bluuebunny/crossref_metadata_2025 huggingface dataset:
A new nomenclature for the livestock-associated Mycobacterium tuberculosis complex based on phylogenomics
Authors: Zwyer Michaela , Çavusoglu Cengiz , Ghielmetti Giovanni , Pacciarini Maria Lodovica , Scaltriti Erika , Van Soolingen Dick , Dötsch Anna , Reinhard Miriam , Gagneux Sebastien , Brites Daniela
Published: December 2021

Background: The bacteria that compose the Mycobacterium tuberculosis complex (MTBC) cause tuberculosis (TB) in humans and in different animals, including livestock. Much progress has been made in understanding the population structure of the human-adapted members of the MTBC by combining phylogenetics with genomics. Accompanying the discovery of new genetic diversity, a body of operational nomenclature has evolved to assist comparative and molecular epidemiological studies of human TB. By contrast, for the livestock-associated MTBC members, Mycobacterium bovis, M. caprae and M. orygis, there has been a lack of comprehensive nomenclature to accommodate new genetic diversity uncovered by emerging phylogenomic studies. We propose to fill this gap by putting forward a new nomenclature covering the main phylogenetic groups within M. bovis, M. caprae and M. orygis.

Methods: We gathered a total of 8,736 whole-genome sequences (WGS) from public sources and 39 newly sequenced strains, and selected a subset of 829 WGS, representative of the worldwide diversity of M. bovis, M. caprae and M. orygis. We used phylogenetics and genetic diversity patterns inferred from WGS to define groups.

Results: We propose to divide M. bovis, M. caprae and M. orygis in three main phylogenetic lineages, which we named La1, La2 and La3, respectively. Within La1, we identified several monophyletic groups, which we propose to classify into eight sublineages (La1.1-La1.8). These sublineages differed in geographic distribution, with some being geographically restricted and others globally widespread, suggesting different expansion abilities. To ease molecular characterization of these MTBC groups by the community, we provide phylogenetically informed, single nucleotide polymorphisms that can be used as barcodes for genotyping. These markers were implemented in KvarQ and TB-Profiler, which are platform-independent, open-source tools.

Conclusions: Our results contribute to an improved classification of the genetic diversity within the livestock-associated MTBC, which will benefit future molecular epidemiological and evolutionary studies.
“Salvación” y “tragedia” en torno al binomio naturaleza/cultura en el pensamiento de José Ortega y Gasset
Authors: De Haro Honrubia Alejandro , Trotta Francesco
Published: December 2021

Este artículo aborda la dialéctica naturaleza/cultura en el pensamiento de José Ortega y Gasset, a partir de su relación con las ideas de salvación y tragedia. Justificamos la elaboración de este trabajo en el hecho de que la temática que se aborda no se ha estudiado en profundidad realizando un recorrido por toda la obra del filósofo de la razón vital. Los resultados/conclusiones a que hemos llegado son los siguientes: en un primer momento, sobresale el primado de la cultura en el pensamiento de Ortega, quien hace de ésta algo salvífico y a la vez antagónico en relación con la naturaleza más instintiva e irracional del individuo como miembro de la humanidad. Para Ortega, el sometimiento de éste a las disposiciones incultas de su naturaleza –a su fondo más bárbaro, salvaje e irracional–, aparecería como una forma de tragedia o “mal radical” (en términos de Kant), todo lo contrario de lo que ocurrirá en su madurez intelectual, cuando Ortega interprete la parte más bárbara o salvaje del individuo en continuidad con la cultura de cuyos peligros o tragedia también nos advertirá.
Network economy or just a new breed of multinationals? relocation of eWork as a window to the restructuring of value chains
Authors: Jörg Flecker
Published: December 2021

The global information economy is subject to processes of profound restructuring based on new information and communication technologies. These processes follow different logics, with centralisation within international companies playing as significant a role as decentralisation or the development of networks. This paper makes use of findings from the EMERGENCE and Asian EMERGENCE case study research into telemediated work and relocation of work to shed light on the restructuring of global companies, the dynamics of boundaries between corporations and the emerging new international division of labour in the information economy.
Navigating the seamless environment in the global supply chain: implications for Canadian regions and workers
Authors: Penny Gurstein
Published: December 2021

When work is ‘boundless’ and ‘seamless’ where and how do workers' lives intersect with the space-time continuum of place-based communities? Who and what are they accountable to? Telemediation is fragmenting work across increasingly complex, transnational networks. Workers in these networks must negotiate through a multitude of temporal, contractual and trans-cultural milieus. This paper traces the trajectory of the work experience using case studies of telemediated work relationships in various points in the global supply chain and analyses the implications of telemediated spaces for the quality of workers' lives. Drawing on an analysis of case studies conducted by the EMERGENCE Canada project, this paper argues that telemediated work represents a shift in the scale at which many aspects of daily life unfold, and that some of the assumptions upon which workers’ lives are governed must be reconsidered.
Productive restructuring and labour: the auto industry in Brazil
Authors: Marcia Leite
Published: December 2021

In the early 1980's, Brazilian industry underwent a crisis of the previous accumulation model, ushering in a period in which the country lost international competitiveness. This paper traces the changes that have taken place since then, including the further changes that have taken place since 2003. It concludes that the last four years have not differed much from the earlier pattern, even though several new industrial policies have been introduced with the aim of spurring technological innovation. The paper investigates the reasons for this, seeking to underline the limits and the potentialities of such policies, given the general global context. In order to do so, it analyses managerial strategies and innovative processes in the Brazilian manufacturing sector as a whole, with a special focus on the automotive sector, and discusses the implications of this restructuring for labour.
The nexus of informatisation and internationalisation: a new stage in the internationalisation of labour
Authors: Andreas Boes  , Tobias Kämpf
Published: December 2021

For a long time, it was the mainstream view that the internationalisation of labour is limited primarily to industrial manufacturing. However there are now signs that service employmrnt, or more precisely, information work, has also become a focus of globalisation. As a result, a new phase of informatisation has arisen, characterised by the rise of the internet as a new global space of action and new opportunities for an international division of labour For almost any activity comprising work with digitised information, global information networks have created a new, globally accessible space of production. By this means, geographical distances can be bridged in real time in many labour processes. The dynamics of this development are illustrated in this paper by the IT Industry and the rise of India to a new strategic position as a site for IT development, drawing on interviews carried out in India and Germany by the ‘Export IT’ project (www.export-it.de).
Hopf index and the helicity of elliptically polarized twisted light
Authors: Koksal K. , Babiker M. , Lembessis V. E. , Yuan J.
Published: December 2021

Here, we describe a systematic derivation of the general form of the optical helicity density of ellipticaly polarized paraxial Laguerre–Gaussian modes

L
G

ℓ
,
p
,
σ

. The treatment incorporates the contributions of the longitudinal field components for both the paraxial electric

E

and magnetic

B

fields, which satisfy Maxwell’s self-consistency condition in the sense that

E

is derivable from

B

and vice versa. Contributions to the helicity density to leading order in

(

k
2

w
0
2

)

−
1

(where

k

is the axial wavenumber and

w
0

the beam waist) include terms proportional to optical spin

σ

and topological charge

ℓ

, as well as a spin-orbit

σ

|

ℓ

|

term. However, evaluations of the space integrals leading to the total helicity confirm that the space integral of the

ℓ

-dependent term in the density (which is due entirely to the longitudinal fields) vanishes identically for all

ℓ

and

p

, so that, in general, only

σ

determines the Hopf index, with the optical vortex

L
G

ℓ
p

character featuring only in the action constant.
Detection of aging in the common explosive RDX using terahertz time-domain spectroscopy
Authors: Yan Zhijin , Shi Wei
Published: December 2021

A method to detect the aging in cyclotrimethylene-trinitramine (RDX), using terahertz (THz) waves, is reported in this paper. The absorption spectra of RDX are analyzed, and any changes of the characteristic absorption peaks (before and after aged treatment of RDX in laboratory) are compared. When RDX samples undergo aging, the characteristic absorption peaks (at 1.02 THz, 1.36 THz, 1.58 THz, and 2.37 THz) disappear, which corresponds to the fracture of N-

N
O

2

bonds in RDX molecules. These results show that THz time-domain spectroscopy technology may be used not only for analysis but also for detection of aging in RDX and similar materials.
WDM-PON Management and Control by Auxiliary Management and Control Channel for 5G Mobile Fronthaul
Authors: Honda Kazuaki , Hara Kazutaka , Nakamura Hirotaka , Sone Kyosuke , Nakagawa Goji , Hirose Yoshio , Hoshida Takeshi , Terada Jun
Published: December 2021

The demand for fifth generation (5G) mobile systems has been exploding. There are strict latency and transmission capacity requirements, especially in the optical fiber section called the mobile fronthaul. A wavelength division multiplexing passive optical network (WDM-PON) system is an attractive solution to accommodate the high demand of traffic. However, wavelength management, which is important in a WDM-PON system, has not been sufficiently studied at the system level. In previous studies, control by a management control channel independent of the client signal, called the auxiliary management and control channel (AMCC), has been considered in many cases. In most of these studies, physical layer evaluation, such as the effect of superimposing the management control channel, was conducted for feasibility studies, and it was only confirmed that the effect was minor by measuring the bit error rate. In this paper, we review and compare the superimposition schemes of the AMCC to clarify operating conditions such as modulation format and modulation index of the AMCC signals. In addition, we propose a WDM-PON system managed using AMCC for ONU activation, wavelength adjustment and alive monitoring. We then discuss the connection of a WDM-PON prototype system we developed to a 5G mobile system to evaluate the effect of throughput on user equipment. The results indicate that the WDM-PON prototype system did not degrade (less than 2%) the downlink throughput even when the wavelength adjustment function was used against wavelength drift.
Two-point coupling method to independently control coupling efficiency at different wavelengths
Authors: Kim Dohyeong , Han Sangyoon , Kim Dae-Gon , Ko Kiyoung , Choi Duk-Yong , Lee Hansuek
Published: December 2021

To efficiently access light waves confined in a high-quality-factor (Q)
microcavity over a wide spectral range, it is necessary to
independently control coupling efficiency at different wavelengths.
Here we suggest an approach to add a degree of freedom to control the
coupling efficiency based on a two-point coupling geometry. By
changing the phase difference between two paths connecting two
coupling points, various combinations of coupling efficiencies at
multiple wavelengths can be achieved. An analytic model describing the
coupling property is derived and confirmed by experimental results. It
is also shown that the coupling property can be modified by adjusting
the effective refractive index difference between a waveguide and a
resonator.
Electronically controlled flexible terahertz metasurface based on the loss modulation of strontium titanate
Authors: Wang Guanchao , Tian Hao , Wang Jing , Li Shuai , Guo Wenpeng , Zhou Zhongxiang
Published: December 2021

A flexible terahertz metamaterial is designed to control the transmittance through an external electric field. Two different metallic structures, the split ring (type I structure) and the split ring inside a ring (type II structure), were prepared and voltage was applied through a forked finger electrode. The structures were wrapped in a thin film made by mixing strontium titanate nanopowder with polyimide in a certain ratio. Under normal incidence, the transmittance is controlled by applying a voltage to adjust the imaginary part of the permittivity of strontium titanate. The modulation depth of the type I structure at 1.08 THz is 40.1%, and that of the type II structure at 1.16 THz is 44.7%. The working bandwidths of the two structures are 0.07 THz and 0.42 THz, respectively, and are greatly broadened by combining with the ring. The proposed design enriches the modulation method of the transmission of metamaterials and broadens the application range of flexible terahertz metasurfaces.
Photoconductive terahertz generation in nitrogen-doped single-crystal diamond
Authors: Chizhov Pavel A. , Komlenok Maxim S. , Kononenko Vitali V. , Bukin Vladimir V. , Ushakov Alexander A. , Bulgakova Vladislava V. , Khomich Andrey A. , Bolshakov Andrey P. , Konov Vitaly I. , Garnov Sergey V.
Published: December 2021

The generation of terahertz radiation in a photoconductive emitter based on nitrogen-doped single-crystal diamond was realized for the first time. Under 400 nm femtosecond laser pumping, the performance of diamond antennas with different dopant levels was investigated and compared with a reference ZnSe antenna. Terahertz waveforms and corresponding spectra were measured. A low saturation level for high-nitrogen-containing diamond substrate was revealed. The results indicate the prospects of doped diamond as a material for high-efficiency large-aperture photoconductive antennas.
Phase optimization algorithm for 3D particle localization with large axial depth
Authors: Wang Famin , Li Hangfeng , Xiao Yun , Zhao Mengyuan , Zhang YunHai
Published: December 2021

We propose an optimization algorithm based on Fresnel approximation
(FA) imaging to optimize an extended-axial-depth point spread function
(PSF) for 3D particle localization. The transfer function efficiency
of the PSF is improved by repeatedly imposing constraints in the
object plane, the spatial domain, and the Fourier domain. During the
iterative calculation, the effective photon number or Cramer–Rao lower
bound is used as the termination condition of the iteration. The
algorithm allows flexible adjustment of the peak intensity ratio of
the two main lobes. Moreover, the transfer function efficiency can be
balanced by increasing the weight of the modulation function of the
expected PSF at each axial position. The twin-Airy (TA) PSF optimized
by the FA optimization algorithm does not require complex
post-processing, whereas post-processing is an essential step for the
unoptimized TA-PSF. The optimization algorithm is significant for
extended-axial-depth PSFs used for 3D particle localization, as it
improves localization precision and temporal resolution.
Active beam manipulation and convolution operation in VO2-integrated coding terahertz metasurfaces
Authors: Li ZengLin , Wang Wei , Deng Shaoxuan , Qu Jia , Li Yuxiang , Lv Bo , Li Wenjia , Gao Xi , Zhu Zheng , Guan Chunying , Shi Jinhui
Published: December 2021

Coding metasurfaces have received tremendous interest due to their unprecedented control of beams through the flexible design of coding sequences. However, realizing tunable coding metasurfaces with scattering-pattern shifts in the terahertz range is still challenging. Here, we propose a VO2-integrated coding metasurface to realize a thermally controlled scattering-pattern shift by convolution operation. The required phase profiles and high amplitudes of 1-bit and 2-bit coding metasurfaces are easily obtained only by changing the length of the VO2 cut-wires. The insulator–metal phase transition of the VO2 cut-wires leads to an ultrafast switching effect between multiple deflected scattering beams and one normally reflected beam. In particular, the VO2 phase transition contributes to dynamical convolution operations of the 2-bit coding metasurface. The proposed VO2-integrated coding metasurfaces are important for realizing tunable terahertz beam manipulation as well as arbitrary required scattering beams.
Physical properties of rhodium retrieved from modeling its dielectric function by a simulated annealing approach
Authors: Abarca-Quesada Denis A. , Vargas-Quirós Carlos E. , Vargas-Castro William E.
Published: December 2021

Optical, charge carriers transport, quantum mechanics, magnetic, thermal, and plasmonic properties of the transition metal rhodium are considered. An extended Drude-Lorentz (DL) model is applied to describe the dielectric function (DF) of rhodium in a spectral range going from the mid-infrared (12.4 μm) to the vacuum ultraviolet (32 nm). The Drude term of the DF includes, as optimization parameters, the inverse of the high frequency dielectric constant, the volume plasma frequency and scattering frequency of the electrons, the scattering frequency of holes relative to that of electrons, the ratio between the effective masses of electrons and holes, the number of holes per atom relative to that of electrons, and the renormalized times between grain boundary scattering events for electrons and holes. The Lorentz contribution to the DF includes the number of conduction electrons per atom, the oscillator strengths, the resonance energies, and the Lorentzian widths. Values of the parameters involved in the DF are optimized by an acceptance-probability-controlled simulated annealing method that minimizes spectral differences between the real and imaginary parts of the DF values obtained from the literature and those evaluated from the DL parametric formulation, accounting for the presence of electrons and holes as charge carriers. Once an optimized spectral description of the DF of rhodium is obtained, a large set of charge-transport, magnetic, thermal, plasmonic, and quantum mechanics derived quantities are evaluated: mobilities, relaxation times, Fermi velocities, effective masses, electrical and thermal conductivities, heat capacity coefficients, Hall coefficient, diamagnetic and paramagnetic susceptibilities, effective number of Bohr magnetons, Fermi energies and corresponding densities of states, energy loss functions, effective number of charge carriers participating in conduction, and effective number of electrons involved in inter-band transitions.
Identification of individual root-knot nematodes using low coverage long-read sequencing
Authors: Sellers Graham S. , Jeffares Daniel C. , Lawson Bex , Prior Tom , Lunt David H.
Published: December 2021

Root-knot nematodes (RKN; genus Meloidogyne) are polyphagous plant pathogens of great economic importance to agriculturalists globally. These species are small, diverse, and can be challenging for accurate taxonomic identification. Many of the most important crop pests confound analysis with simple genetic marker loci as they are polyploids of likely hybrid origin. Here we take a low-coverage, long-read genome sequencing approach to characterisation of individual root-knot nematodes. We demonstrate library preparation for Oxford Nanopore Technologies Flongle sequencing of low input DNA from individual juveniles and immature females, multiplexing up to twelve samples per flow cell. Taxonomic identification with Kraken 2 (a k-mer-based taxonomic assignment tool) is shown to reliably identify individual nematodes to species level, even within the very closely related Meloidogyne incognita group. Our approach forms a robust, low-cost, and scalable method for accurate RKN species diagnostics.
The reliability of the angle of deviation measurement from the Photo-Hirschberg tests and Krimsky tests
Authors: Tengtrisorn S. , Tungsattayathitthan A. , Na Phatthalung S. , Singha P. , Rattanalert N. , Bhurachokviwat S. , Chouyjan S.
Published: December 2021

Objective

To compare the angle of deviation measured from Photo-Hirschberg testing and Krimsky testing, with that from an alternate prism cover test (APCT) in strabismus patients.

Methods

A cross-sectional study was conducted in Songklanagarind Hospital, Thailand. Thirty-three strabismus patients were photographed for analysis by Photo-Hirschberg testing using computer software. The corneal light reflex displacement, converted into prism diopter (PD), was compared to the angle of deviation measured with APCT. Twenty-eight strabismus patients were tested with the Krimsky test. Data were analyzed using Pearson correlation and paired t-tests. The study excluded 4 intermittent exotropia cases, 1 intermittent esotropia case and 2 which cases missing data for krimsky test.

Results

The mean±SD of the deviation angle, measured by APCT with a fixation target at 30 cm and 6 m; were 48.09±16.34PD and 47.82±15.73 PD, respectively. At 1 m, the difference in the angle of deviation measured from APCT and the Photo-Hirschberg test within 10 PD were 58.8% and 63.6%, for ET and XT, respectively. The difference in the angle of deviation measured from APCT and Krimsky tests within 10 PD in ET and XT were 86.7% and 80.0%, respectively. At 4 m, the difference in angle of deviation measured from APCT and Photo-Hirschberg tests within 10 PD in ET and XT were 58.8% and 54.5%, respectively; whereas, the difference in the angle of deviation measured from APCT and Krimsky tests within 10 PD in ET and XT were 80.0% and 70.0%, respectively.

Conclusion

The reliability of Krimsky test was better than Photo-Hirschberg test for measuring an angle of deviation.
Factors associated with early receipt of COVID-19 vaccination and adherence to second dose in the Veterans Affairs healthcare system
Authors: Ioannou George N. , Green Pamela , Locke Emily R. , Berry Kristin
Published: December 2021

Background

We aimed to determine factors independently associated with early COVID-19 vaccination and adherence to two-dose regimens.

Methods

Among persons receiving care in the Veterans Affairs (VA) healthcare system (n = 5,766,638), we identified those who received at least one dose of COVID-19 vaccination through the VA, during the first ~3months following emergency use authorization, from December 11, 2020 to March 9, 2021 (n = 1,569,099, or 27.2%, including 880,200 (56.1%) Moderna, 676,279 (43.1%) Pfizer-BioNTech and 12,620 (0.8%) Janssen vaccines).

Results

Follow-up for receipt of vaccination began on December 11, 2020. After adjustment for baseline characteristics ascertained as of December 11, 2020, factors significantly associated with vaccination included older age, higher comorbidity burden, higher body mass index category, Black (vs. White) race (adjusted hazard ratio [AHR] 1.19, 95% CI 1.19–1.20), Hispanic (vs. non-Hispanic) ethnicity (AHR 1.12, 95% CI 1.11–1.13), urban (vs. rural) residence (AHR 1.31, 95% CI 1.31–1.31), and geographical region, while AI/AN race (vs. White), was associated with lower vaccination rate (AHR 0.85, 95% CI 0.84–0.87). Among persons who received both doses of Moderna or Pfizer-BioNTech vaccines, 95.3% received the second dose within ±4 days of the recommended date. Among persons who received the first vaccine dose, only 3.2% did not receive the second dose within 42 days for Pfizer versus 4.0% for Moderna (p<0.001). Factors independently associated with higher likelihood of missing the second dose included younger age (10.83% in 18–50 yo vs. 2.72% in 70–75 yo), AI/AN race, female sex, rural location, geographical region and prior positive test for SARS-CoV-2.

Conclusions

We identified sociodemographic and clinical factors that may be used to target vaccination efforts and to further improve adherence to second vaccine dosing.
Differential retention contributes to racial/ethnic disparity in U.S. academia
Authors: Shaw Allison K. , Accolla Chiara , Chacón Jeremy M. , Mueller Taryn L. , Vaugeois Maxime , Yang Ya , Sekar Nitin , Stanton Daniel E.
Published: December 2021

Several racial and ethnic identities are widely understood to be under-represented within academia, however, actual quantification of this under-representation is surprisingly limited. Challenges include data availability, demographic inertia and identifying comparison points. We use de-aggregated data from the U.S. National Science Foundation to construct a null model of ethnic and racial representation in one of the world’s largest academic communities. Making comparisons between our model and actual representation in academia allows us to measure the effects of retention (while controlling for recruitment) at different academic stages. We find that, regardless of recruitment, failed retention contributes to mis-representation across academia and that the stages responsible for the largest disparities differ by race and ethnicity: for Black and Hispanic scholars this occurs at the transition from graduate student to postdoctoral researcher whereas for Native American/Alaskan Native and Native Hawaiian/Pacific Islander scholars this occurs at transitions to and within faculty stages. Even for Asian and Asian-Americans, often perceived as well represented, circumstances are complex and depend on choice of baseline. Our findings demonstrate that while recruitment continues to be important, retention is also a pervasive barrier to proportional representation. Therefore, strategies to reduce mis-representation in academia must address retention. Although our model does not directly suggest specific strategies, our framework could be used to project how representation in academia might change in the long-term under different scenarios.
cine 'CliFi' o la rentabilidad de salvar el planeta
Authors: Vicente Torrico David
Published: December 2021

La sociedad del siglo XXI se enfrenta a la emergencia climática, un fenómeno científico que se ha incorporado con fuerza a las esferas política, mediática y social. Su inclusión entre los Objetivos de Desarrollo de la ONU, el incremento de la cobertura informativa y la reciente movilización de la ciudadanía han actuado como catalizadores de un relato marcado tradicionalmente por más sombras que luces. En nuestra investigación proponemos un estudio de agenda en torno a la incorporación del contenido ‘Cli-Fi’ (ficción climática) a las carteleras españolas entre los años 2000 y 2019. A partir de la ficha técnica que presentan los 92 títulos que componen la muestra, ofrecemos un estudio de las variables que delimitan los contextos de producción, distribución y exhibición, con el objetivo de detectar una posible tematización, la consolidación de grupos de trabajo o su rentabilidad en términos económicos y su éxito en certámenes internacionales. Los resultados revelan la madurez alcanzada por la ficción climática en la industria del cine, con una producción estabilizada, reconocida y rentable, pese a la atomización de los equipos responsables de los proyectos analizados.
Prevalence of Acute coronary syndrome (ACS) in COVID-19 affected patients in public hospital facility of Pakistan, a retrospective study
Authors: Ain Noor-Ul , Saeed Talha Bin , Sajjad Saleeha , Ashraf Usama , Mustafa Auj , Naeem Muhammad Zaeem , Faizan Javed Hafiz Muhammad
Published: December 2021

COVID 19 infection is a devastating viral disease-causing multiorgan damage and severity of the complications. Several studies have reported the major effect of COVID 19 on the respiratory, cardiac system as well as on other organs. There has been an increased prevalence of the COVID-19 infection observed in patients with the acute coronary syndrome (ACS) because of many unknown reasons.
P002 Psychiatric Comorbidity and Suicide in Childhood Onset Immune-Mediated Diseases —A Systematic Review and Meta-Analysis
Authors: Jansson Sabine , Malham Mikkel , Wewer Vibeke , Rask Charlotte
Published: December 2021

BACKGROUND:

The course of paediatric onset immune mediated inflammatory diseases (IMID) is both physically and mentally challenging. Emotional distress with anxiety and depressive symptoms is commonly reported, however, data on diagnosed comorbid psychiatric disorders is scarce. The aim of this study was to provide a literature overview of psychiatric comorbidity, suicide rates, and their potential risk factors, in childhood onset IMID.

METHODS:

This was a systematic review following the PRISMA guidelines. The protocol was registered at Prospero (ID: CRD42021233890). A literature search was made in the databases Pubmed, PsychINFO, and Embase. We included the following IMID: paediatric onset inflammatory bowel disease (pIBD), rheumatic diseases (RD) and autoimmune liver diseases. Studies that provided prevalence rates of diagnosed psychiatric disorders and/or suicide, were included. Pooled prevalence rates of psychiatric disorders (grouped according to ICD-10 criteria) reported by three or more studies, within the same IMID, were calculated using random-effects meta-analysis. Two authors independently evaluated risk of bias using the New-Castle Ottawa scale.

RESULTS:

Twenty-three studies met the inclusion criteria; 13 describing psychiatric disorders in pIBD and 10 in RD. No study reported on psychiatric disorders in autoimmune liver diseases. Compared to controls without somatic disease, IMID patients had an increased risk of psychiatric disorders, with anxiety and mood disorders being the most common. Prevalence rates for anxiety and mood disorders in pIBD were 6% (95% confidence interval (CI): 4%-9%) and 4% (95%CI: 2%-8%), respectively, in register-based studies, and 33% (95%CI: 25%-41%) and 18% (95%CI:12%-26%), respectively, in studies using psychiatric assessment. In RD pooled estimates were 13% (95%CI: 12%-15%) for anxiety disorders and 20% (95%CI: 15%-26%) for mood disorders. Based on single studies, risk of suicide was increased in pIBD, but not in juvenile idiopathic arthritis, the most common RD.

CONCLUSION:

In this systematic review, patients with childhood onset IMID had increased prevalence of psychiatric disorders compared to controls. However, only pooled estimates on emotional disorders were possible and studies investigating broad spectrum of psychiatric disorders are needed.
P005 Influence of Immunosuppressive Therapy in Patients With Inflammatory Bowel Diseases on the Level of Immunoglobulins G After a Coronavirus Infection
Authors: Knyazev Oleg , Kagramanova Anna , Lishchinskaya Albina , Chernova Marina , Demchenko Alexandra , Babayan Anait , Parfenov Asfold
Published: December 2021

BACKGROUND:

Currently, there are differences in the results of international studies and treatment outcomes in patients with inflammatory bowel disease (IBD) and COVID-19. Further research is needed to help answer the questions: Do IBD patients have an increased risk of contracting SARS-CoV-2? Do IBD patients have more severe COVID-19 outcomes? Does IBD therapy increase the risk of infection? Do any IBD treatments protect against COVID-19?

OBJECTIVE:

To study the effect of immunosuppressors, genetically engineered biologics, and janus kinase blockers on the level of SARS-CoV-2 class G immunoglobulins in IBD patients who underwent COVID-19.

METHODS:

The level of SARS-CoV-2 class G immunoglobulins was analyzed in 66 patients with IBD after COVID-19 infection, 28 males (42.4%) and 38 women (57.6 %). The median age was 39±4.2 years. The duration of the anamnesis ranged from 1 to 8 years (Iu 4 years). The patients were divided into two groups, depending on the therapy performed: Group 1 (n = 31) received long-term (more than 1 year) immunosuppressants (azathioprine/6-mercaptopurine/tofacitinib), group 2 (n = 35) received anti-TNF-α therapy. The level of SARS-CoV-2 class G immunoglobulins was determined by the immunochemiluminescence method.

RESULTS:

After 4-6 weeks, a twice negative smear of PCR was taken from the nose and oropharynx for SARS-CoV-2 in patients (n=31) receiving anti-relapse therapy with systemic IBD (azathioprine/6-mercaptopurine) and selective (tofacitinib) immunosuppressants, and the average level of Ig G was 44.1 ± 9.8 U/l. Among patients with IBD receiving anti-TNF-α drugs (n = 35), the average level of class G immunoglobulins was 133.6 ± 14.4 U/l. The difference was statistically significant (p = 0.000003).

CONCLUSION:

The level of class G immunoglobulins 3-4 weeks after the COVID-19 infection was significantly higher in IBD patients who received anti-TNF-α drugs.
P010 Precision Dosing Tool Forecasts Trough Infliximab and Associates With Disease Status in Inflammatory Bowel Diseases
Authors: Dervieux Thierry , Primas Christian , Panetta John , Mould Diane , Eser Alexander , Reinisch Walter
Published: December 2021

BACKGROUND:

Substantial inter- and intra-individual variability of infliximab (IFX) pharmacokinetics (PK) necessitates tailored dosing approaches. Here, we evaluated the performances of a Model Informed Precision Dosing (MIPD) Tool in forecasting trough Infliximab (IFX) levels in association with disease status and circulating TNF-α in patients with Inflammatory Bowel Diseases (IBD).

METHODS:

Consented patients undergoing every 8-week maintenance therapy with IFX were enrolled. Midcycle specimens were collected, IFX, antibodies to IFX, albumin were determined and analyzed with weight using nonlinear mixed effect models coupled with Bayesian data assimilation to forecast trough levels. Accuracy of forecasted as compared to observed trough IFX levels were evaluated using Demings regression. Association between IFX levels, CRP-based clinical remission and TNF-α levels were analyzed using logistic regression and linear mixed effect models.

RESULTS:

In 41 patients receiving IFX (median dose = 5.3 mg/Kg), median IFX levels decreased from 13.0 to 3.9 µg/ml from mid to end of cycle time points, respectively. Midcycle IFX levels forecasted trough with Deming’s slope = 0.90 and R2 =0.87. Observed end cycle and forecasted trough levels above 5µg/mL associated with CRP-based clinical remission (OR = 7.2 CI95%: 1.7-30.2; OR = 21.0 CI95%: 3.4-127.9, respectively) (p < 0.01). Median TNF-α levels increased from 4.6 to 8.0 pg/ml from mid to end of cycle time points, respectively (p < 0.01). CRP and TNF-α levels associated independently and additively to decreased IFX levels (p < 0.01).

CONCLUSION:

These data establish the value of our MIPD tool in forecasting trough IFX levels in patients with IBD. Serum TNF-α and CRP are reflective of inflammatory burden which impacts exposure.
P012 Efficacy of Exclusive Enteral Nutrition and Weekly Adalimumab Combination in Crohn's Patients With Fibroinflammatory Stenosis
Authors: Tokmak Salih
Published: December 2021

BACKGROUND:

Clinical remission can be achieved with exclusive enteral nutrition (EEN) in patients with Crohn's Disease with different sites of involvement, varying severity, and complications such as abscess and fistula. In the CHARM study, weekly or every other week administration of adalimumab (ADA) did not provide a significant difference in remission rates. Nevertheless, the subgroup analysis showed that in patients with anti-TNF experience, moderate-to-severely active disease, and high CRP values, rates of remission were significantly higher with weekly doses. Our aim was to determine the efficacy of EEN and weekly adalimumab combination in Crohn's patients with fibroinflammatory stenosis.

METHODS:

Seven consecutive patients with newly diagnosed severe disease and fibro-inflammatory stenosis were included in this retrospective study. The PRO-2 score was used to assess clinical remission, the SES-CD score to determine the severity of endoscopic activity, the Nancy score to determine the severity of inflammation in tissue samples, and the MaRIA score to determine changes in magnetic resonance enterography (MRE). Nestle Modulen® (35kcal/kg) was used for twelve weeks as the EEN solution. In addition to the formulation, patients were only allowed to consume water. At the end of the 12th week, the patients gradually switched to a standard diet. Concomitantly initiated ADA was continued at 40 mg weekly after standard loading doses of 160 mg-80 mg-40 mg. The patients were evaluated with clinical and laboratory findings at the 1st, 4th and 8th weeks of the treatment, and also with colonoscopy and MRE at the 12th week.

RESULTS:

The difference between mean PRO-2 score (24.7 ± 1.97, 20.1 ± 1.63, 15.3 ± 1.81,11.4 ± 2.15, 5 ± 1.1, p = 0.031), CRP (14.3 ± 4.54, 11.2 ± 3.31, 6.92 ± 2.88, 2.16 ± 1.14, 0.25 ± 0.13, p = 0.022), albumin (2.9 ± 0.21, 3.05 ± 0.33, 3.4 ± 0.29, 4.1 ± 0.45, 4.6 ± 0.27, p = 0.044), hemoglobin (11.38 ± 0.97, 12.65 ± 0.87, 13.41 ± 0.91, 13.89 ± 0.76, 14.44 ± 0.65, p = 0.063), SES-CD score (17.14 ± 4.87, 7.66 ± 5.98, p = 0.014), MaRIA score (21.13 ± 7.42, 9.91 ± 4.55, p = 0.003) and Nancy score (3.71±0.48, 1.71±0.36, p=0.028) were all statistically significant. The stenotic segment endoscopically passed at week 12 in every patient but one, which had minimally invasive surgery (ileoascendostomy) because of ileus that developed at the eighth week of therapy. Of note, the patient who underwent surgery had perianal involvement.

CONCLUSION:

Despite the extremely limited number of patients and short-term follow-up results, 12-week EEN and concurrent weekly ADA therapy may be effective in inducing remission in this group of patients. There is a need for large-scale, prospective studies on this subject.
P017 Increased Level of Immunoglobulin G in the Development of Adverse Reactions in Patients With Ulcerative Colitis
Authors: Zvyaglova Mariya , Knyazev Oleg , Noscova Karina
Published: December 2021

BACKGROUND:

Goal: To identify the relationship between the level of immunoglobulins G and E and the development of adverse reaction (AR) in patients with ulcerative colitis (UC) receiving original infliximab (IFХ) and infliximab biosimilar (BS).

METHODS:

35 UC patients with moderate to severe course of the disease (according to Truelove–Witts) who received maintenance therapy with IFХ at a standard dose of 5 mg/kg of body weight for a year were retrospectively analyzed. There were 16 men (45.7%), 19 women (54.3%). The average age is 34±4.2 years. The duration of the anamnesis was from 3 to 7 years. Patients were divided into 3 groups depending on the development of AR and the received biological drug, without taking into account concomitant anti-inflammatory therapy. The 1st group (n=14) alternated the introduction of the original IFХ and its BS; The 2nd group (n=7) consisted of patients alternating between the original IFХ and BS, in whom AR was registered; the 3rd group (n=14) received BS by one trade name. Using enzyme immunoassay, the level of immunoglobulins in the groups of patients was assessed.

RESULTS:

In the 1st and 3rd groups, AR was not observed. AR in 2nd group was characterized by: bronchospasm 3 (42.8%), Quincke's edema 1 (14.3%), urticaria 1 (14.3%), rhinitis 1 (14.3%), anaphylactic shock 1 (14.3%). In patients of 1st group, the level of IgE is 44.8 ± 5.1 IU/ml, IgG is 16.5 ± 1.7 g/l. In 2nd group -IgE-44.5 ± 11.7 IU / ml, IgG-26.1 ± 2.1 g/l, while in patients in group 3-IgE - 31.5 ± 3.04 IU/ml, IgG – 9.46 ± 1.01 g/l. It was reliably established that the highest level of IgG was observed in the 2nd group, while in the 3rd group it was minimal (p < 0.05). The IgG level in 1st group is higher than in 3rd group, although in both groups the IgG level was within the reference values. In all groups, the IgE value remained normal.

CONCLUSION:

AR on the background of therapy with IFL and biosimilars are not associated with an increase in the level of IgE, but are caused by an increase in the level of IgG. The alternation of the original drug and the biosimilar increases the risk of developing AR due to increased IgG levels. Treatment with a biosimilar by one trade name does not increase the risk of developing AR.
P019 Not All Fecal Calprotectin is Specific for Inflammatory Bowel Disease
Authors: Gueorguieva Iana , Jacobs Randall , Piper Marc
Published: December 2021

CASE:

Introduction:Fecal calprotectin is a known inflammatory marker used to evaluate patients with Inflammatory Bowel Disease (IBD). In fact, ACG Clinical Guideline for management of Crohn’s disease recommend fecal calprotectin (FC) as a helpful test to distinguish IBD versus functional disorder such as Irritable Bowel Syndrome. Studies have also shown association of fecal calprotectin with colon cancer. Recent study proposed fecal calprotectin could be a reliable marker for ruling out organic disease with high negative predictive value.

CASE DESCRIPTION:

We present a patient case of a Caucasian, thirty-five years of age male with PMHx of GERD on Prilosec who presented due to acute abdominal pain, nausea, emesis and watery, nonbloody diarrhea of four days duration. Initially, patient had unknown family history of colon cancer which later was revealed that patient’s father had a colon cancer diagnosis in his fifties. On admission, patient had stable vitals with routine labs showing leukocytosis, iron deficiency anemia, normal CRP, and elevated fecal calprotectin of 986mcg/gm. Abdominal imaging with CT abdomen with contrast showed diffuse dilation of ileum and thickening of the distal ileum up to the level of the ileocecal junction, suggestive of enteritis from infectious or inflammatory etiology such as Crohn’s. Patient was managed conservatively, stool studies were negative otherwise and discharged with outpatient endoscopy due to high suspicion for Inflammatory Bowel Disease. Within one week, patient had a subsequent readmission for now partial small bowel obstruction at the level of ileum. Due to high suspicion of Crohn’s, patient was empirically started on IV steroids. Decision for inpatient colonoscopy was made with colonoscopy showing completely obstructing, circumferential, large mass found in the cecum extending into ascending colon. Final pathology revealed invasive mucinous adenocarcinoma, moderately differentiated. Patient subsequently underwent right hemicolectomy with lymph node resection and adjuvant chemotherapy treatment for stage 3 colon.

DISCUSSION:

We present here a case where a common cancer was found in an otherwise healthy, young male with acute abdominal pain and altered bowel habits. While initial symptoms, imaging and laboratory findings pointed towards a biased high suspicion for Inflammatory Bowel Disease, patient's ultimate diagnosis was stage 3 adenocarcinoma of colon requiring surgical resection and chemotherapy. Fecal calprotectin is a known marker for colon inflammation and associated with both IBD and colon cancer. It is important to keep in mind that while fecal calprotectin may have elevated negative predictive value and be used to rule out organic disease, elevation of fecal calprotectin is not always specific for IBD. We want to emphasize the importance of considering colon cancer on the differential despite a patient’s age and diagnostic bias. Lastly, we also want to highlight the importance of tissue diagnosis prior to long term therapy use.
P027 Brain Fog in Patients With Inflammatory Bowel Disease, and Association With Use of Probiotics
Authors: Dadlani Apaar , Gala Khushboo , Rai Jayesh , Rai Shesh , Dryden Gerald
Published: December 2021

BACKGROUND:

Brain fog has been minimally studied in patients with inflammatory bowel disease (IBD). IBD patients frequently consume probiotics, whether sanctioned by a physician or not. However, probiotic consumption in itself has been shown to increase the incidence of brain fog. We aimed to study the association between brain fog in IBD patients with or without probiotic use.

METHODS:

We conducted a cross-sectional study among patients visiting a busy IBD clinic. Patients aged >18 with a biopsy-proven diagnosis of inflammatory bowel disease, without pre-existing psychiatric illness or current use of opioid medications were included. They were divided into 2 groups: those using probiotics and those who did not. Patients were given a questionnaire that included details about symptoms of brain fog. Groups were analyzed by chi-square test for differences in baseline demographics, and Mann Whitney U test to compare outcomes between groups. A p-value < 0.05 was considered statistically significant.

RESULTS:

Of the 66 patients included (mean age 44±2 years), 35 (53%) were female and 59 (89.4%) were Caucasian. Among these patients, 31.8% (n = 21) took probiotics as dietary supplements with the majority (67%, n = 14) taking probiotics for over a year. Overall, there was a trend for an association between probiotic use and brain fog in all patients (p = 0.080) but no statistical significance was attained. However, brain fog was significantly associated with probiotic use among Caucasian patients (p = 0.044). Furthermore, there was a statistically significant association between brain fog and male patients using probiotics (p = 0.004). Duration of probiotic use was also associated with brain fog (p = 0.038).

CONCLUSION:

Consumption of probiotics was independently associated with brain fog in men, as well as Caucasian patients with IBD respectively. Given the high prevalence of probiotic use in IBD patients, prospective studies are warranted to examine the causal relationship between probiotics and IBD-associated brain fog to guide prescription of probiotic supplements for IBD.