bluuebunny/crossref_metadata_2025 huggingface dataset:
The Diagnostics of the rotor misalignment of a permanent magnet motor
Authors: Afanasev A A , Genin V S , Vasileva L N , Grigorev V G
Published: January 2022

A mathematical model of the magnetic field in the working gap of a brushless motor is considered in a case of rotor misalignment arising during manufacture, for example, due to defects in end shields, or in operation due to bearing wear. a gap in a uniform (circular ring). The stator gearing is taken into account on average using the Carter coefficient, the magnetic field in the inhomogeneous air gap, created by the rotor magnets and the stator winding current, is assumed to be plane-parallel, having a two-dimensional character. It was found that the rotor misalignment associated with the rotational movement of the eccentricity causes nonsinusoidality of the idle EMF and pulsation of the electromagnetic moment with a frequency 3p times higher than the rotor speed. When the eccentricity is stationary, a variable EMF is induced along the rotor shaft, causing an alternating current in the circuit: shaft-bearings-bearing shields-stator housing. To clarify the nature of the defect in order to identify the actual misalignment of the rotor, it is recommended to control currents and voltages using specialized software and hardware complexes for spectrum analysis.
Fabrication of bioinspired grid-crimp micropatterns by melt electrospinning writing for bone–ligament interface study
Authors: Xiong Junjie , Wang Han , Lan Xingzi , Wang Yaqi , Wang Zixu , Bai Jianfu , Ou Weicheng , Cai Nian , Wang Wenlong , Tang Yadong
Published: January 2022

Many strategies have been adopted to engineer bone–ligament interface, which is of great value to both the tissue regeneration and the mechanism understanding underlying interface regeneration. However, how to recapitulate the complexity and heterogeneity of the native bone–ligament interface including the structural, cellular and mechanical gradients is still challenging. In this work, a bioinspired grid-crimp micropattern fabricated by melt electrospinning writing (MEW) was proposed to mimic the native structure of bone–ligament interface. The printing strategy of crimped fiber micropattern was developed and the processing parameters were optimized, which were used to mimic the crimp structure of the collagen fibrils in ligament. The guidance effect of the crimp angle and fiber spacing on the orientation of fibroblasts was studied, and both of them showed different levels of cell alignment effect. MEW grid micropatterns with different fiber spacings were fabricated as bone region. Both the alkaline phosphatase activity and calcium mineralization results demonstrated the higher osteoinductive ability of the MEW grid structures, especially for that with smaller fiber spacing. The combined grid-crimp micropatterns were applied for the co-culture of fibroblasts and osteoblasts. The results showed that more cells were observed to migrate into the in-between interface region for the pattern with smaller fiber spacing, suggested the faster migration speed of cells. Finally, a cylindrical triphasic scaffold was successfully generated by rolling the grid-crimp micropatterns up, showing both structural and mechanical similarity to the native bone–ligament interface. In summary, the proposed strategy is reliable to fabricate grid-crimp triphasic micropatterns with controllable structural parameters to mimic the native bone-to-ligament structure, and the generated 3D scaffold shows great potential for the further bone–ligament interface tissue engineering.
Effects of niobium pentoxide nanoparticles on the tribological properties of electrodeposited ZnNi coatings
Authors: Moreira H C R , Oliveira J A B , Carreño N L V , Silva R M , Garcia I T S , Costa H L , Alano J H
Published: January 2022

Electrodeposited ZnNi coatings are widely used to improve the corrosion resistance of steel substrates, but their tribological properties are also relevant for loaded contacts under relative motion. This work investigates the hypothesis of improving tribological properties of electrodeposited ZnNi coatings via dispersion of niobium pentoxide nanoparticles (1 g l−1) in the electrolytic bath. The niobium pentoxide nanoparticles were produced via hydrothermal synthesis assisted by microwave. The surface morphology and chemical composition of the coatings were analysed by scanning electron microscopy coupled with x-ray dispersive energy, X-ray diffraction and x-ray photoelectron spectroscopy. The tribological performance of the coatings was assessed using dry reciprocating ball-on-flat tests at normal loads between 3 and 6 N. The use of niobium pentoxide nanoparticles resulted in significantly denser coatings, with some Nb incorporated in the coated surfaces. Under the lowest normal load, all coated specimens showed relatively low friction (∼0.2) and negligible damage. As the normal load increased, the coating produced using niobium pentoxide nanoparticles showed stronger adherence, while conventional ZnNi coating showed increased friction and spalling for the highest load. It is believed that the Nb2O5 nanoparticles increased the number of sites for heterogeneous nucleation, refining the microstructure, so that tougher and more adherent coatings were produced.
Regulation on tribological performance of tungsten-doped DLC coatings by choline chloride-urea and-thiourea deep eutectic solvents
Authors: Yang Fan , Li Yuting , Yue Zhaofan , Fan Qingbo , Li Hao , Fan Xiaoqiang , Zhu Minhao
Published: January 2022

Solid-liquid composite lubrication system has attracted an increased interest for low friction and wear. Nevertheless, the effect of mechanical and surface properties of the solid materials, especially the mechanical and surface properties governed by doping elements, on the tribological performance solid-liquid composite lubrication system is still not well comprehended. Here, we reported the effect of W content on the mechanical and surface properties of W-DLC coatings as well as the tribological properties of W-DLC coatings under (choline chloride-urea and choline chloride-thiourea) deep eutectic solvents lubrication. Although the wear of W-DLC coatings under dry friction increases with W content, the wear under DESs is slight when coatings show excellent wettability to DESs or a DES-derived tribochemical film is formed. We demonstrate that the tribological behavior of W-DLC and DESs composite lubrication system is related to the mechanical properties of W-DLC coatings together with the contact angle and tribochemical interaction between DESs and W-DLC coatings.
A review on thin films, conducting polymers as sensor devices
Authors: Elanjeitsenni Veera Prabakaran , Vadivu K Senthil , Prasanth B Mouli
Published: January 2022

Thin film sensors are used to monitor environmental conditions by measuring the physical parameters. By using thin film technology, the sensors are capable of conducting precise measurements. Moreover, the measurements are stable and dependable. Furthermore, inexpensive sensor devices can be produced. In this paper, thin film technology for the design and fabrication of sensors that are used in various applications is reviewed. Further, the applications of thin film sensors in the fields of biomedical, energy harvesting, optical, and corrosion applications are also presented. From the review, the future research needs and future perspectives are identified and discussed.
Perspectives on manufacturing simulations of Li-S battery cathodes
Authors: Arcelus Oier , Franco Alejandro A
Published: January 2022

Lithium-sulfur batteries (LSBs) are one of the main contenders for next generation post lithium-ion batteries (LIBs). As the process of scientific discovery advances, many of the challenges that prevent the commercial deployment of LSBs, especially at the most fundamental materials level, are slowly being addressed. However, batteries are complex systems that require not only the identifcation of suitable materials, but also require the knowledge of how to assemble and manufacture all the components together in order to obtain an optimally working battery. This is not a simple task, as battery manufacturing is a multi-stepped, multi-parameter, highly correlated process, where many parameters compete, and deep knowledge of the systems is required in order to achieve the optimal manufacturing conditions, which has already been shown in the case of LIBs. In these regards, manufacturing simulations have proven to be invaluable in order to advance in the knowledge of this exciting and technologically relevant field. Thus, in this work, we aim at providing future perspectives and opportunities that we think are interesting in order to create digital twins for the LSB manufacturing process. We also provide comprehensive and realistic ways in which already existing models could be adapted to LSBs in the short-term, and which are the challenges that might be found along the way.
Sharp quantitative stability for isoperimetric inequalities with homogeneous weights
Authors: Cinti E. , Glaudo F. , Pratelli A. , Ros-Oton X. , Serra J.
Published: January 2022

We prove the sharp quantitative stability for a wide class of weighted isoperimetric inequalities. More precisely, we consider isoperimetric inequalities in convex cones with homogeneous weights.

Inspired by the proof of such isoperimetric inequalities through the ABP method (see X. Cabré, X. Ros-Oton, and J. Serra [J. Eur. Math. Soc. (JEMS) 18 (2016), pp. 2971–2998]), we construct a new convex coupling (i.e., a map that is the gradient of a convex function) between a generic setEEand the minimizer of the inequality (as in Gromov’s proof of the isoperimetric inequality). Even if this map does not come from optimal transport, and even if there is a weight in the inequality, we adapt the methods of [Figalli, Maggi, and Pratelli [Invent. Math. 182 (2010), pp. 167–211] and prove that ifEEis almost optimal for the inequality then it is quantitatively close to a minimizerup to translations. Then, a delicate analysis is necessary to rule out the possibility of translations.

As a step of our proof, we establish a sharp regularity result forrestrictedconvex envelopes of a function that might be of independent interest.
Nanoscale dynamics of actin filaments in the red blood cell membrane skeleton
Authors: Nowak Roberta B. , Alimohamadi Haleh , Pestonjamasp Kersi , Rangamani Padmini , Fowler Velia M.
Published: January 2022

Fluorescence microscopy of F-actin in the red blood cell (RBC) spectrin network reveals brightly stained foci that depend on actin polymerization and undergo local nanoscale motions in live RBCs. Nanoscale clustering of F-actin nodes into foci requires reevaluation of RBC shape and membrane curvature models that rely on uniform network dimensions.
PP2A-dependent TFEB activation is blocked by PIKfyve-induced mTORC1 activity
Authors: Hasegawa Junya , Tokuda Emi , Yao Yao , Sasaki Takehiko , Inoki Ken , Weisman Lois S.
Published: January 2022

This work shows that PIKfyve activity is a key player in the negative regulation of the lysosome-related transcription factor, TFEB. This mechanistic study shows that the regulation is due to a requirement for PIKfyve in the mechanistic target of rapamycin complex 1-dependent phosphorylation of TFEB Ser-211, a key phospho-site that keeps TFEB in an inactive state in the cytoplasm.
Nir1 constitutively localizes at ER–PM junctions and promotes Nir2 recruitment for PIP2 homeostasis
Authors: Quintanilla Carlo Giovanni , Lee Wan-Ru , Liou Jen
Published: January 2022

Plasma membrane (PM) phosphatidylinositol 4,5-bisphosphate (PIP2) homeostasis in stimulated cells is mediated by recruiting the lipid transfer protein Nir2 to endoplasmic reticulum (ER)–PM junctions. In this article, Nir1 is identified as a novel ER–PM junction localized protein that promotes Nir2 recruitment for PIP2 homeostasis.
Perceptions, knowledge and attitudes about COVID-19 vaccine hesitancy in older Portuguese adults
Authors: Silva Tânia Magalhães , Estrela Marta , Roque Vítor , Gomes Eva Rebelo , Figueiras Adolfo , Roque Fátima , Herdeiro Maria Teresa
Published: January 2022

Background

Coronavirus 2019 (COVID-19) has become a public-health emergency of international concern. Most efforts to contain the spread and transmission of the virus rely on campaigns and interventions targeted to reduce Vaccine Hesitancy and Refusal (VHR).

Objective

this study aims to assess the major factors associated with VHR in the older population in Portugal.

Methods

a nation-wide cross-sectional study was conducted in the older Portuguese population (≥65 years old) through computer-assisted telephone interviewing. Logistic regression was used to determine the adjusted odds ratio (OR) of the independent variables (perceptions, knowledge and attitudes) and of the outcome (VHR).

Results

the response rate was 60.1% (602/1,001). Perceptions, knowledge and attitudes were strongly associated with VHR probability. A 1-point Likert scale increase in concerns about the vaccines’ efficacy and safety increased the risk of VHR by 1.96 (95% confidence interval [CI]: 1.40–6.28) and 3.13 (95%CI: 2.08–8.22), respectively. A reduction of VHR probability for ‘reliability of the information released by social media’ (OR = 0.34, 95%CI: 0.16–0.70) and for ‘trust in national and international competent authorities’ (OR = 0.34, 95%CI: 0.17–0.69) is also observed per 1-point increase.

Conclusions

as VHR seems to be strongly associated with perceptions, knowledge and attitudes, the design and promotion of vaccination campaigns/educational interventions specifically targeted at changing these potentially modifiable determinants may help to tackle COVID-19 VHR and achieve a wider vaccine coverage.
An Analysis of the Sensitivity of the Activated Partial Thromboplastin Time (APTT) Assay, as Used in a Large Laboratory Network, to Coagulation Factor Deficiencies
Authors: Do Louis , Favaloro Emmanuel , Pasalic Leonardo
Published: January 2022

Objectives

To advance knowledge in using the ex vivo method to identify factor sensitivity of the activated partial thromboplastin time (APTT), using data from a hemophilia and reference hemostasis laboratory; to evaluate application of inclusion and exclusion criteria to eliminate data outliers; and to discuss outcomes with reference to comparable studies.

Methods

An ex vivo, retrospective analysis was performed on patient samples with conjointly ordered APTT and intrinsic pathway factors (VIII, IX, XI, XII) for application to a large network of laboratories. The relationship between factor levels and APTT, before and after application of exclusion criteria, is demonstrated.

Results

Curvilinear relationships were found between all factor levels and APTTs, which demonstrated both similarities and differences with available studies. Factor sensitivity data are presented. Study strengths include large sample size and use of real-world data. Limitations include inability to exclude all residual outliers and paucity of patient samples singularly deficient in factors other than FVIII.

Conclusions

This ex vivo, retrospective analysis of the sensitivity of the APTT assay to intrinsic pathway factor deficiencies using real-world data from a hemophilia and reference hemostasis laboratory contains the largest sample size using this approach to date. The outcomes assist in informing practice in this area and can be used as a reference for further studies.
Current and investigational therapies for the treatment of refractory ventricular fibrillation
Authors: Scaturo Nicholas , Shomo Eileen , Frank Marshall
Published: January 2022

Purpose

Esmolol, dual sequential defibrillation, vector change defibrillation, and left stellate ganglion block are presented and reviewed for the treatment of refractory ventricular fibrillation.

Although no formal definition has been established for refractory ventricular fibrillation, the literature describes it as a pulseless ventricular arrhythmia that persists despite 3 standard defibrillation attempts, administration of amiodarone 300 mg intravenously, and provision of three 1-mg intravenous doses of epinephrine. Evolving literature surrounding resuscitation in this particular subset of cardiac arrest challenges the efficacy of traditional therapies, such as epinephrine, and suggests that other treatment modalities may improve outcomes. Case reports, case series, and small retrospective studies have pointed to benefit when utilizing a variety of therapies, namely, esmolol, dual sequential defibrillation, vector change defibrillation, or left stellate ganglion block, in patients with refractory ventricular fibrillation arrest.

Conclusion

A mounting, although limited, body of evidence suggests that esmolol, dual sequential defibrillation, vector change defibrillation, or left stellate ganglion block may be effective at terminating refractory ventricular fibrillation and improving patient outcomes. Further evidence is required before these therapies can be adopted as standard practice; however, as key members of the code response team, it is imperative for pharmacists to be familiar with the supporting evidence, safety considerations, and logistical challenges of utilizing these treatments during arrest.
A Comparison Between Ecological Momentary Assessment and the Adapted-Quick Drinking Screen: Alcohol Mixed With Energy Drinks
Authors: Johnson Sean J , Verster Joris C , Alford Chris
Published: January 2022

Aims

To compare alcohol consumption and risk-taking behaviours on alcohol mixed with energy drink (AMED) and alcohol-only (AO) drinking occasions collected via ecological momentary assessment (EMA) versus retrospective survey methods (adapted-Quick Drinking Screen: a-QDS).

Methods

Completing participants were 52 university students who reported AMED consumption during the 30-day data collection period. Alcohol consumption and risk-taking behaviours were captured for recreational AMED and AO consumption occasions using a smartphone-based app across 30 days. Data were aggregated for comparison with the a-QDS conducted at the end of data collection.

Results

Irrespective of data collection method, alcohol was consumed more frequently and at higher quantities on the heaviest drinking occasions when consumed alone compared with when it was mixed with energy drinks. Consistent with this finding, more risk-taking behaviours were experienced on AO occasions compared with AMED occasions. Compared with the a-QDS, the quantity of alcohol consumed on the average and heaviest drinking occasion was significantly higher when reported via EMA. This was consistent across both AO and AMED drinking occasions.

Conclusion

EMA provides a more valid measure of consumption quantity compared with retrospective recall, which was susceptible to under-reporting, although this was not differentially affected across consumption occasions. In line with previous research, this study demonstrated that mixing alcohol with energy drinks does not increase alcohol consumption or risk-taking behaviours.
Isolation of purple nonsulfur bacteria from the digestive tract of ayu (Plecoglossus altivelis)
Authors: Koga Aoi , Yamasaki Takumi , Hayashi Shuhei , Yamamoto Shinjiro , Miyasaka Hitoshi
Published: January 2022

Purple nonsulfur bacteria (PNSB) reportedly have probiotic effects in fish, but whether they are indigenous in the digestive tract of fish is a question that requires answering. We attempted to isolate PNSB from the digestive tract of ayu (Plecoglossus altivelis) from the Kuma River (Kumamoto, Japan) and successfully isolated 12 PNSB strains. All the isolated PNSB belonged to the genus Rhodopseudomonas. Five Rhodopseudomonas strains were also isolated from the soil samples collected along the Kuma River. The phylogenetic tree based on the partial sequence of pufLM gene indicated that the PNSB from ayu and soil were similar. The effects of NaCl concentration in growth medium on growth were also compared between the PNSB from ayu and soil. The PNSB from ayu showed a better growth performance at a higher NaCl concentration, suggesting that the intestinal tract of ayu, a euryhaline fish, might provide suitable environment for halophilic microorganisms.
A weighted bilinear neural collaborative filtering approach for drug repositioning
Authors: Meng Yajie , Lu Changcheng , Jin Min , Xu Junlin , Zeng Xiangxiang , Yang Jialiang
Published: January 2022

Drug repositioning is an efficient and promising strategy for traditional drug discovery and development. Many research efforts are focused on utilizing deep-learning approaches based on a heterogeneous network for modeling complex drug–disease associations. Similar to traditional latent factor models, which directly factorize drug–disease associations, they assume the neighbors are independent of each other in the network and thus tend to be ineffective to capture localized information. In this study, we propose a novel neighborhood and neighborhood interaction-based neural collaborative filtering approach (called DRWBNCF) to infer novel potential drugs for diseases. Specifically, we first construct three networks, including the known drug–disease association network, the drug–drug similarity and disease–disease similarity networks (using the nearest neighbors). To take the advantage of localized information in the three networks, we then design an integration component by proposing a new weighted bilinear graph convolution operation to integrate the information of the known drug–disease association, the drug’s and disease’s neighborhood and neighborhood interactions into a unified representation. Lastly, we introduce a prediction component, which utilizes the multi-layer perceptron optimized by the α-balanced focal loss function and graph regularization to model the complex drug–disease associations. Benchmarking comparisons on three datasets verified the effectiveness of DRWBNCF for drug repositioning. Importantly, the unknown drug–disease associations predicted by DRWBNCF were validated against clinical trials and three authoritative databases and we listed several new DRWBNCF-predicted potential drugs for breast cancer (e.g. valrubicin and teniposide) and small cell lung cancer (e.g. valrubicin and cytarabine).
Boar spermadhesin AWN: novel insights in its binding behavior and localization on sperm
Authors: Kroh Pascal D , Braun Beate C , Liu Fan , Müller Peter , Müller Karin
Published: January 2022

As a major spermadhesin first found in the seminal plasma (SP) of boars, AWN is described to fulfil a variety of reproduction related tasks. Although being the best investigated boar spermadhesin, information about its interaction with membranes is inconsistent. In this regard, previous reports locate AWN either inside or on the surface of sperm cells and at different regions, depending on the method and antibody used. Here, we localize native AWN (natAWN) in/on epididymal, ejaculated, capacitated, and acrosome-reacted boar sperm using epifluorescence and electron microscopy as well as an analysis of potential lipid-binding partners of natAWN and recombinant AWN (recAWN). By applying a custom-made anti-AWN antibody, localization of AWN in the equatorial segment (EQS) of ejaculated, capacitated, and acrosome-reacted boar sperm was discovered. Electron microscopy showed that AWN is localized both on the sperm surface and on the cytoplasmic side of the plasma membrane and in close vicinity to the nuclear and both acrosomal membranes of sperm. Analysis of epididymal sperm indicated migration of AWN from the retral postacrosomal part to the EQS during the epididymal passage. In contrast to hypotheses claiming a specific association of AWN to phosphatidylethanolamine (PE) and in line with our previous study describing an interaction with phosphatidic acid (PA), the current results show a rather electrostatically driven binding mechanism of AWN to negative lipids. In conclusion, this work provides new insights into the arrangement of AWN in the EQS, which suggest a possible role in sperm–oocyte fusion.
Estimation and false discovery control for the analysis of environmental mixtures
Authors: Samanta Srijata , Antonelli Joseph
Published: January 2022

The analysis of environmental mixtures is of growing importance in environmental epidemiology, and one of the key goals in such analyses is to identify exposures and their interactions that are associated with adverse health outcomes. Typical approaches utilize flexible regression models combined with variable selection to identify important exposures and estimate a potentially nonlinear relationship with the outcome of interest. Despite this surge in interest, no approaches to date can identify exposures and interactions while controlling any form of error rates with respect to exposure selection. We propose two novel approaches to estimating the health effects of environmental mixtures that simultaneously (i) estimate and provide valid inference for the overall mixture effect and (ii) identify important exposures and interactions while controlling the false discovery rate (FDR). We show that this can lead to substantial power gains to detect weak effects of environmental exposures. We apply our approaches to a study of persistent organic pollutants and find that controlling the FDR leads to substantially different conclusions.
Patho-immunological mechanisms of vitiligo: the role of the innate and adaptive immunities and environmental stress factors
Authors: Faraj Safa , Kemp Elizabeth Helen , Gawkrodger David John
Published: January 2022

Epidermal melanocyte loss in vitiligo, triggered by stresses ranging from trauma to emotional stress, chemical exposure or metabolite imbalance, to the unknown, can stimulate oxidative stress in pigment cells, which secrete damage-associated molecular patterns that then initiate innate immune responses. Antigen presentation to melanocytes leads to stimulation of autoreactive T-cell responses, with further targeting of pigment cells. Studies show a pathogenic basis for cellular stress, innate immune responses and adaptive immunity in vitiligo. Improved understanding of the aetiological mechanisms in vitiligo has already resulted in successful use of the Jak inhibitors in vitiligo. In this review, we outline the current understanding of the pathological mechanisms in vitiligo and locate loci to which therapeutic attack might be directed.
Predictive biomarker modeling of pediatric atopic dermatitis severity based on longitudinal serum collection
Authors: Engle Sarah M , Chang Ching-Yun , Ulrich Benjamin J , Satterwhite Allyson , Hayes Tristan , Robling Kim , Sissons Sean E , Schmitz Jochen , Tepper Robert S , Kaplan Mark H , Sims Jonathan T
Published: January 2022

The pathogenesis of atopic dermatitis (AD) results from complex interactions between environmental factors, barrier defects, and immune dysregulation resulting in systemic inflammation. Therefore, we sought to characterize circulating inflammatory profiles in pediatric AD patients and identify potential signaling nodes which drive disease heterogeneity and progression. We analyzed a sample set of 87 infants that were at high risk for atopic disease based on AD diagnoses. Clinical parameters, serum, and peripheral blood mononuclear cells (PBMCs) were collected upon entry, and at 1 and 4 years later. Within patient serum, 126 unique analytes were measured using a combination of multiplex platforms and ultrasensitive immunoassays. We assessed the correlation of inflammatory analytes with AD severity (SCORAD). Key biomarkers, such as IL-13 (rmcorr = 0.47) and TARC/CCL17 (rmcorr = 0.37), among other inflammatory signals, significantly correlated with SCORAD across all timepoints in the study. Flow cytometry and pathway analysis of these analytes implies that CD4 T-cell involvement in type 2 immune responses was enhanced at the earliest time point (year 1) relative to the end of study collection (year 5). Importantly, forward selection modeling identified 18 analytes in infant serum at study entry which could be used to predict change in SCORAD 4 years later. We have identified a pediatric AD biomarker signature linked to disease severity which will have predictive value in determining AD persistence in youth and provide utility in defining core systemic inflammatory signals linked to pathogenesis of atopic disease.
Molecular neuroimaging of inflammation in HIV
Authors: Alagaratnam Jasmini , Winston Alan
Published: January 2022

People with HIV now have near-normal life expectancies due to the success of effective combination antiretroviral therapy (cART). Following cART initiation, immune recovery occurs, and opportunistic diseases become rare. Despite this, high rates of non-infectious comorbidities persist in treated people with HIV, hypothesized to be related to persistent immuno-activation. One such comorbidity is cognitive impairment, which may partly be driven by ongoing neuro-inflammation in otherwise effectively treated people with HIV. In order to develop therapeutic interventions to address neuro-inflammation in effectively treated people with HIV, a deeper understanding of the pathogenic mechanisms driving persistent neuro-inflammatory responses and the ability to better characterize and measure neuro-inflammation in the central nervous system is required. This review highlights recent advances in molecular neuroimaging techniques which have the potential to assess neuro-inflammatory responses within the central nervous system in HIV disease. Proton magnetic resonance spectroscopy (1H-MRS) has been utilized to assess neuro-inflammatory responses since early in the HIV pandemic and shows promise in recent studies assessing different antiretroviral regimens. 1H-MRS is widely available in both resource-rich and some resource-constrained settings and is relatively inexpensive. Brain positron emission tomography (PET) imaging using Translocator Protein (TSPO) radioligands is a rapidly evolving field; newer TSPO-radioligands have lower signal-to-noise ratio and have the potential to localize neuro-inflammation within the brain in people with HIV. As HIV therapeutics evolve, people with HIV continue to age and develop age-related comorbidities including cognitive disorders. The use of novel neuroimaging modalities in the field is likely to advance in order to rapidly assess novel therapeutic interventions and may play a role in future clinical assessments.
Seroconversion following COVID-19 vaccination: can we optimize protective response in CD20-treated individuals?
Authors: Baker David , MacDougall Amy , Kang Angray S , Schmierer Klaus , Giovannoni Gavin , Dobson Ruth
Published: January 2022

Although there is an ever-increasing number of disease-modifying treatments for relapsing multiple sclerosis (MS), few appear to influence coronavirus disease 2019 (COVID-19) severity. There is concern about the use of anti-CD20-depleting monoclonal antibodies, due to the apparent increased risk of severe disease following severe acute respiratory syndrome corona virus two (SARS-CoV-2) infection and inhibition of protective anti-COVID-19 vaccine responses. These antibodies are given as maintenance infusions/injections and cause persistent depletion of CD20+ B cells, notably memory B-cell populations that may be instrumental in the control of relapsing MS. However, they also continuously deplete immature and mature/naïve B cells that form the precursors for infection-protective antibody responses, thus blunting vaccine responses. Seroconversion and maintained SARS-CoV-2 neutralizing antibody levels provide protection from COVID-19. However, it is evident that poor seroconversion occurs in the majority of individuals following initial and booster COVID-19 vaccinations, based on standard 6 monthly dosing intervals. Seroconversion may be optimized in the anti-CD20-treated population by vaccinating prior to treatment onset or using extended/delayed interval dosing (3–6 month extension to dosing interval) in those established on therapy, with B-cell monitoring until (1–3%) B-cell repopulation occurs prior to vaccination. Some people will take more than a year to replete and therefore protection may depend on either the vaccine-induced T-cell responses that typically occur or may require prophylactic, or rapid post-infection therapeutic, antibody or small-molecule antiviral treatment to optimize protection against COVID-19. Further studies are warranted to demonstrate the safety and efficacy of such approaches and whether or not immunity wanes prematurely as has been observed in the other populations.
IgLON5 autoimmunity tested positive in patients with isolated chronic insomnia disease
Authors: Aghelan Zahra , Karima Saeed , Ghadami Mohammad Rasoul , Khazaie Habibolah , Bahrehmand Fariborz , Vaisi-Raygani Asad , Abtahi Seyed Hosein , Khodarahmi Reza
Published: January 2022

In the patients with neurological autoimmune diseases such as anti-IgLON5 disease, insomnia symptoms are very common. Clinical diagnosis of the anti-IgLON5 disease is usually made when neurodegenerative processes have occurred. To find the early signs of anti-IgLON5 disease, we evaluate the presence of IgLON5 autoantibodies in the serum of patients with chronic insomnia disease. Based on video-polysomnography, 22 individuals with isolated chronic insomnia disease were found. A control group of 22 healthy people was chosen using the Pittsburgh Sleep Quality Index (PSQI). An indirect immunofluorescence cell-based test of serum anti-IgLON5 antibodies was used to investigate IgLON5 autoimmunity. Anti-IgLON5 antibodies were detected in the serum of four of these patients with the titer of 1/10. The presence of IgLON5 autoantibodies in some patients with chronic insomnia disease can be considered a causing factor of insomnia which can be effective in more specific treatments of these patients. Moreover, the recognition of anti-IgLON5 disease in the early stages and before the progression of tauopathies can be useful in effective and timely treatment.
Diagnosis of HLH: two siblings, two distinct genetic causes
Authors: Escaron Claire , Ralph Elizabeth , Bibi Shahnaz , Visser Johannes , Aricò Maurizio , Rao Kanchan , Veys Paul , Gilmour Kimberly
Published: January 2022

This report highlights case of two siblings who developed haemophagocytic lymphohystiocytosis due to distinct genetic abnormalities. Though their presentation was clinically similar, the cases demonstrate that a shared genetic diagnosis among siblings cannot be assumed.
Macrophages in ovarian cancer and their interactions with monoclonal antibody therapies
Authors: Osborn Gabriel , Stavraka Chara , Adams Rebecca , Sayasneh Ahmad , Ghosh Sharmistha , Montes Ana , Lacy Katie E , Kristeleit Rebecca , Spicer James , Josephs Debra H , Arnold James N , Karagiannis Sophia N
Published: January 2022

The unmet clinical need for effective treatments in ovarian cancer has yet to be addressed using monoclonal antibodies (mAbs), which have largely failed to overcome tumour-associated immunosuppression, restrict cancer growth, and significantly improve survival. In recent years, experimental mAb design has moved away from solely targeting ovarian tumours and instead sought to modulate the wider tumour microenvironment (TME). Tumour-associated macrophages (TAMs) may represent an attractive therapeutic target for mAbs in ovarian cancer due to their high abundance and close proximity to tumour cells and their active involvement in facilitating several pro-tumoural processes. Moreover, the expression of several antibody crystallisable fragment (Fc) receptors and broad phenotypic plasticity of TAMs provide opportunities to modulate TAM polarisation using mAbs to promote anti-tumoural phenotypes. In this review, we discuss the role of TAMs in ovarian cancer TME and the emerging strategies to target the contributions of these cells in tumour progression through the rationale design of mAbs.
Potential role of BAY11-7082, a NF-κB blocker inhibiting experimental autoimmune encephalomyelitis in C57BL/6J mice via declining NLRP3 inflammasomes
Authors: Lang Yue , Chu Fengna , Liu Lingling , Zheng Chao , Li Chunrong , Shen Donghui , Liu Shan , Zhang Weiguanliu , Cui Li , Zhu Jie
Published: January 2022

Multiple sclerosis (MS) is an inflammatory autoimmune demyelinating disease of the central nervous system. NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome is implicated in the pathogenesis of MS and its animal model, experimental autoimmune encephalomyelitis (EAE). However, the exact mechanism by which NLRP3 inflammasome is involved in the development of MS and EAE is not clear. NF-kappaB (NF-κB) is associated with the activity of NLRP3 inflammasomes, but the role of NF-κB is controversial. We sought to demonstrate that both NF-κB and NLRP3 contribute to development of MS and EAE, and NF-κB pathway is positively correlated with NLRP3 activation in EAE. The inhibitor of NF-κB and NLRP3, BAY11-7082, can prevent and treat EAE. BAY11-7082 (5 and 20 mg/kg/i.p.) was intraperitoneally administered to EAE mice at the time of second injection of pertussis toxin (BAY11-7082 prevention group) or at the onset of symptoms (BAY11-7082 treatment group). mRNA expressions of NLRP3 were determined by qPCR. Protein expressions of NLRP3, NF-κB p65, and phosphorylated p65 were determined by western blotting. Serum levels of inflammatory cytokines were measured by cytometric bead array. Mice treated with BAY11-7082 (both prevention and treatment groups) showed lower clinical scores and attenuated pathological changes. NLRP3 inflammasome and activity of NF-κB in spinal cord of EAE mice was higher than that in control group. However, the level of NLRP3 inflammasome decreased in BAY11-7082 prevention and treatment groups. BAY11-7082 is a promising therapeutic agent for MS. NLRP3 activation in EAE maybe related with NF-κB pathway.
Deciphering the Plasmodium falciparum malaria-specific CD4+ T-cell response: ex vivo detection of high frequencies of PD-1+TIGIT+ EXP1-specific CD4+ T cells using a novel HLA-DR11-restricted MHC class II tetramer
Authors: Schulte Sophia , Heide Janna , Ackermann Christin , Peine Sven , Ramharter Michael , Mackroth Maria Sophia , Woost Robin , Jacobs Thomas , Schulze zur Wiesch Julian
Published: January 2022

Relatively little is known about the ex vivo frequency and phenotype of the Plasmodium falciparum-specific CD4+ T-cell response in humans. The exported protein 1 (EXP1) is expressed by plasmodia at both, the liver stage and blood stage, of infection making it a potential target for CD4+ and CD8+ effector T cells. Here, a fluorochrome-labelled HLA-DRB1∗11:01-restriced MHC class II tetramer derived from the P. falciparum EXP1 (aa62-74) was established for ex vivo tetramer analysis and magnetic bead enrichment in 10 patients with acute malaria. EXP1-specific CD4+ T cells were detectable in 9 out of 10 (90%) malaria patients expressing the HLA-DRB1∗11 molecule with an average ex vivo frequency of 0.11% (0–0.22%) of total CD4+ T cells. The phenotype of EXP1-specific CD4+ T cells was further assessed using co-staining with activation (CD38, HLA-DR, CD26), differentiation (CD45RO, CCR7, KLRG1, CD127), senescence (CD57), and co-inhibitory (PD-1, TIGIT, LAG-3, TIM-3) markers as well as the ectonucleotidases CD39 and CD73. EXP1-specific tetramer+ CD4+ T cells had a distinct phenotype compared to bulk CD4+ T cells and displayed a highly activated effector memory phenotype with elevated levels of co-inhibitory receptors and activation markers: EXP1-specific CD4+ T cells universally expressed the co-inhibitory receptors PD-1 and TIGIT as well as the activation marker CD38 and showed elevated frequencies of CD39. These results demonstrate that MHC class II tetramer enrichment is a sensitive approach to investigate ex vivo antigen-specific CD4+ T cells in malaria patients that will aid further analysis of the role of CD4+ T cells during malaria.
Immunity and pain in the eye: focus on the ocular surface
Authors: Lasagni Vitar Romina Mayra , Bonelli Filippo , Rama Paolo , Ferrari Giulio
Published: January 2022

Most ocular diseases are associated with pain. While pain has been generally considered a mere (deleterious) additional symptom, it is now emerging that it is a key modulator of innate/adaptive immunity. Because the cornea receives the highest nerve density of the entire body, it is an ideal site to demonstrate interactions between pain and the immune response. Indeed, most neuropeptides involved in pain generation are also potent regulators of innate and adaptive leukocyte physiology. On the other hand, most inflammatory cells can modulate the generation of ocular pain through release of specific mediators (cytokines, chemokines, growth factors, and lipid mediators). This review will discuss the reciprocal role(s) of ocular surface (and specifically: corneal) pain on the immune response of the eye. Finally, we will discuss the clinical implications of such reciprocal interactions in the context of highly prevalent corneal diseases.
The role of lipid metabolism in shaping the expansion and the function of regulatory T cells
Authors: Pinzon Grimaldos Alessandra , Bini Simone , Pacella Ilenia , Rossi Alessandra , Di Costanzo Alessia , Minicocci Ilenia , D’Erasmo Laura , Arca Marcello , Piconese Silvia
Published: January 2022

Metabolic inflammation, defined as a chronic low-grade inflammation, is implicated in numerous metabolic diseases. In recent years, the role of regulatory T cells (Tregs) as key controllers of metabolic inflammation has emerged, but our comprehension on how different metabolic pathways influence Treg functions needs a deeper understanding. Here we focus on how circulating and intracellular lipid metabolism, in particular cholesterol metabolism, regulates Treg homeostasis, expansion, and functions. Cholesterol is carried through the bloodstream by circulating lipoproteins (chylomicrons, very low-density lipoproteins, low-density lipoproteins). Tregs are equipped with a wide array of metabolic sensors able to perceive and respond to changes in the lipid environment through the activation of different intracellular pathways thus conferring to these cells a crucial metabolic and functional plasticity. Nevertheless, altered cholesterol transport, as observed in genetic dyslipidemias and atherosclerosis, impairs Treg proliferation and function through defective cellular metabolism. The intracellular pathway devoted to the cholesterol synthesis is the mevalonate pathway and several studies have shown that this pathway is essential for Treg stability and suppressive activity. High cholesterol concentrations in the extracellular environment may induce massive accumulation of cholesterol inside the cell thus impairing nutrients sensors and inhibiting the mevalonate pathway. This review summarizes the current knowledge regarding the role of circulating and cellular cholesterol metabolism in the regulation of Treg metabolism and functions. In particular, we will discuss how different pathological conditions affecting cholesterol transport may affect cellular metabolism in Tregs.
Reference range of naïve T and T memory lymphocyte subsets in peripheral blood of healthy adult
Authors: Xia Ying , Liu Aqing , Li Wentao , Liu Yunhe , Zhang Guan , Ye Songshan , Zhao Zhijieruo , Shi Juan , Jia Yingjie , Liu Xu , Guo Yongtie , Chen Huayu , Yu Jianchun
Published: January 2022

Naïve T and T memory cell subsets are closely related to immune response and can provide important information for the diagnosis and treatment of immunological and hematological disorders. Lymphocyte compartment undergoes dramatic changes during adulthood; age-related reference values derived from healthy individuals are crucial. However, extensively detailed reference values of peripheral blood lymphocytes in the whole spectrum of adulthood detected by multi-color flow cytometry on a single platform are rare. Three hundred and nine healthy adult volunteers were recruited from Tianjin in China. The absolute counts and percentages of CD3+CD4+ T cells, CD3+CD8+ T cells, naïve T cells (Tn), T memory stem cells (Tscm), central memory T cells (Tcm), effector memory T cells (Tem), and terminal effector T cells (Tte) were detected by flow cytometry with single platform technologies. Reference range of absolute counts and percentage of T lymphocyte subsets were formulated by different age and gender. The results showed that Tn and Tscm cells, which had stem cell properties, decreased with aging; while, Tcm and Tem increased with aging, which increased from 18 to 64 years old but presented no significant change over the 65 years old. Gender had an influence on the fluctuation of lymphocyte subsets, the absolute count of CD3+CD8+, CD8+Tcm, CD8+Tem in males were higher than those in females. The reference values of percentages and absolute numbers of naïve T and T memory cell subsets can help doctors to understand the immune state of patients and evaluate conditions of prognosis then adjust the treatment for patients. (Chinese Clinic Trial Registry number: ChiCTR-IOR-17014139.)
Trauma moderates the development of the oscillatory dynamics serving working memory in a sex-specific manner
Authors: Killanin Abraham D , Embury Christine M , Picci Giorgia , Heinrichs-Graham Elizabeth , Wang Yu-Ping , Calhoun Vince D , Stephen Julia M , Wilson Tony W
Published: January 2022

Working memory, the ability to hold items in memory stores for further manipulation, is a higher order cognitive process that supports many aspects of daily life. Childhood trauma has been associated with altered cognitive development including particular deficits in verbal working memory (VWM), but the neural underpinnings remain poorly understood. Magnetoencephalography (MEG) studies of VWM have reliably shown decreased alpha activity in left-lateralized language regions during encoding, and increased alpha activity in parieto-occipital cortices during the maintenance phase. In this study, we examined whether childhood trauma affects behavioral performance and the oscillatory dynamics serving VWM using MEG in a cohort of 9- to 15-year-old youth. All participants completed a modified version of the UCLA Trauma History Profile and then performed a VWM task during MEG. Our findings indicated a sex-by-age-by-trauma three-way interaction, whereby younger females experiencing higher levels of trauma had the lowest d’ accuracy scores and the strongest positive correlations with age (i.e. older performed better). Likewise, females with higher levels of childhood trauma exhibited altered age-related alpha changes during the maintenance phase within the right temporal and parietal cortices. These findings suggest that trauma exposure may alter the developmental trajectory of neural oscillations serving VWM processing in a sex-specific way.
Diagnosis and Management of Bacterial Vaginosis: Summary of Evidence Reviewed for the 2021 Centers for Disease Control and Prevention Sexually Transmitted Infections Treatment Guidelines
Authors: Muzny Christina A , Balkus Jennifer , Mitchell Caroline , Sobel Jack D , Workowski Kimberly , Marrazzo Jeanne , Schwebke Jane R
Published: January 2022

In preparation for the 2021 Centers for Disease Control and Prevention (CDC) sexually transmitted infections (STIs) treatment guidelines, the CDC convened an advisory group in 2019 to examine recent literature addressing updates in the epidemiology, diagnosis, and management of STIs. This article summarizes recent data in each of these key topic areas as they pertain to bacterial vaginosis (BV), the most common cause of vaginal discharge. The evidence reviewed primarily focused on updates in the global epidemiology of BV, risk factors for BV, data supportive of sexual transmission of BV-associated bacteria, BV molecular diagnostic tests, and novel treatment regimens. Additionally, recent literature on alcohol abstinence in the setting of 5-nitroimidazole use was reviewed.