bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating Semantic Knowledge Through a Semantic Association Task in Individuals With Dementia
Authors: Luzzatti Claudio , Mauri Ilaria , Castiglioni Stefania , Zuffi Marta , Spartà Chiara , Somalvico Francesco , Franceschi Massimo
Published: April 2020

Conceptual knowledge is supported by multiple semantic systems that are specialized for the analysis of different properties associated with object concepts. Various types of semantic association between concrete concepts—categorical (CA), encyclopedic (EA), functional (FA), and visual-encyclopedic (VEA) associations—were tested through a new picture-to-picture matching task (semantic association task, SAT). Forty individuals with Alzheimer’s disease (AD), 13 with behavioral variant of frontotemporal dementia (bv-FTD), 6 with primary progressive aphasia (PPA), and 37 healthy participants were tested with the SAT. Within-group comparisons highlighted a global impairment of all types of semantic association in bv-FTD individuals but a disproportionate impairment of EA and FA, with relative sparing of CA and VEA, in AD individuals. Single-case analyses detected dissociations in all dementia groups. Conceptual knowledge can be selectively impaired in various types of neurodegenerative disease on the basis of the specific cognitive process that is disrupted.
The Protestant Ethic and the Spirit of Facebook: Updating Identity Economics
Authors: Lim Elisha
Published: April 2020

Scholars and news media generally name Facebook’s two central problems: that its data collection practices are a threat to user privacy, and that stricter regulations are required to prevent “bad actor” from spreading hate and disinformation. However separating these two concerns—personal data collection and bad actors—overlooks the way that one generates the other. First, this article builds on critical race scholarship to examine how identity politics are historically distorted and commodified into profitable vigilance and intolerance, in what I call a transition from identity politics, to personal identity economics. Facebook’s Ad Manager, for example, reveals how personal identities are itemized as advertising assets, which are cultivated through deeper, more trenchant identity politics. Second, this article theorizes about what makes such staunch, intolerant identity politics addictive. Drawing on Max Weber’s theories of the Protestant Ethic, this article explores how Facebook activism thrives on deep-rooted Christian paradigms of dogma, virtue, redemption, and piety. As dogmatic personal identity economics spread across the globe, they testify to how Facebook’s business model manufactures bad actors.
Habitual Disclosure: Routine, Affordance, and the Ethics of Young Peoples Social Media Data Surveillance
Authors: Southerton Clare , Taylor Emmeline
Published: April 2020

Drawing on findings from qualitative interviews and photo elicitation, this article explores young people’s experiences of breaches of trust with social media platforms and how comfort is re-established despite continual violations. It provides rich qualitative accounts of users habitual relations with social media platforms. In particular, we seek to trace the process by which online affordances create conditions in which “sharing” is regarded as not only routine and benign but pleasurable. Rather it is the withholding of data that is abnormalized. This process has significant implications for the ethics of data collection by problematizing a focus on “consent” to data collection by social media platforms. Active engagement with social media, we argue, is premised on a tentative, temporary, shaky trust that is repeatedly ruptured and repaired. We seek to understand the process by which violations of privacy and trust in social media platforms are remediated by their users and rendered ordinary again through everyday habits. We argue that the processes by which users become comfortable with social media platforms, through these routines, call for an urgent reimagining of data privacy beyond the limited terms of consent.
Genetics of systemic sclerosis
Authors: Ishikawa Yuki , Terao Chikashi
Published: April 2020

Systemic sclerosis is an autoimmune disease characterized by generalized fibrosis in connective tissues and internal organs as consequences of microvascular dysfunction and immune dysfunctions, which leads to premature death in affected individuals. The etiology of systemic sclerosis is complex and poorly understood, but as with most autoimmune diseases, it is widely accepted that both environmental and genetic factors contribute to disease risk. During the last decade, the number of genetic markers convincingly associated with systemic sclerosis has exponentially increased. In this article, we briefly mention the genetic components of systemic sclerosis. Then, we review the classical and novel genetic associations with systemic sclerosis, analyzing the firmest and replicated signals within non–human leukocyte antigen genes, identified by both candidate gene approach and genome-wide association studies. We also provide an insight into the future perspectives that will shed more light into the complex genetic background of the disease. Despite the remarkable advance of systemic sclerosis genetics during the last decade, the use of the new genetic technologies such as next-generation sequencing, as well as the deep phenotyping of the study cohorts, to fully characterize the genetic component of this disease is imperative to identify causal variants, which leads to more targeted and effective treatment of systemic sclerosis.
Radicalization as cause and consequence of violence in genocides and mass killings
Authors: McDoom Omar Shahabudin
Published: April 2020

Major theories of participation in genocides and mass killings offer seemingly opposing explanatory logics for how and why individuals come to commit violence. The long-standing consensus on “perpetrator ordinariness” contrasts with explanations that continue to highlight the prior, intensely held negative attitudes and beliefs about the victim group. I propose a theoretical reconciliation. Radicalization would be better theorized not only as an antecedent to the act of violence but also as a consequence of it. Killing transforms individuals. A well-established point in social psychology, not only do attitudes drive behaviors, but behaviors also shape attitudes. Some perpetrators dehumanize their victims, internalize exclusionary ideologies, and otherwise develop negative sentiments toward their victims following their participation in the violence. Attitudinal shift becomes a form of dissonance-reduction. Perpetrators come to espouse radical beliefs in order to justify their actions. This revised theorization has implications for our understanding of (1) perpetrator heterogeneity: individuals must vary in their vulnerability to radicalization, and (2) non-instrumental violence: why we often observe the infliction of gratuitous pain and suffering on victims. I re-interpret testimony of perpetrators from Rwanda, the Holocaust, Bosnia-Herzegovina, and Cambodia to support the article’s central theoretical proposition.
Patterns of care and clinical outcomes with cytarabine-anthracycline induction chemotherapy for AML patients in the United States
Authors: Zeidan Amer M. , Podoltsev Nikolai A. , Wang Xiaoyi , Zhang Chi , Bewersdorf Jan Philipp , Shallis Rory M. , Huntington Scott F. , Neparidze Natalia , Giri Smith , Gore Steven D. , Davidoff Amy J. , Ma Xiaomei , Wang Rong
Published: April 2020

Cytarabine-anthracycline based intensive induction chemotherapy (IC) remains the standard of care for remission induction among fit patients with newly diagnosed acute myeloid leukemia (AML) in the United States (US). However, the mortality rate outside of clinical IC trials, predictors of death, and resource utilization during admission for IC have not been thoroughly examined. We used the Premier Healthcare database to identify adult patients (aged 18-89 years) treated with cytarabine-anthracycline-based IC during their first recorded inpatient stay for AML during the contemporary period of 2010 to 2017. We identified factors associated with inpatient death or discharge to hospice, using multivariable logistic regression models. We also assessed the patterns of inpatient healthcare resource utilization. A total of 6442 patients with AML from 313 hospitals who were treated with IC were identified. Median age was 61 years (interquartile range [IQR], 50-68 years), and 56% were men. Median length of stay was 29 (IQR, 25-38) days, with rates of in-hospital death and discharge to hospice of 12.3% and 3.7% (17.9% and 6.3% among patients aged ≥65 years), respectively. Predictors of in-hospital death or discharge to hospice included older age, geographic region, and lower hospital volume. During admission, 28.0%, 12.6%, and 4.0% of patients required treatment in intensive care units, mechanical ventilation, and dialysis, respectively. Despite improvements in supportive care in the contemporary era, inpatient mortality during first hospitalization for adult patients with AML treated with IC in the US remains high particularly among older patients.
Evaluating the performance of the vessel train concept
Authors: Meersman Hilde , Moschouli Eleni , NanwayBoukani Loghman , Sys Christa , van Hassel Edwin , Vanelslander Thierry , Van de Voorde Eddy
Published: April 2020

Objective

To improve safety and address current employment challenges in the waterborne transport sector, the VT concept is developed. The VT is a vessel platooning concept that is semi-autonomous. The VT is composed by one Leader Vessel (LV) and Follower Vessels (FVs) that will be connected with each other with sensors. The research examines from a business-economic and societal perspective, whether it is interesting to invest in and use the VT, instead of sailing with a conventional vessel.

Methods

The business-economic performance of the VT is tested from theperspective of the vessel owner (VO) for the inland navigation trajectory Antwerp – Rotterdam – Duisburg, using a relevant transport model. With this research, the results allow comparison of the total costs of the reference scenario with alternative VT scenarios and thus allow to see which of the scenarios are interesting for the VOs to invest in and use the VT. From a societal perspective, the expected modal shift from road (and possibly rail) to inland waterways and the external cost savingsfor the society are calculated.

Results

The results show that for some scenarios the expected benefits of the society are high, thanks to the modal shift from road (and rail) to inland waterway transport (IWT) mode and to the reduced external costs. However, for the scenarios with negative business-economic cost savings, negative welfare gains are found due to the likelihood of reverse modal shift from IWT to road (and rail), because the VT is found more expensive than the conventional sailing.

Implications for research/policy

If all the actors of the VT project have benefits, being theVO, the VT organizer (VTO) and the cargo owner (CO), the implementation of the VT concept will be decided. The implementation of the concept can still be decided, if the loss of one of the actors is compensated by the other(s) actor(s). Thus, subsidies by the government are not needed. However, what is needed is the change of the current legislation that would allow the sailing of the VT with reduced crew on board in inland waterways.
Transcriptome analysis of responses in Brachypodium distachyon overexpressing the BdbZIP26 transcription factor
Authors: Martin Ruth C. , Kronmiller Brent A. , Dombrowski James E.
Published: April 2020

Background

Biotic and abiotic stresses are the major cause of reduced growth, persistence, and yield in agriculture. Over the past decade, RNA-Sequencing and the use of transgenics with altered expression of stress related genes have been utilized to gain a better understanding of the molecular mechanisms leading to salt tolerance in a variety of species. Identification of transcription factors that, when overexpressed in plants, improve multiple stress tolerance may be valuable for crop improvement, but sometimes overexpression leads to deleterious effects during normal plant growth.

Results

Brachypodiumconstitutively expressing the BdbZIP26:GFP gene showed reduced stature compared to wild type plants (WT). RNA-Seq analysis comparing WT and bZIP26 transgenic plants revealed 7772 differentially expressed genes (DEGs). Of these DEGs, 987 of the DEGs were differentially expressed in all three transgenic lines. Many of these DEGs are similar to those often observed in response to abiotic and biotic stress, including signaling proteins such as kinases/phosphatases, calcium/calmodulin related proteins, oxidases/reductases, hormone production and signaling, transcription factors, as well as disease responsive proteins. Interestingly, there were many DEGs associated with protein turnover including ubiquitin-related proteins, F-Box and U-box related proteins, membrane proteins, and ribosomal synthesis proteins. Transgenic and control plants were exposed to salinity stress. Many of the DEGs between the WT and transgenic lines under control conditions were also found to be differentially expressed in WT in response to salinity stress. This suggests that the over-expression of the transcription factor is placing the plant in a state of stress, which may contribute to the plants diminished stature.

Conclusion

The constitutive expression of BdbZIP26:GFP had an overall negative effect on plant growth and resulted in stunted plants compared to WT plants under control conditions, and a similar response to WT plants under salt stress conditions. The results of gene expression analysis suggest that the transgenic plants are in a constant state of stress, and that they are trying to allocate resources to survive.
The efficacy of Antipyretic Analgesics administration intravenously for Preventing Rocuronium-Associated Pain/Withdrawal Response: a systematic review and meta-analysis
Authors: Wang Jia , Cui Yu , Liu Bin , Chen Jianfeng
Published: April 2020

Background

Rocuronium-associated injection pain/withdrawal response (RAIPWR) was non-ideal but occurred frequently when injection intravenously during anesthesia induction. Many studies had reported that pretreating with antipyretic analgesics (AAs) could reduce the occurrence of RAIPWR, but there was no consensus yet. Therefore, this meta-analysis was designed to systematically evaluate the benefits of AAs on RAIPWR in patients.

Methods

PubMed, Cochrane Library, Ovid, EMbase, Chinese National Knowledge Infrastructure (CNKI), Wan Fang Data were searched by January 1st 2019 for randomized controlled trials (RCTs) applying AAs to alleviate RAIPWR in patients who underwent elective surgery under general anesthesia. Two investigators assessed quality of RCTs and extracted data respectively and the meta-analysis was carried on Revman 5.3 software. Moreover, we compared AAs in pros and cons directly with lidocaine, the most reported medicine to prevent RAIPWR.

Results

Data were analyzed from 9 RCTs totaling 819 patients. The results of Meta-analysis showed that compared to the control group, pretreating with AAs could prevent the total occurrence of RAIPWR [Risk ratio (RR), 0.52; 95% confidence interval (CI), 0.42 to 0.66; P < 0.0001], and took effect on moderate (RR, 0.56; 95%CI, 0.43 to 0.73; P < 0.0001) and severe RAIPWR (RR = 0.14; 95%CI, 0.08 to 0.24; P < 0.00001). When compared to lidocaine, the preventive effect was not so excellent as the latter but injection pain induced by prophylactic occurred less.

Conclusion

The currently available evidence suggested that pretreating with AAs intravenously could alleviate RAIPWR.

Trial registration

PROSPERO CRD42019129776.
A Chinese case of fragile X-associated tremor/ataxia syndrome (FXTAS) with orthostatic tremor:case report and literature review on tremor in FXTAS
Authors: Zhao Cuiping , Liu Yiming , Wang Yihua , Li Hongyan , Zhang Bin , Yue Yaoxian , Zhang Jianyuan
Published: April 2020

Background

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late onset, X-linked genetic, neurodegenerative disorder caused by a “premutation (PM)” in the fragile X mental retardation 1 (FMR1) gene. Here we report a case of FXTAS from mainland of China who presented with rare orthostatic tremor. A review of tremor of FXTAS in the literature is also included.

Case presentation

A 67-year-old right-handed farmer started with tremor of both legs 8 years ago which was present while standing but absent when sitting or lying and progressed with unsteady gait one and a half years ago. The brain MRI showed high intensity signal in the bilateral middle cerebellar peduncles (MCP) in T2-weighted and fluid-attenuated inversion recovery (FLAIR) images and gene test for premutation for FMR1 was positive with 101 CGG repeats. The patient met the the diagnosis of definite FXTAS. Clonazepam and topiramate were administered to control tremor. We reviewed the literature and identified 64 cases with detailed clinical and genetic information. Orthostatic tremor associated with FXTAS is very rare. We found 85.2% patients reported tremor,42.6% with intention tremor,36.1% with kinetic tremor,32.8% with rest tremor and 29.5% with posture tremor. 37.7% of patients who have tremor showed at least two types of tremor. There were 6 patients with isolated rest tremor. There was 2 patient with voice tremor and 6 with head tremor. We also found that 74.6% FXTAS patients had family history of FMR1 gene associated diseases including Fragile X syndrome (FXS), FXTAS or fragile X-associated primary ovarian insufficiency (FXPOI).

Conclusions

Adding our data to the available literature suggests that orthostatic tremor could be a rare initial manifestation of FXTAS and the review will increasing our understanding the phenotype of tremor in FXTAS. Family history of FMR1 gene associated diseases might be an important clue to the diagnosis.
Multidisciplinary lifestyle intervention in children and adolescents - results of the project GRIT (Growth, Resilience, Insights, Thrive) pilot study
Authors:   Project GRIT Team, Mayr Hannah L. , Cohen Felicity , Isenring Elizabeth , Soenen Stijn , Marshall Skye
Published: April 2020

Background

During childhood and adolescence leading behavioural risk factors for the development of cardiometabolic diseases include poor diet quality and sedentary lifestyle. The aim of this study was to determine the feasibility and effect of a real-world group-based multidisciplinary intervention on cardiorespiratory fitness, diet quality and self-concept in sedentary children and adolescents aged 9 to 15 years.

Methods

Project GRIT (Growth, Resilience, Insights, Thrive) was a pilot single-arm intervention study. The 12-week intervention involved up to three outdoor High Intensity Interval Training (HIIT) running sessions per week, five healthy eating education or cooking demonstration sessions, and one mindful eating and Emotional Freedom Technique psychology session. Outcome measures at baseline and 12-week follow-up included maximal graded cardiorespiratory testing, the Australian Child and Adolescent Eating Survey, and Piers-Harris 2 children’s self-concept scale. Paired samples t-test or Wilcoxon signed-rank test were used to compare baseline and follow-up outcome measures in study completers only.

Results

Of the 38 recruited participants (median age 11.4 years, 53% male), 24 (63%) completed the 12-week intervention. Dropouts had significantly higher diet quality at baseline than completers. Completers attended a median 58 (IQR 55–75) % of the 33 exercise sessions, 60 (IQR 40–95) % of the dietary sessions, and 42% attended the psychology session. No serious adverse events were reported. Absolute VO2peak at 12 weeks changed by 96.2 ± 239.4 mL/min (p = 0.06). As a percentage contribution to energy intake, participants increased their intake of healthy core foods by 6.0 ± 11.1% (p = 0.02) and reduced median intake of confectionary (− 2.0 [IQR 0.0–3.0] %, p = 0.003) and baked products (− 1.0 [IQR 0.0–5.0] %, p = 0.02). Participants significantly improved self-concept with an increase in average T-Score for the total scale by 2.8 ± 5.3 (p = 0.02) and the ‘physical appearance and attributes’ domain scale by median 4.0 [IQR 0.5–4.0] (p = 0.02).

Conclusions

The 12-week group-based multidisciplinary lifestyle intervention for children and adolescents improved diet quality and self-concept in study completers. Future practice and research should focus on providing sustainable multidisciplinary lifestyle interventions for children and adolescents aiming to improve long-term health and wellbeing.

Trial registration

ANZCTR, ACTRN12618001249246. Registered 24 July 2019 - Retrospectively registered
Decreased handgrip strength can predict lung function impairment in male workers: a cross sectional study
Authors: Kanai Makiko , Kanai Osamu , Fujita Kohei , Mio Tadashi , Ito Masato
Published: April 2020

Background

Spirometry is useful for evaluating respiratory health status and predicting health-related outcomes. As spirometry requires skilled technician and takes time, it is useful to find simple way for predicting lung function impairment. The aim of this study was to investigate which tests could predict lung function impairment among workers.

Methods

This prospective study included workers of manufacturing industry who underwent health check-ups in 2017. Subjects underwent the chronic obstructive pulmonary disease (COPD) assessment test (CAT), spirometry, and physical fitness assessments, including handgrip strength (HGS). Lung function impairment was defined as a decline in any of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), or a FEV1/FVC ratio less than the lower limit of normal (LLN).

Results

Complete data on 475 workers (366 men, 50.4% ever smokers) were available. Lung function impairment was observed in 99 subjects (64 men). Men with lung function impairment had significantly higher rate of ever-smoking, passive smoking at home in childhood, high CAT scores, and decreased HGS, compared with those without. On multivariate analyses, ever-smoking (odds ratio [OR], 2.50; 95% confidence intervals [CI], 1.25–4.97), passive smoking at home in childhood (OR, 2.71; 95% CI, 1.16–6.32), CAT scores (OR, 1.06; 95% CI, 1.01–1.12), and HGS (OR, 0.73; 95% CI, 0.57–0.92) were independently associated with lung function impairment in men.

Conclusions

Ever-smoking, passive smoking at home in childhood, high CAT scores, and decreased HGS are significantly associated with lung function impairment in men.

Trial registration

Registration number: UMIN000028011. Date of registration: July 1, 2017.
An evidence-based self-management package for urinary incontinence in older women: a mixed methods feasibility study
Authors: Fu Yu , Nelson E. Andrea , McGowan Linda
Published: April 2020

Background

Urinary incontinence (UI) is a distressing condition that limits women’s quality of life and places a heavy burden on health care services. Behavioural treatments are recommended as a first-line treatment. An evidence-based self-management package was developed following the Medical Research Council (MRC) framework for complex interventions. This study aimed to evaluate the feasibility and acceptability of the intervention.

Methods

A mixed-methods approach was undertaken, namely a randomised controlled feasibility study with nested qualitative study. Fifty women aged 55 or over living with UI, recruited from community centres were randomly assigned to either a 3-month course with the package with a support session or a control group to receive the same package only 3 months later. Principal outcome measures were: self-reported quality of life, UI severity, self-efficacy and psychological status. Analysis of covariance was undertaken to estimate within- and between- group changes for all outcomes. Acceptability was explored using individual interviews at follow-up.

Results

Fifty women were randomised (24 to intervention, 26 to control); mean age of 69.7 (±9.1) years and mean UI frequency 2.2 (±2.2) episodes/day at baseline. Overall, 49 women (98%) completed 3-month follow-up (24 in the intervention, 25 in the control). A positive trend was detected in the impact of UI on their personal relationships (− 3.89, p = 0.088), symptom severity (− 1.77, p = 0.025), UI symptoms scale (− 1.87, p = 0.031) and anxiety status (− 2.31, p = 0.001), respectively. Changes in quality of life and self-efficacy did not differ significantly between groups. Majority of women (71%) in the intervention group reported subjective improvement after 3 months. Spearman correlation coefficient was 0.43 (p < 0.05) between their subjective perception of change and self-efficacy. Women perceived the package being acceptable and described that the package had the potential to increase their knowledge and confidence to manage symptoms and improve quality of life.

Conclusions

The study demonstrated that the self-management package is feasible and acceptable for older women with UI. Further studies are needed with a large sample size in clinical settings to evaluate the effectiveness of this package.

Trial registration

ISRCTN17194896. Registered on 11th September 2019 (retrospectively registered).
Ginger extract versus Loratadine in the treatment of allergic rhinitis: a randomized controlled trial
Authors: Yamprasert Rodsarin , Chanvimalueng Waipoj , Mukkasombut Nichamon , Itharat Arunporn
Published: April 2020

Background

Allergic rhinitis (AR) is a non-infectious immune disease and incidents of the disease has continuously increased in Thailand. Ginger, a Thai herb, is used in food and Thai traditional medicine. This study was designed to assess efficacy and safety of ginger extract in comparison with loratadine for AR treatment.

Methods

AR patients were treated with ginger extract 500 mg (n = 40) against those treated with loratadine 10 mg (n = 40) in a randomized, double-blind, controlled trial for 3 and 6 weeks. The efficacy was evaluated from clinical examinations i.e. total nasal symptom scores (TNSS), cross-sectional area of the nasal cavity with acoustic rhinometry (ARM) and rhinoconjunctivitis quality of life questionnaire (RQLQ). The safety of treatment was measured by blood pressure, blood analysis and history-taking for side effects.

Results

The results showed both ginger extract and loratadine treated groups significantly decreased TNSS scores but there was no significant difference between the two groups. In acoustic rhinometry measurement, the ginger treated group significantly gradually increased the estimated volume of the nasal cavity and decreased distances from the nostril, but the loratadine treated group did not cause a change. Both groups gave significantly improvement in every aspect of the RQLQ at third weeks. The treatment with ginger extract was as safe as loratadine as shown by renal and liver function results obtained from blood analysis. Both treatments had no effect on blood pressure of the patients.

Conclusions

The ginger extract is as good as loratadine in improving nasal symptoms and quality of life in AR patients. However, ginger extract caused less side effects especially, drowsiness, fatigue, dizziness and constipation. Therefore, the ginger extract could be used as alternative treatment for patients with AR.

Trial registration

Registered withClinicalTrials.gov(Registration number:NCT02576808) on 15 October 2015.
Endothelial dysfunction is not a predictor of outcome in chronic obstructive pulmonary disease
Authors: Scherr Andreas , Schumann Desiree M. , Karakioulaki Meropi , Franchetti Léo , Strobel Werner , Zellweger Michael , Tamm Michael , Stolz Daiana
Published: April 2020

Background

Local airway inflammation may cause systemic changes which result in endothelial dysfunction. Only a few studies have used reactive hyperemia peripheral arterial tonometry (RH-PAT) in patients with chronic obstructive pulmonary disease (COPD) in order to measure their endothelial dysfunction.

Objective

To determine the efficacy of endothelial dysfunction, measured by RH-PAT, in assessing disease severity and systemic burden in a cohort of COPD patients.

Methods

In this prospective, monocentric study, 157 patients with moderate to very severe COPD (GOLD class II-IV) were examined for endothelial dysfunction using RH-PAT (Itamar medical Ltd., Caesarea, Israel). In a nested-cohort, examination was repeated at exacerbation. The association between reactive hyperemia index (RHI), augmentation index (AI) and disease severity and outcome parameters was analysed.

Results

57% of the COPD patients had a dysfunctional endothelium and the median (IQR) RHI was 1.42 (1.27–1.53). Exacerbation of COPD was not associated with a significant change in RHI (p = 0.625) or ΑΙ (p = 0.530). None of the diagnostic or clinical outcomes of COPD was associated with RHI or arterial stiffness.

Conclusion

Endothelial dysfunction is common in COPD. However, it does not seem to be a predictor neither of disease severity, nor of outcome and does not change during exacerbations of the disease.
Suppression of peripheral NGF attenuates neuropathic pain induced by chronic constriction injury through the TAK1-MAPK/NF-κB signaling pathways
Authors: Dai Wen-Ling , Yan Bing , Bao Yi-Ni , Fan Ji-Fa , Liu Ji-Hua
Published: April 2020

Background

Anti-nerve growth factor (NGF) monoclonal antibodies (anti-NGF mAbs) have been reported to significantly attenuate pain, but the mechanism involved has not been fully elucidated, and the serious adverse events associated with mAbs seriously limit their clinical use. This study further investigated the mechanism by which peripheral NGF is involved in neuropathic pain and found safe, natural compounds that target NGF to attenuate neuropathic pain.

Methods

Nociception was assessed by the Von Frey hair and Hargreaves’ methods. Western-blotting, qPCR and immunofluorescence were used to detect the cell signaling pathway. RAW264.7 macrophages and RSC96 Schwann cells were cultured for in vitro evaluation.

Results

Intraplantar administration of anti-NGF mAbs suppressed the expression of phosphorylated transforming growth factor-β-activated kinase 1 (TAK1) in the dorsal root ganglion (DRG) and sciatic nerve. Intraplantar administration of a TAK1 inhibitor attenuated CCI-induced neuropathic pain and suppressed the expression of phosphorylated mitogen-activated protein kinases (MAPKs) in the DRG and sciatic nerve. Perisciatic nerve administration oflevo-corydalmine (l-CDL) on the operated side obviously attenuated CCI-induced neuropathic pain and suppressed the expression of mNGF and proNGF. In addition,l-CDL-induced antinociception was reversed by intraplantar administration of NGF. Further results indicated thatl-CDL-induced suppression of phosphorylated TAK1, MAPKs, and p65 and expression of the proinflammatory cytokines TNF-α and IL-1β in the DRG and sciatic nerve were all abolished by NGF. In addition, in vitro experiments indicated thatl-CDL suppressed the secretion of NGF and proNGF in RAW264.7 macrophages and RSC96 Schwann cells, which was abolished by AP-1 and CREB agonists, respectively.

Conclusions

This study showed NGF inhibition suppressed TAK1 in the periphery to attenuate CCI-induced neuropathic pain through inhibition of downstream MAPK and p65 signaling. The natural compoundl-CDL inhibited NGF secretion by macrophages and Schwann cells and downstream TAK1-MAPK/NF-κB signaling in the periphery to attenuate CCI-induced neuropathic pain.

Graphical abstract

Proposed mechanisms underlying the effect ofl-CDL in periphery of CCI rats. In CCI rats, macropahages and Schwann cells could secret NGF to act on the receptors in the periphery to activate TAK1-MAPK/NF-κB axis and promote the release of proinflammatory cytokines, including TNF-α and IL-1β to promote neuropathic pain.l-CDL decreased the secretion of NGF through inhibiting AP-1 and CREB respectively in RAW264.7 and RSC96 Schwann cells to attenuate CCI-induced neuropathic pain by inhibiting the TAK1-p38 MAPK/NF-κB signaling pathway.
High-mobility group box 1 protein antagonizes the immunosuppressive capacity and therapeutic effect of mesenchymal stem cells in acute kidney injury
Authors: Wang Shuo , Cai Songjie , Zhang Weitao , Liu Xigao , Li Yan , Zhang Chao , Zeng Yigang , Xu Ming , Rong Ruiming , Yang Tianshu , Shi Benkang , Chandraker Anil , Yang Cheng , Zhu Tongyu
Published: April 2020

Background

Kidney ischemia reperfusion injury (IRI) is a common cause of acute kidney injury and an unavoidable consequence of kidney transplantation and still lacks specific therapeutics. Recently, mesenchymal stem cell (MSC) has been emerging as a promising cell-based therapy for IRI in the context of transplantation. MSC negatively regulates the secretion of pro-inflammatory as well as the activation of immune cells during IRI through its unique immunosuppressive property.

Methods

We employed mice kidney IRI model and MSC cell line to monitor the IRI related checkpoints. siRNAs were utilized to knock down the potential key factors for mechanistic analysis. Statistical analysis was performed by using one-way ANOVA with Tukey’s post hoc procedure by SPSS.

Results

The expression of high-mobility group box 1 protein (HMGB1) is increased in the acute phase as well as the recovery stage of IRI. Importantly, the HMGB1 upregulation is correlated with the injury severity. HMGB1 diminishes the MSC induced immunosuppressive capacity in the presence of pro-inflammatory cytokines in vitro. Toll like receptor 4 (TLR4)-mediated inducible nitric oxide synthase (iNOS) inhibition contributes to the negative effect of HMGB1 on MSCs. HMGB1-TLR4 signaling inhibition augments the therapeutic efficacy of MSCs in mice renal IRI model.

Conclusions

These findings demonstrate that HMGB1 plays a crucial role in shaping the immunoregulatory property of MSCs within the microenvironments, providing novel insights into the crosstalk between MSCs and microenvironment components, suggesting HMGB1 signals as a promising target to improve MSC-based therapy.
Spinal cord NLRP1 inflammasome contributes to dry skin induced chronic itch in mice
Authors: Fan Jun-Juan , Gao Bo , Song Ao-Qi , Zhu Ya-Jing , Zhou Jun , Li Wei-Zu , Yin Yan-Yan , Wu Wen-Ning
Published: April 2020

Background

Dry skin itch is one of the most common skin diseases and elderly people are believed to be particularly prone to it. The inflammasome has been suggested to play an important role in chronic inflammatory disorders including inflammatory skin diseases such as psoriasis. However, little is known about the role of NLRP1 inflammasome in dry skin-induced chronic itch.

Methods

Dry skin-induced chronic itch model was established by acetone-ether-water (AEW) treatment. Spontaneous scratching behavior was recorded by video monitoring. The expression of nucleotide oligomerization domain (NOD)-like receptor protein 1 (NLRP1) inflammasome complexes, transient receptor potential vanilloid type 1 (TRPV1), and the level of inflammatory cytokines were determined by western blot, quantitative real-time PCR, and enzyme-linked immunosorbent assay (ELISA) kits. Nlrp1a knockdown was performed by an adeno-associated virus (AAV) vector containing Nlrp1a-shRNA-eGFP infusion. H.E. staining was used to evaluate skin lesion.

Results

AEW treatment triggers spontaneous scratching and significantly increases the expression of NLRP1, ASC, and caspase-1 and the levels of IL-1β, IL-18, IL-6, and TNF-α in the spinal cord and the skin of mice. Spinal cord Nlrp1a knockdown prevents AEW-induced NLRP1 inflammasome assembly, TRPV1 channel activation, and spontaneous scratching behavior. Capsazepine, a specific antagonist of TRPV1, can also inhibit AEW-induced inflammatory response and scratching behavior. Furthermore, elderly mice and female mice exhibited more significant AEW-induced scratching behavior than young mice and male mice, respectively. Interestingly, AEW-induced increases in the expression of NLRP1 inflammasome complex and the levels of inflammatory cytokines were more remarkable in elderly mice and female mice than in young mice and male mice, respectively.

Conclusions

Spinal cord NLRP1 inflammasome-mediated inflammatory response contributes to dry skin-induced chronic itch by TRPV1 channel, and it is also involved in age and sex differences of chronic itch. Inhibition of NLRP1 inflammasome may offer a new therapy for dry skin itch.
Cross-sectional analysis of circulating tumor DNA in primary colorectal cancer at surgery and during post-surgery follow-up by liquid biopsy
Authors: Allegretti Matteo , Cottone Giuliano , Carboni Fabio , Cotroneo Ettore , Casini Beatrice , Giordani Elena , Amoreo Carla Azzurra , Buglioni Simonetta , Diodoro Maria , Pescarmona Edoardo , Zazza Settimio , Federici Orietta , Zeuli Massimo , Conti Laura , Cigliana Giovanni , Fiorentino Francesco , Valle Mario , Giacomini Patrizio , Spinella Francesca
Published: April 2020

Background

Liquid biopsy (LB) in early-stage, non-metastatic colorectal cancer (CRC) must be sensitive enough to detect extremely low circulating tumor DNA (ctDNA) levels. This challenge has been seldom and non-systematically investigated.

Methods

Next generation sequencing (NGS) and digital PCR (dPCR) were combined to test tumor DNAs (tDNAs) and paired ctDNAs collected at surgery from 39 patients, 12 of whom were also monitored during the immediate post-surgery follow up. Patients treated for metastatic disease (n = 14) were included as controls.

Results

NGS and dPCR concordantly (100% agreement) called at least one single nucleotide variant (SNV) in 34 tDNAs, estimated differences in allelic frequencies being negligible (±1.4%). However, despite dPCR testing, SNVs were only detectable in 15/34 (44.1%) ctDNAs from patients at surgery, as opposed to 14/14 (100%) metastatic patients. This was likely due to striking differences (average 10 times, up to 500) in ctDNA levels between groups. NGS revealed blood-only SNVs, suggesting spatial heterogeneity since pre-surgery disease stages, and raising the combined NGS/dPCR sensitivity to 58.8%. ctDNA levels at surgery correlated with neither tumor size, stage, grade, or nodal status, nor with variant abundance in paired tDNA. LB sensitivity reached 63.6% when ctDNA was combined with CEA. Finally, persistence and absence of ctDNA on the first conventional (month 3) post-surgery follow-up were associated with fast relapse and a disease-free status in 3 and 7 patients, respectively.

Conclusions

A simple clinical NGS/dPCR/CEA combination effectively addresses the LB challenge in a fraction of non-metastatic CRC patients.
NOTCH2 variant D1853H is mutated in two non-syndromic premature ovarian insufficiency patients from a Chinese pedigree
Authors: Li Lin , Feng Fan , Zhao Minying , Li Tengyan , Yue Wentao , Ma Xu , Wang Binbin , Yin Chenghong
Published: April 2020

Background

Premature ovarian insufficiency (POI) is a severe disorder of female infertility, characterized by 4–6 months of amenorrhea before the age of 40 years, with elevated follicle stimulating hormone (FSH) levels (> 25 IU/L). Although several genes have been reported to contribute to the genetic basis of POI, the molecular mechanism of POI remains unclear.

Methods

Whole-exome sequencing (WES) was performed. Sanger sequencing was carried out to validate the variant in the proband and her mother. In silico algorithms were used to analyze the mutational effect of the variant. Protein 3D structural modeling was used for predicting mutated protein structures. Vector construction and plasmids transfection were performed, and subsequently RNA-sequencing (RNA-seq) was carried out in each group to dissect the differentially expressed genes in wild-type (WT) and D1853H NOTCH2 mutant expressing groups. Gene Ontology analysis was also used to analyze the enriched biological processes or pathways among the differentially expressed genes.

Results

We report two non-syndromic POI patients from a Chinese pedigree. The FSH level of the proband (the daughter) was 46 IU/L at the age of 22. Her menarche was at the age of 12, but she was amenorrhea at the age of 20. By WES, a rare heterozygous variant (c.5557G > C;p.D1853H) in the NOTCH2 gene was identified. In silico analysis suggested that p.D1853H was a pathogenic allele. Protein 3D structural modeling suggested that D1853H may enhance or weaken the electrostatic surface potential. By molecular analysis, we found that cells expressing the D1853H NOTCH2 mutant had similar effect in activating the NOTCH signaling pathway downstream target genes. However, 106 protein-coding genes were differentially expressed between D1853H expressing cells and WT NOTCH2 expressing cells, and these genes were enriched for collagen degradation, NCAM1 interactions and HDACs deacetylate histones, revealing a unknown underlying mechanism of the pathology that leads to POI.

Conclusions

We conclude that the rare heterozygous variant in NOTCH2 may be associated with POI. This finding provides researchers and clinicians with a better understanding of the etiology, molecular mechanism and genetic consulting of POI.
scATAC-pro: a comprehensive workbench for single-cell chromatin accessibility sequencing data
Authors: Yu Wenbao , Uzun Yasin , Zhu Qin , Chen Changya , Tan Kai
Published: April 2020

Single-cell chromatin accessibility sequencing has become a powerful technology for understanding epigenetic heterogeneity of complex tissues. However, there is a lack of open-source software for comprehensive processing, analysis, and visualization of such data generated using all existing experimental protocols. Here, we present scATAC-pro for quality assessment, analysis, and visualization of single-cell chromatin accessibility sequencing data. scATAC-pro computes a range of quality control metrics for several key steps of experimental protocols, with a flexible choice of methods. It generates summary reports for both quality assessment and downstream analysis. scATAC-pro is available athttps://github.com/tanlabcode/scATAC-pro.
High-solids enzymatic hydrolysis of ball-milled corn stover with reduced slurry viscosity and improved sugar yields
Authors: Lu Minsheng , Li Junbao , Han Lujia , Xiao Weihua
Published: April 2020

Background

High-solids enzymatic hydrolysis has attracted increasing attentions for the production of bioethanol from lignocellulosic biomass with its advantages of high product concentration, water saving, and low energy and capital costs. However, the increase of solids content would worsen the rheological properties, resulting in heat/mass transfer limitation and higher mixing energy. To address these issues, ball milling was applied to corn stover prior to enzymatic hydrolysis, and the rheological behaviors and digestibility of ball-milled corn stover under high-solids loading were investigated.

Results

Ball milling significantly modified the physicochemical properties of corn stover. The apparent viscosity of slurries at 30% solid loading decreased by a factor of 500 after milling for 60 min, and the yield stress was less than 10 Pa. The dramatic decrease of viscosity and yield stress enabled the hydrolysis process to be conducted in shake flask, and remained good mixing. Meanwhile, the estimated energy consumption for mixing during saccharification decreased by 400-fold compared to the untreated one. The resultant hydrolysate using 10 FPU g−1solids was determined to contain 130.5 g L−1fermentable sugar, and no fermentation inhibitors were detected.

Conclusions

The proposed ball milling pretreatment improved rheological behavior and sugar yield of high-solids corn stover slurry. Ball milling enables high-solids slurry to maintain low viscosity and yield stress while obtaining a non-toxic high-concentration fermentable syrup, which is undoubtedly of great significance for inter-unit processing, mixing and downstream process. In addition, the energy input for ball milling could be balanced by the reduced mixing energy. Our study indicates ball milling a promising pretreatment process for industrial bioethanol production.
Amblyomma hebraeum is the predominant tick species on goats in the Mnisi Community Area of Mpumalanga Province South Africa and is co-infected with Ehrlichia ruminantium and Rickettsia africae
Authors: Jongejan Frans , Berger Laura , Busser Suzanne , Deetman Iris , Jochems Manon , Leenders Tiffany , de Sitter Barry , van der Steen Francine , Wentzel Jeanette , Stoltsz Hein
Published: April 2020

Background

In sub-Saharan Africa,Amblyommaticks are vectors of heartwater disease in domestic ruminants, caused by the rickettsial pathogenEhrlichia ruminantium. Immature tick stages often bite humans, whereby they act as vectors of tick-bite fever caused byRickettsia africae.Moreover,Amblyommaticks cause damage to livestock due to their feeding behaviour. In South Africa, we studied the abundance ofAmblyomma hebraeumticks on goats of emerging farmers in Mpumalanga Province. A selected number ofA. hebraeumnymphs and adult ticks was tested for co-infection withE. ruminantiumandR. africae.

Methods

A total of 630 indigenous goats, belonging to farmers in the Mnisi Community area, were examined for ticks in 2013 and 2014. All ticks were identified, and a selected number was tested by PCR with reverse line blot hybridisation.

Results

In total, 13,132 ticks were collected from goats distributed over 17 different households.Amblyomma hebraeumwas the predominant species, followed byR. microplus.Rhipicephalus appendiculatus,R. simusandR. zambeziensiswere also identified.Amblyomma hebraeumwas present throughout the year, with peak activity of adults in summer (November) and nymphs in winter (July). The ratio between adults and nymphs ranged from 1:2.7 in summer to 1:55.1 in winter. The mean prevalence of infection forE. ruminantiumby PCR/RLB in adult ticks was 17.4% (31/178), whereas 15.7% (28/178) were infected withR. africae. In pooled nymphs, 28.4% were infected withE. ruminantiumand 38.8% carriedR. africaeinfection. Co-infections ofE. ruminantiumandR. africaein adult and pooled nymphal ticks were 3.9% (7/178) and 10% (14.9), respectively. Lameness of goats due to predilection of ticks for the interdigital space of their feet was observed in 89% of the households.

Conclusions

Goats act as important alternative hosts for cattle ticks, which underscored the necessity to include goats in control programs. It is suggested to use acaricide-impregnated leg-bands as a sustainable method to kill ticks and prevent lameness in goats. The challenge of goats by considerable numbers ofE. ruminantium-infected ticks is a major obstacle for upgrading the indigenous goat breeds. Humans may be at risk to contract tick-bite fever in this area.