six HER2-positive cell lines. The proportions of cells that survived XMT-1522 treatment were smaller as compared with T-DM1, particularly in the T-DM1–resistant cell lines. XMT-1522 induced more cell apoptosis compared with T-DM1. While RN-87 and JIMT-1 xenograft tumors progressed on T-DM1 treatment, all tumors responded to XMT-1522, and all but one tumor disappeared during the XMT-1522 treatment. XMT-1522 had a strong antitumor effect on RN-87 and JIMT-1 xenografts that progressed on T-DM1. We conclude that XMT-1522 was effective in HER2-positive breast cancer and gastric cancer cell lines resistant to T-DM1, and in xenograft models resistant to T-DM1. The results support the testing of XMT-1522 in clinical trials in patients with HER2-positive cancer.
Efficient Tumor Clearance and Diversified Immunity through Neoepitope Vaccines and Combinatorial Immunotherapy
Authors: Lee Karin L. , Benz Stephen C. , Hicks Kristin C. , Nguyen Andrew , Gameiro Sofia R. , Palena Claudia , Sanborn John Z. , Su Zhen , Ordentlich Peter , Rohlin Lars , Lee John H. , Rabizadeh Shahrooz , Soon-Shiong Patrick , Niazi Kayvan , Schlom Jeffrey , Hamilton Duane H. 
Published: July 2019

Abstract
Progressive tumor growth is associated with deficits in the immunity generated against tumor antigens. Vaccines targeting tumor neoepitopes have the potential to address qualitative defects; however, additional mechanisms of immune failure may underlie tumor progression. In such cases, patients would benefit from additional immune-oncology agents targeting potential mechanisms of immune failure. This study explores the identification of neoepitopes in the MC38 colon carcinoma model by comparison of tumor to normal DNA and tumor RNA sequencing technology, as well as neoepitope delivery by both peptide- and adenovirus-based vaccination strategies. To improve antitumor efficacies, we combined the vaccine with a group of rationally selected immune-oncology agents. We utilized an IL15 superagonist to enhance the development of antigen-specific immunity initiated by the neoepitope vaccine, PD-L1 blockade to reduce tumor immunosuppression, and a tumor-targeted IL12 molecule to facilitate T-cell function within the tumor microenvironment. Analysis of tumor-infiltrating leukocytes demonstrated this multifaceted treatment regimen was required to promote the influx of CD8+ T cells and enhance the expression of transcripts relating to T-cell activation/effector function. Tumor-targeted IL12 resulted in a marked increase in clonality of T-cell repertoire infiltrating the tumor, which when sculpted with the addition of either a peptide or adenoviral neoepitope vaccine promoted efficient tumor clearance. In addition, the neoepitope vaccine induced the spread of immunity to neoepitopes expressed by the tumor but not contained within the vaccine. These results demonstrate the importance of combining neoepitope-targeting vaccines with a multifaceted treatment regimen to generate effective antitumor immunity.
ФОРМУВАННЯ МЕДИЧНИХ БІЗНЕС-ПРОЦЕСІВ У СТОМАТОЛОГІЧНОМУ ЦЕНТРІ НА ПРИНЦИПАХ ДЕРЖАВНО-ПРИВАТНОГО ПАРТНЕРСТВА
Authors: Chopchik V. D. , Orlova N. M. 
Published: July 2019

Мета: науково обґрунтувати методологію стандартизації медичних бізнес-процесів у стоматологічному центрі на принципах державно-приватного партнерства.
Матеріали і методи. Методологію стандартизації медичних бізнес-процесів у стоматологічному центрі обґрунтовано на основі системного підходу і системного аналізу із використанням інформаційно-аналітичного методу. Інформаційною базою для її формування є наукові праці фахівців із організації та управління охороною здоров’я, а також результати власних досліджень.
Результати. Основна мета радикальної зміни медичних бізнес-процесів у стоматологічному центрі на принципах державно-приватного партнерства – запровадження абсолютно нових способів виконання робіт, реструктуризація виробництва послуг, що забезпечить підвищення ефективності управління, фінансово-господарської діяльності та якості послуг. У дослідженні здійснено обґрунтування методології структуризації діяльності стоматологічного центру; виділено основні медичні бізнес-процеси із вказанням ключових чинників, які їх формують; визначено вхідні та вихідні події кожної групи бізнес-процесів, а також необхідні ресурси, функції і керуючі впливи для їх реалізації. Все це забезпечує орієнтацію роботи стоматологічного центру на пацієнта, підвищує ефективність використання наявних ресурсів, покращує контроль над діяльністю медичного персоналу і забезпечує підвищення якості медичної допомоги, що в кінцевому результаті сприяє збереженню стоматологічного здоров’я населення.
Висновки. Запропонована у статті методологія стандартизації медичних бізнес-процесів, яка забезпечує формування груп бізнес-процесів при наданні стоматологічної допомоги, забезпечує пацієнторієнтовану організацію роботи стоматологічного центру, підвищує ефективність використання наявних ресурсів, покращує контроль за діяльністю медичного персоналу, забезпечує підвищення якості медичної допомоги.
Tainted Love: The Trials and Tribulations of a Career in Animal Studies
Authors: O’Sullivan Siobhan , Watt Yvette , Probyn-Rapsey Fiona 
Published: July 2019

AbstractDeveloping an academic career can be exciting, rewarding and stimulating. It can also be challenging, disheartening, and highly insecure. Results from a survey of Animal Studies (AS) scholars identifies reasons why pursuing a career in AS might generate additional challenges, over and above those experienced by academics generally. For example, 44 percent of respondents stated that in their view, undertaking research in AS “creates challenges for an academic career.” This is compared to just 16 percent who thought that it is an advantage. Yet despite the challenges, there is much that is positive about AS. Participants described being in “dialogue with clever colleagues,” viewed their work as “totally engaging,” and reported feeling “morally useful.” This in turn affords AS scholars an authenticity that may be of long-term benefit in the competitive and constantly transforming world of higher education.
Activities of essential oils from three Brazilian plants and benzaldehyde analogues against Meloidogyne incognita
Authors: Barros Aline Ferreira , Campos Vicente Paulo , de Oliveira Denilson Ferreira , Silva Fabiola de Jesus , Jardim Iselino Nogueira , Costa Viviane Aparecida , Matrangolo Carlos Augusto Rodrigues , Ribeiro Regina Cássia Ferreira , Silva Geraldo Humberto 
Published: July 2019

Summary
There is a demand for novel products for the control of plant-parasitic nematodes, so we characterised the effectiveness of some plant essential oils against Meloidogyne incognita and verified the efficiency of the major component from the most toxic oils and their analogues using in vitro and in vivo assays. In this study, the essential oils from Piptadenia viridiflora, Hyptis suaveolens and Astronium graveolens against M. incognita were evaluated, but only P. viridiflora oil showed toxicity toward M. incognita. Benzaldehyde was its main component according to GC-MS analysis. In in vitro assays, benzaldehyde (100 and 200 μg ml−1) and its oxime (400 μg ml−1) caused a higher rate of M. incognita second-stage juvenile (J2) mortality than the nematicide carbofuran (170 μg ml−1). Reductions of more than 90% in the number of galls and eggs, even greater than that observed with carbofuran, were observed in the assay where the J2 were placed in solutions of benzaldehyde and its oxime 48 h prior to tomato plant inoculation. Application of benzaldehyde together with M. incognita J2 to the substrate resulted only in a reduction in the number of eggs (42-65%); however, its oxime reduced both the number of galls (43-84%) and eggs (23-89%). Therefore, the P. viridiflora oil, its major component benzaldehyde, and the analogue benzaldehyde oxime are toxic to M. incognita. In two different in vivo assays, benzaldehyde oxime was confirmed as toxic to M. incognita with a greater efficacy than benzaldehyde.