bluuebunny/crossref_metadata_2025 huggingface dataset:
Constructing the three-qudit unextendible product bases with strong nonlocality
Authors: Che Bichen , Dou Zhao , Chen Xiubo , Yang Yu , Li Jian , Yang Yixian
Published: January 2022

Unextendible product bases (UPBs) are interesting members of a family of orthogonal product bases. Here, we investigate the construction of 3-qudit UPBs with strong nonlocality. First, a UPB set in C
3 ⊗ C
3 ⊗ C
3 of size 19 is presented based on the shift UPBs. By mapping the system to a Rubik’s cube, we provide a general method of constructing UPBs in Cd
⊗ Cd
⊗ Cd
of size ( d – 1 )3 + 2d + 5, whose corresponding Rubik’s cube is composed of four parts. Second, for the more general case where the dimensions of parties are different, we extend the classical tile structure to the 3-qudit system and propose the tri-tile structure. By means of this structure, a C
4 ⊗ C
4 ⊗ C
5 system of size 38 is obtained based on a C
3 ⊗ C
3 ⊗ C
4 system of size 19. Then, we generalize this approach to the C

d
1
⊗ C

d
2
⊗ C

d
3
system which also consists of four parts. Our research provides a positive answer to the open question raised in by Halder et al. [Phys. Rev. Lett. 122 040403 (2019)], indicating that there do exist UPBs that can exhibit strong quantum nonlocality without entanglement.
Dynamical quantum phase transition in XY chains with the Dzyaloshinskii-Moriya and XZY–YZX three-site interactions
Authors: Cao Kaiyuan , Zhong Ming , Tong Peiqing
Published: January 2022

We study the dynamical quantum phase transitions (DQPTs) in the XY chains with the Dzyaloshinskii–Moriya interaction and the XZY–YZX type of three-site interaction after a sudden quench. Both the models can be mapped to the spinless free fermion models by the Jordan–Wigner and Bogoliubov transformations with the form

H
=

∑
k

ε
k

(

η
k
†

η
k

−

1
2

)

, where the quasiparticle excitation spectra εk
may be smaller than 0 for some k and are asymmetrical (εk
≠ ε
–k
). It is found that the factors of Loschmidt echo equal 1 for some k corresponding to the quasiparticle excitation spectra of the pre-quench Hamiltonian satisfying εk
⋅ ε
–k
< 0, when the quench is from the gapless phase. By considering the quench from different ground states, we obtain the conditions for the occurrence of DQPTs for the general XY chains with gapless phase, and find that the DQPTs may not occur in the quench across the quantum phase transitions regardless of whether the quench is from the gapless phase to gapped phase or from the gapped phase to gapless phase. This is different from the DQPTs in the case of quench from the gapped phase to gapped phase, in which the DQPTs will always appear. Moreover, we analyze the different reasons for the absence of DQPTs in the quench from the gapless phase and the gapped phase. The conclusion can also be extended to the general quantum spin chains.
Non-invasive and low-artifact in vivo brain imaging by using a scanning acoustic-photoacoustic dual mode microscopy
Authors: Chen Wentian , Tao Chao , Hu Zizhong , Yuan Songtao , Liu Qinghuai , Liu Xiaojun
Published: January 2022

Photoacoustic imaging is a potential candidate for in vivo brain imaging, whereas, its imaging performance could be degraded by inhomogeneous multi-layered media, consisted of scalp and skull. In this work, we propose a low-artifact photoacoustic microscopy (LAPAM) scheme, which combines conventional acoustic-resolution photoacoustic microscopy with scanning acoustic microscopy to suppress the reflection artifacts induced by multi-layers. Based on similar propagation characteristics of photoacoustic signals and ultrasonic echoes, the ultrasonic echoes can be employed as the filters to suppress the reflection artifacts to obtain low-artifact photoacoustic images. Phantom experiment is used to validate the effectiveness of this method. Furthermore, LAPAM is applied for in-vivo imaging mouse brain without removing the scalp and the skull. Experimental results show that the proposed method successfully achieves the low-artifact brain image, which demonstrates the practical applicability of LAPAM. This work might improve the photoacoustic imaging quality in many biomedical applications which involve tissues with complex acoustic properties, such as brain imaging through scalp and skull.
High-precision nuclear magnetic resonance probe suitable for in situ studies of high-temperature metallic melts
Authors: Li Ao , Xu Wei , Chen Xiao , Yao Bing-Nan , Huo Jun-Tao , Wang Jun-Qiang , Li Run-Wei
Published: January 2022

High-temperature nuclear magnetic resonance (NMR) has proven to be very useful for detecting the temperature-induced structural evolution and dynamics in melts. However, the sensitivity and precision of high-temperature NMR probes are limited. Here we report a sensitive and stable high-temperature NMR probe based on laser-heating, suitable for in situ studies of metallic melts, which can work stably at the temperature of up to 2000 K. In our design, a well-designed optical path and the use of a water-cooled copper radio-frequency (RF) coil significantly optimize the signal-to-noise ratio (S/NR) at high temperatures. Additionally, a precise temperature controlling system with an error of less than ± 1 K has been designed. After temperature calibration, the temperature measurement error is controlled within ± 2 K. As a performance testing, 27Al NMR spectra are measured in Zr-based metallic glass-forming liquid in situ. Results show that the S/NR reaches 45 within 90 s even when the sample’s temperature is up to 1500 K and that the isothermal signal drift is better than 0.001 ppm per hour. This high-temperature NMR probe can be used to clarify some highly debated issues about metallic liquids, such as glass transition and liquid–liquid transition.
Reaction mechanism of metal and pyrite under high-pressure and high-temperature conditions and improvement of the properties
Authors: Wang Yao , Xu Dan , Gao Shan , Chen Qi , Zhou Dayi , Fan Xin , Li Xin-Jian , Chang Lijie , Zhang Yuewen , Ma Hongan , Jia Xiao-Peng
Published: January 2022

Pyrite tailings are the main cause of acid mine wastewater. We propose an idea to more effectively use pyrite, and it is modified by exploiting the reducibility of metal represented by Al under high-pressure and high-temperature (HPHT) conditions. Upon increasing the Al addition, the conductivity of pyrite is effectively improved, which is nearly 734 times higher than that of unmodified pyrite at room temperature. First-principles calculations are used to determine the influence of a high pressure on the pyrite lattice. The high pressure increases the thermal stability of pyrite, reduces pyrite to high-conductivity Fe7S8 (pyrrhotite) by Al. Through hardness and density tests the influence of Al addition on the hardness and toughness of samples is explored. Finally we discuss the possibility of using other metal-reducing agents to improve the properties of pyrite.
Systematic study of the (n, 2n) reaction cross section for 121Sb and 123Sb isotopes
Authors: Singh R. K. , Singh N. L. , Chauhan R. D. , Mehta Mayur , Suryanarayana S. V. , Makwana Rajnikant , Nayak B. K. , Naik H. , Nag Tarak Nath , Katovsky K.
Published: January 2022

The cross sections of the 121Sb

120Sbm and 123Sb

122Sb reactions were measured at 12.50, 15.79 and 18.87 MeV neutron energies relative to the standard 27Al

24Na monitor reaction using neutron activation and offline γ-ray spectrometry. Irradiation of the samples was performed at the BARC-TIFR Pelletron Linac Facility, Mumbai, India. The quasi-monoenergetic neutrons were generated via the 7Li

reaction. Statistical model calculations were performed by nuclear reaction codes TALYS (ver. 1.9) and EMPIRE (ver. 3.2.2) using various input parameters and nuclear level density models. The cross sections of the ground and the isomeric state as well as the isomeric cross section ratio were studied theoretically from reaction threshold to 26 MeV energies. The effect of pre-equilibrium emission is also discussed in detail using different theoretical models. The present measured cross sections were discussed and compared with the reported experimental data and evaluation data of the JEFF-3.3, ENDF/B-VIII.0, JENDL/AD-2017 and TENDL-2019 libraries. A detailed analysis of the uncertainties in the measured cross section data was performed using the covariance analysis method. Furthermore, a systematic study of the

reaction cross section for 121Sb and 123Sb isotopes was also performed within 14–15 MeV neutron energies using various systematic formulae. This work helps to overcome discrepancies in Sb data and illustrate a better understanding of pre-equilibrium emission in the

reaction channel.
DC performance and AC loss of sub-size MgB2 CICC conductor for fusion magnet application
Authors: Gao P. , He Y.X. , Ma H.J. , Anvar V.A. , Huang J.F. , Pan X.F. , Zhou C. , Nijhuis A. , Li J.G. , Qin J.G. , Wang W. J. , Yu M. , Jin H.
Published: January 2022

Given the low price and relatively high transition temperature (39 K) of MgB2 conductor, MgB2-based superconductors are a potential candidate for the lower field fusion coils, such as poloidal field (PF) coils, correction coils and feeders. However, to date, the application of MgB2 is limited to demonstrators in a low magnetic field of up to 5 T and at temperatures of up to 10 to 20 K, relying on cryogen-free, helium gas or liquid hydrogen cooling, which significantly reduce the cost of cryogenic systems. To demonstrate the feasibility and performance verification of large size MgB2 PF conductors based on ITER and CFETR requirements, a 4th-stage subsize MgB2 cable-in-conduit conductor (CICC) cable sample is made at the Institute of Plasma Physics, Chinese Academy of Sciences. The CICC contains 96 in situ MgB2 superconducting wires, manufactured by Western Superconducting Technology Ltd. and 48 copper wires. The critical current of the sub-size cables and MgB2 witness wires are examined with different background magnetic fields at 4.2 K. In addition, the AC loss is measured utilizing magnetization and calorimetric methods. To further clarify the influence of electromagnetic force on the AC loss performance, the cable sample is pressed transversely at room temperature and then inserted into a dipole magnet for AC loss measurement at 4.2 K. The critical current at 4.2 K of the subsize MgB2 CICC cable shows 20% degradation compared to the witness wires at 2 T background magnetic field. However, no further critical current degradation is visible during ramping up and down the magnetic field. The coupling loss time constant for 1 T background magnetic field amounts to 480 ms. No significant effect of the applied transverse stress on the coupling loss is observed between 0 and 10 MPa.
The Buffon needle problem for Lévy distributed spacings and renewal theory
Authors: Godrèche Claude
Published: January 2022

What is the probability that a needle dropped at random on a set of points scattered on a line segment does not fall on any of them? We compute the exact scaling expression of this hole probability when the spacings between the points are independent identically distributed random variables with a power-law distribution of index less than unity, implying that the average spacing diverges. The theoretical framework for such a setting is renewal theory, to which the present study brings a new contribution. The question posed here is also related to the study of some correlation functions of simple models of statistical physics.
Simulated sensor characterization for virtual clinical trials in mammography and digital breast tomosynthesis
Authors: Sarno A. , Tucciariello R.M.
Published: January 2022

Virtual clinical trials in X-ray breast imaging permit to compare different technical solutions and imaging modalities at reduced costs, involved personnel, reduced times and reduced radiation risks to patients. In this context, the detector characteristics (spatial resolution, noise level and efficiency) play a key role for an appropriate generation of simulated images. The project AGATA proposes to compute images as dose deposit maps in a detector layer of defined materials. Simulated images are then post-processed on the basis of suitable comparison between intrinsic characteristics of real and simulated detectors. With this scope, as first step for the post-processing manipulations, we evaluated the presampled modulation transfer function (MTF), the detector-response function and the noise power spectrum (NPS) of the simulated detectors. Two detectors were simulated: (1) 0.20 mm-thick a-Se direct flat panel with 70 µm pixel pitch and (2) CsI(Tl) indirect flat panel with 100 µm pixel pitch and scintillator layer 0.25 mm thick. In addition, the impact of simulating the de-excitation processes (Auger emission and fluorescence) was explored. Simulated detector characteristics were evaluated for W/Rh spectra between 25 kV and 31 kV. The in-silico platform used a Monte Carlo software based on Geant4 toolkit (vers. 6). First, the simulation and tracking of electrons generated from photoelectric or Compton interactions was shown to have neglectable influence on the pixel values for the explored spectra, with the produced electrons presenting short ranges with respect to the pixel dimension. In the case of the CsI detector, which has fluorescence energies higher than those of the simulated X-ray photons, the deexcitation processes have not noticeable influence on the calculated pixel values. On the other hand, the MTF of the a-Se detector resulted slightly lower when the fluorescence is simulated in the detector materials, due to the dose spread derived from the fluorescence photons, which can travel far from the initial ionization interaction. Regarding the a-Se detector, the noise power spectrum resulted lower with simulated deexcitation.
Characterization of time-of-flight double-photon Compton imaging system by simulation
Authors: Zhihong Z. , Shimazoe K. , Takahashi H.
Published: January 2022

Double-photon emission computed tomography (DPECT) has been proposed to overcome the disadvantage of a low signal-to-background ratio for conventional Compton imaging. This method has shown significant image reconstruction capability in the 2D plane. However, its performance is unsatisfactory when the field of view is 3-dimensional (3D). To solve this problem, we propose application of the time-of-flight (TOF) technique to DPECT as an enhancement. In this research, we used a Geant4 simulation to demonstrate the effectiveness of TOF in large 3D volume image reconstruction.
Combustion of wood pellets with a high amount of fines
Authors: Lyubov V K , Popov A N , Popova E I
Published: January 2022

A comprehensive study of the efficiency of the 1.5 MW Arimax Bio Energy hot water boiler operating on wood pellets with a high amount of fines has been carried out. Fuel characteristics and its compliance with the quality requirements of Russian and European standards have been investigated. The components of the heat balance and emission of harmful substances have been determined. Thermovision study of the boiler was carried out. The comprehensive study showed that the boiler provides sufficiently high technical and economic performance and minimal emissions of nitrogen oxides and carbon monoxide. However, the high amount of fines in the pellets significantly increases the emissions of particulate matter and especially black carbon into the environment.
Boilers slagging when burning wood pellets
Authors: Lyubov V K , Malkov A V , Alekseev P D
Published: January 2022

A promising trend for upgrading wastes from timber cutting, processing and treatment is their granulation. It allows to increase their specific heats of combustion by 2.5– 3.5 times and their portability characteristics by 3–4 times, to reduce transportation costs by 6– 10 times and to improve all the operations stages. The construction and commissioning of boiler facilities operating on refined biofuel made it possible to form a stable domestic market for wood pellets. However, 0.5 – 1.5 MW nominal capacity hot water boilers equipped with furnaces and profiled burners at the bottom, in cold seasons had fast accumulation of focal residues deposits in the burners and on the furnace chambers lining. The process was complicated by these deposits hardening due to their melting and sintering. These circumstances cause a decrease in the energy and environmental performance of heat-generating installations and their reliability, and also leads to the unplanned shutdowns to clean the boiler furnaces. To find out the reasons for these negative phenomena and to develop recommendations for their elimination, a set of research operations was carried out with wood pellets shipped by the manufacturer and supplied to the burners of the boilers under the analyses; with focal residues accumulated in the burners and on the lining of the furnace chambers; as well as an analysis of the heat generating facilities operation modes. The studies carried out made it possible to identify the main factors that caused these negative phenomena and to develop the recommendations for their elimination.
Low-temperature induction heating of flat metal objects in a traveling electromagnetic field
Authors: Kachanov A N , Stepanov Y S , Kachanov N A , Chernyshov V A , Korenkov D A
Published: January 2022

The article discusses possible options for a low-temperature induction heating system (LTIHS) of flat metal products in a traveling electromagnetic field. The problem of calculating eddy currents, active and reactive powers induced in a heated flat object, as well as electromagnetic forces acting on the object moving it in a given direction, is posed and solved. A mathematical model has been developed that takes into account the dependence of the influence on the main parameters of the electromagnetic field of the following factors: geometric dimensions of the air gap between the poles of the magnetic circuit and the heated flat body; the longitudinal edge effect caused by the open circuit of the magnetic circuit of the inductor, as well as the transverse edge effect associated with the appearance of the longitudinal components of eddy currents in a heated flat object. The solution of particular problems of LTIHS in one- and two-dimensional formulation allows them to be simplified and to perform calculations for various design variants of induction heating devices with a traveling electromagnetic field, using a one-dimensional model that explicitly takes into account the features of electromagnetic processes in the systems under study.
Development of a Range of Modified Multifunctional Residual Current Systems and Their Industrial Implementation
Authors: Nikolsky O К , Khalina T M
Published: January 2022

The developments of the AltSTU have been reviewed in the area of creating a new technology for preventing technogenic hazards based on the residual current devices. The residual current devices are intended for protecting people from electric shock in case of contact with conductive parts of the electric appliances and shall facilitate reduction of fire risks caused by a prolonged flow of leakage currents and fault currents resulting from them. The results of creating different modifications of protective trip circuits and their industrial use are provided.
Color sensor application in high-temperature spectral ratio pyrometer
Authors: Valke A A , Lobov D G , Shkaev A G
Published: January 2022

Contactless thermal control tools play an important role in solving the high-temperature technological processes improving energy efficiency problems. In order to create such controls, the authors analyzed the developing possibility of spectral ratio high-temperature pyrometer using a multispectral radiation receiver (color sensor) TCS34725. In the paper this receiver application coefficients are determined, signals ratio graphs in different spectral intervals on temperature are given for two applications: without additional filtration of the control object radiation infrared component and using an opaque in the infrared spectrum part external filter.
Effect of inaccurate small field output factors on brain SRS plans
Authors: Dobberthien Brennen J , Cao Fred , Zhao Yingli , Harvey Eric , Badragan Genoveva
Published: January 2022

External beam radiotherapy often includes the use of field sizes 3 × 3 cm2or less, which can be defined as small fields. Dosimetry is a difficult, yet important part of the radiotherapy process. The dosimetry of small fields has additional challenges, which can lead to treatment inconsistencies if not done properly. Most important is the use of an appropriate detector, as well as the application of the necessary corrections. The International Atomic Energy Agency and the American Association of Physicists in Medicine provide the International Code of Practice (CoP) TRS-483 for the dosimetry of small static fields used in external MV photon beams. It gives guidelines on how to apply small-field correction factors for small field dosimetry. The purpose of this study was to evaluate the impact of inaccurate small-field output factors on clinical brain stereotactic radiosurgery plans with and without applying the small-field correction factors as suggested in the CoP. Small-field correction factors for a Varian TrueBeam linear accelerator were applied to uncorrected relative dose factors. Uncorrected and corrected clinical plans were created with two different beam configurations, 6 MV with a flattening filter (6 WFF) and 6 MV without a flattening filter (6 FFF). For the corrected plans, the planning target volume mean dose was 1.6 ± 0.9% lower with p < 0.001 for 6 WFF and 1.8 ± 1.5% lower with p < 0.001 for 6 FFF. For brainstem, a major organ at risk, the corrected plans had a dose that was 1.6 ± 0.9% lower with p = 0.03 for 6 WFF and 1.8 ± 1.5% lower with p = 0.10 for 6 FFF. This represents a systematic error that should and can be corrected.
Using materials for quasiparticle engineering
Authors: Catelani G , Pekola J P
Published: January 2022

The fundamental excitations in superconductors—Bogoliubov quasiparticles—can be either a resource or a liability in superconducting devices: they are what enables photon detection in microwave kinetic inductance detectors, but they are a source of errors in qubits and electron pumps. To improve operation of the latter devices, ways to mitigate quasiparticle effects have been devised; in particular, combining different materials quasiparticles can be trapped where they do no harm and their generation can be impeded. We review recent developments in these mitigation efforts and discuss open questions.
Evolutionary 2D organic crystals for optoelectronic transistors and neuromorphic computing
Authors: Qian Fangsheng , Bu Xiaobo , Wang Junjie , Lv Ziyu , Han Su-Ting , Zhou Ye
Published: January 2022

Brain-inspired neuromorphic computing has been extensively researched, taking advantage of increased computer power, the acquisition of massive data, and algorithm optimization. Neuromorphic computing requires mimicking synaptic plasticity and enables near-in-sensor computing. In synaptic transistors, how to elaborate and examine the link between microstructure and characteristics is a major difficulty. Due to the absence of interlayer shielding effects, defect-free interfaces, and wide spectrum responses, reducing the thickness of organic crystals to the 2D limit has a lot of application possibilities in this computing paradigm. This paper presents an update on the progress of 2D organic crystal-based transistors for data storage and neuromorphic computing. The promises and synthesis methodologies of 2D organic crystals (2D OCs) are summarized. Following that, applications of 2D OCs for ferroelectric non-volatile memory, circuit-type optoelectronic synapses, and neuromorphic computing are addressed. Finally, new insights and challenges for the field’s future prospects are presented, pushing the boundaries of neuromorphic computing even farther.
Morphological Differentiation of Ventral Tarsal Setae and Surface Sculpturing of Theraphosids (Araneae: Theraphosidae) With Different Types of Lifestyles
Authors: Szymkowiak Paweł , Grabowski Patryk
Published: January 2022

The ventral surfaces of tarsi in spiders in the infraorder Mygalomorphae group play a key role in locomotion and burrow and nest construction. In our research, we analyzed the diversity of setae and patterns of sculpturing on tarsi in three species with different life strategies: a burrowing spider Brachypelma smithi (F. O. Pickard-Cambridge, 1897), a ground-dwelling spider, Pterinochilus murinus Pocock, 1897, and a arboreal spider, Poecilotheria regalis Pocock, 1899. We showed the presence of three types of setae on the ventral side of tarsi: plumose setae, short-haired spiniform setae, and spirally striated setae. Plumose setae were differentiated within a tarsus and their apical sections among the studied species, while the microtriched ensiform and spirally striated setae did not differ. All setae were characterized by a similar structure. Little differentiation was observed in the number and location of setae on the tarsi of the studied species. Spirally striated setae were absent in the burrowing spiders. In contrast, the shape and size of the sculpturing pattern varied among the studied species. The greatest differentiation was found in the burrowing and ground-dwelling spiders, while the smallest differentiation was found in the arboreal spider. We discuss our findings in relation to preferred habitats, the biology of the spiders, and adaptation of sculpturing and setae on spider feet to surface type. The morphology and diversity of setae and sculpturing patterns on the ventral side of tarsi in P. murinus was reported for the first time.
Myostatin increases human trophoblast cell invasion by upregulating N-cadherin via SMAD2/3-SMAD4 signaling
Authors: AbdelHafez Faten , Klausen Christian , Zhu Hua , Leung Peter C K
Published: January 2022

Placental insufficiency disorders are major obstetric complications that share a common phenomenon of poor placental trophoblast cell invasion and remodeling of uterine tissues. Myostatin is a transforming growth factor (TGF)-β superfamily member well known for its important role in muscle growth control. Myostatin is also produced in the placenta and has been shown to regulate some trophoblast functions. However, its roles in placental development are still poorly understood. In this study, we tested the hypothesis that myostatin increases trophoblast cell invasion by upregulating N-cadherin via SMAD2/3-SMAD4 signaling. Primary and immortalized (HTR8/SVneo) trophoblast cells were used as study models. Matrigel-coated transwell invasion assays were used to study the effects of recombinant human myostatin on trophoblast cell invasion. Reverse transcription quantitative real-time polymerase chain reaction and Western blot were used to measure myostatin effects on N-cadherin mRNA and protein levels, respectively. Small inhibitor molecules as well as siRNA-mediated knockdown were used to block myostatin receptor and downstream signaling, respectively. Data were analyzed either by unpaired Student T test or one-way analysis of variance followed by Newman Keuls test for multiple group comparisons. Myostatin significantly increased primary and HTR8/SVneo trophoblast cell invasion. Moreover, myostatin upregulated N-cadherin mRNA and protein levels in a time-dependent manner in both study models. These effects were blocked by inhibition of TGF-β type I receptors as well as siRNA-mediated knockdown of SMAD2/3 combined or common SMAD4. Importantly, myostatin-induced trophoblast cell invasion was abolished by knockdown of N-cadherin, SMAD2/3, or SMAD4. Myostatin may increase human trophoblast cell invasion by upregulating N-cadherin via SMAD2/3-SMAD4 signaling.
The impact of bisphenol A on the placenta
Authors: Adu-Gyamfi Enoch Appiah , Rosenfeld Cheryl S , Tuteja Geetu
Published: January 2022

Bisphenol A (BPA), an endocrine-disrupting chemical, is used to produce a wide variety of plastic and common house-hold items. Therefore, there is potential continual exposure to this compound. BPA exposure has been linked to certain placenta-associated obstetric complications such as preeclampsia, fetal growth restriction, miscarriage, and preterm birth. However, how BPA exposure results in these disorders remains uncertain. Hence, we have herein summarized the reported impacts of BPA on the morphology and metabolic state of the placenta and have proposed mechanisms by which BPA affects placentation, potentially leading to obstetric complications. Current findings suggest that BPA induces pathological changes in the placenta and disrupts its metabolic activities. Based on exposure concentrations, BPA can elicit apoptotic or anti-apoptotic signals in the trophoblasts, and can exaggerate trophoblast fusion while inhibiting trophoblast migration and invasion to affect pregnancy. Accordingly, the usage of BPA products by pregnant women should be minimized and less harmful alternative chemicals should be explored and employed where possible.
Cost-effectiveness of liver transplantation versus last-resort systemic therapy for colorectal liver metastases
Authors: Bjørnelv Gudrun M W , Zolic-Karlsson Zinajda , Dueland Svein , Line Pål-Dag , Aas Eline
Published: January 2022

This study estimated the cost-effectiveness of liver transplantation in patients with colorectal liver metastases confined to the liver with progressive disease, compared with alternative treatment options: TAS-102, regorafenib, or best supportive care. Using a mathematical simulation model, people’s life expectancy and healthcare costs over 25 years were estimated. Transplanted patients lived for 4.28 years, more than 3 years longer than those who received alternative treatment options. Despite this, the high cost of liver transplantation meant that this treatment was cost-effective only at high willingness-to-pay thresholds.
Association between ultrasonography foetal anomalies and autism spectrum disorder
Authors: Regev Ohad , Hadar Amnon , Meiri Gal , Flusser Hagit , Michaelovski Analya , Dinstein Ilan , Hershkovitz Reli , Menashe Idan
Published: January 2022

Multiple pieces of evidence support the prenatal predisposition of autism spectrum disorder (ASD). Nevertheless, robust data about abnormalities in foetuses later developing into children diagnosed with ASD are lacking. Prenatal ultrasound is an excellent tool to study abnormal foetal development as it is frequently used to monitor foetal growth and identify foetal anomalies throughout pregnancy.

We conducted a retrospective case-sibling-control study of children diagnosed with ASD (cases); their own typically developing, closest-in-age siblings (TDS); and typically developing children from the general population (TDP), matched by year of birth, sex and ethnicity to investigate the association between ultrasonography foetal anomalies and ASD. The case group was drawn from all children diagnosed with ASD enrolled at the National Autism Research Center of Israel. Foetal ultrasound data from the foetal anatomy survey were obtained from prenatal ultrasound clinics of Clalit Health Services in southern Israel.

The study comprised 659 children: 229 ASD, 201 TDS and 229 TDP. Ultrasonography foetal anomalies were found in 29.3% of ASD cases versus only 15.9% and 9.6% in the TDS and TDP groups [adjusted odds ratio (aOR) = 2.23, 95% confidence interval (CI) = 1.32–3.78, and aOR = 3.50, 95%CI = 2.07–5.91, respectively]. Multiple co-occurring ultrasonography foetal anomalies were significantly more prevalent among ASD cases. Ultrasonography foetal anomalies in the urinary system, heart, and head and brain were the most significantly associated with ASD diagnosis (aORUrinary = 2.08, 95%CI = 0.96–4.50 and aORUrinary = 2.90, 95%CI = 1.41–5.95; aORHeart = 3.72, 95%CI = 1.50–9.24 and aORHeart = 8.67, 95%CI = 2.62–28.63; and aORHead&Brain = 1.96, 95%CI = 0.72–5.30 and aORHead&Brain = 4.67, 95%CI = 1.34–16.24; versus TDS and TDP, respectively). ASD females had significantly more ultrasonography foetal anomalies than ASD males (43.1% versus 25.3%, P = 0.013) and a higher prevalence of multiple co-occurring ultrasonography foetal anomalies (15.7% versus 4.5%, P = 0.011). No sex differences were seen among TDS and TDP controls. ASD foetuses were characterized by a narrower head and a relatively wider ocular-distance versus TDP foetuses (ORBPD = 0.81, 95%CI = 0.70–0.94, and aOROcular distance = 1.29, 95%CI = 1.06–1.57). Ultrasonography foetal anomalies were associated with more severe ASD symptoms.

Our findings shed important light on the multiorgan foetal anomalies associated with ASD.
CMTM6: increased circulating level and up-regulated expression in labial salivary glands in patients with primary Sjogren’s syndrome
Authors: Qian Sirui , Xu Jingyi , Zhao Shan , Yang Pingting , Yang Chunshu
Published: January 2022

Chemokine-like factor (CKLF)-like MARVEL transmembrane domain containing family member 6 (CMTM6), which is a key regulator of programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) signaling in patients with primary Sjögren’s syndrome (pSS). In this study, we analyzed the serum levels of CMTM6, PD-1, and PD-L1 in 50 patients with pSS, 42 patients with non-pSS (simply dry mouth and/or eyes symptoms) and 50 healthy controls (HC). The expression of CMTM6, PD-1, and PD-L1 in labial glands of the same 50 pSS patients and 42 non-pSS patients were assessed by immunohistochemistry (IHC). The clinical significance of CMTM6, PD-1, and PD-L1 were analyzed. We found that levels of CMTM6, PD-L1 as well as PD-1 in sera were all increased significantly in patients with pSS compared with non-pSS controls and HC. Serum CMTM6 level showed significantly correlation with PD-L1, PD-1, as well as clinical laboratory indicators and disease activity of pSS patients. CMTM6, PD-1, and PD-L1 expression in labial glands was also higher significantly in pSS patients than non-pSS controls. pSS patients with higher CM grade or ESSDAI score have higher CMTM6, PD-L1, and PD-1 expression in labial glands. These results suggest that CMTM6 may affect peripheral tolerance and lymphocytes activation by PD-1/PD-L1 pathway in sera and target tissue in pSS.
Evaluation of a fit-for-purpose assay to monitor antigen-specific functional CD4+ T-cell subpopulations in rheumatoid arthritis using flow cytometry–based peptide-MHC class-II tetramer staining
Authors: Patel Swati , Ramnoruth Nishta , Wehr Pascale , Rossjohn Jamie , Reid Hugh H , Campbell Kim , Nel Hendrik J , Thomas Ranjeny
Published: January 2022

Antigen-specific T cells can serve as a response biomarker in non-clinical or clinical immunotherapy studies in autoimmune disease. There are protocols with optimized multimer staining methods to detect peptide (p)MHCII+ CD4+ T cells, and some qualified and validated protocols for pMHCI+ CD8+ T cells. However, no protocol is fully or partially qualified to enumerate and characterize antigen-specific pMHCII+ CD4+ T cells from patient samples. Implementing such an assay requires a desired level of specificity and precision, in terms of assay repeatability and reproducibility. In transgenic type II collagen (CII)-immunized HLA-DR1/DR4 humanized mouse models of collagen-induced arthritis (CIA), CII259-273-specific T cells dominantly expand. Therefore antigen-specific T cells recognizing this epitope presented by rheumatoid arthritis (RA)-associated risk HLA-DR allomorphs are of interest to understand disease progression and responses to immunotherapy in RA patients. Using HLA-DRB1∗04:01 or ∗01:01-collagen type II (CII)259–273 tetramers, we evaluated parameters influencing precision and reproducibility of an optimized flow cytometry–based method for antigen-specific CD4+ T cells and eight specific subpopulations with and without tetramer positivity. We evaluated specificity, precision, and reproducibility for research environments and non-regulated laboratories. The assay has excellent overall precision with %CV<25% for intra-assay repeatability, inter-analyst precision, and inter-assay reproducibility. The precision of the assay correlated negatively with the cell viability after thawing, indicating that post-thaw viability is a critical parameter for reproducibility. This assay is suitable for longitudinal analysis of treatment response and disease activity outcome in RA patients, and adaptable for translational or immunotherapy clinical trial settings.
miR-155-overexpressing monocytes resemble HLAhighISG15+ synovial tissue macrophages from patients with rheumatoid arthritis and induce polyfunctional CD4+ T-cell activation
Authors: Olsson Anton M , Povoleri Giovanni A M , Somma Domenico , Ridley Michael L , Rizou Tatiana , Lalnunhlimi Sylvine , Macdonald Lucy , Rajasekhar Megha , Martinez-Nunez Rocio T , Kurowska-Stolarska Mariola , Taams Leonie S
Published: January 2022

MicroRNAs (miRs) are known to regulate pro-inflammatory effector functions of myeloid cells, and miR dysregulation is implicated in rheumatoid arthritis (RA), a condition characterized by inflammation and destruction of the joints. We showed previously that miR-155 is increased in myeloid cells in RA and induces pro-inflammatory activation of monocytes and macrophages; however, its role at the interface between innate and adaptive immunity was not defined. Here, RNA-sequencing revealed that overexpression of miR-155 in healthy donor monocytes conferred a specific gene profile which bears similarities to that of RA synovial fluid-derived CD14+ cells and HLAhighISG15+ synovial tissue macrophages, both of which are characterized by antigen-presenting pathways. In line with this, monocytes in which miR-155 was overexpressed, displayed increased expression of HLA-DR and both co-stimulatory and co-inhibitory molecules, and induced activation of polyfunctional T cells. Together, these data underpin the notion that miR-155-driven myeloid cell activation in the synovium contributes not only to inflammation but may also influence the adaptive immune response.
SARS-CoV-2 vaccine responses following CD20-depletion treatment in patients with haematological and rheumatological disease: a West Midlands Research Consortium study
Authors: Shields Adrian M , Venkatachalam Srinivasan , Shafeek Salim , Paneesha Shankara , Ford Mark , Sheeran Tom , Kelly Melanie , Qureshi Iman , Salhan Beena , Karim Farheen , De Silva Neelakshi , Stones Jacqueline , Lee Sophie , Khawaja Jahanzeb , Kaudlay Praveen Kumar , Whitmill Richard , Kakepoto Ghulam Nabi , Parry Helen M , Moss Paul , Faustini Sian E , Richter Alex G , Drayson Mark T , Basu Supratik
Published: January 2022

B-cell-depleting agents are among the most commonly used drugs to treat haemato-oncological and autoimmune diseases. They rapidly induce a state of peripheral B-cell aplasia with the potential to interfere with nascent vaccine responses, particularly to novel antigens. We have examined the relationship between B-cell reconstitution and SARS-CoV-2 vaccine responses in two cohorts of patients previously exposed to B-cell-depleting agents: a cohort of patients treated for haematological B-cell malignancy and another treated for rheumatological disease. B-cell depletion severely impairs vaccine responsiveness in the first 6 months after administration: SARS-CoV-2 antibody seroprevalence was 42.2% and 33.3% in the haemato-oncological patients and rheumatology patients, respectively and 22.7% in patients vaccinated while actively receiving anti-lymphoma chemotherapy. After the first 6 months, vaccine responsiveness significantly improved during early B-cell reconstitution; however, the kinetics of reconstitution was significantly faster in haemato-oncology patients. The AstraZeneca ChAdOx1 nCoV-19 vaccine and the Pfizer BioNTech 162b vaccine induced equivalent vaccine responses; however, shorter intervals between vaccine doses (<1 m) improved the magnitude of the antibody response in haeamto-oncology patients. In a subgroup of haemato-oncology patients, with historic exposure to B-cell-depleting agents (>36 m previously), vaccine non-responsiveness was independent of peripheral B-cell reconstitution. The findings have important implications for primary vaccination and booster vaccination strategies in individuals clinically vulnerable to SARS-CoV-2.
The autoimmune encephalitis-related cytokine TSLP in the brain primes neuroinflammation by activating the JAK2-NLRP3 axis
Authors: Yu Xueyuan , Lv Jiajia , Wu Jun , Chen Yong , Chen Fei , Wang Li
Published: January 2022

NLRP3 inflammasome hyperactivation contributes to neuroinflammation in autoimmune disorders, but the underlying regulatory mechanism remains to be elucidated. We demonstrate that compared with wild-type (WT) mice, mice lacking thymic stromal lymphopoietin (TSLP) receptor (TSLPR) (Tslpr−/− mice) exhibit a significantly decreased experimental autoimmune encephalomyelitis (EAE) score, reduced CD4+ T cell infiltration, and restored myelin basic protein (MBP) expression in the brain after EAE induction by myelin oligodendrocyte glycoprotein35–55 (MOG35–55). TSLPR signals through Janus kinase (JAK)2, but not JAK1 or JAK3, to induce NLRP3 expression, and Tslpr−/− mice with EAE show decreased JAK2 phosphorylation and NLRP3 expression in the brain. JAK2 inhibition by ruxolitinib mimicked loss of TSLPR function in vivo and further decreased TSLP expression in the EAE mouse brain. The NLRP3 inhibitor MCC950 decreased CD4+ T cell infiltration, restored MBP expression, and decreased IL-1β and TSLP levels, verifying the pro-inflammatory role of NLRP3. In vitro experiments using BV-2 murine microglia revealed that TSLP directly induced NLRP3 expression, phosphorylation of JAK2 but not JAK1orJAK3, and IL-1β release, which were markedly inhibited by ruxolitinib. Furthermore, EAE induction led to an increase in the Th17 cell number, a decrease in the regulatory T (Treg) cell number in the blood, and an increase in the expression of the cytokine IL-17A in the WT mouse brain, which was drastically reversed in Tslpr−/− mice. In addition, ruxolitinib suppressed the increase in IL-17A expression in the EAE mouse brain. These findings identify TSLP as a prospective target for treating JAK2-NLRP3 axis-associated autoimmune inflammatory disorders.
Immunological findings in patients with migraine and other primary headaches: a narrative review
Authors: Biscetti Leonardo , De Vanna Gioacchino , Cresta Elena , Bellotti Alessia , Corbelli Ilenia , Letizia Cupini Maria , Calabresi Paolo , Sarchielli Paola
Published: January 2022

Experimental findings suggest an involvement of neuroinflammatory mechanisms in the pathophysiology of migraine. Specifically, preclinical models of migraine have emphasized the role of neuroinflammation following the activation of the trigeminal pathway at several peripheral and central sites including dural vessels, the trigeminal ganglion, and the trigeminal nucleus caudalis. The evidence of an induction of inflammatory events in migraine pathophysiological mechanisms has prompted researchers to investigate the human leukocyte antigen (HLA) phenotypes as well as cytokine genetic polymorphisms in order to verify their potential relationship with migraine risk and severity. Furthermore, the role of neuroinflammation in migraine seems to be supported by evidence of an increase in pro-inflammatory cytokines, both ictally and interictally, together with the prevalence of Th1 lymphocytes and a reduction in regulatory lymphocyte subsets in peripheral blood of migraineurs. Cytokine profiles of cluster headache (CH) patients and those of tension-type headache patients further suggest an immunological dysregulation in the pathophysiology of these primary headaches, although evidence is weaker than for migraine. The present review summarizes available findings to date from genetic and biomarker studies that have explored the role of inflammation in primary headaches.
The effect of short-chain fatty acids on M2 macrophages polarizationin vitroandin vivo
Authors: Huang Chunrong , Du Wei , Ni Yingmeng , Lan Gelei , Shi Guochao
Published: January 2022

Alternatively activated macrophages (M2 polarization) play an important role in asthma. Short-chain fatty acids (SCFAs) possessed immune-regulatory functions, but their effects on M2 polarization of alveolar macrophages and its underlying mechanisms are still unclear. In our study, murine alveolar macrophage MH-S cell line and human monocyte-derived macrophages were used to polarize to M2 subset with interleukin-4 (IL-4) treatment. The underlying mechanisms involved were investigated using molecule inhibitors/agonists. In vivo, female C57BL/6 mice were divided into five groups: CON group, ovalbumin (OVA) asthma group, OVA+Acetate group, OVA+Butyrate group, and OVA+Propionate group. Mice were fed with or without SCFAs (Acetate, Butyrate, Propionate) in drinking water for 20 days before developing OVA-induced asthma model. In MH-S, SCFAs inhibited IL-4-incuced protein or mRNA expressions of M2-associated genes in a dose-dependent manner. G-protein-coupled receptor 43 (GPR43) agonist 4-CMTB and histone deacetylase (HDAC) inhibitor (trichostatin A, TSA), but not GPR41 agonist AR420626 could inhibit the protein or mRNA expressions M2-associated genes. 4-CMTB, but not TSA, had no synergistic role in the inhibitory effect of SCFAs on M2 polarization. In vivo study indicated Butyrate and Propionate, but not Acetate, attenuated OVA-induced M2 polarization in the lung and airway inflammation. We also found the inhibitory effect of SCFAs on M2 polarization in human-derived macrophages. Therefore, SCFAs inhibited M2 polarization in MH-S likely through GPR43 activation and/or HDAC inhibition. Butyrate and Propionate but not Acetate could inhibit M2 polarization and airway inflammation in asthma model. SCFAs also abrogated M2 polarization in human-derived macrophages.
Kidney infiltrating NK cells and NK-like T-cells in lupus nephritis: presence, localization, and the effect of immunosuppressive treatment
Authors: Scheffschick Andrea , Fuchs Sina , Malmström Vivianne , Gunnarsson Iva , Brauner Hanna
Published: January 2022

Systemic lupus erythematosus (SLE) is a multi-organ inflammatory disease with kidney inflammation, lupus nephritis (LN), being one of the most severe manifestations. Immune complex deposits, particularly in glomeruli, and T cells, B cells, and myeloid cells, mainly with extraglomerular localization, contribute to the inflammatory process. Natural killer (NK) cells have been suggested to play a role in autoimmune diseases, but have not been investigated in detail in renal lupus before. In this exploratory study, we performed the first characterization of NK cell number and distribution in LN kidney biopsies. Twelve SLE patients were analyzed in the active phase of disease and five patients following immunosuppressive therapy. CD56+ cells, corresponding to NK cells or NK-like T-cells, were identified in all patients; however, with reduced numbers in four out of five patients at follow-up. Furthermore, cells were present in the kidney interstitium and peri-glomerular areas, but only rarely in glomeruli. Fluorescent co-staining of CD56 or NKp46 and CD3 revealed the presence of both CD56+/NKp46+CD3-NK cells and CD56+/NKp46+CD3+NK-like T-cells. Compared to healthy kidney sections, one out of four LN patients showed increased numbers of NK cells. A correlation between CD56+ and NK cells with clinical parameters could not be observed, perhaps due to the small patient cohort. In conclusion, we have identified NK cells and NK-like T-cells in the LN kidney and performed the first detailed analysis of their localization during active and inactive diseases. Their role in LN pathogenesis is, however, unclear and deserves further studies.