bluuebunny/crossref_metadata_2025 huggingface dataset:
Complete Arch Monolithic Zirconia Prosthesis Supported By Cobalt Chromium Metal Bar: A Clinical Report
Authors: Bidra Avinash S.
Published: April 2020

Complete arch fixed implant supported prosthesis made of monolithic zirconia is a popular treatment option with minimal complications, as documented in the literature over a 5‐year period. One of the limitations of this material is its inability to be used when the span between adjacent implants is excessively long. A potential solution to mitigate this problem is to support the zirconia prosthesis with a metal substructure, which intrinsically has higher tensile strength. This clinical report describes the successful use of this prosthetic design in a male patient with bruxism and history of multiple implant failures in the maxilla. This resulted in a large anterior‐posterior span between the anterior implants in the maxillary lateral incisor region and the distal implants in the pterygoid region. This article also describes the use of a split file digital workflow to scan the prototype prosthesis and then digitally design and mill the screw‐retained cobalt chromium bar, as well as the overlaying of zirconia prosthesis which was retained by separate screws. This novel approach offers promise for management of the atrophic maxilla where implants with remote anchorage are used resulting in broader distribution of implants.
Are short‐term effects of pollution important for growth and optimal fiscal policy?
Authors: Ghosh Sugata , Ray Barman Trishita , Gupta Manash Ranjan
Published: April 2020

We study optimal fiscal policy in a stock‐flow model of the environment within an endogenous growth framework, where some pollutants have a lasting impact on environmental quality which is restored through abatement expenditure, while others dissipate and hence, have a short‐term effect on the environment. All pollutants, however, affect the productivity of a public good negatively. Given that short‐term pollution, although it dissipates, is irreversible in this sense, a government cannot ignore its negative effects since this type of pollution lowers the productivity of all inputs. We find that a larger negative effect of short‐term pollutants as well as a higher congestion effect of private capital leads to corrective fiscal policies with higher optimal income tax and abatement expenditure rates, which have favorable growth consequences. Interestingly, we find that the rate of short‐term pollution does not affect optimal fiscal policy while that of the long‐term pollution does.
Electrocortical measures of performance monitoring from go/no‐go and flanker tasks: Differential relations with trait dimensions of the triarchic model of psychopathy
Authors: Ribes‐Guardiola Pablo , Poy Rosario , Patrick Christopher J. , Moltó Javier
Published: April 2020

This study examined associations of performance‐monitoring event‐related potentials (ERPs) from go/no‐go and flanker tasks with one another, and with psychopathy‐related traits of disinhibition, meanness, and boldness. A task‐dependent relationship was evident between the error‐related negativity (ERN) and trait disinhibition, with high‐disinhibited participants showing reduced no‐go ERN but not flanker ERN. Disinhibition was also inversely related to variants of the P3 and the error positivity (Pe) from these two tasks. A factor analysis of the ERPs revealed two distinct factors, one reflecting shared variance among the P3 and Pe measures from the two tasks, and the other covariance among the N2 and ERN measures. Scores on the P3/Pe factor, but not the N2/ERN factor, were inversely related to disinhibition, and accounted for associations of this trait with variants of the P3 and Pe across tasks. The implication is that high trait disinhibition relates mainly to reductions in brain responses associated with later elaborative stages in the processing of motivationally significant events across different tasks. Importantly, no‐go ERN predicted disinhibition scores beyond N2/ERN factor scores, indicating that high disinhibition is not generally related to diminished early preresponse conflict and error processing, but rather to processing impairments in conditions calling for inhibition of prepotent response tendencies.
How networks among frontline offices influence regulatory enforcement: Diffusion and justification of interpretation of risk
Authors: Hirata Ayako
Published: April 2020

Street‐level interpretation and enforcement are critical to defining the meaning of law. To understand street‐level regulatory decisions, prior studies have highlighted internal office conditions, neglecting the influence that peer offices can have. This study examines the role of horizontal inter‐office interaction among frontline offices and illustrates how and under what conditions it shapes the meaning of law. Drawing on qualitative and quantitative data on Japan's Soil Contamination Countermeasures Act, this study reveals that inter‐office interaction occurs within fixed groups and comes to shape shared interpretations of law that regulators believe are legally valid. This implies that under legal ambiguity, inter‐office interactions develop institutionalized notions of appropriateness and reinforce the perception of legal consistency, which bolster the legitimacy of enforcement. Although peer office networks encourage convergence on the interpretation of law, because of their clustered structure, legal meanings develop differently across various groups.
A study on the least squares estimator of multivariate isotonic regression function
Authors: Bagchi Pramita , Sankar Dhar Subhra
Published: April 2020

Consider the problem of pointwise estimation of f in a multivariate isotonic regression model Z=f(X1,…,Xd)+ϵ, where Z is the response variable, f is an unknown nonparametric regression function, which is isotonic with respect to each component, and ϵ is the error term. In this article, we investigate the behavior of the least squares estimator of f. We generalize the greatest convex minorant characterization of isotonic regression estimator for the multivariate case and use it to establish the asymptotic distribution of properly normalized version of the estimator. Moreover, we test whether the multivariate isotonic regression function at a fixed point is larger (or smaller) than a specified value or not based on this estimator, and the consistency of the test is established. The practicability of the estimator and the test are shown on simulated and real data as well.
Surgical excision of iridociliary tumors using a postero‐anterior cyclo‐iridectomy and thermocautery in two dogs
Authors: Davis Rachel L. , Reilly Christopher M. , Moore Phillip A.
Published: April 2020

Objective

To report the surgical excision of an iridociliary adenoma and iridal melanocytoma using a postero‐anterior cyclo‐iridectomy in two dogs.

Procedure

A 7 year old neutered male English springer spaniel (case 1) and a 7 year old neutered male Labrador mix (case 2) were presented for evaluation of an intrairidal mass OS.

Results

Complete ophthalmic examination revealed a large, dorsonasal, well‐demarcated, intrairidal mass OS. A tan to pink intrairidal mass extending into the iridocorneal angle (case 1) and a pigmented intrairidal mass (case 2) were present. B‐mode ultrasonography showed a focal, soft tissue, homogenous mass within the uvea adjacent to and contacting the lens. Neither pars plana involvement nor vitreal extension was present. A postero‐anterior cyclo‐iridectomy was performed through a polyhedral scleral flap. Thermocautery was used to complete the cyclo‐iridectomy (case 1) and partial iridectomy (case 2) to excise the mass en bloc. Histopathology revealed a completely excised iridociliary adenoma (case 1) and iris melanocytoma (case 2). The surgery sites healed without complication. Mild uveitis (cases 1 and 2), scant vitreal hemorrhage (case 1), and mild hyphema (case 2) were present three days postoperatively but had resolved ten days postoperatively. The patients remain visual twenty‐two months (case 1) and seven months (case 2) postoperatively with a normal intraocular examination other than an iridal defect and mild dorsonasal lens capsular opacities.

Conclusions

The surgical approach described in these cases is utilized in physician‐based medicine. This approach and the use of thermocautery provide a viable surgical option for excision of large iridociliary tumors in dogs.
Modulatory effect of methanandamide on gastric vagal afferent satiety signals depends on nutritional status
Authors: Christie Stewart , O'Rielly Rebecca , Li Hui , Nunez‐Salces Maria , Wittert Gary A , Page Amanda J
Published: April 2020

Significance Statement

Gastric vagal afferent responses to tension are dampened in high fat diet‐induced obesity.

Endocannabinoids are known to dose‐dependently inhibit and excite gastric vagal afferents but their effect on gastric vagal afferents in diet‐induced obesity are unknown.

In individual gastric vagal afferent neurons of diet‐induced obese mice the co‐expression of components of the endocannabinoid system, including CB1, GHSR, TRPV1 and FAAH, was increased compared with lean mice.

In high fat diet‐induced obese mice, methanandamide only inhibited gastric vagal afferent responses to tension, possibly due to the observed change in the balance of receptors, hormones and breakdown enzymes in this system.

Collectively, these data suggest that endocannabinoid signalling, by gastric vagal afferents, is altered in diet‐induced obesity which may impact satiety and gastrointestinal function.

Gastric vagal afferents (GVAs) play a role in appetite regulation. The endocannabinoid anandamide (AEA) dose‐dependently inhibits and excites tension‐sensitive GVAs. However, it is also known that high fat diet (HFD) feeding alters GVA responses to stretch. The aim of this study was to determine the role of AEA in GVA signalling in lean and HFD‐induced obese mice.

Male C57BL/6 mice were fed (12 weeks) a standard laboratory diet (SLD) or HFD. Protein and mRNA expression of components of the cannabinoid system was determined in individual GVA cell bodies and the gastric mucosa. An in vitro GVA preparation was used to assess the effect of methanandamide (mAEA) on tension‐sensitive GVAs and the second messenger pathways involved.

In individual GVA cell bodies, cannabinoid 1 (CB1) and ghrelin (GHSR) receptor mRNA was higher in HFD mice than SLD mice. Conversely, gastric mucosal AEA and ghrelin protein levels were lower in HFD mice than SLD mice. In SLD mice, mAEA exerted dose‐dependent inhibitory and excitatory effects on tension‐sensitive GVAs. Only an inhibitory effect of mAEA was observed in HFD mice. The excitatory effect of mAEA was dependent on CB1, transient receptor potential vanilloid 1 (TRPV1) and the protein kinase C. Conversely, the inhibitory effect was dependent on CB1, growth hormone secretagogue receptor, TRPV1 and the protein kinase A. Endocannabinoids, acting through CB1 and TRPV1, have a pivotal role in modulating GVA satiety signals depending on the second messenger pathway utilised. In HFD mice only an inhibitory effect was observed. These changes may contribute to the development and/or maintenance of obesity.
A role for neurokinin 1 receptor expressing neurons in the paratrigeminal nucleus in bradykinin‐evoked cough in guinea‐pigs
Authors: Driessen Alexandria K. , McGovern Alice E. , Behrens Robert , Moe Aung Aung Kywe , Farrell Michael J. , Mazzone Stuart B.
Published: April 2020

Key points

Airway projecting sensory neurons arising from the jugular vagal ganglia terminate centrally in the brainstem paratrigeminal nucleus, synapsing upon neurons expressing the neurokinin 1 receptor.

This study aimed to assess the involvement of paratrigeminal neurokinin 1 receptor neurons in the regulation of cough, breathing and airway defensive responses.

Lesioning neurokinin 1 receptor expressing paratrigeminal neurons significantly reduced cough evoked by inhaled bradykinin but not inhaled ATP or tracheal mechanical stimulation.

The reduction in bradykinin‐evoked cough was not accompanied by changes in baseline or evoked respiratory variables (e.g. frequency, volume or timing), animal avoidance behaviours or the laryngeal apnoea reflex.

These findings warrant further investigations into targeting the jugular ganglia and paratrigeminal nucleus as a therapy for treating cough in disease.

Jugular vagal ganglia sensory neurons innervate the large airways and are thought to mediate cough and associated perceptions of airway irritations to a range of chemical irritants. The central terminals of jugular sensory neurons lie within the brainstem paratrigeminal nucleus, where postsynaptic neurons can be differentiated based on the absence or presence of the neurokinin 1 (NK1) receptor. Therefore, in the present study, we set out to test the hypothesis that NK1 receptor expressing paratrigeminal neurons play a role in cough evoked by inhaled chemical irritants. To test this, we performed selective neurotoxin lesions of NK1 receptor expressing neurons in the paratrigeminal nucleus in guinea‐pigs using substance P conjugated to saporin (SSP‐SAP). Sham lesion control or SSP‐SAP lesion guinea‐pigs received nebulised challenges, with the pan‐nociceptor stimulant bradykinin or the nodose ganglia specific stimulant adenosine 5′‐triphosphate (ATP), in conscious whole‐body plethysmography to study cough and associated behaviours. Laryngeal apnoea reflexes and cough evoked by mechanical stimulation of the trachea were additionally investigated in anaesthetised guinea‐pigs. SSP‐SAP significantly and selectively reduced the number of NK1 receptor expressing neurons in the paratrigeminal nucleus. This was associated with a significant reduction in bradykinin‐evoked cough, but not ATP‐evoked cough, mechanical cough or laryngeal apnoeic responses. These data provide further evidence for a role of jugular vagal pathways in cough, and additionally suggest an involvement of NK1 receptor expressing neurons in the paratrigeminal nucleus. Therefore, this neural pathway may provide novel therapeutic opportunities to treat conditions of chronic cough.
Friction and Friction Heat of Micronscale Iron
Authors: Sang Le Van , Yano Akihiko , Isohashi Ai , Sugimura Natsuko , Washizu Hitoshi
Published: April 2020

This paper investigates the friction and friction heat of the micronscale iron under the influences such as the velocity of the slider and temperature of the substrate by using the smoothed particle hydrodynamics simulations. It is found that in the velocity range of 10–100 m/s, the sliding velocity–friction coefficient relationship well complies with the fitted exponent or hyperbolic tangent function, and the friction coefficient approaches a stable value of 0.3 at around the velocity of 50 m/s after a rapidly increasing situation. The steady friction coefficient maintains over the temperature range of 200–400 K. The friction heat is detailed analyzed versus the sliding time. The sliding time–system temperature relationship is well fitted by the sigmoidal functions, except the interfacial particle layers. The layer causing friction shows the highest steady temperature and largest temperature rise. The increment between the initial temperatures of the slider and the substrate strongly results in the temperature rise while it does not affect the configuration of the sliding time–system temperature curves.
Using a Point-Line-Plane Representation for Unified Simulation of Planar and Spherical Mechanisms
Authors: Sharma Shashank , Purwar Anurag
Published: April 2020

This paper presents a geometric constraints driven approach to unified kinematic simulation of n-bar planar and spherical linkage mechanisms consisting of both revolute and prismatic joints. Generalized constraint equations using point, line, and plane coordinates have been proposed which unify simulation of planar and spherical linkages and are demonstrably scalable to spatial mechanisms. As opposed to some of the existing approaches, which seek to derive loop-closure equations for each type of mechanism separately, we have shown that the simulation can be made simpler and more efficient by using unified version of the geometric constraints on joints and links. This is facilitated using homogeneous coordinates and constraints on geometric primitives, such as point, line, and plane. Furthermore, the approach enables simpler programming, real-time computation, and ability to handle any type of planar and spherical mechanism. This work facilitates creation of practical and intuitive design tools for mechanism designers.
Australopithecus afarensis
endocasts suggest ape-like brain organization and prolonged brain growth
Authors: Gunz Philipp , Neubauer Simon , Falk Dean , Tafforeau Paul , Le Cabec Adeline , Smith Tanya M. , Kimbel William H. , Spoor Fred , Alemseged Zeresenay
Published: April 2020

Endocranial imprints suggest that “Lucy’s” species had an ape-like brain and may have had a long dependence on caregivers.
Measles virus nucleo- and phosphoproteins form liquid-like phase-separated compartments that promote nucleocapsid assembly
Authors: Guseva Serafima , Milles Sigrid , Jensen Malene Ringkjøbing , Salvi Nicola , Kleman Jean-Philippe , Maurin Damien , Ruigrok Rob W. H. , Blackledge Martin
Published: April 2020

Measles virus proteins form liquid droplets where they can encapsidate their genomic material.
Molecular targeting of FATP4 transporter for oral delivery of therapeutic peptide
Authors: Hu Zhenhua , Nizzero Sara , Goel Shreya , Hinkle Louis E. , Wu Xiaoyan , Li Chao , Ferrari Mauro , Shen Haifa
Published: April 2020

Targeting the FATP4 transporter is an effective way to transport peptides and enhance oral bioavailability of peptide drugs.
Systems Analysis of NADH Dehydrogenase Mutants Reveals Flexibility and Limits of Pseudomonas taiwanensis VLB120’s Metabolism
Authors: Nies Salome C. , Dinger Robert , Chen Yan , Wordofa Gossa G. , Kristensen Mette , Schneider Konstantin , Büchs Jochen , Petzold Christopher J. , Keasling Jay D. , Blank Lars M. , Ebert Birgitta E.
Published: April 2020

While
Pseudomonas
has the capability for high metabolic activity and the provision of reduced redox cofactors important for biocatalytic applications, exploitation of this characteristic might be hindered by high, constitutive activity of and, consequently, competition with the NADH dehydrogenases of the respiratory chain. The in-depth analysis of NADH dehydrogenase mutants of
Pseudomonas taiwanensis
VLB120 presented here provides insight into the phenotypic and metabolic response of this strain to these redox metabolism perturbations. This high degree of metabolic flexibility needs to be taken into account for rational engineering of this promising biotechnological workhorse toward a host with a controlled and efficient supply of redox cofactors for product synthesis.
Mycoplasma bovis Membrane Protein MilA Is a Multifunctional Lipase with Novel Lipid and Glycosaminoglycan Binding Activity
Authors: Adamu James Yazah , Wawegama Nadeeka Kumari , Kanci Condello Anna , Marenda Marc Serge , Markham Philip Francis , Browning Glenn Francis , Tivendale Kelly Anne
Published: April 2020

The survival, replication, and virulence of mycoplasmas depend on their ability to capture and import host-derived nutrients using poorly characterized membrane proteins. Previous studies on the important bovine pathogen
Mycoplasma bovis
demonstrated that the amino-terminal end of an immunogenic 226-kDa (P226) protein, encoded by
milA
(the full-length product of which has a predicted molecular weight of 303 kDa), had lipase activity. The predicted sequence of MilA contains glycosaminoglycan binding motifs, as well as multiple copies of a domain of unknown function (DUF445) that is also found in apolipoproteins.
Draft Genome Sequence of
Daldinia childiae
JS-1345, an Endophytic Fungus Isolated from Stem Tissue of Korean Fir
Authors: Kim Jung A , Jeon Jongbum , Park Sook-Young , Jeon Mi Jin , Yeo Joo-Hong , Lee Yong-Hwan , Kim Soonok
Published: April 2020

The fungus
Daldinia childiae
strain JS-1345, isolated from stem tissue of
Abies koreana
(Korean fir), has shown strong anti-inflammatory activity. Here, we report the genome sequence of
D. childiae
JS-1345. The final assembly consisted of 133 scaffolds totaling 38,652,569 bp (G+C content, 44.07%).
Clinical and genetical features of probands and affected family members with familial exudative vitreoretinopathy in a large Chinese cohort
Authors: Wang Shiyuan , Zhang Xiang , Hu Yiqian , Fei Ping , Xu Yu , Peng Jie , Zhao Peiquan
Published: April 2020

Aims

To explore the clinical and genetical features of families with strictly confirmed familial
exudative vitreoretinopathy (FEVR) in a large Chinese cohort.

Methods

A retrospective chart review study was conducted on the FEVR families diagnosed by both angiography and targeted next-generation sequencing in six FEVR known genes (FZD4, LRP5, TSPAN12, NDP, KIF11, ZNF408) in the probands and at least one first-degree family member. Variation in expressivity and severity was evaluated in different gene groups.

Results

105 FEVR families (223 FEVR affected subjects with 434 eyes) met the inclusion criteria. There were 105 probands with mean age of 3.8 years old and 118 affected family members of 32.7 years old averagely. Mutations in FZD4 were most prevalent (33.33%), followed by LRP5 (29.52%), TSPAN12 (22.86%), NDP (5.71%), KIF11 (1.9%) and ZNF408 (0.95%). 81% of the probands were classified as stage 4 or worse which most prevalently contributed to FZD4 mutations. All of the three affected family members with stage 4 or worse carried FZD4 variants. More than half (51.43%) of the probands in FZD4 group showed asymmetry. Unilateral FEVR was detected in 11 (10.5%) families consisting of six probands and six affected relatives, and FZD4 mutations accounted for 63.64% of all the cases with variant (c.1282_1285del, p. D428fs) identified in three families.

Conclusions

Genotype-phenotype correlation in FEVR was complex with family dependent. Mutations in FZD4 might initiate the most diverse and asymmetric phenotypes.
New clinical screening strategy to distinguishHNF1Avariant-induced diabetes from young early-onset type 2 diabetes in a Chinese population
Authors: Ma Yumin , Gong Siqian , Wang Xirui , Cai Xiaoling , Xiao Xinhua , Gu Weijun , Yang Jinkui , Zhong Liyong , Xiao Jianzhong , Li Meng , Liu Wei , Zhang Simin , Zhou Xianghai , Li Yufeng , Zhou Lingli , Zhu Yu , Luo Yingying , Ren Qian , Huang Xiuting , Gao Xueying , Zhang Xiuying , Zhang Rui , Chen Ling , Wang Fang , Wang Qiuping , Hu Mengdie , Han Xueyao , Ji Linong
Published: April 2020

Objective

Maturity-onset diabetes of the young caused by hepatocyte nuclear factor-1 alpha (HNF1A) variants (HNF1A-MODY) is a common form of monogenetic diabetes. Although patients withHNF1A-MODY might specifically benefit from sulfonylurea treatment, available methods for screening this specific type of diabetes are not cost-effective. This study was designed to establish an optimized clinical strategy based on multiple biomarkers to distinguish patients withHNF1A-MODY from clinically diagnosed early-onset type 2 diabetes (EOD) for genetic testing in a Chinese population.

Research design and methods

A case–control study including 125 non-related young patients with EOD and 15 probands withHNF1A-MODY (cohort 1) was conducted to evaluate reported biomarkers forHNF1A-MODY. A cut-off for the fasting insulin (Fins) level, the 97.5 percentile of 150 healthy subjects with normal components of metabolic syndrome (cohort 2), was used to filter out individuals with obvious insulin resistance (Fins <102 pmol/L). An optimized clinical screening strategy (HNF1A-CSS) was established, and its effectiveness was assessed in another group of 410 young patients with EOD (cohort 3).

Results

In cohort 1, body mass index (BMI), serum high-density lipoprotein cholesterol (HDL-c) and high-sensitivity C reactive protein (hs-CRP) levels were confirmed to be useful for the differential diagnosis ofHNF1A-MODY. In cohort 3, eight probands withHNF1A-MODY were identified. In cohort 3 and young relatives withHNF1A-MODY, meeting three of four criteria (BMI <28 kg/m2, hs-CRP <0.75 mg/L, Fins <102 pmol/L and HDL-c >1.12 mmol/L), the sensitivity and specificity ofHNF1A-CSS were 100% and 69.3%, respectively. In the pooled analysis of all young patients,HNF1A-CSS displayed 90.5% sensitivity and 73.6% specificity for identifying patients withHNF1A-MODY among those with clinically diagnosed EOD.

Conclusion

OurHNF1A-CSS is useful for distinguishing patients withHNF1A-MODY from patients with EOD in a young Chinese population.
Prevalence, risk factors and consequences of newborns born small for gestational age: a multisite study in Nepal
Authors: Gautam Paudel Pragya , Sunny Avinash K , Gurung Rejina , Gurung Abhishek , Malla Honey , Budhathoki Shyam Sundar , Paudel Prajwal , KC Navraj , KC Ashish
Published: April 2020

Objective

To identify the prevalence, risk factors and health impacts associated with small for gestational age (SGA) births in Nepal.

Methods

A cross-sectional study was conducted in 12 public hospitals in Nepal from 1 July 2017 to 29 August 2018. A total of 60 695 babies delivered in these hospitals during the study period were eligible for inclusion. Clinical information of mothers and newborns was collected by data collectors using a data retrieval form. A semistructured interview was conducted at the time of discharge to gather sociodemographic information from women who provided the consent (n=50 392). Babies weighing less than the 10th percentile for their gestational age were classified as SGA. Demographic, obstetric and neonatal characteristics of study participants were analysed for associations with SGA. The association between SGA and likelihood of babies requiring resuscitation or resulting in stillbirth and neonatal death was also explored.

Results

The prevalence of SGA births across the 12 hospitals observed in Nepal was 11.9%. After multiple variable adjustment, several factors were found to be associated with SGA births, including whether mothers were illiterate compared with those completing secondary and higher education (adjusted OR (AOR)=1.73; 95% CI 1.09 to 2.76), use of polluted fuel compared with use of clean fuel for cooking (AOR=1.51; 95% CI 1.16 to 1.97), first antenatal care (ANC) visit occurring during the third trimester compared with first trimester (AOR=1.82; 95% CI 1.27 to 2.61) and multiple deliveries compared with single delivery (AOR=3.07; 95% CI 1.46 to 6.46). SGA was significantly associated with stillbirth (AOR=7.30; 95% CI 6.26 to 8.52) and neonatal mortality (AOR=5.34; 95% CI 4.65 to 6.12).

Conclusions

Low literacy status of mothers, use of polluted fuel for cooking, time of first ANC visit and multiple deliveries are associated with SGA births. Interventions encouraging pregnant women to attend ANC visits early can reduce the burden of SGA births.
Paediatric drugs trials in China
Authors: Hao Guo-Xiang , Yuan Xiao-Xiao , Guo Wei , Quan Xi-Yu , Qi Xue-Jie , Wang Tian-You , Zhao Wei
Published: April 2020

Objective

Clinical trials of children’s drugs are of great significance to rational drug use in children. However, paediatric drugs trials in China are facing complex challenges. At present, the investigation data on registration status of paediatric drug trials in China are still relatively lacking, and relevant research is urgently needed.

Methods

The advanced retrieval function is used to retrieve clinical trials data in the Clinical Trial.gov and Chinese Clinical Trial Registry databases in 22 April 2019. Fifteen key items were analysed to describe trial characteristics, including: registration number, study start date (year), mode of funding, type of disease, medicine type, research stage, research design, sample size, number of experimental groups, placebo group, blind method, implementation centre, child specific, newborn specific and participant age.

Results

A total of 1388 clinical trials of paediatric drugs conducted in China were registered. The number of paediatric drug trials grew steadily over time, from less than 20 per year before 2005 to more than 100 per year after 2012. Most clinical trials were postmarketing (n=800, 57.6%), single-centre (n=1045, 75.3%), intervention studies (n=1161, 83.6%) without blinded methods (1169, 84.2%) and funded by non-profit organisations (n=838, 60.4%). The number of clinical trials for antineoplastic agents (n=254, 18.3%), anti-infectives (n=156, 11.2%) and vaccines (n=154, 11.1%) is the largest.

Conclusion

Paediatric drug trials in China made a significant progress in recent years. Innovative method and trial design optimisation should be encouraged to accelerate paediatric clinical research. Pharmaceutical companies need to be further stimulated to carry out more high-quality paediatric clinical trials with support of paediatric drug legislation.
Acute recurrent pericarditis: from pathophysiology towards new treatment strategy
Authors: Cacoub Patrice , Marques Cindy
Published: April 2020

Acute idiopathic or so-called viral pericarditis is a frequent and usually benign disease, although recurrences are frequent. Data strongly suggest the presence of underlying autoinflammatory and/or autoimmune disorders. It has been reported that there is an inflammatory response of the innate immune system typical of ‘autoinflammatory diseases’, predominantly mediated by interleukin-1 (IL-1). This may result from the activation of the inflammasome by a cardiotropic virus or a non-specific agent. The inflammatory response of the adaptive immune system, typical of ‘autoimmune diseases’—mainly mediated by autoantibodies or autoreactive T lymphocytes—seems also involved as anti-heart or anti-intercalated disk autoantibodies were associated with a higher number of recurrences and hospitalisations. Current guidelines recommend that aspirin/non-steroidal anti-inflammatory drugs for a few weeks should be associated to colchicine for 6 months in recurrent pericarditis. In refractory cases, low-dose corticosteroids or immunosuppressive drugs have been proposed with limited efficacy. Growing evidences suggest a place of IL-1 receptor antagonists in the treatment of recurrent pericarditis. Many retrospective studies, one recent randomised placebo-controlled study and data of a real-life large international registry showed the good efficacy of anakinra with a good safety profile. Other IL-1 receptor antagonists showed promising results (canakinumab, rilonacept). However, IL-1 receptor antagonists’ position in the treatment algorithm of recurrent pericarditis needs further evaluation in larger prospective clinical trials to replicate initial findings as well as to assess safety, cost-effectiveness and long-term efficacy.
PRKDC: new biomarker and drug target for checkpoint blockade immunotherapy
Authors: Tan Kien Thiam , Yeh Chun-Nan , Chang Yu-Chan , Cheng Jen-Hao , Fang Wen-Liang , Yeh Yi-Chen , Wang Yu-Chao , Hsu Dennis Shin-Shian , Wu Chiao-En , Lai Jiun-I , Chang Peter Mu-Hsin , Chen Ming-Han , Lu Meng-Lun , Chen Shu-Jen , Chao Yee , Hsiao Michael , Chen Ming-Huang
Published: April 2020

Background

Immunological checkpoint blockade is effective in treating various malignancies. Identifying predictive biomarkers to assist patient selection for immunotherapy has become a priority in both clinical and research settings.

Methods

Mutations in patients who responded to immunotherapy were identified through next-generation sequencing. Relationships among protein kinase, DNA-activated, catalytic polypeptide (PRKDC) mutations, mutation load and microsatellite instability (MSI) were analyzed using datasets from The Cancer Genome Atlas. These relationships were validated by conducting an in vitro study and by using tissue samples from 34 patients with gastric cancer. The CT26 animal model was used to evaluate the role of PRKDC as a predictive biomarker and the efficacy of the DNA-PK inhibitor.

Results

From the published literature, we found that among patients whose tumors harboredPRKDCmutations, 75%, 53.8%, and 50% of those with lung cancer, melanoma, and renal cell carcinoma, respectively, responded to immunotherapy. Most of these mutations were truncating and located in functional domains or in a destabilizing PRKDC protein structure. Additional analysis showed that aPRKDCmutation was significantly associated with a high mutation load in cervical cancer, colon adenocarcinoma, head and neck squamous cell carcinoma, lung adenocarcinoma, gastric adenocarcinoma and endometrial cancer. Patients with gastric cancer or colon cancer harboringPRKDCmutations were also highly associated with MSI-high status. Finally, we found that knockout PRKDC or DNA-PK inhibitor (PRKDCencodes the catalytic subunit of DNA-dependent protein kinase) enhanced the efficacy of the anti-programmed cell death protein one pathway monoclonal antibody in the CT26 animal model.

Conclusions

PRKDC is not only a predictive biomarker but also a drug target for immune checkpoint inhibitors.
Consensus for prevention and management of coronavirus disease 2019 (COVID-19) for neurologists
Authors: Jin Huijuan , Hong Candong , Chen Shengcai , Zhou Yifan , Wang Yong , Mao Ling , Li Yanan , He Quanwei , Li Man , Su Ying , Wang David , Wang Longde , Hu Bo
Published: April 2020

Coronavirus disease 2019 (COVID‐19) has become a pandemic disease globally. Although COVID-19 directly invades lungs, it also involves the nervous system. Therefore, patients with nervous system involvement as the presenting symptoms in the early stage of infection may easily be misdiagnosed and their treatment delayed. They become silent contagious sources or ‘virus spreaders’. In order to help neurologists to better understand the occurrence, development and prognosis, we have developed this consensus of prevention and management of COVID‐19. It can also assist other healthcare providers to be familiar with and recognise COVID-19 in their evaluation of patients in the clinic and hospital environment.
Evaluation of the interstorey drift performance of timber beam-hanger connection systems
Authors: Leach Harrison , MacDougall Colin , Tousignant Kyle
Published: April 2020

This paper presents the results of a study on pre-engineered steel and aluminum, nominally “pinned”, bolted-plate (BP), staggered dovetail (S-DT), and dovetail prototype (DTP) beam-hanger connection systems for glue-laminated timber joints under a combination of shear and reversed cyclic loading. A total of seven systems were tested to observe the evolution of damage, failure modes, and moment–rotation behaviour. The interstorey drift and deflection of a building that would cause failure of each system is inferred from the ultimate rotation capacities and compared to the limit(s) prescribed by Clause 4.1.8.13.3 of the National Building Code of Canada for various building categories. The BP systems generally reached an interstorey drift exceeding 2.5%, while the S-DT and DTP systems reached drifts of 0.6% and >1.2%, respectively. The BP systems also exhibited more ductile failure modes than the S-DT and DTP systems, involving withdrawal failure of the wood screws. Recommendations are made for appropriate connectors to use in each building category considered.
Wavevector-dependent optical properties from wavevector-independent proper conductivity tensor
Authors: Starke Ronald , Wirnata René , Schober Giulio A. H. , Bulut Nebahat , Kortus Jens
Published: April 2020

We discuss the calculation of the refractive index by means of the ab initioscalar dielectric functionand point out its inherent limitations. To overcome these, we start from the recently proposed fundamental, microscopic wave equation in materials in terms of the frequency-andwavevector-dependentdielectric tensor,and investigate under which conditions the standard treatment can be justified. Thereby, we address the question of neglecting the wavelength dependence of microscopic response functions. Furthermore, we analyze in how far the fundamental, microscopic wave equation is equivalent to the standard wave equation used intheoretical optics. In particular, we clarify the relation of the “effective” dielectric tensor used there to the microscopic dielectric tensor defined inab initio physics.

Graphical abstract
FLRW cosmology with EDSFD parametrization
Authors: Singh J. K. , Nagpal Ritika
Published: April 2020

In this paper, we study a cosmological model in the background of Friedmann–Lemaitre–Robertson–Walker (FLRW) space time by assuming an appropriate parametrization in the form of a differential equation in terms of energy density of scalar field $$\rho _{\phi } $$ρϕ, which is defined as Energy Density Scalar Field Differential equation (EDSFD) parametrization. The EDSFD parametrization leads to a required phase transition from early deceleration to present cosmic acceleration. This parametrization is used to reconstruct the equation of state parameter $$ \omega _{\phi }$$ωϕ in terms of redshift z i.e. $$ \omega _{\phi }(z) $$ωϕ(z) to examine the evolutionary history of the universe in a flat FLRW space time. Here, we constrain the model parameter using the various observational datasets of Hubble parameter H(z) , latest Union 2.1 compilation dataset SNeIa, BAO, joint dataset $$H(z)+SNeIa $$H(z)+SNeIa and $$ H(z)+SNeIa+BAO $$H(z)+SNeIa+BAO for detail analysis of the behavior of physical parameters and we find its best fit present value. Also, we discuss the dynamics of reheating phase after inflation, analyse the behaviors of the physical features using some diagnostic tools, and examine the viability of our parametric model.
Retraction Note to: Spectrum of cosmological correlation from vacuum fluctuation of stringy axion in entangled de Sitter space
Authors: Choudhury Sayantan , Panda Sudhakar
Published: April 2020

This article [1] has been retracted due to ethical reasons (duplicate simultaneous submission to another journal).
Short Semantic Patterns: A Linguistic Pattern Mining Approach for Content Analysis Applied to Hate Speech
Authors: Sorato Danielly , Goularte Fábio B. , Fileto Renato
Published: April 2020

Microblog posts such as tweets frequently contain users’ opinions and thoughts about events, products, people, institutions, etc. However, the usage of social media to prop-agate hate speech is not an uncommon occurrence. Analyzing hateful speech in social media is essential for understanding, fighting and discouraging such actions. We believe that by extracting fragments of text that are semantically similar it is possible to depict recurrent linguistic patterns in certain kinds of discourse. Therefore, we aim to use these patterns to encapsulate frequent statements textually expressed in microblog posts. In this paper, we propose to exploit such linguistic patterns in the context of hate speech. Through a technique that we call SSP (Short Semantic Pattern) mining, we are able to extract sequences of words that share a similar meaning in their word embedding representation. By analyzing the extracted patterns, we reveal some kinds of discourses that are replayed across a dataset, such as racist and sexist statements. Afterwards, we experiment using SSP as features to build classifiers that detect if a tweet contains hate speech (binary classification) and to distinguish between sexist, racist and clean tweets (ternary classification). The SSP instances encountered in tweets containing sexism have shown that a large number of sexist tweets began with the introduction ‘I’m not sexist but’ and ‘Call me sexist but’. Meanwhile, SSP instances found in tweets reproducing racism revealed a prominence of contents against the Islamic religion, associated entities and organizations.
Fuzzy Information Diffusion in Twitter by Considering User’s Influence
Authors: Kanavos Andreas , Livieris Ioannis E.
Published: April 2020

Does a post with specific emotional content that is posted on Twitter by an influential user have the capability to affect and even alter the opinions of those who read it? Accordingly, “influential” users affected by this post can then affect their followers so that eventually a large number of users may change their opinions about the subject the aforementioned post was made on? Social Influence can be described as the power or even the ability of a person to yet influence the thoughts and actions of other users. So, User Influence stands as a value that depends on the interest of the followers (via replies, mentions, retweets, favorites). Our study focuses on identifying such phenomena on the Twitter graph of posts and on determining which users’ posts can trigger them. Furthermore, we analyze the Influence Metrics of all users taking part in specific discussions and verify the differences among them. Finally the percentage of Graph cover when the diffusion starts from the “influential” users, is measured and corresponding results are extracted. Hence, results show that the proposed implementations and methodology can assist in identifying “influential” users, that play a dominant role in information diffusion.
Corba: Gone but (Hopefully) Not Forgotten
Authors: Coatta Terry
Published: April 2020

Back in the June 2006 issue of Queue, Michi Henning wrote a very good condensed history of CORBA and discussed how some of its technical limitations contributed to its downfall. While those limitations certainly aided CORBA’s demise, there is a very widespread notion that the ultimate cause was the ascendance of Web Services, a notion that is compounded with the further belief that Web Services’ dominance of the distributed computing landscape is indicative of its technical superiority to the systems that preceded it, such as CORBA and DCOM.
Things I Learned in School
Authors: Coatta Terry
Published: April 2020

How many of us have not had the experience of sitting in a classroom wondering idly: "Is this really going to matter out in the real world?" It’s curious, and in no small amount humbling, to realize how many of those nuggets of knowledge really do matter. One cropped up recently for me: the Finite State Machine.
Human thermoregulation during prolonged exposure to warm and extremely humid environments expected to occur in disabled submarine scenarios
Authors: Schlader Zachary J. , Johnson Blair D. , Pryor Riana R. , Stooks Jocelyn , Clemency Brian M. , Hostler David
Published: April 2020

Military and civilian emergency situations often involve prolonged exposures to warm and very humid environments. We tested the hypothesis that increases in core temperature and body fluid losses during prolonged exposure to warm and very humid environments are dependent on dry bulb temperature. On three occasions, 15 healthy males (23 ± 3 yr) sat in 32.1 ± 0.1°C, 33.1 ± 0.2°C, or 35.0 ± 0.1°C and 95 ± 2% relative humidity normobaric environments for 8 h. Core temperature (telemetry pill) and percent change in body weight, an index of changes in total body water occurring secondary to sweat loss, were measured every hour. Linear regression models were fit to core temperature (over the final 4 h) and percent changes in body weight (over the entire 8 h) for each subject. These equations were used to predict core temperature and percent changes in body weight for up to 24 h. At the end of the 8-h exposure, core temperature was higher in 35°C (38.2 ± 0.4°C, P < 0.01) compared with 32°C (37.2 ± 0.2°C) and 33°C (37.5 ± 0.2°C). At this time, percent changes in body weight were greater in 35°C (−1.9 ± 0.5%) compared with 32°C (−1.4 ± 0.3%, P < 0.01) but not 33°C (−1.6 ± 0.6%, P = 0.17). At 24 h, predicted core temperature was higher in 35°C (39.2 ± 1.4°C, P < 0.01) compared with 32°C (37.6 ± 0.9°C) and 33°C (37.5 ± 0.9°C), and predicted percent changes in body weight were greater in 35°C (−6.1 ± 2.4%) compared with 32°C (−4.6 ± 1.5%, P = 0.04) but not 33°C (−5.3 ± 2.0%, P = 0.43). Prolonged exposure to 35°C, but not 32°C or 33°C, dry bulb temperatures and high humidity is uncompensable heat stress, which exacerbates body fluid losses.
Empirical Likelihood for Generalized Functional-Coefficient Regression Models with Multiple Smoothing Variables under Right Censoring Data
Authors: Xu Hong-Xia , Zhong Han-Sheng , Fan Guo-Liang
Published: April 2020

Empirical likelihood as a nonparametric approach has been demonstrated to have many desirable merits for constructing a confidence region. The purpose of this article is to apply the empirical likelihood method to study the generalized functional-coefficient regression models with multiple smoothing variables when the response is subject to random right censoring. The coefficient functions with multiple smoothing variables can accommodate various nonlinear interaction effects between covariates. The empirical log-likelihood ratio of an unknown parameter is constructed and shown to have a standard chi-squared limiting distribution at the true parameter. Based on this, the confidence region of the unknown parameter can be constructed. Simulation studies are carried out to indicate that the empirical likelihood method performs better than a normal approximation-based approach for constructing the confidence region.
Corneal Astigmatism Measurements Comparison among Ray-Tracing Aberrometry, Partial Coherence Interferometry, and Scheimpflug Imaging System
Authors: Zhang Yaqin , Dong Jing , Zhang Suhua , Sun Bin , Wang Xiaoliang , Tang Maolong , Wang Xiaogang
Published: April 2020

Purpose. To investigate interdevice agreement among corneal topography/ray-tracing aberrometry (iTrace), partial coherence interferometry (IOLMaster), and Scheimpflug imaging (Pentacam) for the measurement of corneal astigmatism. Methods. The analysis included 90 eyes of 90 subjects without ocular disease. The main outcome measures were corneal cylinder power and axis of astigmatism. All corneal astigmatism measurements were converted to two perpendicular components by using vector analysis. Interdevice agreement was assessed using Bland–Altman analysis, paired sample t-test, and one-way analysis of variance. Results. No significant interdevice difference existed in the astigmatism magnitude, cardinal component, and oblique component (all P>0.05). On comparing iTrace wavefront and simulated keratometry (SimK) astigmatism, significant differences were observed in the astigmatism magnitude and oblique component (both P<0.01), but not in the cardinal component (P=0.687). On comparing Pentacam pupil 3 mm and corneal vertex 3 mm axial astigmatism, significant difference was observed in the astigmatism magnitude (P<0.001), but not in the cardinal and oblique components (both P>0.05). Conclusions. The iTrace, IOLMaster, and Pentacam devices could be used interchangeably for corneal astigmatism measurement. However, the measurement difference in iTrace wavefront and SimK astigmatism and Pentacam pupil 3 mm and vertex 3 mm axial astigmatism should be considered in clinic practice.
Incidence of Keratoconus and Its Association with Systemic Comorbid Conditions: A Nationwide Cohort Study from South Korea
Authors: Moon Jong Youn , Lee Jesang , Park Yoon Hyung , Park Eun-Cheol , Lee Si Hyung
Published: April 2020

Purpose. To determine the incidence of keratoconus and to determine its possible association with common systemic diseases using a nationwide cohort. Methods. This retrospective nationwide cohort study included 1,025,340 subjects from the Korean National Health Insurance Service-National Sample Cohort database from 2004 to 2013. Estimates for incidence rates of keratoconus were identified. After 1 : 5 matching using propensity scores, associations between keratoconus and certain systemic comorbidities were determined using multivariate logistic regression analysis. Results. The incidence during the same period was 15.1 cases per 100,000 person-years. Adjusted logistic regression analysis after propensity score matching revealed significant associations between keratoconus and allergic rhinitis (odds ratio (OR): 1.86; 95% confidence interval (CI): 1.63–2.13; p<0.001), asthma (OR: 1.20; 95% CI: 1.06–1.36; p<0.001), atopic dermatitis (OR: 1.33; 95% CI: 1.13–1.56; p<0.001), and diabetes mellitus (DM) (OR: 1.35; 95% CI: 1.15–1.58; p<0.001). Conclusion. Estimates of the incidence of keratoconus may help in the planning of eye-care policies, and the results of this study determined the associations between allergic diseases and keratoconus. Conflicting results regarding the association between keratoconus and DM should be further evaluated.