bluuebunny/crossref_metadata_2025 huggingface dataset:
Mortality trends of stroke and dementia: Changing landscapes and new challenges
Authors: Wu Harry , Le Couteur David G. , Hilmer Sarah N.
Published: June 2021

Background/Importance

Stroke and dementia are important causes of death in the United States and may be interrelated as competing risks for mortality. No previous studies have simultaneously compared age‐ and sex‐specific mortality trends between stroke and subtypes of dementia at a population level. Insights gained from this study can help identify high‐risk populations and inform healthcare service requirements for managing stroke and dementia in the United States.

Objectives

To examine nationwide trends in mortality from stroke and subtypes of dementia in the United States by age group and sex.

Design

Population‐based cross‐sectional study.

Setting

U.S. mortality data from 2007 to 2016.

Participants

All U.S. residents whose primary cause of death was stroke, Alzheimer's disease, vascular dementia, or Lewy body dementia.

Measurements

Age‐adjusted mortality, mortality trends among men and women were analyzed separately using joinpoint regression.

Results

From 2007 to 2016, age‐adjusted stroke mortality fell by 21.6%. Age‐adjusted mortality (per 1,000,000) for Alzheimer's disease, vascular dementia, and Lewy body dementia increased by 1.2‐fold, 2‐fold, and 3‐fold, respectively. Annual age‐adjusted stroke mortality decreased by an average rate of 2.67% per year, while annual age‐adjusted mortality for Alzheimer's disease, vascular dementia, and Lewy body dementia increased by an average rate of 2.06%, 4.90%, and 12.13% per year, respectively. Mortality from stroke and dementia increased with age. Greater reductions in stroke mortality and greater increases in dementia mortality were seen in women than men; and in older than younger (<65 years) people.

Conclusions

There has been a striking rising trend in dementia mortality coincident with a reduction in stroke mortality in the United States. There are persistent age and sex disparities in stroke and dementia mortality trends. Our findings support the pathophysiological relationship between stroke and dementia, and have important implications for future research, healthcare planning, and provision.
Ganglioside GD3 is up‐regulated in microglia and regulates phagocytosis following global cerebral ischemia
Authors: Wang Jing , Zhang Quanguang , Lu Yujiao , Dong Yan , Dhandapani Krishnan M. , Brann Darrell W. , Yu Robert K.
Published: June 2021

Gangliosides, the major sialic‐acid containing glycosphingolipids in the mammalian brain, play important roles in brain development and neural functions. Here, we show that the b‐series ganglioside GD3 and its biosynthetic enzyme, GD3‐synthase (GD3S), were up‐regulated predominantly in the microglia of mouse hippocampus from 2 to 7 days following global cerebral ischemia (GCI). Interestingly, GD3S knockout (GD3S‐KO) mice exhibited decreased hippocampal neuronal loss following GCI, as compared to wild‐type (WT) mice. While comparable levels of astrogliosis and microglial proliferation were observed between WT and GD3S‐KO mice, the phagocytic capacity of the GD3S‐KO microglia was significantly compromised after GCI. At 2 and 4 days following GCI, the GD3S‐KO microglia demonstrated decreased amoebic morphology, reduced neuronal material engulfment, and lower expression of the phagolysosome marker CD68, as compared to the WT microglia. Finally, by using a microglia‐primary neuron co‐culture model, we demonstrated that the GD3S‐KO microglia isolated from mouse brains at 2 days after GCI are less neurotoxic to co‐cultured hippocampal neurons than the WT‐GCI microglia. Moreover, the percentage of microglia with engulfed neuronal elements in the co‐cultured wells was also significantly decreased in the GD3S‐KO mice after GCI. Interestingly, the impaired phagocytic capacity of GD3S‐KO microglia could be partially restored by pre‐treatment with exogenous ganglioside GD3. Altogether, this study provides functional evidence that ganglioside GD3 regulates phagocytosis by microglia in an ischemic stroke model. Our data also suggest that the GD3‐linked microglial phagocytosis may contribute to the mechanism of delayed neuronal death following ischemic brain injury.

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Peripheral glia diversity
Authors: Reed Chelsey B. , Feltri M. Laura , Wilson Emma R.
Published: June 2021

Recent years have seen an evolving appreciation for the role of glial cells in the nervous system. As we move away from the typical neurocentric view of neuroscience, the complexity and variability of central nervous system glia is emerging, far beyond the three main subtypes: astrocytes, oligodendrocytes, and microglia. Yet the diversity of the glia found in the peripheral nervous system remains rarely discussed. In this review, we discuss the developmental origin, morphology, and function of the different populations of glia found in the peripheral nervous system, including: myelinating Schwann cells, Remak Schwann cells, repair Schwann cells, satellite glia, boundary cap‐derived glia, perineurial glia, terminal Schwann cells, glia found in the skin, olfactory ensheathing cells, and enteric glia. The morphological and functional heterogeneity of glia found in the periphery reflects the diverse roles the nervous system performs throughout the body. Further, it highlights a complexity that should be appreciated and considered when it comes to a complete understanding of the peripheral nervous system in health and disease.
Non‐Market Strategies and Credit Benefits: Unpacking Heterogeneous Political Connections in Response to Government Anti‐Corruption Initiatives
Authors: Fengyan Yu , Hongjuan Zhang , Tan Justin , Qi Liang
Published: June 2021

This paper explores how political connections influence firms’ credit benefits, especially when the political environment improves. The authors distinguish two types of political connections – connections to government officials and connections to council deputies – according to whether the political benefits they provide are exclusive and definite. Employing a panel data set comprised of Chinese listed firms’ bank‐loan contracts from 2008 to 2014, they find politically connected firms – and particularly firms with connections to government officials – enjoy significantly lower loan costs than their non‐connected counterparts. Moreover, they find that anti‐corruption efforts, which reflect improvement in the political environment, reduce the credit benefits of political connections, but only for firms that have connections to government officials. Results emphasize the value of unpacking the heterogeneity of political connections and illuminate the importance of more complete assessment of corporate political strategies in changing political environments.
Comparative transient expression analyses on two conserved effectors of Colletotrichum orbiculare reveal their distinct cell death‐inducing activities between Nicotiana benthamiana and melon
Authors: Chen Jinlian , Inoue Yoshihiro , Kumakura Naoyoshi , Mise Kazuyuki , Shirasu Ken , Takano Yoshitaka
Published: June 2021

Colletotrichum orbiculare infects cucurbits, such as cucumber and melon (Cucumis melo), as well as the model Solanaceae plant Nicotiana benthamiana, by secreting an arsenal of effectors that suppress the immunity of these distinct plants. Two conserved effectors of C. orbiculare, called NLP1 and NIS1, induce cell death responses in N. benthamiana, but it is unclear whether they exhibit the same activity in Cucurbitaceae plants. In this study, we established a new Agrobacterium‐mediated transient expression system to investigate the cell death‐inducing activity of NLP1 and NIS1 in melon. NLP1 strongly induced cell death in melon but, in contrast to the effects seen in N. benthamiana, mutations either in the heptapeptide motif or in the putative glycosylinositol phosphorylceramide‐binding site did not cancel its cell death‐inducing activity in melon. Furthermore, NLP1 lacking the signal peptide caused cell death in melon but not in N. benthamiana. Study of the transient expression of NIS1 also revealed that, unlike in N. benthamiana, NIS1 did not induce cell death in melon. In contrast, NIS1 suppressed flg22‐induced reactive oxygen species generation in melon, as seen in N. benthamiana. These findings indicate distinct cell death‐inducing activities of NLP1 and NIS1 in these two plant species that C. orbiculare infects.
Limited asymptomatic colonization of apple tree shoots by Neonectria ditissima following infection of leaf scars and pruning wounds
Authors: Olivieri Leone , Saville Robert J. , Gange Alan C. , Xu Xiangming
Published: June 2021

European apple canker, caused by Neonectria ditissima, is an important disease of apple (Malus domestica). The fungus may reside in the tree without causing symptoms for up to a few years, thus making canker control difficult. Asymptomatic infections established in the nursery can result in severe canker outbreaks in newly established apple orchards. It has been suggested that N. ditissima might colonize the tree beyond the infection point during the asymptomatic stage. We investigated whether N. ditissima can colonize the internal tissues of apple shoots, both prior to and after visual symptoms. Apple trees were artificially inoculated via pruning wounds and leaf scars; then the pathogen was tracked at the inoculation point and beyond with isolation or real‐time quantitative PCR (qPCR). Before visual symptoms, N. ditissima could be detected in the infected pruning cut or leaf scar, but not at a distance of 10–15 mm from the entry point, or greater. Conversely, after symptom expression, the pathogen could be detected in the symptomless tissue at 10–15 mm from a canker lesion. This study demonstrated that the asymptomatic infection by N. ditissima can be detected using qPCR and that the pathogen does not grow systemically much beyond the initial entry point inside the plant before visual canker symptoms appear.
Epidemiology of Pierre‐Robin sequence in Europe: A population‐based EUROCAT study
Authors: Santoro Michele , Coi Alessio , Barišić Ingeborg , Pierini Anna , Addor Marie‐Claude , Baldacci Silvia , Ballardini Elisa , Boban Ljubica , Braz Paula , Cavero‐Carbonell Clara , de Walle Hermien E. K. , Draper Elizabeth S. , Gatt Miriam , Haeusler Martin , Klungsøyr Kari , Kurinczuk Jennifer J. , Materna‐Kiryluk Anna , Lanzoni Monica , Lelong Nathalie , Luyt Karen , Mokoroa Olatz , Mullaney Carmel , Nelen Vera , O’Mahony Mary T. , Perthus Isabelle , Randrianaivo Hanitra , Rankin Judith , Rissmann Anke , Rouget Florence , Schaub Bruno , Tucker David , Wellesley Diana , Zymak‐Zakutnia Nataliia , Garne Ester
Published: June 2021

Background

Pierre Robin sequence (PRS) is a rare congenital anomaly. Respiratory disorders and feeding difficulties represent the main burden.

Objective

The aim of this study was to investigate the epidemiology of PRS using a cohort of cases from EUROCAT, the European network of population‐based registries of congenital anomalies.

Methods

We analysed cases of PRS born in the period 1998‐2017 collected by 29 population‐based congenital anomaly registries in 17 different countries. We calculated prevalence estimates, prenatal detection rate, survival up to 1 week, and proportions of associated anomalies. The effect of maternal age was tested using a Poisson regression model.

Results

Out of 11 669 155 surveyed births, a total of 1294 cases of PRS were identified. The estimate of the overall prevalence was 12.0 per 100 000 births (95% CI 9.9, 14.5). There was a total of 882 (68.2%) isolated cases, and the prevalence was 7.8 per 100 000 births (95% CI 6.7, 9.2). A total of 250 cases (19.3%) were associated with other structural congenital anomalies, 77 cases (6.0%) were associated with chromosomal anomalies and 77 (6.0%) with genetic syndromes. The prenatal detection rate in isolated cases was 12.0% (95% CI 9.8, 14.5) and increased to 16.0% (95% CI 12.7, 19.7) in the sub‐period 2008‐2017. The prevalence rate ratio of non‐chromosomal cases with maternal age ≥35 was higher than in cases with maternal age <25 for total (PRR 1.26, 95% CI 1.05, 1.51) and isolated cases (PRR 1.33, 95% CI 1.00, 1.64). Survival of chromosomal cases (94.2%) and multiple anomaly cases (95.3%) were lower than survival of isolated cases (99.4%).

Conclusions

This epidemiological study using a large series of cases of PRS provides insights into the epidemiological profile of PRS in Europe. We observed an association with higher maternal age, but further investigations are needed to test potential risk factors for PRS.
On the Bounds of Eigenvalues of a Clamped Plate in Tension
Authors: Kaul R. K. , Tewari S. G.
Published: June 2021

In this paper, use is made of Temple’s generalizations of Kato’s theorem for the determination of close lower bounds to the fundamental frequency of oscillation of a clamped square plate subjected to uniform biaxial edge tension. The success of the method depends upon the solution of an auxiliary problem governing the residual mode shape; and in the present case, this mode is determined by using the variational method of Ritz. The principle of computation of the number ϵV2 (which corresponds to the ratio of the elastic energies in the residual and the tentative mode) is explained, and the value of the lower bound is determined by using the inequality (1 − ρ/β)(ρ/α − 1) ≤ ϵV2. The results are compared with those obtained previously by Weinstein and Chien, and it is shown that the present method leads to much closer bounds.
Carrying Capacity of an Elastic-Plastic Cylindrical Shell With Linear Strain-Hardening
Authors: Hodge P. G. , Nardo S. V.
Published: June 2021

The approximate capacity of a thin-walled closed circular cylindrical shell, simply supported at each end and subjected to a uniform hydrostatic pressure, is determined. Elastic and plastic strains are considered, and the latter are assumed to follow a linear law of isotropic hardening. The principle of minimum potential energy is used to determine an approximate solution for the stress resultants, displacements, and maximum load. In an example, it is found that the carrying capacity is considerably lower than that predicted by either rigid-plastic theory or elasticity theory.
Thermal Stresses in Transversely Isotropic Semi-Infinite Elastic Solids
Authors: Sharma Brahmadev
Published: June 2021

A general method of solution of the steady-state thermal-stress problem of a transversely isotropic semi-infinite elastic solid is given in this paper.
Spherical Symmetry in the Theory of Elasticity
Authors: Goded F.
Published: June 2021

Part 1 of the paper presents a study of the common characteristics of both plane symmetry and axial symmetry in the theory of elasticity; viz., the form of the stress tensor and the existence of further analogous symmetries. In Part 2, the subject deals with the possibility of the existence of further analogous symmetries which are found to be possible only in some specific cases. In particular, spherical symmetry is treated. The method of obtaining the stress function of this new symmetry and the equation which this function must satisfy also are discussed, together with the stresses expressed by means of this stress function. The paper ends with a brief review of a general solution of the stress function and an example of the application of this stress function to a given problem.
Effect of Finite Rotations on Gyroscopic Sensing Devices
Authors: Goodman L. E. , Robinson A. R.
Published: June 2021

The well-known noncommutativity of three-dimensional finite rotations has long been a curiosity in mechanics since, in actual solution of dynamical problems, the angular velocity, which is conveniently representable as a vector, plays a more natural role. In modern inertial guidance systems, however, the orientation of a body in space, i.e., a rotation, is of primary engineering interest. In this paper a simple method of determining orientation from the time history of three body components of angular velocity is developed by means of a new theorem in kinematics. As a special case of this theorem it is shown that a gyro subjected to a regime of rotations which returns it to the original space orientation will, in general, produce a residual signal. It will have experienced a nonzero and easily calculated mean angular velocity about its input axis. Some implications of the theorem for the design of inertial guidance systems and for the testing of gyros are discussed.
Some Shock Spectra Characteristics and Uses
Authors: Fung Y. C. , Barton M. V.
Published: June 2021

A shock spectrum is a plot showing the peak response of a linear variable-frequency oscillator (of single degree of freedom) to a specific shock wave, as a function of the frequency of the oscillator. Such a spectrum may be measured, for example, by multifrequency reed gages and is sometimes used as a basis either for specifying the shock wave or for computing the response of a multi-degree-of-freedom structure to such a shock. In this paper these applications of the shock spectrum are discussed. In particular, it is shown that, if the fundamental frequency (f1, cps) of the structure is sufficiently high, a close approximation of the peak response of a multi-degree-of-freedom system can be obtained by the algebraic sum (not the sum of absolute values) of the peak responses of the individual degrees of freedom. Numerical results for a uniform cantilever beam subjected to a shock load uniformly distributed over its span show that the high-frequency requirement is satisfied if 2f1tm ≥ 1, where tm(sec) is the rise time of the pulse.
Some Solutions of the Timoshenko Beam Equation for Short Pulse-Type Loading
Authors: Plass H. J.
Published: June 2021

A collection of solutions to the Timoshenko beam equation is presented. Various types of support conditions and impact conditions are included. In every case the impact is assumed to be a pulse in the form of a half-sine wave. The results were found numerically, using the method of characteristics, except for one case, which was done in addition by the Laplace transform method, for check purposes. Agreement with experiment is good except for a pulse of duration comparable to the time required for the bending-type wave to travel a distance of one diameter. Discussion is included of the differences among the various cases studied.
Nonaxial Bending of Ring Plates of Varying Thickness
Authors: Conway H. D.
Published: June 2021

A solution is given to the problem of the bending of circular ring plates of varying thickness which are subjected at their outer and inner edges to any system of forces and moments. The thickness is assumed to be proportional to any power of the radius, this having the effect of making the solution tractable. Numerical results are given for a plate, clamped at its inner, free at its outer, edge and subjected to a normal concentrated load on its outer edge. The constant-thickness version of this problem was first solved by Reissner.
Transient and Residual Stresses in Heat-Treated Plates
Authors: Landau H. G. , Weiner J. H.
Published: June 2021

Equations are given for determining transient and residual thermal stresses in a heat-treated plate. The material of the plate is assumed to be elastic, perfectly plastic. The temperature is assumed uniform on any plane parallel to the faces of the plate but can vary arbitrarily in the direction normal to the face and in time. The stress distribution during the unloading period is determined exactly without the simplifying assumption of simultaneous unloading. Application is made to the determination of stresses during cooling of a uniformly heated plate. The stress-distribution sequence and residual stresses are calculated for several values of cooling rate and yield stress.
Theory of Pitch and Curvature Corrections for the Helical Spring—I (Tension)
Authors: Ancker C. J. , Goodier J. N.
Published: June 2021

The helical spring of round cross section loaded in axial tension is solved. Both pitch and curvature are considered. All deformations and stresses are obtained by a “thin-slice” method which reduces the variables from three to two. The form of the solution is deduced from considerations of symmetry. This knowledge, applied to the equations of the boundary-value problem, produces algebraic equations which are then solved.
Response of Complex Structures From Reed-Gage Data
Authors: Rubin Sheldon
Published: June 2021

The paper considers the general applicability of the reed gage, an instrument which records the peak response to a transient motion of single-degree-of-freedom systems. These recorded data permit the calculation of peak response in each vibrational mode of a complex structure experiencing the measured excitation as a base motion. An upper bound to the maximum structural response can be obtained by summing the peak responses in each of the modes. An analysis is made of the error inherent in this superposition process. In many practical problems the distribution of mode frequencies and the form of the excitation are such that this error is not of great significance.
Design of Accelerometers for Transient Measurements
Authors: Rubin Sheldon
Published: June 2021

The purpose of this study is to find a significant accelerometer accuracy criterion for measuring transients, and to apply it to the investigation of optimum damping and the range of frequency response required. It is proposed that the effect of instrument distortions on the response spectrum of a transient be used to evaluate the acceptability of the measurement. The application of this response-spectrum criterion to some selected acceleration pulses indicates that the optimum instrument damping for a transient measurement is essentially the same as for the measurement of periodic motions and that the accelerometer period should be less than 0.4 of the pulse duration for 5 per cent accuracy. A reasonable generalization of the results to more complex transients is made.
The Plastic Deformation Due to Impact of a Cantilever Beam With an Attached Tip Mass
Authors: Mentel T. J.
Published: June 2021

A theoretical analysis, based on the assumption of ideal plastic-rigid behavior, is made of the deformation of a uniform cantilever beam with an attached lip mass, which results from a transverse acceleration of the base of the cantilever. The problem is also investigated experimentally and an assessment is made of the theoretical work. A simplified analysis based on a one-dimensional model is found to give results which are very close to those obtained by analysis of the continuum model, but in both cases it is found that corrections must be applied to obtain good results, because of effects neglected in both analyses. In the case of the experimental models tested, the principal correction appears to be that for strain-rate effects.
Physical Properties of Plastics for Photothermoelastic Investigations
Authors: Tramposch H. , Gerard G.
Published: June 2021

The optical and physical properties of Paraplex P43, Castolite, and epoxy resin Hysol 6000-OP, which are potentially of interest in photothermoelastic investigations, were investigated over a temperature range from +100 to −60 F. Results on the thermal-expansion coefficient, the material fringe value, and the modulus of elasticity as functions of temperature are presented. Also evaluated were thermal properties of importance in heat conduction. Photothermoelastic figures of merit, which rate the optical sensitivity of materials in photothermoelastic applications, as well as a new method to determine this figure in a relative manner are presented.
Buckling of Struts of Variable Bending Rigidity
Authors: Abbassi Mohammed M.
Published: June 2021

The differential equation (d2y/dx2) + ϕ(x)y = 0 where ϕ(x) is a slowly varying function of x can be solved approximately in terms of trigonometric functions. The solution can be applied to find the critical buckling loads for struts of variable bending rigidity and for uniform struts under the action of varying axial forces. The error in using the approximate formulas for buckling loads is in most cases small, and, for all practical purposes, satisfactory results are obtained.
The Strain-Energy Expression for Thin Elastic Shells
Authors: Haywood J. H. , Wilson L. B.
Published: June 2021

A strain-energy expression is derived for thin isotropic elastic shells in terms of the displacements of the middle surface of the shell. This expression is confined to small-deflection theory, and the condition of plane stress previously used in the theory of thin shells is retained. A simplified expression is also obtained by the introduction of the Kirchhoff-Love hypothesis, and the relative merits of these two expressions are discussed. The strain-energy expression is applied to the thin circular cylinder, and the result is compared with various strain-energy expressions developed by previous authors.
On the Carrying Capacity of Plates of Arbitrary Shape and Variable Fixity Under a Concentrated Load
Authors: Zaid M.
Published: June 2021

The previously known limit-load solution for a circular plate, with a centrally concentrated load, is extended to include a plate of general shape and fixity with arbitrary load location. Considering an ideally plastic material that obeys the Tresca yield criterion, this limit load is equal to 2π times the unit yield moment (M0). The techniques of this paper can be used to establish upper and lower bounds to the limit load for plates under other loading conditions.
Elastic, Plastic Stresses in Free Plate With Periodically Varying Surface Temperature
Authors: Yüksel Halil
Published: June 2021

The paper is concerned with a free plate that consists of an elastic, perfectly plastic material and is subjected to a harmonically varying temperature at one face, while the other face is kept at a constant temperature and the edge is perfectly insulated. The thermal stresses associated with the steady-state temperature oscillations are analyzed, and the development of plastic regions is discussed.
A hybrid underwater robot for multidisciplinary investigation of the ocean twilight zone
Authors: Yoerger Dana R. , Govindarajan Annette F. , Howland Jonathan C. , Llopiz Joel K. , Wiebe Peter H. , Curran Molly , Fujii Justin , Gomez-Ibanez Daniel , Katija Kakani , Robison Bruce H. , Hobson Brett W. , Risi Michael , Rock Stephen M.
Published: June 2021

We present the design and at-sea results from a hybrid marine robot called
Mesobot
that can actively track midwater phenomena.
Development of β-globin gene correction in human hematopoietic stem cells as a potential durable treatment for sickle cell disease
Authors: Lattanzi Annalisa , Camarena Joab , Lahiri Premanjali , Segal Helen , Srifa Waracharee , Vakulskas Christopher A. , Frock Richard L. , Kenrick Josefin , Lee Ciaran , Talbott Narae , Skowronski Jason , Cromer M. Kyle , Charlesworth Carsten T. , Bak Rasmus O. , Mantri Sruthi , Bao Gang , DiGiusto David , Tisdale John , Wright J. Fraser , Bhatia Neehar , Roncarolo Maria Grazia , Dever Daniel P. , Porteus Matthew H.
Published: June 2021

Preclinical efficacy and safety data in mice provide support for ex vivo β-globin gene correction to treat patients with sickle cell disease.
Hexabromocyclododecanes Are Dehalogenated by CYP168A1 from
Pseudomonas aeruginosa
Strain HS9
Authors: Huang Ling , Wang Weiwei , Zanaroli Giulio , Xu Ping , Tang Hongzhi
Published: June 2021

Hexabromocyclododecanes (HBCDs) are environmental pollutants that are wildly used in industry. In this study, we identified and characterized a novel key dehalogenase, CYP168A1, that is responsible for HBCD degradation from
Pseudomonas aeruginosa
strain HS9. This study provides new insights into understanding biodegradation of HBCDs.
The Integrity of Heme Is Essential for Reproducible Detection of Metronidazole-Resistant Clostridioides difficile by Agar Dilution Susceptibility Tests
Authors: Wu Xiaoqian , Shen Wan-Jou , Deshpande Aditi , Olaitan Abiola O. , Palmer Kelli L. , Garey Kevin W. , Hurdle Julian G.
Published: June 2021

Metronidazole resistance in clinical
Clostridioides difficile
is often described as unstable, since resistant strains reportedly appear susceptible following freezer storage or brief passage. This has presented a conundrum for adopting susceptibility testing to accurately evaluate the connection between metronidazole resistance and decreased clinical efficacy of metronidazole in patients with
C. difficile
infections (CDIs).
Cultivation of a Lytic Double-Stranded RNA Bacteriophage Infecting Microvirgula aerodenitrificans Reveals a Mutualistic Parasitic Lifestyle
Authors: Cai Xiaoyao , Tian Fengjuan , Teng Li , Liu Hongmei , Tong Yigang , Le Shuai , Zhang Tingting
Published: June 2021

Viruses with dsRNA genomes are quite diverse and infect organisms in all three domains of life. Although dsRNA viruses that infect humans, plants, and fungi are quite common, dsRNA viruses that infect bacteria, known as bacteriophages, are quite understudied, and only seven dsRNA phages have been sequenced so far.
A Single Amino Acid at Residue 188 of the Hexon Protein Is Responsible for the Pathogenicity of the Emerging Novel Virus Fowl Adenovirus 4
Authors: Zhang Yu , Liu Aijing , Wang Yanan , Cui Hongyu , Gao Yulong , Qi Xiaole , Liu Changjun , Zhang Yanping , Li Kai , Gao Li , Pan Qing , Wang Xiaomei
Published: June 2021

HHS associated with a novel FAdV-4 infection in chickens has caused huge economic losses to the poultry industry in China since 2015. The molecular basis for the increased virulence remains largely unknown.
SARS-CoV-2 NSP12 Protein Is Not an Interferon-β Antagonist
Authors: Li Aixin , Zhao Kaitao , Zhang Bei , Hua Rong , Fang Yujie , Jiang Wuhui , Zhang Jing , Hui Lixia , Zheng Yingcheng , Li Yan , Zhu Chengliang , Wang Pei-Hui , Peng Ke , Xia Yuchen
Published: June 2021

Previous studies investigated the interaction between SARS-CoV-2 viral proteins and interferon signaling and proposed that several SARS-CoV-2 viral proteins, including NSP12, could suppress IFN-β activation. However, most of these results were generated from IFN-β promoter luciferase reporter assay and have not been validated functionally.
Novel Disk Diffusion Assay on Magnesium Oxalate Agar To Evaluate the Susceptibility of Yersinia pestis to Type III Secretion System Inhibitors
Authors: Prashar Sukriti , Portales Guemes Miguel , Shivbaran Poorandai , Jimenez Alvarez Eugenia , Soha Christopher , Nacer Samir , McDonough Michael , Plano Gregory V. , Torruellas Garcia Julie
Published: June 2021

Disk diffusion assays have traditionally been used as a simple and effective way to screen compounds for antibacterial activity and to determine the susceptibility of pathogens to antibiotics; however, they are limited to detecting growth inhibition only. Consequently, antimicrobial agents that inhibit virulence factors, but not growth, would not be detected.
Presence of the Hmq System and Production of 4-Hydroxy-3-Methyl-2-Alkylquinolines Are Heterogeneously Distributed between Burkholderia cepacia Complex Species and More Prevalent among Environmental than Clinical Isolates
Authors: Coulon Pauline M. L. , Zlosnik James E. A. , Déziel Eric
Published: June 2021

Environmental bacteria belonging to the various closely related species forming the
Burkholderia cepacia
complex (Bcc) can infect plants and animals, including humans. Their pathogenicity is regulated by intercellular communication, or quorum sensing, allowing them to collaborate instead of acting individually.
Association of biological antirheumatic therapy with risk for type 2 diabetes: a retrospective cohort study in incident rheumatoid arthritis
Authors: Paul Sanjoy K , Montvida Olga , Best Jennie H , Gale Sara , Pethö-Schramm Attila , Sarsour Khaled
Published: June 2021

Objective

To explore possible associations of treatment with biological disease-modifying antirheumatic drugs (bDMARDs), including T-cell-based and interleukin-6 inhibition (IL-6i)-based therapies, and the risk for type 2 diabetes mellitus (T2DM) in patients with rheumatoid arthritis (RA).

Study design, setting and participants

Five treatment groups were selected from a United States Electronic Medical Records database of 283 756 patients with RA (mean follow-up, 5 years): never received bDMARD (No bDMARD, n=125 337), tumour necrosis factor inhibitors (TNFi, n=34 873), IL-6i (n=1884), T-cell inhibitors (n=5935) and IL-6i+T cell inhibitor abatacept (n=1213). Probability and risk for T2DM were estimated with adjustment for relevant confounders.

Results

In the cohort of 169 242 patients with a mean 4.5 years of follow-up and a mean 641 200 person years of follow-up, the adjusted probability of developing T2DM was significantly lower in the IL-6i (probability, 1%; 95% CI 0.6 to 2.0), T-cell inhibitor (probability, 3%; 95% CI 2.3 to 3.3) and IL-6i+T cell inhibitor (probability, 2%; 95% CI 0.1 to 2.9) groups than in the No bDMARD (probability, 5%; 95% CI 4.6 to 4.9) and TNFi (probability, 4%; 95% CI 3.7 to 4.7) groups. Compared with No bDMARD, the IL-6i and IL-6i+T cell inhibitor groups had 37% (95% CI of HR 0.42 to 0.96) and 34% (95% CI of HR 0.46 to 0.93) significantly lower risk for T2DM, respectively; there was no significant difference in risk in the TNFi (HR 0.99; 95% CI 0.93 to 1.06) and T-cell inhibitor (HR 0.96; 95% CI 0.82 to 1.12) groups.

Conclusions

Treatment with IL-6i, with or without T-cell inhibitors, was associated with reduced risk for T2DM compared with TNFi or No bDMARDs; a less pronounced association was observed for the T-cell inhibitor abatacept.
Realising the full potential of data-enabled trials in the UK: a call for action
Authors: Sydes Matthew R , Barbachano Yolanda , Bowman Louise , Denwood Tom , Farmer Andrew , Garfield-Birkbeck Steph , Gibson Martin , Gulliford Martin C , Harrison David A , Hewitt Catherine , Logue Jennifer , Navaie Will , Norrie John , O'Kane Martin , Quint Jennifer K , Rycroft-Malone Jo , Sheffield Jonathan , Smeeth Liam , Sullivan Frank , Tizzard Juliet , Walker Paula , Wilding John , Williamson Paula R , Landray Martin , Morris Andrew , Walker Rhoswyn R , Williams Hywel C , Valentine Janet
Published: June 2021

Rationale

Clinical trials are the gold standard for testing interventions. COVID-19 has further raised their public profile and emphasised the need to deliver better, faster, more efficient trials for patient benefit. Considerable overlap exists between data required for trials and data already collected routinely in electronic healthcare records (EHRs). Opportunities exist to use these in innovative ways to decrease duplication of effort and speed trial recruitment, conduct and follow-up.

Approach

The National Institute of Health Research (NIHR), Health Data Research UK and Clinical Practice Research Datalink co-organised a national workshop to accelerate the agenda for ‘data-enabled clinical trials’. Showcasing successful examples and imagining future possibilities, the plenary talks, panel discussions, group discussions and case studies covered: design/feasibility; recruitment; conduct/follow-up; collecting benefits/harms; and analysis/interpretation.

Reflection

Some notable studies have successfully accessed and used EHR to identify potential recruits, support randomised trials, deliver interventions and supplement/replace trial-specific follow-up. Some outcome measures are already reliably collected; others, like safety, need detailed work to meet regulatory reporting requirements. There is a clear need for system interoperability and a ‘route map’ to identify and access the necessary datasets. Researchers running regulatory-facing trials must carefully consider how data quality and integrity would be assessed. An experience-sharing forum could stimulate wider adoption of EHR-based methods in trial design and execution.

Discussion

EHR offer opportunities to better plan clinical trials, assess patients and capture data more efficiently, reducing research waste and increasing focus on each trial’s specific challenges. The short-term emphasis should be on facilitating patient recruitment and for postmarketing authorisation trials where research-relevant outcome measures are readily collectable. Sharing of case studies is encouraged. The workshop directly informed NIHR’s funding call for ambitious data-enabled trials at scale. There is the opportunity for the UK to build upon existing data science capabilities to identify, recruit and monitor patients in trials at scale.
Pharmacogenetics to Avoid Loss of Hearing (PALOH) trial: a protocol for a prospective observational implementation trial
Authors: McDermott John Henry , Mahood Rachel , Stoddard Duncan , Mahaveer Ajit , Turner Mark A , Corry Rachel , Garlick Julia , Miele Gino , Ainsworth Shaun , Kemp Laura , Bruce Iain , Body Richard , Ulph Fiona , Macleod Rhona , Harvey Karen , Booth Nicola , Roberts Peter , Wilson Paul , Newman William G
Published: June 2021

Introduction

In conjunction with a beta-lactam, aminoglycosides are the first-choice antibiotic for empirical treatment of sepsis in the neonatal period. The m.1555A>G variant predisposes to ototoxicity after aminoglycoside administration and has a prevalence of 1 in 500. Current genetic testing can take over 24 hours, an unacceptable delay in the acute setting. This prospective-observational trial will implement a rapid point of care test (POCT), facilitating tailored antibiotic prescribing to avoid hearing loss.

Methods and analysis

The genedrive POCT can detect the m.1555A>G variant in 26 min from buccal swab. This system will be integrated into the clinical pathways at two large UK neonatal centres over a minimum 6-month period. The primary outcome is the number of neonates successfully tested for the variant out of all babies prescribed antibiotics. As a secondary outcome, clinical timings will be compared with data collected prior to implementation, measuring the impact on routine practice.

Ethics and dissemination

Approval for the trial was granted by the Research Ethics Committee (REC) and Human Research Authority in August 2019. Results will be published in full on completion of the study.

Trial registration number

ISRCTN13704894.

Protocol version

V 1.3.
Socioeconomic mechanisms of myopia boom in China: a nationwide cross-sectional study
Authors: Ma Yingyan , Lin Senlin , Li Liping , Jia Yingnan , Zou Haidong
Published: June 2021

Objectives

To assess the association between socioeconomic development and the myopia boom in China.

Design

Nationwide cross-sectional study.

Setting

We used data from the China Family Panel Study (CFPS 2010), and the Chinese National Survey on Students’ Constitution and Health (CNSSCH 2010).

Participants

Participants included 33 600 individuals and 14 226 families from the CFPS 2010, and 86 199 students aged 7–12 years from the CNSSCH 2010.

Measures

The main measure was students’ visual impairment (defined as Snellen visual acuity ≤20/25 (0.8) in the worse eye) rate of each province (or municipality or autonomous region); other measures included the Gini coefficient of property, logarithm of average property, Gini coefficient of education, average education duration and return-to-education rate of each province (or municipality or autonomous region). The visual impairment rate was calculated using students’ data, aged 7–12 years, from the CNSSCH 2010. The Gini coefficient of property and logarithm of average property were calculated using the families’ data from the CFPS 2010; the Gini coefficient of education, average education duration and return-to-education rate were calculated using individuals’ data aged 18–44 years from the CFPS 2010.

Results

The urban environment (coefficient: 0.209; p<0.001), Gini coefficient of property (coefficient: 1.979; p=0.005), logarithm of average property (coefficient: 0.114; p<0.001), average education duration (coefficient: 0.041; p<0.001) and return-to-education rate (coefficient: 0.195; p<0.001) were positively associated with the logit function of visual impairment rate.

Conclusions

Economic development may promote an increased desire to pursue wealth. Regarding high return to education and a fairly competitive education system, individuals are likely to pursue wealth through education, which is associated with a heavier education burden and higher prevalence rates of myopia.
Use of infographics as a health-related knowledge translation tool: protocol for a scoping review
Authors: Mc Sween-Cadieux Esther , Chabot Catherine , Fillol Amandine , Saha Trisha , Dagenais Christian
Published: June 2021

Introduction

Efforts to bridge the know–do gap have paved the way for development of the field of knowledge translation (KT). KT aims to understand how evidence use can best be promoted and supported through different activities. For dissemination activities, infographics are gaining in popularity as a promising KT tool to reach multiple health research users (eg, health practitioners, patients and families, decision-makers). However, to our knowledge, no study has yet mapped the available evidence on this tool using a systematic method. This scoping review will explore the depth and breadth of evidence on infographics use and its effectiveness in improving research uptake (eg, raising awareness, influencing attitudes, increasing knowledge, informing practice and changing behaviour).

Methods and analysis

We will use the scoping review methodological framework first proposed by Arksey and O’Malley (2005), improved by Levacet al, and further refined by the Joanna Briggs Institute (2020). The search will be conducted in MEDLINE, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, Social Science Abstracts, Library and Information Science Abstracts, Education Resources Information Center, Cairn and Google Scholar. We will also search for relevant literature from the reference lists of the included publications. Two independent reviewers will select the studies. All study designs will be eligible for inclusion, with no date or publication status restrictions. The included studies will have evaluated infographics that disseminate health research evidence and target a non-scientific audience. A data extraction form will be developed and used to extract and chart the data, which will then be synthesised to present a descriptive summary of the results.

Ethics and dissemination

Ethics approval is not required. To inform the research and KT communities, various dissemination activities will be developed, including user-friendly KT tools (eg, webinars, fact sheets and infographics), open-access publication and presentations at KT events and conferences.
Determinants of acceptance of patients with heart failure and their informal caregivers regarding an interactive decision-making system: a qualitative study
Authors: Zippel-Schultz Bettina , Palant Alexander , Eurlings Casper , F Ski Chantal , Hill Loreena , Thompson David R , Fitzsimons Donna , Dixon Lana J , Brandts Julia , Schuett Katharina Andrea , de Maesschalck Lieven , Barrett Matthew , Furtado da Luz Ermelinda , Hoedemakers Thom , Helms Thomas Maria , Brunner-La Rocca Hans-Peter
Published: June 2021

Objective

Heart failure is a growing challenge to healthcare systems worldwide. Technological solutions have the potential to improve the health of patients and help to reduce costs. Acceptability is a prerequisite for the use and a successful implementation of new disruptive technologies. This qualitative study aimed to explore determinants that influence the acceptance of patients and their informal caregivers regarding a patient-oriented digital decision-making solution—a doctor-at-home system.

Design

We applied a semistructured design using an interview guide that was based on a theoretical framework influenced by established acceptance theories. The interviews were analysed using a content analysis.

Setting

A multicentred study in four European countries.

Participants

We interviewed 49 patients and 33 of their informal caregivers. Most of the patients were male (76%) and aged between 60 and 69 years (43%). Informal caregivers were mostly female (85%). The majority of patients (55%) suffered from heart failure with mild symptoms.

Results

Four main categories emerged from the data: needs and expectations, preferences regarding the care process, perceived risk and trust. Participants expressed clear wishes and expectations regarding a doctor-at-home, especially the need for reassurance and support in the management of heart failure. They were receptive to changes to the current healthcare processes. However, trust was identified as an important basis for acceptance and use. Finally, perceived risk for decision-making errors is a crucial topic in need of attention.

Conclusion

Patients and informal caregivers see clear benefits of digitalisation in healthcare. They perceive that an interactive decision-making system for patients could empower and enable effective self-care. Our results provide important insights for development processes of patient-centred decision-making systems by identifying facilitators and barriers for acceptance. Further research is needed, especially regarding the influence and mitigation of patients and informal caregivers’ perceived risks.
Outcomes and outcome measures reported in clinical studies of therapeutic mammaplasty: a systematic review protocol
Authors: Lee Alice , Kwasnicki Richard M , Leff Daniel R
Published: June 2021

Introduction

Therapeutic mammaplasty (TM) is an oncological procedure which combines tumour resection with breast reduction and mastopexy techniques. Previous systematic reviews have demonstrated oncological safety of TM, but poor and inconsistent reporting of quality-of-life, aesthetic and functional outcomes, often with non-validated measurement tools. Moreover, there is a paucity of patient-reported outcome measures. Standardisation of outcome reporting is required to enable study results to be compared and combined, for example, through core outcome set (COS) development. This systematic review aims to comprehensively describe the outcomes reported in clinical studies of TM, their respective outcome measures and the time points at which they were evaluated. The overall objective is to facilitate the development of a COS for TM.

Methods and analysis

A systematic review of clinical studies evaluating outcomes following TM will be completed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The following electronic databases have been searched from inception to 5 August 2020: Ovid MEDLINE, Embase, CINAHL and Web of Science. Primary outcomes will include the number of reported outcomes of various types (clinical, aesthetic, functional, quality-of-life and cost-effectiveness), whether these are patient-reported or clinician-reported, how outcomes are defined and the outcome measurement tool(s) used. The time point(s) at which outcomes were measured will be a secondary outcome. No studies will be excluded on the basis of methodological quality in order to generate a comprehensive list of reported outcomes and outcome measures; hence, risk of bias assessment is not required. The data will be described narratively. This protocol has been reported in line with PRISMA-Protocols.

Ethics and dissemination

This study does not involve human or animal participants, hence ethical approval is not required. The findings will be published in a peer-reviewed journal and presented at relevant conferences.

PROSPERO registration number

CRD42020200365.