bluuebunny/crossref_metadata_2025_split huggingface dataset:
Partitioning of the primate intraparietal cortex based on connectivity pattern and immunohistochemistry for Cat‐301 and SMI‐32
Authors: Mariani Otavio S. C. , Lima Bruss , Soares Juliana G. M. , Mayer Andrei , Franca João G. , Gattass Ricardo 
Published: March 2018

AbstractWe propose a partitioning of the primate intraparietal sulcus (IPS) using immunoarchitectural and connectivity criteria. We studied the immunoarchitecture of the IPS areas in the capuchin monkey using Cat‐301 and SMI‐32 immunohistochemistry. In addition, we investigated the IPS projections to areas V4, TEO, PO, and MT using retrograde tracer injections in nine hemispheres of seven animals. The pattern and distribution of Cat‐301 and SMI‐32 immunostaining revealed multiple areas in the IPS, in the adjoining PO cleft and in the annectant gyrus, with differential staining patterns found for areas V3d, DM, V3A, DI, PO, POd, CIP‐1, CIP‐2, VIPa, VIPp, LIPva, LIPvp, LIPda, LIPdp, PIPv, PIPd, MIPv, MIPd, AIPda, AIPdp, and AIPv. Areas V4, TEO, PO, MT, which belong to different cortical streams of visual information processing, receive projections from at least twenty different areas within the IPS and adjoining regions. In six animals, we analyzed the distribution of retrogradely labeled cells in tangential sections of flat‐mount IPS preparations. The lateral bank of the IPS projects to regions belonging both to the ventral (V4 and TEO) and dorsal (PO and MT) streams. The region on the floor of the IPS (i.e., VIP) projects predominantly to dorsal stream areas. Finally, the medial bank of the IPS (i.e., MIP) projects solely to the dorsalmedial stream (PO). Therefore, our data suggest that ventral and dorsal streams remain segregated within the IPS, and that its projections to the dorsal stream can be further segregated based on those targeting the dorsolateral versus the dorsomedial subdivisions.
Parallel rule‐based selective sampling and on‐demand learning to rank
Authors: e Freitas Mateus F. , Sousa Daniel X. , Martins Wellington S. , Rosa Thierson C. , Silva Rodrigo M. , Gonçalves Marcos A. 
Published: March 2018

SummaryLearning to rank (L2R) works by constructing a ranking model from training data so that, given a new query, the model is able to generate an effective rank of the objects for the query. Almost all work in L2R focus on ranking accuracy leaving performance and scalability overlooked. However, performance is a critical factor, especially when dealing with on‐demand queries. In this scenario, Learning to Rank using association rules has been shown to be extremely effective but only at a high computational cost. In this work, we show how to exploit parallelism on rule‐based systems to: i) drastically reduce L2R training datasets using selective sampling and ii) to generate query customized ranking models on the fly. We present parallel algorithms and GPU implementations for these two tasks showing that dataset reduction takes only a few seconds with speedups up to 148x over a serial baseline, and that queries can be processed in only a few milliseconds with speedups of 1000x over a serial baseline and 29x over a parallel baseline for the best case. We also extend the implementations to work with multiple GPUs, further increasing the speedup over the baselines and showing the scalability of our proposed algorithms.
Quantification of alignment of vascular smooth muscle cells
Authors: Dorta Marcel P. , de Brito Isis V. , Pereira Alexandre C. , Alencar Adriano M. 
Published: March 2018

AbstractVascular smooth muscle cells (VSMCs) are essential components that keep the tonus of the arterial network, which is the channel used to conduct the blood from the heart to the peripheral areas of the body. It is known that mechanical and architectural changes in VSMCs may lead to functional modifications in the cardiovascular system; therefore, the quantitative characterization of these changes can help to elucidate questions that remain unclear in pathological situations, such as hypertension, vasospasm, vascular hypertrophy, and atherosclerosis. In this work, we have developed a new framework of image processing using the Sobel operator, associated with statistical analysis, to determine the degree of local alignment of actin filaments, which we found to be directly related with the distensibility of the arterial wall. We have also compared these results with the rigidity of the cytoskeleton of VSMCs. The results suggest that the alignment degree increases from peripheral arteries, such as carotid and femoral, to central arteries, as well coronary and thoracic aorta, which can indicate that the level of local alignment of the actin fibers in VSMCs is related with the mechanical behavior of the arterial wall. © 2018 International Society for Advancement of Cytometry
Hepatic and cardiac beneficial effects of a long‐acting Fc‐apelin fusion protein in diet‐induced obese mice
Authors: Wang Weimin , Zhang Dongming , Yang Rongze , Xia Wei , Qian Kun , Shi Zhengrong , Brown Robert , Zhou Huifen , Xi Yue , Shi Lin , Chen Ling , Xu Feng , Sun Xiaojian , Zhu Dalong , Gong Da‐Wei 
Published: March 2018

AbstractBackgroundApelin is a peptide ligand of the G‐protein‐coupled receptor APJ and exhibits anti‐diabetes and anti‐heart failure activities. However, short serum half‐life of the apelin peptide limits its potential clinical applications. This study aimed to develop a long‐acting apelin analog.MethodsTo extend apelin's in vivo half‐life, we made a recombinant protein by fusing the IgG Fc fragment to apelin‐13 (Fc‐apelin‐13), conducted pharmacokinetics studies in mice, and determined in vitro biological activities in suppressing cyclic adenosine monophosphate and activating extracellular signal‐regulated kinase signalling by reporter assays. We investigated the effects of Fc‐apelin‐13 on food intake, body weight, fasting blood glucose and insulin levels, glucose tolerance test, hepatic steatosis, and cardiac function and fibrosis by subcutaneous administration of Fc‐apelin‐13 in diet‐induced obese mice for 4 weeks.ResultsThe estimated half‐life of Fc‐apelin‐13 in blood was approximately 33 hours. Reporter assays showed that Fc‐apelin‐13 was active in suppressing cyclic adenosine monophosphate response element and activating serum response element activities. Four weeks of Fc‐apelin‐13 treatment in obese mice did not affect food intake and body weight, but resulted in a significant improvement of glucose tolerance, and a decrease in hepatic steatosis and fibrosis, as well as in serum alanine transaminase levels. Moreover, cardiac stroke volume and output were increased and cardiac fibrosis was decreased in the treated mice.ConclusionsFc‐apelin‐13 fusion protein has an extended in vivo half‐life and exerts multiple benefits on obese mice with respect to the improvement of glucose disposal, amelioration of liver steatosis and heart fibrosis, and increase of cardiac output. Hence, Fc‐apelin‐13 is potentially a therapeutic for obesity‐associated disease conditions.
Metabolism study for CUMYL‐4CN‐BINACA in human hepatocytes and authentic urine specimens: Free cyanide is formed during the main metabolic pathway
Authors: Åstrand Anna , Vikingsson Svante , Lindstedt Daniel , Thelander Gunilla , Gréen Henrik , Kronstrand Robert , Wohlfarth Ariane 
Published: March 2018

AbstractTo further elucidate the metabolism of CUMYL‐4CN‐BINACA, a new synthetic cannabinoid with a cyano group, and to evaluate biomarkers, we incubated the substance in human hepatocytes and analysed 9 authentic urine specimens. We also quantified CUMYL‐4CN‐BINACA and cyanide in blood and provide comprehensive data on the 7 autopsy cases, 5 of them determined CUMYL‐4CN‐BINACA intoxications. For metabolite elucidation, CUMYL‐4CN‐BINACA was incubated with pooled human hepatocytes for up to 5 hours, urine samples were analysed with and without enzymatic hydrolysis. Data was acquired in data‐dependent mode by ultra‐high performance liquid chromatography–high resolution mass spectrometry (UHPLC–HRMS) with an Agilent 6550 QTOF. For quantitative analysis of CUMYL‐4CN‐BINACA, blood samples were precipitated and analysed by liquid chromatography–tandem mass spectrometry (LC–MS/MS). Cyanide was determined by gas chromatography–headspace–nitrogen phosphorus detection (GC–headspace–NPD). CUMYL‐4CN‐BINACA was metabolised via CYP450‐mediated hydroxylation at 4‐butyl position generating a cyanohydrin (M12), which releases free cyanide to form an aldehyde intermediate and eventually generates 4‐hydroxybutyl CUMYL‐BINACA (M11) and CUMYL‐BINACA butanoic acid (M10). Other minor metabolites were produced by hydroxylation, dihydroxylation, N‐dealkylation, and dihydrodiol formation; glucuronidation was observed. One urine sample showed high intensities of M10 and a wide variety of metabolites; the other samples contained fewer metabolites in low abundance and 1 sample showed no metabolites. CUMYL‐4CN‐BINACA blood concentrations ranged from 0.1 to 8.3 ng/g showing an overlap between fatal and non‐fatal concentrations. One blood sample contained 0.36 μg/g cyanide. Release of free cyanide during metabolism is worrying as it might induce liver toxicity. As suggested earlier, CUMYL‐BINACA butanoic acid is the most abundant biomarker in urine, but monitoring of additional metabolites or, even better, analysis for the parent in blood is recommended.
Effects of sodium‐glucose cotransporter 2 inhibitor, tofogliflozin, on the indices of renal tubular function in patients with type 2 diabetes
Authors: Nunoi Kiyohide , Sato Yuichi , Kaku Kohei , Yoshida Akihiro , Suganami Hideki 
Published: March 2018

SummaryAimsLittle is known of the effect of sodium‐glucose cotransporter 2 (SGLT2) inhibitors on the renal tubules. We investigated the effect of the SGLT2 inhibitor, tofogliflozin (TOFO) on renal tubular indices, according to the degree of albuminuria, in type 2 diabetes mellitus (T2DM) patients with preserved renal function.Materials and methodsA total of 988 patients, receiving TOFO, were enroled and divided into 3 groups, based on the urine albumin‐to‐creatinine ratio (UACR). The tubular indices (urinary N‐acetyl‐beta‐d‐glucosaminidase [NAG]‐to‐creatinine and urinary beta‐2 microglobulin [beta2MG]‐to‐creatinine ratios) and UACR were log‐transformed in the correlation analysis.ResultsTreatment with TOFO led to similar reductions in glycated haemoglobin (HbA1c) levels, from baseline to week 24, across all groups. The NAG level increased in the normoalbuminuria group and decreased in the macroalbuminuria group significantly (P < .001, both), but did not change in the microalbuminuria group. Significant reductions in the UACR were observed in both microalbuminuria and macroalbuminuria groups (P < .001, both). Significant negative correlations between changes in the NAG and beta2MG levels and their corresponding baseline values were observed in all participants. The reduction in the UACR was negatively correlated with baseline levels. The changes in the tubular indices were positively correlated with reductions in the UACR across groups.ConclusionsLogarithmic reductions in the renal tubular indices, via SGLT2 inhibition, were observed in patients with T2DM. TOFO may not only improve the degree of albuminuria but may also have protective effects on the tubules.
Comorbidity between pain and mental illness – Evidence of a bidirectional relationship
Authors: Bondesson E. , Larrosa Pardo F. , Stigmar K. , Ringqvist Å. , Petersson I.F. , Jöud A. , Schelin M.E.C. 
Published: March 2018

AbstractBackgroundPain from various locations in the body and mental illness are common and the comorbidity between the two is well‐known although the temporal relationship remains to be determined. Our aim was to follow patients over time to study if pain (here dorsalgia/abdominal pain) or fibromyalgia lead to an increased risk of developing mental illness (here depression/anxiety) and/or the reverse, that is whether patients with mental illness have an increased risk to develop pain or fibromyalgia, compared to the rest of the population.MethodsThis prospective cohort study used the Skåne Healthcare Register, covering all care in the region of Skåne, southern Sweden (population ~1.3 million). The cohort included healthcare consultations in primary care, outpatient specialized care and inpatient care between 2007 and 2016 for all patients without prior registered diagnosis of mental illness or pain, aged 18 or older (n = 504,365).ResultsThe incidence rate ratio (IRR) for developing mental illness after pain was 2.18 (95% CI = 2.14–2.22) compared to without pain. IRR for developing pain after mental illness was 2.02 (95% CI = 1.98–2.06) compared to without mental illness. Corresponding IRR for developing mental illness after fibromyalgia was 4.05 (95% CI = 3.58–4.59) and for developing fibromyalgia after mental illness 5.54 (95% CI = 4.99–6.16).ConclusionsThis study shows a bidirectional influence of similar magnitude of pain and mental illness, respectively. In monitoring patients with pain or mental illness, a focus on both conditions is thus important to develop appropriate, targeted interventions and may increase the likelihood of improved outcomes.SignificanceWe followed a population‐based cohort over a period of 10 years, including incident cases of both exposure and outcome and found a bidirectional relationship between pain and mental illness. Clinicians need to pay attention on both conditions, in patients seeking care due to mental illness or pain.
Transcranial direct current stimulation for upper limb neuropathic pain: A double‐blind randomized controlled trial
Authors: Lewis G.N. , Rice D.A. , Kluger M. , McNair P.J. 
Published: March 2018

AbstractBackgroundWhile promising, there are mixed findings for the efficacy of transcranial direct current stimulation (tDCS) for the management of chronic pain. The goal of this study was to evaluate the effect of anodal tDCS on pain and function in people with upper limb neuropathic pain.MethodsThe study was a double‐blinded, randomized controlled trial. Thirty participants were randomly allocated into active and sham tDCS groups. Baseline assessments of pain and function, as well as quantitative sensory testing (QST) to probe the function of the nociceptive system, were undertaken prior to participants receiving 5 days of active or sham anodal tDCS (1 mA) over the primary motor cortex. The outcome measures were re‐assessed 1, 3 and 8 weeks following the intervention.ResultsGroup analyses revealed no significant improvement in pain, function, or QST measures over time in either group. However, there were significantly more individual responders (≥30% change in pain) in the active compared to the sham tDCS group at the final follow‐up. In the active group, there was a significant correlation indicating those with higher baseline pain had greater pain relief.ConclusionsOn group analyses, no evidence was provided that 1 mA tDCS is beneficial for people with upper limb neuropathic pain, although it may provide lasting pain relief for some individuals.SignificanceAt the group level, we found no evidence that 5 days of active 1 mA tDCS is effective for people with upper limb neuropathic pain. However, there were more individual responders in the active tDCS group compared to sham, and those who responded early after treatment experienced sustained pain relief.
Efficacy and safety of a T‐type calcium channel blocker in patients with neuropathic pain: A proof‐of‐concept, randomized, double‐blind and controlled trial
Authors: Kerckhove N. , Pereira B. , Soriot‐Thomas S. , Alchaar H. , Deleens R. , Hieng V.S. , Serra E. , Lanteri‐Minet M. , Arcagni P. , Picard P. , Lefebvre‐Kuntz D. , Maindet C. , Mick G. , Balp L. , Lucas C. , Creach C. , Letellier M. , Martinez V. , Navez M. , Delbrouck D. , Kuhn E. , Piquet E. , Bozzolo E. , Brosse C. , Lietar B. , Marcaillou F. , Hamdani A. , Leroux‐Bromberg N. , Perier Y. , Vergne‐Salle P. , Gov C. , Delage N. , Gillet D. , Romettino S. , Richard D. , Mallet C. , Bernard L. , Lambert C. , Dubray C. , Duale C. , Eschalier A. 
Published: March 2018

AbstractBackgroundT‐type calcium channels have been shown to play an important role in the initiation and maintenance of neuropathic pain and represent a promising therapeutic target for new analgesic treatments. Ethosuximide (ETX), an anticonvulsant and a T‐type channel blocker has shown analgesic effect in several chronic pain models but has not yet been evaluated in patients with neuropathic pain.MethodsThis proof‐of‐concept, multicentre, double‐blind, controlled and randomized trial compared the efficacy and safety of ETX (given as add‐on therapy) to an inactive control (IC) in 114 patients with non‐diabetic peripheral neuropathic pain. After a 7‐day run‐in period, eligible patients aged over 18 years were randomly assigned (1:1) to ETX or IC for 6 weeks. The primary outcome was the difference between groups in the pain intensity (% of change from the baseline to end of treatment) assessed in the intention‐to‐treat population. This study is registered with EudraCT (2013‐004801‐26) and ClinicalTrials.gov (NCT02100046).ResultsThe study was stopped during the interim analysis due to the high number of adverse events in the active treatment group. ETX failed to reduce total pain and showed a poor tolerance in comparison to IC. In the per‐protocol analysis, ETX significantly reduced pain intensity by 15.6% (95% CI −25.8; −5.4) from baseline compared to IC (−7.8%, 95% CI −14.3; −1.3; p = 0.033), but this result must be interpreted with caution because of a small subgroup of patients.ConclusionEthosuximide did not reduce the severity of neuropathic pain and induces, at the doses used, many adverse events.SignificanceThis article shows that ETX is not effective to treat neuropathic pain. Nevertheless, per‐protocol analysis suggests a possible analgesic effect of ETX. Thus, our work adds significant knowledge to preclinical and clinical data on the benefits of T‐type calcium channel inhibition for the treatment of neuropathic pain.
Occurrence of filamentous fungi in maize destined for human consumption in South Africa
Authors: Ekwomadu Theodora I. , Gopane Ramokone E. , Mwanza Mulunda 
Published: March 2018

AbstractOne‐hundred maize samples were analyzed for fungal contamination using conventional and molecular methods. The percentage incidence of different genera isolated revealed the predominance of Fusarium (82%), Penicillium (63%), and Aspergillus species (33%) compared to other genera. Fusarium occurred in 90% and 74% of small scale and commercial samples, respectively, while Penicillium occurred in small scale and commercial samples at an incidence rate of 64% and 62%, respectively. However, among the species, Fusarium verticilloides have the highest incidence of 70% and 76% in commercial and small‐scale maize, respectively, while Penicillium digitatum has 56% total incidence. Aspergillus fumigatus (27%) were also the most dominant of these genera. Fungal genera isolated included Alternaria and Cladosporium although occurring at a lower incidence level of 30%, 32% and 16%, 20%, respectively, in small‐scale and commercial samples. The results emphasize that farmers and consumers should be alerted to the danger of fungal contamination in maize.
The digital Thailand strategy and the ASEAN community
Authors: Wongwuttiwat Jittima , Lawanna Adtha 
Published: March 2018

AbstractThe progress of Thailand's development needs to be monitored especially in the environment of the ASEAN Economic Community which started formally at the end of the year 2015. Furthermore, Thailand has also established the Thailand 4.0 strategy in alignment with the Thailand 12th Social and Economic Development Plan (2017–2021) and the ASEAN ICT Master Plan in order to drive the Thailand economy into a high‐income country and to be an ASEAN regional center. Because of the efficiency and effectiveness of ICT that can stimulate and support in most work areas, ICT aims to be the foundation of the country's development in other aspects. Thus, Thailand's Ministry of ICT has launched various ICT policies and programs for ICT administrators of different economic sectors because ICT has been considered as an engine of country development, and this causes Thailand to rely more on the adoption of ICT in various sectors. This study focuses on the progression of ICT development and investments, country infrastructures, the quality of the higher education system, business sophistication, and innovation, which are considered as the principal components of Thailand 4.0 strategy. The findings may assist the responsible authorities in both public and private organizations in monitoring, understanding, and expediting strategies and operations in order to achieve the objectives of Thailand 4.0 and to obtain competitive advantages across the ASEAN Economic Community. Furthermore, the findings also help to detect improvement of the Thailand's performance with respect to the 5 components development relative to the other ASEAN economies.
Benzo[a]pyrene‐decreased gap junctional intercellular communication via calcium/calmodulin signaling increases apoptosis in TM4 cells
Authors: Ji Xiaoli , Chou Xin , Ge Zehe , Ding Fan , Gao Hui , Wu Qing 
Published: March 2018

AbstractThe mechanism of male reproductive toxicity induced by benzo[a]pyrene (BaP) is poorly understood. Gap junctional intercellular communication (GJIC) is known to play a critical role in maintaining spermatogenesis. The aim of the present study was to determine the toxic effects of BaP in Sertoli cells, and to explore the possibility and potential mechanisms of BaP‐induced changes in the level of GJIC, and the relationship between GJIC and BaP‐induced apoptosis. We treated mouse Sertoli cell lines (TM4) with different concentrations (0.1–100 μm) of BaP for 1–48 hours, and found that GJIC exhibited a dose‐ and time‐dependent downregulation. Treatment with 10 μm BaP increased apoptosis, intracellular Ca2+ level ([Ca2+]i) and calmodulin (CaM) protein expression, and decreased the protein level of connexin 43 (Cx43) (also known as gap junction α‐1 protein [GJA1]) in TM4 cells. However, BaP had no effect on the phosphorylation of Cx43 at Ser279/282, Ser255, Ser368 or Ser262. Downregulation of [Ca2+]i by BAPTA‐AM significantly attenuated the BaP‐induced GJIC suppression, Cx43 protein decrease and CaM protein increase. Interestingly, inhibition of CaM expression by W7 partially recovered BaP‐induced GJIC inhibition, but had no effect on BaP‐induced Cx43 protein decrease. Pretreatment with the GJIC activator retinoic acid significantly mitigated BaP‐induced apoptosis. In conclusion, these results suggest that BaP can decrease GJIC via Ca2+/CaM signaling, and that BaP‐induced GJIC suppression increases apoptosis in TM4 cells.