bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temperatures and blood counts in pediatric patients treated with chemotherapy for cancer, NCT01683370
Authors: Lavieri Luana , Koenig Christa , Teuffel Oliver , Agyeman Philipp , Ammann Roland A. 
Published: July 2019

AbstractFever in neutropenia (FN) is the most frequent potentially lethal complication of chemotherapy in patients with cancer. The temperature limit defining fever (TLDF) for FN is based on scarce evidence. This prospective, single center observational study recruited non-selected pediatric patients diagnosed with cancer between ≥1 and ≤17 years in 2012 and 2013. Of 40 patients potentially eligible, 39 participated. Data of 8896 temperature measurements and 1873 complete blood counts (CBCs) were recorded over 289 months (24.1 years) of chemotherapy exposure time. During this time 43 FN episodes were diagnosed. In 32 episodes, FN diagnosis was based on reaching the local (i.e. Bern, Switzerland) standard TLDF of 39.0 °C; another 11 episodes had been captured by clinical judgement (i.e. temperature < 39.0 °C). These data can be used to simulate the effects of various TLDFs on the rate of FN diagnosis. We assume merging these data with other data sets is feasible.
A high-resolution gridded dataset to assess electrification in sub-Saharan Africa
Authors: Falchetta Giacomo , Pachauri Shonali , Parkinson Simon , Byers Edward 
Published: July 2019

AbstractSpatially explicit data on electricity access and use are essential for effective policy-making and infrastructure planning in low-income, data-scarce regions. We present and validate a 1-km resolution electricity access dataset covering sub-Saharan Africa built on gridded nighttime light, population, and land cover data. Using light radiance probability distributions, we define electricity consumption tiers for urban and rural areas and estimate the by-tier split of consumers living in electrified areas. The approach provides new insight into the spatial distribution and temporal evolution of electricity access, and a measure of its quality beyond binary access. We find our estimates to be broadly consistent with recently published province- and national-level statistics. Moreover, we demonstrate consistency between the estimated electricity access quality indicators and survey-based consumption levels defined in accordance with the World Bank Multi-Tier Framework. The dataset is readily reproduced and updated using an open-access scientific computing framework. The data and approach can be applied for improving the assessment of least-cost electrification options, and examining links between electricity access and other sustainable development objectives.
Methylnaltrexone is safe in cancer patients with peritoneal carcinomatosis
Authors: Nelson Kirbylee K. , Schattner Mark A. , Mendelsohn Robin B. 
Published: July 2019

AbstractOpioid-induced constipation (OIC) has become increasingly prevalent with the rise of prescription opioid use and can significantly impact quality of life, especially in patients with advanced illness. Methylnaltrexone has proven effective in treating cancer patients with OIC who have not responded adequately to conventional laxative therapy, though use is relatively contraindicated in those with peritoneal carcinomatosis due to theoretical risk and reported cases of perforation. The aim of this study was to evaluate the safety of methylnaltrexone in patients with carcinomatosis. We performed a retrospective review of 3058 pediatric and adult patients who received methylnaltrexone at Memorial Sloan Kettering Cancer Center from 2009–2016. Data collected included age, cancer diagnosis, history of abdominal surgery, prior radiation therapy, evidence of peritoneal carcinomatosis, and complications. Charts were reviewed for any complications at 24 hours, 72 hours, and one week following drug administration, as well as at present. We identified 3058 patients (median age 56, range 1–95) who received a total of 3995 doses of methylnaltrexone. Three hundred thirty three (median age 55, range 4–88) had peritoneal carcinomatosis. The most common primary malignancies included pancreatic (17.7%), ovarian (13.5%), colon (7.2%), and lung (6.6%). 228/333 (68.4%) had a history of abdominal surgery and 85/333 (25.5%) underwent prior radiation therapy. Three patients had adverse outcomes or complications, with only one (0.3%) thought to be related to methylnaltrexone use. To our knowledge, this is the largest study to evaluate the outcomes of patients with carcinomatosis receiving methylnaltrexone and the first to include pediatric patients. We found one perforation attributed to methylnaltrexone. Methylnaltrexone should be considered for treatment of refractory OIC in cancer patients with peritoneal carcinomatosis due to low risk of complications.
Multiparametric rapid screening of neuronal process pathology for drug target identification in HSP patient-specific neurons
Authors: Rehbach Kristina , Kesavan Jaideep , Hauser Stefan , Ritzenhofen Swetlana , Jungverdorben Johannes , Schüle Rebecca , Schöls Ludger , Peitz Michael , Brüstle Oliver 
Published: July 2019

AbstractAxonal degeneration is a key pathology of neurodegenerative diseases, including hereditary spastic paraplegia (HSP), a disorder characterized by spasticity in the lower limbs. Treatments for HSP and other neurodegenerative diseases are mainly symptomatic. While iPSC-derived neurons are valuable for drug discovery and target identification, these applications require robust differentiation paradigms and rapid phenotypic read-outs ranging between hours and a few days. Using spastic paraplegia type 4 (SPG4, the most frequent HSP subtype) as an exemplar, we here present three rapid phenotypic assays for uncovering neuronal process pathologies in iPSC-derived glutamatergic cortical neurons. Specifically, these assays detected a 51% reduction in neurite outgrowth and a 60% increase in growth cone area already 24 hours after plating; axonal swellings, a hallmark of HSP pathology, was discernible after only 5 days. Remarkably, the identified phenotypes were neuron subtype-specific and not detectable in SPG4-derived GABAergic forebrain neurons. We transferred all three phenotypic assays to a 96-well setup, applied small molecules and found that a liver X receptor (LXR) agonist rescued all three phenotypes in HSP neurons, providing a potential drug target for HSP treatment. We expect this multiparametric and rapid phenotyping approach to accelerate development of therapeutic compounds for HSP and other neurodegenerative diseases.
On the potential of in vitro organ-chip models to define temporal pharmacokinetic-pharmacodynamic relationships
Authors: McAleer Christopher W. , Pointon Amy , Long Christopher J. , Brighton Rocky L. , Wilkin Benjamin D. , Bridges L. Richard , Narasimhan Sriram Narasimham , Fabre Kristin , McDougall Robin , Muse Victorine P. , Mettetal Jerome T. , Srivastava Abhishek , Williams Dominic , Schnepper Mark T. , Roles Jeff L. , Shuler Michael L. , Hickman James J. , Ewart Lorna 
Published: July 2019

AbstractFunctional human-on-a-chip systems hold great promise to enable quantitative translation to in vivo outcomes. Here, we explored this concept using a pumpless heart only and heart:liver system to evaluate the temporal pharmacokinetic/pharmacodynamic (PKPD) relationship for terfenadine. There was a time dependent drug-induced increase in field potential duration in the cardiac compartment in response to terfenadine and that response was modulated using a metabolically competent liver module that converted terfenadine to fexofenadine. Using this data, a mathematical model was developed to predict the effect of terfenadine in preclinical species. Developing confidence that microphysiological models could have a transformative effect on drug discovery, we also tested a previously discovered proprietary AstraZeneca small molecule and correctly determined the cardiotoxic response to its metabolite in the heart:liver system. Overall our findings serve as a guiding principle to future investigations of temporal concentration response relationships in these innovative in vitro models, especially, if validated across multiple time frames, with additional pharmacological mechanisms and molecules representing a broad chemical diversity.
A key variant in the cis-regulatory element of flowering gene Ghd8 associated with cold tolerance in rice
Authors: Wang Peng , Xiong Yin , Gong Rong , Yang Ying , Fan Kai , Yu Sibin 
Published: July 2019

AbstractVariations in the gene promoter play critical roles in the evolution of important adaptive traits in crops, but direct links of the regulatory mutation to the adaptive change are not well understood. Here, we examine the nucleotide variations in the promoter region of a transcription factor (Ghd8) that control grain number, plant height and heading date in rice. We find that a dominant promoter type of subspecies japonica displayed a high activity for Ghd8 expression in comparison with the one in indica. Transgenic analyses revealed that higher expression levels of Ghd8 delayed heading date and enhanced cold tolerance in rice. Furthermore, a single-nucleotide polymorphism (T1279G) at the position −1279 bp that locates on the potential GA-responsive motif in the Ghd8 promoter affected the expression of this gene. The 1279 T variant has elevated expression of Ghd8, thus conferring increased cold tolerance of rice seedlings. Nucleotide diversity analysis revealed that the approximately 25-kb genomic region surrounding Ghd8 in the subspecies japonica was under significant selection pressure. Our findings demonstrate that the join effects of the regulatory and coding variants largely contribute to the divergence of japonica and indica and increase the adaptability of japonica to the cold environment.
Viral hepatitis and Treponema pallidum prevalence in persons who underwent premarital blood tests in Argentina
Authors: Angeleri Patricia , Levite Valeria , Vidiella Gabriela , Solari Joaquín , Coronel Emma , Adaszko Dan , Adaszko Ariel , Moyano Cecilia , Bouchet Diosnel , Cuello Héctor , Molfese Viviana , Skarzauskas Rosario , Vila Marcelo , Falistocco Carlos , Pando Maria A. 
Published: July 2019

AbstractThe objective of this study was to estimate the prevalence of different serological markers of hepatitis A, B and C viruses and Treponema pallidum among the adult population of Argentina. To achieve this, adults who attended health services for premarital exams (which are mandatory and includes screening for syphilis) were recruited. A cross-sectional study was designed with a cluster sampling strategy. Couples who attended selected health services for premarital screening between 2013 and 2014 in Buenos Aires, Cordoba, Mendoza and Santa Fe provinces were included. A total of 3833 individuals were recruited. Anti-HAV prevalence was 63.9%, anti-HCV 0.3%, anti-HBc (without HBsAg) 1.9%, HBsAg 0.3%, and T pallidum 0.8%. Anti-HAV was higher among older participants, foreigners and those from the lower strata. HBV increased with age and was higher among foreigners and those with lower formal educational level. Anti-HCV frequency increased with age. Premarital screening of viral hepatitis could constitute an instance of diagnosis, vaccination and inclusion in care of those in need. Results from this study will allow the national hepatitis programs to design public policies in order to diminish the impact of these infections on the population.
Transcriptional landscape of soybean (Glycine max) embryonic axes during germination in the presence of paclobutrazol, a gibberellin biosynthesis inhibitor
Authors: Gazara Rajesh K. , de Oliveira Eduardo A. G. , Rodrigues Bruno C. , Nunes da Fonseca Rodrigo , Oliveira Antônia Elenir A. , Venancio Thiago M. 
Published: July 2019

AbstractGibberellins (GA) are key positive regulators of seed germination. Although the GA effects on seed germination have been studied in a number of species, little is known about the transcriptional reprogramming modulated by GA during this phase in species other than Arabidopsis thaliana. Here we report the transcriptome analysis of soybean embryonic axes during germination in the presence of paclobutrazol (PBZ), a GA biosynthesis inhibitor. We found a number of differentially expressed cell wall metabolism genes, supporting their roles in cell expansion during germination. Several genes involved in the biosynthesis and signaling of other phytohormones were also modulated, indicating an intensive hormonal crosstalk at the embryonic axis. We have also found 26 photosynthesis genes that are up-regulated by PBZ at 24 hours after imbibition (HAI) and down-regulated at 36 HAI, which led us to suggest that this is part of a strategy to implement an autotrophic growth program in the absence of GA-driven mobilization of reserves. Finally, 30 transcription factors (mostly from the MYB, bHLH, and bZIP families) were down-regulated by PBZ and are likely downstream GA targets that will drive transcriptional changes during germination.
CRISPR knockout screen implicates three genes in lysosome function
Authors: Lenk Guy M. , Park Young N. , Lemons Rosemary , Flynn Emma , Plank Margaret , Frei Christen M. , Davis Michael J. , Gregorka Brian , Swanson Joel A. , Meisler Miriam H. , Kitzman Jacob O. 
Published: July 2019

AbstractDefective biosynthesis of the phospholipid PI(3,5)P2 underlies neurological disorders characterized by cytoplasmic accumulation of large lysosome-derived vacuoles. To identify novel genetic causes of lysosomal vacuolization, we developed an assay for enlargement of the lysosome compartment that is amenable to cell sorting and pooled screens. We first demonstrated that the enlarged vacuoles that accumulate in fibroblasts lacking FIG4, a PI(3,5)P2 biosynthetic factor, have a hyperacidic pH compared to normal cells'. We then carried out a genome-wide knockout screen in human HAP1 cells for accumulation of acidic vesicles by FACS sorting. A pilot screen captured fifteen genes, including VAC14, a previously identified cause of endolysosomal vacuolization. Three genes not previously associated with lysosome dysfunction were selected to validate the screen: C10orf35, LRRC8A, and MARCH7. We analyzed two clonal knockout cell lines for each gene. All of the knockout lines contained enlarged acidic vesicles that were positive for LAMP2, confirming their endolysosomal origin. This assay will be useful in the future for functional evaluation of patient variants in these genes, and for a more extensive genome-wide screen for genes required for endolysosome function. This approach may also be adapted for drug screens to identify small molecules that rescue endolysosomal vacuolization.
On the Elevated Temperature Thermal Stability of Nanoscale Mn-Ni-Si Precipitates Formed at Lower Temperature in Highly Irradiated Reactor Pressure Vessel Steels
Authors: Almirall N. , Wells P. B. , Ke H. , Edmondson P. , Morgan D. , Yamamoto T. , Odette G. R. 
Published: July 2019

AbstractAtom probe tomography (APT) and scanning transmission electron microscopy (STEM) techniques were used to probe the long-time thermal stability of nm-scale Mn-Ni-Si precipitates (MNSPs) formed in intermediate and high Ni reactor pressure vessel steels under high fluence neutron irradiation at ≈320 °C. Post irradiation annealing (PIA) at 425 °C for up to 57 weeks was used to determine if the MNSPs are: (a) non-equilibrium solute clusters formed and sustained by radiation induced segregation (RIS); or, (b) equilibrium G or Γ2 phases, that precipitate at accelerated rates due to radiation enhanced diffusion (RED). Note the latter is consistent with both thermodynamic models and x-ray diffraction (XRD) measurements. Both the experimental and an independently calibrated cluster dynamics (CD) model results show that the stability of the MNSPs is very sensitive to the alloy Ni and, to a lesser extent, Mn content. Thus, a small fraction of the largest MNSPs in the high Ni steel persist, and begin to coarsen at long times. These results suggest that the MNSPs remain a stable phase, even at 105 °C higher than they formed at, thus are most certainly equilibrium phases at much lower service relevant temperatures of ≈290 °C.
Distinct processing of tone offset in two primary auditory cortices
Authors: Sołyga Magdalena , Barkat Tania Rinaldi 
Published: July 2019

AbstractIn the rodent auditory system, the primary cortex is subdivided into two regions, both receiving direct inputs from the auditory thalamus: the primary auditory cortex (A1) and the anterior auditory field (AAF). Although neurons in the two regions display different response properties, like response latency, firing threshold or tuning bandwidth, it is still not clear whether they process sound in a distinct way. Using in vivo electrophysiological recordings in the mouse auditory cortex, we found that AAF neurons have significantly stronger responses to tone offset than A1 neurons. AAF neurons also display faster and more transient responses than A1 neurons. Additionally, offset responses in AAF – unlike in A1, increase with sound duration. Local field potential (LFP) and laminar analyses suggest that the differences in sound responses between these two primary cortices are both of subcortical and intracortical origin. These results emphasize the potentially critical role of AAF for temporal processing. Our study reveals a distinct role of two primary auditory cortices in tone processing and highlights the complexity of sound encoding at the cortical level.
Fusion of multiple heterogeneous networks for predicting circRNA-disease associations
Authors: Deng Lei , Zhang Wei , Shi Yechuan , Tang Yongjun 
Published: July 2019

AbstractCircular RNAs (circRNAs) are a newly identified type of non-coding RNA (ncRNA) that plays crucial roles in many cellular processes and human diseases, and are potential disease biomarkers and therapeutic targets in human diseases. However, experimentally verified circRNA-disease associations are very rare. Hence, developing an accurate and efficient method to predict the association between circRNA and disease may be beneficial to disease prevention, diagnosis, and treatment. Here, we propose a computational method named KATZCPDA, which is based on the KATZ method and the integrations among circRNAs, proteins, and diseases to predict circRNA-disease associations. KATZCPDA not only verifies existing circRNA-disease associations but also predicts unknown associations. As demonstrated by leave-one-out and 10-fold cross-validation, KATZCPDA achieves AUC values of 0.959 and 0.958, respectively. The performance of KATZCPDA was substantially higher than those of previously developed network-based methods. To further demonstrate the effectiveness of KATZCPDA, we apply KATZCPDA to predict the associated circRNAs of Colorectal cancer, glioma, breast cancer, and Tuberculosis. The results illustrated that the predicted circRNA-disease associations could rank the top 10 of the experimentally verified associations.
Apparent Effects of Opioid Use on Neural Responses to Reward in Chronic Pain
Authors: Martucci Katherine T. , MacNiven Kelly H. , Borg Nicholas , Knutson Brian , Mackey Sean C. 
Published: July 2019

AbstractNeural responses to incentives are altered in chronic pain and by opioid use. To understand how opioid use modulates the neural response to reward/value in chronic pain, we compared brain functional magnetic resonance imaging (fMRI) responses to a monetary incentive delay (MID) task in patients with fibromyalgia taking opioids (N = 17), patients with fibromyalgia not taking opioids (N = 17), and healthy controls (N = 15). Both groups of patients with fibromyalgia taking and not taking opioids had similar levels of pain, psychological measures, and clinical symptoms. Neural responses in the nucleus accumbens to anticipated reward and non-loss outcomes did not differ from healthy controls in either fibromyalgia group. However, neural responses in the medial prefrontal cortex differed, such that patients with fibromyalgia not taking opioids demonstrated significantly altered responses to anticipated rewards and non-loss outcomes compared to healthy controls, but patients with fibromyalgia taking opioids did not. Despite limitations including the use of additional non-opioid medications by fibromyalgia patients taking opioids, these preliminary findings suggest relatively “normalized” neural responses to monetary incentives in chronic pain patients who take opioids versus those who do not.
Elevation of endocannabinoids in the brain by synthetic cannabinoid JWH-018: mechanism and effect on learning and memory
Authors: Li Ren-shi , Fukumori Ryo , Takeda Tomoki , Song Yingxia , Morimoto Satoshi , Kikura-Hanajiri Ruri , Yamaguchi Taku , Watanabe Kazuhito , Aritake Kousuke , Tanaka Yoshitaka , Yamada Hideyuki , Yamamoto Tsuneyuki , Ishii Yuji 
Published: July 2019

AbstractThe impairment of learning and memory is a well-documented effect of both natural and synthetic cannabinoids. In the present study, we aimed to investigate the effect of acute administration of JWH-018, a synthetic cannabinoid, on the hippocampal metabolome to assess biochemical changesin vivo. JWH-018 elevated levels of the endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG). The increase of endocannabinoid levels in response to JWH-018 could be inhibited by co-administration of AM251, a CB1 receptor antagonist. Biochemical analyses revealed that this was the result of suppression of two hydrolases involved in endocannabinoid degradation (fatty acid amide hydrolase [FAAH] and monoacylglycerol lipase [MAGL]). Additionally, we showed that JWH-018 causes a reduction in the levels of brain-derived neurotrophic factor (BDNF), which is known to modulate synaptic plasticity and adaptive processes underlying learning and memory. The decrease of BDNF following JWH-018 treatment was also rescued by co-administration of AM251. As both endocannabinoids and BDNF have been shown to modulate learning and memory in the hippocampus, the alteration of their levels in response to JWH-018 may explain the contribution of synthetic cannabinoids to impairment of memory.
Elucidation of the more myopic eye in anisometropia: the interplay of laterality, ocular dominance, and anisometropic magnitude
Authors: Jiang Siyu , Chen Zheyi , Bi Hua , Xia Ruijing , Shen Ting , Zhou Ling , Jiang Jun , Zhang Bin , Lu Fan 
Published: July 2019

AbstractThis study reveals how, in a myopic anisometrope, the odds of an eye being more myopic are related to laterality, ocular dominance, and magnitude of anisometropia. In 193 subjects, objective refraction was performed with cycloplegia. Sighting, motor, and sensory dominance were determined with the hole-in-the-card test, convergence near-point test, continuous flashing technique, respectively. Multiple logistic regression was used for probability analysis. Seventy percent of the subjects had a right eye that was more myopic, while 30% of them had a more myopic left eye. When the right eye was the sensory dominant eye, the probability of the right eye being more myopic increased to 80% if the anisometropia was less than 3.0 D, and decreased below 70% if anisometropia was beyond 3.0 D. When the left eye was the sensory dominant eye, the probability of the left eye being more myopic increased to above 40% if the anisometropia was less than 4.0 D and decreased below 30% if the anisometropia was beyond 4.0 D. Therefore, between the two eyes of anisometropes, laterality tilts the chance of being more myopic to the right. Being the sensory dominant eye increases an eye’s probability of being more myopic by another 10% if the magnitude of anisometropia is moderate.