bluuebunny/crossref_metadata_2025 huggingface dataset:
Aetiology, diagnosis and treatment of moderate-to-severe haemoptysis in a North American academic centre
Authors: Quigley Nicholas , Gagnon Sébastien , Fortin Marc
Published: October 2020

Significant haemoptysis is a frightening event for patients and clinicians alike. There is a paucity of contemporary literature on the subject.

A retrospective analysis of hospitalisations for haemoptysis of more than 50 mL·day−1in a tertiary referral centre during a 5-year period was performed. Patient's characteristics, haemoptysis aetiology, management and outcome were individually recorded. The aim of this study was to detail the causes of moderate (50–200 mL·day−1) to severe (>200 mL·day−1) haemoptysis along with the diagnostic measures and treatment options used in their management in a 21st century, tertiary-care North American centre.

A total of 165 hospitalisations for moderate-to-severe haemoptysis were included in the analysis. Lung cancer (30.3%) and bronchiectasis (27.9%) proved to be most frequent aetiologies. Computed tomography (CT) imaging and bronchoscopy were complementary in identifying the source of bleeding. Bronchial artery embolisation (BAE) was the most common treatment approach (61.8%) and resulted in initial bleeding control in 73.5% of cases. In-hospital mortality was 13.9%, varying from 3.3% in the moderate group to 24.7% in the severe group. Despite being the favoured approach in patients with more severe bleeding, initial BAE therapy was associated with a trend towards lower mortality compared to initial non-BAE therapy.

In summary, lung cancer and bronchiectasis were the main causes of moderate-to-severe haemoptysis in our population, CT and bronchoscopy are complementary in identifying the source of bleeding, bleeding volume is associated with outcomes and BAE is a key management tool.
Current symptom-based risk scores for stable coronary artery disease evaluation are not applicable in COPD patients
Authors: Beyer Christoph , Pizzini Alex , Boehm Anna , Loeffler-Ragg Judith , Weiss Guenter , Feuchtner Gudrun , Bauer Axel , Friedrich Guy , Plank Fabian
Published: October 2020

Background

Cardiovascular diseases are arguably the most important comorbidity in patients with COPD. Despite an increased prevalence of coronary artery disease (CAD) in COPD patients, there are no dedicated diagnostic recommendations.

Objectives

We investigated whether COPD patients receive adequate primary evaluation of CAD despite overlapping symptoms.

Methods

In total, 302 patients with COPD who underwent invasive coronary angiography (ICA) were retrospectively matched (for age, body mass index and cardiovascular risk factors) with 302 patients without functional lung diseases. Quality and onset of symptoms prior to ICA were documented, and individual patients’ pretest probabilities according to European Society of Cardiology (ESC) guidelines were calculated. Endpoints were delay of ICA referral after symptom onset and clinical outcome, defined as subsequent revascularisation.

Results

Mean delay between symptom onset and ICA was 19.9±22.0 months in COPD patients compared to 8.3±12.7 months in the control group (p<0.0001). COPD patients had a lower rate of typical chest pain (25.2%versus38.1%, p=0.0009), and dyspnoea only (18.2%versus26.8%, p=0.015). Sub-analysis of Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades revealed an incremental delay with increasing COPD severity: GOLD 1: 16.1±17.3 months; GOLD 2: 17.6±22.1 months; GOLD 3: 20.1±21.3 months; and GOLD 4: 24.2±23.4 months. Overall significant CAD prevalence (>70% stenosis) was 35.3%; the revascularisation rate increased with higher pretest probability for the control group but decreased for patients with COPD GOLD 1–4.

Conclusion

Patients with COPD are insufficiently evaluated for CAD due to overlapping symptoms. Current CAD risk scores for stable chest pain appear inappropriate for patients with COPD.
Birth preparedness complication readiness and determinants among pregnant women: a community-based survey from Ethiopia
Authors: Ananche Teshale Abosie , Wodajo Legesse Tadesse
Published: October 2020

Background

Maternal death related to obstetric complications remains a great challenge in developing countries. Since these complications are not consistently predictable, it is important to plan different preventive approaches to overcome them when. As the information on birth preparedness, complication readiness, and predictors were limited in the study area, we conducted this study.

Methods

A Cross-sectional study involving 396 pregnant women was conducted from 1st April to 1st May 2018. Data were collected using a pre-tested structured questionnaire. Descriptive, binary and multiple logistic regression analyses were conducted in SPSS for windows version 20. P values < 0.05 were considered significant.

Results

Of 361 women interviewed (91% response rate), birth preparedness and complication readiness were present in 24.10% (87/361) of women. Maternal factors, age 18–19 (AOR = 0.18; 95% CI (0.04,0.94)), 20–34 (AOR = 0.40; 95% CI (0.20,0.78)), education, not able to read/write (AOR = 0.36;95% CI (0.15,0.85),read/write (AOR = 0.41;95% CI (0.19,0.89)), Muslim religion (AOR = 0.40; 95% CI (0.18,0.85)) income ETB, < 1000 (AOR = 0.21; 95% CI (0.07,0.67)),1000–2000, (AOR = 0.38; 95% CI (0.19,0.76)), and the mothers’ knowledge on key danger signs of postpartum (AOR = 0.48; 95% CI (0.26,0.90)) were independent predictors of birth preparedness and complication readiness.

Conclusions

Educational status, age, religion, family income, and knowledge of obstetric danger signs were significantly associated with birth preparedness and complication readiness. The Government and other health sector partners should work to improve women’s education, income, and focus on young age groups on pregnancy danger signs.
Assessment of the anti-virulence potential of extracts from four plants used in traditional Chinese medicine against multidrug-resistant pathogens
Authors: Pu Zhonghui , Tang Huaqiao , Long Nana , Qiu Min , Gao Mingxiang , Sun Fenghui , Dai Min
Published: October 2020

Background

Multidrug-resistant pathogens are resistant to many antibiotics and associated with serious infections. Amomum tsaoko Crevost et Lemaire, Sanguisorba officinalis, Terminalia chebula Retz and Salvia miltiorrhiza Bge, are all used in Traditional Chinese Medicine (TCM) against multidrug-resistant pathogens, and the purpose of this study was to evaluate the antibacterial and anti-virulence activity of extracts derived from them.

Methods

The antibacterial activity of ethanol and aqueous extracts from these four plants was examined against several multi-drug resistant bacterial strains, and their anti-virulence potential (including quorum quenching activity, biofilm inhibition, and blocking production of virulence factor δ-toxin) was assessed against different S. aureus strains. The chemical composition of the most effective extract was determined by LC-FTMS.

Results

Only extracts from S. officinalis and A. tsaoko were shown to exhibit limited growth inhibition activity at a dose of 256 μg·mL-1. The S. officinalis ethanol extract, the ethanol and aqueous extract of A. tsaoko, and the aqueous extract of S. miltiorrhiza all demonstrated quorum quenching activity, but didn’t significantly inhibit bacterial growth. The ethanol extract of S. officinalis inhibited bacterial toxin production and biofilm formation at low concentrations. Chemical composition analysis of the most effective extract of S. officinalis showed that it mainly contained saponins.

Conclusions

The most active extract tested in this study was the ethanol root extract of S. officinalis. It inhibited δ-toxin production and biofilm formation at low concentrations and saponins may be its key active components. While the four plants showed no direct antibacterial effects, their anti-virulence properties may be key to fighting bacterial infections.
Gut bacterial deamination of residual levodopa medication for Parkinson’s disease
Authors: van Kessel Sebastiaan P. , de Jong Hiltje R. , Winkel Simon L. , van Leeuwen Sander S. , Nelemans Sieger A. , Permentier Hjalmar , Keshavarzian Ali , El Aidy Sahar
Published: October 2020

Background

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by both motor and non-motor symptoms. Gastrointestinal tract dysfunction is one of the non-motor features, where constipation is reported as the most common gastrointestinal symptom. Aromatic bacterial metabolites are attracting considerable attention due to their impact on gut homeostasis and host’s physiology. In particular, Clostridium sporogenes is a key contributor to the production of these bioactive metabolites in the human gut.

Results

Here, we show that C. sporogenes deaminates levodopa, the main treatment in Parkinson’s disease, and identify the aromatic aminotransferase responsible for the initiation of the deamination pathway. The deaminated metabolite from levodopa, 3-(3,4-dihydroxyphenyl)propionic acid, elicits an inhibitory effect on ileal motility in an ex vivo model. We detected 3-(3,4-dihydroxyphenyl)propionic acid in fecal samples of Parkinson’s disease patients on levodopa medication and found that this metabolite is actively produced by the gut microbiota in those stool samples.

Conclusions

Levodopa is deaminated by the gut bacterium C. sporogenes producing a metabolite that inhibits ileal motility ex vivo. Overall, this study underpins the importance of the metabolic pathways of the gut microbiome involved in drug metabolism not only to preserve drug effectiveness, but also to avoid potential side effects of bacterial breakdown products of the unabsorbed residue of medication.
Long-term clinical course and outcomes of immunoglobulin G4-related lung disease
Authors: Kang Jieun , Park Shinhee , Chae Eun Jin , Song Joon Seon , Hwang Hee Sang , Kim Sun Jong , Song Tae Jun , Kim Myung-Whan , Song Jin Woo
Published: October 2020

Background

Immunoglobulin G4-related lung disease (IgG4-RLD) is the pulmonary manifestation of a systemic fibroinflammatory disease characterized by lymphoplasmacytic infiltration with an abundance of IgG4-positive plasma cells. Long-term clinical course and outcomes of IgG4-RLD remain unclear. We aimed to identify clinical characteristics, treatment outcomes, and longitudinal pulmonary function changes in patients with IgG4-RLD according to the radiologic classification.

Methods

Chest computed tomography findings of 37 subjects were classified into five subtypes: solid nodular, bronchovascular, alveolar interstitial, round ground glass opacity, and alveolar consolidative. Radiologic treatment outcomes and longitudinal pulmonary function changes were compared among the different radiologic subtypes.

Results

The mean age of the subjects was 55.6 years, and 78.4% were male. Among the five radiologic subtypes, alveolar consolidative and solid nodular type were most common, accounting for approximately 29.7% each of the total cases. Prednisone with or without azathioprine was administered to 31 patients (median treatment duration 14 months). In the treated patients, serial images showed complete response or partial response in 77.4%. However, relapse was documented in 25.0% of those who showed complete or partial response. In patients whose longitudinal lung function data were available (n = 20), the lung function was found to be stable during follow-up. Alveolar consolidative type showed the highest complete response rate, whereas alveolar interstitial type showed the lowest response rate, either complete or partial.

Conclusions

Most patients showed a favorable outcome with regards to radiologic improvement and maintenance of pulmonary function; however, the response differed according to the radiologic subtype.
LINC01006 facilitates cell proliferation, migration and invasion in prostate cancer through targeting miR-34a-5p to up-regulate DAAM1
Authors: Ma Enhui , Wang Qianqian , Li Jinhua , Zhang Xinqi , Guo Zhenjia , Yang Xiaofeng
Published: October 2020

Background

Prostate cancer (PCa) is a kind of malignancy occurring in the prostate gland. Substantial researches have proved the major role of long noncoding RNAs (lncRNAs) in PCa. However, the role of long intergenic non-protein coding RNA 1006 (LINC01006) in PCa has not been investigated yet.

Methods

RT-qPCR was used to examine the expression levels of LINC01006 and its downstream targets. The function of LINC01006 in PCa was tested by in vitro and in vivo assays. With application of RNA pull down, RNA immunoprecipitation (RIP) and luciferase reporter assays, the interaction among LINC01006, miR-34a-5p and disheveled associated activator of morphogenesis 1 (DAAM1) were verified.

Results

LINC01006 expression presented high in PCa cell lines. LINC01006 silencing suppressed cell proliferative, migratory, invasive capacities while accelerated apoptotic rate. Besides, LINC01006 knockdown also suppressed tumor growth and metastasis in vivo. Furthermore, miR-34a-5p, a tumor suppressor in PCa, was sponged by LINC01006. Moreover, DAAM1 was targeted by miR-34a-5p and promoted PCa progression. More intriguingly, rescue assays suggested that the inhibitory effect of LINC01006 knockdown on PCa development was offset by DAAM1 overexpression.

Conclusions

LINC01006 promoted PCa progression by sponging miR-34a-5p to up-regulate DAAM1, providing a novel target for PCa therapy.
Effect of early prophylactic low-dose recombinant human erythropoietin on retinopathy of prematurity in very preterm infants
Authors: Sun Huiqing , Song Juan , Kang Wenqing , Wang Yong , Sun Xiantao , Zhou Chongchen , Xiong Hong , Xu Falin , Li Mingchao , Zhang Xiaoli , Yu Zengyuan , Peng Xirui , Li Bingbing , Xu Yiran , Xing Shan , Wang Xiaoyang , Zhu Changlian
Published: October 2020

Background

Very preterm infants are at risk of developing retinopathy of prematurity (ROP). Recombinant human erythropoietin (rhEPO) is routinely used to prevent anemia in preterm infants; however, the effect of rhEPO on ROP development is still controversial. The purpose of this study was to evaluate the effect of early prophylactic low-dose rhEPO administration on ROP development in very preterm infants.

Methods

A total of 1898 preterm infants born before 32 weeks of gestation were included. Preterm infants received rhEPO (n = 950; 500 U/kg, rhEPO group) or saline (n = 948, control group) intravenously within 72 h of birth and then once every other day for 2 weeks.

Results

The total incidence of ROP was not significantly different between the two groups (10.2% vs.13.2%, p = 0.055). Further analysis showed that rhEPO group had lower rates of type 2 ROP than the control group (2.2% vs.4.1%, RR 0.98; 95% CI 0.96–1.00;p = 0.021). Subgroup analysis found that rhEPO treatment significantly decreased the incidence of type 2 ROP in infant boys (1.8% vs. 4.3%, p = 0.021) and in those with a gestational age of 28–296/7 weeks (1.1% vs. 4.9%, p = 0.002) and birth weight of 1000–1499 g (1.2% vs. 4.2%, p = 0.002). There was a small increasing tendency for the incidence of ROP in infants with a gestational age of < 28 weeks after rhEPO treatment.

Conclusions

Repeated low-dose rhEPO administration has no significant influence on the development of ROP; however, it may be effective for type 2 ROP in infant boys or in infants with gestational age > 28 weeks and birth weight > 1500 g.

Trial registrationThe data of this study were retrieved from two clinical studies registered ClinicalTrials.gov (NCT 02036073) on January 14, 2014,https://clinicaltrials.gov/ct2/show/NCT02036073; and (NCT03919500) on April 18, 2019.https://clinicaltrials.gov/ct2/show/NCT03919500.
Mycobacterium tuberculosis co-infection is associated with increased surrogate marker of the HIV reservoir
Authors: Xun Jingna , Qi Tangkai , Zou Lei , Tang Qi , Shen Yinzhong , Yang Junyang , Xie Luman , Ji Yongjia , Zhang Renfang , Liu Li , Wang Jiangrong , Steinhart Corky , Wang Zhenyan , Tang Yang , Song Wei , Sun Jianjun , Cheng Juan , Le Xiaoqin , Wu Huanmei , He Xiaoqing , Chen Rong , Chen Jun , Lu Hongzhou
Published: October 2020

Background

Tuberculosis (Tb) is the most frequent opportunistic infection among people living with HIV infection. The impact of Tb co-infection in the establishment and maintenance of the HIV reservoir is unclear.

Method

We enrolled 13 HIV-infected patients with microbiologically confirmed Tb and 10 matched mono-HIV infected controls. Total HIV DNA in peripheral blood mononuclear cells (PBMCs), plasma interleukin-7 (IL-7) concentrations and the activities of indoleamine 2,3-dioxygenase (IDO) were measured for all the participants prior to therapy and after antiretroviral therapy (ART).

Results

After a duration of 16 (12, 22) months’ ART, patients co-infected with Tb who were cured of Tb maintained higher levels of HIV DNA compared with mono-HIV infected patients [2.89 (2.65- 3.05) log10copies/106cells vs. 2.30 (2.11–2.84) log10copies/106cells,P = 0.008]. The levels of on-ART HIV DNA were positively correlated with the baseline viral load (r = 0.64,P = 0.02) in Tb co-infected group. However, neither plasma IL-7 concentration nor plasma IDO activity was correlated with the level of on-ART HIV DNA.

Conclusions

Tb co-infection was associated with the increased surrogate marker of the HIV reservoir, while its mechanism warrants further examination.
The loss of flight in ant workers enabled an evolutionary redesign of the thorax for ground labour
Authors: Peeters Christian , Keller Roberto A. , Khalife Adam , Fischer Georg , Katzke Julian , Blanke Alexander , Economo Evan P.
Published: October 2020

Background

Explanations for the ecological dominance of ants generally focus on the benefits of division of labour and cooperation during foraging. However, the principal innovation of ants relative to their wasp ancestors was the evolution of a new phenotype: a wingless worker caste optimized for ground labour. Ant workers are famous for their ability to lift and carry heavy loads, but we know surprisingly little about the morphological basis of their strength. Here we examine the consequences of the universal loss of flight in ant workers on skeletomuscular adaptations in the thorax for enhanced foraging on six legs.

Results

Using X-ray microcomputed tomography and 3D segmentation, we compared winged queens and wingless workers in Euponera sikorae (subfamily Ponerinae) and Cataglyphis savignyi (subfamily Formicinae). Workers are characterized by five major changes to their thorax: i) fusion of the articulated flight thorax (queens) into a rigid box optimized to support the muscles that operate the head, legs and abdomen, ii) redesign of internal cuticular structures for better bracing and muscle attachment, iii) substantial enlargement of the neck muscles for suspending and moving the head, iv) lengthening of the external trochanter muscles, predominant for the leg actions that lift the body off the ground, v) modified angle of the petiole muscles that are key for flexion of the abdomen. We measured volumes and pennation angles for a few key muscles to assess their increased efficacy. Our comparisons of additional workers across five genera in subfamilies Dorylinae and Myrmicinae show these modifications in the wingless thorax to be consistent. In contrast, a mutillid wasp showed a different pattern of muscle adaptations resulting from the lack of wing muscles.

Conclusions

Rather than simply a subtraction of costly flight muscles, we propose the ant worker thorax evolved into a power core underlying stronger mandibles, legs, and sting. This contrasts with solitary flightless insects where the lack of central place foraging generated distinct selective pressures for rearranging the thorax. Stronger emphasis is needed on morphological innovations of social insects to further our understanding of the evolution of social behaviours.
Sustained acoustic medicine as a non-surgical and non-opioid knee osteoarthritis treatment option: a health economic cost-effectiveness analysis for symptom management
Authors: Best Thomas M. , Petterson Stephanie , Plancher Kevin
Published: October 2020

Background

Patients diagnosed with osteoarthritis (OA) and presenting with symptoms are seeking conservative treatment options to reduce pain, improve function, and avoid surgery. Sustained acoustic medicine (SAM), a multi-hour treatment has demonstrated improved clinical outcomes for patients with knee OA. The purpose of this analysis was to compare the costs and effectiveness of multi-hour SAM treatment versus the standard of care (SOC) over a 6-month timeframe for OA symptom management.

Methods

A decision tree analysis was used to compare the costs and effectiveness of SAM treatment versus SOC in patients with OA. Probabilities of success for OA treatment and effectiveness were derived from the literature using systematic reviews and meta-analyses. Costs were derived from Medicare payment rates and manufacturer prices. Functional effectiveness was measured as the effect size of a therapy and treatment pathways compared to a SOC treatment pathway. A sensitivity analysis was performed to determine which cost variables had the greatest effect on deciding which option was the least costly. An incremental cost-effectiveness plot comparing SAM treatment vs. SOC was also generated using 1000 iterations of the model. Lastly, the incremental cost-effectiveness ratio (ICER) was calculated as the (cost of SAM minus cost of SOC) divided by (functional effectiveness of SAM minus functional effectiveness of SOC).

Results

Base case demonstrated that over 6 months, the cost and functional effectiveness of SAM was $8641 and 0.52 versus SOC at: $6281 and 0.39, respectively. Sensitivity analysis demonstrated that in order for SAM to be the less expensive option, the cost per 15-min session of PT would need to be greater than $88, or SAM would need to be priced at less than or equal to $2276. Incremental cost-effectiveness demonstrated that most of the time (84%) SAM treatment resulted in improved functional effectiveness but at a higher cost than SOC.

Conclusion

In patients with osteoarthritis, SAM treatment demonstrated improved pain and functional gains compared to SOC but at an increased cost. Based on the SAM treatment ICER score being ≤ $50,000, it appears that SAM is a cost-effective treatment for knee OA.
Personality traits mediate the association between perceived parental bonding and well-being in adult volunteers from the community
Authors: Murakoshi Akiko , Mitsui Nobuyuki , Masuya Jiro , Fujimura Yota , Higashi Shinji , Kusumi Ichiro , Inoue Takeshi
Published: October 2020

Background

Previous studies reported that subjective well-being in adulthood correlates with perceived parental bonding in childhood as well as personality traits. However, whether personality traits mediate the effect of perceived parental bonding on well-being or not has not been reported to date. In this study, we hypothesized that ‘parental care and overprotection’ in childhood affect ‘well-being’ in adulthood through various ‘personality traits’, and analyzed this using structural equation modeling.

Methods

A total of 402 adult volunteers from the community provided responses to the following questionnaires: 1) Parental Bonding Instrument, 2) Temperament and Character Inventory, and 3) The Subjective Well-being Inventory. Two structural equation models were designed and the maximum likelihood estimation method was used for covariance structure analysis.

Results

Parental care in childhood directly increased well-being in adulthood and indirectly increased it through personality traits (harm avoidance, reward dependence, and self-directedness). Parental overprotection in childhood had no direct effect on well-being in adulthood but decreased well-being in adulthood indirectly through personality traits (harm avoidance, reward dependence, and self-directedness) and increased it through one personality trait (self-transcendence).

Conclusions

This study showed that the influences of perceived parental bonding on well-being in adulthood are mediated by self-directedness, harm avoidance, reward dependence, and self-transcendence among the seven personality dimensions evaluated by the Temperament and Character Inventory.
Brain transcriptome analysis reveals subtle effects on mitochondrial function and iron homeostasis of mutations in the SORL1 gene implicated in early onset familial Alzheimer’s disease
Authors: Barthelson Karissa , Pederson Stephen Martin , Newman Morgan , Lardelli Michael
Published: October 2020

To prevent or delay the onset of Alzheimer’s disease (AD), we must understand its molecular basis. The great majority of AD cases arise sporadically with a late onset after 65 years of age (LOAD). However, rare familial cases of AD can occur due to dominant mutations in a small number of genes that cause an early onset prior to 65 years of age (EOfAD). As EOfAD and LOAD share similar pathologies and disease progression, analysis of EOfAD genetic models may give insight into both subtypes of AD. Sortilin-related receptor 1 (SORL1) is genetically associated with both EOfAD and LOAD and provides a unique opportunity to investigate the relationships between both forms of AD. Currently, the role of SORL1 mutations in AD pathogenesis is unclear. To understand the molecular consequences of SORL1 mutation, we performed targeted mutagenesis of the orthologous gene in zebrafish. We generated an EOfAD-like mutation, V1482Afs, and a putatively null mutation, to investigate whether EOfAD-like mutations in sorl1 display haploinsufficiency by acting through loss-of-function mechanisms. We performed mRNA-sequencing on whole brains, comparing wild type fish with their siblings heterozygous for EOfAD-like or putatively loss-of-function mutations in sorl1, or transheterozygous for these mutations. Differential gene expression analysis identified a small number of differentially expressed genes due to the sorl1 genotypes. We also performed enrichment analysis on all detectable genes to obtain a more complete view on changes to gene expression by performing three methods of gene set enrichment analysis, then calculated an overall significance value using the harmonic mean p-value. This identified subtle effects on expression of genes involved in energy production, mRNA translation and mTORC1 signalling in both the EOfAD-like and null mutant brains, implying that these effects are due to sorl1 haploinsufficiency. Surprisingly, we also observed changes to expression of genes occurring only in the EOfAD-mutation carrier brains, suggesting gain-of-function effects. Transheterozygosity for the EOfAD-like and null mutations (i.e. lacking wild type sorl1), caused apparent effects on iron homeostasis and other transcriptome changes distinct from the single-mutation heterozygous fish. Our results provide insight into the possible early brain molecular effects of an EOfAD mutation in human SORL1. Differential effects of heterozygosity and complete loss of normal SORL1 expression are revealed.
Long-term follow-up of patients with anti-cyclic citrullinated peptide antibody-positive connective tissue disease: a retrospective observational study including information on the HLA-DRB1 allele and citrullination dependency
Authors: Iwasaki Takeshi , Nakabo Shuichiro , Terao Chikashi , Murakami Kosaku , Nakashima Ran , Hashimoto Motomu , Imura Yoshitaka , Yukawa Naoichiro , Yoshifuji Hajime , Miura Yasuo , Yurugi Kimiko , Maekawa Taira , van Delft Myrthe A. M. , Trouw Leendert A. , Fujii Takao , Mimori Tsuneyo , Ohmura Koichiro
Published: October 2020

Background

The anti-cyclic citrullinated peptide (CCP) antibody is a diagnostic biomarker of rheumatoid arthritis (RA). However, some non-RA connective tissue disease (CTD) patients also test positive for the anti-CCP antibody and, thus, may ultimately develop RA. We retrospectively investigated whether anti-CCP-positive non-RA CTD patients developed RA and attempted to identify factors that may differentiate RA-overlapping CTD from pure CTD.

Methods

In total, 842 CTD patients with a primary diagnosis that was not RA were selected from our CTD database as of December 2012. Anti-CCP antibody titers were obtained from a retrospective chart review or measured using stored sera. RA was diagnosed according to the 1987 revised American College of Rheumatology classification criteria. Thirty-three anti-CCP-positive non-RA CTD patients were retrospectively followed up for the development of RA. Bone erosions on the hands and feet were assessed by X-ray. Citrullination dependency was evaluated by an in-house ELISA, the HLA-DRB1 allele was typed, and the results obtained were then compared between RA-overlapping and non-RA anti-CCP-positive CTD patients.

Results

Two out of 33 anti-CCP-positive CTD patients (6.1%) developed RA during a mean follow-up period of 8.9 years. X-rays were examined in 27 out of the 33 patients, and only one (3.7%) showed bone erosions. The frequency of the HLA-DRB1 shared epitope (SE) and anti-CCP antibody titers were both significantly higher in anti-CCP-positive RA-overlapping CTD patients than in anti-CCP-positive non-RA CTD patients, while no significant differences were observed in citrullination dependency.

Conclusions

Anti-CCP-positive non-RA CTD patients rarely developed RA. HLA-DRB1 SE and anti-CCP antibody titers may facilitate the differentiation of RA-overlapping CTD from anti-CCP-positive non-RA CTD.
Correction to: MEIS2 regulates endothelial to hematopoietic transition of human embryonic stem cells by targeting TAL1
Authors: Wang Mengge , Wang Hongtao , Wen Yuqi , Chen Xiaoyuan , Liu Xin , Gao Jie , Su Pei , Xu Yuanfu , Zhou Wen , Shi Lihong , Zhou Jiaxi
Published: October 2020

An amendment to this paper has been published and can be accessed via the original article.
Enhancement of the antioxidant and skin permeation properties of eugenol by the esterification of eugenol to new derivatives
Authors: Makuch Edyta , Nowak Anna , Günther Andrzej , Pełech Robert , Kucharski Łukasz , Duchnik Wiktoria , Klimowicz Adam
Published: October 2020

The aim of the study was to determine the antioxidant activity and assess the lipophilicity and skin penetration of eugenyl chloroacetate (EChA), eugenyl dichloroacetate (EDChA), and eugenyl trichloroacetate (ETChA). Identification of the obtained products was based on gas chromatography (GC), infrared spectroscopy (FTIR/ATR), gas chromatography coupled with mass spectrometry (GC-MS), and the analysis of 13C-NMR and 1H-NMR spectra. The antioxidative capacity of the derivatives obtained was determined by the DPPH free radical reduction method, while the octanol/water partition coefficient (shake-flask method) was tested to determine the lipophilicity of these compounds. In the next stage of testing EDChA and ETChA–(compounds characterized by the highest degree of free radical scavenging), the penetration of DPPH through pig skin and its accumulation in the skin were evaluated. For comparison, penetration studies of eugenol alone as well as dichloroacetic acid (DChAA) and trichloroacetic acid (TChAA) were also carried out. The antioxidant activity (DPPH, ABTS, and Folin–Ciocalteu methods) of the fluid that penetrated through pig skin was also evaluated. The in vitro pig skin penetration study showed that eugenol derivatives are particularly relevant for topical application. The obtained derivatives were characterized by a high level of antioxidant activity estimated after 24 h of conducting the experiment, which indicates long-term protection against reactive oxygen species (ROS) in the deeper layers of the skin.
Electromagnetic radiation-based IC device identification and verification using deep learning
Authors: Zhang Hong-xin , Liu Jia , Xu Jun , Zhang Fan , Cui Xiao-tong , Sun Shao-fei
Published: October 2020

The electromagnetic radiation of electronic equipment carries information and can cause information leakage, which poses a serious threat to the security system; especially the information leakage caused by encryption or other important equipment will have more serious consequences. In the past decade or so, the attack technology and means for the physical layer have developed rapidly. And system designers have no effective method for this situation to eliminate or defend against threats with an absolute level of security. In recent years, device identification has been developed and improved as a physical-level technology to improve the security of integrated circuit (IC)-based multifactor authentication systems. Device identification tasks (including device identification and verification) are accomplished by monitoring and exploiting the characteristics of the IC’s unintentional electromagnetic radiation, without requiring any modification and process to hardware devices, thereby providing versatility and adapting existing hardware devices. Device identification based on deep residual networks and radio frequency is a technology applicable to the physical layer, which can improve the security of integrated circuit (IC)-based multifactor authentication systems. Device identification tasks (identification and verification) are accomplished by passively monitoring and utilizing the inherent properties of IC unintended RF transmissions without requiring any modifications to the analysis equipment. After the device performs a series of operations, the device is classified and identified using a deep residual neural network. The gradient descent method is used to adjust the network parameters, the batch training method is used to speed up the parameter tuning speed, the parameter regularization is used to improve the generalization, and finally, the Softmax classifier is used for classification. In the end, 28 chips of 4 models can be accurately identified into 4 categories, then the individual chips in each category can be identified, and finally 28 chips can be accurately identified, and the verification accuracy reached 100%. Therefore, the identification of radio frequency equipment based on deep residual network is very suitable as a countermeasure for implementing the device cloning technology and is expected to be related to various security issues.
On the modeling of the interaction between tumor growth and the immune system using some new fractional and fractional-fractal operators
Authors: Ghanbari Behzad
Published: October 2020

Humans are always exposed to the threat of infectious diseases. It has been proven that there is a direct link between the strength or weakness of the immune system and the spread of infectious diseases such as tuberculosis, hepatitis, AIDS, and Covid-19 as soon as the immune system has no the power to fight infections and infectious diseases. Moreover, it has been proven that mathematical modeling is a great tool to accurately describe complex biological phenomena. In the recent literature, we can easily find that these effective tools provide important contributions to our understanding and analysis of such problems such as tumor growth. This is indeed one of the main reasons for the need to study computational models of how the immune system interacts with other factors involved. To this end, in this paper, we present some new approximate solutions to a computational formulation that models the interaction between tumor growth and the immune system with several fractional and fractal operators. The operators used in this model are the Liouville–Caputo, Caputo–Fabrizio, and Atangana–Baleanu–Caputo in both fractional and fractal-fractional senses. The existence and uniqueness of the solution in each of these cases is also verified. To complete our analysis, we include numerous numerical simulations to show the behavior of tumors. These diagrams help us explain mathematical results and better describe related biological concepts. In many cases the approximate results obtained have a chaotic structure, which justifies the complexity of unpredictable and uncontrollable behavior of cancerous tumors. As a result, the newly implemented operators certainly open new research windows in further computational models arising in the modeling of different diseases. It is confirmed that similar problems in the field can be also be modeled by the approaches employed in this paper.
A numerical method using Laplace-like transform and variational theory for solving time-fractional nonlinear partial differential equations with proportional delay
Authors: Bekela Alemu Senbeta , Belachew Melisew Tefera , Wole Getinet Alemayehu
Published: October 2020

Time-fractional nonlinear partial differential equations (TFNPDEs) with proportional delay are commonly used for modeling real-world phenomena like earthquake, volcanic eruption, and brain tumor dynamics. These problems are quite challenging, and the transcendental nature of the delay makes them even more difficult. Hence, the development of efficient numerical methods is open for research. In this paper, we use the concepts of Laplace-like transform and variational theory to develop a new numerical method for solving TFNPDEs with proportional delay. The stability and convergence of the method are analyzed in the Banach sense. The efficiency of the proposed method is demonstrated by solving some test problems. The numerical results show that the proposed method performs much better than some recently developed methods and enables us to obtain more accurate solutions.
Inferring an animal’s environment through biologging: quantifying the environmental influence on animal movement
Authors: Eikelboom J. A. J. , de Knegt H. J. , Klaver M. , van Langevelde F. , van der Wal T. , Prins H. H. T.
Published: October 2020

Background

Animals respond to environmental variation by changing their movement in a multifaceted way. Recent advancements in biologging increasingly allow for detailed measurements of the multifaceted nature of movement, from descriptors of animal movement trajectories (e.g., using GPS) to descriptors of body part movements (e.g., using tri-axial accelerometers). Because this multivariate richness of movement data complicates inference on the environmental influence on animal movement, studies generally use simplified movement descriptors in statistical analyses. However, doing so limits the inference on the environmental influence on movement, as this requires that the multivariate richness of movement data can be fully considered in an analysis.

Methods

We propose a data-driven analytic framework, based on existing methods, to quantify the environmental influence on animal movement that can accommodate the multifaceted nature of animal movement. Instead of fitting a simplified movement descriptor to a suite of environmental variables, our proposed framework centres on predicting an environmental variable from the full set of multivariate movement data. The measure of fit of this prediction is taken to be the metric that quantifies how much of the environmental variation relates to the multivariate variation in animal movement. We demonstrate the usefulness of this framework through a case study about the influence of grass availability and time since milking on cow movements using machine learning algorithms.

Results

We show that on a one-hour timescale 37% of the variation in grass availability and 33% of time since milking influenced cow movements. Grass availability mostly influenced the cows’ neck movement during grazing, while time since milking mostly influenced the movement through the landscape and the shared variation of accelerometer and GPS data (e.g., activity patterns). Furthermore, this framework proved to be insensitive to spurious correlations between environmental variables in quantifying the influence on animal movement.

Conclusions

Not only is our proposed framework well-suited to study the environmental influence on animal movement; we argue that it can also be applied in any field that uses multivariate biologging data, e.g., animal physiology, to study the relationships between animals and their environment.
Nilvadipine suppresses inflammation via inhibition of P-SYK and restores spatial memory deficits in a mouse model of repetitive mild TBI
Authors: Morin Alexander , Mouzon Benoit , Ferguson Scott , Paris Daniel , Browning Mackenzie , Stewart William , Mullan Mike , Crawford Fiona
Published: October 2020

Repeated exposure to mild TBI (mTBI) has been linked to an increased risk of Alzheimer’s disease (AD), chronic traumatic encephalopathy (CTE) and other neurodegenerative diseases. Some pathological features typically observed in AD have been found in postmortem brains of TBI and CTE, hence treatments tested for AD have a potential to be effective against r-mTBI outcomes. Neuroinflammation may present a possible answer due to its central role both in acute brain injury and in chronic degenerative-like disorders. Our previous studies have shown that drug nilvadipine, acting as an inhibitor of spleen tyrosine kinase (SYK), is effective at reducing inflammation, tau hyperphosphorylation and amyloid production in AD mouse models. To demonstrate the effect of nilvadipine in the absence of age-related variables, we introduced the same treatment to young r-mTBI mice. We further investigate therapeutic mechanisms of nilvadipine using its racemic properties. Both enantiomers, (+)-nilvadipine and (−)-nilvadipine, can lower SYK activity, whereas (+)-nilvadipine is also a potent L-type calcium channel blocker (CCB) and shown to be anti-hypertensive. All r-mTBI mice exhibited increased neuroinflammation and impaired cognitive performance and motor functions. Treatment with racemic nilvadipine mitigated the TBI-induced inflammatory response and significantly improved spatial memory, whereas (−)-enantiomer decreased microgliosis and improved spatial memory but failed to reduce the astroglial response to as much as the racemate. These results suggest the therapeutic potential of SYK inhibition that is enhanced when combined with the CCB effect, which indicate a therapeutic advantage of multi-action drugs for r-mTBI.
Synaptic and metabolic gene expression alterations in neurons that are recipients of proteopathic tau seeds
Authors: Perez-Rando Marta , Dujardin Simon , Bennett Rachel E. , Commins Caitlin , Nibhanupudy Tara , Hyman Bradley T.
Published: October 2020

Recent studies suggest that misfolded tau molecules can be released, and taken up by adjacent neurons, propagating proteopathic seeds across neural systems. Yet critical to understanding whether tau propagation is relevant in pathophysiology of disease would be to learn if it alters neuronal properties. We utilized high resolution multi-color in situ hybridization technology, RNAScope, in a well-established tau transgenic animal, and found that a subset of neurons in the cortex do not appear to express the transgene, but do develop phospho-tau positive inclusions, consistent with having received tau seeds. Recipient neurons show decreases in their expression of synaptophysin, CAMKIIα, and mouse tau in both young and old animals. These results contrast with neurons that develop tau aggregates and also overexpress the transgene, which have few changes in expression of metabolic and synaptic markers. Taken together, these results strongly suggest that tau propagation impacts neuronal functional integrity.
Prognostic value of 18F-fluorodeoxyglucose positron emission tomography in patients with small hepatocellular carcinoma treated by radiofrequency ablation
Authors: Ida Yoshiyuki , Tamai Hideyuki , Shingaki Naoki , Shimizu Ryo , Maeshima Shuya , Maekita Takao , Iguchi Mikitaka , Terada Masaki , Kitano Masayuki
Published: October 2020

Background

18F-fluorodeoxyglucose (18F-FDG) uptake in hepatocellular carcinoma (HCC) is significantly associated with early recurrence and survival after curative surgical resection. However, there are no reports regarding the relationship between 18F-FDG uptake and outcomes after radiofrequency ablation (RFA). A prospective cohort study was conducted to evaluate the prognostic value of 18F-FDG positron emission tomography (PET) in HCC patients after RFA.

Methods

A total of 121 consecutive patients with primary HCC (≤3 tumors, of diameter ≤ 3 cm) without vascular invasion on imaging were examined by 18F-FDG-PET computed tomography prior to RFA. An HCC with a component of 18F-FDG uptake visibly stronger than that of surrounding liver was defined as 18F-FDG-PET positive.

Results

The median follow-up period was 1267 days. There were 110 18F-FDG-PET negative and 11 positive tumors. The cumulative 1-year recurrence rates in the 18F-FDG negative and positive groups were 30 and 64% (P = 0.017), respectively, and cumulative 1-year metastatic recurrence rates were 6 and 36% (P < 0.001), respectively. The cumulative 5-year survival rates were 88 and 22% (P < 0.001), respectively. Multivariate analysis revealed 18F-FDG-PET positivity and tumor size as independent factors related to metastatic recurrence and survival after RFA.

Conclusions

18F-FDG-PET positivity was significantly associated with outcomes after RFA. RFA should not be readily selected as the first-line treatment for small HCC that includes a component of visually strong 18F-FDG uptake.
Endovascular repair using a covered stent for a ruptured infected aneurysm of the superior mesenteric artery after pancreaticoduodenectomy: a case report
Authors: Yamashita Tokuyuki , Yamanaka Kenya , Izumi Ai , Matsui Jun , Kurimoto Makoto , Aoki Hikaru , Tamura Jun
Published: October 2020

Background

Delayed arterial hemorrhage after pancreaticoduodenectomy is a life-threatening complication. There are no reports about infected aneurysms of the superior mesenteric artery after pancreaticoduodenectomy without clinically relevant pancreatic fistula.

Case presentation

A 78-year-old woman with borderline resectable pancreatic ductal adenocarcinoma involving the superior mesenteric arterial nerve plexus underwent pancreaticoduodenectomy with en bloc resection of the superior mesenteric vein and the superior mesenteric arterial nerve plexus after neoadjuvant chemotherapy. On postoperative day 14, she had bacteremia and sudden fever with chills. During the postoperative course, macroscopic abscesses or distinct infectious signs, including pancreatic fistula or bile fistula, were not present, but pylephlebitis was observed. After the antimicrobial treatment course, the patient was discharged. After 17 days, she was hospitalized for melena. Contrast-enhanced computed tomography showed a ruptured aneurysm of the superior mesenteric artery into the small intestine without a major intraabdominal abscess. E. coli was isolated from blood cultures. The patient was diagnosed with a ruptured infected aneurysm of the superior mesenteric artery. She was treated successfully with a covered stent by the cardiology team. There was no recurrence of bleeding at the 4-month follow-up, and the stent was patent in all subsequent computed tomography scans.

Conclusions

Endovascular repair using a covered stent was effective in palliating acute bleeding from an infected aneurysm of the superior mesenteric artery.