bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Application of Machine Learning in Pharmacovigilance: Estimating Likely Patient Genotype From Phenotypical Manifestations of Fluoropyrimidine Toxicity
Authors: Correia Pinheiro Luis , Durand Julie , Dogné Jean‐Michel 
Published: January 2020

Dihydropyrimidine dehydrogenase (DPD)‐deficient patients might only become aware of their genotype after exposure to dihydropyrimidines, if testing is performed. Case reports to pharmacovigilance databases might only contain phenotypical manifestations of DPD, without information on the genotype. This poses a difficulty in estimating the cases due to DPD. Auto machine learning models were developed to train patterns of phenotypical manifestations of toxicity, which were then used as a surrogate to estimate the number of cases of DPD‐related toxicity. Results indicate that between 8,878 (7.0%) and 16,549 (13.1%) patients have a profile similar to DPD deficient status. Results of the analysis of variable importance match the known end‐organ damage of DPD‐related toxicity, however, accuracies in the range of 90% suggest presence of overfitting, thus, results need to be interpreted carefully. This study shows the potential for use of machine learning in the regulatory context but additional studies are required to better understand regulatory applicability.
Vehicular HetNet load distribution using centralized control of software‐defined network
Authors: Kandar Debdatta , Paul Babu Sena , Chyne Phidahunlang 
Published: January 2020

SummaryCurrent vehicular communication systems experience from nonflexible and costly devices, complicated control‐plane protocols, and vendor‐specific configuration interfaces. In the next generation vehicular communication, a mobile device (MD) will be installed on a car capable of accessing multiple services from different networks. So heterogeneous networks (HetNets) may play a vital role in vehicular communication. Despite heterogeneity, flawless connectivity between different systems is a basic need of the travellers. The key challenge for seamless connectivity is the design of a vertical handover (VHO) scheme. We claim that software‐defined networking (SDN) can make things easier in the design and supervision of VHO in vehicular HetNet. The proposed method maximizes the HetNet utilization with lesser handover by balancing the load among the HetNets. Simulation results performed in MATLAB justified that this novel architecture with proper VHO technique boosts the performance by balancing the load, reducing unnecessary VHO, etc. Performance is analyzed by considering four studies, ie, handover served ratio (HSR), on board units (OBUs), OBU served ratio (OSR), and total throughput and total capacities of road side units (RSUs) to serve handover demands from OBUs. It is observed that the HSR increases rapidly as the number of OBUs increases, which indicates almost all the handover requested OBUs are allocated resources by a connected RSU. We also studied the served total throughput by considering VHO with SDN, without SDN in the average case and without SDN in the best case, and it is observed that with SDN as a central controller, the total OSR and total throughput is increased.
Efficacy of exenatide and insulin glargine on nonalcoholic fatty liver disease in patients with type 2 diabetes
Authors: Liu Lin , Yan Hongmei , Xia MingFeng , Zhao Lin , Lv Minzhi , Zhao Naiqin , Rao Shengxiang , Yao Xiuzhong , Wu Weiyun , Pan Baishen , Bian Hua , Gao Xin 
Published: January 2020

AbstractBackgroundThe aim of this study was to investigate the efficacy of exenatide and insulin glargine in patients with newly diagnosed type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD).MethodsWe performed a 24‐week randomized controlled multicentre clinical trial. Seventy‐six patients were randomly assigned 1:1 to receive exenatide or insulin glargine treatment. The endpoints included changes in liver fat content (LFC), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) measured by magnetic resonance spectroscopy, blood glucose, liver enzymes, lipid profile, body weight, and Fibrosis‐4 index (FIB‐4).ResultsLFC, VAT, SAT, and FIB‐4 were significantly reduced after exenatide treatment (ΔLFC, −17.55 ± 12.93%; ΔVAT, −43.57 ± 68.20 cm2; ΔSAT, −28.44 ± 51.48 cm2; ΔFIB‐4, −0.10 ± 0.26; all P < .05). In comparison, only LFC (ΔLFC, −10.49 ± 11.38%; P < .05), and not VAT, SAT, or FIB‐4 index (all P > .05), was reduced after insulin glargine treatment. Moreover, exenatide treatment resulted in greater reductions in alanine transaminase (ALT), aspartate transaminase (AST), and gamma glutamyl transpeptidase (GGT) than insulin glargine (P < 0.05). The body weight, waist circumference, postprandial plasma glucose, and low‐density lipoprotein cholesterol (LDL‐C) in the exenatide group also presented greater reductions than the insulin glargine group (P < .05). The proportion of adverse events were comparable between the two groups.ConclusionBoth exenatide and insulin glargine reduced LFC in patients with drug‐naive T2DM and NAFLD; however, exenatide showed greater reductions in body weight, visceral fat area, liver enzymes, FIB‐4, postprandial plasma glucose, and LDL‐C.
Hormone‐mediated modulation of the electromotor CPG in pulse‐type weakly electric fish. Commonalities and differences across species
Authors: Borde Michel , Quintana Laura , Comas Virginia , Silva Ana 
Published: January 2020

AbstractLike stomatogastric activity in crustaceans, vocalization in teleosts and frogs, and locomotion in mammals, the electric organ discharge (EOD) of weakly electric fish is a rhythmic and stereotyped electromotor pattern. The EOD, which functions in both perception and communication, is controlled by a two‐layered central pattern generator (CPG), the electromotor CPG, which modifies its basal output in response to environmental and social challenges. Despite major anatomo‐functional commonalities in the electromotor CPG across electric fish species, we show that Gymnotus omarorum and Brachyhypopomus gauderio have evolved divergent neural processes to transiently modify the CPG outputs through descending fast neurotransmitter inputs to generate communication signals. We also present two examples of electric behavioral displays in which it is possible to separately analyze the effects of neuropeptides (mid‐term modulation) and gonadal steroid hormones (long‐term modulation) upon the CPG. First, the nonbreeding territorial aggression of G. omarorum has been an advantageous model to analyze the status‐dependent modulation of the excitability of CPG neuronal components by vasotocin. Second, the seasonal and sexually dimorphic courtship signals of B. gauderio have been useful to understand the effects of sex steroids on the responses to glutamatergic inputs in the CPG. Overall, the electromotor CPG functions in a regime that safeguards the EOD waveform. However, prepacemaker influences and hormonal modulation enable an enormous versatility and allows the EOD to adapt its functional state in a species‐, sex‐, and social context‐specific manners.
Oxygen‐mediated plasticity confers hypoxia tolerance in a corallivorous polychaete
Authors: Lucey Noelle M. , Collins Mary , Collin Rachel 
Published: January 2020

AbstractThere is mounting evidence that the deoxygenation of coastal marine ecosystems has been underestimated, particularly in the tropics. These physical conditions appear to have far‐reaching consequences for marine communities and have been associated with mass mortalities. Yet little is known about hypoxia in tropical habitats or about the effects it has on reef‐associated benthic organisms. We explored patterns of dissolved oxygen (DO) throughout Almirante Bay, Panama and found a hypoxic gradient, with areas closest to the mainland having the largest diel variation in DO, as well as more frequent persistent hypoxia. We then designed a laboratory experiment replicating the most extreme in situ DO regime found on shallow patch reefs (3 m) to assess the response of the corallivorous fireworm, Hermodice carnaculata to hypoxia. Worms were exposed to hypoxic conditions (8 hr ~ 1 mg/L or 3.2 kPa) 16 times over an 8‐week period, and at 4 and 8 weeks, their oxygen consumption (respiration rates) was measured upon reoxygenation, along with regrowth of severed gills. Exposure to low DO resulted in worms regenerating significantly larger gills compared to worms under normoxia. This response to low DO was coupled with an ability to maintain elevated oxygen consumption/respiration rates after low DO exposure. In contrast, worms from the normoxic treatment had significantly depressed respiration rates after being exposed to low DO (week 8). This indicates that oxygen‐mediated plasticity in both gill morphology and physiology may confer tolerance to increasingly frequent and severe hypoxia in one important coral predator associated with reef decline.
Ultrasound‐guided continuous deep serratus anterior plane block versus continuous thoracic paravertebral block for perioperative analgesia in videoscopic‐assisted thoracic surgery
Authors: Hanley Ciara , Wall Tom , Bukowska Irmina , Redmond Karen , Eaton Donna , Ní Mhuircheartaigh Róisín , Hearty Conor 
Published: January 2020

AbstractBackgroundThe deep serratus anterior plane block (SAPB) is a promising novel regional anaesthesia technique for blockade of the anterolateral chest wall. Evidence for the efficacy of SAPB versus other analgesic techniques in thoracic surgery remains inadequate.AimsThis study compared ultrasound‐guided continuous SAPB with a surgically placed continuous thoracic paravertebral block (SPVB) technique in patients undergoing videoscopic‐assisted thoracic surgery (VATS).MethodsIn a single‐centre, double‐blinded, randomized, non‐inferiority study, we allocated 40 patients undergoing VATS to either SAPB or SPVB, with both groups receiving otherwise standardized treatment, including multimodal analgesia. The primary outcome was 48‐hr opioid consumption. Secondary outcomes included numerical rating scale (NRS) for postoperative pain, patient‐reported worst pain score (WPS) as well as functional measures (including mobilization distance and cough strength).ResultsA 48‐hr opioid consumption for the SAPB group was non‐inferior compared with SPVB. SAPB was associated with improved NRS pain scores at rest, with cough and with movement at 24 hr postoperatively (p = .007, p = .001 and p = .012, respectively). SAPB was also associated with a lower WPS (p = .008). Day 1 walking distance was improved in the SAPB group (p = .012), whereas the difference in cough strength did not reach statistical significance (p = .071). There was no difference in haemodynamics, opioid side effects, length of hospital stay or patient satisfaction between the two groups.ConclusionsThe SAPB, as part of a multimodal analgesia regimen, is non‐inferior in terms of 48‐hr opioid consumption compared to SPVB and is associated with improved functional measures in thoracic surgical patients.ClinicalTrials.gov Identifier: NCT03768193.SignificanceThe SAPB interfascial plane block is an efficacious alternative method of opioid‐sparing analgesia in high‐risk thoracic surgical patients as part of an enhanced recovery programme.
Diffuse large B‐cell lymphoma carrying t(9;14)(p13;q32)/PAX5‐immunoglobulin heavy chain gene is characterized by nuclear positivity of MUM1 and PAX5 by immunohistochemistry
Authors: Ohno Hitoshi , Nakagawa Miho , Kishimori Chiyuki , Fukutsuka Katsuhiro , Maekawa Fumiyo , Takeoka Kayo , Hayashida Masahiko , Sakamoto Shinichi , Akasaka Takashi , Honjo Gen 
Published: January 2020

AbstractWe described four patients with diffuse large B‐cell lymphoma (DLBCL) carrying t(9;14)(p13;q32) that places the PAX5 adjacent to the immunoglobulin heavy chain (IGH) gene. Ages ranged between 63 and 80, and three were female. One developed a nodal disease, and the other three involved extranodal organs. The lymphoma cells were CD10−/BCL6−/MUM1+ in three and CD10+/BCL6+/MUM1+ in one. BCL2 was weak or negative. All had t(9;14)(p13;q32), and three had additional 14q32/IGH translocations or +der(14)t(9;14)(p13;q32). Fluorescence in situ hybridization using the PAX5 break‐apart probe showed that the locus was disrupted between the 5′ and 3′ probes or within the 5′ probe. Immunohistochemistry (IHC) using a monoclonal antibody against PAX5 showed strong nuclear positivity in all four patients. Cell block IHC of a CD30+ DLBCL cell line, KIS‐1, which carried the t(9;14)(p13;q32) and PAX5‐IGH fusion gene, reproduced the CD10−/BCL6−/MUM1+ immunophenotype, low‐level BCL2, and strong nuclear PAX5. Uniform nuclear positivity of MUM1 in all four cases and KIS‐1 cells suggest that these lymphomas arose at a late stage of B‐cell differentiation, where expression of PAX5 physiologically becomes downregulated. It is therefore possible that high‐level PAX5 resulting from t(9;14)(p13;q32) at this stage of differentiation perturbs the plasma cell differentiation program initiated by PAX5 repression, thereby contributing to the development of a fraction of DLBCL.
Nutritional ketosis improves exercise metabolism in patients with very long‐chain acyl‐CoA dehydrogenase deficiency
Authors: Bleeker Jeannette C. , Visser Gepke , Clarke Kieran , Ferdinandusse Sacha , de Haan Ferdinand H. , Houtkooper Riekelt H. , IJlst Lodewijk , Kok Irene L. , Langeveld Mirjam , van der Pol W. Ludo , de Sain‐van der Velden Monique G. M. , Sibeijn‐Kuiper Anita , Takken Tim , Wanders Ronald J. A. , van Weeghel Michel , Wijburg Frits A. , van der Woude Luc H. , Wüst Rob C. I. , Cox Pete J. , Jeneson Jeroen A. L. 
Published: January 2020

AbstractA maladaptive shift from fat to carbohydrate (CHO) oxidation during exercise is thought to underlie myopathy and exercise‐induced rhabdomyolysis in patients with fatty acid oxidation (FAO) disorders. We hypothesised that ingestion of a ketone ester (KE) drink prior to exercise could serve as an alternative oxidative substrate supply to boost muscular ATP homeostasis. To establish a rational basis for therapeutic use of KE supplementation in FAO, we tested this hypothesis in patients deficient in Very Long‐Chain acyl‐CoA Dehydrogenase (VLCAD). Five patients (range 17‐45 y; 4 M/1F) patients were included in an investigator‐initiated, randomised, blinded, placebo‐controlled, 2‐way cross‐over study. Patients drank either a KE + CHO mix or an isocaloric CHO equivalent and performed 35 minutes upright cycling followed by 10 minutes supine cycling inside a Magnetic Resonance scanner at individual maximal FAO work rate (fatmax; approximately 40% VO2max). The protocol was repeated after a 1‐week interval with the alternate drink. Primary outcome measures were quadriceps phosphocreatine (PCr), Pi and pH dynamics during exercise and recovery assayed by in vivo 31P‐MR spectroscopy. Secondary outcomes included plasma and muscle metabolites and respiratory gas exchange recordings. Ingestion of KE rapidly induced mild ketosis and increased muscle BHB content. During exercise at FATMAX, VLCADD‐specific plasma acylcarnitine levels, quadriceps glycolytic intermediate levels and in vivo Pi/PCr ratio were all lower in KE + CHO than CHO. These results provide a rational basis for future clinical trials of synthetic ketone ester supplementation therapy in patients with FAO disorders.Trial registration: ClinicalTrials.gov. Protocol ID: NCT03531554; METC2014.492; ABR51222.042.14.
Connecting local‐scale heavy precipitation to large‐scale meteorological patterns over Portland, Oregon
Authors: Aragon Christina M. , Loikith Paul C. , McCullar Nicholas , Mandilag Arnel 
Published: January 2020

AbstractIdentifying and characterizing the large‐scale meteorological patterns (LSMPs) associated with local‐scale heavy precipitation improve our understanding of the processes that drive these high‐impact phenomena. Focusing on Portland, Oregon, we identify and characterize the key LSMPs associated with heavy precipitation days, defined using a daily total and hourly intensity threshold. LSMPs are defined at the synoptic scale using sea level pressure, 500 hPa geopotential height (Z500), and 250 hPa wind speed concurrent with precipitation days between 1980 and 2016, to capture synoptic circulation at three diagnostic atmospheric levels. We employ the self‐organizing map (SOM) approach to group the LSMPs into clusters, spanning the full range of synoptic circulation patterns associated with heavy precipitation days across the seasonal cycle. Using an atmospheric river (AR) catalogue of events, we show that ARs are commonly associated with heavy precipitation days, especially in winter and fall; however, heavy precipitation can occur without an AR in all seasons. Spring and summer heavy precipitation days, which are less common than in the fall and winter, tend to be primarily associated with upper level troughs and localized convective precipitation, while in winter they are more commonly associated with a surface cyclone and more widespread, stratiform precipitation. Examination of two case studies, one occurring in summer and one in winter, supports the ability of the SOM approach to realistically capture key observed storm types. Methods developed here may be extensible to other locations and phenomena and results build an observational foundation for assessing impactful LSMPs in climate models.
El Niño forecasting based on the global atmospheric oscillation
Authors: Serykh Ilya V. , Sonechkin Dmitry M. 
Published: January 2020

AbstractThe predictability of El Niño and La Niña is investigated. In this case, the recently discovered so‐called global atmospheric oscillation (GAO) is considered. Assuming GAO to be the main mode of short‐term climatic variability, this study defines an index that characterizes the dynamics and relationships of the extratropical components of the GAO and El Niño – Southern Oscillation (ENSO). Due to the general propagation of the GAO's spatial structure from west to east, another index – predictor of ENSO is defined. The cross‐wavelet analysis between both of these indices and the Oceanic Niño Index (ONI) is performed. This analysis reveals a range of timescales within which the closest relationship between the GAO and ONI takes place. Using this relationship, it is possible to predict El Niño and La Niña with a lead‐time of approximately 12 months.
Spatiotemporal variability of standardized precipitation evapotranspiration index in mainland China over 1961–2016
Authors: Wu Mengjie , Li Yi , Hu Wei , Yao Ning , Li Linchao , Liu De Li 
Published: January 2020

AbstractA good understanding of spatiotemporal characteristics of historical droughts is important for managing and tackling drought hazards. This paper aims to investigate spatiotemporal variations of drought in mainland China over 1961–2016 based on the standardized precipitation evapotranspiration index (SPEI) at the 1‐ and 12‐month timescales. The trend significance and magnitude of 12‐month SPEI were analysed using the modified Mann–Kendall (MMK) method and Sen's slope values. The empirical orthogonal function (EOF) and ensemble empirical mode decomposition (EEMD) were applied to analyse the spatial patterns and periods in 1‐month SPEI series. The results showed that the temporal fluctuations of SPEI were weaker as the timescale increased. The droughts in 1960s were the severest than in other decades. The sites with SPEI < −5 (denoting the extreme droughts) mainly located in the northwestern and southwestern China. An overall wetter trend was detected in most regions of China, except the belt from northeastern to middle and southwestern China. The 1‐month SPEI had shorter than 1.20‐year of mean periods for the seven sub‐regions and China, while had 0.22–2.95 years of mean periods at different sites. Residuals (decomposed from 1‐month SPEI) showed increasing trends in most of the sub‐regions except sub‐region 3. In northern and northwestern China, longer periods of SPEI were detected. The highest values of EOF1 and EOF2 illustrated the eastern and northeastern China were drought‐sensitive areas. From the correlations between 1‐month SPEI and the atmospheric circulations, the AO was the main physical factor that influenced drought occurrence in mainland China. The identified spatiotemporal characteristics of SPEI could offer references for drought prevention and management in China.
Tutorial on How the US Food and Drug Administration Regulates Parenteral Nutrition Products
Authors: Tabor Edward 
Published: January 2020

AbstractParenteral nutrition (PN) products are regulated in the United States by the Food and Drug Administration (FDA). The FDA regulates PN products as “drugs,” and the approval of a new product depends on there being “substantial evidence” of safety and efficacy obtained from “adequate and well‐controlled studies.” The processes by which the FDA approves PN products in the United States are designed to protect patients from unsafe or ineffective products, but they may also contribute to delaying and preventing access to certain valuable new products. This tutorial is designed to inform the PN community about FDA processes with regard to PN products, including the structure of FDA review teams, requirements for investigational studies, applications for marketing approval, postapproval clinical trial requirements, and requirements for studies in pediatric populations. Knowledge of how the FDA process works and how the FDA regulates PN products can help the PN community work together in advancing the development of new products.
Adjudication rather than experience of data abstraction matters more in reducing errors in abstracting data in systematic reviews
Authors: E Jian‐Yu , Saldanha Ian J. , Canner Joseph , Schmid Christopher H. , Le Jimmy T. , Li Tianjing 
Published: January 2020

BackgroundDuring systematic reviews, “data abstraction” refers to the process of collecting data from reports of studies. The data abstractors' level of experience may affect the accuracy of data abstracted. Using data from a randomized crossover trial in which different data abstraction approaches were compared, we examined the association between abstractors' level of experience and accuracy of data abstraction.MethodsWe classified abstractors as “more experienced” if they had authored three or more published systematic reviews, and “less experienced” otherwise. Each abstractor abstracted data related to study design, baseline characteristics, and outcomes/results from six articles. We considered two types of errors: incorrect abstraction and errors of omission. We estimated the proportion of errors by level of experience using a binomial generalized linear mixed model.ResultsWe used data from 25 less experienced and 25 more experienced data abstractors. Overall error proportions were similar for less experienced abstractors (21%) and more experienced abstractors (19%). Compared with less experienced abstractors, more experienced abstractors had a lower odds of errors for data items related to outcomes/results (adjusted odds ratio [OR] = 0.53; 95% CI, 0.34‐0.82) and potentially for data items related to study design (adjusted OR = 0.83; 95% CI, 0.64‐1.09) but a potentially higher odds of errors for items related to baseline characteristics (adjusted OR = 1.42; 95% CI, 0.97‐2.06).ConclusionExperience of data abstraction matters little. Errors are reduced by adjudication but still remain high for data items related to outcomes/results.