bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabarcoding in two isolated populations of wild roe deer (Capreolus capreolus) reveals variation in gastrointestinal nematode community composition between regions and among age classes
Authors: Beaumelle Camille , Redman Elizabeth M. , de Rijke Jill , Wit Janneke , Benabed Slimania , Debias François , Duhayer Jeanne , Pardonnet Sylvia , Poirel Marie-Thérèse , Capron Gilles , Chabot Stéphane , Rey Benjamin , Yannic Glenn , Gilleard John S. , Bourgoin Gilles
Published: December 2021

Background

Gastrointestinal nematodes are ubiquitous for both domestic and wild ungulates and have varying consequences for health and fitness. They exist as complex communities of multiple co-infecting species, and we have a limited understanding of how these communities vary in different hosts, regions and circumstances or of how this affects their impacts.

Methods

We have undertaken ITS2 rDNA nemabiome metabarcoding with next-generation sequencing on populations of nematode larvae isolated from 149 fecal samples of roe deer of different sex and age classes in the two isolated populations of Chizé and Trois Fontaines in France not co-grazing with any domestic ungulate species.

Results

We identified 100 amplified sequence variants (ASVs) that were assigned to 14 gastrointestinal nematode taxa overall at either genus (29%) or species (71%) level. These taxa were dominated by parasites classically found in cervids—e.g.Ostertagia leptospicularis,Spiculopteragiaspp. Higher parasite species diversity was present in the Trois Fontaines population than in the Chizé population including the presence of species more typically seen in domestic livestock (Haemonchus contortus,Bunostomumsp.,Cooperia punctata,Teladorsagia circumcincta). No differences in parasite species diversity or community composition were seen in the samples collected from three zones of differing habitat quality within the Chizé study area. Young roe deer hosted the highest diversity of gastrointestinal nematodes, with more pronounced effects of age apparent in Trois Fontaines. The effect of host age differed between gastrointestinal nematode species, e.g. there was little effect onO. leptospicularisbut a large effect onTrichostrongylusspp. No effect of host sex was detected in either site.

Conclusions

The presence of some livestock parasite species in the Trois Fontaines roe deer population was unexpected given the isolation of this population away from grazing domestic livestock since decades. Overall, our results illustrate the influence of host traits and the local environment on roe deer nemabiome and demonstrate the power of the nemabiome metabarcoding approach to elucidate the composition of gastrointestinal nematode communities in wildlife.

Graphical Abstract
Discovery of mosquitocides from fungal extracts through a high-throughput cytotoxicity-screening approach
Authors: Jin Liang , Niu Guodong , Guan Limei , Ramelow Julian , Zhan Zhigao , Zhou Xi , Li Jun
Published: December 2021

Background

Mosquitoes transmit a variety of diseases. Due to widespread insecticide resistance, new effective pesticides are urgently needed. Entomopathogenic fungi are widely utilized to control pest insects in agriculture. We hypothesized that certain fungal metabolites may be effective insecticides against mosquitoes.

Methods

A high-throughput cytotoxicity-based screening approach was developed to search for insecticidal compounds in our newly established global fungal extract library. We first determined cell survival rates after adding various fungal extracts. Candidate insecticides were further analyzed using traditional larval and adult survival bioassays.

Results

Twelve ethyl acetate extracts from a total of 192 fungal extracts displayed > 85% inhibition of cabbage looper ovary cell proliferation. Ten of these 12 candidates were confirmed to be toxic to Anopheles gambiae Sua5B cell line, and six showed > 85% inhibition of Anopheles mosquito cell growth. Further bioassays determined a LC50, the lethal concentration that kills 50% of larval or adult mosquitoes, of 122 µg/mL and 1.7 µg/mosquito, respectively, after 24 h for extract 76F6 from Penicillium toxicarium.

Conclusions

We established a high-throughput MTT-based cytotoxicity screening approach for the discovery of new mosquitocides from fungal extracts. We discovered a candidate extract from P. toxicarium that exhibited high toxicity to mosquito larvae and adults, and thus were able to demonstrate the value of our recently developed approach. The active fungal extracts discovered here are ideal candidates for further development as mosquitocides.

Graphical abstract
Seroprevalence of antibodies against Borrelia burgdorferi sensu lato in healthy blood donors in Romania: an update
Authors: Kalmár Zsuzsa , Briciu Violeta , Coroian Mircea , Flonta Mirela , Rădulescu Amanda-Lelia , Topan Adriana , Mihalca Andrei Daniel , Lupșe Mihaela
Published: December 2021

Background

The Borrelia burgdorferi sensu lato (s.l.) genogroup is the causative agent responsible for Lyme borreliosis, a common tick-borne infectious disease in some temperate regions of the Northern Hemisphere. In humans, the clinical manifestations of Lyme borreliosis vary from dermatological infection to severe systemic manifestations. In Romania, data on the seroprevalence of Lyme borreliosis and associated risk factors are scarce and outdated, as the only seroprevalence study with a large dataset was published more than 20 years ago. Therefore, the aim of the present study was to evaluate the seroprevalence for Borrelia burgdorferi s.l. in healthy blood donors from six Romanian counties and identify the associated risk factors.

Methods

The study was conducted among 1200 healthy blood donors aged between 18 and 65 years during November 2019 and September 2020 from six counties in the northwestern and central parts of Romania. A two-tiered testing strategy was applied. Positive and equivocal immunoenzymatic test results for IgG and IgM antibodies were further confirmed by Western blot.

Results

Serum samples from 20% of the blood donors had positive or equivocal IgG and IgM ELISA index values. In total, 2.3% of the serum samples for IgG and 1.8% for IgM were positive by Western blot. The seroprevalence for both antibodies varied between 1.5% (Satu-Mare) and 6.5% (Bistrița-Năsăud) in the six counties investigated. The highest seroprevalence was observed in men (4.7%), in blood donors performing their professional activities outdoors (4.2%), and in those aged  ≥ 56 years (8%).

Conclusions

These findings confirm the presence of specific IgG and IgM antibodies to B. burgdorferi s.l. among healthy blood donors from Romania. Furthermore, potential risk factors, such as gender, age, and behavior, associated with the presence of positive B. burgdorferi s.l. antibodies among healthy blood donors were identified.

Graphical Abstract
Cyathostomin resistance to moxidectin and combinations of anthelmintics in Australian horses
Authors: Abbas Ghazanfar , Ghafar Abdul , Hurley John , Bauquier Jenni , Beasley Anne , Wilkes Edwina J. A. , Jacobson Caroline , El-Hage Charles , Cudmore Lucy , Carrigan Peter , Tennent-Brown Brett , Gauci Charles G. , Nielsen Martin K. , Hughes Kristopher J. , Beveridge Ian , Jabbar Abdul
Published: December 2021

Background

Cyathostomins are the most important and common parasitic nematodes of horses, with > 50 species known to occur worldwide. The frequent and indiscriminate use of anthelmintics has resulted in the development of anthelmintic resistance (AR) in horse nematodes. In this study we assessed the efficacy of commonly used anthelmintics against cyathostomins in Australian thoroughbred horses.

Methods

Two drug efficacy trials per farm were conducted on two thoroughbred horse farms in the state of Victoria, Australia. In the first trial, the horses on Farm A were treated with single and combinations of anthelmintics, including oxfendazole (OFZ), abamectin (ABM), abamectin and morantel (ABM + MOR), moxidectin (MOX) and oxfendazole and pyrantel (OFZ + PYR), at the recommended doses, whereas the horses on Farm B only received MOX, at the recommended dose. The faecal egg count reduction test (FECRT) was used to determine the efficacy and egg reappearance period (ERP) of anthelmintics. Based on the results of the first trial, the efficacies of MOX and a combination of ABM + MOR were reassessed to confirm their activities against cyathostomins.

Results

Of the five anthelmintic products tested on Farm A, resistance against OFZ, ABM and OFZ + PYR was found, with efficacies of − 41% (− 195% lower confidence limit [LCL]), 73% (60% LCL) and 82% (66% LCL) at 2 weeks post-treatment, respectively. The FECRT showed high efficacies of MOX and ABM + MOR (100%) at 2 week post-treatment and shortened ERPs for these anthelmintics (ABM + MOR: 4 weeks; MOX: 5 weeks). Resistance to MOX was found on Farm B, with a reduced efficacy of 90% (70% LCL) and 89% (82% LCL) at 2 weeks post-treatment in trials one and two, respectively.

Conclusions

This study provides the first evidence of MOX- and multidrug-resistant (ABM and combinations of anthelmintics) cyathostomins in Australia and indicates the need for continuous surveillance of the efficacy of currently effective anthelmintics and large-scale investigations to assess the ERP for various anthelmintics.

Graphical Abstract
Effects of adenovirus-mediated knockdown of IRAK4 on synovitis in the osteoarthritis rabbit model
Authors: Li Muzhe , Li Huiyun , Ran Xun , Yin Han , Luo Xuling , Chen Zhiwei
Published: December 2021

Background

The use of interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitor as a treatment for the inflammatory joint disease is a promising method. However, its underlying mechanism in osteoarthritis (OA) remains unclear. The purpose of this study is to look into the effects of adenovirus-mediated knockdown of IRAK4 on synovitis in the OA rabbit model.

Methods

Ad-shIRAK4 was injected two weeks after anterior cruciate ligament resection. Six weeks later, the rabbits were killed. The expression of IRAK4, TNFR-associated factor 6(TRAF6), TGF-activated kinase 1(TAK1), p-IKB kinase (p-IKK), p-nuclear factor kappa-B (p-NFκB), p38, and p-p38 in the synovial membrane was detected by western blot, qRT-PCR, and immunohistochemistry analysis. Immunohistochemistry was to detect the expression of IRAK4 proteins in articular cartilage. H&E staining was to assess the pathological changes of synovium and cartilage. The levels of interleukin (IL)-1β, tumor necrosis factor-α(TNF-α), and MMP-13 in the synovial fluid were measured by ELISA. X-ray and micro-computerized tomography (μCT) scans were used to assess knee joint conditions and microstructure of subchondral bone.

Results

IRAK4 expression levels in synovial tissues of the OA model group exhibited a significant upward trend. Ad-shIRAK4 significantly reduced IRAK4 mRNA expression in synovium tissues. Notably, Ad-shIRAK4 suppressed the Toll-like receptor/interleukin-1 receptor (TLR/IL-1R) signaling. In addition, in the Ad-shIRAK4 treatment group, we can see less inflammatory cell infiltration and reduced hyperplasia and angiogenesis. The levels of IL-1β, TNF-α, and MMP-13 in the synovial fluid in the OA model group were significantly higher than that in the control group, which were reduced by Ad-shIRAK4 treatment. Finally, Results of HE stains, immunohistochemistry, and μCT showed that Ad-shIRAK4 treatment has a protective effect on cartilage damage.

Conclusions

IRAK4 is significantly upregulated in the synovium from the osteoarthritis rabbit model. In addition, Ad-shIRAK4 reduced the expression of IRAK4 and suppressed TLR/IL-1R signaling in the synovium from the osteoarthritis rabbit model. Ad-shIRAK4 could alleviate synovitis and cartilage degradation in the osteoarthritis rabbit model, and thus alleviate the symptoms of OA and prevent the progression of OA.

Graphical abstract
Circ-FBXW12 aggravates the development of diabetic nephropathy by binding to miR-31-5p to induce LIN28B
Authors: Sun Aidong , Sun Ningshuang , Liang Xiao , Hou Zhenbo
Published: December 2021

Background

The involvement of circular RNAs (circRNAs) in diabetic nephropathy (DN) has been gradually identified. In this study, we aimed to explore the functions of circRNA F-box/WD repeat-containing protein 12 (circ-FBXW12) in DN development.

Methods

Reverse transcription quantitative polymerase chain reaction (RT-qPCR) assay was performed for the levels of circ-FBXW12, FBXW12 mRNA, microRNA-31-5p (miR-31-5p) and Lin-28 homolog B (LIN28B) mRNA. RNase R assay was used to analyze the stability of circ-FBXW12. Cell Counting Kit-8 (CCK-8) assay, flow cytometry analysis and 5-ethynyl-2′- deoxyuridine (EdU) assay were employed to evaluate cell viability, cell cycle and proliferation, respectively. Enzyme linked immunosorbent assay (ELISA) was done to measure the concentrations of inflammatory cytokines. Western blot assay was conducted for protein levels. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) level were examined with commercial kits. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to verify the relationships among circ-FBXW12, miR-31-5p and LIN28B.

Results

Circ-FBXW12 level was increased in DN patients’ serums and high glucose (HG)-induced human mesangial cells (HMCs). Circ-FBXW12 knockdown suppressed cell proliferation, arrested cell cycle, reduced extracellular matrix (ECM) production and oxidative stress in HG-induced HMCs. Circ-FBXW12 was identified as the sponge for miR-31-5p, which then directly targeted LIN28B. MiR-31-5p inhibition reversed circ-FBXW12 knockdown-mediated effects on cell proliferation, cell cycle process, ECM production and oxidative in HG-triggered HMCs. Moreover, miR-31-5p overexpression showed similar results with circ-FBXW12 knockdown in HG-stimulated HMC progression, while LIN28B elevation reversed the effects.

Conclusion

Circ-FBXW12 knockdown suppressed HG-induced HMC growth, inflammation, ECM accumulation and oxidative stress by regulating miR-31-5p/LIN28B axis.
Serum free triiodothyronine is inversely associated with diabetic peripheral neuropathy but not with carotid atherosclerotic lesions in euthyroid patients with type 2 diabetes
Authors: Li Mei-Fang , Ke Jiang-Feng , Li Shuai , Wang Jun-Wei , Zhu Zhi-Hui , Li Jing-Bo
Published: December 2021

Background

The associations between serum free triiodothyronine (FT3) and diabetic peripheral neuropatprohy (DPN)/carotid atherosclerotic lesions in euthyroid patients with type 2 diabetes are still unclear. The purpose of our study was to explore the relations of FT3 to DPN and carotid atherosclerotic lesions in Chinese type 2 diabetes inpatients with euthyroid function.

Methods

2477 euthyroid inpatients with type 2 diabetes were recruited and they were stratified into quartiles by FT3 levels in this cross-sectional study. Peripheral neuropathy was assessed by neurological symptoms and signs as well as nerve conduction velocity tests. Carotid atherosclerotic lesions, including carotid intima-media thickness, plaque and stenosis, were evaluated by Doppler ultrasound.

Results

The prevalence of DPN in type 2 diabetic patients exhibited the significant decrease across the FT3 quartiles (23.5%, 20.9%, 18.8%, and 11.2%, respectively, p < 0.001). Multiple logistical regression analysis also revealed that FT3 quartiles were significantly and inversely associated with DPN. Compared with the subjects in the highest FT3 quartile, the adjusted odds ratios (95% confidence interval) of DPN from the first to third FT3 quartile were successively 2.338 (1.407–3.884), 1.903 (1.134–3.194) and 1.598 (0.960–1.125). The patients with DPN had significantly higher prevalence of carotid atherosclerotic lesions compared with non-DPN patients. However, no statistical association was observed between FT3 quartiles and carotid atherosclerotic lesions after adjusting for confounder factors.

Conclusions

Lower FT3 within the normal range was independently associated with DPN, but not with carotid atherosclerotic lesions in Chinese euthyroid inpatients with type 2 diabetes.
MusicCohort: Pilot feasibility of a protocol to assess students’ physical and mental health in a Canadian post-secondary school of music
Authors: Bruder Julius , Ballenberger Nikolaus , Villas Bethany , Haugan Charlotte , McKenzie Kimiko , Patel Zalak , Zalpour Christoff , Mevawala Amynah , Handl Melisa , Guptill Christine
Published: December 2021

Objective

Music-related physical and mental health conditions are common among post-secondary music students, with many studies reporting a prevalence greater than 70%. However, there is currently no consensus on appropriate, validated assessments for this population. The aim of this pilot study was to test the feasibility of an assessment protocol developed for a German longitudinal study with Canadian post-secondary music students, and to compare the health of music students to non-music students. Using a cross-sectional design, first-semester music and non-music control students were recruited at two campuses at the same university. Both groups completed questionnaires and physical testing, including range of motion, core strength, and pressure pain threshold. Nineteen music students and 50 non-music student controls participated in this study.

Results

The German protocol is feasible in a Canadian post-secondary setting. Canadian music students demonstrated similar health outcomes to those in the parent study. All participants demonstrated poorer mental and physical quality of life than the Canadian norms, though this was not statistically significant. The results of this study should be confirmed in a larger study. Future studies with larger sample sizes can provide further insight into the health of Canadian music students, providing a basis for prevention and intervention.
Epigenome-wide association studies: current knowledge, strategies and recommendations
Authors: Campagna Maria Pia , Xavier Alexandre , Lechner-Scott Jeannette , Maltby Vicky , Scott Rodney J. , Butzkueven Helmut , Jokubaitis Vilija G. , Lea Rodney A.
Published: December 2021

The aetiology and pathophysiology of complex diseases are driven by the interaction between genetic and environmental factors. The variability in risk and outcomes in these diseases are incompletely explained by genetics or environmental risk factors individually. Therefore, researchers are now exploring the epigenome, a biological interface at which genetics and the environment can interact. There is a growing body of evidence supporting the role of epigenetic mechanisms in complex disease pathophysiology. Epigenome-wide association studies (EWASes) investigate the association between a phenotype and epigenetic variants, most commonly DNA methylation. The decreasing cost of measuring epigenome-wide methylation and the increasing accessibility of bioinformatic pipelines have contributed to the rise in EWASes published in recent years. Here, we review the current literature on these EWASes and provide further recommendations and strategies for successfully conducting them. We have constrained our review to studies using methylation data as this is the most studied epigenetic mechanism; microarray-based data as whole-genome bisulphite sequencing remains prohibitively expensive for most laboratories; and blood-based studies due to the non-invasiveness of peripheral blood collection and availability of archived DNA, as well as the accessibility of publicly available blood-cell-based methylation data. Further, we address multiple novel areas of EWAS analysis that have not been covered in previous reviews: (1) longitudinal study designs, (2) the chip analysis methylation pipeline (ChAMP), (3) differentially methylated region (DMR) identification paradigms, (4) methylation quantitative trait loci (methQTL) analysis, (5) methylation age analysis and (6) identifying cell-specific differential methylation from mixed cell data using statistical deconvolution.
Alterations of DNA methylation were associated with the rapid growth of cortisol-producing adrenocortical adenoma during pregnancy
Authors: Wang Chuan , Sun Yujing , Yin Xiaofei , Feng Ruoqi , Feng Ruiying , Xu Mingyue , Liang Kai , Zhao Ruxing , Gu Gangli , Jiang Xuewen , Su Peng , Zhang Xiaofang , Liu Jinbo
Published: December 2021

Background

Cortisol-producing adrenocortical adenoma (CPA) during pregnancy rarely occurs in clinic. Growing evidence suggests that DNA methylation plays a key role in adrenocortical adenomas. The present study aims to examine the genome-wide DNA methylation profiles and identify the differences in DNA methylation signatures of non-pregnant and pregnant patients with CPA.

Results

Four pregnant and twelve non-pregnant patients with CPA were enrolled. The pregnant patients with CPA had higher serum cortisol, Estradiol, Progesterone, and human chorionic gonadotropin concentration, while having lower serum FSH (follicle-stimulating hormone) and luteinizing hormone concentrations (P < 0.01). Compared with the non-pregnant patients, the duration is shorter, and the growth rate of the tumor is faster in pregnant patients with CPA (P < 0.05). Morphology and cell proliferation assay showed that the percentage of Ki-67 positive cells in CPA were higher in pregnant group than non-pregnant group (8.0% vs 5.5%, P < 0.05). The DNA methylation analysis showed that Genome-wide DNA methylation signature difference between pregnant and non-pregnant with CPA, that the pregnant group had more hypermethylated DMPs (67.94% vs 22.16%) and less hypomethylated DMPs (32.93% vs 77.84%). The proportion of hypermethylated DMPs was relatively high on chromosomes 1 (9.68% vs 8.67%) and X (4.99% vs 3.35%) but lower on chromosome 2(7.98% vs 12.92%). In pregnant patients with CPA, 576 hypomethylated DMPs and 1109 hypermethylated DMPs were identified in the DNA promoter region. Bioinformatics analysis indicated that the Wnt/β-Catenin pathway, Ras/MAPK Pathway and PI3K-AKT Pathway were associated with the development of CPA during pregnancy.

Conclusions

Genome-wide DNA methylation profiling of CPA in non-pregnant and pregnant patients was identified in the present study. Alterations of DNA methylation were associated with the pathogenesis and exacerbation of CPA during pregnancy.
Novel pediatric granulomatosis with polyangiitis with a marked bloody pericardial effusion and bloody stool: a case report
Authors: Kato Memi , Jimbo Keisuke , Nagata Masumi , Endo Yoshiko , Kashiwagi Kosuke , Maruyama Kimiko , Ito Natsuki , Tokushima Kaori , Arai Nobuyasu , Kyodo Reiko , Sato Masamichi , Miyata Eri , Hosoi Kenji , Inage Eisuke , Ikuse Tamaki , Fukunaga Hideo , Kudo Takahiro , Shimizu Toshiaki
Published: December 2021

Background

Granulomatosis with polyangiitis (GPA) is a syndrome of refractory vasculitis involving the upper respiratory tract, lungs, kidneys, and systemic small and medium-sized arteries that affects all age groups. No pediatric case with a bloody pericardial effusion resulting in cardiac tamponade and co-existing hematochezia has been reported.

Case presentation

A 14-year-old boy was referred for evaluation of prolonged fever, chest pain, and intermittent hematochezia. Diagnostic imaging showed a prominent pericardial effusion. Immediately after admission, his systolic blood pressure decreased. Emergent pericardiocentesis resulted in aspiration of a massive amount of bloody pericardial fluid. This was diagnosed as cardiac tamponade because his blood pressure recovered immediately after the drainage. The patient had an elevated serine proteinase 3-anti-neutrophil cytoplasmic antibody (PR3-ANCA) level on serological examination. Head MRI showed thickening of nasal and sinusoidal mucosa and a cystic mass in the left sphenoid sinus. After ruling out malignancy based on the cytology of the effusion, chest MRI, and gallium scintigraphy, total colonoscopy showed multiple irregular-shaped aphthae from the right transverse colon to the cecum on the contralateral side of the mesenteric attachments. Biopsy specimens of aphthous lesions confirmed necrotizing granulomatous inflammation. A diagnosis of GPA was made based on these findings, and oral prednisolone (PSL) and azathioprine were started. The hematochezia disappeared rapidly, and no recurrence of pericardial effusion was seen after PSL tapering was completed. The PR3-ANCA level decreased into the normal range immediately after the initial therapy.

Conclusions

Pericarditis is a common cardiac complication of GPA, but there have been no reports of resultant cardiac tamponade. This is the first case of pediatric GPA with cardiac and gastrointestinal complications preceding the common symptoms such as respiratory or renal symptoms. A case of pediatric GPA with hematochezia is also extremely rare. In conclusion, serial measurement of ANCA levels is important in patients with persistent fever and bloody stool, such as in inflammatory bowel disease, to make the diagnosis of a vasculitic syndrome.
Rupatadine to prevent local allergic reactions to sublingual allergy immunotherapy: a case series
Authors: Ellis Anne K. , Connors Lori , Francoeur Marie-Josee , Mack Douglas P.
Published: December 2021

Background

Sublingual immunotherapy tablets (SLIT-T) are an effective treatment for allergic rhinitis (AR), but some patients experience local allergic reactions (LAR) in the first few weeks of treatment that can lead to treatment discontinuation. Although oral antihistamines are recommended for the treatment and pretreatment of LAR associated with SLIT-T, there are no clinical trial data to support this recommendation. Rupatadine is an H1 antihistamine that also inhibits platelet activating factor activity. The objective of this case series is to describe real-world clinical situations in which rupatadine was used to treat or mitigate SLIT-T–related LAR.

Case presentations

Five cases are presented by the managing allergist and off-label use of rupatadine is their expert opinion only. Patients in all 5 cases were treated with a SLIT-T (e.g. ragweed, tree, grass, or house dust mites) for the management of allergic rhinitis and experienced bothersome LAR with the first SLIT-T administration. In 3 cases, rupatadine 10 mg was administered for the immediate treatment of LAR (either in-office with the first SLIT-T dose or for subsequent LAR experienced at home) and the symptoms resolved. In 3 cases, pretreatment with other second-generation H1 antihistamines was unable to prevent LAR and the patients discontinued the SLIT-T. In these 3 cases, switching to pretreatment with rupatadine allowed the patients to restart and tolerate SLIT-T treatment with minimal or no LAR. In these patients with an established history of LAR, proactive pretreatment with rupatadine in subsequent seasons or with initiation of a different SLIT-T mitigated the previously experienced LARs.

Conclusions

In the cases presented, treatment with rupatadine resolved LAR associated with SLIT-T treatment and rupatadine pretreatment appeared to mitigate subsequent LAR. Rupatadine may be an option to treat or improve the tolerability of the SLIT-T, potentially improving early treatment persistence.
Spinal disorders mimicking infection
Authors: Boudabbous Sana , Paulin Emilie Nicodème , Delattre Bénédicte Marie Anne , Hamard Marion , Vargas Maria Isabel
Published: December 2021

Spinal infections are very commonly encountered by radiologists in their routine clinical practice. In case of typical MRI features, the diagnosis is relatively easy to interpret, all the more so if the clinical and laboratory findings are in agreement with the radiological findings. In many cases, the radiologist is able to make the right diagnosis, thereby avoiding a disco-vertebral biopsy, which is technically challenging and associated with a risk of negative results. However, several diseases mimic similar patterns, such as degenerative changes (Modic) and crystal-induced discopathy. Differentiation between these diagnoses relies on imaging changes in endplate contours as well as in disc signal. This review sought to illustrate the imaging pattern of spinal diseases mimicking an infection and to define characteristic MRI and CT patterns allowing to distinguish between these different disco-vertebral disorders. The contribution of advanced techniques, such as DWI and dual-energy CT (DECT) is also discussed.
Magnetic resonance imaging-based body composition is associated with nutritional and inflammatory status: a longitudinal study in patients with Crohn's disease
Authors: Zhou Ziling , Xiong Ziman , Shen Yaqi , Li Zhen , Hu Xuemei , Hu Daoyu
Published: December 2021

Objective

To evaluate the changes in magnetic resonance imaging-based body composition parameters during follow-ups in patients with Crohn's disease (CD).

Methods

Between November 1, 2017, and June 30, 2021, patients diagnosed with CD, who underwent two or more magnetic resonance enterography (MRE) scans at our institution were retrospectively reviewed. The baseline and one subsequent follow-up scan for each patient were paired to form longitudinal comparisons. Skeletal muscle, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) indexes were calculated from tissue areas measured at the third lumbar vertebra level per scan, standardized by dividing the height2 and lumbar height2 (heightL1–L5). We also assessed the correlation between changes in VAT to total adipose tissue ratio (VA/TA index) and CD activity scores (5-point MRE classification) using Spearman’s correlation analysis. A multivariate linear regression model was used to adjust for the follow-up duration and treatment type.

Results

Overall, 49 patients (with 49 paired scans) were enrolled. VA/TA index changes were negatively correlated with changes in skeletal muscle index (SMI; r =  − 0.339, p < 0.05). The VA/TA index (52.69 ± 10.66% vs. 49.18 ± 10.80%, p < 0.001) and the total MRE score (8.0 ± 3.9 vs. 5.7 ± 3.4, p < 0.001) decreased significantly during follow-up, regardless of follow-up duration and treatment type (both p > 0.05). Changes in total MRE score were negatively correlated with SMI changes (r =  − 0.408, p < 0.01) but positively correlated with VA/TA index changes (r = 0.479, p < 0.01).

Conclusion

An increase in SMI and a decrease in VA/TA index could reflect improved nutritional and inflammatory status.
Magnetism of materials: theory and practice in magnetic resonance imaging
Authors: Gaeta Michele , Cavallaro Marco , Vinci Sergio Lucio , Mormina Enricomaria , Blandino Alfredo , Marino Maria Adele , Granata Francesca , Tessitore Agostino , Galletta Karol , D’Angelo Tommaso , Visalli Carmela
Published: December 2021

All substances exert magnetic properties in some extent when placed in an external magnetic field. Magnetic susceptibility represents a measure of the magnitude of magnetization of a certain substance when the external magnetic field is applied. Depending on the tendency to be repelled or attracted by the magnetic field and in the latter case on the magnitude of this effect, materials can be classified as diamagnetic or paramagnetic, superparamagnetic and ferromagnetic, respectively. Knowledge of type and extent of susceptibility of common endogenous and exogenous substances and how their magnetic properties affect the conventional sequences used in magnetic resonance imaging (MRI) can help recognize them and exalt or minimize their presence in the acquired images, so as to improve diagnosis in a wide variety of benign and malignant diseases. Furthermore, in the context of diamagnetic susceptibility, chemical shift imaging enables to assess the intra-voxel ratio between water and fat content, analyzing the tissue composition of various organs and allowing a precise fat quantification. The following article reviews the fundamental physical principles of magnetic susceptibility and examines the magnetic properties of the principal endogenous and exogenous substances of interest in MRI, providing potential through representative cases for improved diagnosis in daily clinical routine.
Genome-wide differential expression profiling of lncRNAs and mRNAs in human induced pluripotent stem cell-derived endothelial cells exposed to e-cigarette extract
Authors: Le Hoai Huong Thi , Liu Chen-wei , Denaro Philip , Jousma Jordan , Shao Ning-Yi , Rahman Irfan , Lee Won Hee
Published: December 2021

Background

Electronic-cigarette (e-cig) usage, particularly in the youth population, is a growing concern. It is known that e-cig causes endothelial dysfunction, which is a risk factor for the development of cardiovascular diseases; however, the mechanisms involved remain unclear. We hypothesized that long noncoding RNAs (lncRNAs) may play a role in e-cig-induced endothelial dysfunction.

Methods

Here, we identified lncRNAs that are dysregulated in human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) following 24 h of e-cig aerosol extract treatment via microarray analysis. We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analyses of the dysregulated mRNAs following e-cig exposure and constructed co-expression networks of the top 5 upregulated lncRNAs and the top 5 downregulated lncRNAs and the mRNAs that are correlated with them. Furthermore, the functional effects of knocking down lncRNA lung cancer-associated transcript 1 (LUCAT1) on EC phenotypes were determined as it was one of the significantly upregulated lncRNAs following e-cig exposure based on our profiling.

Results

183 lncRNAs and 132 mRNAs were found to be upregulated, whereas 297 lncRNAs and 413 mRNAs were found to be downregulated after e-cig exposure. We also observed that e-cig caused dysregulation of endothelial metabolism resulting in increased FAO activity, higher mitochondrial membrane potential, and decreased glucose uptake and glycolysis. These results suggest that e-cig alters EC metabolism by increasing FAO to compensate for energy deficiency in ECs. Finally, the knockdown of LUCAT1 prevented e-cig-induced EC dysfunction by maintaining  vascular barrier, reducing reactive oxygen species level, and increasing migration capacity.

Conclusion

This study identifies an expression profile of differentially expressed lncRNAs and several potential regulators and pathways in ECs exposed to e-cig, which provide insights into the regulation of lncRNAs and mRNAs and the role of lncRNA and mRNA networks in ECs associated e-cig exposure.
Cytokine-induced memory-like natural killer cells for cancer immunotherapy
Authors: Tarannum Mubin , Romee Rizwan
Published: December 2021

Natural killer cells are an important part of the innate immune system mediating robust responses to virus-infected and malignant cells without needing prior antigen priming. NK cells have always been thought to be short-lived and with no antigen specificity; however, recent data support the presence of NK cell memory including in the hapten-specific contact hypersensitivity model and in certain viral infections. The memory-like features can also be generated by short-term activation of both murine and human NK cells with cytokine combination of IL-12, IL-15 and IL-18, imparting increased longevity and enhanced anticancer functionality. Preclinical studies and very early clinical trials demonstrate safety and very promising clinical activity of these cytokine-induced memory-like (CIML) NK cells, making them an attractive cell type for developing novel adoptive cellular immunotherapy strategies. Furthermore, efforts are on to arm them with novel gene constructs for enhanced tumor targeting and function.
A novel mutation of SATB2 inhibits odontogenesis of human dental pulp stem cells through Wnt/β-catenin signaling pathway
Authors: Xin Tianyi , Li Qian , Bai Rushui , Zhang Ting , Zhou Yanheng , Zhang Yuehua , Han Bing , Yang Ruili
Published: December 2021

Background

SATB2-associated syndrome (SAS) is a multisystem disorder caused by mutation of humanSATB2gene. Tooth agenesis is one of the most common phenotypes observed in SAS. Our study aimed at identifying novel variant of SATB2 in a patient with SAS, and to investigate the cellular and molecular mechanism of tooth agenesis caused bySATB2mutation.

Methods

We applied whole exome sequencing (WES) to identify the novel mutation ofSATB2in a Chinese patient with SAS. Construction and overexpression of wild-type and the mutant vector was performed, followed by functional analysis including flow cytometry assay, fluorescent immunocytochemistry, western blot, quantitative real-time PCR and Alizarin Red S staining to investigate its impact on hDPSCs and the underlying mechanisms.

Results

As a result, we identified a novel frameshift mutation ofSATB2(c. 376_378delinsTT) in a patient with SAS exhibiting tooth agenesis. Human DPSCs transfected with mutant SATB2 showed decreased cell proliferation and odontogenic differentiation capacity compared with hDPSCs transfected with wild-type SATB2 plasmid. Mechanistically, mutant SATB2 failed to translocate into nucleus and distributed in the cytoplasm, failing to activate Wnt/β-catenin signaling pathway, whereas the wild-type SATB2 translocated into the nucleus and upregulated the expression of activeβ-catenin. When we used Wnt inhibitor XAV939 to treat hDPSCs transfected with wild-type SATB2 plasmid, the increased odontogenic differentiation capacity was attenuated. Furthermore, we found that SATB2 mutation resulted in the upregulation of DKK1 and histone demethylase JHDM1D to inhibit Wnt/β-catenin signaling pathway.

Conclusion

We identified a novel frameshift mutation of SATB2 (c.376_378delinsTT, p.Leu126SerfsX6) in a Chinese patient withSATB2-associated syndrome (SAS) exhibiting tooth agenesis. Mechanistically, SATB2 regulated osteo/odontogenesis of human dental pulp stem cells through Wnt/β-catenin signaling pathway by regulating DKK1 and histone demethylase JHDM1D.
MSCs and their exosomes: a rapidly evolving approach in the context of cutaneous wounds therapy
Authors: Marofi Faroogh , Alexandrovna Kozlitina Iuliia , Margiana Ria , Bahramali Mahta , Suksatan Wanich , Abdelbasset Walid Kamal , Chupradit Supat , Nasimi Maryam , Maashi Marwah Suliman
Published: December 2021

Currently, mesenchymal stem/stromal stem cell (MSC) therapy has become a promising option for accelerating cutaneous wound healing. In vivo reports have outlined the robust competences of MSCs to offer a solid milieu by inhibition of inflammatory reactions, which in turn, enables skin regeneration. Further, due to their great potential to stimulate angiogenesis and also facilitate matrix remodeling, MSCs hold substantial potential as future therapeutic strategies in this context. The MSCs-induced wound healing is thought to mainly rely on the secretion of a myriad of paracrine factors in addition to their direct differentiation to skin-resident cells. Besides, MSCs-derived exosomes as nanoscale and closed membrane vesicles have recently been suggested as an effective and cell-free approach to support skin regeneration, circumventing the concerns respecting direct application of MSCs. The MSCs-derived exosomes comprise molecular components including lipid, proteins, DNA, microRNA, and also mRNA, which target molecular pathways and also biological activities in recipient cells (e.g., endothelial cell, keratinocyte, and fibroblast). The secreted exosome modifies macrophage activation, stimulates angiogenesis, and instigates keratinocytes and dermal fibroblast proliferations as well as migrations concurrently regulate inherent potential of myofibroblast for adjustment of turnover of the ECM. In the present review, we will focus on the recent findings concerning the application of MSCs and their derivative exosome to support wound healing and skin regeneration, with special focus on last decade in vivo reports.
Role of PD-L1 in licensing immunoregulatory function of dental pulp mesenchymal stem cells
Authors: Di Tinco Rosanna , Bertani Giulia , Pisciotta Alessandra , Bertoni Laura , Pignatti Elisa , Maccaferri Monia , Bertacchini Jessika , Sena Paola , Vallarola Antonio , Tupler Rossella , Croci Stefania , Bonacini Martina , Salvarani Carlo , Carnevale Gianluca
Published: December 2021

Background

Dental pulp stem cells (DPSCs) are low immunogenic and hold immunomodulatory properties that, along with their well-established multi-potency, might enhance their potential application in autoimmune and inflammatory diseases. The present study focused on the ability of DPSCs to modulate the inflammatory microenvironment through PD1/PD-L1 pathway.

Methods

Inflammatory microenvironment was created in vitro by the activation of T cells isolated from healthy donors and rheumatoid arthritis (RA) patients with anti-CD3 and anti-CD28 antibodies. Direct and indirect co-cultures between DPSCs and PBMCs were carried out to evaluate the activation of immunomodulatory checkpoints in DPSCs and the inflammatory pattern in PBMCs.

Results

Our data suggest that the inflammatory stimuli trigger DPSCs immunoregulatory functions that can be exerted by both direct and indirect contact. As demonstrated by using a selective PD-L1 inhibitor, DPSCs were able to activate compensatory pathways targeting to orchestrate the inflammatory process by modulating pro-inflammatory cytokines in pre-activated T lymphocytes. The involvement of PD-L1 mechanism was also observed in autologous inflammatory status (pulpitis) and after direct exposure to pre-activated T cells from RA patients suggesting that immunomodulatory/anti-inflammatory properties are strictly related to their stemness status.

Conclusions

Our findings point out that the communication with the inflammatory microenvironment is essential in licensing their immunomodulatory properties.
Receiver selection for multi-target tracking in multi-static Doppler radar systems
Authors: Zhu Yun , Zhao Li , Zhang Yumei , Wu Xiaojun
Published: December 2021

This paper presents a novel receiver selection method for multi-target tracking in multi-static Doppler radar systems. The assumption is that in the surveillance volume of interest, a single transmitter with a known frequency is active and several spatially distributed radar receivers collect and report Doppler-only measurements. The Doppler measurements are not only affected by the additive noise but also contaminated by false and missed detections. In this paper, multi-target tracking is obtained by modeling the multi-target state as a labeled multi-Bernoulli random finite set and receiver selection is implemented during tracking. Receiver selection is solved under the partially observed Markov decision framework, and the variance of the cardinality estimate is used as the selection criterion. To increase the diversity of the selected sensors and overcome the low observability of the Doppler measurement, the receivers selected at previous time steps are taken into account by adding a window. Simulation studies demonstrate the tracking performance of the proposed method with different window lengths. The results show that the observability of the target state is a crucial factor in determining the performance of receiver selection. The proposed method with a suitable window length can effectively improve the tracking accuracy.
Detection of illicit cryptomining using network metadata
Authors: Russo Michele , Šrndić Nedim , Laskov Pavel
Published: December 2021

Illicit cryptocurrency mining has become one of the prevalent methods for monetization of computer security incidents. In this attack, victims’ computing resources are abused to mine cryptocurrency for the benefit of attackers. The most popular illicitly mined digital coin is Monero as it provides strong anonymity and is efficiently mined on CPUs.Illicit mining crucially relies on communication between compromised systems and remote mining pools using the de facto standard protocol Stratum. While prior research primarily focused on endpoint-based detection of in-browser mining, in this paper, we address network-based detection of cryptomining malware in general. We propose XMR-Ray, a machine learning detector using novel features based on reconstructing the Stratum protocol from raw NetFlow records. Our detector is trained offline using only mining traffic and does not require privacy-sensitive normal network traffic, which facilitates its adoption and integration.In our experiments, XMR-Ray attained 98.94% detection rate at 0.05% false alarm rate, outperforming the closest competitor. Our evaluation furthermore demonstrates that it reliably detects previously unseen mining pools, is robust against common obfuscation techniques such as encryption and proxies, and is applicable to mining in the browser or by compiled binaries. Finally, by deploying our detector in a large university network, we show its effectiveness in protecting real-world systems.
Text-to-speech system for low-resource language using cross-lingual transfer learning and data augmentation
Authors: Byambadorj Zolzaya , Nishimura Ryota , Ayush Altangerel , Ohta Kengo , Kitaoka Norihide
Published: December 2021

Deep learning techniques are currently being applied in automated text-to-speech (TTS) systems, resulting in significant improvements in performance. However, these methods require large amounts of text-speech paired data for model training, and collecting this data is costly. Therefore, in this paper, we propose a single-speaker TTS system containing both a spectrogram prediction network and a neural vocoder for the target language, using only 30 min of target language text-speech paired data for training. We evaluate three approaches for training the spectrogram prediction models of our TTS system, which produce mel-spectrograms from the input phoneme sequence: (1) cross-lingual transfer learning, (2) data augmentation, and (3) a combination of the previous two methods. In the cross-lingual transfer learning method, we used two high-resource language datasets, English (24 h) and Japanese (10 h). We also used 30 min of target language data for training in all three approaches, and for generating the augmented data used for training in methods 2 and 3. We found that using both cross-lingual transfer learning and augmented data during training resulted in the most natural synthesized target speech output. We also compare single-speaker and multi-speaker training methods, using sequential and simultaneous training, respectively. The multi-speaker models were found to be more effective for constructing a single-speaker, low-resource TTS model. In addition, we trained two Parallel WaveGAN (PWG) neural vocoders, one using 13 h of our augmented data with 30 min of target language data and one using the entire 12 h of the original target language dataset. Our subjective AB preference test indicated that the neural vocoder trained with augmented data achieved almost the same perceived speech quality as the vocoder trained with the entire target language dataset. Overall, we found that our proposed TTS system consisting of a spectrogram prediction network and a PWG neural vocoder was able to achieve reasonable performance using only 30 min of target language training data. We also found that by using 3 h of target language data, for training the model and for generating augmented data, our proposed TTS model was able to achieve performance very similar to that of the baseline model, which was trained with 12 h of target language data.