bluuebunny/crossref_metadata_2025 huggingface dataset:
Capability, Opportunity and Motivation of pregnant women to enact social distancing behaviour in the Covid-19 pandemic in the UK: A qualitative interview study
Authors: Anderson Emma , Brigden Amberly , Davies Anna , Shepherd Emily , Ingram Jenny
Published: December 2020

Background Covid-19 triggered the rapid roll-out of mass social distancing behavioural measures for infection control. Pregnant women were categorised as ‘at risk’ requiring extra vigilance with behavioural guidelines. Their understanding and ability to adhere to recommendations was unknown.Objectives To complete a behavioural analysis of the determinants of recommended social distancing behaviour in pregnant women, according to the ‘capability, opportunity, motivation and behaviour’ (‘COM-B’) model to inform the development of recommendations/materials to support pregnant women in understanding and adhering to behavioural guidelines.Design Qualitative interview study with pregnant women in the Bristol area (UK).Methods Semi-structured telephone/videoconference interviews were conducted following a topic guide informed by the COM-B model, transcribed verbatim and subjected to framework analysis. Infographic materials were iteratively produced with stakeholder consultation, to support pregnant women’s behaviour.Results Thirty-one women participated (selected for demographic range). Women reported adhering to social distancing recommendations and intended to continue. COM-B analysis identified gaps in understanding around risk, vulnerability, and the extent of required social distancing, as well as facilitators of social distancing behaviour (e.g. social support, motivation to stay safe, home environment/resources). Additional themes around detrimental mental health effects and changes to maternity healthcare from the social distancing measures were identified. Infographic resources (plus midwife report) addressing women’s key concerns were produced and disseminated.Conclusions The COM-B model provided useful details of determinants of pregnant women’s adherence to social distancing behaviours. The confusion of what being ‘at risk’ meant and varying interpretation of what was expected indicates a need for greater clarity around categories and guidance. The loss of maternity care and negative mental health effects of social distancing suggests a growing area of unmet health needs to be addressed in future.
GC–MS analysis of phytoconstituents of Acacia nilotica and its molecular docking with drug-targets of Leishmania donovani to combat leishmanaisis
Authors: Tabrez Shams , Rahman Fazlur , Alshehri Bader , Alouffi Abdulaziz , Ali Rahat , Alshammari Fahdah , Alaidarous Mohammed , Banawas Saeed , Dukhyil Abdul Aziz , Rub Abdur
Published: December 2020

Acacia nilotica is an important medicinal plant, found in Africa, Middle East, and Indian subcontinent. Every part of the plant possesses a wide array of biologically-active and therapeutically important compounds and have been used in traditional-system of medicine. We reported the antileishmanial activity of Acacia nilotica (A. nilotica) bark methanolic extract through in vitro assays and dissected the mechanism of its action through in silico studies. Bark methanolic extract exhibited anti-promastigote and anti-amastigote potency with IC50 value of 19.6 + 0.9037 µg/ml and 77.52 + 5.167 µg/ml respectively in time and dose dependent manner. It showed very low cytotoxicity having CC50 value of 432.7 + 7.71 µg/ml on human-macrophage cell line, THP-1. The major constituents identified by GC-MS analysis are 13-docosenoic acid (34.06%), lupeol(20.15 %), 9,12-octadecadienoic acid (9.92 %) and 6-octadecanoic acid (8.43 %) bind effectively with the potential drug-targets of Leishmania donovani (L. donovani ) including sterol 24-c-methytransferase (SMT), trypanothione reductase (TR), pteridine reductase (PTR1) and adenine phosphorybosyl transferase (APRT); suggest the possible mechanism of its antileishmanial action. The highest affinity with all these targets was shown by lupeol. The pharmacokinetic studies, predicted bioactivity scores and acute toxicity studies of major extract constituents support safe antileishmanial drug candidate. This study proved the antileishmanial potential of bark-methanolic extract A. nilotica and its mechanism of action through the inhibition of potential drug targets of L. donovani.
Different Top-Down Goals Modulate Early Stage of Attention Bias: Irrelevant Task Suppresses the N170 of Automatic Attention Allocation to Threat Faces
Authors: Dou Haoran , Liang Limei , Ma Jie , Lu Jiachen , Zhang Wenhai , Li Yang
Published: December 2020

Recent research has evidenced that stimulus-driven attention bias for threat can be modulated by top-down goals. However, it remains unclear how different top-down goals affect the early stage of attention processing and its early neural mechanism. We collected electroencephalographic data from 28 healthy volunteers during four inconsistent levels in a modified spatial cueing task according to cue validity and task relevance. Our data revealed that reaction time(RT) to the target in the irrelevant task were much slower than that in the relevant task. In the irrelevant task, we did not find the difference between the RTs to the fearful and neutral face. In the relevant task, we found RTs of fearful face were faster than that of neutral face in valid cue condition(weak inconsistent level), whereas the RTs of fearful face were slower than that of neutral face in invalid cue condition(medium inconsistent level). The ERPs results showed that in relevant task(weak, medium inconsistent levels), fearful face in cue position of the target evoked larger N170 amplitudes than neutral face did, whereas this effect was suppressed in irrelevant task(strong, very strong inconsistent levels). Besides, fearful face in cue position of the target also evoked larger vertex positive potential (VPP) amplitudes than the neutral face did in valid cue condition( weak inconsistent level). These results suggest that irrelevant task may inhibit the early attention allocation to the fearful face. Furthermore, the top-down processing modulates the early attention bias for threatening faces.
Identifying Pivotal microRNAs and Target Genes Associated With the Pathogenesis of Atrial Fibrillation
Authors: Xiao Shengjue , Zhou Yufei , Liu Qiaozhi , Zhang Tiantian , Zhu Hong , Pan Defeng
Published: December 2020

Background: Atrial fibrillation (AF) is the most common arrhythmia. However, specific molecular mechanism of AF remains unclear. Our study aimed to identify pivotal target genes and miRNAs in the process of AF, which help provide the basis for clinical diagnosis and the methods for early intervention. Methods: Three gene expression array datasets (GSE31821, GSE41177 and GSE79768) and a miRNA expression array dataset of AF dataset (GSE68475) were downloaded. Differential expressed genes (DEGs) were identified using the LIMMA package and differential expressed miRNAs (DEMs) were screened from GSE68475. Target genes of DEMs were predicted using the miRTarbase database, the number of the intersection between DEGs and these target genes was 26, named CDEGs. The common DEGs (CDEGs) was subject to following analysis. Results: A total of 264 DEGs and 40 DEMs were identified between the AF and control groups. Functional and pathway enrichment analyses of up-regulated DEGs and down-regulated DEGs were performed. The CDEGs were mainly enriched in PI3K-Akt signaling pathway, negative regulation of cell division and response to hypoxia. Subsequently, the protein-protein interaction (PPI) network, the microRNA‐transcription factor‐target regulatory network and drug‐gene network were also constructed by Cytoscape software. Conclusion: The present study revealed several novel genes and miRNAs involved in AF. We speculated that PI3K-Akt signaling pathway might participate in the pathogenesis of AF with the interaction of MYC proto-oncogene (MYC), heat shock protein 90 kDA alpha, class B, member 1 (HSP90AB1) and DNA damage-inducible transcript 4 (DDIT4), moreover, SOD2 (superoxide dismutase 2) could target miR-671-5p, miR-4306, miR-3125, miR-4298 in the progression of AF.
Association Between Dementia and Clinical Outcome After COVID-19: A Nationwide Cohort Study with Propensity Score Matched Control in South Korea
Authors: Wang Sheng-Min , Park Si-Hyun , Kim Nak-Young , Kang Dong Woo , Na Hae-Ran , Um Yoo Hyun , Han Seunghoon , Park Sung-Soo , Lim Hyun Kook
Published: December 2020

Despite a high prevalence of dementia in older adults hospitalized with severe acute respiratory syndrome coronavirus 2 infection (COVID-19), research investigating association between preexisting diagnoses of dementia and prognosis of COVID-19 is scarce. We explored a nationwide cohort with a total of 2,800 subjects older than 50 years who were diagnosed with COVID-19 between January and April 2020. Among them, 223 patients had underlying dementia (dementia group). We matched 1:1 for each dementia-non-dementia group pair yielding 223 patients without dementia (no dementia group) using propensity score matching. The primary outcome measure was group difference in mortality after COVID-19. Mortality rate after COVID-19 were significantly higher in dementia group than in no dementia group (33.6% vs. 20.2%, p=0.002). In addition, dementia group had higher proportion of patients requiring invasive ventilatory support than no dementia group (34.1% vs. 22.0%, p=0.006). Multivariable analysis showed that dementia group had a higher risk of mortality than no dementia group (odds ratio=3.05, p<0.001). We also found that patients in dementia group had a higher risk of needing invasive ventilatory support than those in no dementia group. Our results suggest that system including strengthen quarantines are required for patients with dementia during the COVID-19 pandemic.
The neuroprotective effects of AMN082 on neuronal apoptosis in rat after traumatic brain injury
Authors: Lu Chung-Che , Wang Che-Chuan , Lee Yao-Lin , Chio Chung-Ching , Lim Sher-Wei , Kuo Jinn-Rung
Published: December 2020

The aim of this study is to investigate whether the neuroprotective effect of AMN082 is via attenuating glutamic receptor associated neuronal apoptosis and improves functional outcomes after traumatic brain injury (TBI). Anesthetized male Sprague-Dawley rats were divided into sham-operated, TBI + vehicle, and TBI + AMN082 groups. AMN082 was intraperitoneally injected (10 mg/kg) at 0, 24, and 48 hr after TBI. During the 120 minutes after TBI, heart rate, mean arterial pressure, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) were continuously measured. The motor function, infarction volume, and neuronal nitrosative stress-associated apoptosis, N-Methyl-D-aspartate receptor 2A (NR2A) and NR2B expression were measured on the 3rd day after TBI. The results showed AMN082-treated group had the lower ICP and higher CPP after TBI. The TBI-induced motor deficits, increased infarction volume, neuronal apoptosis, 3-nitrotyrosine and inducible nitric oxide synthase expression in the peri-contusion cortex were significantly improved by AMN082 therapy. Simultaneously, AMN082 increased the NR2A and NR2B expression in neuronal cells. We concluded intraperitoneal injection of AMN082 for 3 days may ameliorate TBI insults by attenuating glutamic receptor associated nitrosative stress and neuronal apoptosis in the peri-contusion cortex. We suggest AMN082 administration in acute stage may be a promising strategy for TBI.
An observational study on usage of insulin and self-injection practises among patients with diabetes attending to Diabetic Centre and Medical outpatient clinics of a tertiary care hospital of Northern Sri Lanka
Authors: Narayanapillai Sathyasagaran , Thambipillai Peranantharajah , Mahalingam Aravinthan , Nadarajah Rajeshkannan
Published: December 2020

Background: Prevalence of diabetes increasing world-wide particularly in low income countries. Management of diabetes sometimes requires insulin injection due to various reasons. Proper usage of insulin and injection techniques are important for diabetes control among who requires insulin. This study was aimed to assess current insulin practices and associated complications.Methods and material: This was a cross sectional study conducted among diabetes patients attended all medical clinics and Diabetic Centre in Jaffna teaching Hospital which is the only tertiary hospital in the Northern Sri Lanka in May 2020.Insulin practices retrieved by using interviewer administered questionnaire. Data was analyses by using SPSS 26.Results: Out of 360 patients 64.2% were female and mean age was 58.19 (12-89).Majority (61.9%) of them belongs to low income category and most (73.3%) of them using insulin more than 1 year. Main reason for the insulin initiation was oral hypoglycaemic failure (81.7%) and majority of them (80.0%) were using twice daily premixed insulin regime followed by daily basal insulin (11.4%) and basal bolus insulin (5.6%) regime. Most of the participants (81.4%) reported they do cleaning of the injection site before injection and 89.7% usually rotate the injection site. Approximately half of them (50.8%) inject themselves and majority use syringes (91.4%). Common injection site complications reported were skin changes (25%), followed by 15.3% persistent swelling (15.3%) and thinning of skin(7.8%). Angle of injection (P-0.039) and insulin regime (P<0.001) showed statistically significant association with skin changes.High proportion of participants 68.6% (95%CI: 63.7%-73.2%) experienced hypoglycaemia, using syringes 2.21 times (95%CI-1.05-4.64) more risk of compare to pen users and missing meals 2.22 times more risk of hypoglycaemic events (95%CI: 1.18-4.17). Majority of them reported reusing the needles for injection (83.6%) and 35% were disposing needle into common garbage pin.Conclusion: This study revealed significant gaps in current insulin practices from expected norm and hypoglycaemic events alarmingly high among participants. Exploring Continuous Glucose Monitoring Devices or flash monitoring can be a mitigation strategy and urgent attention from health professionals needed to improve the safe insulin practices.
The Association Between Fluoroquinolones and Aortic Dissection and Aortic Aneurysms: A Systematic Review and Meta-Analysis
Authors: Wee Ian , Chin Brian , Syn Nicholas , Lee Keng Siang , Ng Jun Jie , Choong Andrew
Published: December 2020

Previous studies have drawn causal associations between fluoroquinolone use and collagen pathologies including tendon rupture and retinopathy. This meta-analysis attempted to assess the association between fluoroquinolone use and the risk of aortic dissection or aortic aneurysm. A systematic search was performed on Medline, EMBASE, and the Cochrane library. 9 studies were included in final analysis. Primary random-effects meta-analysis of 7 studies, excluding 2 pharmacovigilance studies demonstrated statistically increased odds of aortic dissection (OR, 2.38; 95% CI, 1.71 – 3.32) aortic aneurysm (OR, 1.98; 95% CI, 1.59 – 2.48), and aortic aneurysm or dissection (OR, 1.47; 95% CI, 1.13 – 1.89; I2 = 72%) with current use of fluoroquinolones compared to their nonuser counterparts. Based on the “number needed-to-harm” analysis, 7246 (95% CI: 4329 to 14085) patients would need to be treated with fluoroquinolones for a duration of at least three days in order for one additional patient to be harmed, assuming a population baseline incidence of aortic dissection and aneurysm rupture to be 10 per 100,000 patient-years. With strong statistical association, these findings suggest a causal relationship, warranting future research to elucidate the pathophysiological and mechanistic plausibility of this association. These findings however, should not cease prescription of fluoroquinolones, especially when clinically indicated.
Prevalence and Risk Factors of Refractive Error in Qinghai, China: A Cross-Sectional Study in Han and Tibetan Adults in Xining and Surrounding Areas
Authors: Wang Meng , Gan Lingyang , Cui Jiantao , Chen Ting , Wang Xianghua , Wang Yuhan , Pan Li , Li Zhanquan , Cui Sen , Yang Airong , Li Wenfang , Jia Guoqiang , Han Ximing , Shan Guangliang , He Huijing , Zhong Yong , Ma Jin
Published: December 2020

Background Our study aimed to explore the prevalence and risk factors of refractive error (RE) in Han and Tibetan population aged 50-79 years in Xining and surrounding areas in Qinghai Province on Qinghai-Tibet Plateau.Methods As part of the China National Health Survey, our cross-sectional study compared the age-adjusted prevalence of RE in Han and Tibetan elder adults aged 50-79 years in Xining and surrounding areas. A multivariate logistic regression model was used to identify risk factors for myopia and hyperopia.Results Among 769 Han participants and 476 Tibetan participants, the age-adjusted prevalence of myopia, hyperopia, high myopia and astigmatism were 28.56%, 22.82%, 2.80%, and 69.38%. Han population have higher age-adjusted prevalence of myopia (32.93% vs 21.64%, p<0.001), high myopia (3.93% vs 1.02%, p=0.001) and astigmatism (72.14% vs 64.94%, p=0.021) compared to Tibetan population. Being Tibetan is the protective factor of myopia compared to being Han (OR 0.58, 95%CI 0.42-0.79, p<0.001). Elder age (p=0.032), longer time length in rural area (p=0.048), undergraduate/graduate education level (p=0.031), lighter active level (p=0.007) and lower BMI index (p=0.015) are risk factors for myopia. Elder age (all p<0.001) and pterygium status of the same eye (p=0.013) also increases the hyperopia risk.Conclusions Our study found an overall prevalence of myopia of 28.56% in Xining and surrounding areas in adults elder than 50 years. Han population has higher myopia risk than Tibetan population. More medical and social resources should be allocated to improve the vision and life quality of elder adults.
Insights into the Aggregation Mechanism of RRM domains in TDP-43: A Molecular Dynamics Study
Authors: Liu Wei , Li Chaoqun , Shan Jiankai , Wang Yan , Chen Guangju
Published: December 2020

The transactive response DNA-binding protein 43 (TDP-43) is associated with several diseases such as Amyotrophic lateral sclerosis (ALS) and Frontotemporal lobar degeneration (FTLD) due to pathogenic aggregations. In this work, we examined the dimer, tetramer and hexamer models built from the RRM domains of TDP-43 using molecular dynamics simulations in combination with the protein-protein docking. Our results show that the parallel β-sheet layers in the RRM1 domains in these oligomer models were formed energetically favorable, which provide the potential binding sites in the aggregation process. The closeness of the parallel β-sheet layers from small oligomer models gradually expanded to large ones through the communication of the interaction between α1/α2 helices of RRM domains, which enhanced the binding affinities and interactions in these aggregation models to further promote the aggregation. Using the repeatable-superimposing method based on the tetramer models, we propose a new aggregation mechanism of RRM domains in TDP-43 which mediates the formation of large aggregation structure with the repeated, helical and rope-like characteristics. These new insights help to understand the amyloid-like aggregation phenomena of TDP-43 protein in ALS and FTLD diseases.
Influence of Structural Reinforcements on the Twist-to-bend Ratio of Plant Stems
Authors: Wolff-Vorbeck Steve , Speck Olga , Speck Thomas , Dondl Patrick
Published: December 2020

During biological evolution, plants have developed a wide variety of body plans and concepts that enable them to react or adapt to changing environmental conditions. Their morphological-anatomical and mechanical adaptations to conflicting conditions are especially interesting. A good example is the trade-off between flexural and torsional rigidity, as represented by the dimensionless twist-to-bend ratio. We have developed geometric models of a plant tissue reflecting the 2D situation of triangular cross-sections comprising of a parenchymatous matrix with vascular bundles surrounded by an epidermis and analysed them by using mathematical models (finite element analysis) to measure the effect of either reinforcements of the epidermal tissue or fibre reinforcements such as collenchyma and sclerenchyma on the twist-to-bend ratio. The change from an epidermis to a covering tissue of corky periderm increases both the flexural and the torsional rigidity and decreases the twist-to-bend ratio. Furthermore, additional fibre reinforcement strands in a parenchymatous ground tissue lead to a strong increase of the flexural and a weaker increase of the torsional rigidity and thus resulting in a marked increase of the twist-to-bend ratio. Within the developed model, a reinforcement by 49 sclerenchyma fibre strands or 24 collenchyma fibre strands is optimal in order to achieve high twist-to-bend ratios. Dependent on the mechanical quality of the fibres, the twist-to-bend ratio of collenchyma-reinforced axes is noticeably smaller, with collenchyma having an elastic modulus that is approximately 20 times smaller than that of sclerenchyma.
Comparison of the Morphological and Biomechanical Characteristics of Keratoconus, Forme Fruste Keratoconus, and Normal Corneas
Authors: Guo Li-Li , Tian Lei , Cao Kai , Li Yu-Xin , Li Na , Yang Wei-Qiang , Jie Ying
Published: December 2020

Background: To explore the feasibility of corneal morphological and biomechanical parameters for keratoconus and forme fruste keratoconus diagnosis.Methods: This case-control study included a total of 517 eyes from 408 keratoconus patients (KC group), 83 eyes from 83 forme fruste keratoconus patients (FFKC group), and 158 eyes from 158 patients with normal corneas (NL group). All subjects underwent routine ophthalmology examinations. Pentacam and Corneal Visualization Scheimpflug Technology were used to obtain corneal morphological and biomechanical parameters. Differences between the groups were compared using receiver operating characteristic (ROC) curve analysis.Results: Comparison of the NL group with the KC and FFKC groups (P<0.05), and the NL and KC groups alone (P<0.017), revealed statistically significant differences in corneal morphological and biomechanical parameters, except time from the start until the highest concavity (HCT), deflection length of the first applanation (A1 DfL), and deflection length of the second applanation (A2 DfL). Comparison of the NL and FFKC groups revealed 12 significantly different parameters (P<0.017). ROC analysis showed that all corneal morphological parameters and most biomechanical parameters distinguished KC from NL, with an area under the curve (AUC) greater than 0.80, of which Belin-Ambrósio enhanced ectasia total deviation index (BAD-D) and tomographic and biomechanical index (TBI) were most efficient. Except for central astigmatism from the anterior corneal surface (AstigF), the AUC that distinguished FFKC from NL was 0.862. Other parameters distinguished FFKC from NL with low efficiency. Conclusion: All corneal morphological and most biomechanical parameters are different in KC versus NL, but only a few parameters are different in FFKC versus NL. BAD-D and TBI have the highest efficiency, sensitivity, and specificity for distinguishing KC from NL. The parameters had a low ability to distinguish FFKC from NL. The application of biomechanical instruments to diagnose early keratoconus needs further study.
Genome Survey Sequencing of Nomocharis forrestii, Assembly of Its Complete Chloroplast Genome and Analysis of Simple Sequence Repeat (SSR) Markers
Authors: Zhang Da , Li LianLian , Wu XueWei , Wang TianXi , Ping Na , Liu HaiYing , Li YongPing , Zhang YiPing , Wang LiHua
Published: December 2020

Background: Nomocharis is a genus that is closely related to Lilium in the Liliaceae family. It’s useful to study the influence of the uplift of the Qinghai-Tibet Plateau on plants and their biological diversity. Nomocharis is a genus of such plants, and research on this genus will be especially informative, considering the genetic diversity of flowers. However, the genetic information of Nomocharis has not been fully elucidated. Results: To obtain a complete Nomocharis reference genome, the paper first performed a general survey. Next-generation sequencing (NGS) was utilized to perform de novo sequencing of the entire Nomocharis forrestii genome. In this study, the sequencing process yielded approximately 137.4 Gb of high-quality data, the total sequencing depth was approximately 63X, and the Q30 ratio was 91.95%; the estimated genome size was approximately 2.17 Gb; the repetitive sequence content was approximately 84.7%, the heterozygosity rate was 3.99%, and the estimated GC content of the genome was 43%. Furthermore, an annotated circular chloroplast gene map was generated, and a preliminary evolutionary analysis was performed. In addition, a total of 78,045 high-quality SSR markers were developed. Conclusion: Nomocharis forrestii has a 2.17 Gb heterozygous genome, its SSR markers are predominantly dinucleotides, and its chloroplast genome shows that Nomocharis forrestii and Lilium bakerianum have the highest homology followed by Lilium distichum. To the best of our knowledge, this report describes the first de novo whole-genome sequencing and assembly process to be performed for Nomocharis. The results of this study may provide new resources for the future genetic analysis and molecular breeding of Nomocharis.
Longitudinal Health Behaviour Patterns Among Chinese Adults Aged ≥ 50 Years and Their Associations With Trajectories of Depressive Symptoms Over Time: A Latent Class Analysis
Authors: Feng Zeyun , Broek Thijs van den , Cramm Jane , Nieboer Anna
Published: December 2020

Background Whether different longitudinal patterns of multiple health behaviours are associated with different trajectories of depressive symptoms is not well understood.Purpose To identify distinct longitudinal patterns of multiple health behaviours and their associations with trajectories of depressive symptoms among people aged ≥ 50 years in China.Methods We used longitudinal data from the Harmonized China Health and Retirement Longitudinal Study (three waves, 2010–2015; n = 8439). We performed latent class analyses to identify distinct patterns of multiple health behaviours at three timepoints. We estimated longitudinal random-effects models to predict differences in depressive symptoms trajectories by health behaviour class.Results The best-fitting model had five latent classes, all of which showed strong behavioural stability over time: 1) socially active, moderately physically active non-smokers (29.4%); 2) socially inactive, physically active non-smokers (22.3%); 3) socially and physically inactive non-smokers (17.9%); 4) socially inactive, moderately physically active smokers (14.6%); and (5) socially active, moderately physically active smokers (14.2%). All classes characterized by low social participation (classes 2–4) were associated with significantly higher predicted depressive symptom scores compared with the other classes (1 and 5). Conclusions Longitudinal behavioural patterns involving low probabilities of social participation were associated with more depressive symptoms. This overshadowing effect suggests that the damage caused by socially inactivity may render the effects of co-existing (un)healthy behaviours meaningless. The stability of the patterns of multiple health behaviours across survey waves suggests that interventions are needed earlier in life.
A Dissemination Strategy to Promote Relational Coordination in the Veterans Health Administration: A Case Study
Authors: Connelly Brigid , Battaglia Catherine , Gilmartin Heather M.
Published: December 2020

Background Implementing new healthcare practices across large organizations can be difficult due to inefficient diffusion of information. Using social marketing theory and additional evidence-based dissemination strategies, we spread relational coordination, an empirically supported theory of organizational performance, throughout the large Veterans Health Administration (VA). Relational Coordination drives performance outcomes including quality, efficiency, client satisfaction, and worker well-being and engagement and proposes interdependent work is most effectively coordinated by workers with each other, their customers, and their leaders. We aimed to develop a best-practice dissemination plan to educate and motivate researchers and operational staff in the VA to study and implement relational coordination within their programs of research or areas of operation.Methods In this observational case study, we followed the four Ps of social marketing theory to develop a strategy to disseminate relational coordination across the VA in two phases. In phase one, we created and distributed relational coordination information and invited VA staff to join the Relational Coordination Research Collaborative. In phase two dissemination efforts targeted researchers who were ready to study and implement relational coordination within existing programs of research. Primarily observational data were collected through both stages of the project and a final, post-project survey was administered after the second phase. The quantitative results were calculated using descriptive statistics and text responses in the survey were analyzed using deductive content analysis. A structured categorization matrix was developed to code the responses based on the survey questions. Results The first phase saw instances of social media dissemination, presentations, as well as phone or email communication between project staff and the target audience. 47 members of VA staff joined the Relational Coordination Research Collaborative and 50% participated in online research seminars. 13 research projects applied for the second stage and 5 projects were ultimately chosen to access the Relational Coordination survey. Relational coordination-related trainings, presentations, and publications also occurred.Conclusions Dissemination approaches that involved personalized, one-on-one efforts seemed to be more effective at spreading relational coordination compared to social media or other online presentations. Participants in the second phase overwhelmingly agreed to that relational coordination should be adopted in the VA but indicated the cost of the program would have been a barrier. Results reiterate the importance of an intentional dissemination plan, including addressing the costs and benefits of programs
An Inventory on Black Carbon and Organic Carbon Emission by the Different Vegetative Ecosystem Over India
Authors: Venkatraman Karthik , Bhaskar Vijay , Kesarkar Amit
Published: December 2020

Fires provoke land degradation, deforestation, imbalance in the ecosystem, and promote changes in land use. To add more vein aerosols such as Black Carbon (BC) and Organic Carbon (OC) were emitted during the combustion event which plays a major role in climate change, pollution, and health. Hence this study aims to estimate the emission, residence, dry deposition flux, and sequestering ability of deposited BC and OC from different vegetative fires across India using MODIS satellite data from 2013 to 2019. It was observed that the mean OC and BC emission were about 5.08 × 107 tonnes 4.48 × 106 tonnes during the fire season across India. On a national scale, cropland fires contributed the largest portion (80%) of total carbonaceous aerosol emissions from open fires. In co-emission of species, forest shares a maximum relationship (> 92 percent) among carbonaceous aerosols. Estimation of deposition flux of emitted species showed cropland has higher deposition rates with a residence period ranging between 7hours to 23days. From the observed results, it is evident that higher aerosol emission combined with negligible deposition will be a potential threat to the environment. Waste utilization promoting strategies has to be adopted in India since agriculture contributes to major aerosols emission.
A broad-range survey of Borrelia burgdorferi sensu lato infection in small mammals in Yunnan Province, China
Authors: He Zhihai , Jiang Baogui , Gao Zihou , Shao Zongti , Zhang Yun , Liu Zhengxiang , Li Yuqiong , Pu Ennian , Tang Li , Yao Mingguo , Jia Na , Fricken Michael E. von , Jiang Jiafu , Du Chunhong
Published: December 2020

Background: Lyme disease, caused by Borrelia burgdorferi sensu lato (BBSL), is commonly found in wild and domestic mammals worldwide. In China, human cases of B. burgdorferi infections have been identified across a wide distribution, but little direct surveillance of potential small mammal reservoirs has been performed in Yunnan Province, a tropical region in southwestern China. Here we report a thorough investigation of BBSL in small mammals collected from 2011 to 2016 from this region.Methods: Small mammals were captured using snap traps in 23 counties located in Yunnan Province. DNA was extracted from spleen tissue using DNA blood and tissue kits. A nested PCR targeting the 5S-23S rRNA intergenic spacer gene of BBSL was used for pathogen detection. Amplicons of 252bp expected sizes were sequenced directly and analyzed using BLAST algorithm. A phylogenetic tree was constructed using MEGA software and statistical analysis were conducted using SPSS version 17.0.Results: Overall, 3659 mammals belonging to 57 species were captured at 159 sample sites located in 23 counties in Yunnan Province. Borrelia burgdorferi s.l. was found in 146 mammals (3.99%), from 30 different species, 20 of which represent the first reported detection in that species. Sequence analysis revealed five genotypes of B. burgdorferi s.l., including B. afzelii, B. burgdorferi sensu stricto, B. japonica, B. garinii and B. valaisiana.Conclusions: Significant differences in prevalence rates of BBSL were observed at varying landscape types and altitudes. Small mammals in forested areas had higher prevalence rates than other landscape types, as did small mammals found at altitudes greater than 2500 meters. The five genotypes of BBSL detected, suggests high genetic diversity within this province.
The Effect of Talaromyces Marneffei Infection on CD86 Expression in THP-1 Cells
Authors: Yang Di , Shen Lin , Chen Ri , Fu Yu , Zhang Li , Xu Hong , Liu Dong
Published: December 2020

Background: Talaromyces Marneffei (T.marneffei) is an destructive opportunistic dimorphic fungal which can cause lethiferous Talaromycosis, but the clearance of T.marneffei mainly depends on the innate immune response. Objectives: To investigate the effect of T.marneffei on CD86 expression in THP-1 cells after infection and discuss the potential mechanisms. Methods: Western blot and immunoelectron microscopy were used to detect the CD86 expression on T.marneffei cultured on BHI medium at 37℃. Western blot、enzyme-linked immunoassay and immunofluorescence were used to detect the change of CD86 expression on macrophages incubating with T.marneffei. Enzyme-linked immunoassay was used to detect the content of CD86 in supernatant in the co-culture system. Immunohistochemistry and immunoelectron microscopy were used to detect the expression of CD86 on T.marneffei incubating with macrophages. Results: T.marneffei didn’t express CD86 when cultured separately at 37℃ detected by western blot and immunoelectron microscopy, but it did express CD86 when incubated with macrophages detected by immunohistochemistry and immunoelectron microscopy. The CD86 expression of macrophages significantly decreased at 72 hours when infected with T.marneffei while the content of CD86 in supernatant significantly increased at 72 hours compared with the control group which were detected by western blot, enzyme-linked immunoassay and immunofluorescence. Conclusion: 1.After T.marneffei infection，CD86 expression on THP-1 decreased，and with the progression of infection, insufficient polarization of M1 macrophages gradually appeared；2.T.marneffei may adsorb or uptake CD86 in supernatant produced by macrophages during the contact with THP-1 cells, thus leading to the consumption of CD86 in macrophages.
Advance Research Directives: Avoiding Double Standards
Authors: Heinrichs Bert
Published: December 2020

Background: Advance research directives (ARD) have been suggested to facilitate research with incapacitated subjects, in particular in the context of dementia research. However, established disclosure requirements for study participation raise an ethical problem for the application of ARDs: While regular consent procedures call for detailed information on a specific study (“token disclosure”), ARDs can typically only include generic information (“type disclosure”). ARDs, therefore, run the risk of introducing an ethically problematic double standard. Methods: This paper provides an ethical analysis of ARDs, taking into account the results of numerous empirical studies that have been performed so far. It will be argued that a revised understanding of informed consent can allow for context-sensitive disclosure standards. As a consequence, ARDs that include “type disclosure” can be acceptable under suitable circumstances. Discussion: Such an approach raises objections, two of which are especially important. A thorough examination shows, however, that they are not sufficient to justify a rejection of the approach. Conclusion: The approach presented in this paper avoids introducing a double-standard for particular types of research such as dementia research. It is, therefore, more suitable for the implementation of ARDs than established approaches.
Evaluation of HER 2-overexpression Status in Breast Cancer Patients: Results From a Breast Cancer Registry
Authors: Nourmohammadi Hassan , Beigi Seyedeh Negin Mir , Bonyadi Mahtab , Shafiei Elham
Published: December 2020

Background: The expression level of HER2 gene is low in normal breast tissue, but levels of these receptors are higher in half of cases of breast cancer. Different expression levels of HER2 gene in normal and malignant cells have made this gene an ideal biomarker for therapeutic purposes. In this study, the extent of HER2 overexpression and its relationship with the age and the occurrence of metastasis were evaluated in breast cancer patients. Methods: In this cross-sectional study, 62 patients with breast cancer were evaluated at oncology clinics in Ilam province. Clinical examination for metastasis, examination of tissue samples for HER2 gene expression, and information related to variables were recorded in a breast cancer registry. The obtained data were analyzed using SPSS 20 statistical software by appropriate statistical tests.Results: The mean age of the participants was 48.37 ± 10.98, and 98.4% were women. The prevalence of increased HER2 gene expression was 37.1% in patients. There was an inverse relationship between patients' age and HER2 positivity (P value = 0.02). The chance of metastasis was 9 times higher (OR = 9.82) in cancer patients who had the HER2 gene expression Conclusion: In Ilam province, the prevalence of HER2 positivity in breast cancer patients is almost similar to other parts of the country and is associated with the occurrence of metastasis and low age of breast cancer patients.
WITHDRAWN: TP53 Drives Abscopal Effect by Secretion of Senescence-associated Molecular Signals in Non Small Cell Lung Cancer
Authors: Tesei Anna , Arienti Chiara , Bossi Gianluca , Santi Spartaco , De Santis Ilaria , Bevilacqua Alessandro , Zanoni Michele , Pignatta Sara , Cortesi Michela , Zamagni Alice , Storci Gianluca , Bonafè Massimiliano , Sarnelli Anna , Romeo Antonino , Cavallo Carola , Bartolazzi Armando , Rossi Stefania , Soriani Antonella , Strigari Lidia
Published: December 2020

Background. Recent developments in abscopal effect strongly support the use of radiotherapy for the treatment of metastatic disease. However, deeper understanding of the molecular mechanisms underlying the abscopal effect are required to best benefit a larger proportion of patients with metastasis. Several groups including ours, reported the involvement of wild-type (wt) p53 in radiation-induced abscopal effects, however very little is known on the role of wtp53 dependent molecular mechanisms. Methods. We investigated through in vivo and in vitro approaches how wtp53 orchestrates radiation-induced abscopal effects. Wtp53 bearing (A549) and p53-null (H1299) NSCLC lines were xenotransplanted in nude mice, and cultured in 2D monolayers and 3D tumor spheroids. Extracellular vesicles (EVs) were isolated from medium cell culture by ultracentrifugation protocol followed by Nanoparticle Tracking Analysis. Gene expression was evaluated by RT-Real Time, digital qRT-PCR, and dot blot technique. Protein levels were determined by immunohistochemistry, confocal anlysis, western blot techniques, and immunoassay.Results. We demonstrated that single high-dose irradiation (20 Gy) induces significant tumor growth inhibition in contralateral non-irradiated (NIR) A549 xenograft tumors but not in NIR p53-null H1299 or p53-silenced A549 (A549sh/p53) xenografts. We further demonstrates that irradiation of A549 cells in vitro induces a senescence-associated secretory phenotype (SASP) producing extracellular vesicles (EVs) expressing CD63 and carrying DNA:RNA hybrids and LINE-1 retrotransposon. IR-A549 EVs also hamper the colony-forming capability of recipient NIR A549 cells, induce senescent phenotype, nuclear expression of DNA:RNA hybrids, and M1 macrophage polarization. Conclusions. In our models, we demonstrate that p53-mediated abscopal effect was accompanied by the onset of SASP and was mediated by CD63+ EVs conveying in NIR counterpart as abscopal messengers DNA:RNA hybrids and LINE-1 retrotransposons.
The Anti-Dysenteric Drug Fraxetin Enhances Anti-Tumor Efficacy of Gemcitabine and Suppresses Pancreatic Cancer Development by Antagonizing STAT3 Activation
Authors: Guo Yangyang , Xiao Yanyi , Guo Hangcheng , Zhu Hengyue , Chen Dong , Wang Jilong , Deng Junjie , Xu Zheng , Lan Junjie , Liu Xiaodong , Zhang Qiyu , Bai Yongheng
Published: December 2020

BackgroundFraxetin, a natural product isolated and purified from the bark of Fraxinus bungeana A.DC., has anti-inflammatory, analgesic and anti-dysenteric activities. This study aimed to investigate the anti-tumor effects of fraxetin in pancreatic ductal adenocarcinoma (PDA) and elucidate the underlying molecular mechanism. MethodsThe effects of quercetin on the proliferation, apoptosis, migration and invasion of pancreatic cancer cells (PCCs), and tumor growth and metastasis in PDA xenograft mouse models were evaluated. Besides, the effects of fraxetin on the sensitivity of PCCs to gemcitabine were evaluated. Moreover, angiogenesis, glucose metabolism, the epithelial-mesenchymal transition (EMT), reactive oxygen species (ROS), and STAT3 activity were analyzed.ResultsIn PCCs, fraxetin inhibited the proliferation, induced mitochondrial-dependent apoptosis, and suppressed the invasion and migration by reversing the EMT. In nude mouse models, PDA growth and metastasis were reduced by fraxetin treatment. Moreover, fraxetin enhanced the sensitivity of PCCs to the chemotherapy drug gemcitabine. Mechanically, oncogenic KRAS-triggered STAT3 activation in PCCs and PDA tissues was suppressed by fraxetin treatment. Fraxetin shows important interactions with STAT3 Src Homology 2 (SH2) domain residues to occupy the pTyr‐recognition site of its SH2 domain of another STAT3 monomer, thereby preventing its homo-dimer formation, which then blocks the activation of downstream signal pathways. The anti-tumor activity of fraxetin in PDA was functionally rescued by a STAT3 activator colivelin. As a result, fraxetin hindered hypoxia-induced angiogenesis by decreasing HIF-1α and VEGFA expression, controlled glucose metabolism by reducing GLUT1 expression, inhibited the EMT by blocking the Slug-E-cadherin axis, and drove ROS-mediated apoptosis by regulating STAT3-Ref1 axis.Conclusion﻿These findings indicate that fraxetin enhances anti-tumor activity of gemcitabine and suppresses pancreatic cancer development by antagonizing STAT3 activation.
The XBP1-MARCH5-MFN2 Axis Confers ER Stress Resistance by Coordinating Mitochondrial Fission and Mitophagy in Melanoma
Authors: Wang Huina , Yi Xiuli , Guo Sen , Wang Sijia , Ma Jinyuan , Zhao Tao , Shi Qiong , Tian Yangzi , Wang Hao , Jia Lintao , Gao Tianwen , Li Chunying , Guo Weinan
Published: December 2020

Background: Melanoma cells are relatively resistant to ER stress, which contributes to tumor progression under stressful conditions and renders tolerance to ER stress-inducing therapeutic agents. Mitochondria are tightly interconnected with ER. However, whether mitochondria play a role in regulating ER stress resistance in melanoma remains elusive.Methods: Integrative bioinformatics was employed to figure out the implication of mitochondria in the resistance of melanoma cells to ER stress. A panel of biochemical assays and pre-clinical xenograft mouse model were used to investigate the role of mitochondrial fission and mitophagy in affecting ER stress sensitivity and the underlying mechanisms. Results: Our integrative bioinformatics analysis revealed that the down-regulation of mitochondrial genes was highly correlated with UPR activation in melanoma. Then we proved that mitochondrial fission and mitophagy were prominently induced in melanoma cells upon ER stress. Pharmacological inhibition of either mitochondrial fission or mitophagy effectively restored the sensitivity of melanoma cells to ER stress both in vitro and in vivo. Mechanistically, the down-regulation of MFN2 was essential for rendering the resistance by promoting mitochondrial fission and mitophagy. XBP1-mediated transcriptional up-regulation of E3 ligase MARCH5 contributed to the ubiquitination and degradation of MFN2 in ER stress-resistant cells, whereas the impaired transduction of this axis indicated the fragile to ER stress. Finally, the relationships among UPR pathway molecules, MARCH5 and mitochondrial genes were confirmed in both publicly accessible databases and tumor specimens.Conclusions: Together, our findings demonstrate a novel regulatory axis that links mitochondrial fission and mitophagy to the resistance to ER stress. Targeting mitochondrial quality control machinery can be exploited as an approach to reinforce the efficacy of ER stress-inducing agents against cancer.
Surufatinib Plus Toripalimab in Patients with Advanced Solid Tumors: A Single-Arm, Open-Label, Phase 1 Trial
Authors: Cao Yanshuo , Lu Ming , Sun Yu , Gong Jifang , Li Jie , Lu Zhihao , Li Jian , Zhang Xiaotian , Li Yan , Peng Zhi , Zhou Jun , Wang Xicheng , Shen Lin
Published: December 2020

BackgroundPreclinical studies have supported a potential synergistic antitumor activity between surufatinib and anti-programed death ligand-1 (PD-L1). We describe here the results of a single-arm, open-label phase 1 trial to evaluate the safety, preliminary efficacy, and pharmacokinetics (PK) in patients with advanced solid tumors treated with surufatinib combined with toripalimab, an inhibitor of PD-L1.MethodsThis is an open-label, dose escalation and expansion study in patients with solid tumors who had failed standard therapies or had no effective treatment. In the dose escalation stage, 3 cohorts of patients were treated with surufatinib, at dose levels of 200, 250, or 300 mg once daily (QD) in combination with a fixed dose of toripalimab 240 mg, every 3 weeks (Q3W), to evaluate maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D). Additional patients were enrolled in the dose expansion phase to further assess the efficacy, safety, and PK profile.ResultsFrom April 1, 2019 to July 10, 2020, 31 patients were screened, of which 28 patients were enrolled. One patient in the 300 mg cohort experienced dose limited toxicity (DLT), a grade 3 hyperthyroidism. The top 3 most common treatment-related adverse events of ≥ grade 3 were transaminases increased (17.9%), hypertension (14.3%) and blood bilirubin increased (10.7%). No treatment-related death or treatment discontinuation was identified. The RP2D was determined to be surufatinib 250 mg QD plus toripalimab 240 mg Q3W. Overall objective response rate was 22.2% [95% confidential interval (CI) 8.6‒42.3], and disease control rate reached 81.5% (95% CI 61.9‒93.7). ConclusionsSurufatinib plus toripalimab was well-tolerated, with no unexpected safety signals, and showed promising antitumor activity in patients with advanced solid tumors. Trial registrationclinicaltrials.gov, NCT03879057; Registered March 18, 2019, https://clinicaltrials.gov/ct2/show/NCT03879057