bluuebunny/crossref_metadata_2025 huggingface dataset:
Switching first-line targeted therapy after not reaching low disease activity within 6 months is superior to conservative approach: a propensity score-matched analysis from the ATTRA registry
Authors: Nekvindová Lucie , Vencovský Jiří , Pavelka Karel , Horák Pavel , Křístková Zlatuše , Závada Jakub
Published: January 2021

Background

Treat-to-target (T2T) is a widely accepted strategy for patients with rheumatoid arthritis (RA). It recommends attaining a goal of at least low disease activity (LDA) within 6 months; otherwise, the current therapy should be modified. We aimed to investigate whether switching a first-line targeted therapy (TT) in patients not reaching LDA within 6 months leads to a higher probability of meeting LDA at the 12-month visit in daily clinical practice using data from Czech registry ATTRA.

Methods

We included patients with RA starting the first-line TT from 1 January 2012 to 31 January 2017 with at least 1-year follow-up. We created four mutually exclusive cohorts based on (1) switching to another TT within the first year and (2) reaching a treatment target (DAS28-ESR ≤ 3.2) at the 6-month visit. The primary outcome was the comparison of odds for reaching remission (REM) or LDA at the 12-month visit between patients switching and not switching TT after not reaching treatment target at 6 months. Before using logistic regression to estimate the odds ratio, we employed the propensity score to match patients at the 6-month visit.

Results

A total of 1275 patients were eligible for the analysis. Sixty-two patients switched within the first 5 months of the treatment before evaluating treatment response at the 6-month visit (C1); 598 patients reached the treatment target within 6 months of therapy (C2); 124 patients did not reach treatment response at 6-month visit and switched to another therapy (C3), and 491 patients continued with the same treatment despite not reaching LDA at the 6-month visit (C4). We matched 75 patients from cohort C3 and 75 patients from C4 using the propensity score. Patients following the T2T principle (C3) showed 2.8 (95% CI 1.4–5.8;p = 0.005) times increased likelihood of achieving REM/LDA at the 12-month visit compared to patients not following the T2T strategy (C4).

Conclusions

In daily clinical practice, the application of the T2T strategy is underused. Switching TT after not reaching REM/LDA within the first 6 months leads to a higher probability of achieving REM/LDA in RA patients at the 12-month visit.
Associations between metabolic syndrome and type of dementia: analysis based on the National Health Insurance Service database of Gangwon province in South Korea
Authors: Kim Yeo Jin , Kim Sang Mi , Jeong Dae Hyun , Lee Sang-Kyu , Ahn Moo-Eob , Ryu Ohk-Hyun
Published: January 2021

Background

Metabolic syndrome is a cluster of conditions that occur together, increasing the risk of cardiovascular disease. However, the relationship between metabolic syndrome and dementia has remained controversial. Using nationwide population cohort data, we investigated the association between metabolic syndrome and dementia, according to the dementia type.

Methods

We analyzed data of 84,144 individuals, in the aged group of more than 60 years, between January 1, 2009, to December 31, 2009, at Gangwon province by using the information of the (Korean) National Health Insurance Service. After eight years of gap, in 2017, we investigated the relationship between metabolic syndrome and dementia. We classified Dementia either as dementia of the Alzheimer type (AD) or vascular dementia (VD). AD and VD were defined as per the criteria of International Classification of Disease, Tenth Revision, Clinical Modification codes. Multiple logistic regression analyses examined the associations between metabolic syndrome or five metabolic syndrome components and dementia. Analyses included factors like age, sex, smoking, alcohol, physical inactivity, previous stroke, and previous cardiac disease.

Results

Metabolic syndrome was associated with AD (OR = 11.48, 95% CI 9.03–14.59), not with VD. Each of five components of metabolic syndrome were also associated with AD. (high serum triglycerides: OR = 1.87, 95% CI 1.60–2.19; high blood pressure: OR = 1.85, 95% CI 1.55–2.21; high glucose: OR = 1.77, 95% CI 1.52–2.06; abdominal obesity: OR = 1.88, 95% CI 1.57–2.25; low serum high-density lipoprotein cholesterol: OR = 1.91, 95% CI 1.63–2.24) However, among components of metabolic syndrome, only the high glucose level was associated with VD. (OR = 1.26, 95% CI 1.01–1.56) body mass index (BMI), fasting glucose, and smoking were also associated with AD. (BMI: OR = 0.951, 95% CI 0.927–0.975; fasting glucose: OR = 1.003, 95% CI 1.001–1.005; smoking: OR = 1.020, 95% CI 1.003–1.039) A history of the previous stroke was associated with both AD and VD. (AD: OR = 1.827, 95% CI 1.263–2.644; VD: OR 2.775, 95% CI 1.747–4.406)

Conclusions

Metabolic syndrome was associated with AD but not with VD. Patients with metabolic syndrome had an 11.48 times more likeliness to develop AD compared to those without metabolic syndrome. VD was associated only with several risk factors that could affect the vascular state rather than a metabolic syndrome. We suggested that the associations between metabolic syndrome and dementia would vary depending on the type of dementia.
Transposable element-derived sequences in vertebrate development
Authors: Etchegaray Ema , Naville Magali , Volff Jean-Nicolas , Haftek-Terreau Zofia
Published: January 2021

Transposable elements (TEs) are major components of all vertebrate genomes that can cause deleterious insertions and genomic instability. However, depending on the specific genomic context of their insertion site, TE sequences can sometimes get positively selected, leading to what are called “exaptation” events. TE sequence exaptation constitutes an important source of novelties for gene, genome and organism evolution, giving rise to new regulatory sequences, protein-coding exons/genes and non-coding RNAs, which can play various roles beneficial to the host. In this review, we focus on the development of vertebrates, which present many derived traits such as bones, adaptive immunity and a complex brain. We illustrate how TE-derived sequences have given rise to developmental innovations in vertebrates and how they thereby contributed to the evolutionary success of this lineage.
Composition of the metabolomic bio-coronas isolated from Ocimum sanctum and Rubia tinctorum
Authors: Kurepa Jasmina , Smalle Jan A.
Published: January 2021

Objective

Nanoharvesting from intact plants, organs, and cultured cells is a method in which nanoparticles are co-incubated with the target tissue, which leads to the internalization of nanoparticles. Internalized nanoparticles are coated in situ with specific metabolites that form a dynamic surface layer called a bio-corona. Our previous study showed that metabolites that form the bio-corona around anatase TiO2 nanoparticles incubated with leaves of the model plant Arabidopsis thaliana are enriched for flavonoids and lipids. The present study focused on the identification of metabolites isolated by nanoharvesting from two medicinal plants, Ocimum sanctum (Tulsi) and Rubia tinctorum (common madder).

Results

To identify metabolites that form the bio-corona, Tulsi leaves and madder roots were incubated with ultra-small anatase TiO2 nanoparticles, the coated nanoparticles were collected, and the adsorbed molecules were released from the nanoparticle surface and analyzed using an untargeted metabolomics approach. Similar to the results in which Arabidopsis tissue was used as a source of metabolites, TiO2 nanoparticle bio-coronas from Tulsi and madder were enriched for flavonoids and lipids, suggesting that nanoharvesting has a wide-range application potential. The third group of metabolites enriched in bio-coronas isolated from both plants were small peptides with C-terminal arginine and lysine residues.
Pre-adolescence DNA methylation is associated with lung function trajectories from pre-adolescence to adulthood
Authors: Sunny Shadia Khan , Zhang Hongmei , Mzayek Fawaz , Relton Caroline L. , Ring Susan , Henderson A. John , Ewart Susan , Holloway John W. , Arshad S. Hasan
Published: January 2021

Background

The pattern of lung function development from pre-adolescence to adulthood plays a significant role in the pathogenesis of respiratory diseases. Inconsistent findings in genetic studies on lung function trajectories, the importance of DNA methylation (DNA-M), and the critical role of adolescence in lung function development motivated the present study of pre-adolescent DNA-M with lung function trajectories. This study investigated epigenome-wide associations of DNA-M at cytosine-phosphate-guanine dinucleotide sites (CpGs) at childhood with lung function trajectories from childhood to young adulthood.

Methods

DNA-M was measured in peripheral blood at age 10 years in the Isle of Wight (IOW) birth cohort. Spirometry was conducted at ages 10, 18, and 26 years. A training/testing-based method was used to screen CpGs. Multivariable logistic regressions were applied to assess the association of DNA-M with lung function trajectories from pre-adolescence to adulthood. To detect differentially methylated regions (DMRs) among CpGs, DMR enrichment analysis was conducted. Findings were further tested in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Pathway analyses were performed on the mapped genes of the identified CpGs and DMRs. Biological relevance of the identified CpGs was assessed with gene expression. All analyses were stratified by sex.

Results

High and low trajectories of FVC, FEV1, and FEV1/FVC in each sex were identified. At PBonferroni < 0.05, DNA-M at 96 distinct CpGs (41 in males) showed associations with FVC, FEV1, and FEV1/FVC trajectories in IOW cohort. These 95 CpGs (cg24000797 was disqualified) were further tested in ALSPAC; 44 CpGs (19 in males) of these 95 showed the same directions of association as in the IOW cohort; and three CpGs (two in males) were replicated. DNA-M at two and four CpGs showed significant associations with the corresponding gene expression in males and females, respectively. At PFDR < 0.05, 23 and 10 DMRs were identified in males and females, respectively. Pathways were identified; some of those were linked to lung function and chronic obstructive lung diseases.

Conclusion

The identified CpGs at pre-adolescence have the potential to serve as candidate markers for lung function trajectory prediction and chronic lung diseases.
Performance of the QPLEX™ Alz plus assay, a novel multiplex kit for screening cerebral amyloid deposition
Authors: Park Jong-Chan , Jung Keum Sim , Kim Jiyeong , Jang Ji Sung , Kwon Sunghoon , Byun Min Soo , Yi Dahyun , Byeon Gihwan , Jung Gijung , Kim Yu Kyeong , Lee Dong Young , Han Sun-Ho , Mook-Jung Inhee
Published: January 2021

Background

Alzheimer’s disease (AD) is an irreversible neurodegenerative disease characterized by the hallmark finding of cerebral amyloid deposition. Many researchers have tried to predict the existence of cerebral amyloid deposition by using easily accessible blood plasma samples, but the effectiveness of such strategies remains controversial.

Methods

We developed a new multiplex kit, the QPLEX™ Alz plus assay kit, which uses proteomics-based blood biomarkers to prescreen for cerebral amyloid deposition. A total of 300 participants who underwent Pittsburgh compound B (PiB)-positron emission tomography (PET) which allows imaging of cerebral amyloid deposition were included in this study. We compared the levels of QPLEX™ biomarkers between patients who were classified as PiB-negative or PiB-positive, regardless of their cognitive function. Logistic regression analysis followed by receiver operating characteristic (ROC) curve analysis was performed. The kit accuracy was tested using a randomized sample selection method.

Results

The results obtained using our assay kit reached 89.1% area under curve (AUC) with 80.0% sensitivity and 83.0% specificity. Further validation of the QPLEX™ Alz plus assay kit using a randomized sample selection method showed an average accuracy of 81.5%.

Conclusions

Our QPLEX™ Alz plus assay kit provides preliminary evidence that it can be used as blood marker to predict cerebral amyloid deposition but independent validation is needed.
Distinct network topology in Alzheimer’s disease and behavioral variant frontotemporal dementia
Authors: Ng Adeline Su Lyn , Wang Juan , Ng Kwun Kei , Chong Joanna Su Xian , Qian Xing , Lim Joseph Kai Wei , Tan Yi Jayne , Yong Alisa Cui Wen , Chander Russell Jude , Hameed Shahul , Ting Simon Kang Seng , Kandiah Nagaendran , Zhou Juan Helen
Published: January 2021

Background

Alzheimer’s disease (AD) and behavioral variant frontotemporal dementia (bvFTD) cause distinct atrophy and functional disruptions within two major intrinsic brain networks, namely the default network and the salience network, respectively. It remains unclear if inter-network relationships and whole-brain network topology are also altered and underpin cognitive and social–emotional functional deficits.

Methods

In total, 111 participants (50 AD, 14 bvFTD, and 47 age- and gender-matched healthy controls) underwent resting-state functional magnetic resonance imaging (fMRI) and neuropsychological assessments. Functional connectivity was derived among 144 brain regions of interest. Graph theoretical analysis was applied to characterize network integration, segregation, and module distinctiveness (degree centrality, nodal efficiency, within-module degree, and participation coefficient) in AD, bvFTD, and healthy participants. Group differences in graph theoretical measures and empirically derived network community structures, as well as the associations between these indices and cognitive performance and neuropsychiatric symptoms, were subject to general linear models, with age, gender, education, motion, and scanner type controlled.

Results

Our results suggested that AD had lower integration in the default and control networks, while bvFTD exhibited disrupted integration in the salience network. Interestingly, AD and bvFTD had the highest and lowest degree of integration in the thalamus, respectively. Such divergence in topological aberration was recapitulated in network segregation and module distinctiveness loss, with AD showing poorer modular structure between the default and control networks, and bvFTD having more fragmented modules in the salience network and subcortical regions. Importantly, aberrations in network topology were related to worse attention deficits and greater severity in neuropsychiatric symptoms across syndromes.

Conclusions

Our findings underscore the reciprocal relationships between the default, control, and salience networks that may account for the cognitive decline and neuropsychiatric symptoms in dementia.
Targeting the IL-5 pathway in eosinophilic asthma: a comparison of mepolizumab to benralizumab in the reduction of peripheral eosinophil counts
Authors: Ghassemian Arian , Park Jane Jiyoon , Tsoulis Michael W. , Kim Harold
Published: January 2021

Background

Mepolizumab and benralizumab are biologics approved for severe eosinophilic asthma. Mepolizumab is an anti-interlukin-5 (IL-5) antibody while benralizumab is an anti-interleukin-5 receptor alpha (IL-5Rα) antibody targeting the IL-5 receptor on eosinophils. Both therapies reduce oral corticosteroid requirements and asthma exacerbations. However, no head-to-head studies have been published. The aim of the present study was to compare the efficacy of peripheral eosinophil reduction of mepolizumab and benralizumab.

Methods

A retrospective chart review was conducted on patients with severe eosinophilic asthma who were approved for either IL-5 agent. Patients with noted non-adherence or those who were on fluctuating doses of corticosteroids for non-asthma related illnesses were excluded. The last detectable eosinophil count for each patient prior to start of therapy was compared to the highest eosinophil count noted after therapy start with at least 30 days of adherence.

Results

Thirty-six patients taking mepolizumab and 19 patients taking benralizumab met the inclusion criteria and had both pre-treatment and post-treatment eosinophil counts. Baseline characteristics were not statistically different between those on mepolizumab and benralizumab therapy. The mean pre-therapy serum eosinophil count did not statistically differ between patients on mepolizumab (597.2 cells/µL) compared to benralizumab (521.6 cells/µL), p = 0.3769. While both therapies resulted in a significant decrease in eosinophil count (p < 0.0001); the mean decrease did not statistically differ between patients taking mepolizumab compared to those on benralizumab, p = 0.9079. Nonetheless, 100% of patients receiving benralizumab had undetectable eosinophil counts post-therapy compared to 31% of patients receiving mepolizumab (p < 0.0001).

Conclusion

Both mepolizumab and benralizumab are potent targets of the IL-5 pathway with the ability to significantly reduce peripheral eosinophil counts. While there is there is no statistical difference in the magnitude of eosinophil reduction offered by each agent, benralizumab is able to decrease peripheral eosinophil counts to 0 cells/µL in more patients than mepolizumab.
Hypoxic hUCMSC-derived extracellular vesicles attenuate allergic airway inflammation and airway remodeling in chronic asthma mice
Authors: Dong Liyang , Wang Ying , Zheng Tingting , Pu Yanan , Ma Yongbin , Qi Xin , Zhang Wenzhe , Xue Fei , Shan Zirui , Liu Jiameng , Wang Xuefeng , Mao Chaoming
Published: January 2021

Background

As one of the main functional forms of mesenchymal stem cells (MSCs), MSC-derived extracellular vesicles (MSC-EVs) have shown an alternative therapeutic option in experimental models of allergic asthma. Oxygen concentration plays an important role in the self-renewal, proliferation, and EV release of MSCs and a recent study found that the anti-asthma effect of MSCs was enhanced by culture in hypoxic conditions. However, the potential of hypoxic MSC-derived EVs (Hypo-EVs) in asthma is still unknown.

Methods

BALB/c female mice were sensitized and challenged with ovalbumin (OVA), and each group received PBS, normoxic human umbilical cord MSC-EVs (Nor-EVs), or Hypo-EVs weekly. After treatment, the animals were euthanized, and their lungs and bronchoalveolar lavage fluid (BALF) were collected. With the use of hematoxylin and eosin (HE), periodic acid-Schiff (PAS) and Masson’s trichrome staining, enzyme-linked immune sorbent assay (ELISA), Western blot analysis, and real-time PCR, the inflammation and collagen fiber content of airways and lung parenchyma were investigated.

Results

Hypoxic environment can promote human umbilical cord MSCs (hUCMSCs) to release more EVs. In OVA animals, the administration of Nor-EVs or Hypo-EVs significantly ameliorated the BALF total cells, eosinophils, and pro-inflammatory mediators (IL-4 and IL-13) in asthmatic mice. Moreover, Hypo-EVs were generally more potent than Nor-EVs in suppressing airway inflammation in asthmatic mice. Compared with Nor-EVs, Hypo-EVs further prevented mouse chronic allergic airway remodeling, concomitant with the decreased expression of pro-fibrogenic markers α-smooth muscle actin (α-SMA), collagen-1, and TGF-β1-p-smad2/3 signaling pathway. In vitro, Hypo-EVs decreased the expression of p-smad2/3, α-SMA, and collagen-1 in HLF-1 cells (human lung fibroblasts) stimulated by TGF-β1. In addition, we showed that miR-146a-5p was enriched in Hypo-EVs compared with that in Nor-EVs, and Hypo-EV administration unregulated the miR-146a-5p expression both in asthma mice lung tissues and in TGF-β1-treated HLF-1. More importantly, decreased miR-146a-5p expression in Hypo-EVs impaired Hypo-EV-mediated lung protection in OVA mice.

Conclusion

Our findings provided the first evidence that hypoxic hUCMSC-derived EVs attenuated allergic airway inflammation and airway remodeling in chronic asthma mice, potentially creating new avenues for the treatment of asthma.
Fetal sex and maternal postpartum depressive symptoms: findings from two prospective pregnancy cohorts
Authors: Cowell Whitney , Colicino Elena , Askowitz Talia , Nentin Farida , Wright Rosalind J.
Published: January 2021

Background

Fetal sex is known to modify the course and complications of pregnancy, with recent evidence of sex-differential fetal influences on the maternal immune and endocrine systems. In turn, heightened inflammation and surges in reproductive hormone levels associated with pregnancy and parturition have been linked with the development of perinatal depression. Here, we examined whether there is an association between fetal sex and maternal depression assessed during the prenatal and postnatal periods.

Methods

The study included two multi-ethnic, prospective pregnancy cohorts that enrolled women from prenatal clinics in the Northeastern United States between 2001 and 2018. Maternal depressive symptoms were measured during the prenatal and postnatal periods using the Edinburgh Postpartum Depression Scale (EPDS), and newborn sex was reported by the mother following delivery. We used logistic regression to examine associations between fetal sex and maternal depressive symptoms (EPDS > 10) during the prenatal period only, postnatal period only, or both periods versus no depressive symptoms during either period. We considered both unadjusted models and models adjusted for a core set of sociodemographic and lifestyle variables.

Results

In adjusted models using PRISM data (N= 528), women pregnant with a male versus female fetus had significantly greater odds of depressive symptoms during the postnatal period compared to women without depressive symptoms during either period (odds ratio [OR] = 5.24, 95% confidence interval [CI] = 1.93, 14.21). The direction of results was consistent in the ACCESS cohort, although the findings did not reach statistical significance (OR = 2.05, 95% CI = 0.86, 4.93). Significant associations were not observed in either cohort among women with prenatal symptoms only or women with prenatal and postnatal symptoms.

Conclusions

Male fetal sex was associated with the onset of depressive symptoms during the postnatal period.
ANCA-negative microscopic polyangiitis with diffuse alveolar hemorrhage masquerading as congestive heart failure
Authors: Mollaeian Arash , Chan Nina , Aloor Rohit , Iding Jeffery S. , Arend Lois J. , Saeidabadi Seyed Hootan Forghani , Haas Christopher J.
Published: January 2021

Background

Microscopic polyangiitis (MPA) is a subtype of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), involving small and medium sized vessels, often affecting the kidneys and lungs. Anti-neutrophil cytoplasmic antibody (ANCA) is detected in up to 90% of cases of MPA and its detection helps guide diagnosis, however cases of ANCA-negative MPA have been reported, hence definitive diagnosis relies on tissue biopsy.

Case report

A 23-year-old man was evaluated for dyspnea and pleuritic chest pain, and found to have bilateral intra-alveolar opacities and hilar adenopathy. Diagnostic work up revealed positive anti-nuclear antibodies (ANA) and negative ANCA, which in the setting of a non-classical presentation, delayed diagnosis and appropriate treatment. Due to persistent symptoms and a high suspicion for autoimmune disease with pulmonary-renal syndrome, he underwent lung biopsy which revealed intra-alveolar hemorrhage and capillaritis indicative of microscopic polyangiitis (MPA). Surprisingly, kidney biopsy was not typical of classic MPA, but revealed less common features. Due to therapeutic noncompliance he was readmitted multiple times thereafter with rare complications of MPA such as acute pancreatitis and hemorrhagic pericardial effusion with tamponade.

Conclusion

This case serves as an important clinical reminder to consider AAV even in those with negative ANCA serologies and a high suspicion for pulmonary-renal syndrome. It also demonstrates the high morbidity in cases of diagnostic delay and inadequate treatment.
The significance of equivocal bone findings in staging PSMA imaging in the preoperative setting: validation of the PSMA-RADS version 1.0
Authors: Kuten Jonathan , Dekalo Snir , Mintz Ishai , Yossepowitch Ofer , Mano Roy , Even-Sapir Einat
Published: January 2021

Background

Assessing the extent of disease in newly diagnosed prostate cancer (PC) patients is crucial for tailoring an appropriate treatment approach. Prostate-specific membrane antigen (PSMA)–targeted positron emission tomography/computed tomography (PET/CT) reportedly has greater accuracy than conventional imaging for staging PC. As with any imaging modality, pitfalls and nonspecific findings do occur. The PSMA reporting and data system (PSMA-RADS) version 1.0 offers structured interpretation of PSMA-targeted studies and classifies lesions by likelihood of clinical significance. The aim of this retrospective study was to evaluate the clinical significance of equivocal bone findings on staging PSMA-targeted imaging, as defined by PSMA-RADS version 1.0, in the preoperative setting. Fifteen of 406 consecutive patients staged by PET/CT prior to radical prostatectomy had equivocal bone lesions. The scans were retrospectively scored with the PSMA-RADS version 1.0 system, blinded to disease course and follow-up data. Postoperative persistence of prostate-specific antigen levels supported by imaging and histological findings was used as the reference standard for the true significance of equivocal imaging findings.

Results

Thirteen of the 15 patients had an overall PSMA-RADS score of 3B, of whom only two had true metastatic disease. The remaining patients had scores of 4 (n = 1) or 5 (n = 1), all confirmed as true positive prostate-related malignant lesions. A per-lesion analysis identified 29 bone lesions, of which 27 were scored PSMA-RADS 3B, and only three of them were true metastases. Thus, debatable lesions proved to have no clinical significance in 84.6% of cases, and only 11% of equivocal PSMA-RADS 3B bone lesions were true positive.

Conclusions

In intermediate and high-risk patients staged prior to radical prostatectomy, the majority of PSMA-RADS 3B lesions are of no clinical relevance. Bone lesions judged as being highly suspicious for metastases (PSMA-RADS 4/5) were all validated as true positives.
Isolation and characterisation of Methylocystis spp. for poly-3-hydroxybutyrate production using waste methane feedstocks
Authors: Rumah Bashir L. , Stead Christopher E. , Claxton Stevens Benedict H. , Minton Nigel P. , Grosse-Honebrink Alexander , Zhang Ying
Published: January 2021

Waste plastic and methane emissions are two anthropogenic by-products exacerbating environmental pollution. Methane-oxidizing bacteria (methanotrophs) hold the key to solving these problems simultaneously by utilising otherwise wasted methane gas as carbon source and accumulating the carbon as poly-3-hydroxybutyrate, a biodegradable plastic polymer. Here we present the isolation and characterisation of two novel Methylocystis strains with the ability to produce up to 55.7 ± 1.9% poly-3-hydroxybutyrate of cell dry weight when grown on methane from different waste sources such as landfill and anaerobic digester gas. Methylocystis rosea BRCS1 isolated from a recreational lake and Methylocystis parvus BRCS2 isolated from a bog were whole genome sequenced using PacBio and Illumina genome sequencing technologies. In addition to potassium nitrate, these strains were also shown to grow on ammonium chloride, glutamine and ornithine as nitrogen source. Growth of Methylocystis parvus BRCS2 on Nitrate Mineral Salt (NMS) media with 0.1% methanol vapor as carbon source was demonstrated. The genetic tractability by conjugation was also determined with conjugation efficiencies up to 2.8 × 10–2 and 1.8 × 10–2 for Methylocystis rosea BRCS1 and Methylocystis parvus BRCS2 respectively using a plasmid with ColE1 origin of replication. Finally, we show that Methylocystis species can produce considerable amounts of poly-3-hydroxybutyrate on waste methane sources without impaired growth, a proof of concept which opens doors to their use in integrated bio-facilities like landfills and anaerobic digesters.
Agricultural by-products and oyster shell as alternative nutrient sources for microbial sealing of early age cracks in mortar
Authors: Hong Minyoung , Jang Indong , Son Yongjun , Yi Chongku , Park Woojun
Published: January 2021

Bio-concrete using bacterially produced calcium carbonate can repair microcracks but is still relatively expensive due to the addition of bacteria, nutrients, and calcium sources. Agricultural by-products and oyster shells were used to produce economical bio-concrete. Sesame meal was the optimal agricultural by-product for low-cost spore production of the alkaliphilic Bacillus miscanthi strain AK13. Transcriptomic dataset was utilized to compare the gene expressions of AK13 strain under neutral and alkaline conditions, which suggested that NaCl and riboflavin could be chosen as growth-promoting factors at alkaline pH. The optimal levels of sesame meal, NaCl, and riboflavin were induced with the central composite design to create an economical medium, in which AK13 strain formed more spores with less price than in commercial sporulation medium. Calcium nitrate obtained from nitric acid treatment of oyster shell powder increased the initial compressive strength of cement mortar. Non-ureolytic calcium carbonate precipitation by AK13 using oyster shell-derived calcium ions was verified by energy-dispersive X-ray spectroscopy and X-ray diffraction analysis. Stereomicroscope and field emission scanning electron microscopy confirmed that oyster shell-derived calcium ions, along with soybean meal-solution, increased the bacterial survival and calcium carbonate precipitation inside mortar cracks. These data suggest the possibility of commercializing bacterial self-healing concrete with economical substitutes for culture medium, growth nutrient, and calcium sources.
Development and validation of a competitive ELISA based on virus-like particles of serotype Senecavirus A to detect serum antibodies
Authors: Bai Manyuan , Wang Rui , Sun Shiqi , Zhang Yun , Dong Hu , Guo Huichen
Published: January 2021

Virus-like particles (VLPs) are high-priority antigens with highly ordered repetitive structures, which are similar to natural viral particles. We have developed a competitive enzyme-linked immunosorbent assay (cELISA) for detecting antibodies directed against Senecavirus A (SVA). Our assay utilizes SVA VLPs that were expressed and assembled in an E. coli expression system as the coating antigens. VLPs have better safety and immunogenicity than intact viral particles or peptides. The VLPs-based cELISA was used to test 342 serum samples collected from different pig farms, and the results showed that its specificity and sensitivity were 100% and 94%, respectively. The consistency rates of cELISA with the BIOSTONE AsurDx™ Senecavirus A (SVA) Antibody Test Kit and an indirect immunofluorescent assay were 90.0% and 94.2%, respectively. Therefore, this VLPs-based cELISA can be effectively and reliably used for the detection and discrimination of SVA infection in serum samples.
Effect of different sweeteners on the oral microbiota and immune system of Sprague Dawley rats
Authors: Cheng Xi , Guo Xiurong , Huang Feihong , Lei Hui , Zhou Quan , Song Can
Published: January 2021

Sucrose, xylose, and saccharin are commonly used beverage additives and long-term consumption of these compounds inevitably affects the oral immune system and the composition of oral microbiomes. In this study, we used 24 Sprague Dawley rats divided into four groups, i.e., sucrose, saccharin, xylose, or pure water treated over an eight week period to evaluate any changes in the composition, community structure, and function of the oral microbiomes. At the end of the treatment period, we collected oral microbiome samples from each animal and subjected them to high-throughput sequencing. We also used ELISA to determine the concentration of salivary immunoglobulin in these rats to reveal the effect of sweetener on the oral immune system. Sequencing results demonstrated that Firmicutes and Proteobacteria, remained the predominant phyla, but we found that the oral microbial diversity of rats drinking sucrose water was significantly higher than that of the other groups. Our results indicate that drinking water supplemented with sweeteners may influence oral immunity as well as the composition, metabolic function, and diversity of the oral microbiota, thereby disrupting the oral microbiome.
Retinol from hepatic stellate cells via STRA6 induces lipogenesis on hepatocytes during fibrosis
Authors: Hwang Injoo , Lee Eun Ju , Park Hyomin , Moon Dodam , Kim Hyo-Soo
Published: January 2021

Background

Hepatic stellate cells (HSCs) are activated in response to liver injury with TIF1γ-suppression, leading to liver fibrosis. Here, we examined the mechanism how reduction of TIF1γ in HSCs induces damage on hepatocytes and liver fibrosis.

Method

Lrat:Cas9-ERT2:sgTif1γ mice were treated Tamoxifen (TMX) or wild-type mice were treated Thioacetamide (TAA). HSCs were isolated from mice liver and analyzed role of Tif1γ. HepG2 were treated retinol with/without siRNA for Stimulated by retinoic acid 6 (STRA6) or Retinoic acid receptor(RAR)-antagonist, and LX2 were treated siTIF1γ and/or siSTRA6. TAA treated mice were used for evaluation of siSTRA6 effect in liver fibrosis.

Results

When we blocked the Tif1γ in HSCs using Lrat:Cas9-ERT2:sgTif1γ mice, retinol is distributed into hepatocytes. Retinol influx was confirmed using HepG2, and the increased intracellular retinol led to the upregulation of lipogenesis-related-genes and triglyceride. This effect was inhibited by a RAR-antagonist or knock-down of STRA6. In the LX2, TIF1γ-suppression resulted in upregulation of STRA6 and retinol release, which was inhibited by STRA6 knock-down. The role of STRA6-mediated retinol transfer from HSCs to hepatocytes in liver fibrosis was demonstrated by in vivo experiments where blocking of STRA6 reduced fibrosis.

Conclusions

Retinol from HSCs via STRA6 in response to injury with TIF1γ-reduction is taken up by hepatocytes via STRA6, leading to fat-deposition and damage, and liver fibrosis.
Potential roles and prognostic significance of exosomes in cancer drug resistance
Authors: Mostafazadeh Mostafa , Samadi Nasser , Kahroba Houman , Baradaran Behzad , Haiaty Sanya , Nouri Mohammad
Published: January 2021

Drug resistance is a major impediment in cancer therapy which strongly reduces the efficiency of anti-cancer drugs. Exosomes are extracellular vesicles with cup or spherical shape with a size range of 40–150 nm released by eukaryotic cells that contain genetic materials, proteins, and lipids which mediate a specific cell-to-cell communication. The potential roles of exosomes in intrinsic and acquired drug resistance have been reported in several studies. Furthermore, a line of evidence suggested that the content of exosomes released from tumor cells in biological samples may be associated with the clinical outcomes of cancer patients. In this review, we highlighted the recent studies regarding the potential roles of exosomes in tumor initiation, progression, and chemoresistance. This study suggests the possible role of exosomes for drug delivery and their contents in prognosis and resistance to chemotherapy in cancer patients.
Two-step generation of mesenchymal stem/stromal cells from human pluripotent stem cells with reinforced efficacy upon osteoarthritis rabbits by HA hydrogel
Authors: Zhang Leisheng , Wei Yimeng , Chi Ying , Liu Dengke , Yang Sijun , Han Zhongchao , Li Zongjin
Published: January 2021

Background

Current studies have enlightened the rosy prospects of human pluripotent stem cell (hPSC)-derived mesenchymal stem/stromal cells (MSCs) in regenerative medicine. However, systematic investigation of their signatures and applications with alternative biomaterials in osteoarthritis (OA) remains indistinct.

Methods

Herein, we initially took advantage of a small molecule library-mediated programming strategy for hPSC-MSC induction. Then, with the aid of multifaceted analyses such as flow cytometry (FCM), chromosome karyocyte and cell vitality, wound healing and microtubule formation assay and coculturing with T lymphocytes, we systematically evaluated the characterizations of signatures in vitro and the in vivo efficacy of hPSC-MSCs and HA hydrogel composite on rabbit osteoarthritis model.

Results

We found the combination of LLY-507 and AZD5153 was sufficient for high-efficiency CD73+CD90+CD105+CD31−CD34−CD45−HLA-DR−MSC induction from both hESCs and hiPSCs with stemness (POU5F1/SOX2/NANOG). The programmed hPSC-MSCs revealed conservative transcriptome variations and went through a heterogeneous intermediate-stage with mesenchymal-associated gene expression (NT5E,ENG,VIMandFN1) as well as displayed typical cytomorphology, immunophenotypes and normal karyotyping, multilineage differentiation potential, favorable cell vitality, proangiogenic and immunoregulatory properties in vitro. Meanwhile, the cell population exhibited preferable restorative and ameliorative function on OA rabbits with HA hydrogel in vivo.

Conclusions

Collectively, we established a rapid and convenient procedure for hPSC-MSC generation without redundant manipulations. The fundamental and clinical studies upon osteoarthritis (OA) treatment would benefit tremendously from the combination of the inexhaustible hPSC-MSCs and advantageous biomaterials.
Prevalence of sexual dysfunction in men with multiple sclerosis: a systematic review and meta-analysis
Authors: Dastoorpoor Maryam , Zamanian Maryam , Moradzadeh Rahmatollah , Nabavi Seyed Massood , Kousari Raana
Published: January 2021

Background

Symptoms in multiple sclerosis (MS) can lead to different types and ranges of sexual dysfunction in MS patients. Studies in different parts of the world have reported a high range of sexual dysfunction in men with MS. This study aimed to estimate pooled prevalence of sexual dysfunction in men with MS.

Methods

The authors searched Web of Science, PubMed, Scopus, Embase, Magiran, SID, and Iran Medical Papers Database using the keywords “multiple sclerosis”, “sexual dysfunctions”, “men”, “prevalence”, and their synonyms systematically. Meta-analysis was performed using the random effects model with inverse variance-weighted method to estimate the overall prevalence of sexual dysfunction in men with MS. The protocol for this meta-analysis is available in PROSPERO (ID CRD42020199005).

Results

A total of 351 documents were identified, and 20 articles published from 1996 to 2019 were analyzed. The articles used sample sizes from 9 to 101 individuals. However, two studies conducted online used 388 and 1568 samples. Prevalence of sexual dysfunction in all studies was reported from 31 to 92%, and the pooled prevalence of sexual dysfunction in men with MS in all studies was 62.9% with a 95% confidence interval 53 to 72.7% (heterogeneity: I2 = 96.3%, Q-statistic = 12.48, P value < 0.001). According to the results of Egger’s test, there was publication bias in the current study (β = 4.55, Se = 1.38, P value = 0.004).

Conclusion

Sexual dysfunction is highly prevalent in men with MS. Diagnosing sexual dysfunction in MS patients in clinics by specialists have to be considered a necessity.
Investigation and control of an outbreak of urinary tract infections caused by Burkholderia cepacian-contaminated anesthetic gel
Authors: Du Mingmei , Song Linjian , Wang Yan , Suo Jijiang , Bai Yanling , Xing Yubin , Xie Lijun , Liu Bowei , Li Lu , Luo Yanping , Liu Yunxi
Published: January 2021

Background

This report describes an outbreak of 71 patients developed B. cepacia urinary tract infection (UTI) by contaminated single-use anesthetic gel.

Methods

Epidemiological investigation of patients with B. cepacia-positive urine or blood samples between March 19, 2018 and Novemeber 15, 2018 was conducted to identify the source of infection. Microbiological samples from hospital surfaces, endoscopes, disposable items, and the hands of staff were tested for B. cepacia contamination. Pulsed-field gel electrophoresis (PFGE) was used to compare homology in B. cepacia isolates.

Results

During the outbreak, nosocomial B. cepacia UTI was confirmed in 71 patients. Epidemiological investigation showed that 66 patients underwent invasive urological diagnosis and treatment, while the remaining five patients underwent bedside indwelling catheterization, with all patients exposed to single-use anesthetic gel. All batches of anesthetic gel were recalled and the outbreak abated. Overall, 155 samples were collected from environmental surfaces and disposable items, and B. cepacia contamination was confirmed in samples from one used cystoscope and three anesthetic gels from the same batch. PFGE showed homology between 17 out of 20 B. cepacia isolates from patients and three isolates from the contaminated anesthetic gel. All patients achieved cure.

Conclusion

Contaminated single-use anesthetic gel was confirmed as the source of the B. cepacia outbreak, with infection occurring during invasive urological diagnostic and treatments. Thus, investigations of nosocomial outbreaks of B. cepacia infection should consider contamination of diagnostic and treatment items used in infected patients.
Experience and practice of the Emergency Operations Center, Chinese Center for Disease Control and Prevention: a case study of response to the H7N9 outbreak
Authors: Ding Fan , Li Qun , Jin Lian-Mei
Published: January 2021

Background

Emergency Operations Center (EOC) is a place to provide response to public health emergencies. Chinese Center for Disease Control and Prevention (China CDC)’s EOC was officially established in 2016, which has been the core department for the public health emergencies and risk response. In recent years, we have been continuously improving the function of EOC through many incidents. In the study, we hope to share the construction status, operation management experience of China CDC’s EOC and the response process in the human avian influenza A (H7N9) outbreak.

Main text

The China CDC’s EOC mainly focus on building the five core elements including sites/places and facilities, information and data, plans and procedures, training and exercises, and logistics. Based on summarizing previous emergency response, the China CDC’s EOC established its own incident management and the standardized response procedures. The event-specific data, context-specific data and event management data could be obtained through various source. The logistics department of the EOC also provides comprehensive support. The well-trained staff is another necessary conditions for its operation. Through sharing the response process of H7N9 outbreak, it further explains the EOC’s functions in the five phases of outbreak response, such as the formulation of the incident response framework, monitoring, personnel dispatch and resource mobilization.

Conclusions

The EOC contributes to faster and more efficient responses during emergencies which enable a greater reduction in morbidity and mortality. Compared with the traditional incident response process, under the command and coordination of China CDC’s EOC, each group involved in the response has a clearer goal, responsibilities and tasks at each stage. Meanwhile, each group also gave full play to its own expertise and advantages. As a whole, incident response tended to be more specialized and precise, which generally improves the efficiency of incident response. However, different countries and regions have different response processes to the events. We still suggested that appropriate emergency operation plan should be made according to the complexity of incident response in the region when constructing response mechanism, through our experience. And the China CDC’s EOC is still at growing and groping phase.

Graphic abstract
Prehabilitation in head and neck cancer patients: A literature review
Authors: Loewen Irene , Jeffery Caroline C. , Rieger Jana , Constantinescu Gabriela
Published: January 2021

Background

Dysphagia is one consequence of head and neck cancer that has a significant impact on quality of life for head and neck cancer survivors. While survival rates continue to improve, focus has shifted to maximizing long-term function, with prevention or prehabilitation programs becoming more common. Prehabilitation programs typically include an exercise regime that specifies the exercise type, the number of repetitions to complete per set, the number of sets of each exercise to complete per day, as well as the length of the treatment block. Ideally, exercise programs are designed with principles of neuromuscular plasticity in mind.

Methods

Twenty-nine original research articles published between 2006 and 2020 were included in this state-of-the-art review and examined for program timing and details.

Results

Two definitions for prehabilitation were noted: one third of the studies defined prehabilitation as preventative exercises prior to the start of acute cancer treatment; the remaining two thirds defined prehabilitation as treatment concurrent prehabilitation. Exercises prescribed ranged from general stretching and range of motion exercises, to trismus and swallowing specific exercises. The most common swallowing specific exercise was the Mendelsohn's maneuver, followed by the effortful swallow, Shaker, and Masako maneuver. The most common dose was 10 repetitions of an exercise, three times per day for the duration of radiation therapy. The most common measures were questionnaires, followed by g-tube dependence, mouth opening, and MBS reports.

Conclusion

This review of the literature has shed light on the variability of prehabilitation timing, exercise type, dose, duration of treatment, and outcomes associated with prehabilitation, making the selection of an optimal prehabilitation program difficult at this time.
Resampling imbalanced data for network intrusion detection datasets
Authors: Bagui Sikha , Li Kunqi
Published: January 2021

Machine learning plays an increasingly significant role in the building of Network Intrusion Detection Systems. However, machine learning models trained with imbalanced cybersecurity data cannot recognize minority data, hence attacks, effectively. One way to address this issue is to use resampling, which adjusts the ratio between the different classes, making the data more balanced. This research looks at resampling’s influence on the performance of Artificial Neural Network multi-class classifiers. The resampling methods, random undersampling, random oversampling, random undersampling and random oversampling, random undersampling with Synthetic Minority Oversampling Technique, and random undersampling with Adaptive Synthetic Sampling Method were used on benchmark Cybersecurity datasets, KDD99, UNSW-NB15, UNSW-NB17 and UNSW-NB18. Macro precision, macro recall, macro F1-score were used to evaluate the results. The patterns found were: First, oversampling increases the training time and undersampling decreases the training time; second, if the data is extremely imbalanced, both oversampling and undersampling increase recall significantly; third, if the data is not extremely imbalanced, resampling will not have much of an impact; fourth, with resampling, mostly oversampling, more of the minority data (attacks) were detected.