bluuebunny/crossref_metadata_2025 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

Current 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

Background

The 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).

Methods

We 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).

Results

LFC, 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.

Conclusion

Both 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

Like 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

There 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

Background

The 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.

Aims

This study compared ultrasound‐guided continuous SAPB with a surgically placed continuous thoracic paravertebral block (SPVB) technique in patients undergoing videoscopic‐assisted thoracic surgery (VATS).

Methods

In 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).

Results

A 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.

Conclusions

The 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.

Significance

The 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.
Smart Electrochromic Supercapacitors Made of Metal Mesh Electrodes with Polyaniline as Charge Storage Indicator
Authors: Kiruthika S. , Kulkarni Giridhar U.
Published: January 2020

Herein, the design and fabrication of a smart electrochromic supercapacitor using Au mesh and polyaniline (PANI) electrodes is reported. The Au mesh is obtained through the crackle templating method, whereas PANI is brought in by electrodeposition. The device exhibits a high capacitance of ≈15 mF cm−2 with good charge–discharge cycling stability. What is attractive about this device is that it can switch its color rapidly to yellow, green, or blue, depending on the operable voltage window that should serve to indicate the level of energy stored in the supercapacitor, visually.
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

We 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

A 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

Identifying 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

The 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

A 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

Parenteral 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

Background

During 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.

Methods

We 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.

Results

We 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).

Conclusion

Experience of data abstraction matters little. Errors are reduced by adjudication but still remain high for data items related to outcomes/results.
A comparison of Bayesian and frequentist methods in random‐effects network meta‐analysis of binary data
Authors: Seide Svenja E. , Jensen Katrin , Kieser Meinhard
Published: January 2020

The performance of statistical methods is often evaluated by means of simulation studies. In case of network meta‐analysis of binary data, however, simulations are not currently available for many practically relevant settings. We perform a simulation study for sparse networks of trials under between‐trial heterogeneity and including multi‐arm trials. Results of the evaluation of two popular frequentist methods and a Bayesian approach using two different prior specifications are presented. Methods are evaluated using coverage, width of intervals, bias, and root mean squared error (RMSE). In addition, deviations from the theoretical surface under the cumulative rankings (SUCRAs) or P‐scores of the treatments are evaluated. Under low heterogeneity and when a large number of trials informs the contrasts, all methods perform well with respect to the evaluated performance measures. Coverage is observed to be generally higher for the Bayesian than the frequentist methods. The width of credible intervals is larger than those of confidence intervals and is increasing when using a flatter prior for between‐trial heterogeneity. Bias was generally small, but increased with heterogeneity, especially in netmeta. In some scenarios, the direction of bias differed between frequentist and Bayesian methods. The RMSE was comparable between methods but larger in indirectly than in directly estimated treatment effects. The deviation of the SUCRAs or P‐scores from their theoretical values was mostly comparable over the methods but differed depending on the heterogeneity and the geometry of the investigated network. Multivariate meta‐regression or Bayesian estimation using a half‐normal prior scaled to 0.5 seems to be promising with respect to the evaluated performance measures in network meta‐analysis of sparse networks.
Load‐transfer in the human vertebral body following lumbar total disc arthroplasty: Effects of implant size and stiffness in axial compression and forward flexion
Authors: Bonnheim Noah B. , Keaveny Tony M.
Published: January 2020

Adverse clinical outcomes for total disc arthroplasty (TDA), including subsidence, heterotopic ossification, and adjacent‐level vertebral fracture, suggest problems with the underlying biomechanics. To gain insight, we investigated the role of size and stiffness of TDA implants on load‐transfer within a vertebral body. Uniquely, we accounted for the realistic multi‐scale geometric features of the trabecular micro‐architecture and cortical shell. Using voxel‐based finite element analysis derived from a micro‐computed tomography scan of one human L1 vertebral body (74‐μm‐sized elements), a series of generic elliptically shaped implants were analyzed. We parametrically modeled three implant sizes (small, medium [a typical clinical size], and large) and three implant materials (metallic, E = 100 GPa; polymeric, E = 1 GPa; and tissue‐engineered, E = 0.01 GPa). Analyses were run for two load cases: 800 N in uniform compression and flexion‐induced anterior impingement. Results were compared to those of an intact model without an implant and loaded instead via a disc‐like material. We found that TDA implantation increased stress in the bone tissue by over 50% in large portions of the vertebra. These changes depended more on implant size than material, and there was an interaction between implant size and loading condition. For the small implant, flexion increased the 98th‐percentile of stress by 32 ± 24% relative to compression, but the overall stress distribution and trabecular‐cortical load‐sharing were relatively insensitive to loading mode. In contrast, for the medium and large implants, flexion increased the 98th‐percentile of stress by 42 ± 9% and 87 ± 29%, respectively, and substantially re‐distributed stress within the vertebra; in particular overloading the anterior trabecular centrum and cortex. We conclude that TDA implants can substantially alter stress deep within the lumbar vertebra, depending primarily on implant size. For implants of typical clinical size, bending‐induced impingement can substantially increase stress in local regions and may therefore be one factor driving subsidence in vivo.
Boronic acid functionalized fibrous cellulose for the selective enrichment of glycopeptides
Authors: Sajid Muhammad Salman , Jabeen Fahmida , Hussain Dilshad , Gardner Qurra‐tul‐Ann Afza , Ashiq Muhammad Naeem , Najam‐ul‐Haq Muhammad
Published: January 2020

Enrichment of glycoproteins has been important because of their dynamicity and role in biological systems. Study of glycoproteins is complex because of the simultaneous glycosylation and deglycosylation inside the body. Often employed affinities for glycopeptides are hydrazide, boronic acid, or physiosorbed lectin on support materials. Cellulose, a natural polysaccharide, has rich surface chemistry, stable structure, low cost and availability in different variants. In present study, fibrous cellulose is oxidized using periodate to modify with boronic acid. Attachment of boronic acid is confirmed by Fourier transform infrared spectroscopy. Particle size and morphology of boronic acid@fibrous cellulose is studied by scanning electron microscopy. The enrichment efficiency is evaluated by using horseradish peroxidase as model protein. Boronic acid@fibrous cellulose is selective up to 1:250 for spiked horseradish peroxidase in bovine serum albumin digest, sensitive down to 0.1 femtomol and recovering 88.15% glycopeptides. Moreover, protein binding capacity is determined as 213 mg/g and 41% sequence coverage of horseradish peroxidase protein with all eight glycosylation sites detected. Total of 18 glycopeptides are enriched from immunoglobulin digest showing ability of boronic acid@fibrous cellulose to enrich glycoproteins from multiglycoforms. Enrichment from human serum recovers 18% extracellular and 72% secreted glycoproteins via bottom‐up approach and online tools.
Early Screening for Aortic Dissection With Point‐of‐Care Ultrasound by Emergency Physicians
Authors: Wang Yuan , Yu Haifang , Cao Yu , Wan Zhi
Published: January 2020

Objectives

To investigate the effect of point‐of‐care ultrasound (POCUS) use by emergency physician (EPs) on the diagnosis, treatment, and safety of POCUS in patients with aortic dissection (AD) in emergency settings.

Methods

Patients presenting to the emergency department of West China Hospital of Sichuan University with suspected AD from July 1, 2016, to December 31, 2016 were divided into a control group and an ultrasound (US) group. The control group was evaluated by routine procedures for triage, diagnosis, and treatment. In addition, an EP POCUS examination was performed in the US group. The patients in the US group were furtherly divided into subgroup A and subgroup B according to the Stanford type of AD. The sensitivity and specificity of EP POCUS compared to computed tomographic angiography (CTA) were compared. The door‐to‐CTA examination time, door‐to‐diagnosis time, door‐to‐targeted treatment time, and outcome were compared between the groups.

Results

A total of 127 patients were enrolled: 72 in the US group and 55 in the control group. In the US group, compared with CTA, the sensitivity of EP POCUS was 86.4%, and the specificity was 100.0%. The door‐to‐diagnosis times were 10.5 minutes in the US group and 79.0 minutes in the control group (P < .05). The door‐to‐CTA examination time and the door‐to‐targeted‐treatment time had no differences between the US and control groups (P > .05). The in‐hospital mortality and mortality within 3 months after discharge were 4.2% and 25.0% in the US group and 9.1% and 20.8% in the control group (P > .05).

Conclusions

Compared with CTA, EP POCUS in patients suspected of having AD is highly sensitive and specific and has shown no adverse effect on the treatment start‐up time, in‐hospital mortality, and mortality within 3 months after discharge.
Live barriers and associated organic amendments mitigate land degradation and improve crop productivity in hillside agricultural systems of the Ecuadorian Andes
Authors: Caulfield Mark , Groot Jeroen C. J. , Fonte Steven J. , Sherwood Stephen , Oyarzun Pedro , Borja Ross Mary , Dumble Sam , Tittonell Pablo
Published: January 2020

Land degradation caused by erosion and nutrient depletion in the Andes poses serious existential threats to small‐scale farming. Although the potential of hedgerows to decrease water erosion is well recognised, their potential dual‐use as a source of organic amendments to supplement farmer inputs is much less studied. The objective of this investigation was therefore to explore locally developed options for hedgerows that address these twin challenges. Experimental plots were installed to assess water erosion control by hedgerows and the effect of organic amendments harvested from the hedgerows on soil productivity, soil moisture, and soil fertility over the course of 2 years and three crop cycles (two of barley and one of rye). The experiment was conducted in two sites within the community at distinct elevations and associated biophysical contexts. At each site, four treatments were established, comparing a control treatment versus three types of hedgerows: (a) Andean alder, (b) canary grass strips, and (c) mixed canary grass and Andean alder. Results demonstrated that hedgerows and associated organic inputs comprised canary grass, and mixed canary grass and Andean alder reduced water erosion by 50–60% and increased biomass production by up to 1.1 Mg ha−1 and grain yield by up to 0.5 Mg ha−1. We conclude that although hedgerows are unlikely to produce sufficient quantities of organic resources to satisfy all nutrient input requirements, their potential to decrease erosion and supplement existing organic matter inputs indicates that they should be strongly considered as an option for improved agricultural management within this and similar resource constrained contexts.
Electronic tumor board presentations as the basis for the development of a head and neck cancer database
Authors: Rangabashyam Mahalakshmi , Wee Hide E. , Wang Weining , Mueller Stefan , Karim Khairul A. B. A. , Skanthakumar Thakshayeni , Hariraman Bhuvaneshwari , Sommat Kiattisa , Soong Yoke‐Lim , Chua Melvin L. K. , Tay Gerald , Tan Ngian ‐Chye , Tan Hiang Khoon‐ , Iyer N. Gopalakrishna
Published: January 2020

Background

Multidisciplinary team meetings or tumor boards (TBs) form a pivotal component of oncology practice. The crux of a TB revolves around making treatment decisions based on succinct head and neck cancer (HNC) patient data presentations, which can be challenging and complex. Apart from meticulous TB presentations, discussions and treatment plan documentation is equally important. The aim of this study was to structure an electronic synoptic TB data presentation to address all these areas. The overarching benefits of systematic TB data collection include facilitating audits and research.

Methods

We utilized a secure web‐based tool that was used for common scientific research purposes but customized to store HNC patient data. The data points were tabulated across eight TB pages: (a) TB scheduling, (b) patient biodata, (c) diagnosis details, (d) index presentation, (e) images, (f) management and histopathology, (g) TB presentation, and (h) TB discussion and decisions. Each data point leads to additional fields by branching logic to permit further relevant data entry. This was integrated within the patient electronic medical records allowing for a direct internal trajectory to recall TB data.

Results

From October 2015 to October 2018, we recorded over 2000 presentations for 1279 individual patients. This is a quality improvement initiative, and hence, the results are more of a broad analysis of our TB presentation process. The most common cancers were squamous cell (523, 41%), thyroid (207, 16%), and nasopharyngeal (139, 11%) carcinomas. Importantly, this system has formed the basis for a number of clinical and translational research projects and audit outcomes.

Conclusion

Despite TBs being vital to oncologic practice, little attempt has been made to report TB data management. In this study, we present an efficient system that permits the integration of dual functions: TB data presentation and oncologic data collection for research, recall, and audit purposes.
Pathology‐Proven Corticobasal Degeneration Presenting as Richardson's Syndrome
Authors: Bayram Ece , Dickson Dennis W. , Reich Stephen G. , Litvan Irene
Published: January 2020

Background

Corticobasal degeneration (CBD) can present with various clinical phenotypes including Richardson's syndrome (RS). Although neuropathological examination can differentiate CBD and progressive supranuclear palsy (PSP) pathologies, no clinical or imaging findings can differentiate CBD from other pathologies when a patient presents with a variant type of CBD. As these various phenotypes are associated with non‐CBD pathologies, clinical diagnostic accuracy can be low for such patients.

Objectives

To present clinical features of two cases with symptom progression in line with PSP‐RS, who were diagnosed with CBD based on neuropathological examination.

Methods

Baseline, follow up examinations, and detailed neuropathological examinations of two CBD cases presenting and progressing in line with probable PSP‐RS are demonstrated.

Results

The two cases clinically diagnosed as probable PSP‐RS were shown to have CBD upon neuropathological examination, which is the gold standard for diagnosis of both PSP and CBD.

Conclusions

These cases emphasize the importance of neuropathology for the definite diagnosis, and stress the need for distinctive markers to increase the reliability of clinical diagnosis before death.
Worker poaching in a supply chain: Enemy from within?
Authors: Barlow Evan , Allon Gad , Bassamboo Achal
Published: January 2020

Worker poaching represents the primary mode by which workers change employers. We examine worker poaching between firms linked in a value chain. We find that, in a value chain, the less productive firm may offer its workers higher wages and poach workers from the more productive firm. We also find that worker flows accomplished via poaching impact supply chain management: (a) the identity of the bottleneck firm may depend on whether poaching is available; (b) poaching between linked firms may benefit both, and (c) the value chain cannot be fully coordinated without controlling wages in the labor market.
Real‐time 4DMRI‐based internal target volume definition for moving lung tumors
Authors: Rabe Moritz , Thieke Christian , Düsberg Mathias , Neppl Sebastian , Gerum Sabine , Reiner Michael , Nicolay Nils Henrik , Schlemmer Heinz‐Peter , Debus Jürgen , Dinkel Julien , Landry Guillaume , Parodi Katia , Belka Claus , Kurz Christopher , Kamp Florian
Published: January 2020

Purpose

In photon radiotherapy, respiratory‐induced target motion can be accounted for by internal target volumes (ITV) or mid‐ventilation target volumes (midV) defined on the basis of four‐dimensional computed tomography (4D‐CT). Intrinsic limitations of these approaches can result in target volumes that are not representative for the gross tumor volume (GTV) motion over the course of treatment. To address these limitations, we propose a novel patient‐specific ITV definition method based on real‐time 4D magnetic resonance imaging (rt‐4DMRI).

Methods

Three lung cancer patients underwent weekly rt‐4DMRI scans. A total of 24 datasets were included in this retrospective study. The GTV was contoured on breath‐hold MR images and propagated to all rt‐4DMRI images by deformable image registration. Different targets were created for the first (reference) imaging sessions: ITVs encompassing all GTV positions over the complete (ITV) or partial acquisition time (), ITVs including only voxels with a GTV probability‐of‐presence (POP) of at least 5% () or 10% (), and the mid‐ventilation GTV position. Reference planning target volumes () were created by adding margins around the ITVs and midV target volumes. The geometrical overlap of the with from the six to eight subsequent imaging sessions on days n was quantified in terms of the Dice similarity coefficient (DSC), sensitivity [SE: ()/] and precision [PRE: ()/] as surrogates for target coverage and normal tissue sparing.

Results

Patient‐specific analysis yielded a high variance of the overlap values of , when different periods within the reference imaging session were sampled. The mid‐ventilation‐based PTVs were smaller than the ITV‐based PTVs. While the SE was high for patients with small breathing pattern variations, changes of the median breathing amplitudes in different imaging sessions led to inferior SE values for the mid‐ventilation PTV for one patient. In contrast, and showed higher SE values with a higher robustness against interfractional changes, at the cost of larger target volumes.

Conclusions

The results indicate that rt‐4DMRI could be valuable for the definition of target volumes based on the GTV POP to achieve a higher robustness against interfractional changes than feasible with today’s 4D‐CT‐based target definition concepts.
A DNA damage multiscale model for NTCP in proton and hadron therapy
Authors: Abolfath Ramin , Peeler Chris , Mirkovic Dragan , Mohan Radhe , Grosshans David
Published: January 2020

Purpose

To develop a first principle and multiscale model for normal tissue complication probability (NTCP) as a function of dose and LET for proton and in general for particle therapy with a goal of incorporating nanoscale radio‐chemical to macroscale cell biological pathways, spanning from initial DNA damage to tissue late effects.

Methods

The method is a combination of analytical and multiscale computational steps including (a) derivation of functional dependencies of NTCP on DNA‐driven cell lethality in nanometer and mapping to dose and LET in millimeter, and (b) three‐dimensional‐surface fitting to Monte Carlo data set generated based on postradiation image change and gathered for a cohort of 14 pediatric patients treated by scanning beam of protons for ependymoma. We categorize voxel‐based dose and LET associated with development of necrosis in NTCP.

Result

Our model fits well the clinical data, generated for postradiation tissue toxicity and necrosis. The fitting procedure results in extraction of in vivo radio‐biological α‐β indices and their numerical values.

Discussion and conclusion

The NTCP model, explored in this work, allows to correlate the tissue toxicities to DNA initial damage, cell lethality and the properties and qualities of radiation, dose, and LET.
Improving PCASL at ultra‐high field using a VERSE‐guided parallel transmission strategy
Authors: Tong Yan , Jezzard Peter , Okell Thomas W. , Clarke William T.
Published: January 2020

Purpose

To improve the labeling efficiency of pseudo‐continuous arterial spin labeling (PCASL) at 7T using parallel transmission (pTx).

Methods

Five healthy subjects were scanned on an 8‐channel‐transmit 7T human MRI scanner. Time‐of‐flight (TOF) angiography was acquired to identify regions of interest (ROIs) around the 4 major feeding arteries to the brain, and and B0 maps were acquired in the labeling plane for tagging pulse design. Complex weights of the labeling pulses for each of the 8 transmit channels were calculated to produce a homogenous radiofrequency (RF) ‐shimmed labeling across the ROIs. Variable‐Rate Selective Excitation (VERSE) pulses were also implemented as a part of the labeling pulse train. Whole‐brain perfusion‐weighted images were acquired under conditions of RF shimming, VERSE with RF shimming, and standard circularly polarized (CP) mode. The same subjects were scanned on a 3T scanner for comparison.

Results

In simulation, VERSE with RF shimming improved the flip‐angles across the ROIs in the labeling plane by 90% compared with CP mode. VERSE with RF shimming improved the temporal signal‐to‐noise ratio by 375% compared with CP mode, but did not outperform a matched 3T sequence with a matched flip‐angle.

Conclusion

We have demonstrated improved PCASL tagging at 7T using VERSE with RF shimming on a commercial head coil under conservative SAR limits at 7T. However, improvements of 7T over 3T may require strategies with less conservative SAR restrictions.
Effects of a labour and delivery simulated practice programme for elderly primigravidas
Authors: Seong Chun hee , Park Kyung min , Moon Kyoung ja
Published: January 2020

Aim

Increasing numbers of older gravidas compel research into best practices for their labour‐related outcomes. Responding to this need, this study sought to develop and evaluate a programme for older primigravidas.

Design

The authors developed a simulated practice programme for older primigravidas and tested its effects.

Methods

A non‐equivalent control group pre‐ and post‐test design was used with 49 community‐dwelling primigravidas. The programme taught the stages of labour using a realistic scenario‐based practice and a debriefing session. Data were collected between June and September 2015. Participants were divided into intervention (N = 25) and control (N = 24) groups. Postintervention group effects were analysed with independent t tests.

Results

The intervention group's levels of anxiety and stress decreased and their knowledge and self‐confidence increased. The intervention group's labour duration was also shorter than that of the control group.
Genetically Engineered Escherichia coli Nissle 1917 Secreting GLP‐1 Analog Exhibits Potential Antiobesity Effect in High‐Fat Diet‐Induced Obesity Mice
Authors: Ma Jie , Li Cuiying , Wang Junrui , Gu Jianwen
Published: January 2020

Objective

This study aimed to investigate the potential antiobesity effect of genetically modified Escherichia coli Nissle 1917 (EcN‐GM) in mice fed a high‐fat diet (HFD).

Methods

The mice were randomly divided into six groups: a normal diet group (ND), a HFD group, a HFD + EcN group, and three HFD + EcN‐GM groups. The effects of EcN‐GM on body weight, food intake, fat pad and organ weight, and an oral glucose tolerance test were measured, in addition to hepatic biochemistry and histological analysis. The mRNA expression of neuropeptides related to food intake regulation in the hypothalamus was also detected.

Results

The results showed that EcN‐GM decreased body weight, body weight gain, food intake, fat pad weight, and hepatic weight of HFD mice. There were beneficial effects of EcN‐GM on blood glucose, hepatic biochemistry, and hepatic histological alterations. A dramatic switch of food intake‐regulating gene expression in the hypothalamus was also observed in mice.

Conclusions

This work has revealed that a modified live bacterial therapeutic, EcN‐GM, has potential beneficial effects on obesity. This effect may be related to the regulating of the neuropeptide expression of energy intake and expenditure in the hypothalamus. This study demonstrates a successful example of engineered EcN‐GM as a novel approach for weight management.
Proposal for an implicit stigma measure in mental illness: A multigroup study
Authors: González‐Sanguino Clara , Muñoz Manuel , Orihuela‐Villameriel Teresa , Pérez‐Santos Eloísa
Published: January 2020

An Implicit Association Test was developed to assess the mental illness stigma in people from the general population, mental health professionals, people with a diagnosis, and family members. No differences were found between groups. Implicit stigma was found throughout the sample, with lower scores in the younger age group.